Tanvir Singh, MD

CASE: She’s not herself

Mrs. M, age 74, is brought to the ER by her husband after he finds her lying on their bedroom floor, incoherent and extremely drowsy. He reports that his wife, who suffers chronic arthritic back and joint pain, might have overdosed on pain medications.

According to her husband, Mrs. M has been taking combination oxycodone/acetaminophen and transdermal fentanyl at unknown dosages, but he is unsure when she started using these medications or if she is taking others. Serum toxicology screening shows twice the normal values for opioids and benzodiazepines; other laboratory results are normal.

Mrs. M is medically stable but her mental status is altered. She is oblivious to time, place and person, speaks to no one, and seems lost in her own world. The hospital’s medical service admits Mrs. M for stabilization and to determine whether the overdose was intentional.

Two days later, we evaluate Mrs. M’s mental status at the attending physician’s request. She appears confused and cannot answer our questions. Her husband tells us she was “doing fine” until approximately 4 months ago, when she started becoming increasingly forgetful and lethargic. He says she has been forgetting routine chores such as paying bills and grocery shopping. Recently, she has been getting lost during her evening walk; neighbors often help her find her way home.

The authors’ observations

Two opioid medications—oxycodone/acetaminophen combination and transdermal fentanyl—are commonly used to manage moderate or severe pain from any type of chronic arthritis.

• Oxycodone, a semisynthetic opioid analgesic indicated for moderate to moderately severe pain, is used when nondrug measures and nonnarcotic medications do not control the pain.
  
• Transdermal fentanyl, a potent analgesic indicated for persistent moderate to severe chronic pain, typically is prescribed to patients who tolerate oral oxycodone, 30 mg/d; morphine, 60 mg; hydromorphone, 8 mg; or an equianalgesic dosage of another opioid for ≥1 week.
  

Mrs. M also was taking a benzodiazepine, but which medication—and why she was taking it—were unclear. She had no psychiatric diagnosis, and her husband could not recall her medication history.

We also cannot explain Mrs. M’s negative cognitive and behavioral changes. Opioid overuse and onset of dementia-related cognitive decline are possibilities.

TRANSFER Why is she confused?

Based on information from the pharmacy department, doctors at the medical unit restart oxycodone/acetaminophen, 7.5/325 mg tid, and transdermal fentanyl, 25 mcg/hr every 3 days. After discussing how to treat Mrs. M, the psychiatric and medical services transfer her to the geriatric psychiatric inpatient unit 3 days after admission.

We visit Mrs. M hours after her transfer. She seems lethargic but not confused, although Mini-Mental State Examination (MMSE) score of 15 suggests moderate cognitive impairment. Vitamin B₁₂ and thyroid levels, erythrocyte sedimentation rate, and syphilis test results are normal, allowing us to rule out organic causes for her dementia. Brain MRI shows no neurologic damage. On a scale of 1 to 5 with 5 being most severe, Mrs. M scores her pain as 2 (mild) and her sedation as 3 (moderate).

With Mrs. M’s permission, we call her primary care physician for collateral information. The physician tells us Mrs. M has suffered severe joint pain for 2 years. Nonnarcotic medications and treatments—including counseling, support groups, massage, yoga, exercise, biofeedback, relaxation therapy, and physical therapy—were ineffective.

Approximately 10 months ago, the physician started oxycodone/acetaminophen at 2.5/325 mg bid and titrated it over 6 weeks to 7.5/325 mg tid for Mrs. M’s persistent joint pain. Four months ago, with her pain still severe, the physician added transdermal fentanyl, 25 mcg/hr every 3 days, after which the patient reported mild improvement.

One month after starting the fentanyl patch, Mrs. M complained of sudden forgetfulness, low energy, poor concentration, and increased sleep. The physician suspected depression with possible comorbid anxiety and prescribed sertraline, 50 mg/d, and alprazolam, 0.5 mg bid. Mrs. M stopped sertraline after 3 days because it was causing diarrhea but kept taking alprazolam.

Mrs. M saw her primary care physician once after starting alprazolam and sertraline but missed her most recent appointment last month. The physician says he inadvertently approved at least 1 premature request for an alprazolam refill.

Six days after admission, Mrs. M’s sedation, cognitive impairment, and lethargy persist. She reports no mood and anxiety problems, and we have not restarted alprazolam.

The authors’ observations

The fentanyl patch most likely began to diminish Mrs. M’s alertness soon after she started using it. The doctor, however, mistook cognitive slowing for new-onset depression or anxiety. Depressive symptoms can imitate dementia, but Mrs. M’s severe sedation and denial of depressive symptoms suggest a medication side effect.

The primary care physician’s reconstruction of Mrs. M’s history explained her positive benzodiazepine reading, and her use of the short-acting benzodiazepine alprazolam could account for her sudden-onset paranoia and cognitive decline (Box). Benzodiazepines can cause behavioral side effects such as disinhibition, agitation, or paranoia, and patients age ≥65 are at increased risk for these side effects.⁴ In particular, benzodiazepines with half-lives ≥6 to 8 hours such as clonazepam and oxazepam can cause short-term memory impairment, confusion, and delirium.^5-7

Box

When prescribing benzodiazepines (especially in older patients) watch for signs of overuse or abuse, such as early requests for refills, unkempt appearance, excessive sleepiness, or agitation (Table 1).

Warning signs of opioid, benzodiazepine overuse

The authors’ observations

Persistent chronic pain in the elderly can diminish health and quality of life, resulting in depression, social isolation, immobility, and sleep disturbance.

Managing an older patient’s pain can be challenging (Table 2). Opioids are effective painkillers, but even at relatively low dosages they can diminish function and cognition and increase risk of delirium. Also, patients’ ability to tolerate different opioids at different dosages varies widely.

Mrs. M’s opioid regimen was intolerable and numerous other treatments did not alleviate her pain. At this point, replacing fentanyl with another opioid was our best option.⁸

We decided to try methadone, which is indicated for moderate to severe pain that does not respond to nonnarcotic treatments. Methadone often is used for chronic pain associated with arthritis or malignancy.

Methadone is less sedating, more tolerable, and carries a lower risk of cognitive side effects than other opioids. Methadone also is fast- and long-acting—its analgesic effects begin within 30 minutes to 1 hour of oral administration⁹ and last approximately 12 hours, thus reducing the risk of breakthrough pain. Methadone also:

• has no active metabolites, which decreases the risk of hepatic side effects
  
• offers a high volume of distribution, thus allowing clinical effect with minimal dosing.
  

• watch for symptoms such as oversedation, memory and concentration problems, and sudden changes in personality
  
• call you to clarify if these symptoms are methadone side effects.
  

Watch for other potential side effects of methadone, such as constipation, sedation, breakthrough pain, sexual dysfunction, decreased immunity, respiratory depression, or prolonged corrected QT intervals.

Patients usually tolerate an immediate switch from transdermal fentanyl to methadone, but a sudden switch from high-dose fentanyl can reduce methadone’s effectiveness. Starting methadone at a high dosage to compensate for loss of effectiveness could increase side effect risk. If the fentanyl dosage exceeds 100 mcg/hr, taper by 25 mcg weekly. Simultaneously start methadone at a low dosage and titrate by 5 to 10 mg weekly as needed.

Table 2

Chronic pain management in the elderly: Dos and don’ts

TREATMENT Medication change

We stop transdermal fentanyl and start oral methadone, 5 mg bid, while continuing oxycodone/acetaminophen at the previous dosage.

Two days later, Mrs. M is much more alert. Since admission 1 week ago, her sedation rating has improved from 3 (mildly sedated) to 4 (almost fully alert). She rates her pain as mild and reports no breakthrough pain or other side effects from methadone. Her MMSE score has improved to 24—suggesting close to normal cognition—and she is much more interactive with staff and family.

Eight days after we start methadone, we stop oxycodone/acetaminophen and increase methadone to 10 mg bid to further improve cognition and alertness and to see if 1 pain medication is suffcient. Two days later, we discharge Mrs. M. She is fully alert, feels little or no joint pain, and is tolerating the methadone increase.

At outpatient follow-up 4 weeks later, Mrs. M remains pain-free and her MMSE score is 29, suggesting normal cognition. Over 8 months, we continue to see her monthly and then bi-monthly, after which we refer her to her primary care physician.

Related resources

• American Association for Geriatric Psychiatry. www.aagponline.org.
  
• American Pain Society. www.ampainsoc.org.
  

• Alprazolam • Xanax
  
• Clonazepam • Klonopin
  
• Fentanyl (transdermal) • Duragesic
  
• Hydromorphone • Dilaudid
  
• Meperidine • Demerol
  
• Methadone • Dolophine
  
• Oxazepam • Serax
  
• Oxycodone • OxyContin, Roxicodone
  
• Oxycodone/acetaminophen • Percocet
  
• Propoxyphene • Darvon
  
• Sertraline • Zoloft
  

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: She’s not herself

Mrs. M, age 74, is brought to the ER by her husband after he finds her lying on their bedroom floor, incoherent and extremely drowsy. He reports that his wife, who suffers chronic arthritic back and joint pain, might have overdosed on pain medications.

According to her husband, Mrs. M has been taking combination oxycodone/acetaminophen and transdermal fentanyl at unknown dosages, but he is unsure when she started using these medications or if she is taking others. Serum toxicology screening shows twice the normal values for opioids and benzodiazepines; other laboratory results are normal.

Mrs. M is medically stable but her mental status is altered. She is oblivious to time, place and person, speaks to no one, and seems lost in her own world. The hospital’s medical service admits Mrs. M for stabilization and to determine whether the overdose was intentional.

Two days later, we evaluate Mrs. M’s mental status at the attending physician’s request. She appears confused and cannot answer our questions. Her husband tells us she was “doing fine” until approximately 4 months ago, when she started becoming increasingly forgetful and lethargic. He says she has been forgetting routine chores such as paying bills and grocery shopping. Recently, she has been getting lost during her evening walk; neighbors often help her find her way home.

The authors’ observations

Two opioid medications—oxycodone/acetaminophen combination and transdermal fentanyl—are commonly used to manage moderate or severe pain from any type of chronic arthritis.

• Oxycodone, a semisynthetic opioid analgesic indicated for moderate to moderately severe pain, is used when nondrug measures and nonnarcotic medications do not control the pain.
  
• Transdermal fentanyl, a potent analgesic indicated for persistent moderate to severe chronic pain, typically is prescribed to patients who tolerate oral oxycodone, 30 mg/d; morphine, 60 mg; hydromorphone, 8 mg; or an equianalgesic dosage of another opioid for ≥1 week.
  

Mrs. M also was taking a benzodiazepine, but which medication—and why she was taking it—were unclear. She had no psychiatric diagnosis, and her husband could not recall her medication history.

We also cannot explain Mrs. M’s negative cognitive and behavioral changes. Opioid overuse and onset of dementia-related cognitive decline are possibilities.

TRANSFER Why is she confused?

Based on information from the pharmacy department, doctors at the medical unit restart oxycodone/acetaminophen, 7.5/325 mg tid, and transdermal fentanyl, 25 mcg/hr every 3 days. After discussing how to treat Mrs. M, the psychiatric and medical services transfer her to the geriatric psychiatric inpatient unit 3 days after admission.

We visit Mrs. M hours after her transfer. She seems lethargic but not confused, although Mini-Mental State Examination (MMSE) score of 15 suggests moderate cognitive impairment. Vitamin B₁₂ and thyroid levels, erythrocyte sedimentation rate, and syphilis test results are normal, allowing us to rule out organic causes for her dementia. Brain MRI shows no neurologic damage. On a scale of 1 to 5 with 5 being most severe, Mrs. M scores her pain as 2 (mild) and her sedation as 3 (moderate).

With Mrs. M’s permission, we call her primary care physician for collateral information. The physician tells us Mrs. M has suffered severe joint pain for 2 years. Nonnarcotic medications and treatments—including counseling, support groups, massage, yoga, exercise, biofeedback, relaxation therapy, and physical therapy—were ineffective.

Approximately 10 months ago, the physician started oxycodone/acetaminophen at 2.5/325 mg bid and titrated it over 6 weeks to 7.5/325 mg tid for Mrs. M’s persistent joint pain. Four months ago, with her pain still severe, the physician added transdermal fentanyl, 25 mcg/hr every 3 days, after which the patient reported mild improvement.

One month after starting the fentanyl patch, Mrs. M complained of sudden forgetfulness, low energy, poor concentration, and increased sleep. The physician suspected depression with possible comorbid anxiety and prescribed sertraline, 50 mg/d, and alprazolam, 0.5 mg bid. Mrs. M stopped sertraline after 3 days because it was causing diarrhea but kept taking alprazolam.

Mrs. M saw her primary care physician once after starting alprazolam and sertraline but missed her most recent appointment last month. The physician says he inadvertently approved at least 1 premature request for an alprazolam refill.

Six days after admission, Mrs. M’s sedation, cognitive impairment, and lethargy persist. She reports no mood and anxiety problems, and we have not restarted alprazolam.

The authors’ observations

The fentanyl patch most likely began to diminish Mrs. M’s alertness soon after she started using it. The doctor, however, mistook cognitive slowing for new-onset depression or anxiety. Depressive symptoms can imitate dementia, but Mrs. M’s severe sedation and denial of depressive symptoms suggest a medication side effect.

The primary care physician’s reconstruction of Mrs. M’s history explained her positive benzodiazepine reading, and her use of the short-acting benzodiazepine alprazolam could account for her sudden-onset paranoia and cognitive decline (Box). Benzodiazepines can cause behavioral side effects such as disinhibition, agitation, or paranoia, and patients age ≥65 are at increased risk for these side effects.⁴ In particular, benzodiazepines with half-lives ≥6 to 8 hours such as clonazepam and oxazepam can cause short-term memory impairment, confusion, and delirium.^5-7

Box

When prescribing benzodiazepines (especially in older patients) watch for signs of overuse or abuse, such as early requests for refills, unkempt appearance, excessive sleepiness, or agitation (Table 1).

Warning signs of opioid, benzodiazepine overuse

The authors’ observations

Persistent chronic pain in the elderly can diminish health and quality of life, resulting in depression, social isolation, immobility, and sleep disturbance.

Managing an older patient’s pain can be challenging (Table 2). Opioids are effective painkillers, but even at relatively low dosages they can diminish function and cognition and increase risk of delirium. Also, patients’ ability to tolerate different opioids at different dosages varies widely.

Mrs. M’s opioid regimen was intolerable and numerous other treatments did not alleviate her pain. At this point, replacing fentanyl with another opioid was our best option.⁸

We decided to try methadone, which is indicated for moderate to severe pain that does not respond to nonnarcotic treatments. Methadone often is used for chronic pain associated with arthritis or malignancy.

Methadone is less sedating, more tolerable, and carries a lower risk of cognitive side effects than other opioids. Methadone also is fast- and long-acting—its analgesic effects begin within 30 minutes to 1 hour of oral administration⁹ and last approximately 12 hours, thus reducing the risk of breakthrough pain. Methadone also:

• has no active metabolites, which decreases the risk of hepatic side effects
  
• offers a high volume of distribution, thus allowing clinical effect with minimal dosing.
  

• watch for symptoms such as oversedation, memory and concentration problems, and sudden changes in personality
  
• call you to clarify if these symptoms are methadone side effects.
  

Watch for other potential side effects of methadone, such as constipation, sedation, breakthrough pain, sexual dysfunction, decreased immunity, respiratory depression, or prolonged corrected QT intervals.

Patients usually tolerate an immediate switch from transdermal fentanyl to methadone, but a sudden switch from high-dose fentanyl can reduce methadone’s effectiveness. Starting methadone at a high dosage to compensate for loss of effectiveness could increase side effect risk. If the fentanyl dosage exceeds 100 mcg/hr, taper by 25 mcg weekly. Simultaneously start methadone at a low dosage and titrate by 5 to 10 mg weekly as needed.

Table 2

Chronic pain management in the elderly: Dos and don’ts

TREATMENT Medication change

We stop transdermal fentanyl and start oral methadone, 5 mg bid, while continuing oxycodone/acetaminophen at the previous dosage.

Two days later, Mrs. M is much more alert. Since admission 1 week ago, her sedation rating has improved from 3 (mildly sedated) to 4 (almost fully alert). She rates her pain as mild and reports no breakthrough pain or other side effects from methadone. Her MMSE score has improved to 24—suggesting close to normal cognition—and she is much more interactive with staff and family.

Eight days after we start methadone, we stop oxycodone/acetaminophen and increase methadone to 10 mg bid to further improve cognition and alertness and to see if 1 pain medication is suffcient. Two days later, we discharge Mrs. M. She is fully alert, feels little or no joint pain, and is tolerating the methadone increase.

At outpatient follow-up 4 weeks later, Mrs. M remains pain-free and her MMSE score is 29, suggesting normal cognition. Over 8 months, we continue to see her monthly and then bi-monthly, after which we refer her to her primary care physician.

Related resources

• American Association for Geriatric Psychiatry. www.aagponline.org.
  
• American Pain Society. www.ampainsoc.org.
  

• Alprazolam • Xanax
  
• Clonazepam • Klonopin
  
• Fentanyl (transdermal) • Duragesic
  
• Hydromorphone • Dilaudid
  
• Meperidine • Demerol
  
• Methadone • Dolophine
  
• Oxazepam • Serax
  
• Oxycodone • OxyContin, Roxicodone
  
• Oxycodone/acetaminophen • Percocet
  
• Propoxyphene • Darvon
  
• Sertraline • Zoloft
  

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: She’s not herself

Mrs. M, age 74, is brought to the ER by her husband after he finds her lying on their bedroom floor, incoherent and extremely drowsy. He reports that his wife, who suffers chronic arthritic back and joint pain, might have overdosed on pain medications.

According to her husband, Mrs. M has been taking combination oxycodone/acetaminophen and transdermal fentanyl at unknown dosages, but he is unsure when she started using these medications or if she is taking others. Serum toxicology screening shows twice the normal values for opioids and benzodiazepines; other laboratory results are normal.

Mrs. M is medically stable but her mental status is altered. She is oblivious to time, place and person, speaks to no one, and seems lost in her own world. The hospital’s medical service admits Mrs. M for stabilization and to determine whether the overdose was intentional.

Two days later, we evaluate Mrs. M’s mental status at the attending physician’s request. She appears confused and cannot answer our questions. Her husband tells us she was “doing fine” until approximately 4 months ago, when she started becoming increasingly forgetful and lethargic. He says she has been forgetting routine chores such as paying bills and grocery shopping. Recently, she has been getting lost during her evening walk; neighbors often help her find her way home.

The authors’ observations

Two opioid medications—oxycodone/acetaminophen combination and transdermal fentanyl—are commonly used to manage moderate or severe pain from any type of chronic arthritis.

• Oxycodone, a semisynthetic opioid analgesic indicated for moderate to moderately severe pain, is used when nondrug measures and nonnarcotic medications do not control the pain.
  
• Transdermal fentanyl, a potent analgesic indicated for persistent moderate to severe chronic pain, typically is prescribed to patients who tolerate oral oxycodone, 30 mg/d; morphine, 60 mg; hydromorphone, 8 mg; or an equianalgesic dosage of another opioid for ≥1 week.
  

Mrs. M also was taking a benzodiazepine, but which medication—and why she was taking it—were unclear. She had no psychiatric diagnosis, and her husband could not recall her medication history.

We also cannot explain Mrs. M’s negative cognitive and behavioral changes. Opioid overuse and onset of dementia-related cognitive decline are possibilities.

TRANSFER Why is she confused?

Based on information from the pharmacy department, doctors at the medical unit restart oxycodone/acetaminophen, 7.5/325 mg tid, and transdermal fentanyl, 25 mcg/hr every 3 days. After discussing how to treat Mrs. M, the psychiatric and medical services transfer her to the geriatric psychiatric inpatient unit 3 days after admission.

We visit Mrs. M hours after her transfer. She seems lethargic but not confused, although Mini-Mental State Examination (MMSE) score of 15 suggests moderate cognitive impairment. Vitamin B₁₂ and thyroid levels, erythrocyte sedimentation rate, and syphilis test results are normal, allowing us to rule out organic causes for her dementia. Brain MRI shows no neurologic damage. On a scale of 1 to 5 with 5 being most severe, Mrs. M scores her pain as 2 (mild) and her sedation as 3 (moderate).

With Mrs. M’s permission, we call her primary care physician for collateral information. The physician tells us Mrs. M has suffered severe joint pain for 2 years. Nonnarcotic medications and treatments—including counseling, support groups, massage, yoga, exercise, biofeedback, relaxation therapy, and physical therapy—were ineffective.

Approximately 10 months ago, the physician started oxycodone/acetaminophen at 2.5/325 mg bid and titrated it over 6 weeks to 7.5/325 mg tid for Mrs. M’s persistent joint pain. Four months ago, with her pain still severe, the physician added transdermal fentanyl, 25 mcg/hr every 3 days, after which the patient reported mild improvement.

One month after starting the fentanyl patch, Mrs. M complained of sudden forgetfulness, low energy, poor concentration, and increased sleep. The physician suspected depression with possible comorbid anxiety and prescribed sertraline, 50 mg/d, and alprazolam, 0.5 mg bid. Mrs. M stopped sertraline after 3 days because it was causing diarrhea but kept taking alprazolam.

Mrs. M saw her primary care physician once after starting alprazolam and sertraline but missed her most recent appointment last month. The physician says he inadvertently approved at least 1 premature request for an alprazolam refill.

Six days after admission, Mrs. M’s sedation, cognitive impairment, and lethargy persist. She reports no mood and anxiety problems, and we have not restarted alprazolam.

The authors’ observations

The fentanyl patch most likely began to diminish Mrs. M’s alertness soon after she started using it. The doctor, however, mistook cognitive slowing for new-onset depression or anxiety. Depressive symptoms can imitate dementia, but Mrs. M’s severe sedation and denial of depressive symptoms suggest a medication side effect.

The primary care physician’s reconstruction of Mrs. M’s history explained her positive benzodiazepine reading, and her use of the short-acting benzodiazepine alprazolam could account for her sudden-onset paranoia and cognitive decline (Box). Benzodiazepines can cause behavioral side effects such as disinhibition, agitation, or paranoia, and patients age ≥65 are at increased risk for these side effects.⁴ In particular, benzodiazepines with half-lives ≥6 to 8 hours such as clonazepam and oxazepam can cause short-term memory impairment, confusion, and delirium.^5-7

Box

When prescribing benzodiazepines (especially in older patients) watch for signs of overuse or abuse, such as early requests for refills, unkempt appearance, excessive sleepiness, or agitation (Table 1).

Warning signs of opioid, benzodiazepine overuse

The authors’ observations

Persistent chronic pain in the elderly can diminish health and quality of life, resulting in depression, social isolation, immobility, and sleep disturbance.

Managing an older patient’s pain can be challenging (Table 2). Opioids are effective painkillers, but even at relatively low dosages they can diminish function and cognition and increase risk of delirium. Also, patients’ ability to tolerate different opioids at different dosages varies widely.

Mrs. M’s opioid regimen was intolerable and numerous other treatments did not alleviate her pain. At this point, replacing fentanyl with another opioid was our best option.⁸

We decided to try methadone, which is indicated for moderate to severe pain that does not respond to nonnarcotic treatments. Methadone often is used for chronic pain associated with arthritis or malignancy.

Methadone is less sedating, more tolerable, and carries a lower risk of cognitive side effects than other opioids. Methadone also is fast- and long-acting—its analgesic effects begin within 30 minutes to 1 hour of oral administration⁹ and last approximately 12 hours, thus reducing the risk of breakthrough pain. Methadone also:

• has no active metabolites, which decreases the risk of hepatic side effects
  
• offers a high volume of distribution, thus allowing clinical effect with minimal dosing.
  

• watch for symptoms such as oversedation, memory and concentration problems, and sudden changes in personality
  
• call you to clarify if these symptoms are methadone side effects.
  

Watch for other potential side effects of methadone, such as constipation, sedation, breakthrough pain, sexual dysfunction, decreased immunity, respiratory depression, or prolonged corrected QT intervals.

Patients usually tolerate an immediate switch from transdermal fentanyl to methadone, but a sudden switch from high-dose fentanyl can reduce methadone’s effectiveness. Starting methadone at a high dosage to compensate for loss of effectiveness could increase side effect risk. If the fentanyl dosage exceeds 100 mcg/hr, taper by 25 mcg weekly. Simultaneously start methadone at a low dosage and titrate by 5 to 10 mg weekly as needed.

Table 2

Chronic pain management in the elderly: Dos and don’ts

TREATMENT Medication change

We stop transdermal fentanyl and start oral methadone, 5 mg bid, while continuing oxycodone/acetaminophen at the previous dosage.

Two days later, Mrs. M is much more alert. Since admission 1 week ago, her sedation rating has improved from 3 (mildly sedated) to 4 (almost fully alert). She rates her pain as mild and reports no breakthrough pain or other side effects from methadone. Her MMSE score has improved to 24—suggesting close to normal cognition—and she is much more interactive with staff and family.

Eight days after we start methadone, we stop oxycodone/acetaminophen and increase methadone to 10 mg bid to further improve cognition and alertness and to see if 1 pain medication is suffcient. Two days later, we discharge Mrs. M. She is fully alert, feels little or no joint pain, and is tolerating the methadone increase.

At outpatient follow-up 4 weeks later, Mrs. M remains pain-free and her MMSE score is 29, suggesting normal cognition. Over 8 months, we continue to see her monthly and then bi-monthly, after which we refer her to her primary care physician.

Related resources

• American Association for Geriatric Psychiatry. www.aagponline.org.
  
• American Pain Society. www.ampainsoc.org.
  

• Alprazolam • Xanax
  
• Clonazepam • Klonopin
  
• Fentanyl (transdermal) • Duragesic
  
• Hydromorphone • Dilaudid
  
• Meperidine • Demerol
  
• Methadone • Dolophine
  
• Oxazepam • Serax
  
• Oxycodone • OxyContin, Roxicodone
  
• Oxycodone/acetaminophen • Percocet
  
• Propoxyphene • Darvon
  
• Sertraline • Zoloft
  

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

History: ‘A zillion racing thoughts’

Ms. R, age 44, is referred by her primary care physician. She complains of tenseness, irritability, avolition, and fatigue. She worries incessantly that her children will get sick, a catastrophe will befall her husband, or she’ll do something wrong. She says she sometimes feels as if she’s thinking “a zillion racing thoughts.”

Once fun-loving, outgoing, and energetic, Ms. R says she began feeling unusually anxious 3 years ago. A psychiatrist diagnosed bipolar disorder type II based on her racing thoughts, irritability, low energy, and history of mood swings. Over 2 years, the psychiatrist tried combining valproic acid with bupropion, citalopram, or extended-release venlafaxine, then tried lithium monotherapy. Nothing worked.

Frustrated, Ms. R left the psychiatrist and consulted her primary care physician, who prescribed gabapentin, 200 mg each morning and 300 mg at night; fluoxetine, 50 mg/d; and quetiapine, 12.5 mg/d. Ms. R noticed no improvement and stopped the medications after 6 weeks. The physician urged her to see another psychiatrist, and she presented to us 2 weeks after stopping the medications.

Ms. R also has been feeling depressed and irritable the past 4 months and has trouble falling and staying asleep at night. She sleeps 4 to 5 hours nightly, constantly feels tired, cannot concentrate, and overeats to try to alleviate her stress. She has gained 6 pounds over 2 to 3 months and weighs 160 lb; her body mass index of 26 indicates she is overweight.

She says her worries overwhelm her and cause heart palpitations and muscle tension in her neck and shoulders. She admits to feeling “worthless,” but denies suicidal thoughts.

Ms. R describes her husband and two teenage daughters as “very supportive,” but admits that her fatigue and irritability have strained these relationships; she says she snaps at them for minor things, such as coming to dinner 1 minute late. She misses her job, which she recently quit because of her decreasing ability to function.

At intake, Ms. R says she will not resume previous medications but will consider alternatives. She refuses psychotherapy because of time constraints and transportation problems but is willing to return every 2 weeks for medication checks. She says she adhered to every prescription over 3 years with no major side effects. She has never taken an antidepressant or anxiolytic without a mood stabilizer.

Ms. R reports no medical problems, past substance use, current or past psychotic symptoms, or psychiatric hospitalizations. Her family history shows depression in one first-degree relative and anxiety in others. Her Hamilton Anxiety Scale (HAM-A) score of 20 indicates moderate anxiety. Laboratory tests ordered by her primary care physician are normal.

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The authors’ observations

Racing thoughts, irritable mood, decreased sleep, and concentration problems can point to GAD, mania associated with bipolar disorder type I, or hypomania suggesting bipolar disorder type I or II (Table 1).¹

We suspect GAD because:

• Ms. R’s thoughts “race” only when she worries
• her irritability and concentration problems seem more sustained than episodic
• she has difficulty falling and staying asleep, but her need for sleep has not decreased
• she complains of constant fatigue, whereas abnormally high energy characterizes bipolar disorder’s manic or hypomanic phase.

Does Ms. R have depression? Determining if the patient’s depressive symptoms are secondary to GAD or warrant a separate diagnosis can be difficult (Table 1). With Ms. R’s permission, we talked to her family, because collateral information often helps clarify the diagnosis. Her husband and daughters offered no significant new insights, however.

Table 1

Overlap among symptoms that suggest GAD, mania, or major depression

Treatment: Targeting the anxiety

To address Ms. R’s anxiety symptoms, we start buspirone, 5 mg tid, and titrate to 15 mg bid over 2 weeks. We choose buspirone—which is FDA-approved to treat GAD—because it is unlikely to cause a mood switch if bipolar disorder is causing Ms. R’s depression. We discuss with her the drug’s indications, benefits, and potential side effects (such as vertigo, headache, lightheadedness, and nausea).

At the first 2-week follow-up, Ms. R reports no side effects but little improvement. After another 2 weeks, she says she feels less anxiety, irritability, pain, and fewer racing thoughts. She reports less difficulty falling asleep, though she’s still sleeping only about 6 hours nightly. Her HAM-A score falls to 12, indicating mild anxiety.

Ms. R, however, says she still feels depressed, tired, distracted, unmotivated, and worthless. Her Hamilton Rating Scale for Depression (HAM-D) score of 16 indicates moderate depression.

poll here

The authors’ observations

The persistence of Ms. R’s depressive symptoms suggests comorbid major depressive disorder (MDD). In fact, MDD and GAD are considered the most common mood-anxiety comorbidities.²

Determining whether Ms. R has unipolar depression or bipolar disorder is extremely important, considering the treatment implications. In patients with bipolar disorder, any antidepressant can trigger mania or hypomania if used without a mood stabilizer. Some studies also have associated rare cases of suicidal behavior with antidepressant use.^3,4 Lifetime risk of suicide in bipolar disorder is approximately 20 times that in the general population.⁵

Although Ms. R’s history does not reveal a previous manic episode, ruling out hypomania is difficult because it usually does not impair work or social functioning. Hypomania often goes unreported because others hardly notice it. Collateral history can uncover clues to hypomania (See For Your Patient), but Ms. R’s husband and daughters say they have not seen such episodes.

On the other hand, normal behavior can be mistaken for hypomania. Ms. R’s previous psychiatrist and primary care physician might have misinterpreted Ms. R’s baseline extroverted personality as hypomanic behavior. Also, her over-whelming depressive and anxiety symptoms between depressive episodes made her normal moods appear hypomanic.

Compared with unipolar depression, bipolar depression is more frequently associated with psychomotor retardation, hypersomnia, early onset, and family history of bipolar disorder.⁶ Ms. R, however, suffered low energy, terminal insomnia, and late onset, and had no known family history of bipolar disorder.

The Mood Disorder Questionnaire, a scale of self-administered questions, can help screen for symptoms that suggest bipolar disorder. A positive questionnaire result demands further clinical evaluation.⁷

Box

Continued treatment: ‘normal’ again

In addition to the HAM-D, we also administer the Mood Disorder Questionnaire. Results suggest Ms. R does not have bipolar illness.

To address Ms. R’s depressive symptoms, we start the selective serotonin reuptake inhibitor escitalopram at a low dosage (5 mg/d) to avoid exacerbating her anxiety. We discuss the drug’s potential to induce mania, hypomania, or other adverse effects such as nausea, anxiety, sleep disturbance, headache, and sexual dysfunction. Buspirone is maintained at 15 mg bid.

Two weeks later, Ms. R reports some increase in energy and motivation. After another 2 weeks, she reports significantly improved mood and concentration. She consistently falls asleep at 10 PM and sleeps 8 hours each night. She also finds time to read and go out with her friends and she gets along more amicably with her daughters and husband.

One month later, we increase escitalopram to 10 mg/d, a normal therapeutic dosage. Ms. R continues to respond positively and reports no side effects. Two months after starting the antidepressant, her HAM-D score of 8 suggests normal mood. We decrease follow-up visits to once monthly.

At a subsequent visit, Ms. R tells us she wants to find a job. A month later, she says she is enjoying her new job in a department store. Over the next 6 months, she remains free of anxiety, depressive symptoms, hypomanic behavior, and side effects. She tells us it’s nice to feel “normal” again.

We reduce Ms. R’s appointments to every 3 months. After another year, we refer her back to her primary care physician at her request.

The authors’ observations

DSM-IV-TR¹ divides bipolar disorder into three categories:

• type I, in which the patient has had at least one manic episode with or without major depression
• type II, characterized by one or more major depressive episodes and at least one hypomanic episode
• cyclothymia, which is defined as fluctuation between hypomanic and minor depressive episodes.

Much is said about how underdiagnosis of bipolar disorder⁸ delays or prevents proper therapy with mood stabilizers, leading to suboptimal symptom resolution. As with Ms. R, however, an incorrect bipolar disorder diagnosis can be just as harmful. Three years of unnecessary and ineffective treatment worsened her anxiety and depressive symptoms and quality of life.

A comprehensive clinical interview supplemented with insights from family and friends can minimize the risk of misdiagnosis when patients present with symptoms that suggest bipolar disorder, depression, or GAD.

Differentiating between the following clinical features can also help you reach a diagnosis:

Sleep/energy level. Mania/hypomania is characterized by decreased need for sleep; patients often feel energetic even after 2 to 4 hours of sleep. Both depression and GAD diminish energy level, although mood is more depressed in depression. Patients with GAD have trouble falling asleep, while those with depression awaken early or have hypersomnia.

Behavior. Patients in the manic phase of bipolar disorder engage in risky, pleasurable activities with high potential for painful consequences. This drastic behavior change is not seen in depression or GAD (Table 2).

Table 2

Differentiating symptoms common to GAD, major depression, and mania

Related resources

• Depression and Bipolar Support Alliance. www.dbsalliance.org.
• Anxiety Disorders Association of America. www.adaa.org.

Drug brand names

• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Quetiapine • Seroquel
• Valproic acid • Depakene
• Venlafaxine • Effexor

Disclosures

Dr. Williams is a speaker for Wyeth.

Dr. Singh reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘A zillion racing thoughts’

Ms. R, age 44, is referred by her primary care physician. She complains of tenseness, irritability, avolition, and fatigue. She worries incessantly that her children will get sick, a catastrophe will befall her husband, or she’ll do something wrong. She says she sometimes feels as if she’s thinking “a zillion racing thoughts.”

Once fun-loving, outgoing, and energetic, Ms. R says she began feeling unusually anxious 3 years ago. A psychiatrist diagnosed bipolar disorder type II based on her racing thoughts, irritability, low energy, and history of mood swings. Over 2 years, the psychiatrist tried combining valproic acid with bupropion, citalopram, or extended-release venlafaxine, then tried lithium monotherapy. Nothing worked.

Frustrated, Ms. R left the psychiatrist and consulted her primary care physician, who prescribed gabapentin, 200 mg each morning and 300 mg at night; fluoxetine, 50 mg/d; and quetiapine, 12.5 mg/d. Ms. R noticed no improvement and stopped the medications after 6 weeks. The physician urged her to see another psychiatrist, and she presented to us 2 weeks after stopping the medications.

Ms. R also has been feeling depressed and irritable the past 4 months and has trouble falling and staying asleep at night. She sleeps 4 to 5 hours nightly, constantly feels tired, cannot concentrate, and overeats to try to alleviate her stress. She has gained 6 pounds over 2 to 3 months and weighs 160 lb; her body mass index of 26 indicates she is overweight.

She says her worries overwhelm her and cause heart palpitations and muscle tension in her neck and shoulders. She admits to feeling “worthless,” but denies suicidal thoughts.

Ms. R describes her husband and two teenage daughters as “very supportive,” but admits that her fatigue and irritability have strained these relationships; she says she snaps at them for minor things, such as coming to dinner 1 minute late. She misses her job, which she recently quit because of her decreasing ability to function.

At intake, Ms. R says she will not resume previous medications but will consider alternatives. She refuses psychotherapy because of time constraints and transportation problems but is willing to return every 2 weeks for medication checks. She says she adhered to every prescription over 3 years with no major side effects. She has never taken an antidepressant or anxiolytic without a mood stabilizer.

Ms. R reports no medical problems, past substance use, current or past psychotic symptoms, or psychiatric hospitalizations. Her family history shows depression in one first-degree relative and anxiety in others. Her Hamilton Anxiety Scale (HAM-A) score of 20 indicates moderate anxiety. Laboratory tests ordered by her primary care physician are normal.

poll here

The authors’ observations

Racing thoughts, irritable mood, decreased sleep, and concentration problems can point to GAD, mania associated with bipolar disorder type I, or hypomania suggesting bipolar disorder type I or II (Table 1).¹

We suspect GAD because:

• Ms. R’s thoughts “race” only when she worries
• her irritability and concentration problems seem more sustained than episodic
• she has difficulty falling and staying asleep, but her need for sleep has not decreased
• she complains of constant fatigue, whereas abnormally high energy characterizes bipolar disorder’s manic or hypomanic phase.

Does Ms. R have depression? Determining if the patient’s depressive symptoms are secondary to GAD or warrant a separate diagnosis can be difficult (Table 1). With Ms. R’s permission, we talked to her family, because collateral information often helps clarify the diagnosis. Her husband and daughters offered no significant new insights, however.

Table 1

Overlap among symptoms that suggest GAD, mania, or major depression

Treatment: Targeting the anxiety

To address Ms. R’s anxiety symptoms, we start buspirone, 5 mg tid, and titrate to 15 mg bid over 2 weeks. We choose buspirone—which is FDA-approved to treat GAD—because it is unlikely to cause a mood switch if bipolar disorder is causing Ms. R’s depression. We discuss with her the drug’s indications, benefits, and potential side effects (such as vertigo, headache, lightheadedness, and nausea).

At the first 2-week follow-up, Ms. R reports no side effects but little improvement. After another 2 weeks, she says she feels less anxiety, irritability, pain, and fewer racing thoughts. She reports less difficulty falling asleep, though she’s still sleeping only about 6 hours nightly. Her HAM-A score falls to 12, indicating mild anxiety.

Ms. R, however, says she still feels depressed, tired, distracted, unmotivated, and worthless. Her Hamilton Rating Scale for Depression (HAM-D) score of 16 indicates moderate depression.

poll here

The authors’ observations

The persistence of Ms. R’s depressive symptoms suggests comorbid major depressive disorder (MDD). In fact, MDD and GAD are considered the most common mood-anxiety comorbidities.²

Determining whether Ms. R has unipolar depression or bipolar disorder is extremely important, considering the treatment implications. In patients with bipolar disorder, any antidepressant can trigger mania or hypomania if used without a mood stabilizer. Some studies also have associated rare cases of suicidal behavior with antidepressant use.^3,4 Lifetime risk of suicide in bipolar disorder is approximately 20 times that in the general population.⁵

Although Ms. R’s history does not reveal a previous manic episode, ruling out hypomania is difficult because it usually does not impair work or social functioning. Hypomania often goes unreported because others hardly notice it. Collateral history can uncover clues to hypomania (See For Your Patient), but Ms. R’s husband and daughters say they have not seen such episodes.

On the other hand, normal behavior can be mistaken for hypomania. Ms. R’s previous psychiatrist and primary care physician might have misinterpreted Ms. R’s baseline extroverted personality as hypomanic behavior. Also, her over-whelming depressive and anxiety symptoms between depressive episodes made her normal moods appear hypomanic.

Compared with unipolar depression, bipolar depression is more frequently associated with psychomotor retardation, hypersomnia, early onset, and family history of bipolar disorder.⁶ Ms. R, however, suffered low energy, terminal insomnia, and late onset, and had no known family history of bipolar disorder.

The Mood Disorder Questionnaire, a scale of self-administered questions, can help screen for symptoms that suggest bipolar disorder. A positive questionnaire result demands further clinical evaluation.⁷

Box

Continued treatment: ‘normal’ again

In addition to the HAM-D, we also administer the Mood Disorder Questionnaire. Results suggest Ms. R does not have bipolar illness.

To address Ms. R’s depressive symptoms, we start the selective serotonin reuptake inhibitor escitalopram at a low dosage (5 mg/d) to avoid exacerbating her anxiety. We discuss the drug’s potential to induce mania, hypomania, or other adverse effects such as nausea, anxiety, sleep disturbance, headache, and sexual dysfunction. Buspirone is maintained at 15 mg bid.

Two weeks later, Ms. R reports some increase in energy and motivation. After another 2 weeks, she reports significantly improved mood and concentration. She consistently falls asleep at 10 PM and sleeps 8 hours each night. She also finds time to read and go out with her friends and she gets along more amicably with her daughters and husband.

One month later, we increase escitalopram to 10 mg/d, a normal therapeutic dosage. Ms. R continues to respond positively and reports no side effects. Two months after starting the antidepressant, her HAM-D score of 8 suggests normal mood. We decrease follow-up visits to once monthly.

At a subsequent visit, Ms. R tells us she wants to find a job. A month later, she says she is enjoying her new job in a department store. Over the next 6 months, she remains free of anxiety, depressive symptoms, hypomanic behavior, and side effects. She tells us it’s nice to feel “normal” again.

We reduce Ms. R’s appointments to every 3 months. After another year, we refer her back to her primary care physician at her request.

The authors’ observations

DSM-IV-TR¹ divides bipolar disorder into three categories:

• type I, in which the patient has had at least one manic episode with or without major depression
• type II, characterized by one or more major depressive episodes and at least one hypomanic episode
• cyclothymia, which is defined as fluctuation between hypomanic and minor depressive episodes.

Much is said about how underdiagnosis of bipolar disorder⁸ delays or prevents proper therapy with mood stabilizers, leading to suboptimal symptom resolution. As with Ms. R, however, an incorrect bipolar disorder diagnosis can be just as harmful. Three years of unnecessary and ineffective treatment worsened her anxiety and depressive symptoms and quality of life.

A comprehensive clinical interview supplemented with insights from family and friends can minimize the risk of misdiagnosis when patients present with symptoms that suggest bipolar disorder, depression, or GAD.

Differentiating between the following clinical features can also help you reach a diagnosis:

Sleep/energy level. Mania/hypomania is characterized by decreased need for sleep; patients often feel energetic even after 2 to 4 hours of sleep. Both depression and GAD diminish energy level, although mood is more depressed in depression. Patients with GAD have trouble falling asleep, while those with depression awaken early or have hypersomnia.

Behavior. Patients in the manic phase of bipolar disorder engage in risky, pleasurable activities with high potential for painful consequences. This drastic behavior change is not seen in depression or GAD (Table 2).

Table 2

Differentiating symptoms common to GAD, major depression, and mania

Related resources

• Depression and Bipolar Support Alliance. www.dbsalliance.org.
• Anxiety Disorders Association of America. www.adaa.org.

Drug brand names

• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Quetiapine • Seroquel
• Valproic acid • Depakene
• Venlafaxine • Effexor

Disclosures

Dr. Williams is a speaker for Wyeth.

Dr. Singh reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘A zillion racing thoughts’

Ms. R, age 44, is referred by her primary care physician. She complains of tenseness, irritability, avolition, and fatigue. She worries incessantly that her children will get sick, a catastrophe will befall her husband, or she’ll do something wrong. She says she sometimes feels as if she’s thinking “a zillion racing thoughts.”

Once fun-loving, outgoing, and energetic, Ms. R says she began feeling unusually anxious 3 years ago. A psychiatrist diagnosed bipolar disorder type II based on her racing thoughts, irritability, low energy, and history of mood swings. Over 2 years, the psychiatrist tried combining valproic acid with bupropion, citalopram, or extended-release venlafaxine, then tried lithium monotherapy. Nothing worked.

Frustrated, Ms. R left the psychiatrist and consulted her primary care physician, who prescribed gabapentin, 200 mg each morning and 300 mg at night; fluoxetine, 50 mg/d; and quetiapine, 12.5 mg/d. Ms. R noticed no improvement and stopped the medications after 6 weeks. The physician urged her to see another psychiatrist, and she presented to us 2 weeks after stopping the medications.

Ms. R also has been feeling depressed and irritable the past 4 months and has trouble falling and staying asleep at night. She sleeps 4 to 5 hours nightly, constantly feels tired, cannot concentrate, and overeats to try to alleviate her stress. She has gained 6 pounds over 2 to 3 months and weighs 160 lb; her body mass index of 26 indicates she is overweight.

She says her worries overwhelm her and cause heart palpitations and muscle tension in her neck and shoulders. She admits to feeling “worthless,” but denies suicidal thoughts.

Ms. R describes her husband and two teenage daughters as “very supportive,” but admits that her fatigue and irritability have strained these relationships; she says she snaps at them for minor things, such as coming to dinner 1 minute late. She misses her job, which she recently quit because of her decreasing ability to function.

At intake, Ms. R says she will not resume previous medications but will consider alternatives. She refuses psychotherapy because of time constraints and transportation problems but is willing to return every 2 weeks for medication checks. She says she adhered to every prescription over 3 years with no major side effects. She has never taken an antidepressant or anxiolytic without a mood stabilizer.

Ms. R reports no medical problems, past substance use, current or past psychotic symptoms, or psychiatric hospitalizations. Her family history shows depression in one first-degree relative and anxiety in others. Her Hamilton Anxiety Scale (HAM-A) score of 20 indicates moderate anxiety. Laboratory tests ordered by her primary care physician are normal.

poll here

The authors’ observations

Racing thoughts, irritable mood, decreased sleep, and concentration problems can point to GAD, mania associated with bipolar disorder type I, or hypomania suggesting bipolar disorder type I or II (Table 1).¹

We suspect GAD because:

• Ms. R’s thoughts “race” only when she worries
• her irritability and concentration problems seem more sustained than episodic
• she has difficulty falling and staying asleep, but her need for sleep has not decreased
• she complains of constant fatigue, whereas abnormally high energy characterizes bipolar disorder’s manic or hypomanic phase.

Does Ms. R have depression? Determining if the patient’s depressive symptoms are secondary to GAD or warrant a separate diagnosis can be difficult (Table 1). With Ms. R’s permission, we talked to her family, because collateral information often helps clarify the diagnosis. Her husband and daughters offered no significant new insights, however.

Table 1

Overlap among symptoms that suggest GAD, mania, or major depression

Treatment: Targeting the anxiety

To address Ms. R’s anxiety symptoms, we start buspirone, 5 mg tid, and titrate to 15 mg bid over 2 weeks. We choose buspirone—which is FDA-approved to treat GAD—because it is unlikely to cause a mood switch if bipolar disorder is causing Ms. R’s depression. We discuss with her the drug’s indications, benefits, and potential side effects (such as vertigo, headache, lightheadedness, and nausea).

At the first 2-week follow-up, Ms. R reports no side effects but little improvement. After another 2 weeks, she says she feels less anxiety, irritability, pain, and fewer racing thoughts. She reports less difficulty falling asleep, though she’s still sleeping only about 6 hours nightly. Her HAM-A score falls to 12, indicating mild anxiety.

Ms. R, however, says she still feels depressed, tired, distracted, unmotivated, and worthless. Her Hamilton Rating Scale for Depression (HAM-D) score of 16 indicates moderate depression.

poll here

The authors’ observations

The persistence of Ms. R’s depressive symptoms suggests comorbid major depressive disorder (MDD). In fact, MDD and GAD are considered the most common mood-anxiety comorbidities.²

Determining whether Ms. R has unipolar depression or bipolar disorder is extremely important, considering the treatment implications. In patients with bipolar disorder, any antidepressant can trigger mania or hypomania if used without a mood stabilizer. Some studies also have associated rare cases of suicidal behavior with antidepressant use.^3,4 Lifetime risk of suicide in bipolar disorder is approximately 20 times that in the general population.⁵

Although Ms. R’s history does not reveal a previous manic episode, ruling out hypomania is difficult because it usually does not impair work or social functioning. Hypomania often goes unreported because others hardly notice it. Collateral history can uncover clues to hypomania (See For Your Patient), but Ms. R’s husband and daughters say they have not seen such episodes.

On the other hand, normal behavior can be mistaken for hypomania. Ms. R’s previous psychiatrist and primary care physician might have misinterpreted Ms. R’s baseline extroverted personality as hypomanic behavior. Also, her over-whelming depressive and anxiety symptoms between depressive episodes made her normal moods appear hypomanic.

Compared with unipolar depression, bipolar depression is more frequently associated with psychomotor retardation, hypersomnia, early onset, and family history of bipolar disorder.⁶ Ms. R, however, suffered low energy, terminal insomnia, and late onset, and had no known family history of bipolar disorder.

The Mood Disorder Questionnaire, a scale of self-administered questions, can help screen for symptoms that suggest bipolar disorder. A positive questionnaire result demands further clinical evaluation.⁷

Box

Continued treatment: ‘normal’ again

In addition to the HAM-D, we also administer the Mood Disorder Questionnaire. Results suggest Ms. R does not have bipolar illness.

To address Ms. R’s depressive symptoms, we start the selective serotonin reuptake inhibitor escitalopram at a low dosage (5 mg/d) to avoid exacerbating her anxiety. We discuss the drug’s potential to induce mania, hypomania, or other adverse effects such as nausea, anxiety, sleep disturbance, headache, and sexual dysfunction. Buspirone is maintained at 15 mg bid.

Two weeks later, Ms. R reports some increase in energy and motivation. After another 2 weeks, she reports significantly improved mood and concentration. She consistently falls asleep at 10 PM and sleeps 8 hours each night. She also finds time to read and go out with her friends and she gets along more amicably with her daughters and husband.

One month later, we increase escitalopram to 10 mg/d, a normal therapeutic dosage. Ms. R continues to respond positively and reports no side effects. Two months after starting the antidepressant, her HAM-D score of 8 suggests normal mood. We decrease follow-up visits to once monthly.

At a subsequent visit, Ms. R tells us she wants to find a job. A month later, she says she is enjoying her new job in a department store. Over the next 6 months, she remains free of anxiety, depressive symptoms, hypomanic behavior, and side effects. She tells us it’s nice to feel “normal” again.

We reduce Ms. R’s appointments to every 3 months. After another year, we refer her back to her primary care physician at her request.

The authors’ observations

DSM-IV-TR¹ divides bipolar disorder into three categories:

• type I, in which the patient has had at least one manic episode with or without major depression
• type II, characterized by one or more major depressive episodes and at least one hypomanic episode
• cyclothymia, which is defined as fluctuation between hypomanic and minor depressive episodes.

Much is said about how underdiagnosis of bipolar disorder⁸ delays or prevents proper therapy with mood stabilizers, leading to suboptimal symptom resolution. As with Ms. R, however, an incorrect bipolar disorder diagnosis can be just as harmful. Three years of unnecessary and ineffective treatment worsened her anxiety and depressive symptoms and quality of life.

A comprehensive clinical interview supplemented with insights from family and friends can minimize the risk of misdiagnosis when patients present with symptoms that suggest bipolar disorder, depression, or GAD.

Differentiating between the following clinical features can also help you reach a diagnosis:

Sleep/energy level. Mania/hypomania is characterized by decreased need for sleep; patients often feel energetic even after 2 to 4 hours of sleep. Both depression and GAD diminish energy level, although mood is more depressed in depression. Patients with GAD have trouble falling asleep, while those with depression awaken early or have hypersomnia.

Behavior. Patients in the manic phase of bipolar disorder engage in risky, pleasurable activities with high potential for painful consequences. This drastic behavior change is not seen in depression or GAD (Table 2).

Table 2

Differentiating symptoms common to GAD, major depression, and mania

Related resources

• Depression and Bipolar Support Alliance. www.dbsalliance.org.
• Anxiety Disorders Association of America. www.adaa.org.

Drug brand names

• Bupropion • Wellbutrin
• Buspirone • BuSpar
• Escitalopram • Lexapro
• Fluoxetine • Prozac
• Gabapentin • Neurontin
• Quetiapine • Seroquel
• Valproic acid • Depakene
• Venlafaxine • Effexor

Disclosures

Dr. Williams is a speaker for Wyeth.

Dr. Singh reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘I can’t face myself’

Jimmy, age 12, is referred to us by his pediatrician, who is concerned about his “frequent nighttime accidents.” His parents report that he wets his bed 5 to 6 times weekly and has never stayed consistently dry for more than a few days.

The accidents occur only at night, his parents say. Numerous interventions have failed, including restricting fluids after dinner and awakening the boy overnight to make him go to the bathroom.

Jimmy, a sixth-grader, wonders if he will ever stop wetting his bed. He refuses to go to summer camp or stay overnight at a friend’s house, fearful that other kids will make fun of him after an accident. Asked how “wet nights” are affecting his life, he says, “I can’t face myself in the mirror.”

The authors’ observations

Primary nocturnal enuresis is diagnosed in children age ≥5 who have never gone 6 consecutive months without an overnight accident. Pediatricians generally discover enuresis incidentally during regular checkups and refer to a psychiatrist only if the child has an emotional problem secondary to enuresis or a comorbid psychiatric disorder.

Once identified, enuresis requires a thorough assessment—including its emotional consequences, which for Jimmy are significant. In its practice parameter for treating enuresis, the American Academy of Child and Adolescent Psychiatry (AACAP)¹ suggests that you:

Take an extensive developmental and family history. Find out if the child was toilet trained and started walking, talking, or running at an appropriate age. Delays in reaching developmental milestones can predict enuresis.¹

Also find out if either parent had enuresis during childhood. Enuresis is heritable,² and children often outgrow the problem at the same age as did the parent(s).

Focus on the bedwetting and the child’s reaction to it. Treat enuresis aggressively if it is hurting the child’s performance at school, social or emotional development, or self-esteem, or if the youth appears emotionally withdrawn or distressed.

Interview the child and parents separately, as each often reacts differently to the problem. In some cases, for example, the child’s bedwetting upsets the parents but the child hardly seems to care. Also, children often feel more at ease talking to a doctor alone, and parents can vent frustration without upsetting their child.

While interviewing the child, listen for psychosocial stressors that can lead to enuresis, such as parents’ marital problems, problems at school, recent hospitalization, physical or sexual abuse, or the recent birth of a sibling.

We spend about one half-hour with the child and another half-hour with the parents to thoroughly gauge enuresis’ emotional impact. To engage the child and hold his attention during that half-hour, we offer toys or play a game.

Check for physical causes. According to the AACAP practice parameter for enuresis treatment, you should:

• assess nare patency and voice quality to rule out enlarged adenoids
  
• check the nasal pharynx for enlarged tonsils
  
• palpate the abdomen to check for bladder distention or fecal impaction
  
• examine genitalia for abnormalities
  
• view the back for a sacral dimple or other sign of a vertebral or spinal cord anomaly.
  

Perform a urinalysis and urine culture to rule out urinary tract infection (UTI).

Order urodynamic studies or renal ultrasound if enuresis persists after two unsuccessful treatment trials, the physical examination uncovers positive findings, or the child has had a UTI.

Psychotherapy has a limited role in treating primary enuresis unless you suspect a psychological cause.¹ We offered Jimmy supportive counseling to help alleviate emotional problems caused by bedwetting. He and his parents declined but agreed to reconsider later.

Further history: Toilet trained At 2

Jimmy was toilet trained at age 2 and reached all other age-appropriate developmental milestones, his mother says. Results of urine culture, repeated urinalyses, and neurologic and physical examinations are normal. Neither Jimmy nor his family have a history of UTI, dysuria, urgency, or increased urination frequency.

When Jimmy was age 9, his pediatrician prescribed imipramine, 25 mg/d, to try to stop his bedwetting. He did not respond after 6 months, so his parents stopped giving the drug to him.

A few months later, Jimmy’s parents heard about a “bedwetting alarm” designed to condition children not to urinate while asleep, but the boy and his parents viewed this treatment as “humiliating” and refused to try it. They have not attempted another intervention for 2 years.

poll here

The authors’ observations

Having found no medical or psychological basis for Jimmy’s enuresis (Box), we pondered our next clinical move.

Box

Among behavioral treatments, only the bedwetting alarm has shown effectiveness in clinical trials,^1,3 and it carries the lowest risk of post-treatment relapse.³ Urine moistens a sensor in the bed pad or inside cloth, triggering an alarm that awakens the child when wetting starts. The child gradually awakens earlier in an enuretic episode until the sensation of bladder fullness awakens him.

Many parents/guardians and their children—particularly older youths—consider alarm systems demeaning. We again suggested this treatment to Jimmy and his parents, but they refused.

Medication. Six months of low-dose imipramine, a tricyclic antidepressant often prescribed for enuresis, produced no response. We did not restart imipramine at a higher dosage because of its association with increased arrhythmia risk.

We instead considered desmopressin acetate, a synthetic analog of ADH vasopressin that regulates diurnal variation, which is usually abnormal in children with enuresis. Desmopressin, often used to treat clozapine-induced enuresis in adults, has been associated with successful outcomes in as many as 65% of children in clinical trials.^1,4

Desmopressin, however, can reduce urine production. Water intoxication or hyponatremia is rare but can lead to seizures or coma, and the risk increases with the dosage. Obtain informed consent from the parents before starting this drug. Check electrolytes 2 or 3 days after the first dose, 1 month later, then again every 2 to 3 months. Discontinue at once if serum sodium decreases significantly from baseline or is

Treatment: Meaningless response

We start Jimmy on oral desmopressin, 0.2 mg at bedtime, after discussing its benefits and risks with his parents. We increase the dosage to 0.4 mg after 3 days and to 0.6 mg the following week, as the lower dosages have not worked. Serum electrolytes, gauged before starting desmopressin and again 2 weeks later, are normal. We see Jimmy every 2 weeks to check progress and monitor for side effects.

Soon after the second dosage increase, Jimmy’s accidents gradually decrease to 2 to 3 per week, but no improvement is seen after that.

Two months later, Jimmy is still avoiding sleepovers and has trouble making friends. His parents worry about his increasing frustration, hopelessness, and low self-esteem. We again offer supportive counseling, but the boy refuses.

poll here

The authors’ observations

We were running out of treatment options. Two medication trials failed, and the family still would not try a bedwetting alarm.

Urodynamic testing usually is not ordered unless the child has a history of urge incontinence or UTI. For some treatment-resistant patients, the test can reveal detruser muscle or bladder capacity deficits that might be causing enuresis.

Testing: Below the norm

We refer Jimmy to a urologist for a urodynamic test. Results showed mild detruser muscle instability and slightly low maximum bladder capacity compared with age-predicted norms.

The authors’ observations

Based on this finding, we considered oxybutynin, an anticholinergic agent that increases bladder control by relaxing the smooth muscles. Patients with detruser instability and inadequate bladder capacity have responded well to oxybutynin in clinical trials,^5,6 and combination oxybutynin/desmopressin therapy has been shown effective in treatment-resistant patients.^7-9

Oxybutynin and desmopressin complement each other; reduced urinary output and bladder filling associated with desmopressin can reduce uninhibited bladder contractions, thus enhancing oxybutynin’s action.

Treatment: Happy summer

We continue desmopressin, 0.6 mg nightly, and add extended-release oxybutynin, 2.5 mg/d. We increase oxybutynin to 5 mg/d after 3 days and to 10 mg/d the following week, as Jimmy reported no side effects from the lower dosages.

We see Jimmy 1 week after adding oxybutynin, then again 3 weeks later. He reports no wet nights after 1 month of combination therapy, then wets his bed once over the next 2 months. We continue to see him every 3 to 4 weeks and check his electrolytes every 2 to 3 months. He reports no side effects

Five months after starting combination therapy, Jimmy seems much more confident. He has gone 2 months without a bedwetting accident, and his face lights up while discussing the fun he had last week in summer camp. He remains free of side effects, and his parents are thrilled with his progress.

We see Jimmy three more times, once every 2 months. He is staying “dry” but says he wishes to stop his medication because he wants to control his bladder without it.

poll here

The authors’ observations

Medications and behavioral treatments can preserve the child’s self-esteem until he or she outgrows enuresis (Table).

No guidelines address drug regimen duration. Tapering Jimmy’s medications after 7 to 8 months seemed reasonable, but children with enuresis often relapse after stopping treatment. Researchers have recorded relapse rates as high as 60% after stopping imipramine and 80% after stopping desmopressin.^1,4

Taper medications slowly to avoid withdrawal, immediate relapse, and anticholinergic effects. If the child relapses, restart medication at the previous therapeutic dosage(s), then start tapering after the child has been accident-free for 3 months.

Table

Medication strategies for treating enuresis

Follow-up: Still dry

After discussing the relapse risk with Jimmy’s parents, we withdraw both oxybutynin and desmopressin over 2 months, reducing each dosage 25% every 2 weeks. We see Jimmy every 4 to 6 weeks during the taper period, then for two bimonthly follow-up visits. He reports no adverse effects and has been accident-free for 8 months.

After consulting with his pediatrician and family, we refer Jimmy, now age 13, back to the pediatrician. We have not seen him for more than 1 year.

Related resources

• National Association For Continence. www.nafc.org.
  
• Mayo ME, Burns MW. Urodynamic studies in children who wet. Br J Urol 1990 65;641-5.
  

• Desmopressin • DDAVP
  
• Imipramine • Tofranil
  
• Oxybutynin • Ditropan
  

Dr. Williams is a speaker for Wyeth.

Dr. Singh reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘I can’t face myself’

Jimmy, age 12, is referred to us by his pediatrician, who is concerned about his “frequent nighttime accidents.” His parents report that he wets his bed 5 to 6 times weekly and has never stayed consistently dry for more than a few days.

The accidents occur only at night, his parents say. Numerous interventions have failed, including restricting fluids after dinner and awakening the boy overnight to make him go to the bathroom.

Jimmy, a sixth-grader, wonders if he will ever stop wetting his bed. He refuses to go to summer camp or stay overnight at a friend’s house, fearful that other kids will make fun of him after an accident. Asked how “wet nights” are affecting his life, he says, “I can’t face myself in the mirror.”

The authors’ observations

Primary nocturnal enuresis is diagnosed in children age ≥5 who have never gone 6 consecutive months without an overnight accident. Pediatricians generally discover enuresis incidentally during regular checkups and refer to a psychiatrist only if the child has an emotional problem secondary to enuresis or a comorbid psychiatric disorder.

Once identified, enuresis requires a thorough assessment—including its emotional consequences, which for Jimmy are significant. In its practice parameter for treating enuresis, the American Academy of Child and Adolescent Psychiatry (AACAP)¹ suggests that you:

Take an extensive developmental and family history. Find out if the child was toilet trained and started walking, talking, or running at an appropriate age. Delays in reaching developmental milestones can predict enuresis.¹

Also find out if either parent had enuresis during childhood. Enuresis is heritable,² and children often outgrow the problem at the same age as did the parent(s).

Focus on the bedwetting and the child’s reaction to it. Treat enuresis aggressively if it is hurting the child’s performance at school, social or emotional development, or self-esteem, or if the youth appears emotionally withdrawn or distressed.

Interview the child and parents separately, as each often reacts differently to the problem. In some cases, for example, the child’s bedwetting upsets the parents but the child hardly seems to care. Also, children often feel more at ease talking to a doctor alone, and parents can vent frustration without upsetting their child.

While interviewing the child, listen for psychosocial stressors that can lead to enuresis, such as parents’ marital problems, problems at school, recent hospitalization, physical or sexual abuse, or the recent birth of a sibling.

We spend about one half-hour with the child and another half-hour with the parents to thoroughly gauge enuresis’ emotional impact. To engage the child and hold his attention during that half-hour, we offer toys or play a game.

Check for physical causes. According to the AACAP practice parameter for enuresis treatment, you should:

• assess nare patency and voice quality to rule out enlarged adenoids
  
• check the nasal pharynx for enlarged tonsils
  
• palpate the abdomen to check for bladder distention or fecal impaction
  
• examine genitalia for abnormalities
  
• view the back for a sacral dimple or other sign of a vertebral or spinal cord anomaly.
  

Perform a urinalysis and urine culture to rule out urinary tract infection (UTI).

Order urodynamic studies or renal ultrasound if enuresis persists after two unsuccessful treatment trials, the physical examination uncovers positive findings, or the child has had a UTI.

Psychotherapy has a limited role in treating primary enuresis unless you suspect a psychological cause.¹ We offered Jimmy supportive counseling to help alleviate emotional problems caused by bedwetting. He and his parents declined but agreed to reconsider later.

Further history: Toilet trained At 2

Jimmy was toilet trained at age 2 and reached all other age-appropriate developmental milestones, his mother says. Results of urine culture, repeated urinalyses, and neurologic and physical examinations are normal. Neither Jimmy nor his family have a history of UTI, dysuria, urgency, or increased urination frequency.

When Jimmy was age 9, his pediatrician prescribed imipramine, 25 mg/d, to try to stop his bedwetting. He did not respond after 6 months, so his parents stopped giving the drug to him.

A few months later, Jimmy’s parents heard about a “bedwetting alarm” designed to condition children not to urinate while asleep, but the boy and his parents viewed this treatment as “humiliating” and refused to try it. They have not attempted another intervention for 2 years.

poll here

The authors’ observations

Having found no medical or psychological basis for Jimmy’s enuresis (Box), we pondered our next clinical move.

Box

Among behavioral treatments, only the bedwetting alarm has shown effectiveness in clinical trials,^1,3 and it carries the lowest risk of post-treatment relapse.³ Urine moistens a sensor in the bed pad or inside cloth, triggering an alarm that awakens the child when wetting starts. The child gradually awakens earlier in an enuretic episode until the sensation of bladder fullness awakens him.

Many parents/guardians and their children—particularly older youths—consider alarm systems demeaning. We again suggested this treatment to Jimmy and his parents, but they refused.

Medication. Six months of low-dose imipramine, a tricyclic antidepressant often prescribed for enuresis, produced no response. We did not restart imipramine at a higher dosage because of its association with increased arrhythmia risk.

We instead considered desmopressin acetate, a synthetic analog of ADH vasopressin that regulates diurnal variation, which is usually abnormal in children with enuresis. Desmopressin, often used to treat clozapine-induced enuresis in adults, has been associated with successful outcomes in as many as 65% of children in clinical trials.^1,4

Desmopressin, however, can reduce urine production. Water intoxication or hyponatremia is rare but can lead to seizures or coma, and the risk increases with the dosage. Obtain informed consent from the parents before starting this drug. Check electrolytes 2 or 3 days after the first dose, 1 month later, then again every 2 to 3 months. Discontinue at once if serum sodium decreases significantly from baseline or is

Treatment: Meaningless response

We start Jimmy on oral desmopressin, 0.2 mg at bedtime, after discussing its benefits and risks with his parents. We increase the dosage to 0.4 mg after 3 days and to 0.6 mg the following week, as the lower dosages have not worked. Serum electrolytes, gauged before starting desmopressin and again 2 weeks later, are normal. We see Jimmy every 2 weeks to check progress and monitor for side effects.

Soon after the second dosage increase, Jimmy’s accidents gradually decrease to 2 to 3 per week, but no improvement is seen after that.

Two months later, Jimmy is still avoiding sleepovers and has trouble making friends. His parents worry about his increasing frustration, hopelessness, and low self-esteem. We again offer supportive counseling, but the boy refuses.

poll here

The authors’ observations

We were running out of treatment options. Two medication trials failed, and the family still would not try a bedwetting alarm.

Urodynamic testing usually is not ordered unless the child has a history of urge incontinence or UTI. For some treatment-resistant patients, the test can reveal detruser muscle or bladder capacity deficits that might be causing enuresis.

Testing: Below the norm

We refer Jimmy to a urologist for a urodynamic test. Results showed mild detruser muscle instability and slightly low maximum bladder capacity compared with age-predicted norms.

The authors’ observations

Based on this finding, we considered oxybutynin, an anticholinergic agent that increases bladder control by relaxing the smooth muscles. Patients with detruser instability and inadequate bladder capacity have responded well to oxybutynin in clinical trials,^5,6 and combination oxybutynin/desmopressin therapy has been shown effective in treatment-resistant patients.^7-9

Oxybutynin and desmopressin complement each other; reduced urinary output and bladder filling associated with desmopressin can reduce uninhibited bladder contractions, thus enhancing oxybutynin’s action.

Treatment: Happy summer

We continue desmopressin, 0.6 mg nightly, and add extended-release oxybutynin, 2.5 mg/d. We increase oxybutynin to 5 mg/d after 3 days and to 10 mg/d the following week, as Jimmy reported no side effects from the lower dosages.

We see Jimmy 1 week after adding oxybutynin, then again 3 weeks later. He reports no wet nights after 1 month of combination therapy, then wets his bed once over the next 2 months. We continue to see him every 3 to 4 weeks and check his electrolytes every 2 to 3 months. He reports no side effects

Five months after starting combination therapy, Jimmy seems much more confident. He has gone 2 months without a bedwetting accident, and his face lights up while discussing the fun he had last week in summer camp. He remains free of side effects, and his parents are thrilled with his progress.

We see Jimmy three more times, once every 2 months. He is staying “dry” but says he wishes to stop his medication because he wants to control his bladder without it.

poll here

The authors’ observations

Medications and behavioral treatments can preserve the child’s self-esteem until he or she outgrows enuresis (Table).

No guidelines address drug regimen duration. Tapering Jimmy’s medications after 7 to 8 months seemed reasonable, but children with enuresis often relapse after stopping treatment. Researchers have recorded relapse rates as high as 60% after stopping imipramine and 80% after stopping desmopressin.^1,4

Taper medications slowly to avoid withdrawal, immediate relapse, and anticholinergic effects. If the child relapses, restart medication at the previous therapeutic dosage(s), then start tapering after the child has been accident-free for 3 months.

Table

Medication strategies for treating enuresis

Follow-up: Still dry

After discussing the relapse risk with Jimmy’s parents, we withdraw both oxybutynin and desmopressin over 2 months, reducing each dosage 25% every 2 weeks. We see Jimmy every 4 to 6 weeks during the taper period, then for two bimonthly follow-up visits. He reports no adverse effects and has been accident-free for 8 months.

After consulting with his pediatrician and family, we refer Jimmy, now age 13, back to the pediatrician. We have not seen him for more than 1 year.

Related resources

• National Association For Continence. www.nafc.org.
  
• Mayo ME, Burns MW. Urodynamic studies in children who wet. Br J Urol 1990 65;641-5.
  

• Desmopressin • DDAVP
  
• Imipramine • Tofranil
  
• Oxybutynin • Ditropan
  

Dr. Williams is a speaker for Wyeth.

Dr. Singh reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.

History: ‘I can’t face myself’

Jimmy, age 12, is referred to us by his pediatrician, who is concerned about his “frequent nighttime accidents.” His parents report that he wets his bed 5 to 6 times weekly and has never stayed consistently dry for more than a few days.

The accidents occur only at night, his parents say. Numerous interventions have failed, including restricting fluids after dinner and awakening the boy overnight to make him go to the bathroom.

Jimmy, a sixth-grader, wonders if he will ever stop wetting his bed. He refuses to go to summer camp or stay overnight at a friend’s house, fearful that other kids will make fun of him after an accident. Asked how “wet nights” are affecting his life, he says, “I can’t face myself in the mirror.”

The authors’ observations

Primary nocturnal enuresis is diagnosed in children age ≥5 who have never gone 6 consecutive months without an overnight accident. Pediatricians generally discover enuresis incidentally during regular checkups and refer to a psychiatrist only if the child has an emotional problem secondary to enuresis or a comorbid psychiatric disorder.

Once identified, enuresis requires a thorough assessment—including its emotional consequences, which for Jimmy are significant. In its practice parameter for treating enuresis, the American Academy of Child and Adolescent Psychiatry (AACAP)¹ suggests that you:

Take an extensive developmental and family history. Find out if the child was toilet trained and started walking, talking, or running at an appropriate age. Delays in reaching developmental milestones can predict enuresis.¹

Also find out if either parent had enuresis during childhood. Enuresis is heritable,² and children often outgrow the problem at the same age as did the parent(s).

Focus on the bedwetting and the child’s reaction to it. Treat enuresis aggressively if it is hurting the child’s performance at school, social or emotional development, or self-esteem, or if the youth appears emotionally withdrawn or distressed.

Interview the child and parents separately, as each often reacts differently to the problem. In some cases, for example, the child’s bedwetting upsets the parents but the child hardly seems to care. Also, children often feel more at ease talking to a doctor alone, and parents can vent frustration without upsetting their child.

While interviewing the child, listen for psychosocial stressors that can lead to enuresis, such as parents’ marital problems, problems at school, recent hospitalization, physical or sexual abuse, or the recent birth of a sibling.

We spend about one half-hour with the child and another half-hour with the parents to thoroughly gauge enuresis’ emotional impact. To engage the child and hold his attention during that half-hour, we offer toys or play a game.

Check for physical causes. According to the AACAP practice parameter for enuresis treatment, you should:

• assess nare patency and voice quality to rule out enlarged adenoids
  
• check the nasal pharynx for enlarged tonsils
  
• palpate the abdomen to check for bladder distention or fecal impaction
  
• examine genitalia for abnormalities
  
• view the back for a sacral dimple or other sign of a vertebral or spinal cord anomaly.
  

Perform a urinalysis and urine culture to rule out urinary tract infection (UTI).

Order urodynamic studies or renal ultrasound if enuresis persists after two unsuccessful treatment trials, the physical examination uncovers positive findings, or the child has had a UTI.

Psychotherapy has a limited role in treating primary enuresis unless you suspect a psychological cause.¹ We offered Jimmy supportive counseling to help alleviate emotional problems caused by bedwetting. He and his parents declined but agreed to reconsider later.

Further history: Toilet trained At 2

Jimmy was toilet trained at age 2 and reached all other age-appropriate developmental milestones, his mother says. Results of urine culture, repeated urinalyses, and neurologic and physical examinations are normal. Neither Jimmy nor his family have a history of UTI, dysuria, urgency, or increased urination frequency.

When Jimmy was age 9, his pediatrician prescribed imipramine, 25 mg/d, to try to stop his bedwetting. He did not respond after 6 months, so his parents stopped giving the drug to him.

A few months later, Jimmy’s parents heard about a “bedwetting alarm” designed to condition children not to urinate while asleep, but the boy and his parents viewed this treatment as “humiliating” and refused to try it. They have not attempted another intervention for 2 years.

poll here

The authors’ observations

Having found no medical or psychological basis for Jimmy’s enuresis (Box), we pondered our next clinical move.

Box

Among behavioral treatments, only the bedwetting alarm has shown effectiveness in clinical trials,^1,3 and it carries the lowest risk of post-treatment relapse.³ Urine moistens a sensor in the bed pad or inside cloth, triggering an alarm that awakens the child when wetting starts. The child gradually awakens earlier in an enuretic episode until the sensation of bladder fullness awakens him.

Many parents/guardians and their children—particularly older youths—consider alarm systems demeaning. We again suggested this treatment to Jimmy and his parents, but they refused.

Medication. Six months of low-dose imipramine, a tricyclic antidepressant often prescribed for enuresis, produced no response. We did not restart imipramine at a higher dosage because of its association with increased arrhythmia risk.

We instead considered desmopressin acetate, a synthetic analog of ADH vasopressin that regulates diurnal variation, which is usually abnormal in children with enuresis. Desmopressin, often used to treat clozapine-induced enuresis in adults, has been associated with successful outcomes in as many as 65% of children in clinical trials.^1,4

Desmopressin, however, can reduce urine production. Water intoxication or hyponatremia is rare but can lead to seizures or coma, and the risk increases with the dosage. Obtain informed consent from the parents before starting this drug. Check electrolytes 2 or 3 days after the first dose, 1 month later, then again every 2 to 3 months. Discontinue at once if serum sodium decreases significantly from baseline or is

Treatment: Meaningless response

We start Jimmy on oral desmopressin, 0.2 mg at bedtime, after discussing its benefits and risks with his parents. We increase the dosage to 0.4 mg after 3 days and to 0.6 mg the following week, as the lower dosages have not worked. Serum electrolytes, gauged before starting desmopressin and again 2 weeks later, are normal. We see Jimmy every 2 weeks to check progress and monitor for side effects.

Soon after the second dosage increase, Jimmy’s accidents gradually decrease to 2 to 3 per week, but no improvement is seen after that.

Two months later, Jimmy is still avoiding sleepovers and has trouble making friends. His parents worry about his increasing frustration, hopelessness, and low self-esteem. We again offer supportive counseling, but the boy refuses.

poll here

The authors’ observations

We were running out of treatment options. Two medication trials failed, and the family still would not try a bedwetting alarm.

Urodynamic testing usually is not ordered unless the child has a history of urge incontinence or UTI. For some treatment-resistant patients, the test can reveal detruser muscle or bladder capacity deficits that might be causing enuresis.

Testing: Below the norm

We refer Jimmy to a urologist for a urodynamic test. Results showed mild detruser muscle instability and slightly low maximum bladder capacity compared with age-predicted norms.

The authors’ observations

Based on this finding, we considered oxybutynin, an anticholinergic agent that increases bladder control by relaxing the smooth muscles. Patients with detruser instability and inadequate bladder capacity have responded well to oxybutynin in clinical trials,^5,6 and combination oxybutynin/desmopressin therapy has been shown effective in treatment-resistant patients.^7-9

Oxybutynin and desmopressin complement each other; reduced urinary output and bladder filling associated with desmopressin can reduce uninhibited bladder contractions, thus enhancing oxybutynin’s action.

Treatment: Happy summer

We continue desmopressin, 0.6 mg nightly, and add extended-release oxybutynin, 2.5 mg/d. We increase oxybutynin to 5 mg/d after 3 days and to 10 mg/d the following week, as Jimmy reported no side effects from the lower dosages.

We see Jimmy 1 week after adding oxybutynin, then again 3 weeks later. He reports no wet nights after 1 month of combination therapy, then wets his bed once over the next 2 months. We continue to see him every 3 to 4 weeks and check his electrolytes every 2 to 3 months. He reports no side effects

Five months after starting combination therapy, Jimmy seems much more confident. He has gone 2 months without a bedwetting accident, and his face lights up while discussing the fun he had last week in summer camp. He remains free of side effects, and his parents are thrilled with his progress.

We see Jimmy three more times, once every 2 months. He is staying “dry” but says he wishes to stop his medication because he wants to control his bladder without it.

poll here

The authors’ observations

Medications and behavioral treatments can preserve the child’s self-esteem until he or she outgrows enuresis (Table).

No guidelines address drug regimen duration. Tapering Jimmy’s medications after 7 to 8 months seemed reasonable, but children with enuresis often relapse after stopping treatment. Researchers have recorded relapse rates as high as 60% after stopping imipramine and 80% after stopping desmopressin.^1,4

Taper medications slowly to avoid withdrawal, immediate relapse, and anticholinergic effects. If the child relapses, restart medication at the previous therapeutic dosage(s), then start tapering after the child has been accident-free for 3 months.

Table

Medication strategies for treating enuresis

Follow-up: Still dry

After discussing the relapse risk with Jimmy’s parents, we withdraw both oxybutynin and desmopressin over 2 months, reducing each dosage 25% every 2 weeks. We see Jimmy every 4 to 6 weeks during the taper period, then for two bimonthly follow-up visits. He reports no adverse effects and has been accident-free for 8 months.

After consulting with his pediatrician and family, we refer Jimmy, now age 13, back to the pediatrician. We have not seen him for more than 1 year.

Related resources

• National Association For Continence. www.nafc.org.
  
• Mayo ME, Burns MW. Urodynamic studies in children who wet. Br J Urol 1990 65;641-5.
  

• Desmopressin • DDAVP
  
• Imipramine • Tofranil
  
• Oxybutynin • Ditropan
  

Dr. Williams is a speaker for Wyeth.

Dr. Singh reports no financial relationship with any company whose products are mentioned in this article, or with manufacturers of competing products.