Henry A. Nasrallah, MD

The psychopharmacology era that began 6 decades ago has had a momentous and transformative effect on the identity and practice of psychiatry. It enabled community-based treatment and follow-up to supplant institutional warehousing of persons with serious mental disorders. The discovery of neurotransmitter pathways and receptors involved in the mechanism of action of antipsychotic, antidepressant, and anxiolytic agents sparked the neuroscience revolution that has become 1 of the fastest-moving frontiers in medicine.

Over the past few years, the shine seems to have worn off and psychopharmacology appears to be in limbo between the serendipitous but aging discoveries of the past and the exciting but unfulfilled promise of future breakthroughs. Psychopharmacology is in urgent need of a renaissance to propel it into new directions that will maintain its credibility as the core of psychiatric therapeutics. The following are some issues and challenges that may influence how psychopharmacology can surge forward and restore its “mojo.”

Scientific challenges. Psychopharmacology must decisively move from serendipity and its corollaries to rational, pathophysiology-based drug development. We need a translational “Marshall Plan” to exploit genetic and molecular neurobiology advances to develop radically new pharmacologic biotherapies for psychiatric brain disorders.

Conceptual challenges. As long as psychiatric diagnoses are based on clusters of symptoms assembled by committees, it makes little sense for the FDA to mandate that a drug must work for a DSM diagnosis instead of specific symptoms. Psychiatric disorders share many symptoms such as depressed mood, anxiety, agitation, hallucinations, delusions, insomnia, impulsivity, etc. Approving new drugs for target symptoms rather than a DSM diagnosis might eliminate the often deplored—yet necessary—practice referred to as “off-label” pharmacotherapy. Frankly, it is silly that an antipsychotic must be approved separately for schizophrenia, schizoaffective disorder, psychotic mania, delusional disorder, or brief reactive psychosis when these disorders all share delusions or hallucinations that respond to that same agent. The high cost of conducting redundant clinical trials for all antipsychotic drugs in each psychotic disorder is far better invested in discovering agents with new mechanisms of action.

Disease heterogeneity. Research strongly points to a substantial heterogeneity in practically every psychiatric disorder, with multiple genotypes and phenotypes that share common features. Therefore, there will always be full responders, partial responders, and refractory patients in any psychiatric illness. Rational psychopharmacology must develop strategies to prospectively identify these subgroups by using pharmacogenetic markers that should become a vital component of guiding treatment selection.

Big picture issues

Who will spearhead the psychopharmacology of the future? There is a tremendous unmet need, with >80% of psychiatric disorders having no FDA-approved medication, and a substantial proportion of patients who do receive an approved drug often remain disabled even after symptomatic improvement. This unmet need is not just for new drugs, but more effective drugs.

Funding. It is expensive to develop new mediations. Only the private sector (pharmaceutical industry) develops drugs for psychiatry. Unless the government decides to allocate a trillion dollars to take over that role, it should provide incentives to attract the private sector to invest in psychiatry instead of abandoning it, as some companies recently have done. One possibility is to substantially extend the patent life for a medication with a new mechanism of action. This will spur innovation and benefit millions of sick individuals.

Medico-legal liability. The antidote to innovation is a class-action lawsuit. All drugs will inevitably cause side effects. When millions of people receive a vaccine during an epidemic, a couple hundred may die or suffer serious side effects. Imagine if vaccine development stops and many millions die as a consequence. The FDA currently approves a drug after careful study. Therefore, shouldn’t the FDA share liability for unexpected serious adverse effects or waive such liability altogether if these effects were completely unforeseen during the clinical trials?

So quo vadis, psychopharmacology? This temporary lull is worrisome but there is reason to believe brighter days lie ahead. However, it is obvious that innovative advances in psychopharmacology are not only dependent on scientific breakthroughs but also on completely new paradigms of clinical diagnosis, less rigid regulatory policies, creative financing, and a change in liability laws that stifle drug development. All these are feasible and achievable. This is a time to stop dithering and to start envisioning new directions. Millions of patients are eagerly awaiting the psychopharmacology of the future.

The psychopharmacology era that began 6 decades ago has had a momentous and transformative effect on the identity and practice of psychiatry. It enabled community-based treatment and follow-up to supplant institutional warehousing of persons with serious mental disorders. The discovery of neurotransmitter pathways and receptors involved in the mechanism of action of antipsychotic, antidepressant, and anxiolytic agents sparked the neuroscience revolution that has become 1 of the fastest-moving frontiers in medicine.

Over the past few years, the shine seems to have worn off and psychopharmacology appears to be in limbo between the serendipitous but aging discoveries of the past and the exciting but unfulfilled promise of future breakthroughs. Psychopharmacology is in urgent need of a renaissance to propel it into new directions that will maintain its credibility as the core of psychiatric therapeutics. The following are some issues and challenges that may influence how psychopharmacology can surge forward and restore its “mojo.”

Scientific challenges. Psychopharmacology must decisively move from serendipity and its corollaries to rational, pathophysiology-based drug development. We need a translational “Marshall Plan” to exploit genetic and molecular neurobiology advances to develop radically new pharmacologic biotherapies for psychiatric brain disorders.

Conceptual challenges. As long as psychiatric diagnoses are based on clusters of symptoms assembled by committees, it makes little sense for the FDA to mandate that a drug must work for a DSM diagnosis instead of specific symptoms. Psychiatric disorders share many symptoms such as depressed mood, anxiety, agitation, hallucinations, delusions, insomnia, impulsivity, etc. Approving new drugs for target symptoms rather than a DSM diagnosis might eliminate the often deplored—yet necessary—practice referred to as “off-label” pharmacotherapy. Frankly, it is silly that an antipsychotic must be approved separately for schizophrenia, schizoaffective disorder, psychotic mania, delusional disorder, or brief reactive psychosis when these disorders all share delusions or hallucinations that respond to that same agent. The high cost of conducting redundant clinical trials for all antipsychotic drugs in each psychotic disorder is far better invested in discovering agents with new mechanisms of action.

Disease heterogeneity. Research strongly points to a substantial heterogeneity in practically every psychiatric disorder, with multiple genotypes and phenotypes that share common features. Therefore, there will always be full responders, partial responders, and refractory patients in any psychiatric illness. Rational psychopharmacology must develop strategies to prospectively identify these subgroups by using pharmacogenetic markers that should become a vital component of guiding treatment selection.

Big picture issues

Who will spearhead the psychopharmacology of the future? There is a tremendous unmet need, with >80% of psychiatric disorders having no FDA-approved medication, and a substantial proportion of patients who do receive an approved drug often remain disabled even after symptomatic improvement. This unmet need is not just for new drugs, but more effective drugs.

Funding. It is expensive to develop new mediations. Only the private sector (pharmaceutical industry) develops drugs for psychiatry. Unless the government decides to allocate a trillion dollars to take over that role, it should provide incentives to attract the private sector to invest in psychiatry instead of abandoning it, as some companies recently have done. One possibility is to substantially extend the patent life for a medication with a new mechanism of action. This will spur innovation and benefit millions of sick individuals.

Medico-legal liability. The antidote to innovation is a class-action lawsuit. All drugs will inevitably cause side effects. When millions of people receive a vaccine during an epidemic, a couple hundred may die or suffer serious side effects. Imagine if vaccine development stops and many millions die as a consequence. The FDA currently approves a drug after careful study. Therefore, shouldn’t the FDA share liability for unexpected serious adverse effects or waive such liability altogether if these effects were completely unforeseen during the clinical trials?

So quo vadis, psychopharmacology? This temporary lull is worrisome but there is reason to believe brighter days lie ahead. However, it is obvious that innovative advances in psychopharmacology are not only dependent on scientific breakthroughs but also on completely new paradigms of clinical diagnosis, less rigid regulatory policies, creative financing, and a change in liability laws that stifle drug development. All these are feasible and achievable. This is a time to stop dithering and to start envisioning new directions. Millions of patients are eagerly awaiting the psychopharmacology of the future.

The psychopharmacology era that began 6 decades ago has had a momentous and transformative effect on the identity and practice of psychiatry. It enabled community-based treatment and follow-up to supplant institutional warehousing of persons with serious mental disorders. The discovery of neurotransmitter pathways and receptors involved in the mechanism of action of antipsychotic, antidepressant, and anxiolytic agents sparked the neuroscience revolution that has become 1 of the fastest-moving frontiers in medicine.

Over the past few years, the shine seems to have worn off and psychopharmacology appears to be in limbo between the serendipitous but aging discoveries of the past and the exciting but unfulfilled promise of future breakthroughs. Psychopharmacology is in urgent need of a renaissance to propel it into new directions that will maintain its credibility as the core of psychiatric therapeutics. The following are some issues and challenges that may influence how psychopharmacology can surge forward and restore its “mojo.”

Scientific challenges. Psychopharmacology must decisively move from serendipity and its corollaries to rational, pathophysiology-based drug development. We need a translational “Marshall Plan” to exploit genetic and molecular neurobiology advances to develop radically new pharmacologic biotherapies for psychiatric brain disorders.

Conceptual challenges. As long as psychiatric diagnoses are based on clusters of symptoms assembled by committees, it makes little sense for the FDA to mandate that a drug must work for a DSM diagnosis instead of specific symptoms. Psychiatric disorders share many symptoms such as depressed mood, anxiety, agitation, hallucinations, delusions, insomnia, impulsivity, etc. Approving new drugs for target symptoms rather than a DSM diagnosis might eliminate the often deplored—yet necessary—practice referred to as “off-label” pharmacotherapy. Frankly, it is silly that an antipsychotic must be approved separately for schizophrenia, schizoaffective disorder, psychotic mania, delusional disorder, or brief reactive psychosis when these disorders all share delusions or hallucinations that respond to that same agent. The high cost of conducting redundant clinical trials for all antipsychotic drugs in each psychotic disorder is far better invested in discovering agents with new mechanisms of action.

Disease heterogeneity. Research strongly points to a substantial heterogeneity in practically every psychiatric disorder, with multiple genotypes and phenotypes that share common features. Therefore, there will always be full responders, partial responders, and refractory patients in any psychiatric illness. Rational psychopharmacology must develop strategies to prospectively identify these subgroups by using pharmacogenetic markers that should become a vital component of guiding treatment selection.

Big picture issues

Who will spearhead the psychopharmacology of the future? There is a tremendous unmet need, with >80% of psychiatric disorders having no FDA-approved medication, and a substantial proportion of patients who do receive an approved drug often remain disabled even after symptomatic improvement. This unmet need is not just for new drugs, but more effective drugs.

Funding. It is expensive to develop new mediations. Only the private sector (pharmaceutical industry) develops drugs for psychiatry. Unless the government decides to allocate a trillion dollars to take over that role, it should provide incentives to attract the private sector to invest in psychiatry instead of abandoning it, as some companies recently have done. One possibility is to substantially extend the patent life for a medication with a new mechanism of action. This will spur innovation and benefit millions of sick individuals.

Medico-legal liability. The antidote to innovation is a class-action lawsuit. All drugs will inevitably cause side effects. When millions of people receive a vaccine during an epidemic, a couple hundred may die or suffer serious side effects. Imagine if vaccine development stops and many millions die as a consequence. The FDA currently approves a drug after careful study. Therefore, shouldn’t the FDA share liability for unexpected serious adverse effects or waive such liability altogether if these effects were completely unforeseen during the clinical trials?

So quo vadis, psychopharmacology? This temporary lull is worrisome but there is reason to believe brighter days lie ahead. However, it is obvious that innovative advances in psychopharmacology are not only dependent on scientific breakthroughs but also on completely new paradigms of clinical diagnosis, less rigid regulatory policies, creative financing, and a change in liability laws that stifle drug development. All these are feasible and achievable. This is a time to stop dithering and to start envisioning new directions. Millions of patients are eagerly awaiting the psychopharmacology of the future.

Have you noticed the tattoo craze sweeping the country? It seems many of the younger generation are impulsively rushing to ostentatiously brandish various patterns and/or phrases on the most visible part of their bodies. For now, they proudly display their permanent stigmata (Greek for “to mark” or “puncture with a pointed instrument”) but no one knows how they will feel when the tattoos persist long after the fad dissipates, like many other fads before it.

In contrast to fad-obsessed youth, our psychiatric patients never sought or wanted the stigmata imposed on them: the invisible yet palpable tattoos of mental illness. Unlike the superficial dermatological versions, the invisible tattoos (ie, the stigmas of mental illness) are burnt deep into the soul of those unfortunate persons afflicted with psychiatric brain disorders. No greater injustice occurs every day in our country than the prejudice, scorn, ostracism, avoidance, fear, intolerance, and prejudgment attached to the subset of medical brain disorders that affect thinking, emotions, behavior, or cognition. If mental illness is the injury, then stigma is the insult.

If employers, neighbors, police, landlords, or the public would treat mentally ill individuals with half the sympathy, compassion, and understanding they bestow on persons with physical disability, life would be much more bearable for those with a disabling psychiatric illness. Instead, they are cursed with disdain and avoidance, and the additional stigma of becoming “felons” caged in prisons and jails instead of being afforded the dignity of being cared for in a health care facility like other sick individuals.

But the stigma does not stop with patients: it spills over to psychiatry itself. We all can feel the invisible tattoos imposed on our medical discipline, a bizarre “guilt by association” despite our professional role and service. Consider the following examples of subtle and not-so-subtle discrimination toward psychiatry:

• Our families and friends think we are not “real” doctors, although our medical training and education are practically identical in rigor and duration to that of our colleagues in surgery, cardiology, or neurology.
• Psychiatric services are devalued by third-party payers with ridiculously low reimbursement, high co-payments, and arbitrarily meager annual or lifetime caps. Insurance executives often foolishly decide psychotherapy is not worth paying for despite its enormous value to many patients.
• Managed care invented the diabolical concept of “carve out” to exclude psychiatric services from parity with other medical/surgical services to relegate mental health to a lower tier (ie, less important) reimbursement. And how absurd is the one-size-fits-all 15-minute check?
• Insurance companies discriminate against the “high cost” of the latest psychiatric drugs, yet happily pay for much costlier drugs for nonpsychiatric disorders. For example, they consider $5,000 a year for an antipsychotic too high—as if our patients are not worth it—and demand that cheaper, 45-year-old drugs such as haloperidol continue to be used, although numerous studies have shown haloperidol is neurotoxic.^1-4 Yet the same insurance company does not hesitate to pay $50,000 a year for the latest multiple sclerosis drug, $60,000 a year to prolong a terminal cancer patient’s life by just a few months, $120,000 a year to treat patients with hemophilia, $200,000 a year for Fabry’s disease, $350,000 a year for hereditary angioedema, etc.
• Despite the serious shortage of psychiatrists, the law of supply and demand does not seem to apply to psychiatrists’ compensation. Many believe psychiatrists should receive significantly higher compensation than they currently do, given the severe shortages around the country.
• Psychiatrists are experts in determining whether patients are a danger to themselves and require involuntary hospitalization and pharmacotherapy. Yet those medical decisions are made by the courts. Can anyone imagine the courts usurping the right of cardiologists or neurologists to hospitalize or rapidly medicate an unconscious heart attack or stroke patient?
• Despite the fact that rates of response, remission, and recovery observed in psychiatry are similar to those seen with many medical or surgical treatments, the perception persists that psychiatric therapies have minimal efficacy, an insidious devaluation of what we can do for our patients. The antipsychiatry movement never ceases to viciously attack the scientific validity and benefits of antidepressants,⁵ antipsychotics, or mood stabilizers.

Stigma is like an old, ugly, unwanted tattoo that’s hard to shed. My research-oriented brain is hopeful the unwanted stigmata will rapidly fade away when the physiological causes of psychiatric disorders finally are discovered. The most effective antidote for stigma is relentless research. A cure for mental illness will undoubtedly erase our invisible tattoos.

Have you noticed the tattoo craze sweeping the country? It seems many of the younger generation are impulsively rushing to ostentatiously brandish various patterns and/or phrases on the most visible part of their bodies. For now, they proudly display their permanent stigmata (Greek for “to mark” or “puncture with a pointed instrument”) but no one knows how they will feel when the tattoos persist long after the fad dissipates, like many other fads before it.

In contrast to fad-obsessed youth, our psychiatric patients never sought or wanted the stigmata imposed on them: the invisible yet palpable tattoos of mental illness. Unlike the superficial dermatological versions, the invisible tattoos (ie, the stigmas of mental illness) are burnt deep into the soul of those unfortunate persons afflicted with psychiatric brain disorders. No greater injustice occurs every day in our country than the prejudice, scorn, ostracism, avoidance, fear, intolerance, and prejudgment attached to the subset of medical brain disorders that affect thinking, emotions, behavior, or cognition. If mental illness is the injury, then stigma is the insult.

If employers, neighbors, police, landlords, or the public would treat mentally ill individuals with half the sympathy, compassion, and understanding they bestow on persons with physical disability, life would be much more bearable for those with a disabling psychiatric illness. Instead, they are cursed with disdain and avoidance, and the additional stigma of becoming “felons” caged in prisons and jails instead of being afforded the dignity of being cared for in a health care facility like other sick individuals.

But the stigma does not stop with patients: it spills over to psychiatry itself. We all can feel the invisible tattoos imposed on our medical discipline, a bizarre “guilt by association” despite our professional role and service. Consider the following examples of subtle and not-so-subtle discrimination toward psychiatry:

• Our families and friends think we are not “real” doctors, although our medical training and education are practically identical in rigor and duration to that of our colleagues in surgery, cardiology, or neurology.
• Psychiatric services are devalued by third-party payers with ridiculously low reimbursement, high co-payments, and arbitrarily meager annual or lifetime caps. Insurance executives often foolishly decide psychotherapy is not worth paying for despite its enormous value to many patients.
• Managed care invented the diabolical concept of “carve out” to exclude psychiatric services from parity with other medical/surgical services to relegate mental health to a lower tier (ie, less important) reimbursement. And how absurd is the one-size-fits-all 15-minute check?
• Insurance companies discriminate against the “high cost” of the latest psychiatric drugs, yet happily pay for much costlier drugs for nonpsychiatric disorders. For example, they consider $5,000 a year for an antipsychotic too high—as if our patients are not worth it—and demand that cheaper, 45-year-old drugs such as haloperidol continue to be used, although numerous studies have shown haloperidol is neurotoxic.^1-4 Yet the same insurance company does not hesitate to pay $50,000 a year for the latest multiple sclerosis drug, $60,000 a year to prolong a terminal cancer patient’s life by just a few months, $120,000 a year to treat patients with hemophilia, $200,000 a year for Fabry’s disease, $350,000 a year for hereditary angioedema, etc.
• Despite the serious shortage of psychiatrists, the law of supply and demand does not seem to apply to psychiatrists’ compensation. Many believe psychiatrists should receive significantly higher compensation than they currently do, given the severe shortages around the country.
• Psychiatrists are experts in determining whether patients are a danger to themselves and require involuntary hospitalization and pharmacotherapy. Yet those medical decisions are made by the courts. Can anyone imagine the courts usurping the right of cardiologists or neurologists to hospitalize or rapidly medicate an unconscious heart attack or stroke patient?
• Despite the fact that rates of response, remission, and recovery observed in psychiatry are similar to those seen with many medical or surgical treatments, the perception persists that psychiatric therapies have minimal efficacy, an insidious devaluation of what we can do for our patients. The antipsychiatry movement never ceases to viciously attack the scientific validity and benefits of antidepressants,⁵ antipsychotics, or mood stabilizers.

Stigma is like an old, ugly, unwanted tattoo that’s hard to shed. My research-oriented brain is hopeful the unwanted stigmata will rapidly fade away when the physiological causes of psychiatric disorders finally are discovered. The most effective antidote for stigma is relentless research. A cure for mental illness will undoubtedly erase our invisible tattoos.

Have you noticed the tattoo craze sweeping the country? It seems many of the younger generation are impulsively rushing to ostentatiously brandish various patterns and/or phrases on the most visible part of their bodies. For now, they proudly display their permanent stigmata (Greek for “to mark” or “puncture with a pointed instrument”) but no one knows how they will feel when the tattoos persist long after the fad dissipates, like many other fads before it.

In contrast to fad-obsessed youth, our psychiatric patients never sought or wanted the stigmata imposed on them: the invisible yet palpable tattoos of mental illness. Unlike the superficial dermatological versions, the invisible tattoos (ie, the stigmas of mental illness) are burnt deep into the soul of those unfortunate persons afflicted with psychiatric brain disorders. No greater injustice occurs every day in our country than the prejudice, scorn, ostracism, avoidance, fear, intolerance, and prejudgment attached to the subset of medical brain disorders that affect thinking, emotions, behavior, or cognition. If mental illness is the injury, then stigma is the insult.

If employers, neighbors, police, landlords, or the public would treat mentally ill individuals with half the sympathy, compassion, and understanding they bestow on persons with physical disability, life would be much more bearable for those with a disabling psychiatric illness. Instead, they are cursed with disdain and avoidance, and the additional stigma of becoming “felons” caged in prisons and jails instead of being afforded the dignity of being cared for in a health care facility like other sick individuals.

But the stigma does not stop with patients: it spills over to psychiatry itself. We all can feel the invisible tattoos imposed on our medical discipline, a bizarre “guilt by association” despite our professional role and service. Consider the following examples of subtle and not-so-subtle discrimination toward psychiatry:

• Our families and friends think we are not “real” doctors, although our medical training and education are practically identical in rigor and duration to that of our colleagues in surgery, cardiology, or neurology.
• Psychiatric services are devalued by third-party payers with ridiculously low reimbursement, high co-payments, and arbitrarily meager annual or lifetime caps. Insurance executives often foolishly decide psychotherapy is not worth paying for despite its enormous value to many patients.
• Managed care invented the diabolical concept of “carve out” to exclude psychiatric services from parity with other medical/surgical services to relegate mental health to a lower tier (ie, less important) reimbursement. And how absurd is the one-size-fits-all 15-minute check?
• Insurance companies discriminate against the “high cost” of the latest psychiatric drugs, yet happily pay for much costlier drugs for nonpsychiatric disorders. For example, they consider $5,000 a year for an antipsychotic too high—as if our patients are not worth it—and demand that cheaper, 45-year-old drugs such as haloperidol continue to be used, although numerous studies have shown haloperidol is neurotoxic.^1-4 Yet the same insurance company does not hesitate to pay $50,000 a year for the latest multiple sclerosis drug, $60,000 a year to prolong a terminal cancer patient’s life by just a few months, $120,000 a year to treat patients with hemophilia, $200,000 a year for Fabry’s disease, $350,000 a year for hereditary angioedema, etc.
• Despite the serious shortage of psychiatrists, the law of supply and demand does not seem to apply to psychiatrists’ compensation. Many believe psychiatrists should receive significantly higher compensation than they currently do, given the severe shortages around the country.
• Psychiatrists are experts in determining whether patients are a danger to themselves and require involuntary hospitalization and pharmacotherapy. Yet those medical decisions are made by the courts. Can anyone imagine the courts usurping the right of cardiologists or neurologists to hospitalize or rapidly medicate an unconscious heart attack or stroke patient?
• Despite the fact that rates of response, remission, and recovery observed in psychiatry are similar to those seen with many medical or surgical treatments, the perception persists that psychiatric therapies have minimal efficacy, an insidious devaluation of what we can do for our patients. The antipsychiatry movement never ceases to viciously attack the scientific validity and benefits of antidepressants,⁵ antipsychotics, or mood stabilizers.

Stigma is like an old, ugly, unwanted tattoo that’s hard to shed. My research-oriented brain is hopeful the unwanted stigmata will rapidly fade away when the physiological causes of psychiatric disorders finally are discovered. The most effective antidote for stigma is relentless research. A cure for mental illness will undoubtedly erase our invisible tattoos.

The placebo effect—when a patient’s symptoms improve with an inert pill—is widely recognized in medicine. Placebo has an especially important role in psychiatry, especially given the fact that a substantial proportion of patients with mood, anxiety, or psychotic disorders improve and experience some side effects with placebo in double-blind studies conducted by drug manufacturers as part of FDA registration trials.

On the other hand, non-psychiatric medical disorders such as pneumonia and diabetes are unlikely to improve with placebo. Thus, psychiatric brain disorders appear to be particularly susceptible to the placebo effect, which implies it could be harnessed in psychiatric care. A component of every medication prescribed in psychiatry is a variable placebo effect in addition to the actual pharmacodynamic effects.

Some physicians (including non-psychiatrists) openly admit to using placebo—which is sold as Obecalp capsules—to treat patients with vague aches, pains, insomnia, or low energy. Some published studies have shown patients respond to inert pills even when the physician tells them in advance they will be receiving a placebo!¹ This reflects the power of the placebo effect programmed in the human brain, which may have an evolutionary advantage of instilling hope and sustaining faith things will get better despite serious physical or psychological adversity.

What health care professionals often overlook is that the placebo effect transcends the pill itself. The most powerful placebo is the psychiatrist or nurse practitioner who prescribes the pill. In fact, the placebo effect of a clinician occurs even without prescribing any medication.

The shape and color of a placebo pill may endow it with a greater effect (eg, a red and blue striped placebo caplet looks more impressive and may project an aura of being more effective than a plain white tablet). Similarly, a patient is influenced positively or negatively by a range of attributes that characterize his or her psychiatrist, and the totality of the impressions (positive or negative) the psychiatrist “projects” may enhance or detract from whatever treatment is administered, including medication or psychotherapy. This is why different prescribers may achieve disparate results when prescribing the same psychotropic.

Many subtle and not-so-subtle verbal and nonverbal aspects of a clinician can project an “aura” of competence and trust for the patient, which will contribute to a better treatment outcome because of the patient’s stronger unconscious expectation of improvement. These include the psychiatrist’s grooming and clothing, his facial expression and demeanor, the neatness of his desk, the décor of his office, the cleanliness of the waiting room, even the appearance of the neighborhood where his clinic is located. Wearing a white coat instead of street clothes can evoke the image of a physician/healer, which is a strong positive placebo effect that can be exploited for many patients. Direct eye contact an open body posture, a firm, reassuring voice, and a handshake or caring pat on the back at the end of the session when appropriate all contribute to patient improvement even before he or she ingests any pills. A psychiatrist can enhance the response and tolerability of a drug by expressing confidence in the medication and assuring the patient if taken as prescribed the medication will help and will be tolerable according to published studies. Even slight uncertainty by the psychiatrist about the potential usefulness of a medication—even if realistic—may compromise the patient’s response.

Take the following extreme illustration of a psychiatrist whose image projects a powerful negative placebo effect that could undermine therapeutic outcome and even patient adherence: Dr. X works in a dilapidated building in a downtrodden neighborhood. Several furniture pieces in his waiting room are torn or broken. The carpet is worn and features several stains. His office is poorly lit and reeks of mildew and stale cigarette butts. He barely looks at the patient but types on a laptop as the patient speaks. Dr. X is dressed in a casual sports shirt and blue jeans. His hair is disheveled. The floor of his office is littered with piles of journals and books. Dr. X speaks in a hurried, impatient tone and often interrupts the patient to ask a barrage of questions unrelated to what the patient was talking about. Occasionally, Dr. X stops typing, leans back in his worn creaky chair, crosses his arms, and just stares at the patient. He then abruptly ends the session because “there are many other patients waiting.” He scribbles a prescription, slides it over the desk to the patient, and says “Here, take this until next visit and we’ll see if it works for you.” The psychiatrist never leaves his chair and keeps typing as the patient dejectedly leaves the office.

Dr. X clearly has squandered the valuable placebo effect inherent in his role that not only can enhance the medication efficacy but also usually bolsters the therapeutic alliance. The many negative aspects of his demeanor, behavior, relatedness, and office probably will decrease the likelihood of a good outcome in his patient

Every clinician can achieve better treatment results by creating a set of positive personal and environmental cues to reinforce that powerful and intangible force that expedites the relief of psychiatric symptoms. It would be folly to squander the remarkable placebo inherent in us “healers.”

The placebo effect—when a patient’s symptoms improve with an inert pill—is widely recognized in medicine. Placebo has an especially important role in psychiatry, especially given the fact that a substantial proportion of patients with mood, anxiety, or psychotic disorders improve and experience some side effects with placebo in double-blind studies conducted by drug manufacturers as part of FDA registration trials.

On the other hand, non-psychiatric medical disorders such as pneumonia and diabetes are unlikely to improve with placebo. Thus, psychiatric brain disorders appear to be particularly susceptible to the placebo effect, which implies it could be harnessed in psychiatric care. A component of every medication prescribed in psychiatry is a variable placebo effect in addition to the actual pharmacodynamic effects.

Some physicians (including non-psychiatrists) openly admit to using placebo—which is sold as Obecalp capsules—to treat patients with vague aches, pains, insomnia, or low energy. Some published studies have shown patients respond to inert pills even when the physician tells them in advance they will be receiving a placebo!¹ This reflects the power of the placebo effect programmed in the human brain, which may have an evolutionary advantage of instilling hope and sustaining faith things will get better despite serious physical or psychological adversity.

What health care professionals often overlook is that the placebo effect transcends the pill itself. The most powerful placebo is the psychiatrist or nurse practitioner who prescribes the pill. In fact, the placebo effect of a clinician occurs even without prescribing any medication.

The shape and color of a placebo pill may endow it with a greater effect (eg, a red and blue striped placebo caplet looks more impressive and may project an aura of being more effective than a plain white tablet). Similarly, a patient is influenced positively or negatively by a range of attributes that characterize his or her psychiatrist, and the totality of the impressions (positive or negative) the psychiatrist “projects” may enhance or detract from whatever treatment is administered, including medication or psychotherapy. This is why different prescribers may achieve disparate results when prescribing the same psychotropic.

Many subtle and not-so-subtle verbal and nonverbal aspects of a clinician can project an “aura” of competence and trust for the patient, which will contribute to a better treatment outcome because of the patient’s stronger unconscious expectation of improvement. These include the psychiatrist’s grooming and clothing, his facial expression and demeanor, the neatness of his desk, the décor of his office, the cleanliness of the waiting room, even the appearance of the neighborhood where his clinic is located. Wearing a white coat instead of street clothes can evoke the image of a physician/healer, which is a strong positive placebo effect that can be exploited for many patients. Direct eye contact an open body posture, a firm, reassuring voice, and a handshake or caring pat on the back at the end of the session when appropriate all contribute to patient improvement even before he or she ingests any pills. A psychiatrist can enhance the response and tolerability of a drug by expressing confidence in the medication and assuring the patient if taken as prescribed the medication will help and will be tolerable according to published studies. Even slight uncertainty by the psychiatrist about the potential usefulness of a medication—even if realistic—may compromise the patient’s response.

Take the following extreme illustration of a psychiatrist whose image projects a powerful negative placebo effect that could undermine therapeutic outcome and even patient adherence: Dr. X works in a dilapidated building in a downtrodden neighborhood. Several furniture pieces in his waiting room are torn or broken. The carpet is worn and features several stains. His office is poorly lit and reeks of mildew and stale cigarette butts. He barely looks at the patient but types on a laptop as the patient speaks. Dr. X is dressed in a casual sports shirt and blue jeans. His hair is disheveled. The floor of his office is littered with piles of journals and books. Dr. X speaks in a hurried, impatient tone and often interrupts the patient to ask a barrage of questions unrelated to what the patient was talking about. Occasionally, Dr. X stops typing, leans back in his worn creaky chair, crosses his arms, and just stares at the patient. He then abruptly ends the session because “there are many other patients waiting.” He scribbles a prescription, slides it over the desk to the patient, and says “Here, take this until next visit and we’ll see if it works for you.” The psychiatrist never leaves his chair and keeps typing as the patient dejectedly leaves the office.

Dr. X clearly has squandered the valuable placebo effect inherent in his role that not only can enhance the medication efficacy but also usually bolsters the therapeutic alliance. The many negative aspects of his demeanor, behavior, relatedness, and office probably will decrease the likelihood of a good outcome in his patient

Every clinician can achieve better treatment results by creating a set of positive personal and environmental cues to reinforce that powerful and intangible force that expedites the relief of psychiatric symptoms. It would be folly to squander the remarkable placebo inherent in us “healers.”

The placebo effect—when a patient’s symptoms improve with an inert pill—is widely recognized in medicine. Placebo has an especially important role in psychiatry, especially given the fact that a substantial proportion of patients with mood, anxiety, or psychotic disorders improve and experience some side effects with placebo in double-blind studies conducted by drug manufacturers as part of FDA registration trials.

On the other hand, non-psychiatric medical disorders such as pneumonia and diabetes are unlikely to improve with placebo. Thus, psychiatric brain disorders appear to be particularly susceptible to the placebo effect, which implies it could be harnessed in psychiatric care. A component of every medication prescribed in psychiatry is a variable placebo effect in addition to the actual pharmacodynamic effects.

Some physicians (including non-psychiatrists) openly admit to using placebo—which is sold as Obecalp capsules—to treat patients with vague aches, pains, insomnia, or low energy. Some published studies have shown patients respond to inert pills even when the physician tells them in advance they will be receiving a placebo!¹ This reflects the power of the placebo effect programmed in the human brain, which may have an evolutionary advantage of instilling hope and sustaining faith things will get better despite serious physical or psychological adversity.

What health care professionals often overlook is that the placebo effect transcends the pill itself. The most powerful placebo is the psychiatrist or nurse practitioner who prescribes the pill. In fact, the placebo effect of a clinician occurs even without prescribing any medication.

The shape and color of a placebo pill may endow it with a greater effect (eg, a red and blue striped placebo caplet looks more impressive and may project an aura of being more effective than a plain white tablet). Similarly, a patient is influenced positively or negatively by a range of attributes that characterize his or her psychiatrist, and the totality of the impressions (positive or negative) the psychiatrist “projects” may enhance or detract from whatever treatment is administered, including medication or psychotherapy. This is why different prescribers may achieve disparate results when prescribing the same psychotropic.

Many subtle and not-so-subtle verbal and nonverbal aspects of a clinician can project an “aura” of competence and trust for the patient, which will contribute to a better treatment outcome because of the patient’s stronger unconscious expectation of improvement. These include the psychiatrist’s grooming and clothing, his facial expression and demeanor, the neatness of his desk, the décor of his office, the cleanliness of the waiting room, even the appearance of the neighborhood where his clinic is located. Wearing a white coat instead of street clothes can evoke the image of a physician/healer, which is a strong positive placebo effect that can be exploited for many patients. Direct eye contact an open body posture, a firm, reassuring voice, and a handshake or caring pat on the back at the end of the session when appropriate all contribute to patient improvement even before he or she ingests any pills. A psychiatrist can enhance the response and tolerability of a drug by expressing confidence in the medication and assuring the patient if taken as prescribed the medication will help and will be tolerable according to published studies. Even slight uncertainty by the psychiatrist about the potential usefulness of a medication—even if realistic—may compromise the patient’s response.

Take the following extreme illustration of a psychiatrist whose image projects a powerful negative placebo effect that could undermine therapeutic outcome and even patient adherence: Dr. X works in a dilapidated building in a downtrodden neighborhood. Several furniture pieces in his waiting room are torn or broken. The carpet is worn and features several stains. His office is poorly lit and reeks of mildew and stale cigarette butts. He barely looks at the patient but types on a laptop as the patient speaks. Dr. X is dressed in a casual sports shirt and blue jeans. His hair is disheveled. The floor of his office is littered with piles of journals and books. Dr. X speaks in a hurried, impatient tone and often interrupts the patient to ask a barrage of questions unrelated to what the patient was talking about. Occasionally, Dr. X stops typing, leans back in his worn creaky chair, crosses his arms, and just stares at the patient. He then abruptly ends the session because “there are many other patients waiting.” He scribbles a prescription, slides it over the desk to the patient, and says “Here, take this until next visit and we’ll see if it works for you.” The psychiatrist never leaves his chair and keeps typing as the patient dejectedly leaves the office.

Dr. X clearly has squandered the valuable placebo effect inherent in his role that not only can enhance the medication efficacy but also usually bolsters the therapeutic alliance. The many negative aspects of his demeanor, behavior, relatedness, and office probably will decrease the likelihood of a good outcome in his patient

Every clinician can achieve better treatment results by creating a set of positive personal and environmental cues to reinforce that powerful and intangible force that expedites the relief of psychiatric symptoms. It would be folly to squander the remarkable placebo inherent in us “healers.”

It sounds like science fiction, but it may soon become a reality. The young science of epigenetics is revolutionizing the traditional principles of genetics and weaving them into countless environmental factors, from biologic to behavioral, that can modify and direct gene expression toward health or disease. When nature and nurture collide, epigenetic events occur. The most exciting implications of gene-environment interactions are the endless possibilities to exploit and manipulate epigenetics to prevent or ameliorate psychiatric disorders.

Lamarckism, the discredited “inheritance of acquired characteristics,” was a primitive version of epigenetics proposed by Jean-Baptiste Lamarck (1744-1829), to build on Charles Darwin’s theory of evolution and explain adaptation to the environment. Lamarck’s ideas preceded the discovery of “heredity” introduced by the Austrian monk Gregor Johann Mendel in 1865. The terms “gene” and “genetics” were coined by William Bateson in 1902 and the location of genes within the chromosomes was discovered in 1910 by Thomas Morgan. The term “epigenetics” was coined in 1940 by Conrad Hal Waddington, and this science has accelerated dramatically over the past decade when it was discovered that:

1. Certain biologic substances such as histones and methyl groups can attach to the “promoter” region (ie, the switch) of a gene and either silence the gene or turn it on to increase its expression. This explains how >200 distinctly different tissues develop in a fetus although every single cell of those tissues contains the same 23 chromosomes, with a total of approximately 20,000 genes.
2. Behaviors or activities by adults may, unbeknownst to them, lead to disease in their yet-to-be-born offspring by switching certain genes on or off, without any change in the structure or sequence of DNA. For example, one study found that men who began to smoke before puberty (when sperm production begins) had offspring with significantly higher body weight than men who did not smoke before puberty.¹ Animal studies show that organisms subjected to caloric restriction will live 30% longer than those with normal caloric intake, and their offspring have 20% longer longevity without being subjected to caloric restriction!² That’s Lamarckism, but a much more sophisticated version than the original.

How does this link to psychiatry? We already have a large body of evidence that the environment can have a substantial deleterious or salutary impact on the development of psychiatric brain disorders. One set of evidence comes from studying that most important environment, the womb. Prenatal, neonatal (obstetric), and postnatal adverse events can disrupt brain development and lead to serious psychopathology, such as schizophrenia. Another type of evidence is seen in childhood abuse (physical, sexual, or verbal), which can lead to sensitization of the HPA axis and result in serious mood and anxiety disorders in adulthood. On the positive side, an enriched environment during infancy can stimulate neuroplasticity, connectivity, and enhanced brain growth.

Imagine what we will be able to do once research elucidates more than the epigenetic changes caused by adverse intrauterine events for a fetus or unhealthy pre-conception behaviors in future parents. Imagine, too, if psychiatric scientists discover parental behaviors that may improve offspring temperament, bolster resilience under stress, blunt impulsivity, suppress antisocial behavior, reduce the susceptibility to addiction(s), enhance cognitive ability, inhibit emergence of psychiatric symptoms, increase motivation, and, importantly, extinguish inherited suicidal or homicidal urges.

Of all medical disciplines, I believe psychiatry stands to benefit the most from advances in what may be designated as the field of “therapeutic epigenetics.” Two reasons justify this assertion:

1. A very high proportion (50%) of our 20,000 genes are expressed only in the brain, creating huge opportunities for “interventional epigenetics” to prevent, modify, modulate, or ameliorate psychiatric diseases by silencing abnormal genes (once we identify them) or turbocharging the expression of adaptive genes (once they are identified).
2. The brain is the most plastic organ in the body, changing on an ongoing basis by interacting with the environment (ie, the human experiences of everyday life). The unique ongoing neuroplasticity of the brain is driven by gene expression stimulated by environmental stimuli, which can be targeted for therapeutic purposes. In fact, it is likely that psychotherapy and pharmacotherapy exert their efficacy and certain adverse effects via selective gene expression.

Yes, it does sound like science fiction that some day we will be able to capitalize on gene-environment interactions to heal the body, the brain, and the mind, thus circumventing the use of medications. Psychiatric destiny is not in the DNA but in how targeted environmental influences can bring out the best in DNA, that magically malleable matter of life.

It sounds like science fiction, but it may soon become a reality. The young science of epigenetics is revolutionizing the traditional principles of genetics and weaving them into countless environmental factors, from biologic to behavioral, that can modify and direct gene expression toward health or disease. When nature and nurture collide, epigenetic events occur. The most exciting implications of gene-environment interactions are the endless possibilities to exploit and manipulate epigenetics to prevent or ameliorate psychiatric disorders.

Lamarckism, the discredited “inheritance of acquired characteristics,” was a primitive version of epigenetics proposed by Jean-Baptiste Lamarck (1744-1829), to build on Charles Darwin’s theory of evolution and explain adaptation to the environment. Lamarck’s ideas preceded the discovery of “heredity” introduced by the Austrian monk Gregor Johann Mendel in 1865. The terms “gene” and “genetics” were coined by William Bateson in 1902 and the location of genes within the chromosomes was discovered in 1910 by Thomas Morgan. The term “epigenetics” was coined in 1940 by Conrad Hal Waddington, and this science has accelerated dramatically over the past decade when it was discovered that:

1. Certain biologic substances such as histones and methyl groups can attach to the “promoter” region (ie, the switch) of a gene and either silence the gene or turn it on to increase its expression. This explains how >200 distinctly different tissues develop in a fetus although every single cell of those tissues contains the same 23 chromosomes, with a total of approximately 20,000 genes.
2. Behaviors or activities by adults may, unbeknownst to them, lead to disease in their yet-to-be-born offspring by switching certain genes on or off, without any change in the structure or sequence of DNA. For example, one study found that men who began to smoke before puberty (when sperm production begins) had offspring with significantly higher body weight than men who did not smoke before puberty.¹ Animal studies show that organisms subjected to caloric restriction will live 30% longer than those with normal caloric intake, and their offspring have 20% longer longevity without being subjected to caloric restriction!² That’s Lamarckism, but a much more sophisticated version than the original.

How does this link to psychiatry? We already have a large body of evidence that the environment can have a substantial deleterious or salutary impact on the development of psychiatric brain disorders. One set of evidence comes from studying that most important environment, the womb. Prenatal, neonatal (obstetric), and postnatal adverse events can disrupt brain development and lead to serious psychopathology, such as schizophrenia. Another type of evidence is seen in childhood abuse (physical, sexual, or verbal), which can lead to sensitization of the HPA axis and result in serious mood and anxiety disorders in adulthood. On the positive side, an enriched environment during infancy can stimulate neuroplasticity, connectivity, and enhanced brain growth.

Imagine what we will be able to do once research elucidates more than the epigenetic changes caused by adverse intrauterine events for a fetus or unhealthy pre-conception behaviors in future parents. Imagine, too, if psychiatric scientists discover parental behaviors that may improve offspring temperament, bolster resilience under stress, blunt impulsivity, suppress antisocial behavior, reduce the susceptibility to addiction(s), enhance cognitive ability, inhibit emergence of psychiatric symptoms, increase motivation, and, importantly, extinguish inherited suicidal or homicidal urges.

Of all medical disciplines, I believe psychiatry stands to benefit the most from advances in what may be designated as the field of “therapeutic epigenetics.” Two reasons justify this assertion:

1. A very high proportion (50%) of our 20,000 genes are expressed only in the brain, creating huge opportunities for “interventional epigenetics” to prevent, modify, modulate, or ameliorate psychiatric diseases by silencing abnormal genes (once we identify them) or turbocharging the expression of adaptive genes (once they are identified).
2. The brain is the most plastic organ in the body, changing on an ongoing basis by interacting with the environment (ie, the human experiences of everyday life). The unique ongoing neuroplasticity of the brain is driven by gene expression stimulated by environmental stimuli, which can be targeted for therapeutic purposes. In fact, it is likely that psychotherapy and pharmacotherapy exert their efficacy and certain adverse effects via selective gene expression.

Yes, it does sound like science fiction that some day we will be able to capitalize on gene-environment interactions to heal the body, the brain, and the mind, thus circumventing the use of medications. Psychiatric destiny is not in the DNA but in how targeted environmental influences can bring out the best in DNA, that magically malleable matter of life.

It sounds like science fiction, but it may soon become a reality. The young science of epigenetics is revolutionizing the traditional principles of genetics and weaving them into countless environmental factors, from biologic to behavioral, that can modify and direct gene expression toward health or disease. When nature and nurture collide, epigenetic events occur. The most exciting implications of gene-environment interactions are the endless possibilities to exploit and manipulate epigenetics to prevent or ameliorate psychiatric disorders.

Lamarckism, the discredited “inheritance of acquired characteristics,” was a primitive version of epigenetics proposed by Jean-Baptiste Lamarck (1744-1829), to build on Charles Darwin’s theory of evolution and explain adaptation to the environment. Lamarck’s ideas preceded the discovery of “heredity” introduced by the Austrian monk Gregor Johann Mendel in 1865. The terms “gene” and “genetics” were coined by William Bateson in 1902 and the location of genes within the chromosomes was discovered in 1910 by Thomas Morgan. The term “epigenetics” was coined in 1940 by Conrad Hal Waddington, and this science has accelerated dramatically over the past decade when it was discovered that:

1. Certain biologic substances such as histones and methyl groups can attach to the “promoter” region (ie, the switch) of a gene and either silence the gene or turn it on to increase its expression. This explains how >200 distinctly different tissues develop in a fetus although every single cell of those tissues contains the same 23 chromosomes, with a total of approximately 20,000 genes.
2. Behaviors or activities by adults may, unbeknownst to them, lead to disease in their yet-to-be-born offspring by switching certain genes on or off, without any change in the structure or sequence of DNA. For example, one study found that men who began to smoke before puberty (when sperm production begins) had offspring with significantly higher body weight than men who did not smoke before puberty.¹ Animal studies show that organisms subjected to caloric restriction will live 30% longer than those with normal caloric intake, and their offspring have 20% longer longevity without being subjected to caloric restriction!² That’s Lamarckism, but a much more sophisticated version than the original.

How does this link to psychiatry? We already have a large body of evidence that the environment can have a substantial deleterious or salutary impact on the development of psychiatric brain disorders. One set of evidence comes from studying that most important environment, the womb. Prenatal, neonatal (obstetric), and postnatal adverse events can disrupt brain development and lead to serious psychopathology, such as schizophrenia. Another type of evidence is seen in childhood abuse (physical, sexual, or verbal), which can lead to sensitization of the HPA axis and result in serious mood and anxiety disorders in adulthood. On the positive side, an enriched environment during infancy can stimulate neuroplasticity, connectivity, and enhanced brain growth.

Imagine what we will be able to do once research elucidates more than the epigenetic changes caused by adverse intrauterine events for a fetus or unhealthy pre-conception behaviors in future parents. Imagine, too, if psychiatric scientists discover parental behaviors that may improve offspring temperament, bolster resilience under stress, blunt impulsivity, suppress antisocial behavior, reduce the susceptibility to addiction(s), enhance cognitive ability, inhibit emergence of psychiatric symptoms, increase motivation, and, importantly, extinguish inherited suicidal or homicidal urges.

Of all medical disciplines, I believe psychiatry stands to benefit the most from advances in what may be designated as the field of “therapeutic epigenetics.” Two reasons justify this assertion:

1. A very high proportion (50%) of our 20,000 genes are expressed only in the brain, creating huge opportunities for “interventional epigenetics” to prevent, modify, modulate, or ameliorate psychiatric diseases by silencing abnormal genes (once we identify them) or turbocharging the expression of adaptive genes (once they are identified).
2. The brain is the most plastic organ in the body, changing on an ongoing basis by interacting with the environment (ie, the human experiences of everyday life). The unique ongoing neuroplasticity of the brain is driven by gene expression stimulated by environmental stimuli, which can be targeted for therapeutic purposes. In fact, it is likely that psychotherapy and pharmacotherapy exert their efficacy and certain adverse effects via selective gene expression.

Yes, it does sound like science fiction that some day we will be able to capitalize on gene-environment interactions to heal the body, the brain, and the mind, thus circumventing the use of medications. Psychiatric destiny is not in the DNA but in how targeted environmental influences can bring out the best in DNA, that magically malleable matter of life.

Everybody loves progress. People feel uplifted by the notion of progress, by the dynamic feeling it evokes of “moving forward,” of achieving new milestones and reaching new heights. Progress implies improvement in the human condition and an upgrade in quality of life. In medical disciplines such as psychiatry, it connotes less suffering, better treatments, more hope, improved social and vocational functioning, and full restoration of wellness.

But let’s be realistic. Overall evolution of psychiatry is not as “progressive” as we like to believe. Yes, there are thrilling breakthroughs in basic neuroscience research and understanding brain structure and function at the cellular and molecular levels. However, in many other areas of psychiatric practice, I feel we have moved backward since I began my career 3 decades ago. Egress, not progress, appears to be the state of psychiatry. In a tango-like fashion, psychiatry seems to take 1 step forward on 1 level (science and discovery) and 2 steps back on another level (practice realities). As an optimistic person, it pains me to admit that we have moved backward in several aspects of psychiatry:

• The discovery of chlorpromazine, the first antipsychotic, was a miraculous event for our field, but was it “progress” for our patients? Their symptoms improved partially but they developed serious side effects and remained functionally disabled throughout their lives. Patients were “freed” from locked hospital wards, then hurled into a poorly prepared and under-resourced community mental health care system, resulting in revolving door relapses, extensive drug abuse, rampant stigma, abject poverty, physical neglect, early death, homelessness, and for many psychiatric patients, incarceration in jails and prisons, an environment more restrictive than the reviled asylums. Our patients who were medically ill individuals cared for by doctors, nurses, and other health professionals are now lowly felons. It seems that those unfortunate enough to suffer from a psychotic brain disorder are destined to be further punished for it, a great injustice in the name of “progress.”
• Insurance hassles for serious mental illness did not exist in the asylum era. If an individual developed a psychotic disorder, he or she was admitted to the nearest state hospital without hesitation and provided medical and psychosocial care, even if the stay lasted months or years. Now, the same patient cannot afford psychiatric hospitalization even if he or she has “health insurance” (a euphemism for “restricted health coverage”). Equality of psychiatric disorders with other medical and surgical disorders remains a farce, and the lack of parity for mental illness has deprived millions of patients from adequate care. How many victims of mental illness have suffered or died in the name of “progress” in the health insurance industry?
• Who is the “genius” who stipulated that a psychotic, bipolar, suicidal, or homicidal patient could be effectively treated after 3 to 4 days of hospitalization? How did patients become widgets on an assembly line? Medical students and residents on inpatient wards no longer have the rewarding experience or witnessing full improvement in their patients. Is it progress when a patient with schizophrenia or severe depression is discharged after barely 30% to 40% improvement in symptoms? No wonder relapse, suicide, and homicide rates are very high in the 3 weeks after discharge. Long-term hospitals, the last refuge for severely disabled patients who cannot care for themselves, now are rare. Is that progress?
• Why are psychiatrists shackled by more legal constraints than physicians in other medical specialties? Why should lawyers and judges tell us how to practice medicine and who, when, and how to treat? Legal progress sounds like an oxymoron to me.
• Why is the public mental health system so broken in every state? Why is it so ineffective, chaotic, underfunded, hard to navigate, and demedicalized? Why have psychiatrists—the traditional leaders in mental health—been marginalized to sign prescriptions instead of being executives and policy-setters for mental illness? Respiratory and physical therapists have important roles but the pulmonologist or the orthopedist runs the clinic. Why is it not so in public psychiatry? This is not progress, but a travesty.
• Why is psychiatry now referred to as “behavioral health”? Who decided to fix the name of psychiatric care when the original term is much more comprehensive, factual, and inclusive and uses medical terminology (iatros = “healer” or “medicine”). It is not progress to reduce to “behavior” psychiatric illnesses that involve a broad spectrum of pathologies, including thought disorders, mood disorders, perceptual disorders, cognitive disorders, pain, addictions, and many general medical conditions that manifest with psychiatric signs and symptoms. Redefining psychiatric care with inaccurate terminology certainly is not progress.
• Why are pharmaceutical companies, the only source of drug development, abandoning CNS research? Is it because cardiovascular, oncologic, and GI drugs are more profitable and less “challenging” to develop? Is it progress to turn away from the most critical medical frontier, the human brain, and its diseases? At a time when 80% of psychiatric disorders have no approved medication, it is inexcusable to shirk from discovering drugs that trigger hope for recovery for patients with untreatable mental illness.

Ogden Nash once wrote: “Progress might have been all right once, but it has gone on too long.” I will add to that for psychiatry, progress isn’t what it used to be.

Everybody loves progress. People feel uplifted by the notion of progress, by the dynamic feeling it evokes of “moving forward,” of achieving new milestones and reaching new heights. Progress implies improvement in the human condition and an upgrade in quality of life. In medical disciplines such as psychiatry, it connotes less suffering, better treatments, more hope, improved social and vocational functioning, and full restoration of wellness.

But let’s be realistic. Overall evolution of psychiatry is not as “progressive” as we like to believe. Yes, there are thrilling breakthroughs in basic neuroscience research and understanding brain structure and function at the cellular and molecular levels. However, in many other areas of psychiatric practice, I feel we have moved backward since I began my career 3 decades ago. Egress, not progress, appears to be the state of psychiatry. In a tango-like fashion, psychiatry seems to take 1 step forward on 1 level (science and discovery) and 2 steps back on another level (practice realities). As an optimistic person, it pains me to admit that we have moved backward in several aspects of psychiatry:

• The discovery of chlorpromazine, the first antipsychotic, was a miraculous event for our field, but was it “progress” for our patients? Their symptoms improved partially but they developed serious side effects and remained functionally disabled throughout their lives. Patients were “freed” from locked hospital wards, then hurled into a poorly prepared and under-resourced community mental health care system, resulting in revolving door relapses, extensive drug abuse, rampant stigma, abject poverty, physical neglect, early death, homelessness, and for many psychiatric patients, incarceration in jails and prisons, an environment more restrictive than the reviled asylums. Our patients who were medically ill individuals cared for by doctors, nurses, and other health professionals are now lowly felons. It seems that those unfortunate enough to suffer from a psychotic brain disorder are destined to be further punished for it, a great injustice in the name of “progress.”
• Insurance hassles for serious mental illness did not exist in the asylum era. If an individual developed a psychotic disorder, he or she was admitted to the nearest state hospital without hesitation and provided medical and psychosocial care, even if the stay lasted months or years. Now, the same patient cannot afford psychiatric hospitalization even if he or she has “health insurance” (a euphemism for “restricted health coverage”). Equality of psychiatric disorders with other medical and surgical disorders remains a farce, and the lack of parity for mental illness has deprived millions of patients from adequate care. How many victims of mental illness have suffered or died in the name of “progress” in the health insurance industry?
• Who is the “genius” who stipulated that a psychotic, bipolar, suicidal, or homicidal patient could be effectively treated after 3 to 4 days of hospitalization? How did patients become widgets on an assembly line? Medical students and residents on inpatient wards no longer have the rewarding experience or witnessing full improvement in their patients. Is it progress when a patient with schizophrenia or severe depression is discharged after barely 30% to 40% improvement in symptoms? No wonder relapse, suicide, and homicide rates are very high in the 3 weeks after discharge. Long-term hospitals, the last refuge for severely disabled patients who cannot care for themselves, now are rare. Is that progress?
• Why are psychiatrists shackled by more legal constraints than physicians in other medical specialties? Why should lawyers and judges tell us how to practice medicine and who, when, and how to treat? Legal progress sounds like an oxymoron to me.
• Why is the public mental health system so broken in every state? Why is it so ineffective, chaotic, underfunded, hard to navigate, and demedicalized? Why have psychiatrists—the traditional leaders in mental health—been marginalized to sign prescriptions instead of being executives and policy-setters for mental illness? Respiratory and physical therapists have important roles but the pulmonologist or the orthopedist runs the clinic. Why is it not so in public psychiatry? This is not progress, but a travesty.
• Why is psychiatry now referred to as “behavioral health”? Who decided to fix the name of psychiatric care when the original term is much more comprehensive, factual, and inclusive and uses medical terminology (iatros = “healer” or “medicine”). It is not progress to reduce to “behavior” psychiatric illnesses that involve a broad spectrum of pathologies, including thought disorders, mood disorders, perceptual disorders, cognitive disorders, pain, addictions, and many general medical conditions that manifest with psychiatric signs and symptoms. Redefining psychiatric care with inaccurate terminology certainly is not progress.
• Why are pharmaceutical companies, the only source of drug development, abandoning CNS research? Is it because cardiovascular, oncologic, and GI drugs are more profitable and less “challenging” to develop? Is it progress to turn away from the most critical medical frontier, the human brain, and its diseases? At a time when 80% of psychiatric disorders have no approved medication, it is inexcusable to shirk from discovering drugs that trigger hope for recovery for patients with untreatable mental illness.

Ogden Nash once wrote: “Progress might have been all right once, but it has gone on too long.” I will add to that for psychiatry, progress isn’t what it used to be.

Everybody loves progress. People feel uplifted by the notion of progress, by the dynamic feeling it evokes of “moving forward,” of achieving new milestones and reaching new heights. Progress implies improvement in the human condition and an upgrade in quality of life. In medical disciplines such as psychiatry, it connotes less suffering, better treatments, more hope, improved social and vocational functioning, and full restoration of wellness.

But let’s be realistic. Overall evolution of psychiatry is not as “progressive” as we like to believe. Yes, there are thrilling breakthroughs in basic neuroscience research and understanding brain structure and function at the cellular and molecular levels. However, in many other areas of psychiatric practice, I feel we have moved backward since I began my career 3 decades ago. Egress, not progress, appears to be the state of psychiatry. In a tango-like fashion, psychiatry seems to take 1 step forward on 1 level (science and discovery) and 2 steps back on another level (practice realities). As an optimistic person, it pains me to admit that we have moved backward in several aspects of psychiatry:

• The discovery of chlorpromazine, the first antipsychotic, was a miraculous event for our field, but was it “progress” for our patients? Their symptoms improved partially but they developed serious side effects and remained functionally disabled throughout their lives. Patients were “freed” from locked hospital wards, then hurled into a poorly prepared and under-resourced community mental health care system, resulting in revolving door relapses, extensive drug abuse, rampant stigma, abject poverty, physical neglect, early death, homelessness, and for many psychiatric patients, incarceration in jails and prisons, an environment more restrictive than the reviled asylums. Our patients who were medically ill individuals cared for by doctors, nurses, and other health professionals are now lowly felons. It seems that those unfortunate enough to suffer from a psychotic brain disorder are destined to be further punished for it, a great injustice in the name of “progress.”
• Insurance hassles for serious mental illness did not exist in the asylum era. If an individual developed a psychotic disorder, he or she was admitted to the nearest state hospital without hesitation and provided medical and psychosocial care, even if the stay lasted months or years. Now, the same patient cannot afford psychiatric hospitalization even if he or she has “health insurance” (a euphemism for “restricted health coverage”). Equality of psychiatric disorders with other medical and surgical disorders remains a farce, and the lack of parity for mental illness has deprived millions of patients from adequate care. How many victims of mental illness have suffered or died in the name of “progress” in the health insurance industry?
• Who is the “genius” who stipulated that a psychotic, bipolar, suicidal, or homicidal patient could be effectively treated after 3 to 4 days of hospitalization? How did patients become widgets on an assembly line? Medical students and residents on inpatient wards no longer have the rewarding experience or witnessing full improvement in their patients. Is it progress when a patient with schizophrenia or severe depression is discharged after barely 30% to 40% improvement in symptoms? No wonder relapse, suicide, and homicide rates are very high in the 3 weeks after discharge. Long-term hospitals, the last refuge for severely disabled patients who cannot care for themselves, now are rare. Is that progress?
• Why are psychiatrists shackled by more legal constraints than physicians in other medical specialties? Why should lawyers and judges tell us how to practice medicine and who, when, and how to treat? Legal progress sounds like an oxymoron to me.
• Why is the public mental health system so broken in every state? Why is it so ineffective, chaotic, underfunded, hard to navigate, and demedicalized? Why have psychiatrists—the traditional leaders in mental health—been marginalized to sign prescriptions instead of being executives and policy-setters for mental illness? Respiratory and physical therapists have important roles but the pulmonologist or the orthopedist runs the clinic. Why is it not so in public psychiatry? This is not progress, but a travesty.
• Why is psychiatry now referred to as “behavioral health”? Who decided to fix the name of psychiatric care when the original term is much more comprehensive, factual, and inclusive and uses medical terminology (iatros = “healer” or “medicine”). It is not progress to reduce to “behavior” psychiatric illnesses that involve a broad spectrum of pathologies, including thought disorders, mood disorders, perceptual disorders, cognitive disorders, pain, addictions, and many general medical conditions that manifest with psychiatric signs and symptoms. Redefining psychiatric care with inaccurate terminology certainly is not progress.
• Why are pharmaceutical companies, the only source of drug development, abandoning CNS research? Is it because cardiovascular, oncologic, and GI drugs are more profitable and less “challenging” to develop? Is it progress to turn away from the most critical medical frontier, the human brain, and its diseases? At a time when 80% of psychiatric disorders have no approved medication, it is inexcusable to shirk from discovering drugs that trigger hope for recovery for patients with untreatable mental illness.

Ogden Nash once wrote: “Progress might have been all right once, but it has gone on too long.” I will add to that for psychiatry, progress isn’t what it used to be.

A substantial proportion of psychiatric patients suffer from a somatic illness concomitantly with a mood, thought, or behavioral disorder. Some complicated patients may be afflicted by a combination of 4 or 5 different psychiatric or general medical disorders, requiring the use of multiple medications, which almost always increases the risk of adverse effects, pharmacokinetic interactions, and adherence gaps, and also escalates costs.

In addition, multiple medications may set off other iatrogenic consequences, such as exacerbation of psychiatric symptoms caused by a nonpsychotropic medication (such as an antihypertensive worsening depressive symptoms) or aggravation of a general medical condition by a psychotropic (such as prolongation of the QT interval or hyperglycemia secondary to an atypical antipsychotic).

Thus, it is quite pleasing when the use of a single medication can simultaneously relieve ≥2 unrelated medical disorders, preempting the need for multiple medications. This is the essence of parsimonious pharmacotherapy, a “2 birds with 1 stone” approach that evades polypharmacy and its side effect burden and added cost.

Consider the following examples of how a single psychotropic—by virtue of both its efficacy and what may be considered a side effect—can relieve 2 psychiatric disorders, or a psychiatric and a physical disorder, or even 2 physical disorders:

Depression with premature ejaculation. Delayed orgasm associated with selective serotonin reuptake inhibitors (SSRIs) administered for depression can simultaneously mitigate premature ejaculation as an added benefit.

Bipolar disorder with migraine. Valproate is a commonly used mood stabilizer that also is effective and indicated for migraines. Lithium, another widely used mood stabilizer, can relieve cluster headaches.

A mood or psychotic disorder with insomnia. Antidepressant medications with sedating properties can treat unipolar or bipolar depression and simultaneously allay the insomnia that often coexists with a mood disorder. Similarly, sedating antipsychotic medications administered at bedtime can relieve psychosis and its coexisting insomnia.

A mood or psychotic disorder with anxiety. Anxiety frequently accompanies unipolar or bipolar depression or schizophrenia. An SSRI can help both depression and anxiety, and some antipsychotics also can relieve both psychosis and anxiety.

Bipolar disorder or schizophrenia with obesity. Some metabolically neutral atypical agents (aripiprazole, lurasidone, ziprasidone) can control schizophrenia symptoms and/or bipolar mania while helping obese patients shed weight acquired during previous treatment with an obesogenic antipsychotic.

Depression and/or anxiety with thrombotic disease. SSRIs treat both depression and anxiety, and their anticoagulant side effect reduces the risk of thrombus formation in patients at risk for thrombotic disease.

Bipolar disorder with leukopenia. Lithium is a standard mood stabilizer that controls bipolar disorder, and its leukocytosis side effect helps increase white blood cell production and alleviate leukopenia.

Depression or anxiety with pain. This is a well-known parsimonious pharmacotherapy. Pain symptoms are a common feature or comorbidity of depression, and practically all antidepressants have analgesic effects.

Bipolar disorder with alcohol or cocaine addiction. The anticonvulsant/mood stabilizer valproate has been shown to significantly reduce both manic symptoms and comorbid heavy drinking in placebo- controlled studies. Another anticonvulsant/antimanic agent, carbamazepine, has been reported to reduce cocaine craving.

Migraine and obesity in a psychiatric patient. Topiramate is approved for migraines but its appetite-suppressing side effect can help decrease weight in patients with a high body mass index.

Posttraumatic stress disorder (PTSD) patients with depression, anxiety, obsessive-compulsive disorder, impulsivity, and insomnia. Here is a good example of how a sedating antidepressant agent—especially an SSRI—can help multiple symptom domains of PTSD.

Most psychiatric practitioners are aware of how to exploit side effects to help a coexisting medical disorder, or how to employ a multi-action drug to relieve a cluster of coexisting symptoms. Thus, psychiatric patients’ medical history can and should influence drug selection for the possible employment of parsimonious pharmacotherapy, which is gratifying for clinicians and a welcome antidote to polypharmacy in some patients with multiple medical disorders.

A substantial proportion of psychiatric patients suffer from a somatic illness concomitantly with a mood, thought, or behavioral disorder. Some complicated patients may be afflicted by a combination of 4 or 5 different psychiatric or general medical disorders, requiring the use of multiple medications, which almost always increases the risk of adverse effects, pharmacokinetic interactions, and adherence gaps, and also escalates costs.

In addition, multiple medications may set off other iatrogenic consequences, such as exacerbation of psychiatric symptoms caused by a nonpsychotropic medication (such as an antihypertensive worsening depressive symptoms) or aggravation of a general medical condition by a psychotropic (such as prolongation of the QT interval or hyperglycemia secondary to an atypical antipsychotic).

Thus, it is quite pleasing when the use of a single medication can simultaneously relieve ≥2 unrelated medical disorders, preempting the need for multiple medications. This is the essence of parsimonious pharmacotherapy, a “2 birds with 1 stone” approach that evades polypharmacy and its side effect burden and added cost.

Consider the following examples of how a single psychotropic—by virtue of both its efficacy and what may be considered a side effect—can relieve 2 psychiatric disorders, or a psychiatric and a physical disorder, or even 2 physical disorders:

Depression with premature ejaculation. Delayed orgasm associated with selective serotonin reuptake inhibitors (SSRIs) administered for depression can simultaneously mitigate premature ejaculation as an added benefit.

Bipolar disorder with migraine. Valproate is a commonly used mood stabilizer that also is effective and indicated for migraines. Lithium, another widely used mood stabilizer, can relieve cluster headaches.

A mood or psychotic disorder with insomnia. Antidepressant medications with sedating properties can treat unipolar or bipolar depression and simultaneously allay the insomnia that often coexists with a mood disorder. Similarly, sedating antipsychotic medications administered at bedtime can relieve psychosis and its coexisting insomnia.

A mood or psychotic disorder with anxiety. Anxiety frequently accompanies unipolar or bipolar depression or schizophrenia. An SSRI can help both depression and anxiety, and some antipsychotics also can relieve both psychosis and anxiety.

Bipolar disorder or schizophrenia with obesity. Some metabolically neutral atypical agents (aripiprazole, lurasidone, ziprasidone) can control schizophrenia symptoms and/or bipolar mania while helping obese patients shed weight acquired during previous treatment with an obesogenic antipsychotic.

Depression and/or anxiety with thrombotic disease. SSRIs treat both depression and anxiety, and their anticoagulant side effect reduces the risk of thrombus formation in patients at risk for thrombotic disease.

Bipolar disorder with leukopenia. Lithium is a standard mood stabilizer that controls bipolar disorder, and its leukocytosis side effect helps increase white blood cell production and alleviate leukopenia.

Depression or anxiety with pain. This is a well-known parsimonious pharmacotherapy. Pain symptoms are a common feature or comorbidity of depression, and practically all antidepressants have analgesic effects.

Bipolar disorder with alcohol or cocaine addiction. The anticonvulsant/mood stabilizer valproate has been shown to significantly reduce both manic symptoms and comorbid heavy drinking in placebo- controlled studies. Another anticonvulsant/antimanic agent, carbamazepine, has been reported to reduce cocaine craving.

Migraine and obesity in a psychiatric patient. Topiramate is approved for migraines but its appetite-suppressing side effect can help decrease weight in patients with a high body mass index.

Posttraumatic stress disorder (PTSD) patients with depression, anxiety, obsessive-compulsive disorder, impulsivity, and insomnia. Here is a good example of how a sedating antidepressant agent—especially an SSRI—can help multiple symptom domains of PTSD.

Most psychiatric practitioners are aware of how to exploit side effects to help a coexisting medical disorder, or how to employ a multi-action drug to relieve a cluster of coexisting symptoms. Thus, psychiatric patients’ medical history can and should influence drug selection for the possible employment of parsimonious pharmacotherapy, which is gratifying for clinicians and a welcome antidote to polypharmacy in some patients with multiple medical disorders.

A substantial proportion of psychiatric patients suffer from a somatic illness concomitantly with a mood, thought, or behavioral disorder. Some complicated patients may be afflicted by a combination of 4 or 5 different psychiatric or general medical disorders, requiring the use of multiple medications, which almost always increases the risk of adverse effects, pharmacokinetic interactions, and adherence gaps, and also escalates costs.

In addition, multiple medications may set off other iatrogenic consequences, such as exacerbation of psychiatric symptoms caused by a nonpsychotropic medication (such as an antihypertensive worsening depressive symptoms) or aggravation of a general medical condition by a psychotropic (such as prolongation of the QT interval or hyperglycemia secondary to an atypical antipsychotic).

Thus, it is quite pleasing when the use of a single medication can simultaneously relieve ≥2 unrelated medical disorders, preempting the need for multiple medications. This is the essence of parsimonious pharmacotherapy, a “2 birds with 1 stone” approach that evades polypharmacy and its side effect burden and added cost.

Consider the following examples of how a single psychotropic—by virtue of both its efficacy and what may be considered a side effect—can relieve 2 psychiatric disorders, or a psychiatric and a physical disorder, or even 2 physical disorders:

Depression with premature ejaculation. Delayed orgasm associated with selective serotonin reuptake inhibitors (SSRIs) administered for depression can simultaneously mitigate premature ejaculation as an added benefit.

Bipolar disorder with migraine. Valproate is a commonly used mood stabilizer that also is effective and indicated for migraines. Lithium, another widely used mood stabilizer, can relieve cluster headaches.

A mood or psychotic disorder with insomnia. Antidepressant medications with sedating properties can treat unipolar or bipolar depression and simultaneously allay the insomnia that often coexists with a mood disorder. Similarly, sedating antipsychotic medications administered at bedtime can relieve psychosis and its coexisting insomnia.

A mood or psychotic disorder with anxiety. Anxiety frequently accompanies unipolar or bipolar depression or schizophrenia. An SSRI can help both depression and anxiety, and some antipsychotics also can relieve both psychosis and anxiety.

Bipolar disorder or schizophrenia with obesity. Some metabolically neutral atypical agents (aripiprazole, lurasidone, ziprasidone) can control schizophrenia symptoms and/or bipolar mania while helping obese patients shed weight acquired during previous treatment with an obesogenic antipsychotic.

Depression and/or anxiety with thrombotic disease. SSRIs treat both depression and anxiety, and their anticoagulant side effect reduces the risk of thrombus formation in patients at risk for thrombotic disease.

Bipolar disorder with leukopenia. Lithium is a standard mood stabilizer that controls bipolar disorder, and its leukocytosis side effect helps increase white blood cell production and alleviate leukopenia.

Depression or anxiety with pain. This is a well-known parsimonious pharmacotherapy. Pain symptoms are a common feature or comorbidity of depression, and practically all antidepressants have analgesic effects.

Bipolar disorder with alcohol or cocaine addiction. The anticonvulsant/mood stabilizer valproate has been shown to significantly reduce both manic symptoms and comorbid heavy drinking in placebo- controlled studies. Another anticonvulsant/antimanic agent, carbamazepine, has been reported to reduce cocaine craving.

Migraine and obesity in a psychiatric patient. Topiramate is approved for migraines but its appetite-suppressing side effect can help decrease weight in patients with a high body mass index.

Posttraumatic stress disorder (PTSD) patients with depression, anxiety, obsessive-compulsive disorder, impulsivity, and insomnia. Here is a good example of how a sedating antidepressant agent—especially an SSRI—can help multiple symptom domains of PTSD.

Most psychiatric practitioners are aware of how to exploit side effects to help a coexisting medical disorder, or how to employ a multi-action drug to relieve a cluster of coexisting symptoms. Thus, psychiatric patients’ medical history can and should influence drug selection for the possible employment of parsimonious pharmacotherapy, which is gratifying for clinicians and a welcome antidote to polypharmacy in some patients with multiple medical disorders.

You’ve heard about the 2 certainties in life: death and taxes. In psychiatric practice with complex and chronic patients, there is a third certainty: polypharmacy. It ranges from thoughtful to indiscriminate and seems to be entrenched in clinical practice, possibly reflecting practitioners’ desperation in trying to manage severely ill, treatment-resistant patients, usually in the absence of evidence-based guidelines.

I never fail to encounter polypharmacy in hospitals or clinics where I consult. I always wondered how the patient’s doctor knew which drug was exerting a therapeutic effect or which drug was causing side effects (parkinsonism, akathisia, sedation, orthostasis, dizziness, headache, blurry vision, etc. ). Over time, I came to categorize polypharmacy into 4 subtypes that span the spectrum from sensible to absurd. Here is my personal classification, which I trust that you, my readers, have witnessed as well.

Necessary polypharmacy. This variant of polypharmacy is evidence-based and proven in double-blind studies to be more effective than monotherapy. The most prominent example is adding an atypical antipsychotic to a mood stabilizer in bipolar mania. In fact, the superior efficacy of combination therapy in bipolar disorder is one of the oldest forms of rational polypharmacy, is supported by FDA trials, and is indicated whenever mood stabilizer monotherapy is not sufficient. For example, combining lithium and valproate is superior to either drug alone. Another example of FDA-approved combinations is combining small doses of an atypical antipsychotic to an antidepressant for treatment-resistant depression.

Reasonable polypharmacy. Although many of the combinations in this category are not FDA-approved, controlled studies support their use for suffering patients. Examples include:

• An atypical antipsychotic added to a selective serotonin reuptake inhibitor (SSRI) for obsessive-compulsive disorder (OCD) patients who do not improve on SSRI monotherapy.
• Modafinil added to clozapine in patients who suffer substantial and persistent daytime sedation or somnolence.
• Combining 2 antidepressants for major depressive disorder patients who partially respond to 1 antidepressant.
• Combining a mood stabilizer with an antidepressant for bipolar depression to prevent mood switching.

Ridiculous polypharmacy. The sky is the limit to the variations and degrees of ridiculous polypharmacy, but the theme is the same: an absurd concoction of psychotropic drugs across several classes, often including multiple agents from 1 or several classes. Here are examples I have seen in patient records:

• Two atypicals, an anticholinergic, a mood stabilizer, an antidepressant, and 2 benzodiazepines.
• Three antipsychotics (2 atypicals and 1 typical), 2 antidepressants, 3 sedative/hypnotics, and an anticonvulsant for weight control.
• This one takes the cake: 6 antipsychotics (2 typicals and 4 atypicals), plus an anticholinergic, 3 mood stabilizers, 2 antidepressants, 2 sleeping pills, a hypoglycemic agent, 2 antihypertensives, and a statin.

Hazardous polypharmacy. In this category, serious medical complications, toxic effects, or death may occur because of careless combinations of drugs that may interact to produce dangerous kinetic interactions or exacerbate a pre-existing medical condition. Examples include:

• Combining 1 psychotropic with another that may inhibit its metabolism (eg, prescribing fluvoxamine to a severely psychotic patient who developed OCD while receiving clozapine). There have been several toxic reactions and even death because fluvoxamine inhibits cytochrome 1A2, which metabolizes clozapine, thus increasing clozapine blood level by 400% to 500%.
• Combining 2 injectable drugs for agitation that may cause a serious medical complication. An example would be injecting a benzodiazepine such as lorazepam in a patient receiving olanzapine IM, which can cause severe respiratory depression or death.
• Combining several drugs, each of which may prolong the QTc interval, resulting in syncope or torsade de pointes.

Psychopharmacology can relieve the terrible anguish of psychosis, depression, or anxiety, but it also can carry iatrogenic risks if it is not based on scientific evidence. The practice of psychopharmacology requires the fully integrated skills of medical and psychiatric training to maximize benefit while avoiding harm. It also requires basic arithmetic skills: to consider subtracting drugs, not only adding them!

You’ve heard about the 2 certainties in life: death and taxes. In psychiatric practice with complex and chronic patients, there is a third certainty: polypharmacy. It ranges from thoughtful to indiscriminate and seems to be entrenched in clinical practice, possibly reflecting practitioners’ desperation in trying to manage severely ill, treatment-resistant patients, usually in the absence of evidence-based guidelines.

I never fail to encounter polypharmacy in hospitals or clinics where I consult. I always wondered how the patient’s doctor knew which drug was exerting a therapeutic effect or which drug was causing side effects (parkinsonism, akathisia, sedation, orthostasis, dizziness, headache, blurry vision, etc. ). Over time, I came to categorize polypharmacy into 4 subtypes that span the spectrum from sensible to absurd. Here is my personal classification, which I trust that you, my readers, have witnessed as well.

Necessary polypharmacy. This variant of polypharmacy is evidence-based and proven in double-blind studies to be more effective than monotherapy. The most prominent example is adding an atypical antipsychotic to a mood stabilizer in bipolar mania. In fact, the superior efficacy of combination therapy in bipolar disorder is one of the oldest forms of rational polypharmacy, is supported by FDA trials, and is indicated whenever mood stabilizer monotherapy is not sufficient. For example, combining lithium and valproate is superior to either drug alone. Another example of FDA-approved combinations is combining small doses of an atypical antipsychotic to an antidepressant for treatment-resistant depression.

Reasonable polypharmacy. Although many of the combinations in this category are not FDA-approved, controlled studies support their use for suffering patients. Examples include:

• An atypical antipsychotic added to a selective serotonin reuptake inhibitor (SSRI) for obsessive-compulsive disorder (OCD) patients who do not improve on SSRI monotherapy.
• Modafinil added to clozapine in patients who suffer substantial and persistent daytime sedation or somnolence.
• Combining 2 antidepressants for major depressive disorder patients who partially respond to 1 antidepressant.
• Combining a mood stabilizer with an antidepressant for bipolar depression to prevent mood switching.

Ridiculous polypharmacy. The sky is the limit to the variations and degrees of ridiculous polypharmacy, but the theme is the same: an absurd concoction of psychotropic drugs across several classes, often including multiple agents from 1 or several classes. Here are examples I have seen in patient records:

• Two atypicals, an anticholinergic, a mood stabilizer, an antidepressant, and 2 benzodiazepines.
• Three antipsychotics (2 atypicals and 1 typical), 2 antidepressants, 3 sedative/hypnotics, and an anticonvulsant for weight control.
• This one takes the cake: 6 antipsychotics (2 typicals and 4 atypicals), plus an anticholinergic, 3 mood stabilizers, 2 antidepressants, 2 sleeping pills, a hypoglycemic agent, 2 antihypertensives, and a statin.

Hazardous polypharmacy. In this category, serious medical complications, toxic effects, or death may occur because of careless combinations of drugs that may interact to produce dangerous kinetic interactions or exacerbate a pre-existing medical condition. Examples include:

• Combining 1 psychotropic with another that may inhibit its metabolism (eg, prescribing fluvoxamine to a severely psychotic patient who developed OCD while receiving clozapine). There have been several toxic reactions and even death because fluvoxamine inhibits cytochrome 1A2, which metabolizes clozapine, thus increasing clozapine blood level by 400% to 500%.
• Combining 2 injectable drugs for agitation that may cause a serious medical complication. An example would be injecting a benzodiazepine such as lorazepam in a patient receiving olanzapine IM, which can cause severe respiratory depression or death.
• Combining several drugs, each of which may prolong the QTc interval, resulting in syncope or torsade de pointes.

Psychopharmacology can relieve the terrible anguish of psychosis, depression, or anxiety, but it also can carry iatrogenic risks if it is not based on scientific evidence. The practice of psychopharmacology requires the fully integrated skills of medical and psychiatric training to maximize benefit while avoiding harm. It also requires basic arithmetic skills: to consider subtracting drugs, not only adding them!

You’ve heard about the 2 certainties in life: death and taxes. In psychiatric practice with complex and chronic patients, there is a third certainty: polypharmacy. It ranges from thoughtful to indiscriminate and seems to be entrenched in clinical practice, possibly reflecting practitioners’ desperation in trying to manage severely ill, treatment-resistant patients, usually in the absence of evidence-based guidelines.

I never fail to encounter polypharmacy in hospitals or clinics where I consult. I always wondered how the patient’s doctor knew which drug was exerting a therapeutic effect or which drug was causing side effects (parkinsonism, akathisia, sedation, orthostasis, dizziness, headache, blurry vision, etc. ). Over time, I came to categorize polypharmacy into 4 subtypes that span the spectrum from sensible to absurd. Here is my personal classification, which I trust that you, my readers, have witnessed as well.

Necessary polypharmacy. This variant of polypharmacy is evidence-based and proven in double-blind studies to be more effective than monotherapy. The most prominent example is adding an atypical antipsychotic to a mood stabilizer in bipolar mania. In fact, the superior efficacy of combination therapy in bipolar disorder is one of the oldest forms of rational polypharmacy, is supported by FDA trials, and is indicated whenever mood stabilizer monotherapy is not sufficient. For example, combining lithium and valproate is superior to either drug alone. Another example of FDA-approved combinations is combining small doses of an atypical antipsychotic to an antidepressant for treatment-resistant depression.

Reasonable polypharmacy. Although many of the combinations in this category are not FDA-approved, controlled studies support their use for suffering patients. Examples include:

• An atypical antipsychotic added to a selective serotonin reuptake inhibitor (SSRI) for obsessive-compulsive disorder (OCD) patients who do not improve on SSRI monotherapy.
• Modafinil added to clozapine in patients who suffer substantial and persistent daytime sedation or somnolence.
• Combining 2 antidepressants for major depressive disorder patients who partially respond to 1 antidepressant.
• Combining a mood stabilizer with an antidepressant for bipolar depression to prevent mood switching.

Ridiculous polypharmacy. The sky is the limit to the variations and degrees of ridiculous polypharmacy, but the theme is the same: an absurd concoction of psychotropic drugs across several classes, often including multiple agents from 1 or several classes. Here are examples I have seen in patient records:

• Two atypicals, an anticholinergic, a mood stabilizer, an antidepressant, and 2 benzodiazepines.
• Three antipsychotics (2 atypicals and 1 typical), 2 antidepressants, 3 sedative/hypnotics, and an anticonvulsant for weight control.
• This one takes the cake: 6 antipsychotics (2 typicals and 4 atypicals), plus an anticholinergic, 3 mood stabilizers, 2 antidepressants, 2 sleeping pills, a hypoglycemic agent, 2 antihypertensives, and a statin.

Hazardous polypharmacy. In this category, serious medical complications, toxic effects, or death may occur because of careless combinations of drugs that may interact to produce dangerous kinetic interactions or exacerbate a pre-existing medical condition. Examples include:

• Combining 1 psychotropic with another that may inhibit its metabolism (eg, prescribing fluvoxamine to a severely psychotic patient who developed OCD while receiving clozapine). There have been several toxic reactions and even death because fluvoxamine inhibits cytochrome 1A2, which metabolizes clozapine, thus increasing clozapine blood level by 400% to 500%.
• Combining 2 injectable drugs for agitation that may cause a serious medical complication. An example would be injecting a benzodiazepine such as lorazepam in a patient receiving olanzapine IM, which can cause severe respiratory depression or death.
• Combining several drugs, each of which may prolong the QTc interval, resulting in syncope or torsade de pointes.

Psychopharmacology can relieve the terrible anguish of psychosis, depression, or anxiety, but it also can carry iatrogenic risks if it is not based on scientific evidence. The practice of psychopharmacology requires the fully integrated skills of medical and psychiatric training to maximize benefit while avoiding harm. It also requires basic arithmetic skills: to consider subtracting drugs, not only adding them!

Psychiatrists occasionally encounter a case of folie à deux, where 2 persons share the same false belief. Paradoxically, it is more common for a large number of people to share a false belief (folie en masse) and uphold it as fact because the idea appears enticingly valid as an “explanation” for a problem or event.

“Conspiracy theories” abound in our society and yet conspiracy theory advocates would express shock and disdain at the infamous event when 918 followers of Jim Jones drank cyanide-laced Kool-Aid because they believed their leader’s irrational ideas. Apart from recognizable cults—some of whom claim to have their own “solutions” for mental illness—many ordinary people uphold beliefs that are not supported by evidence but widely “accepted” as true:

Persons with psychosis are dangerous. This incorrect belief was prevalent before the tragic events at Virginia Tech and Tucson, AZ (remember the “Son of Sam” in New York?) and was reinforced by them. Clinicians know that, similar to the general population, only a small proportion of persons suffering from a psychotic illness exhibit violent behavior. In fact, their illness renders them more likely to be victims than perpetrators of crime.

Atypical antipsychotics are associated with high weight gain, but older neuroleptics are not. Many psychiatrists uphold this clinical mantra and believe that older antipsychotics, such as haloperidol, which cause a lot of movement disorders, are associated with minimal weight gain. Most also believe that some atypicals are weight-neutral compared with other atypicals. The evidence from the European First Episode Schizophrenia Trial (EUFEST) debunked both beliefs by finding substantial weight gain with all antipsychotic drugs, old or new, after 1 year of treatment with haloperidol and several atypicals ( Table ).¹ Neither old antipsychotics, such as haloperidol, nor metabolically “benign” atypicals, such as ziprasidone, are exceptions. Yet this belief likely will persist.

Table 1

Weight gain with antipsychotics: EUFEST results

The U. S. obesity epidemic is caused by too much fast food and too little exercise. This widely accepted explanation sounds like a no-brainer. However, by taking a “big-picture” view, a recent study² pointed to completely different reasons for rising obesity in the United States. Researchers found that other species such as rats and mice (rarely seen waiting in line at McDonald’s) experienced dramatic per-decade increases in obesity rates over the past 50 years, including 38% in pet cats, 34% in chimpanzees in research labs, 21% in alley rats, and 12% in government lab mice. Only pet dogs escaped the escalating obesity rates with 3% per decade. Alternate explanations for rising obesity include less sleep, which increases ghrelin (an appetite-stimulating hormone) and decreases leptin (a satiety hormone); proliferation of fat cells from chemicals such as bisphenol A; central heating (less burning of calories) and air conditioning (prevents the appetite-suppressing heat of summer); infections such as adenoviruses that can cause obesity in animals; and changes in gut bacteria, some of which increase caloric extraction from food.

Many false beliefs have been adopted by a large proportion of the general population. This tendency for folie en masse is consistent with studies that show pre-psychotic thinking is found in more than half of the general population, suggesting a continuum between psychosis proneness and clinical psychosis.³ This raises the question: could psychosis proneness mean that the brain can produce its own “endogenous” Kool-Aid?

Psychiatrists occasionally encounter a case of folie à deux, where 2 persons share the same false belief. Paradoxically, it is more common for a large number of people to share a false belief (folie en masse) and uphold it as fact because the idea appears enticingly valid as an “explanation” for a problem or event.

“Conspiracy theories” abound in our society and yet conspiracy theory advocates would express shock and disdain at the infamous event when 918 followers of Jim Jones drank cyanide-laced Kool-Aid because they believed their leader’s irrational ideas. Apart from recognizable cults—some of whom claim to have their own “solutions” for mental illness—many ordinary people uphold beliefs that are not supported by evidence but widely “accepted” as true:

Persons with psychosis are dangerous. This incorrect belief was prevalent before the tragic events at Virginia Tech and Tucson, AZ (remember the “Son of Sam” in New York?) and was reinforced by them. Clinicians know that, similar to the general population, only a small proportion of persons suffering from a psychotic illness exhibit violent behavior. In fact, their illness renders them more likely to be victims than perpetrators of crime.

Atypical antipsychotics are associated with high weight gain, but older neuroleptics are not. Many psychiatrists uphold this clinical mantra and believe that older antipsychotics, such as haloperidol, which cause a lot of movement disorders, are associated with minimal weight gain. Most also believe that some atypicals are weight-neutral compared with other atypicals. The evidence from the European First Episode Schizophrenia Trial (EUFEST) debunked both beliefs by finding substantial weight gain with all antipsychotic drugs, old or new, after 1 year of treatment with haloperidol and several atypicals ( Table ).¹ Neither old antipsychotics, such as haloperidol, nor metabolically “benign” atypicals, such as ziprasidone, are exceptions. Yet this belief likely will persist.

Table 1

Weight gain with antipsychotics: EUFEST results

The U. S. obesity epidemic is caused by too much fast food and too little exercise. This widely accepted explanation sounds like a no-brainer. However, by taking a “big-picture” view, a recent study² pointed to completely different reasons for rising obesity in the United States. Researchers found that other species such as rats and mice (rarely seen waiting in line at McDonald’s) experienced dramatic per-decade increases in obesity rates over the past 50 years, including 38% in pet cats, 34% in chimpanzees in research labs, 21% in alley rats, and 12% in government lab mice. Only pet dogs escaped the escalating obesity rates with 3% per decade. Alternate explanations for rising obesity include less sleep, which increases ghrelin (an appetite-stimulating hormone) and decreases leptin (a satiety hormone); proliferation of fat cells from chemicals such as bisphenol A; central heating (less burning of calories) and air conditioning (prevents the appetite-suppressing heat of summer); infections such as adenoviruses that can cause obesity in animals; and changes in gut bacteria, some of which increase caloric extraction from food.

Many false beliefs have been adopted by a large proportion of the general population. This tendency for folie en masse is consistent with studies that show pre-psychotic thinking is found in more than half of the general population, suggesting a continuum between psychosis proneness and clinical psychosis.³ This raises the question: could psychosis proneness mean that the brain can produce its own “endogenous” Kool-Aid?

Psychiatrists occasionally encounter a case of folie à deux, where 2 persons share the same false belief. Paradoxically, it is more common for a large number of people to share a false belief (folie en masse) and uphold it as fact because the idea appears enticingly valid as an “explanation” for a problem or event.

“Conspiracy theories” abound in our society and yet conspiracy theory advocates would express shock and disdain at the infamous event when 918 followers of Jim Jones drank cyanide-laced Kool-Aid because they believed their leader’s irrational ideas. Apart from recognizable cults—some of whom claim to have their own “solutions” for mental illness—many ordinary people uphold beliefs that are not supported by evidence but widely “accepted” as true:

Persons with psychosis are dangerous. This incorrect belief was prevalent before the tragic events at Virginia Tech and Tucson, AZ (remember the “Son of Sam” in New York?) and was reinforced by them. Clinicians know that, similar to the general population, only a small proportion of persons suffering from a psychotic illness exhibit violent behavior. In fact, their illness renders them more likely to be victims than perpetrators of crime.

Atypical antipsychotics are associated with high weight gain, but older neuroleptics are not. Many psychiatrists uphold this clinical mantra and believe that older antipsychotics, such as haloperidol, which cause a lot of movement disorders, are associated with minimal weight gain. Most also believe that some atypicals are weight-neutral compared with other atypicals. The evidence from the European First Episode Schizophrenia Trial (EUFEST) debunked both beliefs by finding substantial weight gain with all antipsychotic drugs, old or new, after 1 year of treatment with haloperidol and several atypicals ( Table ).¹ Neither old antipsychotics, such as haloperidol, nor metabolically “benign” atypicals, such as ziprasidone, are exceptions. Yet this belief likely will persist.

Table 1

Weight gain with antipsychotics: EUFEST results

The U. S. obesity epidemic is caused by too much fast food and too little exercise. This widely accepted explanation sounds like a no-brainer. However, by taking a “big-picture” view, a recent study² pointed to completely different reasons for rising obesity in the United States. Researchers found that other species such as rats and mice (rarely seen waiting in line at McDonald’s) experienced dramatic per-decade increases in obesity rates over the past 50 years, including 38% in pet cats, 34% in chimpanzees in research labs, 21% in alley rats, and 12% in government lab mice. Only pet dogs escaped the escalating obesity rates with 3% per decade. Alternate explanations for rising obesity include less sleep, which increases ghrelin (an appetite-stimulating hormone) and decreases leptin (a satiety hormone); proliferation of fat cells from chemicals such as bisphenol A; central heating (less burning of calories) and air conditioning (prevents the appetite-suppressing heat of summer); infections such as adenoviruses that can cause obesity in animals; and changes in gut bacteria, some of which increase caloric extraction from food.

Many false beliefs have been adopted by a large proportion of the general population. This tendency for folie en masse is consistent with studies that show pre-psychotic thinking is found in more than half of the general population, suggesting a continuum between psychosis proneness and clinical psychosis.³ This raises the question: could psychosis proneness mean that the brain can produce its own “endogenous” Kool-Aid?

Discuss this article at http://currentpsychiatry.blogspot.com/2011/02/two-vastly-underutilized-interventions.html#comments

Many psychiatrists would agree that schizophrenia is the most devastating psychiatric brain disease. Its disabling effects result in stigma, unemployment, poverty, loneliness, homelessness, victimization, incarceration, malnutrition, infections, social isolation, ostracism, discrimination, suicide, poor health, medical neglect, and early death.

The consequences of schizophrenia are in many ways more malignant than those of cancer, where sympathy, prompt medical care, and preservation of friends and employment are assured. Also, unlike schizophrenia patients, persons with cancer are never hauled to jail, even when a slow-growing brain tumor causes erratic or violent behavior.

The outcome of schizophrenia has not improved much since patients were “freed” from state hospitals before the psychopharmacology era. Despite the availability of antipsychotics that can control delusions and hallucinations, few persons with schizophrenia achieve remission, let alone recovery. Although negative symptoms and cognitive deficits remain untreatable, the quality of life for persons with schizophrenia can be far less miserable if psychotic symptoms are fully remitted. So why do so many patients with schizophrenia suffer continuous or episodic psychosis that renders their lives a living hell and leads them to inexorable clinical, social, and functional deterioration?

Based on 3 decades of clinical and research work with thousands of patients afflicted with schizophrenia, I have observed that most psychiatrists are not exploiting 2 treatment options that could effectively alleviate continuous or relapsing psychosis. Let me elaborate:

• Continuous, unabated psychotic symptoms (delusions, hallucinations, bizarre behavior, and thought derailment) implies either refractory or treatment-resistant schizophrenia. This means that several antipsychotic trials already have failed to suppress psychotic symptoms. Only 1 drug has been proven to help such patients: clozapine. It was FDA-approved for refractory schizophrenia 22 years ago, and many studies—including the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial—show that it also is superior to other antipsychotics for treatment-resistant schizophrenia. Yet while about 30% to 35% of patients have refractory or treatment-resistant schizophrenia, only one-sixth of that eligible pool receive clozapine. Reasons include the “hassle” of monitoring, the fear of agranulocytosis (which is rare), and concern about serious side effects. As a result, hundreds of thousands of patients suffer needlessly because they have not received clozapine (full response may take 6 to 12 months in some patients, but only 3 months in others).
• For patients whose delusions and hallucinations do respond to nonclozapine antipsychotics, psychotic episodes are most likely caused by nonadherence to oral medications. All psychiatrists are aware that partial or complete nonadherence is ubiquitous in schizophrenia for multiple reasons, including lack of insight about being ill and needing treatment, suspiciousness (positive symptoms) about drugs, amotivation and avolition (negative symptoms), poor memory or planning ability (cognitive deficits), and toxic effects of alcohol and drugs. Therefore, many psychotic relapses occur needlessly because of inevitable nonadherence with oral medications. In my clinical estimate, this occurs in 50% to 60% of patients who had responded well to oral antipsychotics in the past. The tragic consequences of recurrent relapses is not only re-experiencing the anguish of reality-shattering psychotic states, but also progressive brain atrophy resulting from the “neurotoxic” effects of psychosis, and, unfortunately, progressive development of treatment resistance with each relapse.

The most logical solution to avoid psychotic relapses resulting from nonadherence is long-acting injectable (depot) antipsychotics, which have a large body of data (including FDA registration trials) documenting successful relapse prevention. It is incomprehensible why long-acting formulations are not used in at least 30% to 40% of patients instead of the 6% to 8% who currently receive them. They also should be given to all schizophrenia patients incarcerated for violent acts. Furthermore, there is no reason not to use injectable formulations early in the illness course—after 1 or 2 relapses—to halt or prevent the clinical and functional deterioration that occurs with multiple relapses. In my experience, the stabilization and full remission that occur after 18 to 24 months of continuous adherence with a long-acting injectable antipsychotic can be remarkable and gratifying to patients, families, and psychiatrists.

In summary, intensified research is needed to discover the next generation of pharmacotherapeutic agents that can treat all symptom domains of schizophrenia (positive, negative, cognitive, mood, and substance use). In the meantime, a wider use of those 2 available interventions—clozapine in refractory and treatment-resistant patients and long-acting injectable antipsychotics in nonadherent patients—can make a palpable impact on improving clinical and functional outcomes of patients suffering with schizophrenia. These 2 interventions might make a significant dent in the atrociously high rate of incarceration because of psychosis-induced illegal behaviors. The financial savings in hospitalization and forensic costs can be substantial. But most important, preventing psychosis and incarceration would mean a measurably better life for patients.

Discuss this article at http://currentpsychiatry.blogspot.com/2011/02/two-vastly-underutilized-interventions.html#comments

Many psychiatrists would agree that schizophrenia is the most devastating psychiatric brain disease. Its disabling effects result in stigma, unemployment, poverty, loneliness, homelessness, victimization, incarceration, malnutrition, infections, social isolation, ostracism, discrimination, suicide, poor health, medical neglect, and early death.

The consequences of schizophrenia are in many ways more malignant than those of cancer, where sympathy, prompt medical care, and preservation of friends and employment are assured. Also, unlike schizophrenia patients, persons with cancer are never hauled to jail, even when a slow-growing brain tumor causes erratic or violent behavior.

The outcome of schizophrenia has not improved much since patients were “freed” from state hospitals before the psychopharmacology era. Despite the availability of antipsychotics that can control delusions and hallucinations, few persons with schizophrenia achieve remission, let alone recovery. Although negative symptoms and cognitive deficits remain untreatable, the quality of life for persons with schizophrenia can be far less miserable if psychotic symptoms are fully remitted. So why do so many patients with schizophrenia suffer continuous or episodic psychosis that renders their lives a living hell and leads them to inexorable clinical, social, and functional deterioration?

Based on 3 decades of clinical and research work with thousands of patients afflicted with schizophrenia, I have observed that most psychiatrists are not exploiting 2 treatment options that could effectively alleviate continuous or relapsing psychosis. Let me elaborate:

• Continuous, unabated psychotic symptoms (delusions, hallucinations, bizarre behavior, and thought derailment) implies either refractory or treatment-resistant schizophrenia. This means that several antipsychotic trials already have failed to suppress psychotic symptoms. Only 1 drug has been proven to help such patients: clozapine. It was FDA-approved for refractory schizophrenia 22 years ago, and many studies—including the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial—show that it also is superior to other antipsychotics for treatment-resistant schizophrenia. Yet while about 30% to 35% of patients have refractory or treatment-resistant schizophrenia, only one-sixth of that eligible pool receive clozapine. Reasons include the “hassle” of monitoring, the fear of agranulocytosis (which is rare), and concern about serious side effects. As a result, hundreds of thousands of patients suffer needlessly because they have not received clozapine (full response may take 6 to 12 months in some patients, but only 3 months in others).
• For patients whose delusions and hallucinations do respond to nonclozapine antipsychotics, psychotic episodes are most likely caused by nonadherence to oral medications. All psychiatrists are aware that partial or complete nonadherence is ubiquitous in schizophrenia for multiple reasons, including lack of insight about being ill and needing treatment, suspiciousness (positive symptoms) about drugs, amotivation and avolition (negative symptoms), poor memory or planning ability (cognitive deficits), and toxic effects of alcohol and drugs. Therefore, many psychotic relapses occur needlessly because of inevitable nonadherence with oral medications. In my clinical estimate, this occurs in 50% to 60% of patients who had responded well to oral antipsychotics in the past. The tragic consequences of recurrent relapses is not only re-experiencing the anguish of reality-shattering psychotic states, but also progressive brain atrophy resulting from the “neurotoxic” effects of psychosis, and, unfortunately, progressive development of treatment resistance with each relapse.

The most logical solution to avoid psychotic relapses resulting from nonadherence is long-acting injectable (depot) antipsychotics, which have a large body of data (including FDA registration trials) documenting successful relapse prevention. It is incomprehensible why long-acting formulations are not used in at least 30% to 40% of patients instead of the 6% to 8% who currently receive them. They also should be given to all schizophrenia patients incarcerated for violent acts. Furthermore, there is no reason not to use injectable formulations early in the illness course—after 1 or 2 relapses—to halt or prevent the clinical and functional deterioration that occurs with multiple relapses. In my experience, the stabilization and full remission that occur after 18 to 24 months of continuous adherence with a long-acting injectable antipsychotic can be remarkable and gratifying to patients, families, and psychiatrists.

In summary, intensified research is needed to discover the next generation of pharmacotherapeutic agents that can treat all symptom domains of schizophrenia (positive, negative, cognitive, mood, and substance use). In the meantime, a wider use of those 2 available interventions—clozapine in refractory and treatment-resistant patients and long-acting injectable antipsychotics in nonadherent patients—can make a palpable impact on improving clinical and functional outcomes of patients suffering with schizophrenia. These 2 interventions might make a significant dent in the atrociously high rate of incarceration because of psychosis-induced illegal behaviors. The financial savings in hospitalization and forensic costs can be substantial. But most important, preventing psychosis and incarceration would mean a measurably better life for patients.

Discuss this article at http://currentpsychiatry.blogspot.com/2011/02/two-vastly-underutilized-interventions.html#comments

Many psychiatrists would agree that schizophrenia is the most devastating psychiatric brain disease. Its disabling effects result in stigma, unemployment, poverty, loneliness, homelessness, victimization, incarceration, malnutrition, infections, social isolation, ostracism, discrimination, suicide, poor health, medical neglect, and early death.

The consequences of schizophrenia are in many ways more malignant than those of cancer, where sympathy, prompt medical care, and preservation of friends and employment are assured. Also, unlike schizophrenia patients, persons with cancer are never hauled to jail, even when a slow-growing brain tumor causes erratic or violent behavior.

The outcome of schizophrenia has not improved much since patients were “freed” from state hospitals before the psychopharmacology era. Despite the availability of antipsychotics that can control delusions and hallucinations, few persons with schizophrenia achieve remission, let alone recovery. Although negative symptoms and cognitive deficits remain untreatable, the quality of life for persons with schizophrenia can be far less miserable if psychotic symptoms are fully remitted. So why do so many patients with schizophrenia suffer continuous or episodic psychosis that renders their lives a living hell and leads them to inexorable clinical, social, and functional deterioration?

Based on 3 decades of clinical and research work with thousands of patients afflicted with schizophrenia, I have observed that most psychiatrists are not exploiting 2 treatment options that could effectively alleviate continuous or relapsing psychosis. Let me elaborate:

• Continuous, unabated psychotic symptoms (delusions, hallucinations, bizarre behavior, and thought derailment) implies either refractory or treatment-resistant schizophrenia. This means that several antipsychotic trials already have failed to suppress psychotic symptoms. Only 1 drug has been proven to help such patients: clozapine. It was FDA-approved for refractory schizophrenia 22 years ago, and many studies—including the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) trial—show that it also is superior to other antipsychotics for treatment-resistant schizophrenia. Yet while about 30% to 35% of patients have refractory or treatment-resistant schizophrenia, only one-sixth of that eligible pool receive clozapine. Reasons include the “hassle” of monitoring, the fear of agranulocytosis (which is rare), and concern about serious side effects. As a result, hundreds of thousands of patients suffer needlessly because they have not received clozapine (full response may take 6 to 12 months in some patients, but only 3 months in others).
• For patients whose delusions and hallucinations do respond to nonclozapine antipsychotics, psychotic episodes are most likely caused by nonadherence to oral medications. All psychiatrists are aware that partial or complete nonadherence is ubiquitous in schizophrenia for multiple reasons, including lack of insight about being ill and needing treatment, suspiciousness (positive symptoms) about drugs, amotivation and avolition (negative symptoms), poor memory or planning ability (cognitive deficits), and toxic effects of alcohol and drugs. Therefore, many psychotic relapses occur needlessly because of inevitable nonadherence with oral medications. In my clinical estimate, this occurs in 50% to 60% of patients who had responded well to oral antipsychotics in the past. The tragic consequences of recurrent relapses is not only re-experiencing the anguish of reality-shattering psychotic states, but also progressive brain atrophy resulting from the “neurotoxic” effects of psychosis, and, unfortunately, progressive development of treatment resistance with each relapse.

The most logical solution to avoid psychotic relapses resulting from nonadherence is long-acting injectable (depot) antipsychotics, which have a large body of data (including FDA registration trials) documenting successful relapse prevention. It is incomprehensible why long-acting formulations are not used in at least 30% to 40% of patients instead of the 6% to 8% who currently receive them. They also should be given to all schizophrenia patients incarcerated for violent acts. Furthermore, there is no reason not to use injectable formulations early in the illness course—after 1 or 2 relapses—to halt or prevent the clinical and functional deterioration that occurs with multiple relapses. In my experience, the stabilization and full remission that occur after 18 to 24 months of continuous adherence with a long-acting injectable antipsychotic can be remarkable and gratifying to patients, families, and psychiatrists.

In summary, intensified research is needed to discover the next generation of pharmacotherapeutic agents that can treat all symptom domains of schizophrenia (positive, negative, cognitive, mood, and substance use). In the meantime, a wider use of those 2 available interventions—clozapine in refractory and treatment-resistant patients and long-acting injectable antipsychotics in nonadherent patients—can make a palpable impact on improving clinical and functional outcomes of patients suffering with schizophrenia. These 2 interventions might make a significant dent in the atrociously high rate of incarceration because of psychosis-induced illegal behaviors. The financial savings in hospitalization and forensic costs can be substantial. But most important, preventing psychosis and incarceration would mean a measurably better life for patients.

Like all other medical specialties, psychiatry has its share of dogmas that are perpetuated via the clinical apprenticeship model from one generation of physicians to the next, despite the lack of hard evidence. They become “articles of faith” that go unchallenged by trainees who acquire them from their supervisors. A dogma masquerades as a truism and eventually becomes a sacred feature of the “clinical lore.”

Sooner or later, however, the bright light of scientific evidence will reveal the ersatz nature of a dogma and it will come crashing down. Similar to a revolution to depose a dictator, the demise of a dogma will have a salutary effect on medical practice and a liberating effect on practitioners.

Here are examples of psychiatric dogmas that were part of my training but have been/or are in the process of being taken to the slaughterhouse of obsolete tenets:

Psychiatrists should not touch their patients. Really! How can we be practicing physicians if we don’t? This dogma arbitrarily sexualized the physical exam, including drawing blood, measuring blood pressure or waist circumference, assessing neuroleptic-induced cogwheeling, or checking the body for a drug-induced rash. This dogma is the antithesis of good medical care for psychiatric patients, who frequently suffer from serious physical ailments and often do not have a primary care provider. It was created during the primordial phase of psychiatry (aka psychoanalysis) and is irrelevant in modern-era psychiatry.

Push the dose of neuroleptics higher and higher until the patient becomes parkinsonian, which is the sign that psychosis will improve. This dogma dominated the pharmacotherapy of schizophrenia for 40 years because of the erroneous linkage of extrapyramidal symptoms (EPS) with therapeutic response to antipsychotics. We did not realize the neurologic harm of this dogma until the computer revolution and related scientific advances enabled researchers to measure the dopamine receptor occupancy in patients’ brains.¹ Positron emission tomography (PET) scan studies revealed that only 60% to 65% of dopamine D2 receptors need to be blocked to suppress psychotic symptoms, whereas EPS will occur at ≥78% occupancy. Millions of patients needlessly suffered intolerable rigidity, dyskinesia, restlessness, and tremors and routinely received large doses of anticholinergic drugs that destroyed their quality of life due to memory loss, dry mouth, constipation, and blurry vision.

Medications must be administered daily. The same landmark receptor imaging studies described above may soon debunk this ubiquitously entrenched clinical dogma. Recent data showed that administering the same antipsychotic dose every other day instead of every day was equally efficacious.² Dopamine receptors do not require 24/7 blockade to treat psychosis as was formerly believed; apparently, intermittent occupancy is sufficient. Shattering this dogma can save 50% of the cost of the (expensive) antipsychotic medications, which chronic schizophrenia patients have to take for many years.

Patients with schizophrenia will ingest their oral medications as prescribed. This dogma continues to dominate clinical practice despite numerous studies that show up to 80% of schizophrenia patients relapse due to poor adherence to oral antipsychotics. Yet many psychiatrists continue to prescribe oral medications even though they know core symptoms of schizophrenia—lack of insight, amotivation, impaired memory, suspiciousness, and substance use—contribute heavily to nonadherence. The dogma of oral meds has been “attenuated” in Europe, where 30% of patients are treated with long-acting injectable depot medications, compared with about 7% in the United States.³

Academic psychiatrists must not collaborate with the pharmaceutical industry. This dogma was hatched recently and ignores the huge unmet needs of psychiatric patients. More than 80% of DSM-IV disorders do not have any FDA-approved drug.⁴ Whether we like it or not, the pharmaceutical industry is the only source of new medication. Instead of avoiding an academic-industry collaboration, Europe has boldly moved ahead of the United States by formalizing a unique initiative called Novel Methods leading to New Medications in Depression and Schizophrenia (NEWMEDS).

This large collaboration intends to accelerate new drug discovery via a partnership between several prestigious European academic psychiatry institutes and global drug companies. By discarding the strident, dogmatic attitudes of shirking collaboration, NEWMEDS promises to expedite and accelerate the discovery and development of urgently needed therapeutic agents with innovative mechanisms. Dr. S. Kapur, the PET imaging pioneer, serves as the academic leader of NEWMEDS.

Psychiatrists are experts at detecting erroneous thinking in individuals or groups. We should vigorously rid our specialty of unproven tenets and detrimental dogmas. The best and only way to accomplish that worthy goal is to seek scientific basis for everything we do or teach.

Like all other medical specialties, psychiatry has its share of dogmas that are perpetuated via the clinical apprenticeship model from one generation of physicians to the next, despite the lack of hard evidence. They become “articles of faith” that go unchallenged by trainees who acquire them from their supervisors. A dogma masquerades as a truism and eventually becomes a sacred feature of the “clinical lore.”

Sooner or later, however, the bright light of scientific evidence will reveal the ersatz nature of a dogma and it will come crashing down. Similar to a revolution to depose a dictator, the demise of a dogma will have a salutary effect on medical practice and a liberating effect on practitioners.

Here are examples of psychiatric dogmas that were part of my training but have been/or are in the process of being taken to the slaughterhouse of obsolete tenets:

Psychiatrists should not touch their patients. Really! How can we be practicing physicians if we don’t? This dogma arbitrarily sexualized the physical exam, including drawing blood, measuring blood pressure or waist circumference, assessing neuroleptic-induced cogwheeling, or checking the body for a drug-induced rash. This dogma is the antithesis of good medical care for psychiatric patients, who frequently suffer from serious physical ailments and often do not have a primary care provider. It was created during the primordial phase of psychiatry (aka psychoanalysis) and is irrelevant in modern-era psychiatry.

Push the dose of neuroleptics higher and higher until the patient becomes parkinsonian, which is the sign that psychosis will improve. This dogma dominated the pharmacotherapy of schizophrenia for 40 years because of the erroneous linkage of extrapyramidal symptoms (EPS) with therapeutic response to antipsychotics. We did not realize the neurologic harm of this dogma until the computer revolution and related scientific advances enabled researchers to measure the dopamine receptor occupancy in patients’ brains.¹ Positron emission tomography (PET) scan studies revealed that only 60% to 65% of dopamine D2 receptors need to be blocked to suppress psychotic symptoms, whereas EPS will occur at ≥78% occupancy. Millions of patients needlessly suffered intolerable rigidity, dyskinesia, restlessness, and tremors and routinely received large doses of anticholinergic drugs that destroyed their quality of life due to memory loss, dry mouth, constipation, and blurry vision.

Medications must be administered daily. The same landmark receptor imaging studies described above may soon debunk this ubiquitously entrenched clinical dogma. Recent data showed that administering the same antipsychotic dose every other day instead of every day was equally efficacious.² Dopamine receptors do not require 24/7 blockade to treat psychosis as was formerly believed; apparently, intermittent occupancy is sufficient. Shattering this dogma can save 50% of the cost of the (expensive) antipsychotic medications, which chronic schizophrenia patients have to take for many years.

Patients with schizophrenia will ingest their oral medications as prescribed. This dogma continues to dominate clinical practice despite numerous studies that show up to 80% of schizophrenia patients relapse due to poor adherence to oral antipsychotics. Yet many psychiatrists continue to prescribe oral medications even though they know core symptoms of schizophrenia—lack of insight, amotivation, impaired memory, suspiciousness, and substance use—contribute heavily to nonadherence. The dogma of oral meds has been “attenuated” in Europe, where 30% of patients are treated with long-acting injectable depot medications, compared with about 7% in the United States.³

Academic psychiatrists must not collaborate with the pharmaceutical industry. This dogma was hatched recently and ignores the huge unmet needs of psychiatric patients. More than 80% of DSM-IV disorders do not have any FDA-approved drug.⁴ Whether we like it or not, the pharmaceutical industry is the only source of new medication. Instead of avoiding an academic-industry collaboration, Europe has boldly moved ahead of the United States by formalizing a unique initiative called Novel Methods leading to New Medications in Depression and Schizophrenia (NEWMEDS).

This large collaboration intends to accelerate new drug discovery via a partnership between several prestigious European academic psychiatry institutes and global drug companies. By discarding the strident, dogmatic attitudes of shirking collaboration, NEWMEDS promises to expedite and accelerate the discovery and development of urgently needed therapeutic agents with innovative mechanisms. Dr. S. Kapur, the PET imaging pioneer, serves as the academic leader of NEWMEDS.

Psychiatrists are experts at detecting erroneous thinking in individuals or groups. We should vigorously rid our specialty of unproven tenets and detrimental dogmas. The best and only way to accomplish that worthy goal is to seek scientific basis for everything we do or teach.

Like all other medical specialties, psychiatry has its share of dogmas that are perpetuated via the clinical apprenticeship model from one generation of physicians to the next, despite the lack of hard evidence. They become “articles of faith” that go unchallenged by trainees who acquire them from their supervisors. A dogma masquerades as a truism and eventually becomes a sacred feature of the “clinical lore.”

Sooner or later, however, the bright light of scientific evidence will reveal the ersatz nature of a dogma and it will come crashing down. Similar to a revolution to depose a dictator, the demise of a dogma will have a salutary effect on medical practice and a liberating effect on practitioners.

Here are examples of psychiatric dogmas that were part of my training but have been/or are in the process of being taken to the slaughterhouse of obsolete tenets:

Psychiatrists should not touch their patients. Really! How can we be practicing physicians if we don’t? This dogma arbitrarily sexualized the physical exam, including drawing blood, measuring blood pressure or waist circumference, assessing neuroleptic-induced cogwheeling, or checking the body for a drug-induced rash. This dogma is the antithesis of good medical care for psychiatric patients, who frequently suffer from serious physical ailments and often do not have a primary care provider. It was created during the primordial phase of psychiatry (aka psychoanalysis) and is irrelevant in modern-era psychiatry.

Push the dose of neuroleptics higher and higher until the patient becomes parkinsonian, which is the sign that psychosis will improve. This dogma dominated the pharmacotherapy of schizophrenia for 40 years because of the erroneous linkage of extrapyramidal symptoms (EPS) with therapeutic response to antipsychotics. We did not realize the neurologic harm of this dogma until the computer revolution and related scientific advances enabled researchers to measure the dopamine receptor occupancy in patients’ brains.¹ Positron emission tomography (PET) scan studies revealed that only 60% to 65% of dopamine D2 receptors need to be blocked to suppress psychotic symptoms, whereas EPS will occur at ≥78% occupancy. Millions of patients needlessly suffered intolerable rigidity, dyskinesia, restlessness, and tremors and routinely received large doses of anticholinergic drugs that destroyed their quality of life due to memory loss, dry mouth, constipation, and blurry vision.

Medications must be administered daily. The same landmark receptor imaging studies described above may soon debunk this ubiquitously entrenched clinical dogma. Recent data showed that administering the same antipsychotic dose every other day instead of every day was equally efficacious.² Dopamine receptors do not require 24/7 blockade to treat psychosis as was formerly believed; apparently, intermittent occupancy is sufficient. Shattering this dogma can save 50% of the cost of the (expensive) antipsychotic medications, which chronic schizophrenia patients have to take for many years.

Patients with schizophrenia will ingest their oral medications as prescribed. This dogma continues to dominate clinical practice despite numerous studies that show up to 80% of schizophrenia patients relapse due to poor adherence to oral antipsychotics. Yet many psychiatrists continue to prescribe oral medications even though they know core symptoms of schizophrenia—lack of insight, amotivation, impaired memory, suspiciousness, and substance use—contribute heavily to nonadherence. The dogma of oral meds has been “attenuated” in Europe, where 30% of patients are treated with long-acting injectable depot medications, compared with about 7% in the United States.³

Academic psychiatrists must not collaborate with the pharmaceutical industry. This dogma was hatched recently and ignores the huge unmet needs of psychiatric patients. More than 80% of DSM-IV disorders do not have any FDA-approved drug.⁴ Whether we like it or not, the pharmaceutical industry is the only source of new medication. Instead of avoiding an academic-industry collaboration, Europe has boldly moved ahead of the United States by formalizing a unique initiative called Novel Methods leading to New Medications in Depression and Schizophrenia (NEWMEDS).

This large collaboration intends to accelerate new drug discovery via a partnership between several prestigious European academic psychiatry institutes and global drug companies. By discarding the strident, dogmatic attitudes of shirking collaboration, NEWMEDS promises to expedite and accelerate the discovery and development of urgently needed therapeutic agents with innovative mechanisms. Dr. S. Kapur, the PET imaging pioneer, serves as the academic leader of NEWMEDS.

Psychiatrists are experts at detecting erroneous thinking in individuals or groups. We should vigorously rid our specialty of unproven tenets and detrimental dogmas. The best and only way to accomplish that worthy goal is to seek scientific basis for everything we do or teach.