Mixed Topics

Evidence is strong that sexual partners transmit microbiota (bacteria, viruses, fungi, protozoa, and archaea) to each other. While microbial flora are abundant in the gastrointestinal tract, they are also present in the vagina, penis, urethra, mouth, and skin.¹ For better or worse, sexual contact of all types means that participants will acquire each other’s microbiota.

The 39 trillion microbiota in the body (which exceed the 30 trillion cells in the body) are commensal and influence both the larger brain in the skull and the smaller enteric brain in the gut. The microbiota and their microbiome genes (1,000 times larger than the human genome) have been linked to depression, anxiety, psychosis, and autism.^2-4 They produce 90% of the body’s serotonin, as well as catecholamines (norepinephrine, epinephrine, dopamine), make hormones (eg, cortisol), and modulate the immune system. Microbiota have several important functions, including food digestion, synthesis of vitamins, autoimmunity, hypothalamic-pituitary-adrenal axis regulation, and CNS modulation.

Consequences of dysbiosis

Everyone should be concerned about maintaining a healthy diversity of microbiota in their body, with a predominance of beneficial bacteria such as Lactobacillus and Bacteroides, and avoiding acquiring pathogenic bacteria such as Gardnerella, Prevotella, and Atopobium. Sexual activity involving a partner with unhealthy microbiota may increase the risk of dysbiosis, defined as a reduction in microbiota diversity, including a loss of beneficial bacteria and a rise in harmful bacteria.

Dysbiosis is associated with multiple symptoms, including⁵:

• brain “fog,” irritability, mood changes, and anxiety
• bloating, loss of intestinal permeability, and insufficient reclamation of nutrients
• congestion of certain organs, such as the liver, gallbladder, and pancreas
• production of antigen-antibody complexes in response to chemicals in partially digested food
• aggravation of inflammatory disorders such as migraine, arthritis, and autoimmune disorders.

Apart from intimate sexual contact, simply sharing a household with someone leads to sharing of gut microflora. Persons who live together, whether genetically related or not, have similar microbiota. Compared with people living in separate households, cohabiting human pairs, dog pairs, and human-dog pairs share most of their microbiota (especially in the skin).

A consequence of acquiring pathogenic microbiota in the vagina is bacterial vaginosis (BV), which is not an infection but an ecologic imbalance in the composition of the vaginal microbiota. BV is caused by a significant decline in the beneficial vaginal Lactobacillus and a marked increase in the non-Lactobacillus taxa (especially Gardnerella and Atopobium).⁶ It can last for a least 1 week after sexual intercourse. BV is rare or absent among virgins. For a male partner, penile microbiota changes significantly after unprotected sex.⁶

Pathogenic bacteria can be cultivated from the glans, the coronal sulcus, and the prepuce, as well as from the penile skin, semen, urethra, and urine.⁶ Diverse bacteria exist in human semen, regardless if the male is fertile or infertile.⁷Anaerococcus is a biomarker for low sperm quality. Many of the semen bacteria are also found in the vagina of women with BV.⁷ Semen is a medium for the transmission of bacteria and viruses between men and women, and can contribute to sexually transmitted diseases.⁸

There are approximately 21 million cases of BV in the United States each year, and BV can also increase the risk of HIV and poor obstetric outcomes.⁹ The microbiota in the penile skin and urethra in males who have monogamous relationships with females are very similar to the vaginal microbiota of their female partner.

Consequences of BV include:

• decrease in hydrogen peroxide–producing bacilli
• prevalence of anaerobic bacteria (Prevotella, Gardnerella, and Atopobium)
• alkalinization, fishy odor, and gray-white vaginal discharge
• increase in the rate of pelvic inflammatory disease, ectopic pregnancy, endometriosis, preterm birth, and tubal factor infertility.⁹

Circumcision decreases the risk of BV. There is an increased rate of BV bacterial taxa in men with extramarital affairs and in women with multiple partners. Both oral and vaginal sex increase the abundance of Lactobacillus in the male oral and penile microbiota. Gingivitis has also been reported after oral sex.¹⁰

A link to psychiatric disorders

Given that all forms of sexual contact (vaginal, oral, anal, or skin) can transmit microbiota bidirectionally between partners, it is vital to practice safe sex and consider a monogamous relationship rather than indiscriminate promiscuity. Unfortunately, certain psychiatric disorders, such as bipolar disorder, are associated with hypersexuality and multiple partners, which may disrupt the microbiota. This can further disrupt the diversity of an individual’s microbiome and may put them at risk for mood, anxiety, and other psychiatric disorders. Another problem is sexually transmitted infections such as gonorrhea or syphilis require antibiotic therapy. It is well established that antibiotics kill both the bad pathogenic and the good nonpathogenic microbiota, further exacerbating dysbiosis and leading to disruptions in the microbiota-gut-brain (MGB) axis, which then results in psychiatric disorders.

The MGB axis modulates neurological processes via the vagus nerve, the major “highway” connecting the gut and brain for bidirectional traffic. The MGB axis produces microbial metabolites and immune factors that can lead to changes in brain neurotransmitters as well as neuroinflammation and psychiatric symptoms such as depression and anxiety.⁵

Many researchers are focusing on how to exploit the microbiome to develop novel therapeutic strategies, and encouraging advances are emerging.⁵ But the exact mechanisms by which the gut microbiome can impact mental health is still a work in progress. It is highly likely that dysbiosis is associated with mood and anxiety symptoms.

The bottom line: Sexual activity—whether it is heavy kissing, vaginal intercourse, oral sex, anal sex, or extensive skin contact—can lead to the exchange of microbiota. If an individual has dysbiosis, that could impact the mental health of their sexual partner(s). This raises the question of whether counseling patients about avoiding indiscriminate sex and practicing safe sex is as important for mental health as diet and exercise counseling is for physical health.

Evidence is strong that sexual partners transmit microbiota (bacteria, viruses, fungi, protozoa, and archaea) to each other. While microbial flora are abundant in the gastrointestinal tract, they are also present in the vagina, penis, urethra, mouth, and skin.¹ For better or worse, sexual contact of all types means that participants will acquire each other’s microbiota.

The 39 trillion microbiota in the body (which exceed the 30 trillion cells in the body) are commensal and influence both the larger brain in the skull and the smaller enteric brain in the gut. The microbiota and their microbiome genes (1,000 times larger than the human genome) have been linked to depression, anxiety, psychosis, and autism.^2-4 They produce 90% of the body’s serotonin, as well as catecholamines (norepinephrine, epinephrine, dopamine), make hormones (eg, cortisol), and modulate the immune system. Microbiota have several important functions, including food digestion, synthesis of vitamins, autoimmunity, hypothalamic-pituitary-adrenal axis regulation, and CNS modulation.

Consequences of dysbiosis

Everyone should be concerned about maintaining a healthy diversity of microbiota in their body, with a predominance of beneficial bacteria such as Lactobacillus and Bacteroides, and avoiding acquiring pathogenic bacteria such as Gardnerella, Prevotella, and Atopobium. Sexual activity involving a partner with unhealthy microbiota may increase the risk of dysbiosis, defined as a reduction in microbiota diversity, including a loss of beneficial bacteria and a rise in harmful bacteria.

Dysbiosis is associated with multiple symptoms, including⁵:

• brain “fog,” irritability, mood changes, and anxiety
• bloating, loss of intestinal permeability, and insufficient reclamation of nutrients
• congestion of certain organs, such as the liver, gallbladder, and pancreas
• production of antigen-antibody complexes in response to chemicals in partially digested food
• aggravation of inflammatory disorders such as migraine, arthritis, and autoimmune disorders.

Apart from intimate sexual contact, simply sharing a household with someone leads to sharing of gut microflora. Persons who live together, whether genetically related or not, have similar microbiota. Compared with people living in separate households, cohabiting human pairs, dog pairs, and human-dog pairs share most of their microbiota (especially in the skin).

A consequence of acquiring pathogenic microbiota in the vagina is bacterial vaginosis (BV), which is not an infection but an ecologic imbalance in the composition of the vaginal microbiota. BV is caused by a significant decline in the beneficial vaginal Lactobacillus and a marked increase in the non-Lactobacillus taxa (especially Gardnerella and Atopobium).⁶ It can last for a least 1 week after sexual intercourse. BV is rare or absent among virgins. For a male partner, penile microbiota changes significantly after unprotected sex.⁶

Pathogenic bacteria can be cultivated from the glans, the coronal sulcus, and the prepuce, as well as from the penile skin, semen, urethra, and urine.⁶ Diverse bacteria exist in human semen, regardless if the male is fertile or infertile.⁷Anaerococcus is a biomarker for low sperm quality. Many of the semen bacteria are also found in the vagina of women with BV.⁷ Semen is a medium for the transmission of bacteria and viruses between men and women, and can contribute to sexually transmitted diseases.⁸

There are approximately 21 million cases of BV in the United States each year, and BV can also increase the risk of HIV and poor obstetric outcomes.⁹ The microbiota in the penile skin and urethra in males who have monogamous relationships with females are very similar to the vaginal microbiota of their female partner.

Consequences of BV include:

• decrease in hydrogen peroxide–producing bacilli
• prevalence of anaerobic bacteria (Prevotella, Gardnerella, and Atopobium)
• alkalinization, fishy odor, and gray-white vaginal discharge
• increase in the rate of pelvic inflammatory disease, ectopic pregnancy, endometriosis, preterm birth, and tubal factor infertility.⁹

Circumcision decreases the risk of BV. There is an increased rate of BV bacterial taxa in men with extramarital affairs and in women with multiple partners. Both oral and vaginal sex increase the abundance of Lactobacillus in the male oral and penile microbiota. Gingivitis has also been reported after oral sex.¹⁰

A link to psychiatric disorders

Given that all forms of sexual contact (vaginal, oral, anal, or skin) can transmit microbiota bidirectionally between partners, it is vital to practice safe sex and consider a monogamous relationship rather than indiscriminate promiscuity. Unfortunately, certain psychiatric disorders, such as bipolar disorder, are associated with hypersexuality and multiple partners, which may disrupt the microbiota. This can further disrupt the diversity of an individual’s microbiome and may put them at risk for mood, anxiety, and other psychiatric disorders. Another problem is sexually transmitted infections such as gonorrhea or syphilis require antibiotic therapy. It is well established that antibiotics kill both the bad pathogenic and the good nonpathogenic microbiota, further exacerbating dysbiosis and leading to disruptions in the microbiota-gut-brain (MGB) axis, which then results in psychiatric disorders.

The MGB axis modulates neurological processes via the vagus nerve, the major “highway” connecting the gut and brain for bidirectional traffic. The MGB axis produces microbial metabolites and immune factors that can lead to changes in brain neurotransmitters as well as neuroinflammation and psychiatric symptoms such as depression and anxiety.⁵

Many researchers are focusing on how to exploit the microbiome to develop novel therapeutic strategies, and encouraging advances are emerging.⁵ But the exact mechanisms by which the gut microbiome can impact mental health is still a work in progress. It is highly likely that dysbiosis is associated with mood and anxiety symptoms.

The bottom line: Sexual activity—whether it is heavy kissing, vaginal intercourse, oral sex, anal sex, or extensive skin contact—can lead to the exchange of microbiota. If an individual has dysbiosis, that could impact the mental health of their sexual partner(s). This raises the question of whether counseling patients about avoiding indiscriminate sex and practicing safe sex is as important for mental health as diet and exercise counseling is for physical health.

Evidence is strong that sexual partners transmit microbiota (bacteria, viruses, fungi, protozoa, and archaea) to each other. While microbial flora are abundant in the gastrointestinal tract, they are also present in the vagina, penis, urethra, mouth, and skin.¹ For better or worse, sexual contact of all types means that participants will acquire each other’s microbiota.

The 39 trillion microbiota in the body (which exceed the 30 trillion cells in the body) are commensal and influence both the larger brain in the skull and the smaller enteric brain in the gut. The microbiota and their microbiome genes (1,000 times larger than the human genome) have been linked to depression, anxiety, psychosis, and autism.^2-4 They produce 90% of the body’s serotonin, as well as catecholamines (norepinephrine, epinephrine, dopamine), make hormones (eg, cortisol), and modulate the immune system. Microbiota have several important functions, including food digestion, synthesis of vitamins, autoimmunity, hypothalamic-pituitary-adrenal axis regulation, and CNS modulation.

Consequences of dysbiosis

Everyone should be concerned about maintaining a healthy diversity of microbiota in their body, with a predominance of beneficial bacteria such as Lactobacillus and Bacteroides, and avoiding acquiring pathogenic bacteria such as Gardnerella, Prevotella, and Atopobium. Sexual activity involving a partner with unhealthy microbiota may increase the risk of dysbiosis, defined as a reduction in microbiota diversity, including a loss of beneficial bacteria and a rise in harmful bacteria.

Dysbiosis is associated with multiple symptoms, including⁵:

• brain “fog,” irritability, mood changes, and anxiety
• bloating, loss of intestinal permeability, and insufficient reclamation of nutrients
• congestion of certain organs, such as the liver, gallbladder, and pancreas
• production of antigen-antibody complexes in response to chemicals in partially digested food
• aggravation of inflammatory disorders such as migraine, arthritis, and autoimmune disorders.

Apart from intimate sexual contact, simply sharing a household with someone leads to sharing of gut microflora. Persons who live together, whether genetically related or not, have similar microbiota. Compared with people living in separate households, cohabiting human pairs, dog pairs, and human-dog pairs share most of their microbiota (especially in the skin).

A consequence of acquiring pathogenic microbiota in the vagina is bacterial vaginosis (BV), which is not an infection but an ecologic imbalance in the composition of the vaginal microbiota. BV is caused by a significant decline in the beneficial vaginal Lactobacillus and a marked increase in the non-Lactobacillus taxa (especially Gardnerella and Atopobium).⁶ It can last for a least 1 week after sexual intercourse. BV is rare or absent among virgins. For a male partner, penile microbiota changes significantly after unprotected sex.⁶

Pathogenic bacteria can be cultivated from the glans, the coronal sulcus, and the prepuce, as well as from the penile skin, semen, urethra, and urine.⁶ Diverse bacteria exist in human semen, regardless if the male is fertile or infertile.⁷Anaerococcus is a biomarker for low sperm quality. Many of the semen bacteria are also found in the vagina of women with BV.⁷ Semen is a medium for the transmission of bacteria and viruses between men and women, and can contribute to sexually transmitted diseases.⁸

There are approximately 21 million cases of BV in the United States each year, and BV can also increase the risk of HIV and poor obstetric outcomes.⁹ The microbiota in the penile skin and urethra in males who have monogamous relationships with females are very similar to the vaginal microbiota of their female partner.

Consequences of BV include:

• decrease in hydrogen peroxide–producing bacilli
• prevalence of anaerobic bacteria (Prevotella, Gardnerella, and Atopobium)
• alkalinization, fishy odor, and gray-white vaginal discharge
• increase in the rate of pelvic inflammatory disease, ectopic pregnancy, endometriosis, preterm birth, and tubal factor infertility.⁹

Circumcision decreases the risk of BV. There is an increased rate of BV bacterial taxa in men with extramarital affairs and in women with multiple partners. Both oral and vaginal sex increase the abundance of Lactobacillus in the male oral and penile microbiota. Gingivitis has also been reported after oral sex.¹⁰

A link to psychiatric disorders

Given that all forms of sexual contact (vaginal, oral, anal, or skin) can transmit microbiota bidirectionally between partners, it is vital to practice safe sex and consider a monogamous relationship rather than indiscriminate promiscuity. Unfortunately, certain psychiatric disorders, such as bipolar disorder, are associated with hypersexuality and multiple partners, which may disrupt the microbiota. This can further disrupt the diversity of an individual’s microbiome and may put them at risk for mood, anxiety, and other psychiatric disorders. Another problem is sexually transmitted infections such as gonorrhea or syphilis require antibiotic therapy. It is well established that antibiotics kill both the bad pathogenic and the good nonpathogenic microbiota, further exacerbating dysbiosis and leading to disruptions in the microbiota-gut-brain (MGB) axis, which then results in psychiatric disorders.

The MGB axis modulates neurological processes via the vagus nerve, the major “highway” connecting the gut and brain for bidirectional traffic. The MGB axis produces microbial metabolites and immune factors that can lead to changes in brain neurotransmitters as well as neuroinflammation and psychiatric symptoms such as depression and anxiety.⁵

Many researchers are focusing on how to exploit the microbiome to develop novel therapeutic strategies, and encouraging advances are emerging.⁵ But the exact mechanisms by which the gut microbiome can impact mental health is still a work in progress. It is highly likely that dysbiosis is associated with mood and anxiety symptoms.

The bottom line: Sexual activity—whether it is heavy kissing, vaginal intercourse, oral sex, anal sex, or extensive skin contact—can lead to the exchange of microbiota. If an individual has dysbiosis, that could impact the mental health of their sexual partner(s). This raises the question of whether counseling patients about avoiding indiscriminate sex and practicing safe sex is as important for mental health as diet and exercise counseling is for physical health.

Mr. B, age 64, is being treated in the psychiatric clinic for generalized anxiety disorder. He also has a history of type 2 diabetes mellitus and osteoarthritis. His present medications include metformin 500 mg twice daily, escitalopram 20 mg/d, and a multivitamin.

Three months after a shingles outbreak on his left trunk, Mr. B develops a sharp, burning pain and hypersensitivity to light in the same area as the shingles flare-up. He is diagnosed with postherpetic neuralgia. Despite a 12-week trial of cognitive-behavioral therapy, Mr. B continues to report excessive worry, irritability, poor concentration, psycho­motor restlessness, and poor sleep.

Contrasting with the serendipitous discovery of iproniazid and chlorpromazine leading to the development of the current spectrum of antidepressant and antipsychotic agents, discovery of the benefits various antiepileptic agents have in bipolar disorder has not led to a similar proliferation of medication development for bipolar mania or depression.^1-3 Divalproex, one of the most commonly used antiepileptic drugs (AEDs) in psychiatry, was thought to be an inactive organic solvent until it was used in 1962 to test the anticonvulsant activity of other compounds. This led to the discovery and subsequent use of divalproex in patients with epilepsy, followed by FDA approval in bipolar disorder.^4,5 Off-label use of many AEDs as mood-stabilizing agents in bipolar disorder led to the emergence of carbamazepine, divalproex, and lamotrigine, which joined lithium as classic mood-stabilizing agents.^4,6-8 Amid varying definitions of “mood stabilizer,” many AEDs have failed to demonstrate mood-stabilizing effects in bipolar disorder and therefore should not all be considered mood stabilizers.⁹ Nonetheless, the dual use of a single AED for both psychiatric and nonpsychiatric indications can decrease polypharmacy and increase acceptability of medications in patients who have low insight into their illness.^10,11

Because AEDs were originally purposed to treat neurologic disease, psychiatric indications must first be established before considering other indications. AEDs as a class have broad pharmacologic actions, but are generally CNS depressants, decreasing brain signaling through mechanisms such as ion channel antagonism (carbamazepine, gabapentin) or alterations to gamma-aminobutyric acid/glutamate signaling (divalproex, topiramate).^4,6,12,13 Compared to antidepressants and antipsychotics, whose primary use for psychiatric conditions is firmly rooted in evidence, rational use of AEDs for psychiatric conditions and symptoms depends on the agent-specific efficacy. Patients with comorbid psychiatric and neurologic disorders are ideal candidates for dually indicated AEDs due to these agents’ class effects rooted in epilepsy. Due to the history of positive psychiatric benefits with AEDs, newer agents may be psychiatrically beneficial but will likely follow the discovery of these benefits in patients for whom epilepsy is the primary diagnosis.

Consider the limitations

Using AEDs to reduce polypharmacy should be done judiciously from a drug-drug interaction perspective, because certain AEDs (eg, carbamazepine, divalproex) can greatly influence the metabolism of other medications, which may defeat the best intentions of the original intervention.^4,6

Several other limitations should be considered. This article does not include all AEDs, only those commonly used for psychiatric indications with known nonpsychiatric benefits. Some may worsen psychiatric conditions (such as rage and irritability in the case of levetiracetam), and all AEDs have an FDA warning regarding suicidal behaviors and ideation.^14,15 Another important limitation is the potential for differential dosing across indications; tolerability concerns may limit adequate dosing across multiple uses. For example, topiramate’s migraine prophylaxis effect can be achieved at much lower doses than the patient-specific efficacy dosing seen in binge eating disorder, with higher doses increasing the propensity for adverse effects.^13,16Dual-use AEDs should be considered wherever possible, but judicious review of evidence is necessary to appropriately adjudicate a specific patient’s risk vs benefit. The Table^{4,6-9,12,13,16-68}  provides information on select AEDs with both psychiatric and nonpsychiatric indications, including both FDA-approved and common off-label uses. These indications are limited to adult use only.

CASE CONTINUED

After reviewing Mr. B’s medical history, the treating medical team decides to cross-taper escitalopram to duloxetine 30 mg twice daily. Though his pain lessens after several weeks, it persists enough to interfere with Mr. B’s daily life. In addition to duloxetine, he is started on pregabalin 50 mg 3 times a day. Mr. B’s pain decreases to a tolerable level, and he reports decreased worrying and restlessness, and improvements in concentration and sleep.

Mr. B, age 64, is being treated in the psychiatric clinic for generalized anxiety disorder. He also has a history of type 2 diabetes mellitus and osteoarthritis. His present medications include metformin 500 mg twice daily, escitalopram 20 mg/d, and a multivitamin.

Three months after a shingles outbreak on his left trunk, Mr. B develops a sharp, burning pain and hypersensitivity to light in the same area as the shingles flare-up. He is diagnosed with postherpetic neuralgia. Despite a 12-week trial of cognitive-behavioral therapy, Mr. B continues to report excessive worry, irritability, poor concentration, psycho­motor restlessness, and poor sleep.

Contrasting with the serendipitous discovery of iproniazid and chlorpromazine leading to the development of the current spectrum of antidepressant and antipsychotic agents, discovery of the benefits various antiepileptic agents have in bipolar disorder has not led to a similar proliferation of medication development for bipolar mania or depression.^1-3 Divalproex, one of the most commonly used antiepileptic drugs (AEDs) in psychiatry, was thought to be an inactive organic solvent until it was used in 1962 to test the anticonvulsant activity of other compounds. This led to the discovery and subsequent use of divalproex in patients with epilepsy, followed by FDA approval in bipolar disorder.^4,5 Off-label use of many AEDs as mood-stabilizing agents in bipolar disorder led to the emergence of carbamazepine, divalproex, and lamotrigine, which joined lithium as classic mood-stabilizing agents.^4,6-8 Amid varying definitions of “mood stabilizer,” many AEDs have failed to demonstrate mood-stabilizing effects in bipolar disorder and therefore should not all be considered mood stabilizers.⁹ Nonetheless, the dual use of a single AED for both psychiatric and nonpsychiatric indications can decrease polypharmacy and increase acceptability of medications in patients who have low insight into their illness.^10,11

Because AEDs were originally purposed to treat neurologic disease, psychiatric indications must first be established before considering other indications. AEDs as a class have broad pharmacologic actions, but are generally CNS depressants, decreasing brain signaling through mechanisms such as ion channel antagonism (carbamazepine, gabapentin) or alterations to gamma-aminobutyric acid/glutamate signaling (divalproex, topiramate).^4,6,12,13 Compared to antidepressants and antipsychotics, whose primary use for psychiatric conditions is firmly rooted in evidence, rational use of AEDs for psychiatric conditions and symptoms depends on the agent-specific efficacy. Patients with comorbid psychiatric and neurologic disorders are ideal candidates for dually indicated AEDs due to these agents’ class effects rooted in epilepsy. Due to the history of positive psychiatric benefits with AEDs, newer agents may be psychiatrically beneficial but will likely follow the discovery of these benefits in patients for whom epilepsy is the primary diagnosis.

Consider the limitations

Using AEDs to reduce polypharmacy should be done judiciously from a drug-drug interaction perspective, because certain AEDs (eg, carbamazepine, divalproex) can greatly influence the metabolism of other medications, which may defeat the best intentions of the original intervention.^4,6

Several other limitations should be considered. This article does not include all AEDs, only those commonly used for psychiatric indications with known nonpsychiatric benefits. Some may worsen psychiatric conditions (such as rage and irritability in the case of levetiracetam), and all AEDs have an FDA warning regarding suicidal behaviors and ideation.^14,15 Another important limitation is the potential for differential dosing across indications; tolerability concerns may limit adequate dosing across multiple uses. For example, topiramate’s migraine prophylaxis effect can be achieved at much lower doses than the patient-specific efficacy dosing seen in binge eating disorder, with higher doses increasing the propensity for adverse effects.^13,16Dual-use AEDs should be considered wherever possible, but judicious review of evidence is necessary to appropriately adjudicate a specific patient’s risk vs benefit. The Table^{4,6-9,12,13,16-68}  provides information on select AEDs with both psychiatric and nonpsychiatric indications, including both FDA-approved and common off-label uses. These indications are limited to adult use only.

CASE CONTINUED

After reviewing Mr. B’s medical history, the treating medical team decides to cross-taper escitalopram to duloxetine 30 mg twice daily. Though his pain lessens after several weeks, it persists enough to interfere with Mr. B’s daily life. In addition to duloxetine, he is started on pregabalin 50 mg 3 times a day. Mr. B’s pain decreases to a tolerable level, and he reports decreased worrying and restlessness, and improvements in concentration and sleep.

Mr. B, age 64, is being treated in the psychiatric clinic for generalized anxiety disorder. He also has a history of type 2 diabetes mellitus and osteoarthritis. His present medications include metformin 500 mg twice daily, escitalopram 20 mg/d, and a multivitamin.

Three months after a shingles outbreak on his left trunk, Mr. B develops a sharp, burning pain and hypersensitivity to light in the same area as the shingles flare-up. He is diagnosed with postherpetic neuralgia. Despite a 12-week trial of cognitive-behavioral therapy, Mr. B continues to report excessive worry, irritability, poor concentration, psycho­motor restlessness, and poor sleep.

Contrasting with the serendipitous discovery of iproniazid and chlorpromazine leading to the development of the current spectrum of antidepressant and antipsychotic agents, discovery of the benefits various antiepileptic agents have in bipolar disorder has not led to a similar proliferation of medication development for bipolar mania or depression.^1-3 Divalproex, one of the most commonly used antiepileptic drugs (AEDs) in psychiatry, was thought to be an inactive organic solvent until it was used in 1962 to test the anticonvulsant activity of other compounds. This led to the discovery and subsequent use of divalproex in patients with epilepsy, followed by FDA approval in bipolar disorder.^4,5 Off-label use of many AEDs as mood-stabilizing agents in bipolar disorder led to the emergence of carbamazepine, divalproex, and lamotrigine, which joined lithium as classic mood-stabilizing agents.^4,6-8 Amid varying definitions of “mood stabilizer,” many AEDs have failed to demonstrate mood-stabilizing effects in bipolar disorder and therefore should not all be considered mood stabilizers.⁹ Nonetheless, the dual use of a single AED for both psychiatric and nonpsychiatric indications can decrease polypharmacy and increase acceptability of medications in patients who have low insight into their illness.^10,11

Because AEDs were originally purposed to treat neurologic disease, psychiatric indications must first be established before considering other indications. AEDs as a class have broad pharmacologic actions, but are generally CNS depressants, decreasing brain signaling through mechanisms such as ion channel antagonism (carbamazepine, gabapentin) or alterations to gamma-aminobutyric acid/glutamate signaling (divalproex, topiramate).^4,6,12,13 Compared to antidepressants and antipsychotics, whose primary use for psychiatric conditions is firmly rooted in evidence, rational use of AEDs for psychiatric conditions and symptoms depends on the agent-specific efficacy. Patients with comorbid psychiatric and neurologic disorders are ideal candidates for dually indicated AEDs due to these agents’ class effects rooted in epilepsy. Due to the history of positive psychiatric benefits with AEDs, newer agents may be psychiatrically beneficial but will likely follow the discovery of these benefits in patients for whom epilepsy is the primary diagnosis.

Consider the limitations

Using AEDs to reduce polypharmacy should be done judiciously from a drug-drug interaction perspective, because certain AEDs (eg, carbamazepine, divalproex) can greatly influence the metabolism of other medications, which may defeat the best intentions of the original intervention.^4,6

Several other limitations should be considered. This article does not include all AEDs, only those commonly used for psychiatric indications with known nonpsychiatric benefits. Some may worsen psychiatric conditions (such as rage and irritability in the case of levetiracetam), and all AEDs have an FDA warning regarding suicidal behaviors and ideation.^14,15 Another important limitation is the potential for differential dosing across indications; tolerability concerns may limit adequate dosing across multiple uses. For example, topiramate’s migraine prophylaxis effect can be achieved at much lower doses than the patient-specific efficacy dosing seen in binge eating disorder, with higher doses increasing the propensity for adverse effects.^13,16Dual-use AEDs should be considered wherever possible, but judicious review of evidence is necessary to appropriately adjudicate a specific patient’s risk vs benefit. The Table^{4,6-9,12,13,16-68}  provides information on select AEDs with both psychiatric and nonpsychiatric indications, including both FDA-approved and common off-label uses. These indications are limited to adult use only.

CASE CONTINUED

After reviewing Mr. B’s medical history, the treating medical team decides to cross-taper escitalopram to duloxetine 30 mg twice daily. Though his pain lessens after several weeks, it persists enough to interfere with Mr. B’s daily life. In addition to duloxetine, he is started on pregabalin 50 mg 3 times a day. Mr. B’s pain decreases to a tolerable level, and he reports decreased worrying and restlessness, and improvements in concentration and sleep.

Obsessive-compulsive disorder (OCD) is a chronic, debilitating neuropsychiatric disorder that affects 1% to 3% of the population worldwide.^1,2 Together, serotonin reuptake inhibitors (SRIs) and cognitive-behavior therapy (CBT) are considered the first-line treatment for OCD.³ In children and adults, CBT is considered at least as effective as pharmacotherapy.⁴ Despite being an effective treatment, CBT continues to have barriers to its widespread use, including limited availability of trained CBT therapists, delayed clinical response, and high costs.⁵

Only approximately one-half of patients with OCD respond to SRI therapy, and a considerable percentage (30% to 40%) show significant residual symptoms even after multiple trials of SRIs.^6-8 In addition, SRIs may have adverse effects (eg, sexual dysfunction, gastrointestinal symptoms) that impair patient adherence to these medications.⁹ Therefore, finding better treatment options is important for managing patients with OCD.

Augmentation strategies are recommended for patients who show partial response to SRI treatment or poor response to multiple SRIs. Augmentation typically includes incorporating additional medications with the primary drug with the goal of boosting the therapeutic efficacy of the primary drug. Typically, these additional medications have different mechanisms of action. However, there are no large-scale randomized controlled trials (RCTs) to inform treatment augmentation after first-line treatments for OCD produce suboptimal outcomes. The available evidence is predominantly based on small-scale RCTs, open-label trials, and case series.

In this article, we review the evidence for treatment augmentation strategies for OCD and summarize 8 studies that show promising results (Table^10-17). We focus only on pharmacologic agents and do not include other biological interventions, such as repetitive transcranial magnetic stimulation over supplementary motor area, ablative neurosurgery, or deep brain stimulation.

Continue to: Reference 1...

Numerous studies support the role of glutamate dysregulation in the pathophysiology of OCD. Cortico-striato-thalamo-cortical (CSTC) abnormalities play a major role in the pathophysiology of OCD as suggested by neuroimaging research studies that indicate glutamate is the fundamental neurotransmitter of the CSTC circuit. Dysregulation of glutamatergic signaling within this circuit has been linked to OCD. Patients with OCD have been found to have an increase of glutamate in the CSF. As a result, medications that affect glutamate levels can be used to treat patients with OCD who do not respond to first-line agents. In patients already taking SRIs, augmentation of glutamate-modulating medications can reduce OCD symptoms. As an uncompetitive antagonist of the N-methyl-d-aspartate (NMDA)-type glutamate receptor, amantadine has been proposed as 1 of these medications.

Naderi et al¹⁰ evaluated amantadine as augmentative therapy to fluvoxamine for treating patients with moderate to severe OCD.

Study design

• This 12-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of amantadine as an augmentative agent to fluvoxamine in 106 patients age 18 to 60 with moderate to severe OCD.
• Participants met DSM-5 criteria for OCD and had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score >21. Participants were excluded if they had any substance dependence; an IQ <70; any other Axis I mental disorder; any serious cardiac, renal, or hepatic disease; had received psychotropic medications during the last 6 weeks, were pregnant or breastfeeding, or had rising liver transaminases to 3 times the upper limit of normal or higher.
• Participants received fluvoxamine 100 mg twice daily plus amantadine 100 mg/d, or fluvoxamine 100 mg twice daily plus placebo. All patients received fluvoxamine 100 mg/d for 28 days followed by 200 mg/d for the remainder of the trial.
• The primary outcome measure was difference in Y-BOCS total scores between the amantadine and placebo groups. The secondary outcome was the difference in Y-BOCS obsession and compulsion subscale scores.

Outcomes

• Patients who received amantadine augmentation experienced a significant reduction in Y-BOCS total score (P < .001) and obsession subscale score (P < .01).
• The amantadine group showed good tolerability and safety. There were no clinically significant adverse effects.

• Amantadine is an effective adjuvant to fluvoxamine for reducing OCD symptoms.

Conclusion

• Ondansetron and granisetron can be beneficial as an augmentation strategy for patients with treatment-resistant OCD.

2. Sharafkhah M, Aghakarim Alamdar M, Massoudifar A, et al. Comparing the efficacy of ondansetron and granisetron augmentation in treatment-resistant obsessive-compulsive disorder: a randomized double-blind placebo-controlled study. Int Clin Psychopharmacol. 2019;34(5):222- 233. doi:10.1097/YIC.0000000000000267

Although selective serotonin reuptake inhibitors (SSRIs) are considered a first-line treatment when teamed with CBT and antipsychotic augmentation, symptom resolution is not always achieved, and treatment resistance is a common problem. Sharafkhah et al¹¹ compared the efficacy of ondansetron and granisetron augmentation specifically for patients with treatment-resistant OCD.

Study Design

• In this 18-week, randomized, double-blind, placebo-controlled study, 135 patients with treatment-resistant OCD who were previously treated with a combination of an SSRI and an antipsychotic received augmentation with ondansetron (n = 45, 4 mg/d), granisetron (n = 45, 2 mg/d), or placebo.
• Patients were rated using Y-BOCS every 2 weeks during phase I (intervention period), which lasted 14 weeks. After completing the intervention, patients were followed for 4 more weeks during phase II (discontinuation period).
• The aim of this study was to determine the safety, efficacy, and tolerability of ondansetron vs granisetron as augmentation for patients with treatment-resistant OCD. A secondary aim was to determine the rate of relapse of OCD symptoms after discontinuing ondansetron as compared with granisetron at 4 weeks after intervention.

Outcomes

• At Week 14, the reductions in Y-BOCS scores in the ondansetron, granisetron, and placebo groups were 41.5%, 39.7%, and 15.2%, respectively (P = .001). The reduction in Y-BOCS score in the ondansetron and granisetron groups was significantly greater than placebo at all phase I visits.
• Complete response was higher in the ondansetron group compared with the granisetron group (P = .041).
• Y-BOCS scores increased in both the ondansetron and granisetron groups during the discontinuation phase, but OCD symptoms were not significantly exacerbated.

Conclusion

• Ondansetron and granisetron can be beneficial as an augmentation strategy for patients with treatment-resistant OCD.

3. Modarresi A, Sayyah M, Razooghi S, et al. Memantine augmentation improves symptoms in serotonin reuptake inhibitorrefractory obsessive-compulsive disorder: a randomized controlled trial. Pharmacopsychiatry. 2018;51(6):263-269. doi:10.1055/s-0043-120268

Increased glutamate levels in CSF, glutamatergic overactivity, and polymorphisms of genes coding the NMDA receptor have been shown to contribute to the occurrence of OCD. Memantine is a noncompetitive antagonist of the NMDA receptor. Various control trials have shown augmentation with memantine 5 mg/d to 20 mg/d significantly reduced symptom severity in patients with moderate to severe OCD. Modarresi et al¹² evaluated memantine as a treatment option for patients with severe OCD who did not respond to SRI monotherapy.

Study design

• This 12-week, double-blind, randomized, placebo-controlled trial evaluated the efficacy of memantine augmentation in 32 patients age 18 to 40 who met DSM-5 criteria for OCD, had a Y-BOCS score ≥24, and no psychiatric comorbidity. Participants had not responded to ≥3 adequate trials (minimum 3 months) of SRI therapy, 1 of which was clomipramine.
• Individuals were excluded if they were undergoing CBT; had an additional anxiety disorder, mood disorder, or current drug or alcohol use disorder, or any systemic disorder; had a history of seizures; were pregnant or breastfeeding; or had a history of memantine use.
• Participants already receiving the maximum tolerated dose of an SRI received augmentation with memantine 20 mg/d or placebo.
• The primary outcome measure was change in Y-BOCS score from baseline. The secondary outcome was the number of individuals who achieved treatment response (defined as ≥35% reduction in Y-BOCS score).

Continue to: Outcomes...

Outcomes

• There was a statistically significant difference in Y-BOCS score in patients treated with memantine at Week 8 and Week 12 vs those who received placebo. By Week 8, 17.2% of patients in the memantine group showed a decrease in Y-BOCS score, compared with -0.8% patients in the placebo group. The difference became more significant by Week 12, with 40.9% in the memantine group showing a decrease in Y-BOCS score vs -0.3% in the placebo group. This resulted in 73.3% of patients achieving treatment response.
• Eight weeks of memantine augmentation was necessary to observe a significant improvement in OCD symptoms, and 12 weeks was needed for treatment response.
• The mean Y-BOCS total score decreased significantly in the memantine group from Week 4 to Week 8 (16.8%) and again from Week 8 to Week 12 (28.5%).
• The memantine group showed good tolerability and safety. There were no clinically significant adverse effects.

Conclusion

• Memantine augmentation in patients with severe OCD who do not respond to an SRI is effective and well-tolerated.

4. Shalbafan M, Malekpour F, Tadayon Najafabadi B, et al. Fluvoxamine combination therapy with tropisetron for obsessive-compulsive disorder patients: a placebo-controlled, randomized clinical trial. J Psychopharmacol. 2019;33(11):1407- 1414. doi:10.1177/0269881119878177

Studies have demonstrated the involvement of the amygdala, medial and lateral orbitofrontal cortex, and dorsal anterior cingulate cortex in OCD. Additionally, studies have also investigated the role of serotonin, dopamine, and glutamate system dysregulation in the pathology of OCD.

The 5-HT3 receptors are ligand-gated ion channels found in the prefrontal cortex, amygdala, and hippocampus. Studies of 5-HT3 receptor antagonists such as ondansetron and granisetron have shown beneficial results in augmentation with SSRIs for patients with OCD.¹¹ Tropisetron, a 5-HT3 receptor antagonist, is highly lipophilic and able to cross the blood brain barrier. It also has dopamine-inhibiting properties that could have benefits in OCD management. Shalbafan et al¹³ evaluated the efficacy of tropisetron augmentation to fluvoxamine for patients with OCD.

Study design

• In a 10-week, randomized, double-blind, placebo-controlled, parallel-group trial, 108 individuals age 18 to 60 who met DSM-5 criteria for OCD and had a Y-BOCS score >21 received fluvoxamine plus tropisetron or fluvoxamine plus placebo. A total of 48 (44.4%) participants in each group completed the trial. Participants were evaluated using the Y-BOCS scale at baseline and at Week 4 and Week 10.
• The primary outcome was decrease in total Y-BOCS score from baseline to Week 10. The secondary outcome was the difference in change in Y-BOCS obsession and compulsion subscale scores between the groups.

Outcomes

• The Y-BOCS total score was not significantly different between the 2 groups (P = .975). Repeated measures analysis of variance determined a significant effect for time in both tropisetron and placebo groups (Greenhouse-Geisser F [2.72–2303.84] = 152.25, P < .001; and Greenhouse-Geisser F [1.37–1736.81] = 75.57, P < .001, respectively). At Week 10, 35 participants in the tropisetron group and 19 participants in the placebo group were complete responders.
• The baseline Y-BOCS obsession and compulsion subscales did not significantly differ between treatment groups.

Conclusion

• Compared with participants in the placebo group, those in the tropisetron group experienced a significantly greater reduction in OCD symptoms as measured by Y-BOCS score. More participants in the tropisetron group experienced complete response and remission.
• This study demonstrated that compared with placebo, when administered as augmentation with fluvoxamine, tropisetron can have beneficial effects for patients with OCD.

Continue to: Reference 5...

5. Yousefzadeh F, Sahebolzamani E, Sadri A, et al. 5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a doubleblind randomized trial with placebo control. Int Clin Psychopharmacol. 2020;35(5):254- 262. doi:10.1097/YIC.0000000000000321

Nutraceuticals such as glycine, milk thistle, myoinositol, and serotonin (5-hydroxytryptophan) have been proposed as augmentation options for OCD. Yousefzadeh et al¹⁴ investigated the effectiveness of using 5-hydroxytryptophan in treating OCD.

Study design

• In a 12-week, randomized, double-blind study, 60 patients who met DSM-5 criteria for moderate to severe OCD (Y-BOCS score >21) were randomly assigned to receive fluoxetine plus 5-hydroxytryptophan 100 mg twice daily or fluoxetine plus placebo.
• All patients were administered fluoxetine 20 mg/d for the first 4 weeks of the study followed by fluoxetine 60 mg/d for the remainder of the trial.
• Symptoms were assessed using the Y-BOCS at baseline, Week 4, Week 8, and Week 12.
• The primary outcome measure was the difference between the 2 groups in change in Y-BOCS total score from baseline to the end of the trial. Secondary outcome measures were the differences in the Y-BOCS obsession and compulsion subscale scores from baseline to Week 12.

Outcomes

• Compared to the placebo group, the 5-hydroxytryptophan group experienced a statistically significant greater improvement in Y-BOCS total score from baseline to Week 8 (P = .002) and Week 12 (P < .001).
• General linear model repeated measure showed significant effects for time × treatment interaction on Y-BOCS total (F = 12.07, df = 2.29, P < .001), obsession subscale (F = 8.25, df = 1.91, P = .001), and compulsion subscale scores (F = 6.64, df = 2.01, P = .002).
• The 5-hydroxytryptophan group demonstrated higher partial and complete treatment response rates (P = .032 and P = .001, respectively) as determined by change in Y-BOCS total score.
• The 5-hydroxytryptophan group showed a significant improvement from baseline to Week 12 in Y-BOCS obsession subscale score (5.23 ± 2.33 vs 3.53 ± 2.13, P = .009).
• There was a significant change from baseline to the end of the trial in the Y-BOCS compulsion subscale score (3.88 ± 2.04 vs 2.30 ± 1.37, P = .002).

Conclusion

• This trial demonstrated the potential benefits of 5-hydroxytryptophan in combination with fluoxetine for patients with OCD.

6. Mowla A, Ghaedsharaf M. Pregabalin augmentation for resistant obsessive-compulsive disorder: a double-blind placebo-controlled clinical trial. CNS Spectr. 2020;25(4):552-556. doi:10.1017/S1092852919001500

Glutamatergic dysfunction has been identified as a potential cause of OCD. Studies have found elevated levels of glutamatergic transmission in the cortical-striatal-thalamic circuit of the brain and elevated glutamate concentration in the CSF in patients with OCD. Pregabalin has multiple mechanisms of action that inhibit the release of glutamate. Mowla et al¹⁵ evaluated pregabalin as an augmentation treatment for resistant OCD.

Study design

• This 12-week, double-blind, placebo-controlled clinical trial evaluated the efficacy of adjunctive pregabalin in 56 patients who met DSM-5 criteria for OCD and had not responded to ≥12 weeks of treatment with an adequate and stable dose of sertraline (baseline Y-BOCS score ≥18).
• Individuals who had other major psychiatric disorders, major medical problems, were pregnant, or had past substance or alcohol abuse were excluded.
• Participants were randomly assigned to receive sertraline plus pregabalin (n = 28) or sertraline plus placebo (n = 28). Mean sertraline dosage was 256.5 mg/d; range was 100 mg/d to 300 mg/d. Pregabalin was started at 75 mg/d and increased by 75 mg increments weekly. The mean dosage was 185.9 mg/d; range was 75 mg/d to 225 mg/d.
• The primary outcome measure was change in Y-BOCS score. A decrease >35% in Y-BOCS score was considered a significant response rate.

Outcomes

• There was a statistically significant decrease in Y-BOCS score in patients who received pregabalin. In the pregabalin group, 57.14% of patients (n = 16) showed a >35% decrease in Y-BOCS score compared with 7.14% of patients (n = 2) in the placebo group (P < .01).
• The pregabalin group showed good tolerability and safety. There were no clinically significant adverse effects.

Conclusion

• In patients with treatment-resistant OCD who did not respond to sertraline monotherapy, augmentation with pregabalin significantly decreases Y-BOCS scores compared with placebo.

Continue to: Reference 7...

Recent evidence suggests dysregulation of serotonin and dopamine in patients with OCD. Methylphenidate is a dopamine and norepinephrine inhibitor and releaser. A limited number of studies have suggested stimulants might be useful for OCD patients. Zheng et al¹⁶ conducted a pilot trial to determine whether methylphenidate augmentation may be of benefit in the management of outpatients with OCD.

Study design

• In an 8-week, double-blind, randomized, placebo-controlled trial, 44 patients (29 [66%] men, with a mean [SD] age of 24.7 [6]) with treatment-refractory OCD were randomized to receive fluvoxamine 250 mg/d plus methylphenidate extended-release (MPH-ER) 36 mg/d or fluvoxamine 250 mg/d plus placebo. The MPH-ER dose was 18 mg/d for the first 4 weeks and 36 mg/d for the rest of the trial.
• Biweekly assessments consisted of scores on the Y-BOCS, Hamilton Depression Rating Scale (HDRS), and Hamilton Anxiety Rating Scale (HAM-A).
• The primary outcomes were improvement in Y-BOCS score and the clinical response rate. Secondary outcomes included a change in score on the Y-BOCS subscales, HARS, and HAM-A. Data were analyzed with the intention-to-treat sample.

Outcomes

• Forty-one patients finished the trial. The baseline Y-BOCS total scores and subscale scores did not differ significantly between the 2 groups.
• Improvements in Y-BOCS total score and obsession subscale score were more prominent in the fluvoxamine plus MPH-ER group compared with the placebo group (P < .001).
• HDRS score decreased in both the placebo and MPH-ER groups. HAM-A scores decreased significantly in the MPH-ER plus fluvoxamine group compared with the placebo group.

Conclusion

• This study demonstrated that the combination of fluvoxamine and MPH-ER produces a higher and faster response rate than fluvoxamine plus placebo in patients with OCD.

8. Arabzadeh S, Shahhossenie M, Mesgarpour B, et al. L-carnosine as an adjuvant to fluvoxamine in treatment of obsessive compulsive disorder: a randomized double-blind study. Hum Psychopharmacol. 2017;32(4). doi:10.1002/hup.2584

Glutamate dysregulation is implicated in the pathogenesis of OCD. Glutamate-modulating agents have been used to treat OCD. Studies have shown L-carnosine has a neuroprotective role via its modulatory effect on glutamate. Arabzadeh et al¹⁷ evaluated the efficacy of L-carnosine as an adjuvant to fluvoxamine for treating OCD.

Study design

• This 10-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of adjunctive L-carnosine in 40 patients age 18 to 60 who met DSM-5 criteria for OCD and had moderate to severe OCD (Y-BOCS score ≥21).
• Individuals with any other DSM-5 major psychiatric disorders, serious medical or neurologic illness, substance dependence (other than caffeine or nicotine), mental retardation (based on clinical judgment), were pregnant or breastfeeding, had any contraindication for the use of L‐carnosine or fluvoxamine, or received any psychotropic drugs in the previous 6 weeks were excluded.
• Participants received fluvoxamine 100 mg/d for the first 4 weeks and 200 mg/d for the next 6 weeks plus either L-carnosine 500 mg twice daily or placebo. This dosage of L-carnosine was chosen because previously it had been tolerated and effective.
• The primary outcome measure was difference in Y-BOCS total scores. Secondary outcomes were differences in Y-BOCS obsession and compulsion subscale scores and differences in change in score on Y-BOCS total and subscale scores from baseline.

Outcomes

• The L-carnosine group experienced a significant decrease in Y-BOCS total score (P < .001), obsession subscale score (P < .01), and compulsion subscale score (P < .01).
• The group that received fluvoxamine plus L-carnosine also experienced a more complete response (P = .03).
• The L-carnosine group showed good tolerability and safety. There were no clinically significant adverse effects.

Conclusion

• L-carnosine significantly reduces OCD symptoms when used as an adjuvant to fluvoxamine.

Obsessive-compulsive disorder (OCD) is a chronic, debilitating neuropsychiatric disorder that affects 1% to 3% of the population worldwide.^1,2 Together, serotonin reuptake inhibitors (SRIs) and cognitive-behavior therapy (CBT) are considered the first-line treatment for OCD.³ In children and adults, CBT is considered at least as effective as pharmacotherapy.⁴ Despite being an effective treatment, CBT continues to have barriers to its widespread use, including limited availability of trained CBT therapists, delayed clinical response, and high costs.⁵

Only approximately one-half of patients with OCD respond to SRI therapy, and a considerable percentage (30% to 40%) show significant residual symptoms even after multiple trials of SRIs.^6-8 In addition, SRIs may have adverse effects (eg, sexual dysfunction, gastrointestinal symptoms) that impair patient adherence to these medications.⁹ Therefore, finding better treatment options is important for managing patients with OCD.

Augmentation strategies are recommended for patients who show partial response to SRI treatment or poor response to multiple SRIs. Augmentation typically includes incorporating additional medications with the primary drug with the goal of boosting the therapeutic efficacy of the primary drug. Typically, these additional medications have different mechanisms of action. However, there are no large-scale randomized controlled trials (RCTs) to inform treatment augmentation after first-line treatments for OCD produce suboptimal outcomes. The available evidence is predominantly based on small-scale RCTs, open-label trials, and case series.

In this article, we review the evidence for treatment augmentation strategies for OCD and summarize 8 studies that show promising results (Table^10-17). We focus only on pharmacologic agents and do not include other biological interventions, such as repetitive transcranial magnetic stimulation over supplementary motor area, ablative neurosurgery, or deep brain stimulation.

Continue to: Reference 1...

Numerous studies support the role of glutamate dysregulation in the pathophysiology of OCD. Cortico-striato-thalamo-cortical (CSTC) abnormalities play a major role in the pathophysiology of OCD as suggested by neuroimaging research studies that indicate glutamate is the fundamental neurotransmitter of the CSTC circuit. Dysregulation of glutamatergic signaling within this circuit has been linked to OCD. Patients with OCD have been found to have an increase of glutamate in the CSF. As a result, medications that affect glutamate levels can be used to treat patients with OCD who do not respond to first-line agents. In patients already taking SRIs, augmentation of glutamate-modulating medications can reduce OCD symptoms. As an uncompetitive antagonist of the N-methyl-d-aspartate (NMDA)-type glutamate receptor, amantadine has been proposed as 1 of these medications.

Naderi et al¹⁰ evaluated amantadine as augmentative therapy to fluvoxamine for treating patients with moderate to severe OCD.

Study design

• This 12-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of amantadine as an augmentative agent to fluvoxamine in 106 patients age 18 to 60 with moderate to severe OCD.
• Participants met DSM-5 criteria for OCD and had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score >21. Participants were excluded if they had any substance dependence; an IQ <70; any other Axis I mental disorder; any serious cardiac, renal, or hepatic disease; had received psychotropic medications during the last 6 weeks, were pregnant or breastfeeding, or had rising liver transaminases to 3 times the upper limit of normal or higher.
• Participants received fluvoxamine 100 mg twice daily plus amantadine 100 mg/d, or fluvoxamine 100 mg twice daily plus placebo. All patients received fluvoxamine 100 mg/d for 28 days followed by 200 mg/d for the remainder of the trial.
• The primary outcome measure was difference in Y-BOCS total scores between the amantadine and placebo groups. The secondary outcome was the difference in Y-BOCS obsession and compulsion subscale scores.

Outcomes

• Patients who received amantadine augmentation experienced a significant reduction in Y-BOCS total score (P < .001) and obsession subscale score (P < .01).
• The amantadine group showed good tolerability and safety. There were no clinically significant adverse effects.

• Amantadine is an effective adjuvant to fluvoxamine for reducing OCD symptoms.

Conclusion

• Ondansetron and granisetron can be beneficial as an augmentation strategy for patients with treatment-resistant OCD.

2. Sharafkhah M, Aghakarim Alamdar M, Massoudifar A, et al. Comparing the efficacy of ondansetron and granisetron augmentation in treatment-resistant obsessive-compulsive disorder: a randomized double-blind placebo-controlled study. Int Clin Psychopharmacol. 2019;34(5):222- 233. doi:10.1097/YIC.0000000000000267

Although selective serotonin reuptake inhibitors (SSRIs) are considered a first-line treatment when teamed with CBT and antipsychotic augmentation, symptom resolution is not always achieved, and treatment resistance is a common problem. Sharafkhah et al¹¹ compared the efficacy of ondansetron and granisetron augmentation specifically for patients with treatment-resistant OCD.

Study Design

• In this 18-week, randomized, double-blind, placebo-controlled study, 135 patients with treatment-resistant OCD who were previously treated with a combination of an SSRI and an antipsychotic received augmentation with ondansetron (n = 45, 4 mg/d), granisetron (n = 45, 2 mg/d), or placebo.
• Patients were rated using Y-BOCS every 2 weeks during phase I (intervention period), which lasted 14 weeks. After completing the intervention, patients were followed for 4 more weeks during phase II (discontinuation period).
• The aim of this study was to determine the safety, efficacy, and tolerability of ondansetron vs granisetron as augmentation for patients with treatment-resistant OCD. A secondary aim was to determine the rate of relapse of OCD symptoms after discontinuing ondansetron as compared with granisetron at 4 weeks after intervention.

Outcomes

• At Week 14, the reductions in Y-BOCS scores in the ondansetron, granisetron, and placebo groups were 41.5%, 39.7%, and 15.2%, respectively (P = .001). The reduction in Y-BOCS score in the ondansetron and granisetron groups was significantly greater than placebo at all phase I visits.
• Complete response was higher in the ondansetron group compared with the granisetron group (P = .041).
• Y-BOCS scores increased in both the ondansetron and granisetron groups during the discontinuation phase, but OCD symptoms were not significantly exacerbated.

Conclusion

• Ondansetron and granisetron can be beneficial as an augmentation strategy for patients with treatment-resistant OCD.

3. Modarresi A, Sayyah M, Razooghi S, et al. Memantine augmentation improves symptoms in serotonin reuptake inhibitorrefractory obsessive-compulsive disorder: a randomized controlled trial. Pharmacopsychiatry. 2018;51(6):263-269. doi:10.1055/s-0043-120268

Increased glutamate levels in CSF, glutamatergic overactivity, and polymorphisms of genes coding the NMDA receptor have been shown to contribute to the occurrence of OCD. Memantine is a noncompetitive antagonist of the NMDA receptor. Various control trials have shown augmentation with memantine 5 mg/d to 20 mg/d significantly reduced symptom severity in patients with moderate to severe OCD. Modarresi et al¹² evaluated memantine as a treatment option for patients with severe OCD who did not respond to SRI monotherapy.

Study design

• This 12-week, double-blind, randomized, placebo-controlled trial evaluated the efficacy of memantine augmentation in 32 patients age 18 to 40 who met DSM-5 criteria for OCD, had a Y-BOCS score ≥24, and no psychiatric comorbidity. Participants had not responded to ≥3 adequate trials (minimum 3 months) of SRI therapy, 1 of which was clomipramine.
• Individuals were excluded if they were undergoing CBT; had an additional anxiety disorder, mood disorder, or current drug or alcohol use disorder, or any systemic disorder; had a history of seizures; were pregnant or breastfeeding; or had a history of memantine use.
• Participants already receiving the maximum tolerated dose of an SRI received augmentation with memantine 20 mg/d or placebo.
• The primary outcome measure was change in Y-BOCS score from baseline. The secondary outcome was the number of individuals who achieved treatment response (defined as ≥35% reduction in Y-BOCS score).

Continue to: Outcomes...

Outcomes

• There was a statistically significant difference in Y-BOCS score in patients treated with memantine at Week 8 and Week 12 vs those who received placebo. By Week 8, 17.2% of patients in the memantine group showed a decrease in Y-BOCS score, compared with -0.8% patients in the placebo group. The difference became more significant by Week 12, with 40.9% in the memantine group showing a decrease in Y-BOCS score vs -0.3% in the placebo group. This resulted in 73.3% of patients achieving treatment response.
• Eight weeks of memantine augmentation was necessary to observe a significant improvement in OCD symptoms, and 12 weeks was needed for treatment response.
• The mean Y-BOCS total score decreased significantly in the memantine group from Week 4 to Week 8 (16.8%) and again from Week 8 to Week 12 (28.5%).
• The memantine group showed good tolerability and safety. There were no clinically significant adverse effects.

Conclusion

• Memantine augmentation in patients with severe OCD who do not respond to an SRI is effective and well-tolerated.

4. Shalbafan M, Malekpour F, Tadayon Najafabadi B, et al. Fluvoxamine combination therapy with tropisetron for obsessive-compulsive disorder patients: a placebo-controlled, randomized clinical trial. J Psychopharmacol. 2019;33(11):1407- 1414. doi:10.1177/0269881119878177

Studies have demonstrated the involvement of the amygdala, medial and lateral orbitofrontal cortex, and dorsal anterior cingulate cortex in OCD. Additionally, studies have also investigated the role of serotonin, dopamine, and glutamate system dysregulation in the pathology of OCD.

The 5-HT3 receptors are ligand-gated ion channels found in the prefrontal cortex, amygdala, and hippocampus. Studies of 5-HT3 receptor antagonists such as ondansetron and granisetron have shown beneficial results in augmentation with SSRIs for patients with OCD.¹¹ Tropisetron, a 5-HT3 receptor antagonist, is highly lipophilic and able to cross the blood brain barrier. It also has dopamine-inhibiting properties that could have benefits in OCD management. Shalbafan et al¹³ evaluated the efficacy of tropisetron augmentation to fluvoxamine for patients with OCD.

Study design

• In a 10-week, randomized, double-blind, placebo-controlled, parallel-group trial, 108 individuals age 18 to 60 who met DSM-5 criteria for OCD and had a Y-BOCS score >21 received fluvoxamine plus tropisetron or fluvoxamine plus placebo. A total of 48 (44.4%) participants in each group completed the trial. Participants were evaluated using the Y-BOCS scale at baseline and at Week 4 and Week 10.
• The primary outcome was decrease in total Y-BOCS score from baseline to Week 10. The secondary outcome was the difference in change in Y-BOCS obsession and compulsion subscale scores between the groups.

Outcomes

• The Y-BOCS total score was not significantly different between the 2 groups (P = .975). Repeated measures analysis of variance determined a significant effect for time in both tropisetron and placebo groups (Greenhouse-Geisser F [2.72–2303.84] = 152.25, P < .001; and Greenhouse-Geisser F [1.37–1736.81] = 75.57, P < .001, respectively). At Week 10, 35 participants in the tropisetron group and 19 participants in the placebo group were complete responders.
• The baseline Y-BOCS obsession and compulsion subscales did not significantly differ between treatment groups.

Conclusion

• Compared with participants in the placebo group, those in the tropisetron group experienced a significantly greater reduction in OCD symptoms as measured by Y-BOCS score. More participants in the tropisetron group experienced complete response and remission.
• This study demonstrated that compared with placebo, when administered as augmentation with fluvoxamine, tropisetron can have beneficial effects for patients with OCD.

Continue to: Reference 5...

5. Yousefzadeh F, Sahebolzamani E, Sadri A, et al. 5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a doubleblind randomized trial with placebo control. Int Clin Psychopharmacol. 2020;35(5):254- 262. doi:10.1097/YIC.0000000000000321

Nutraceuticals such as glycine, milk thistle, myoinositol, and serotonin (5-hydroxytryptophan) have been proposed as augmentation options for OCD. Yousefzadeh et al¹⁴ investigated the effectiveness of using 5-hydroxytryptophan in treating OCD.

Study design

• In a 12-week, randomized, double-blind study, 60 patients who met DSM-5 criteria for moderate to severe OCD (Y-BOCS score >21) were randomly assigned to receive fluoxetine plus 5-hydroxytryptophan 100 mg twice daily or fluoxetine plus placebo.
• All patients were administered fluoxetine 20 mg/d for the first 4 weeks of the study followed by fluoxetine 60 mg/d for the remainder of the trial.
• Symptoms were assessed using the Y-BOCS at baseline, Week 4, Week 8, and Week 12.
• The primary outcome measure was the difference between the 2 groups in change in Y-BOCS total score from baseline to the end of the trial. Secondary outcome measures were the differences in the Y-BOCS obsession and compulsion subscale scores from baseline to Week 12.

Outcomes

• Compared to the placebo group, the 5-hydroxytryptophan group experienced a statistically significant greater improvement in Y-BOCS total score from baseline to Week 8 (P = .002) and Week 12 (P < .001).
• General linear model repeated measure showed significant effects for time × treatment interaction on Y-BOCS total (F = 12.07, df = 2.29, P < .001), obsession subscale (F = 8.25, df = 1.91, P = .001), and compulsion subscale scores (F = 6.64, df = 2.01, P = .002).
• The 5-hydroxytryptophan group demonstrated higher partial and complete treatment response rates (P = .032 and P = .001, respectively) as determined by change in Y-BOCS total score.
• The 5-hydroxytryptophan group showed a significant improvement from baseline to Week 12 in Y-BOCS obsession subscale score (5.23 ± 2.33 vs 3.53 ± 2.13, P = .009).
• There was a significant change from baseline to the end of the trial in the Y-BOCS compulsion subscale score (3.88 ± 2.04 vs 2.30 ± 1.37, P = .002).

Conclusion

• This trial demonstrated the potential benefits of 5-hydroxytryptophan in combination with fluoxetine for patients with OCD.

6. Mowla A, Ghaedsharaf M. Pregabalin augmentation for resistant obsessive-compulsive disorder: a double-blind placebo-controlled clinical trial. CNS Spectr. 2020;25(4):552-556. doi:10.1017/S1092852919001500

Glutamatergic dysfunction has been identified as a potential cause of OCD. Studies have found elevated levels of glutamatergic transmission in the cortical-striatal-thalamic circuit of the brain and elevated glutamate concentration in the CSF in patients with OCD. Pregabalin has multiple mechanisms of action that inhibit the release of glutamate. Mowla et al¹⁵ evaluated pregabalin as an augmentation treatment for resistant OCD.

Study design

• This 12-week, double-blind, placebo-controlled clinical trial evaluated the efficacy of adjunctive pregabalin in 56 patients who met DSM-5 criteria for OCD and had not responded to ≥12 weeks of treatment with an adequate and stable dose of sertraline (baseline Y-BOCS score ≥18).
• Individuals who had other major psychiatric disorders, major medical problems, were pregnant, or had past substance or alcohol abuse were excluded.
• Participants were randomly assigned to receive sertraline plus pregabalin (n = 28) or sertraline plus placebo (n = 28). Mean sertraline dosage was 256.5 mg/d; range was 100 mg/d to 300 mg/d. Pregabalin was started at 75 mg/d and increased by 75 mg increments weekly. The mean dosage was 185.9 mg/d; range was 75 mg/d to 225 mg/d.
• The primary outcome measure was change in Y-BOCS score. A decrease >35% in Y-BOCS score was considered a significant response rate.

Outcomes

• There was a statistically significant decrease in Y-BOCS score in patients who received pregabalin. In the pregabalin group, 57.14% of patients (n = 16) showed a >35% decrease in Y-BOCS score compared with 7.14% of patients (n = 2) in the placebo group (P < .01).
• The pregabalin group showed good tolerability and safety. There were no clinically significant adverse effects.

Conclusion

• In patients with treatment-resistant OCD who did not respond to sertraline monotherapy, augmentation with pregabalin significantly decreases Y-BOCS scores compared with placebo.

Continue to: Reference 7...

Recent evidence suggests dysregulation of serotonin and dopamine in patients with OCD. Methylphenidate is a dopamine and norepinephrine inhibitor and releaser. A limited number of studies have suggested stimulants might be useful for OCD patients. Zheng et al¹⁶ conducted a pilot trial to determine whether methylphenidate augmentation may be of benefit in the management of outpatients with OCD.

Study design

• In an 8-week, double-blind, randomized, placebo-controlled trial, 44 patients (29 [66%] men, with a mean [SD] age of 24.7 [6]) with treatment-refractory OCD were randomized to receive fluvoxamine 250 mg/d plus methylphenidate extended-release (MPH-ER) 36 mg/d or fluvoxamine 250 mg/d plus placebo. The MPH-ER dose was 18 mg/d for the first 4 weeks and 36 mg/d for the rest of the trial.
• Biweekly assessments consisted of scores on the Y-BOCS, Hamilton Depression Rating Scale (HDRS), and Hamilton Anxiety Rating Scale (HAM-A).
• The primary outcomes were improvement in Y-BOCS score and the clinical response rate. Secondary outcomes included a change in score on the Y-BOCS subscales, HARS, and HAM-A. Data were analyzed with the intention-to-treat sample.

Outcomes

• Forty-one patients finished the trial. The baseline Y-BOCS total scores and subscale scores did not differ significantly between the 2 groups.
• Improvements in Y-BOCS total score and obsession subscale score were more prominent in the fluvoxamine plus MPH-ER group compared with the placebo group (P < .001).
• HDRS score decreased in both the placebo and MPH-ER groups. HAM-A scores decreased significantly in the MPH-ER plus fluvoxamine group compared with the placebo group.

Conclusion

• This study demonstrated that the combination of fluvoxamine and MPH-ER produces a higher and faster response rate than fluvoxamine plus placebo in patients with OCD.

8. Arabzadeh S, Shahhossenie M, Mesgarpour B, et al. L-carnosine as an adjuvant to fluvoxamine in treatment of obsessive compulsive disorder: a randomized double-blind study. Hum Psychopharmacol. 2017;32(4). doi:10.1002/hup.2584

Glutamate dysregulation is implicated in the pathogenesis of OCD. Glutamate-modulating agents have been used to treat OCD. Studies have shown L-carnosine has a neuroprotective role via its modulatory effect on glutamate. Arabzadeh et al¹⁷ evaluated the efficacy of L-carnosine as an adjuvant to fluvoxamine for treating OCD.

Study design

• This 10-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of adjunctive L-carnosine in 40 patients age 18 to 60 who met DSM-5 criteria for OCD and had moderate to severe OCD (Y-BOCS score ≥21).
• Individuals with any other DSM-5 major psychiatric disorders, serious medical or neurologic illness, substance dependence (other than caffeine or nicotine), mental retardation (based on clinical judgment), were pregnant or breastfeeding, had any contraindication for the use of L‐carnosine or fluvoxamine, or received any psychotropic drugs in the previous 6 weeks were excluded.
• Participants received fluvoxamine 100 mg/d for the first 4 weeks and 200 mg/d for the next 6 weeks plus either L-carnosine 500 mg twice daily or placebo. This dosage of L-carnosine was chosen because previously it had been tolerated and effective.
• The primary outcome measure was difference in Y-BOCS total scores. Secondary outcomes were differences in Y-BOCS obsession and compulsion subscale scores and differences in change in score on Y-BOCS total and subscale scores from baseline.

Outcomes

• The L-carnosine group experienced a significant decrease in Y-BOCS total score (P < .001), obsession subscale score (P < .01), and compulsion subscale score (P < .01).
• The group that received fluvoxamine plus L-carnosine also experienced a more complete response (P = .03).
• The L-carnosine group showed good tolerability and safety. There were no clinically significant adverse effects.

Conclusion

• L-carnosine significantly reduces OCD symptoms when used as an adjuvant to fluvoxamine.

Obsessive-compulsive disorder (OCD) is a chronic, debilitating neuropsychiatric disorder that affects 1% to 3% of the population worldwide.^1,2 Together, serotonin reuptake inhibitors (SRIs) and cognitive-behavior therapy (CBT) are considered the first-line treatment for OCD.³ In children and adults, CBT is considered at least as effective as pharmacotherapy.⁴ Despite being an effective treatment, CBT continues to have barriers to its widespread use, including limited availability of trained CBT therapists, delayed clinical response, and high costs.⁵

Only approximately one-half of patients with OCD respond to SRI therapy, and a considerable percentage (30% to 40%) show significant residual symptoms even after multiple trials of SRIs.^6-8 In addition, SRIs may have adverse effects (eg, sexual dysfunction, gastrointestinal symptoms) that impair patient adherence to these medications.⁹ Therefore, finding better treatment options is important for managing patients with OCD.

Augmentation strategies are recommended for patients who show partial response to SRI treatment or poor response to multiple SRIs. Augmentation typically includes incorporating additional medications with the primary drug with the goal of boosting the therapeutic efficacy of the primary drug. Typically, these additional medications have different mechanisms of action. However, there are no large-scale randomized controlled trials (RCTs) to inform treatment augmentation after first-line treatments for OCD produce suboptimal outcomes. The available evidence is predominantly based on small-scale RCTs, open-label trials, and case series.

In this article, we review the evidence for treatment augmentation strategies for OCD and summarize 8 studies that show promising results (Table^10-17). We focus only on pharmacologic agents and do not include other biological interventions, such as repetitive transcranial magnetic stimulation over supplementary motor area, ablative neurosurgery, or deep brain stimulation.

Continue to: Reference 1...

Numerous studies support the role of glutamate dysregulation in the pathophysiology of OCD. Cortico-striato-thalamo-cortical (CSTC) abnormalities play a major role in the pathophysiology of OCD as suggested by neuroimaging research studies that indicate glutamate is the fundamental neurotransmitter of the CSTC circuit. Dysregulation of glutamatergic signaling within this circuit has been linked to OCD. Patients with OCD have been found to have an increase of glutamate in the CSF. As a result, medications that affect glutamate levels can be used to treat patients with OCD who do not respond to first-line agents. In patients already taking SRIs, augmentation of glutamate-modulating medications can reduce OCD symptoms. As an uncompetitive antagonist of the N-methyl-d-aspartate (NMDA)-type glutamate receptor, amantadine has been proposed as 1 of these medications.

Naderi et al¹⁰ evaluated amantadine as augmentative therapy to fluvoxamine for treating patients with moderate to severe OCD.

Study design

• This 12-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of amantadine as an augmentative agent to fluvoxamine in 106 patients age 18 to 60 with moderate to severe OCD.
• Participants met DSM-5 criteria for OCD and had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score >21. Participants were excluded if they had any substance dependence; an IQ <70; any other Axis I mental disorder; any serious cardiac, renal, or hepatic disease; had received psychotropic medications during the last 6 weeks, were pregnant or breastfeeding, or had rising liver transaminases to 3 times the upper limit of normal or higher.
• Participants received fluvoxamine 100 mg twice daily plus amantadine 100 mg/d, or fluvoxamine 100 mg twice daily plus placebo. All patients received fluvoxamine 100 mg/d for 28 days followed by 200 mg/d for the remainder of the trial.
• The primary outcome measure was difference in Y-BOCS total scores between the amantadine and placebo groups. The secondary outcome was the difference in Y-BOCS obsession and compulsion subscale scores.

Outcomes

• Patients who received amantadine augmentation experienced a significant reduction in Y-BOCS total score (P < .001) and obsession subscale score (P < .01).
• The amantadine group showed good tolerability and safety. There were no clinically significant adverse effects.

• Amantadine is an effective adjuvant to fluvoxamine for reducing OCD symptoms.

Conclusion

• Ondansetron and granisetron can be beneficial as an augmentation strategy for patients with treatment-resistant OCD.

2. Sharafkhah M, Aghakarim Alamdar M, Massoudifar A, et al. Comparing the efficacy of ondansetron and granisetron augmentation in treatment-resistant obsessive-compulsive disorder: a randomized double-blind placebo-controlled study. Int Clin Psychopharmacol. 2019;34(5):222- 233. doi:10.1097/YIC.0000000000000267

Although selective serotonin reuptake inhibitors (SSRIs) are considered a first-line treatment when teamed with CBT and antipsychotic augmentation, symptom resolution is not always achieved, and treatment resistance is a common problem. Sharafkhah et al¹¹ compared the efficacy of ondansetron and granisetron augmentation specifically for patients with treatment-resistant OCD.

Study Design

• In this 18-week, randomized, double-blind, placebo-controlled study, 135 patients with treatment-resistant OCD who were previously treated with a combination of an SSRI and an antipsychotic received augmentation with ondansetron (n = 45, 4 mg/d), granisetron (n = 45, 2 mg/d), or placebo.
• Patients were rated using Y-BOCS every 2 weeks during phase I (intervention period), which lasted 14 weeks. After completing the intervention, patients were followed for 4 more weeks during phase II (discontinuation period).
• The aim of this study was to determine the safety, efficacy, and tolerability of ondansetron vs granisetron as augmentation for patients with treatment-resistant OCD. A secondary aim was to determine the rate of relapse of OCD symptoms after discontinuing ondansetron as compared with granisetron at 4 weeks after intervention.

Outcomes

• At Week 14, the reductions in Y-BOCS scores in the ondansetron, granisetron, and placebo groups were 41.5%, 39.7%, and 15.2%, respectively (P = .001). The reduction in Y-BOCS score in the ondansetron and granisetron groups was significantly greater than placebo at all phase I visits.
• Complete response was higher in the ondansetron group compared with the granisetron group (P = .041).
• Y-BOCS scores increased in both the ondansetron and granisetron groups during the discontinuation phase, but OCD symptoms were not significantly exacerbated.

Conclusion

• Ondansetron and granisetron can be beneficial as an augmentation strategy for patients with treatment-resistant OCD.

3. Modarresi A, Sayyah M, Razooghi S, et al. Memantine augmentation improves symptoms in serotonin reuptake inhibitorrefractory obsessive-compulsive disorder: a randomized controlled trial. Pharmacopsychiatry. 2018;51(6):263-269. doi:10.1055/s-0043-120268

Increased glutamate levels in CSF, glutamatergic overactivity, and polymorphisms of genes coding the NMDA receptor have been shown to contribute to the occurrence of OCD. Memantine is a noncompetitive antagonist of the NMDA receptor. Various control trials have shown augmentation with memantine 5 mg/d to 20 mg/d significantly reduced symptom severity in patients with moderate to severe OCD. Modarresi et al¹² evaluated memantine as a treatment option for patients with severe OCD who did not respond to SRI monotherapy.

Study design

• This 12-week, double-blind, randomized, placebo-controlled trial evaluated the efficacy of memantine augmentation in 32 patients age 18 to 40 who met DSM-5 criteria for OCD, had a Y-BOCS score ≥24, and no psychiatric comorbidity. Participants had not responded to ≥3 adequate trials (minimum 3 months) of SRI therapy, 1 of which was clomipramine.
• Individuals were excluded if they were undergoing CBT; had an additional anxiety disorder, mood disorder, or current drug or alcohol use disorder, or any systemic disorder; had a history of seizures; were pregnant or breastfeeding; or had a history of memantine use.
• Participants already receiving the maximum tolerated dose of an SRI received augmentation with memantine 20 mg/d or placebo.
• The primary outcome measure was change in Y-BOCS score from baseline. The secondary outcome was the number of individuals who achieved treatment response (defined as ≥35% reduction in Y-BOCS score).

Continue to: Outcomes...

Outcomes

• There was a statistically significant difference in Y-BOCS score in patients treated with memantine at Week 8 and Week 12 vs those who received placebo. By Week 8, 17.2% of patients in the memantine group showed a decrease in Y-BOCS score, compared with -0.8% patients in the placebo group. The difference became more significant by Week 12, with 40.9% in the memantine group showing a decrease in Y-BOCS score vs -0.3% in the placebo group. This resulted in 73.3% of patients achieving treatment response.
• Eight weeks of memantine augmentation was necessary to observe a significant improvement in OCD symptoms, and 12 weeks was needed for treatment response.
• The mean Y-BOCS total score decreased significantly in the memantine group from Week 4 to Week 8 (16.8%) and again from Week 8 to Week 12 (28.5%).
• The memantine group showed good tolerability and safety. There were no clinically significant adverse effects.

Conclusion

• Memantine augmentation in patients with severe OCD who do not respond to an SRI is effective and well-tolerated.

4. Shalbafan M, Malekpour F, Tadayon Najafabadi B, et al. Fluvoxamine combination therapy with tropisetron for obsessive-compulsive disorder patients: a placebo-controlled, randomized clinical trial. J Psychopharmacol. 2019;33(11):1407- 1414. doi:10.1177/0269881119878177

Studies have demonstrated the involvement of the amygdala, medial and lateral orbitofrontal cortex, and dorsal anterior cingulate cortex in OCD. Additionally, studies have also investigated the role of serotonin, dopamine, and glutamate system dysregulation in the pathology of OCD.

The 5-HT3 receptors are ligand-gated ion channels found in the prefrontal cortex, amygdala, and hippocampus. Studies of 5-HT3 receptor antagonists such as ondansetron and granisetron have shown beneficial results in augmentation with SSRIs for patients with OCD.¹¹ Tropisetron, a 5-HT3 receptor antagonist, is highly lipophilic and able to cross the blood brain barrier. It also has dopamine-inhibiting properties that could have benefits in OCD management. Shalbafan et al¹³ evaluated the efficacy of tropisetron augmentation to fluvoxamine for patients with OCD.

Study design

• In a 10-week, randomized, double-blind, placebo-controlled, parallel-group trial, 108 individuals age 18 to 60 who met DSM-5 criteria for OCD and had a Y-BOCS score >21 received fluvoxamine plus tropisetron or fluvoxamine plus placebo. A total of 48 (44.4%) participants in each group completed the trial. Participants were evaluated using the Y-BOCS scale at baseline and at Week 4 and Week 10.
• The primary outcome was decrease in total Y-BOCS score from baseline to Week 10. The secondary outcome was the difference in change in Y-BOCS obsession and compulsion subscale scores between the groups.

Outcomes

• The Y-BOCS total score was not significantly different between the 2 groups (P = .975). Repeated measures analysis of variance determined a significant effect for time in both tropisetron and placebo groups (Greenhouse-Geisser F [2.72–2303.84] = 152.25, P < .001; and Greenhouse-Geisser F [1.37–1736.81] = 75.57, P < .001, respectively). At Week 10, 35 participants in the tropisetron group and 19 participants in the placebo group were complete responders.
• The baseline Y-BOCS obsession and compulsion subscales did not significantly differ between treatment groups.

Conclusion

• Compared with participants in the placebo group, those in the tropisetron group experienced a significantly greater reduction in OCD symptoms as measured by Y-BOCS score. More participants in the tropisetron group experienced complete response and remission.
• This study demonstrated that compared with placebo, when administered as augmentation with fluvoxamine, tropisetron can have beneficial effects for patients with OCD.

Continue to: Reference 5...

5. Yousefzadeh F, Sahebolzamani E, Sadri A, et al. 5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a doubleblind randomized trial with placebo control. Int Clin Psychopharmacol. 2020;35(5):254- 262. doi:10.1097/YIC.0000000000000321

Nutraceuticals such as glycine, milk thistle, myoinositol, and serotonin (5-hydroxytryptophan) have been proposed as augmentation options for OCD. Yousefzadeh et al¹⁴ investigated the effectiveness of using 5-hydroxytryptophan in treating OCD.

Study design

• In a 12-week, randomized, double-blind study, 60 patients who met DSM-5 criteria for moderate to severe OCD (Y-BOCS score >21) were randomly assigned to receive fluoxetine plus 5-hydroxytryptophan 100 mg twice daily or fluoxetine plus placebo.
• All patients were administered fluoxetine 20 mg/d for the first 4 weeks of the study followed by fluoxetine 60 mg/d for the remainder of the trial.
• Symptoms were assessed using the Y-BOCS at baseline, Week 4, Week 8, and Week 12.
• The primary outcome measure was the difference between the 2 groups in change in Y-BOCS total score from baseline to the end of the trial. Secondary outcome measures were the differences in the Y-BOCS obsession and compulsion subscale scores from baseline to Week 12.

Outcomes

• Compared to the placebo group, the 5-hydroxytryptophan group experienced a statistically significant greater improvement in Y-BOCS total score from baseline to Week 8 (P = .002) and Week 12 (P < .001).
• General linear model repeated measure showed significant effects for time × treatment interaction on Y-BOCS total (F = 12.07, df = 2.29, P < .001), obsession subscale (F = 8.25, df = 1.91, P = .001), and compulsion subscale scores (F = 6.64, df = 2.01, P = .002).
• The 5-hydroxytryptophan group demonstrated higher partial and complete treatment response rates (P = .032 and P = .001, respectively) as determined by change in Y-BOCS total score.
• The 5-hydroxytryptophan group showed a significant improvement from baseline to Week 12 in Y-BOCS obsession subscale score (5.23 ± 2.33 vs 3.53 ± 2.13, P = .009).
• There was a significant change from baseline to the end of the trial in the Y-BOCS compulsion subscale score (3.88 ± 2.04 vs 2.30 ± 1.37, P = .002).

Conclusion

• This trial demonstrated the potential benefits of 5-hydroxytryptophan in combination with fluoxetine for patients with OCD.

6. Mowla A, Ghaedsharaf M. Pregabalin augmentation for resistant obsessive-compulsive disorder: a double-blind placebo-controlled clinical trial. CNS Spectr. 2020;25(4):552-556. doi:10.1017/S1092852919001500

Glutamatergic dysfunction has been identified as a potential cause of OCD. Studies have found elevated levels of glutamatergic transmission in the cortical-striatal-thalamic circuit of the brain and elevated glutamate concentration in the CSF in patients with OCD. Pregabalin has multiple mechanisms of action that inhibit the release of glutamate. Mowla et al¹⁵ evaluated pregabalin as an augmentation treatment for resistant OCD.

Study design

• This 12-week, double-blind, placebo-controlled clinical trial evaluated the efficacy of adjunctive pregabalin in 56 patients who met DSM-5 criteria for OCD and had not responded to ≥12 weeks of treatment with an adequate and stable dose of sertraline (baseline Y-BOCS score ≥18).
• Individuals who had other major psychiatric disorders, major medical problems, were pregnant, or had past substance or alcohol abuse were excluded.
• Participants were randomly assigned to receive sertraline plus pregabalin (n = 28) or sertraline plus placebo (n = 28). Mean sertraline dosage was 256.5 mg/d; range was 100 mg/d to 300 mg/d. Pregabalin was started at 75 mg/d and increased by 75 mg increments weekly. The mean dosage was 185.9 mg/d; range was 75 mg/d to 225 mg/d.
• The primary outcome measure was change in Y-BOCS score. A decrease >35% in Y-BOCS score was considered a significant response rate.

Outcomes

• There was a statistically significant decrease in Y-BOCS score in patients who received pregabalin. In the pregabalin group, 57.14% of patients (n = 16) showed a >35% decrease in Y-BOCS score compared with 7.14% of patients (n = 2) in the placebo group (P < .01).
• The pregabalin group showed good tolerability and safety. There were no clinically significant adverse effects.

Conclusion

• In patients with treatment-resistant OCD who did not respond to sertraline monotherapy, augmentation with pregabalin significantly decreases Y-BOCS scores compared with placebo.

Continue to: Reference 7...

Recent evidence suggests dysregulation of serotonin and dopamine in patients with OCD. Methylphenidate is a dopamine and norepinephrine inhibitor and releaser. A limited number of studies have suggested stimulants might be useful for OCD patients. Zheng et al¹⁶ conducted a pilot trial to determine whether methylphenidate augmentation may be of benefit in the management of outpatients with OCD.

Study design

• In an 8-week, double-blind, randomized, placebo-controlled trial, 44 patients (29 [66%] men, with a mean [SD] age of 24.7 [6]) with treatment-refractory OCD were randomized to receive fluvoxamine 250 mg/d plus methylphenidate extended-release (MPH-ER) 36 mg/d or fluvoxamine 250 mg/d plus placebo. The MPH-ER dose was 18 mg/d for the first 4 weeks and 36 mg/d for the rest of the trial.
• Biweekly assessments consisted of scores on the Y-BOCS, Hamilton Depression Rating Scale (HDRS), and Hamilton Anxiety Rating Scale (HAM-A).
• The primary outcomes were improvement in Y-BOCS score and the clinical response rate. Secondary outcomes included a change in score on the Y-BOCS subscales, HARS, and HAM-A. Data were analyzed with the intention-to-treat sample.

Outcomes

• Forty-one patients finished the trial. The baseline Y-BOCS total scores and subscale scores did not differ significantly between the 2 groups.
• Improvements in Y-BOCS total score and obsession subscale score were more prominent in the fluvoxamine plus MPH-ER group compared with the placebo group (P < .001).
• HDRS score decreased in both the placebo and MPH-ER groups. HAM-A scores decreased significantly in the MPH-ER plus fluvoxamine group compared with the placebo group.

Conclusion

• This study demonstrated that the combination of fluvoxamine and MPH-ER produces a higher and faster response rate than fluvoxamine plus placebo in patients with OCD.

8. Arabzadeh S, Shahhossenie M, Mesgarpour B, et al. L-carnosine as an adjuvant to fluvoxamine in treatment of obsessive compulsive disorder: a randomized double-blind study. Hum Psychopharmacol. 2017;32(4). doi:10.1002/hup.2584

Glutamate dysregulation is implicated in the pathogenesis of OCD. Glutamate-modulating agents have been used to treat OCD. Studies have shown L-carnosine has a neuroprotective role via its modulatory effect on glutamate. Arabzadeh et al¹⁷ evaluated the efficacy of L-carnosine as an adjuvant to fluvoxamine for treating OCD.

Study design

• This 10-week, randomized, double-blind, placebo-controlled trial evaluated the efficacy of adjunctive L-carnosine in 40 patients age 18 to 60 who met DSM-5 criteria for OCD and had moderate to severe OCD (Y-BOCS score ≥21).
• Individuals with any other DSM-5 major psychiatric disorders, serious medical or neurologic illness, substance dependence (other than caffeine or nicotine), mental retardation (based on clinical judgment), were pregnant or breastfeeding, had any contraindication for the use of L‐carnosine or fluvoxamine, or received any psychotropic drugs in the previous 6 weeks were excluded.
• Participants received fluvoxamine 100 mg/d for the first 4 weeks and 200 mg/d for the next 6 weeks plus either L-carnosine 500 mg twice daily or placebo. This dosage of L-carnosine was chosen because previously it had been tolerated and effective.
• The primary outcome measure was difference in Y-BOCS total scores. Secondary outcomes were differences in Y-BOCS obsession and compulsion subscale scores and differences in change in score on Y-BOCS total and subscale scores from baseline.

Outcomes

• The L-carnosine group experienced a significant decrease in Y-BOCS total score (P < .001), obsession subscale score (P < .01), and compulsion subscale score (P < .01).
• The group that received fluvoxamine plus L-carnosine also experienced a more complete response (P = .03).
• The L-carnosine group showed good tolerability and safety. There were no clinically significant adverse effects.

Conclusion

• L-carnosine significantly reduces OCD symptoms when used as an adjuvant to fluvoxamine.

In this month’s issue of GI & Hepatology News, we celebrate the recently named recipients of this year’s AGA Recognition Prizes, several of whom I am privileged to work with on a daily basis. We also welcome the newest members of AGA’s Governing Board, Maria T. Abreu, MD, AGAF, who is an outstanding leader and representative of a much larger group of volunteer members who work tirelessly to advance AGA’s initiatives to enhance the clinical practice of gastroenterology and improve patient outcomes. The nominating committee also appointed the following slate of councilors, which is subject to membership vote: Kim Barrett, PhD, AGAF; Lawrence Kosinski, MD, MBA, AGAF; and Sheryl Pfeil, MD, AGAF.

This month’s issue also highlights two newly-developed clinical risk-prediction tools – one designed to assist clinicians in predicting alcoholic hepatitis mortality, and another designed to identify inflammatory bowel disease (IBD) patients at high-risk of developing venous thromboembolism (VTE) post-hospitalization. While no prediction model is perfect, these tools can positively impact clinical decision-making and contribute to improved patient outcomes. We also include recommendations on managing IBD in older patients, and report on a study suggesting an increase in late-stage cancer diagnoses in the wake of the COVID-19 pandemic. AGA’s new clinical guideline on systemic therapy for hepatocellular carcinoma and Clinical Practice Update on non-invasive colorectal cancer screening also are featured. Finally, in this month’s Practice Management Toolbox, Dr. Feuerstein, Dr. Sofia, Dr. Guha, and Dr. Streett offer timely recommendations regarding how to overcome existing barriers to achieve high-value IBD care.

Megan A. Adams, MD, JD, MSc
Editor in Chief

In this month’s issue of GI & Hepatology News, we celebrate the recently named recipients of this year’s AGA Recognition Prizes, several of whom I am privileged to work with on a daily basis. We also welcome the newest members of AGA’s Governing Board, Maria T. Abreu, MD, AGAF, who is an outstanding leader and representative of a much larger group of volunteer members who work tirelessly to advance AGA’s initiatives to enhance the clinical practice of gastroenterology and improve patient outcomes. The nominating committee also appointed the following slate of councilors, which is subject to membership vote: Kim Barrett, PhD, AGAF; Lawrence Kosinski, MD, MBA, AGAF; and Sheryl Pfeil, MD, AGAF.

This month’s issue also highlights two newly-developed clinical risk-prediction tools – one designed to assist clinicians in predicting alcoholic hepatitis mortality, and another designed to identify inflammatory bowel disease (IBD) patients at high-risk of developing venous thromboembolism (VTE) post-hospitalization. While no prediction model is perfect, these tools can positively impact clinical decision-making and contribute to improved patient outcomes. We also include recommendations on managing IBD in older patients, and report on a study suggesting an increase in late-stage cancer diagnoses in the wake of the COVID-19 pandemic. AGA’s new clinical guideline on systemic therapy for hepatocellular carcinoma and Clinical Practice Update on non-invasive colorectal cancer screening also are featured. Finally, in this month’s Practice Management Toolbox, Dr. Feuerstein, Dr. Sofia, Dr. Guha, and Dr. Streett offer timely recommendations regarding how to overcome existing barriers to achieve high-value IBD care.

Megan A. Adams, MD, JD, MSc
Editor in Chief

In this month’s issue of GI & Hepatology News, we celebrate the recently named recipients of this year’s AGA Recognition Prizes, several of whom I am privileged to work with on a daily basis. We also welcome the newest members of AGA’s Governing Board, Maria T. Abreu, MD, AGAF, who is an outstanding leader and representative of a much larger group of volunteer members who work tirelessly to advance AGA’s initiatives to enhance the clinical practice of gastroenterology and improve patient outcomes. The nominating committee also appointed the following slate of councilors, which is subject to membership vote: Kim Barrett, PhD, AGAF; Lawrence Kosinski, MD, MBA, AGAF; and Sheryl Pfeil, MD, AGAF.

This month’s issue also highlights two newly-developed clinical risk-prediction tools – one designed to assist clinicians in predicting alcoholic hepatitis mortality, and another designed to identify inflammatory bowel disease (IBD) patients at high-risk of developing venous thromboembolism (VTE) post-hospitalization. While no prediction model is perfect, these tools can positively impact clinical decision-making and contribute to improved patient outcomes. We also include recommendations on managing IBD in older patients, and report on a study suggesting an increase in late-stage cancer diagnoses in the wake of the COVID-19 pandemic. AGA’s new clinical guideline on systemic therapy for hepatocellular carcinoma and Clinical Practice Update on non-invasive colorectal cancer screening also are featured. Finally, in this month’s Practice Management Toolbox, Dr. Feuerstein, Dr. Sofia, Dr. Guha, and Dr. Streett offer timely recommendations regarding how to overcome existing barriers to achieve high-value IBD care.

Megan A. Adams, MD, JD, MSc
Editor in Chief

Correct answer: B. Absence of ganglion cells on rectal biopsy. 
 
Rationale  
Hirschsprung's disease occurs in approximately 1 out of 5,000 live births and is caused by absence of ganglion cells in the myenteric plexus of the intestine. The condition arises from failure of the neural crest cells to fully migrate caudally along the intestine during early gestation, resulting in a distal portion of the intestine being aganglionic. Rectal and distal sigmoid involvement is seen in around 85% of cases, with the other 15 percent involving more proximal intestine. It can rarely involve the entire colon and small intestine. Ganglion cells inhibit local smooth muscles, resulting in the characteristic inability for aganglionic bowel to relax. This lack of inhibition gives rise to the absence of rectoanal inhibitory reflex (RAIRs) during anorectal manometry. The lack of inhibition also produces a transition zone on contrast enema, with the distal aganglionic bowel being narrow and the more proximal bowel containing ganglia being dilated. Lack of meconium passage in the first 48 hours of life raises concern for Hirschsprung's disease. Other causes for possible failure to pass meconium include cystic fibrosis, anorectal malformation, small left colon syndrome, meconium plug syndrome and megacystis-microcolon-intestinal hypoperistalsis syndrome.  
 
References 
Kenny, S et al. Semin Pediatr Surg. 2010 Aug;19(3):194-200. 
Wyllie R et al. Pediatric Gastrointestinal and Liver Disease. 4th edition. Elsevier Saunders, Philadelphia, 2011.

Correct answer: B. Absence of ganglion cells on rectal biopsy. 
 
Rationale  
Hirschsprung's disease occurs in approximately 1 out of 5,000 live births and is caused by absence of ganglion cells in the myenteric plexus of the intestine. The condition arises from failure of the neural crest cells to fully migrate caudally along the intestine during early gestation, resulting in a distal portion of the intestine being aganglionic. Rectal and distal sigmoid involvement is seen in around 85% of cases, with the other 15 percent involving more proximal intestine. It can rarely involve the entire colon and small intestine. Ganglion cells inhibit local smooth muscles, resulting in the characteristic inability for aganglionic bowel to relax. This lack of inhibition gives rise to the absence of rectoanal inhibitory reflex (RAIRs) during anorectal manometry. The lack of inhibition also produces a transition zone on contrast enema, with the distal aganglionic bowel being narrow and the more proximal bowel containing ganglia being dilated. Lack of meconium passage in the first 48 hours of life raises concern for Hirschsprung's disease. Other causes for possible failure to pass meconium include cystic fibrosis, anorectal malformation, small left colon syndrome, meconium plug syndrome and megacystis-microcolon-intestinal hypoperistalsis syndrome.  
 
References 
Kenny, S et al. Semin Pediatr Surg. 2010 Aug;19(3):194-200. 
Wyllie R et al. Pediatric Gastrointestinal and Liver Disease. 4th edition. Elsevier Saunders, Philadelphia, 2011.

Correct answer: B. Absence of ganglion cells on rectal biopsy. 
 
Rationale  
Hirschsprung's disease occurs in approximately 1 out of 5,000 live births and is caused by absence of ganglion cells in the myenteric plexus of the intestine. The condition arises from failure of the neural crest cells to fully migrate caudally along the intestine during early gestation, resulting in a distal portion of the intestine being aganglionic. Rectal and distal sigmoid involvement is seen in around 85% of cases, with the other 15 percent involving more proximal intestine. It can rarely involve the entire colon and small intestine. Ganglion cells inhibit local smooth muscles, resulting in the characteristic inability for aganglionic bowel to relax. This lack of inhibition gives rise to the absence of rectoanal inhibitory reflex (RAIRs) during anorectal manometry. The lack of inhibition also produces a transition zone on contrast enema, with the distal aganglionic bowel being narrow and the more proximal bowel containing ganglia being dilated. Lack of meconium passage in the first 48 hours of life raises concern for Hirschsprung's disease. Other causes for possible failure to pass meconium include cystic fibrosis, anorectal malformation, small left colon syndrome, meconium plug syndrome and megacystis-microcolon-intestinal hypoperistalsis syndrome.  
 
References 
Kenny, S et al. Semin Pediatr Surg. 2010 Aug;19(3):194-200. 
Wyllie R et al. Pediatric Gastrointestinal and Liver Disease. 4th edition. Elsevier Saunders, Philadelphia, 2011.

Correct answer: A. Amyloidosis involving the small intestine 
 
Rationale  
This patient has a protein-losing enteropathy as indicated by his diarrhea, peripheral edema, and positive stool alpha-1 antitrypsin test. Multiple diseases, particularly in their later stages, can be associated with a protein-losing enteropathy including primary intestinal lymphangectasia, Crohn's disease of the small intestine, small intestinal bacterial overgrowth (SIBO), and amyloidosis of the small intestine (A). Celiac disease (B) is not associated with protein-losing enteropathy. While Crohn's disease can be associated with protein-losing enteropathy, ulcerative colitis (C) is not usually associated with it. Small bowel dysmotility (D) does not impact absorption or secretion unless associated with SIBO, making this a wrong answer.

Correct answer: A. Amyloidosis involving the small intestine 
 
Rationale  
This patient has a protein-losing enteropathy as indicated by his diarrhea, peripheral edema, and positive stool alpha-1 antitrypsin test. Multiple diseases, particularly in their later stages, can be associated with a protein-losing enteropathy including primary intestinal lymphangectasia, Crohn's disease of the small intestine, small intestinal bacterial overgrowth (SIBO), and amyloidosis of the small intestine (A). Celiac disease (B) is not associated with protein-losing enteropathy. While Crohn's disease can be associated with protein-losing enteropathy, ulcerative colitis (C) is not usually associated with it. Small bowel dysmotility (D) does not impact absorption or secretion unless associated with SIBO, making this a wrong answer.

Correct answer: A. Amyloidosis involving the small intestine 
 
Rationale  
This patient has a protein-losing enteropathy as indicated by his diarrhea, peripheral edema, and positive stool alpha-1 antitrypsin test. Multiple diseases, particularly in their later stages, can be associated with a protein-losing enteropathy including primary intestinal lymphangectasia, Crohn's disease of the small intestine, small intestinal bacterial overgrowth (SIBO), and amyloidosis of the small intestine (A). Celiac disease (B) is not associated with protein-losing enteropathy. While Crohn's disease can be associated with protein-losing enteropathy, ulcerative colitis (C) is not usually associated with it. Small bowel dysmotility (D) does not impact absorption or secretion unless associated with SIBO, making this a wrong answer.

Only a small number of pediatric hematologist oncologists and even fewer of our adult counterparts feel comfortable evaluating and treating vascular anomalies. 

While admittedly rare, these conditions are still common enough that clinicians in many disciplines encounter them. Hematologist/oncologists are most likely to see vascular malformations, which often present as mass lesions. Complications of these disorders occur across the hematology-oncology spectrum and include clots, pulmonary emboli, cancer predisposition, and an array of functional and psychosocial disorders. 

Vascular anomalies are broadly categorized as vascular tumors or malformations. The tumors include hemangiomas, locally aggressive lesions, and true cancers. Malformations can be isolated disorders of one or more blood vessel types (veins, arteries, capillaries or lymphatics), or they can be one part of syndromic disorders. Lymphedema also falls under the heading of vascular anomalies. To make the terminology less confusing, in 2018 the International Society for the Study of Vascular Anomalies refined its classification scheme.

Vascular malformations are thought to be congenital. Although some are obvious at birth, others aren’t apparent until adulthood. In most cases, they grow with a child and may do so disproportionately at puberty and with pregnancies. The fact that vascular malformations persist into adulthood is one reason why their care should be integral to medical hematology-oncology. 

Although the cause of a vascular malformation is not always known, a wide range of genetic mutations thought to be pathogenic have been reported. These mutations are usually somatic (only within the involved tissues, not in the blood or germ cells and therefore, not heritable) and tend to cluster in the VEGF-PIK3CA and RAS-MAP signaling pathways. 

These genes and pathways will be familiar to any oncologist who cares for patients with solid tumors, notably breast cancer or melanoma. However, unlike the clonal expansion seen in cancers, most vascular malformations will express pathogenic mutations in less than 20% of vascular endothelium within a malformation. 

Since 2008, medical management has been limited to sirolimus (rapamycin), a mammalian target of rapamycin inhibitor, which can be effective even when mTOR mutations aren’t apparent. In a seminal phase 2 trial of 57 patients with complex vascular anomalies who were aged 0-29 years, 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. None had complete responses. These data highlight the need for more effective treatments.

Recently, vascular anomalists have begun to repurpose drugs from adult oncology that specifically target pathogenic mutations. Some studies underway include Novartis’ international Alpelisib (Piqray) clinical trial for adults and children with PIK3CA-related overgrowth syndromes (NCT04589650) and Merck’s follow-up study of the AKT inhibitor miransertib for PROS and Proteus syndrome. Doses tend to be lower than those used to treat cancers. To date, these have been generally well-tolerated, with sometimes striking but preliminary evidence of efficacy. 

During the past 2 years, symposia on vascular anomalies at the annual meeting of the American Society of Hematology have launched what we are hoping is just the start of a broader discussion. In 2020, Fran Blei, MD, chaired Vascular Anomalies 101: Case-Based Discussion on the Diagnosis, Treatment and Lifelong Care of These Patients, and in 2021, Adrienne Hammill, MD, PhD, and Dr. Raj Kasthuri, MBBS, MD, chaired a more specialized symposium: Hereditary Hemorrhagic Telangiectasia (HHT): A Practical Guide to Management. 

As awareness of vascular anomalies grows and research on effective treatments continues, a new focus on this natural offshoot of hematology and oncology offers adult and pediatric specialists in our field a fertile area for career development.

Dr. Blatt is in the division of pediatric hematology oncology at the University of North Carolina at Chapel Hill. She disclosed no relevant financial relationships.

Only a small number of pediatric hematologist oncologists and even fewer of our adult counterparts feel comfortable evaluating and treating vascular anomalies. 

While admittedly rare, these conditions are still common enough that clinicians in many disciplines encounter them. Hematologist/oncologists are most likely to see vascular malformations, which often present as mass lesions. Complications of these disorders occur across the hematology-oncology spectrum and include clots, pulmonary emboli, cancer predisposition, and an array of functional and psychosocial disorders. 

Vascular anomalies are broadly categorized as vascular tumors or malformations. The tumors include hemangiomas, locally aggressive lesions, and true cancers. Malformations can be isolated disorders of one or more blood vessel types (veins, arteries, capillaries or lymphatics), or they can be one part of syndromic disorders. Lymphedema also falls under the heading of vascular anomalies. To make the terminology less confusing, in 2018 the International Society for the Study of Vascular Anomalies refined its classification scheme.

Vascular malformations are thought to be congenital. Although some are obvious at birth, others aren’t apparent until adulthood. In most cases, they grow with a child and may do so disproportionately at puberty and with pregnancies. The fact that vascular malformations persist into adulthood is one reason why their care should be integral to medical hematology-oncology. 

Although the cause of a vascular malformation is not always known, a wide range of genetic mutations thought to be pathogenic have been reported. These mutations are usually somatic (only within the involved tissues, not in the blood or germ cells and therefore, not heritable) and tend to cluster in the VEGF-PIK3CA and RAS-MAP signaling pathways. 

These genes and pathways will be familiar to any oncologist who cares for patients with solid tumors, notably breast cancer or melanoma. However, unlike the clonal expansion seen in cancers, most vascular malformations will express pathogenic mutations in less than 20% of vascular endothelium within a malformation. 

Since 2008, medical management has been limited to sirolimus (rapamycin), a mammalian target of rapamycin inhibitor, which can be effective even when mTOR mutations aren’t apparent. In a seminal phase 2 trial of 57 patients with complex vascular anomalies who were aged 0-29 years, 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. None had complete responses. These data highlight the need for more effective treatments.

Recently, vascular anomalists have begun to repurpose drugs from adult oncology that specifically target pathogenic mutations. Some studies underway include Novartis’ international Alpelisib (Piqray) clinical trial for adults and children with PIK3CA-related overgrowth syndromes (NCT04589650) and Merck’s follow-up study of the AKT inhibitor miransertib for PROS and Proteus syndrome. Doses tend to be lower than those used to treat cancers. To date, these have been generally well-tolerated, with sometimes striking but preliminary evidence of efficacy. 

During the past 2 years, symposia on vascular anomalies at the annual meeting of the American Society of Hematology have launched what we are hoping is just the start of a broader discussion. In 2020, Fran Blei, MD, chaired Vascular Anomalies 101: Case-Based Discussion on the Diagnosis, Treatment and Lifelong Care of These Patients, and in 2021, Adrienne Hammill, MD, PhD, and Dr. Raj Kasthuri, MBBS, MD, chaired a more specialized symposium: Hereditary Hemorrhagic Telangiectasia (HHT): A Practical Guide to Management. 

As awareness of vascular anomalies grows and research on effective treatments continues, a new focus on this natural offshoot of hematology and oncology offers adult and pediatric specialists in our field a fertile area for career development.

Dr. Blatt is in the division of pediatric hematology oncology at the University of North Carolina at Chapel Hill. She disclosed no relevant financial relationships.

Only a small number of pediatric hematologist oncologists and even fewer of our adult counterparts feel comfortable evaluating and treating vascular anomalies. 

While admittedly rare, these conditions are still common enough that clinicians in many disciplines encounter them. Hematologist/oncologists are most likely to see vascular malformations, which often present as mass lesions. Complications of these disorders occur across the hematology-oncology spectrum and include clots, pulmonary emboli, cancer predisposition, and an array of functional and psychosocial disorders. 

Vascular anomalies are broadly categorized as vascular tumors or malformations. The tumors include hemangiomas, locally aggressive lesions, and true cancers. Malformations can be isolated disorders of one or more blood vessel types (veins, arteries, capillaries or lymphatics), or they can be one part of syndromic disorders. Lymphedema also falls under the heading of vascular anomalies. To make the terminology less confusing, in 2018 the International Society for the Study of Vascular Anomalies refined its classification scheme.

Vascular malformations are thought to be congenital. Although some are obvious at birth, others aren’t apparent until adulthood. In most cases, they grow with a child and may do so disproportionately at puberty and with pregnancies. The fact that vascular malformations persist into adulthood is one reason why their care should be integral to medical hematology-oncology. 

Although the cause of a vascular malformation is not always known, a wide range of genetic mutations thought to be pathogenic have been reported. These mutations are usually somatic (only within the involved tissues, not in the blood or germ cells and therefore, not heritable) and tend to cluster in the VEGF-PIK3CA and RAS-MAP signaling pathways. 

These genes and pathways will be familiar to any oncologist who cares for patients with solid tumors, notably breast cancer or melanoma. However, unlike the clonal expansion seen in cancers, most vascular malformations will express pathogenic mutations in less than 20% of vascular endothelium within a malformation. 

Since 2008, medical management has been limited to sirolimus (rapamycin), a mammalian target of rapamycin inhibitor, which can be effective even when mTOR mutations aren’t apparent. In a seminal phase 2 trial of 57 patients with complex vascular anomalies who were aged 0-29 years, 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. None had complete responses. These data highlight the need for more effective treatments.

Recently, vascular anomalists have begun to repurpose drugs from adult oncology that specifically target pathogenic mutations. Some studies underway include Novartis’ international Alpelisib (Piqray) clinical trial for adults and children with PIK3CA-related overgrowth syndromes (NCT04589650) and Merck’s follow-up study of the AKT inhibitor miransertib for PROS and Proteus syndrome. Doses tend to be lower than those used to treat cancers. To date, these have been generally well-tolerated, with sometimes striking but preliminary evidence of efficacy. 

During the past 2 years, symposia on vascular anomalies at the annual meeting of the American Society of Hematology have launched what we are hoping is just the start of a broader discussion. In 2020, Fran Blei, MD, chaired Vascular Anomalies 101: Case-Based Discussion on the Diagnosis, Treatment and Lifelong Care of These Patients, and in 2021, Adrienne Hammill, MD, PhD, and Dr. Raj Kasthuri, MBBS, MD, chaired a more specialized symposium: Hereditary Hemorrhagic Telangiectasia (HHT): A Practical Guide to Management. 

As awareness of vascular anomalies grows and research on effective treatments continues, a new focus on this natural offshoot of hematology and oncology offers adult and pediatric specialists in our field a fertile area for career development.

Dr. Blatt is in the division of pediatric hematology oncology at the University of North Carolina at Chapel Hill. She disclosed no relevant financial relationships.

Pointing a finger at COVID-19

The battle against COVID-19 is seemingly never ending. It’s been 2 years and still we struggle against the virus. But now, a new hero rises against the eternal menace, a powerful weapon against this scourge of humanity. And that weapon? Finger length.

Before you break out the sad trombone, hear us out. One of the big questions around COVID-19 is the role testosterone plays in its severity: Does low testosterone increase or decrease the odds of contracting severe COVID-19? To help answer that question, English researchers have published a study analyzing finger length ratios in both COVID-19 patients and a healthy control group. That seems random, but high testosterone in the womb leads to longer ring fingers in adulthood, while high estrogen leads to longer index fingers.

PxHere

According to the researchers, those who had significant left hand–right hand differences in the ratio between the second and fourth digits, as well as the third and fifth digits, were significantly more likely to have severe COVID-19 compared with those with more even ratios. Those with “feminized” short little fingers were also at risk. Those large ratio differences indicate low testosterone and high estrogen, which may explain why elderly men are at such high risk for severe COVID-19. Testosterone naturally falls off as men get older.

The results add credence to clinical trials looking to use testosterone-boosting drugs against COVID-19, the researchers said. It also gives credence to LOTME’s brand-new 12-step finger strength fitness routine and our branded finger weights. Now just $19.95! It’s the bargain of the century! Boost your testosterone naturally and protect yourself from COVID-19! We promise it’s not a scam.
 

Some emergencies need a superhero

Last week, we learned about the most boring person in the world. This week just happens to be opposite week, so we’re looking at a candidate for the most interesting person. Someone who can swoop down from the sky to save the injured and helpless. Someone who can go where helicopters fear to tread. Someone with jet engines for arms. Superhero-type stuff.

Richard Browning/Gravity Industries

The Great North Air Ambulance Service (GNAAS), a charitable organization located in the United Kingdom, recently announced that one of its members has completed training on the Gravity Industries Jet Suit. The suit “has two engines on each arm and a larger engine on the back [that] provide up to 317 pounds of thrust,” Interesting Engineering explained.

GNAAS is putting the suit into operation in England’s Lake District National Park, which includes mountainous terrain that is not very hospitable to helicopter landings. A paramedic using the suit can reach hikers stranded on mountainsides much faster than rescuers who have to run or hike from the nearest helicopter landing site.

“Everyone looks at the wow factor and the fact we are the world’s first jet suit paramedics, but for us, it’s about delivering patient care,” GNAAS’ Andy Mawson told Interesting Engineering. Sounds like superhero-speak to us.

So if you’re in the Lake District and have taken a bit of a tumble, you can call a superhero on your cell phone or you can use this to summon one.
 

Why we’re rejecting food as medicine

Humans have been using food to treat ailments much longer than we’ve had the advances of modern medicine. So why have we rejected its worth in our treatment processes? And what can be done to change that? The Center for Food as Medicine and the Hunter College NYC Food Policy Center just released a 335-page report that answers those questions.

phototake/ThinkStock

First, the why: Meals in health care settings are not medically designed to help with the specific needs of the patient. Produce-prescription and nutrition-incentive programs don’t have the government funds to fully support them. And a lot of medical schools don’t even require students to take a basic nutrition course. So there’s a lack of knowledge and a disconnect between health care providers and food as a resource.

Then there’s a lack of trust in the food industry and their validity. Social media uses food as a means of promoting “pseudoscientific alternative medicine” or spreading false info, pushing away legitimate providers. The food industry has had its fingers in food science studies and an almost mafia-esque chokehold on American dietary guidelines. No wonder food for medicine is getting the boot!

To change the situation, the report offers 10 key recommendations on how to advance the idea of incorporating food into medicine for treatment and prevention. They include boosting the funding for research, making hospitals more food-as-medicine focused, expanding federal programs, and improving public awareness on the role nutrition can play in medical treatment or prevention.

So maybe instead of rejecting food outright, we should be looking a little deeper at how we can use it to our advantage. Just a thought: Ice cream as an antidepressant.
 

Being rude is a good thing, apparently

If you’ve ever been called argumentative, stubborn, or unpleasant, then this LOTME is for you. Researchers at the University of Geneva have found that people who are more stubborn and hate to conform have brains that are more protected against Alzheimer’s disease. That type of personality seems to preserve the part of the brain that usually deteriorates as we grow older.

Piqsels

The original hypothesis that personality may have a protective effect against brain degeneration led the investigators to conduct cognitive and personality assessments of 65 elderly participants over a 5-year period. Researchers have been attempting to create vaccines to protect against Alzheimer’s disease, but these new findings offer a nonbiological way to help.

“For a long time, the brain is able to compensate by activating alternative networks; when the first clinical signs appear, however, it is unfortunately often too late. The identification of early biomarkers is therefore essential for … effective disease management,” lead author Panteleimon Giannakopoulos, MD, said in a Study Finds report.

You may be wondering how people with more agreeable and less confrontational personalities can seek help. Well, researchers are working on that, too. It’s a complex situation, but as always, we’re rooting for you, science!

At least now you can take solace in the fact that your elderly next-door neighbor who yells at you for stepping on his lawn is probably more protected against Alzheimer’s disease.

Pointing a finger at COVID-19

The battle against COVID-19 is seemingly never ending. It’s been 2 years and still we struggle against the virus. But now, a new hero rises against the eternal menace, a powerful weapon against this scourge of humanity. And that weapon? Finger length.

Before you break out the sad trombone, hear us out. One of the big questions around COVID-19 is the role testosterone plays in its severity: Does low testosterone increase or decrease the odds of contracting severe COVID-19? To help answer that question, English researchers have published a study analyzing finger length ratios in both COVID-19 patients and a healthy control group. That seems random, but high testosterone in the womb leads to longer ring fingers in adulthood, while high estrogen leads to longer index fingers.

PxHere

According to the researchers, those who had significant left hand–right hand differences in the ratio between the second and fourth digits, as well as the third and fifth digits, were significantly more likely to have severe COVID-19 compared with those with more even ratios. Those with “feminized” short little fingers were also at risk. Those large ratio differences indicate low testosterone and high estrogen, which may explain why elderly men are at such high risk for severe COVID-19. Testosterone naturally falls off as men get older.

The results add credence to clinical trials looking to use testosterone-boosting drugs against COVID-19, the researchers said. It also gives credence to LOTME’s brand-new 12-step finger strength fitness routine and our branded finger weights. Now just $19.95! It’s the bargain of the century! Boost your testosterone naturally and protect yourself from COVID-19! We promise it’s not a scam.
 

Some emergencies need a superhero

Last week, we learned about the most boring person in the world. This week just happens to be opposite week, so we’re looking at a candidate for the most interesting person. Someone who can swoop down from the sky to save the injured and helpless. Someone who can go where helicopters fear to tread. Someone with jet engines for arms. Superhero-type stuff.

Richard Browning/Gravity Industries

The Great North Air Ambulance Service (GNAAS), a charitable organization located in the United Kingdom, recently announced that one of its members has completed training on the Gravity Industries Jet Suit. The suit “has two engines on each arm and a larger engine on the back [that] provide up to 317 pounds of thrust,” Interesting Engineering explained.

GNAAS is putting the suit into operation in England’s Lake District National Park, which includes mountainous terrain that is not very hospitable to helicopter landings. A paramedic using the suit can reach hikers stranded on mountainsides much faster than rescuers who have to run or hike from the nearest helicopter landing site.

“Everyone looks at the wow factor and the fact we are the world’s first jet suit paramedics, but for us, it’s about delivering patient care,” GNAAS’ Andy Mawson told Interesting Engineering. Sounds like superhero-speak to us.

So if you’re in the Lake District and have taken a bit of a tumble, you can call a superhero on your cell phone or you can use this to summon one.
 

Why we’re rejecting food as medicine

Humans have been using food to treat ailments much longer than we’ve had the advances of modern medicine. So why have we rejected its worth in our treatment processes? And what can be done to change that? The Center for Food as Medicine and the Hunter College NYC Food Policy Center just released a 335-page report that answers those questions.

phototake/ThinkStock

First, the why: Meals in health care settings are not medically designed to help with the specific needs of the patient. Produce-prescription and nutrition-incentive programs don’t have the government funds to fully support them. And a lot of medical schools don’t even require students to take a basic nutrition course. So there’s a lack of knowledge and a disconnect between health care providers and food as a resource.

Then there’s a lack of trust in the food industry and their validity. Social media uses food as a means of promoting “pseudoscientific alternative medicine” or spreading false info, pushing away legitimate providers. The food industry has had its fingers in food science studies and an almost mafia-esque chokehold on American dietary guidelines. No wonder food for medicine is getting the boot!

To change the situation, the report offers 10 key recommendations on how to advance the idea of incorporating food into medicine for treatment and prevention. They include boosting the funding for research, making hospitals more food-as-medicine focused, expanding federal programs, and improving public awareness on the role nutrition can play in medical treatment or prevention.

So maybe instead of rejecting food outright, we should be looking a little deeper at how we can use it to our advantage. Just a thought: Ice cream as an antidepressant.
 

Being rude is a good thing, apparently

If you’ve ever been called argumentative, stubborn, or unpleasant, then this LOTME is for you. Researchers at the University of Geneva have found that people who are more stubborn and hate to conform have brains that are more protected against Alzheimer’s disease. That type of personality seems to preserve the part of the brain that usually deteriorates as we grow older.

Piqsels

The original hypothesis that personality may have a protective effect against brain degeneration led the investigators to conduct cognitive and personality assessments of 65 elderly participants over a 5-year period. Researchers have been attempting to create vaccines to protect against Alzheimer’s disease, but these new findings offer a nonbiological way to help.

“For a long time, the brain is able to compensate by activating alternative networks; when the first clinical signs appear, however, it is unfortunately often too late. The identification of early biomarkers is therefore essential for … effective disease management,” lead author Panteleimon Giannakopoulos, MD, said in a Study Finds report.

You may be wondering how people with more agreeable and less confrontational personalities can seek help. Well, researchers are working on that, too. It’s a complex situation, but as always, we’re rooting for you, science!

At least now you can take solace in the fact that your elderly next-door neighbor who yells at you for stepping on his lawn is probably more protected against Alzheimer’s disease.

Pointing a finger at COVID-19

The battle against COVID-19 is seemingly never ending. It’s been 2 years and still we struggle against the virus. But now, a new hero rises against the eternal menace, a powerful weapon against this scourge of humanity. And that weapon? Finger length.

Before you break out the sad trombone, hear us out. One of the big questions around COVID-19 is the role testosterone plays in its severity: Does low testosterone increase or decrease the odds of contracting severe COVID-19? To help answer that question, English researchers have published a study analyzing finger length ratios in both COVID-19 patients and a healthy control group. That seems random, but high testosterone in the womb leads to longer ring fingers in adulthood, while high estrogen leads to longer index fingers.

PxHere

According to the researchers, those who had significant left hand–right hand differences in the ratio between the second and fourth digits, as well as the third and fifth digits, were significantly more likely to have severe COVID-19 compared with those with more even ratios. Those with “feminized” short little fingers were also at risk. Those large ratio differences indicate low testosterone and high estrogen, which may explain why elderly men are at such high risk for severe COVID-19. Testosterone naturally falls off as men get older.

The results add credence to clinical trials looking to use testosterone-boosting drugs against COVID-19, the researchers said. It also gives credence to LOTME’s brand-new 12-step finger strength fitness routine and our branded finger weights. Now just $19.95! It’s the bargain of the century! Boost your testosterone naturally and protect yourself from COVID-19! We promise it’s not a scam.
 

Some emergencies need a superhero

Last week, we learned about the most boring person in the world. This week just happens to be opposite week, so we’re looking at a candidate for the most interesting person. Someone who can swoop down from the sky to save the injured and helpless. Someone who can go where helicopters fear to tread. Someone with jet engines for arms. Superhero-type stuff.

Richard Browning/Gravity Industries

The Great North Air Ambulance Service (GNAAS), a charitable organization located in the United Kingdom, recently announced that one of its members has completed training on the Gravity Industries Jet Suit. The suit “has two engines on each arm and a larger engine on the back [that] provide up to 317 pounds of thrust,” Interesting Engineering explained.

GNAAS is putting the suit into operation in England’s Lake District National Park, which includes mountainous terrain that is not very hospitable to helicopter landings. A paramedic using the suit can reach hikers stranded on mountainsides much faster than rescuers who have to run or hike from the nearest helicopter landing site.

“Everyone looks at the wow factor and the fact we are the world’s first jet suit paramedics, but for us, it’s about delivering patient care,” GNAAS’ Andy Mawson told Interesting Engineering. Sounds like superhero-speak to us.

So if you’re in the Lake District and have taken a bit of a tumble, you can call a superhero on your cell phone or you can use this to summon one.
 

Why we’re rejecting food as medicine

Humans have been using food to treat ailments much longer than we’ve had the advances of modern medicine. So why have we rejected its worth in our treatment processes? And what can be done to change that? The Center for Food as Medicine and the Hunter College NYC Food Policy Center just released a 335-page report that answers those questions.

phototake/ThinkStock

First, the why: Meals in health care settings are not medically designed to help with the specific needs of the patient. Produce-prescription and nutrition-incentive programs don’t have the government funds to fully support them. And a lot of medical schools don’t even require students to take a basic nutrition course. So there’s a lack of knowledge and a disconnect between health care providers and food as a resource.

Then there’s a lack of trust in the food industry and their validity. Social media uses food as a means of promoting “pseudoscientific alternative medicine” or spreading false info, pushing away legitimate providers. The food industry has had its fingers in food science studies and an almost mafia-esque chokehold on American dietary guidelines. No wonder food for medicine is getting the boot!

To change the situation, the report offers 10 key recommendations on how to advance the idea of incorporating food into medicine for treatment and prevention. They include boosting the funding for research, making hospitals more food-as-medicine focused, expanding federal programs, and improving public awareness on the role nutrition can play in medical treatment or prevention.

So maybe instead of rejecting food outright, we should be looking a little deeper at how we can use it to our advantage. Just a thought: Ice cream as an antidepressant.
 

Being rude is a good thing, apparently

If you’ve ever been called argumentative, stubborn, or unpleasant, then this LOTME is for you. Researchers at the University of Geneva have found that people who are more stubborn and hate to conform have brains that are more protected against Alzheimer’s disease. That type of personality seems to preserve the part of the brain that usually deteriorates as we grow older.

Piqsels

The original hypothesis that personality may have a protective effect against brain degeneration led the investigators to conduct cognitive and personality assessments of 65 elderly participants over a 5-year period. Researchers have been attempting to create vaccines to protect against Alzheimer’s disease, but these new findings offer a nonbiological way to help.

“For a long time, the brain is able to compensate by activating alternative networks; when the first clinical signs appear, however, it is unfortunately often too late. The identification of early biomarkers is therefore essential for … effective disease management,” lead author Panteleimon Giannakopoulos, MD, said in a Study Finds report.

You may be wondering how people with more agreeable and less confrontational personalities can seek help. Well, researchers are working on that, too. It’s a complex situation, but as always, we’re rooting for you, science!

At least now you can take solace in the fact that your elderly next-door neighbor who yells at you for stepping on his lawn is probably more protected against Alzheimer’s disease.

Apologies up front to anyone who spends their weekends bird-watching or doing math for fun. They are among the people expected to be boring, based on stereotypes about what they do for work or how they spend their spare time, new research reveals.

Researchers surveyed more than 500 people across five related experiments to identify what people perceive as the most boring jobs, traits, and hobbies. They also report how we could all be missing out by spending as little time as possible with our tax consultant, accountant, or financial adviser outside of work.

People who work in banking, finance, accounting, data analytics, and cleaning topped the most boring list in the study, published earlier this month in Personality and Social Psychology Bulletin.

Sleeping, religion, watching television, observing animals, and spending spare time on mathematics were the stereotypical most boring hobbies and activities. The “observing animals” group includes people who bird-watch or study ants.

On the flip side, the top five most exciting jobs, in order, were in the performing arts, science, journalism, health professions, and teaching.

The researchers also looked at the how likely people are to avoid spending time with stereotypical dullards.

“Are people who are stereotyped as being boring avoided, if possible? Our current research shows that this is likely,” says Wijnand A.P. Van Tilburg, PhD, one of the researchers who did the study.

Beyond specific traits and stereotypes, Dr. Van Tilburg and colleagues found that boring people are seen as lacking skills and warmth.

“To our surprise, it appears that they are seen as both unfriendly and incompetent,” says Dr. Van Tilburg, an experimental social psychologist at the University of Essex in the United Kingdom.

What qualities do people most often ascribe to boring people? Besides being “dull,” “dry,” “bland,” and “not interesting,” common stereotypes include thinking someone who is likely boring will have no sense of humor, lack opinions, or complain.

The people surveyed also were more likely to place boring people in towns and small cities rather than large metropolitan areas.

A vicious cycle?

What’s the possible harm of relying on boring stereotypes? If people are stereotyped as being boring solely based on professions and hobbies, “then that suggests that they will incur the negative consequences associated with being a stereotypically boring person -- even when others haven’t actually interacted with them,” Dr. Van Tilburg says.

“Having a stereotypically boring profession or hobby may come with the inability to prove the biased perceivers wrong,” he says.

So making distinctions between stereotypes and realities is important, Dr. Van Tilburg says. “Those who have hobbies or occupations that are stereotypically boring do, of course, not actually have to be boring.”

Mark Leary, PhD, a professor in the department of psychology and neuroscience at Duke University in Durham, N.C., agrees. “The research actually dealt with stereotypes about the kinds of people who hold certain jobs, have certain hobbies, and live in certain places -- and not about boring people per se,” he says.

Dr. Leary points out that few people encounter bankers, tax experts, and others perceived as most boring outside a professional setting.

“When we have interactions with data analysts, accountants, insurance agents, and bankers, for example, those interactions are often boring not because the people are boring, but rather because the context is not interesting.”

To get past the preconceptions, “the best advice might be to get people to try to separate people from their roles when forming impressions of them.”

“We need to recognize that many of our interactions with other people are tied up in particular roles and topics and, thus, don’t reveal much about the other people themselves,” Dr. Leary says. “Maybe my accountant is the life of the party in other contexts.”
 

Dollars to avoid the dull?

The researchers also found that as the perception of how boring a person is increased, people were more likely to say they would avoid them.

To find a way to measure this avoidance, they asked people in the study how much money they would have to be paid to pal around with a perceived bore for 1 to 7 days. The payments people said they would need varied by perceptions that their boredom would be low, intermediate, or high.

As an example, they would require an average of $50 to spend one day with a highly boring person. That amount would double to $100 to spend almost 4 days in their company, and up to $230 for the week.

Dr. Leary says boredom happens when people try to pay attention to an experience or event. This means boredom goes beyond simple disinterest or trying to pay attention to someone that is not “intrinsically captivating.” When it takes more brain power to pay attention, you’ll perceive the experience as even more boring.

“Perhaps the best way to see if other people are actually boring is to talk about interesting things and see how they respond,” Dr. Leary says. “But, be careful: The topics you think make interesting conversations may be boring to others.”

A version of this article first appeared on WebMD.com.

Apologies up front to anyone who spends their weekends bird-watching or doing math for fun. They are among the people expected to be boring, based on stereotypes about what they do for work or how they spend their spare time, new research reveals.

Researchers surveyed more than 500 people across five related experiments to identify what people perceive as the most boring jobs, traits, and hobbies. They also report how we could all be missing out by spending as little time as possible with our tax consultant, accountant, or financial adviser outside of work.

People who work in banking, finance, accounting, data analytics, and cleaning topped the most boring list in the study, published earlier this month in Personality and Social Psychology Bulletin.

Sleeping, religion, watching television, observing animals, and spending spare time on mathematics were the stereotypical most boring hobbies and activities. The “observing animals” group includes people who bird-watch or study ants.

On the flip side, the top five most exciting jobs, in order, were in the performing arts, science, journalism, health professions, and teaching.

The researchers also looked at the how likely people are to avoid spending time with stereotypical dullards.

“Are people who are stereotyped as being boring avoided, if possible? Our current research shows that this is likely,” says Wijnand A.P. Van Tilburg, PhD, one of the researchers who did the study.

Beyond specific traits and stereotypes, Dr. Van Tilburg and colleagues found that boring people are seen as lacking skills and warmth.

“To our surprise, it appears that they are seen as both unfriendly and incompetent,” says Dr. Van Tilburg, an experimental social psychologist at the University of Essex in the United Kingdom.

What qualities do people most often ascribe to boring people? Besides being “dull,” “dry,” “bland,” and “not interesting,” common stereotypes include thinking someone who is likely boring will have no sense of humor, lack opinions, or complain.

The people surveyed also were more likely to place boring people in towns and small cities rather than large metropolitan areas.

A vicious cycle?

What’s the possible harm of relying on boring stereotypes? If people are stereotyped as being boring solely based on professions and hobbies, “then that suggests that they will incur the negative consequences associated with being a stereotypically boring person -- even when others haven’t actually interacted with them,” Dr. Van Tilburg says.

“Having a stereotypically boring profession or hobby may come with the inability to prove the biased perceivers wrong,” he says.

So making distinctions between stereotypes and realities is important, Dr. Van Tilburg says. “Those who have hobbies or occupations that are stereotypically boring do, of course, not actually have to be boring.”

Mark Leary, PhD, a professor in the department of psychology and neuroscience at Duke University in Durham, N.C., agrees. “The research actually dealt with stereotypes about the kinds of people who hold certain jobs, have certain hobbies, and live in certain places -- and not about boring people per se,” he says.

Dr. Leary points out that few people encounter bankers, tax experts, and others perceived as most boring outside a professional setting.

“When we have interactions with data analysts, accountants, insurance agents, and bankers, for example, those interactions are often boring not because the people are boring, but rather because the context is not interesting.”

To get past the preconceptions, “the best advice might be to get people to try to separate people from their roles when forming impressions of them.”

“We need to recognize that many of our interactions with other people are tied up in particular roles and topics and, thus, don’t reveal much about the other people themselves,” Dr. Leary says. “Maybe my accountant is the life of the party in other contexts.”
 

Dollars to avoid the dull?

The researchers also found that as the perception of how boring a person is increased, people were more likely to say they would avoid them.

To find a way to measure this avoidance, they asked people in the study how much money they would have to be paid to pal around with a perceived bore for 1 to 7 days. The payments people said they would need varied by perceptions that their boredom would be low, intermediate, or high.

As an example, they would require an average of $50 to spend one day with a highly boring person. That amount would double to $100 to spend almost 4 days in their company, and up to $230 for the week.

Dr. Leary says boredom happens when people try to pay attention to an experience or event. This means boredom goes beyond simple disinterest or trying to pay attention to someone that is not “intrinsically captivating.” When it takes more brain power to pay attention, you’ll perceive the experience as even more boring.

“Perhaps the best way to see if other people are actually boring is to talk about interesting things and see how they respond,” Dr. Leary says. “But, be careful: The topics you think make interesting conversations may be boring to others.”

A version of this article first appeared on WebMD.com.

Apologies up front to anyone who spends their weekends bird-watching or doing math for fun. They are among the people expected to be boring, based on stereotypes about what they do for work or how they spend their spare time, new research reveals.

Researchers surveyed more than 500 people across five related experiments to identify what people perceive as the most boring jobs, traits, and hobbies. They also report how we could all be missing out by spending as little time as possible with our tax consultant, accountant, or financial adviser outside of work.

People who work in banking, finance, accounting, data analytics, and cleaning topped the most boring list in the study, published earlier this month in Personality and Social Psychology Bulletin.

Sleeping, religion, watching television, observing animals, and spending spare time on mathematics were the stereotypical most boring hobbies and activities. The “observing animals” group includes people who bird-watch or study ants.

On the flip side, the top five most exciting jobs, in order, were in the performing arts, science, journalism, health professions, and teaching.

The researchers also looked at the how likely people are to avoid spending time with stereotypical dullards.

“Are people who are stereotyped as being boring avoided, if possible? Our current research shows that this is likely,” says Wijnand A.P. Van Tilburg, PhD, one of the researchers who did the study.

Beyond specific traits and stereotypes, Dr. Van Tilburg and colleagues found that boring people are seen as lacking skills and warmth.

“To our surprise, it appears that they are seen as both unfriendly and incompetent,” says Dr. Van Tilburg, an experimental social psychologist at the University of Essex in the United Kingdom.

What qualities do people most often ascribe to boring people? Besides being “dull,” “dry,” “bland,” and “not interesting,” common stereotypes include thinking someone who is likely boring will have no sense of humor, lack opinions, or complain.

The people surveyed also were more likely to place boring people in towns and small cities rather than large metropolitan areas.

A vicious cycle?

What’s the possible harm of relying on boring stereotypes? If people are stereotyped as being boring solely based on professions and hobbies, “then that suggests that they will incur the negative consequences associated with being a stereotypically boring person -- even when others haven’t actually interacted with them,” Dr. Van Tilburg says.

“Having a stereotypically boring profession or hobby may come with the inability to prove the biased perceivers wrong,” he says.

So making distinctions between stereotypes and realities is important, Dr. Van Tilburg says. “Those who have hobbies or occupations that are stereotypically boring do, of course, not actually have to be boring.”

Mark Leary, PhD, a professor in the department of psychology and neuroscience at Duke University in Durham, N.C., agrees. “The research actually dealt with stereotypes about the kinds of people who hold certain jobs, have certain hobbies, and live in certain places -- and not about boring people per se,” he says.

Dr. Leary points out that few people encounter bankers, tax experts, and others perceived as most boring outside a professional setting.

“When we have interactions with data analysts, accountants, insurance agents, and bankers, for example, those interactions are often boring not because the people are boring, but rather because the context is not interesting.”

To get past the preconceptions, “the best advice might be to get people to try to separate people from their roles when forming impressions of them.”

“We need to recognize that many of our interactions with other people are tied up in particular roles and topics and, thus, don’t reveal much about the other people themselves,” Dr. Leary says. “Maybe my accountant is the life of the party in other contexts.”
 

Dollars to avoid the dull?

The researchers also found that as the perception of how boring a person is increased, people were more likely to say they would avoid them.

To find a way to measure this avoidance, they asked people in the study how much money they would have to be paid to pal around with a perceived bore for 1 to 7 days. The payments people said they would need varied by perceptions that their boredom would be low, intermediate, or high.

As an example, they would require an average of $50 to spend one day with a highly boring person. That amount would double to $100 to spend almost 4 days in their company, and up to $230 for the week.

Dr. Leary says boredom happens when people try to pay attention to an experience or event. This means boredom goes beyond simple disinterest or trying to pay attention to someone that is not “intrinsically captivating.” When it takes more brain power to pay attention, you’ll perceive the experience as even more boring.

“Perhaps the best way to see if other people are actually boring is to talk about interesting things and see how they respond,” Dr. Leary says. “But, be careful: The topics you think make interesting conversations may be boring to others.”

A version of this article first appeared on WebMD.com.

Spring is the time for new beginnings, cleaning out your dusty musty basement, battling seasonal allergies, and, of course, discovering the latest TikTok trends.

With potentially permanent daylight savings on the table, that extra time spent luxuriating in the sunshine could mean more time to scroll (and scroll and scroll) through the latest health fads on the platform – for better or for worse.
 

The good: Doctor explains menstrual pain in an unexpected place

For a long time, menstrual cycles were considered taboo, and discussing them is still seen as inappropriate in many parts of the world. Organizations and online resources such as Clue or Flo are seeking to normalize period-talk. Pixar has jumped on board with its latest film, Turning Red, which depicts a 13-year-old’s experience getting her first period. With a 95% rating on Rotten Tomatoes, it’s clear that the public is willing to talk about periods.

Many people feel shame around discussing their periods, but this is something that social media has actually handled positively (for once).

Karan Raj, MD, a National Health Service surgeon and educator at Imperial College London, uses his TikTok account to educate his followers and explain health concerns and issues. Dr. Raj stitched this video from someone else that was captioned, “When you’re on your [period] and feel the stab in your booty.”

In his video, Dr. Raj uses anatomical diagrams to explain exactly what’s going on with this pain in the butt. The pain, which Dr. Raj says is called proctalgia fugax, is caused by a type of hormone released during menstruation called prostaglandins. Prostaglandins tell the uterus to contract and shed its lining, but the uterus isn’t the only part of the body receiving that message from the prostaglandins.

“The prostaglandins also cause contraction of the rectum, pelvic floor muscles, and muscles around the anal canal,” Dr. Raj tells viewers. “These intense contractions can cause muscle spasms and anal cramps.”
 

The bad: Lettuce water sleep aid

This video from Elliott Norris (@callmebelly) shows him preparing an unusual sleep aid. It’s one of many videos of people trying the same trend, usually with the tag #lettucewater attached.

As Mr. Elliott explains, the rumor is that boiling romaine lettuce and then drinking the water is a way to help one fall asleep faster, or sleep better at night. At the end of the video, Mr. Elliott even said that it worked for him. So where does this come from, and is it just a placebo?

Videos on TikTok recreating this trend cite a 2017 study titled, “Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep” (there’s even a New York Times article about it). The star of the study is lactucarium, a milky white substance that›s found in lettuce, usually visible if you squeeze it or break the stalks. The study suggests that lactucarium has “sedative-hypnotic” properties after lettuce extract was used in tandem with pentobarbital on mice, and it was found that the mice›s sleep latency then decreased.

In an article from Parade discussing the trend, Rachel Salas, MD, MEd, weighs in. Dr. Salas is the assistant medical director at Johns Hopkins Center for Sleep and Wellness in Baltimore, so you could say she knows a thing or two about sleep. Her response to the mice study was that its limitations made the results not entirely reliable.

According to Dr. Salas, there was no control group, the extract the mice were given is much more concentrated than what’s found in lettuce, and the mice were given a sedative that was going to make them sleepy anyway: “The mice were drugged to put the animals to sleep soon after they took the lettuce water.”

So while Dr. Salas thinks it’s good that people are open to talking about sleeping solutions, “lettuce tea” just doesn’t have any evidence to back up what people claim it does.
 

The ugly: Using a book to pop ganglion cysts

Everyone knows how popular pimple popping, blackhead squeezing, and cyst squashing are on social media. Dermatologist Sandra Lee, better known as Dr. Pimple Popper, used her YouTube platform of the same name – which boasts over 7.42 million subscribers – to cinch a reality television show on TLC. Viewers on TikTok are no different and love the satisfying (and often gross) relief of clearing out a nasty pimple or two.

In this stitched TikTok from emergency medicine physician Fayez Ajib, DO, aka @lifeofadoctor, Dr. Ajib reacts to an original video of someone popping a ganglion cyst with a textbook.

There are plenty of other videos on TikTok of people using books to smack ganglion cysts, which develop on the wrist. People have looked for remedies for ganglion cysts since the 1700s, at which point many strange options arose, as discussed in BBC Future. The one that still holds up, however, is smacking the cyst with a heavy book, like a Bible (hence the ganglion cyst’s nickname, “Bible bump”).

In his video, Dr. Ajib explains why smacking the cyst is a bad idea, even if it appears to temporarily resolve the issue.

“Not only have people broken the delicate bones in their wrist from getting hit,” Dr. Ajib says, “but they actually have a high chance of recurrence. A doctor will actually remove the sac itself rather than just draining it from being hit.”

The lessons we glean from TikTok remain the same: Leave it up to the professionals.

A version of this article first appeared on Medscape.com.

Spring is the time for new beginnings, cleaning out your dusty musty basement, battling seasonal allergies, and, of course, discovering the latest TikTok trends.

With potentially permanent daylight savings on the table, that extra time spent luxuriating in the sunshine could mean more time to scroll (and scroll and scroll) through the latest health fads on the platform – for better or for worse.
 

The good: Doctor explains menstrual pain in an unexpected place

For a long time, menstrual cycles were considered taboo, and discussing them is still seen as inappropriate in many parts of the world. Organizations and online resources such as Clue or Flo are seeking to normalize period-talk. Pixar has jumped on board with its latest film, Turning Red, which depicts a 13-year-old’s experience getting her first period. With a 95% rating on Rotten Tomatoes, it’s clear that the public is willing to talk about periods.

Many people feel shame around discussing their periods, but this is something that social media has actually handled positively (for once).

Karan Raj, MD, a National Health Service surgeon and educator at Imperial College London, uses his TikTok account to educate his followers and explain health concerns and issues. Dr. Raj stitched this video from someone else that was captioned, “When you’re on your [period] and feel the stab in your booty.”

In his video, Dr. Raj uses anatomical diagrams to explain exactly what’s going on with this pain in the butt. The pain, which Dr. Raj says is called proctalgia fugax, is caused by a type of hormone released during menstruation called prostaglandins. Prostaglandins tell the uterus to contract and shed its lining, but the uterus isn’t the only part of the body receiving that message from the prostaglandins.

“The prostaglandins also cause contraction of the rectum, pelvic floor muscles, and muscles around the anal canal,” Dr. Raj tells viewers. “These intense contractions can cause muscle spasms and anal cramps.”
 

The bad: Lettuce water sleep aid

This video from Elliott Norris (@callmebelly) shows him preparing an unusual sleep aid. It’s one of many videos of people trying the same trend, usually with the tag #lettucewater attached.

As Mr. Elliott explains, the rumor is that boiling romaine lettuce and then drinking the water is a way to help one fall asleep faster, or sleep better at night. At the end of the video, Mr. Elliott even said that it worked for him. So where does this come from, and is it just a placebo?

Videos on TikTok recreating this trend cite a 2017 study titled, “Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep” (there’s even a New York Times article about it). The star of the study is lactucarium, a milky white substance that›s found in lettuce, usually visible if you squeeze it or break the stalks. The study suggests that lactucarium has “sedative-hypnotic” properties after lettuce extract was used in tandem with pentobarbital on mice, and it was found that the mice›s sleep latency then decreased.

In an article from Parade discussing the trend, Rachel Salas, MD, MEd, weighs in. Dr. Salas is the assistant medical director at Johns Hopkins Center for Sleep and Wellness in Baltimore, so you could say she knows a thing or two about sleep. Her response to the mice study was that its limitations made the results not entirely reliable.

According to Dr. Salas, there was no control group, the extract the mice were given is much more concentrated than what’s found in lettuce, and the mice were given a sedative that was going to make them sleepy anyway: “The mice were drugged to put the animals to sleep soon after they took the lettuce water.”

So while Dr. Salas thinks it’s good that people are open to talking about sleeping solutions, “lettuce tea” just doesn’t have any evidence to back up what people claim it does.
 

The ugly: Using a book to pop ganglion cysts

Everyone knows how popular pimple popping, blackhead squeezing, and cyst squashing are on social media. Dermatologist Sandra Lee, better known as Dr. Pimple Popper, used her YouTube platform of the same name – which boasts over 7.42 million subscribers – to cinch a reality television show on TLC. Viewers on TikTok are no different and love the satisfying (and often gross) relief of clearing out a nasty pimple or two.

In this stitched TikTok from emergency medicine physician Fayez Ajib, DO, aka @lifeofadoctor, Dr. Ajib reacts to an original video of someone popping a ganglion cyst with a textbook.

There are plenty of other videos on TikTok of people using books to smack ganglion cysts, which develop on the wrist. People have looked for remedies for ganglion cysts since the 1700s, at which point many strange options arose, as discussed in BBC Future. The one that still holds up, however, is smacking the cyst with a heavy book, like a Bible (hence the ganglion cyst’s nickname, “Bible bump”).

In his video, Dr. Ajib explains why smacking the cyst is a bad idea, even if it appears to temporarily resolve the issue.

“Not only have people broken the delicate bones in their wrist from getting hit,” Dr. Ajib says, “but they actually have a high chance of recurrence. A doctor will actually remove the sac itself rather than just draining it from being hit.”

The lessons we glean from TikTok remain the same: Leave it up to the professionals.

A version of this article first appeared on Medscape.com.

Spring is the time for new beginnings, cleaning out your dusty musty basement, battling seasonal allergies, and, of course, discovering the latest TikTok trends.

With potentially permanent daylight savings on the table, that extra time spent luxuriating in the sunshine could mean more time to scroll (and scroll and scroll) through the latest health fads on the platform – for better or for worse.
 

The good: Doctor explains menstrual pain in an unexpected place

For a long time, menstrual cycles were considered taboo, and discussing them is still seen as inappropriate in many parts of the world. Organizations and online resources such as Clue or Flo are seeking to normalize period-talk. Pixar has jumped on board with its latest film, Turning Red, which depicts a 13-year-old’s experience getting her first period. With a 95% rating on Rotten Tomatoes, it’s clear that the public is willing to talk about periods.

Many people feel shame around discussing their periods, but this is something that social media has actually handled positively (for once).

Karan Raj, MD, a National Health Service surgeon and educator at Imperial College London, uses his TikTok account to educate his followers and explain health concerns and issues. Dr. Raj stitched this video from someone else that was captioned, “When you’re on your [period] and feel the stab in your booty.”

In his video, Dr. Raj uses anatomical diagrams to explain exactly what’s going on with this pain in the butt. The pain, which Dr. Raj says is called proctalgia fugax, is caused by a type of hormone released during menstruation called prostaglandins. Prostaglandins tell the uterus to contract and shed its lining, but the uterus isn’t the only part of the body receiving that message from the prostaglandins.

“The prostaglandins also cause contraction of the rectum, pelvic floor muscles, and muscles around the anal canal,” Dr. Raj tells viewers. “These intense contractions can cause muscle spasms and anal cramps.”
 

The bad: Lettuce water sleep aid

This video from Elliott Norris (@callmebelly) shows him preparing an unusual sleep aid. It’s one of many videos of people trying the same trend, usually with the tag #lettucewater attached.

As Mr. Elliott explains, the rumor is that boiling romaine lettuce and then drinking the water is a way to help one fall asleep faster, or sleep better at night. At the end of the video, Mr. Elliott even said that it worked for him. So where does this come from, and is it just a placebo?

Videos on TikTok recreating this trend cite a 2017 study titled, “Sleep-inducing effect of lettuce (Lactuca sativa) varieties on pentobarbital-induced sleep” (there’s even a New York Times article about it). The star of the study is lactucarium, a milky white substance that›s found in lettuce, usually visible if you squeeze it or break the stalks. The study suggests that lactucarium has “sedative-hypnotic” properties after lettuce extract was used in tandem with pentobarbital on mice, and it was found that the mice›s sleep latency then decreased.

In an article from Parade discussing the trend, Rachel Salas, MD, MEd, weighs in. Dr. Salas is the assistant medical director at Johns Hopkins Center for Sleep and Wellness in Baltimore, so you could say she knows a thing or two about sleep. Her response to the mice study was that its limitations made the results not entirely reliable.

According to Dr. Salas, there was no control group, the extract the mice were given is much more concentrated than what’s found in lettuce, and the mice were given a sedative that was going to make them sleepy anyway: “The mice were drugged to put the animals to sleep soon after they took the lettuce water.”

So while Dr. Salas thinks it’s good that people are open to talking about sleeping solutions, “lettuce tea” just doesn’t have any evidence to back up what people claim it does.
 

The ugly: Using a book to pop ganglion cysts

Everyone knows how popular pimple popping, blackhead squeezing, and cyst squashing are on social media. Dermatologist Sandra Lee, better known as Dr. Pimple Popper, used her YouTube platform of the same name – which boasts over 7.42 million subscribers – to cinch a reality television show on TLC. Viewers on TikTok are no different and love the satisfying (and often gross) relief of clearing out a nasty pimple or two.

In this stitched TikTok from emergency medicine physician Fayez Ajib, DO, aka @lifeofadoctor, Dr. Ajib reacts to an original video of someone popping a ganglion cyst with a textbook.

There are plenty of other videos on TikTok of people using books to smack ganglion cysts, which develop on the wrist. People have looked for remedies for ganglion cysts since the 1700s, at which point many strange options arose, as discussed in BBC Future. The one that still holds up, however, is smacking the cyst with a heavy book, like a Bible (hence the ganglion cyst’s nickname, “Bible bump”).

In his video, Dr. Ajib explains why smacking the cyst is a bad idea, even if it appears to temporarily resolve the issue.

“Not only have people broken the delicate bones in their wrist from getting hit,” Dr. Ajib says, “but they actually have a high chance of recurrence. A doctor will actually remove the sac itself rather than just draining it from being hit.”

The lessons we glean from TikTok remain the same: Leave it up to the professionals.

A version of this article first appeared on Medscape.com.