Henry A. Nasrallah, MD

What is the future of psychiatric practice? The emerging trend in medicine is toward more and more specialization, but will psychiatry follow suit?

Explosive growth in scientific knowledge and increasingly technical aspects of treatment are making it harder than ever for specialists— let alone generalists—to remain current. Gone are the days of Marcus Welby, MD, television’s 1970s paragon of the “do-it-all” generalist.

Physicians now differentiate into specialists immediately after medical school and train for up to 7 additional years in fields such as psychiatry, surgery, internal medicine, radiology, pediatrics, or dermatology. Even family medicine—an advanced form of “general practice”—requires 3 additional years of post-MD residency. The Accreditation Council for Graduate Medical Education (ACGME) recognizes and regulates residency training in 26 medical specialties.

But the trend does not stop there. Specialists have differentiated further into subspecialists who focus on narrower areas that require additional qualifications. Internal medicine has 18 subspecialties that offer board certification (such as interventional cardiology, gastroenterology, infectious disease, and rheumatology). Psychiatry has 5 (child and adolescent psychiatry, geriatric psychiatry, forensic psychiatry, addiction psychiatry, and psychosomatic medicine).

The ACGME now accredits nearly 100 subspecialties! A unique feature of subspecialty training is that important research takes place in those programs, advancing knowledge at the molecular, translational, and clinical levels.

An emerging practice model. The trend towards subspecialization is likely to continue and could culminate in a “diseasologist” model of medicine. Already, a number of psychiatry “diseasologists” are focusing on only 1 disorder, such as anxiety, bipolar disorder, eating disorders, psychosis, or borderline personality disorders. Similarly:

• In our sister specialty, neurology, some clinicians are focusing on stroke, multiple sclerosis, dementia, movement disorders, or epilepsy.
• Ophthalmology—a superspecialty in its own right—has fractionated into “diseasologists” who restrict their practices to cataracts, vitreo-retinal diseases, corneal disorders, or onco-ophthalmology.

Is the day approaching when there will be 2,000 types of diseasology, one for each recognized medical illness?

In psychiatry, the diseasologist paradigm of clinical practice may be more difficult to implement than in other specialties. Clinical features overlap across many psychiatric disorders, and comorbidity is the rule. We need to maintain “big picture” competence in diagnosis and treatment, being mindful of the “forest” while addressing one or more “trees” with intertwining branches and/or roots.

Psychiatrists may decide to focus on a single major disorder, but we always will need broad-based knowledge of mental disorders. Perhaps we practice “mental primary care,” in which the diseasology model will not be as feasible as in other medical specialties.

What is the future of psychiatric practice? The emerging trend in medicine is toward more and more specialization, but will psychiatry follow suit?

Explosive growth in scientific knowledge and increasingly technical aspects of treatment are making it harder than ever for specialists— let alone generalists—to remain current. Gone are the days of Marcus Welby, MD, television’s 1970s paragon of the “do-it-all” generalist.

Physicians now differentiate into specialists immediately after medical school and train for up to 7 additional years in fields such as psychiatry, surgery, internal medicine, radiology, pediatrics, or dermatology. Even family medicine—an advanced form of “general practice”—requires 3 additional years of post-MD residency. The Accreditation Council for Graduate Medical Education (ACGME) recognizes and regulates residency training in 26 medical specialties.

But the trend does not stop there. Specialists have differentiated further into subspecialists who focus on narrower areas that require additional qualifications. Internal medicine has 18 subspecialties that offer board certification (such as interventional cardiology, gastroenterology, infectious disease, and rheumatology). Psychiatry has 5 (child and adolescent psychiatry, geriatric psychiatry, forensic psychiatry, addiction psychiatry, and psychosomatic medicine).

The ACGME now accredits nearly 100 subspecialties! A unique feature of subspecialty training is that important research takes place in those programs, advancing knowledge at the molecular, translational, and clinical levels.

An emerging practice model. The trend towards subspecialization is likely to continue and could culminate in a “diseasologist” model of medicine. Already, a number of psychiatry “diseasologists” are focusing on only 1 disorder, such as anxiety, bipolar disorder, eating disorders, psychosis, or borderline personality disorders. Similarly:

• In our sister specialty, neurology, some clinicians are focusing on stroke, multiple sclerosis, dementia, movement disorders, or epilepsy.
• Ophthalmology—a superspecialty in its own right—has fractionated into “diseasologists” who restrict their practices to cataracts, vitreo-retinal diseases, corneal disorders, or onco-ophthalmology.

Is the day approaching when there will be 2,000 types of diseasology, one for each recognized medical illness?

In psychiatry, the diseasologist paradigm of clinical practice may be more difficult to implement than in other specialties. Clinical features overlap across many psychiatric disorders, and comorbidity is the rule. We need to maintain “big picture” competence in diagnosis and treatment, being mindful of the “forest” while addressing one or more “trees” with intertwining branches and/or roots.

Psychiatrists may decide to focus on a single major disorder, but we always will need broad-based knowledge of mental disorders. Perhaps we practice “mental primary care,” in which the diseasology model will not be as feasible as in other medical specialties.

What is the future of psychiatric practice? The emerging trend in medicine is toward more and more specialization, but will psychiatry follow suit?

Explosive growth in scientific knowledge and increasingly technical aspects of treatment are making it harder than ever for specialists— let alone generalists—to remain current. Gone are the days of Marcus Welby, MD, television’s 1970s paragon of the “do-it-all” generalist.

Physicians now differentiate into specialists immediately after medical school and train for up to 7 additional years in fields such as psychiatry, surgery, internal medicine, radiology, pediatrics, or dermatology. Even family medicine—an advanced form of “general practice”—requires 3 additional years of post-MD residency. The Accreditation Council for Graduate Medical Education (ACGME) recognizes and regulates residency training in 26 medical specialties.

But the trend does not stop there. Specialists have differentiated further into subspecialists who focus on narrower areas that require additional qualifications. Internal medicine has 18 subspecialties that offer board certification (such as interventional cardiology, gastroenterology, infectious disease, and rheumatology). Psychiatry has 5 (child and adolescent psychiatry, geriatric psychiatry, forensic psychiatry, addiction psychiatry, and psychosomatic medicine).

The ACGME now accredits nearly 100 subspecialties! A unique feature of subspecialty training is that important research takes place in those programs, advancing knowledge at the molecular, translational, and clinical levels.

An emerging practice model. The trend towards subspecialization is likely to continue and could culminate in a “diseasologist” model of medicine. Already, a number of psychiatry “diseasologists” are focusing on only 1 disorder, such as anxiety, bipolar disorder, eating disorders, psychosis, or borderline personality disorders. Similarly:

• In our sister specialty, neurology, some clinicians are focusing on stroke, multiple sclerosis, dementia, movement disorders, or epilepsy.
• Ophthalmology—a superspecialty in its own right—has fractionated into “diseasologists” who restrict their practices to cataracts, vitreo-retinal diseases, corneal disorders, or onco-ophthalmology.

Is the day approaching when there will be 2,000 types of diseasology, one for each recognized medical illness?

In psychiatry, the diseasologist paradigm of clinical practice may be more difficult to implement than in other specialties. Clinical features overlap across many psychiatric disorders, and comorbidity is the rule. We need to maintain “big picture” competence in diagnosis and treatment, being mindful of the “forest” while addressing one or more “trees” with intertwining branches and/or roots.

Psychiatrists may decide to focus on a single major disorder, but we always will need broad-based knowledge of mental disorders. Perhaps we practice “mental primary care,” in which the diseasology model will not be as feasible as in other medical specialties.

The slaying of 32 Virginia Tech University students and faculty by a mentally ill student sparked a national dialogue about mental illness on college campuses. The April 16 rampage—in which the shooter also killed himself—raises many questions about mental health care and the stigma of psychiatric illness:

• Why did TV commentators assume the crime was caused by “evil” and “psychopathy,” instead of a medical illness in a young man with many psychiatric manifestations?
• Why do most people assume that a psychotic individual driven by delusions is too “incompetent” or “confused” to plan and carry out a complex series of deadly assaults?
• Why did the mentally ill student receive no follow-up care before the crimes, even though he had received psychiatric treatment?
• Do medical record requirements in the Health Insurance Portability and Accountability Act (HIPAA) protect individual privacy at the expense of public safety if a patient is seriously mentally ill?
• If the university administration had known about the student’s psychiatric disorder, would he have received better treatment and supervision? Or would he have been stigmatized or expelled, whether or not he responded well to medications and counseling?
• How can roommates or teachers receive adequate information to help a mentally ill student or monitor for treatment adherence when HIPAA rules prevent even families from knowing details of mentally ill adults’ diagnosis or treatment?
• Can laws prohibiting gun sales to persons with a history of serious mental illness be made foolproof, or will guns remain accessible from underground sources?
• Because the home-to-college transition can be very stressful, should colleges require freshman courses on how to recognize distress and seek help?
• Given that schizophrenia, bipolar mania, and psychotic depression often emerge between ages 18 and 25, why have colleges and universities not adopted early screening and intervention?
• Are mentally ill persons more dangerous than the general population, or is that perception based on highly dramatized media reports of isolated incidents?
• When will the public understand that patients with serious mental illness who adhere to treatment often have positive outcomes?
• Why are alcohol and substance abuse—which cause morbidity and death among college students—not “feared” as much as mental illness?
• When will health insurance cover brain diseases that manifest as thought disorders or behavioral aberrations, such as schizophrenia or obsessive-compulsive disorder, in parity with brain diseases that manifest as muscle paralysis, such as stroke or multiple sclerosis?
• Given that >25% of the U.S. population has a diagnosable and treatable mental disorder, why is our mental health system so fragmented, so inadequate, and so underfunded? And why is there no public outcry to fix it?

Virginia Tech’s tragedy has thrust these questions and many more into the public consciousness. To address them, the medical establishment, public health officials, teachers, education administrators, and advocacy groups have a lot of work to do, and regrettably—given past patterns—more bloodshed may occur before answers emerge.

Finally, as a parent and husband, I have one last question: how can we console the bereaved families of the Virginia Tech students and faculty who suddenly lost a son or daughter, husband or wife in the prime of life? For them, improvements in mental health care on our college campuses will come too late.

See related article: Does this patient have prodromal psychosis?

The slaying of 32 Virginia Tech University students and faculty by a mentally ill student sparked a national dialogue about mental illness on college campuses. The April 16 rampage—in which the shooter also killed himself—raises many questions about mental health care and the stigma of psychiatric illness:

• Why did TV commentators assume the crime was caused by “evil” and “psychopathy,” instead of a medical illness in a young man with many psychiatric manifestations?
• Why do most people assume that a psychotic individual driven by delusions is too “incompetent” or “confused” to plan and carry out a complex series of deadly assaults?
• Why did the mentally ill student receive no follow-up care before the crimes, even though he had received psychiatric treatment?
• Do medical record requirements in the Health Insurance Portability and Accountability Act (HIPAA) protect individual privacy at the expense of public safety if a patient is seriously mentally ill?
• If the university administration had known about the student’s psychiatric disorder, would he have received better treatment and supervision? Or would he have been stigmatized or expelled, whether or not he responded well to medications and counseling?
• How can roommates or teachers receive adequate information to help a mentally ill student or monitor for treatment adherence when HIPAA rules prevent even families from knowing details of mentally ill adults’ diagnosis or treatment?
• Can laws prohibiting gun sales to persons with a history of serious mental illness be made foolproof, or will guns remain accessible from underground sources?
• Because the home-to-college transition can be very stressful, should colleges require freshman courses on how to recognize distress and seek help?
• Given that schizophrenia, bipolar mania, and psychotic depression often emerge between ages 18 and 25, why have colleges and universities not adopted early screening and intervention?
• Are mentally ill persons more dangerous than the general population, or is that perception based on highly dramatized media reports of isolated incidents?
• When will the public understand that patients with serious mental illness who adhere to treatment often have positive outcomes?
• Why are alcohol and substance abuse—which cause morbidity and death among college students—not “feared” as much as mental illness?
• When will health insurance cover brain diseases that manifest as thought disorders or behavioral aberrations, such as schizophrenia or obsessive-compulsive disorder, in parity with brain diseases that manifest as muscle paralysis, such as stroke or multiple sclerosis?
• Given that >25% of the U.S. population has a diagnosable and treatable mental disorder, why is our mental health system so fragmented, so inadequate, and so underfunded? And why is there no public outcry to fix it?

Virginia Tech’s tragedy has thrust these questions and many more into the public consciousness. To address them, the medical establishment, public health officials, teachers, education administrators, and advocacy groups have a lot of work to do, and regrettably—given past patterns—more bloodshed may occur before answers emerge.

Finally, as a parent and husband, I have one last question: how can we console the bereaved families of the Virginia Tech students and faculty who suddenly lost a son or daughter, husband or wife in the prime of life? For them, improvements in mental health care on our college campuses will come too late.

See related article: Does this patient have prodromal psychosis?

The slaying of 32 Virginia Tech University students and faculty by a mentally ill student sparked a national dialogue about mental illness on college campuses. The April 16 rampage—in which the shooter also killed himself—raises many questions about mental health care and the stigma of psychiatric illness:

• Why did TV commentators assume the crime was caused by “evil” and “psychopathy,” instead of a medical illness in a young man with many psychiatric manifestations?
• Why do most people assume that a psychotic individual driven by delusions is too “incompetent” or “confused” to plan and carry out a complex series of deadly assaults?
• Why did the mentally ill student receive no follow-up care before the crimes, even though he had received psychiatric treatment?
• Do medical record requirements in the Health Insurance Portability and Accountability Act (HIPAA) protect individual privacy at the expense of public safety if a patient is seriously mentally ill?
• If the university administration had known about the student’s psychiatric disorder, would he have received better treatment and supervision? Or would he have been stigmatized or expelled, whether or not he responded well to medications and counseling?
• How can roommates or teachers receive adequate information to help a mentally ill student or monitor for treatment adherence when HIPAA rules prevent even families from knowing details of mentally ill adults’ diagnosis or treatment?
• Can laws prohibiting gun sales to persons with a history of serious mental illness be made foolproof, or will guns remain accessible from underground sources?
• Because the home-to-college transition can be very stressful, should colleges require freshman courses on how to recognize distress and seek help?
• Given that schizophrenia, bipolar mania, and psychotic depression often emerge between ages 18 and 25, why have colleges and universities not adopted early screening and intervention?
• Are mentally ill persons more dangerous than the general population, or is that perception based on highly dramatized media reports of isolated incidents?
• When will the public understand that patients with serious mental illness who adhere to treatment often have positive outcomes?
• Why are alcohol and substance abuse—which cause morbidity and death among college students—not “feared” as much as mental illness?
• When will health insurance cover brain diseases that manifest as thought disorders or behavioral aberrations, such as schizophrenia or obsessive-compulsive disorder, in parity with brain diseases that manifest as muscle paralysis, such as stroke or multiple sclerosis?
• Given that >25% of the U.S. population has a diagnosable and treatable mental disorder, why is our mental health system so fragmented, so inadequate, and so underfunded? And why is there no public outcry to fix it?

Virginia Tech’s tragedy has thrust these questions and many more into the public consciousness. To address them, the medical establishment, public health officials, teachers, education administrators, and advocacy groups have a lot of work to do, and regrettably—given past patterns—more bloodshed may occur before answers emerge.

Finally, as a parent and husband, I have one last question: how can we console the bereaved families of the Virginia Tech students and faculty who suddenly lost a son or daughter, husband or wife in the prime of life? For them, improvements in mental health care on our college campuses will come too late.

See related article: Does this patient have prodromal psychosis?

Clinical psychiatry, like other medical specialties, eagerly awaits treatment breakthroughs. Despite the availability of many pharmacotherapies, even common illnesses such as diabetes, hypertension, and bipolar disorder cannot be cured.

Until investigators unravel a disease’s pathophysiology, treatments tend to remain symptomatic. Molecular genetics research ultimately may revolutionize the treatment of serious body and mind disorders, but how long must we wait?

As naïve medical students in the 1970s, my friends and I believed cures certainly would be discovered before the new millennium for cancer, arthritis, Alzheimer’s dementia, schizophrenia, diabetes, major depression, and anxiety. Although progress has been made, the pace of developing effective new treatments has been much slower than we expected.

As a researcher, I understand why brave new treatments are elusive. Even so, I keep hoping to see “disruptive” discoveries that will bring solutions to our patients’ suffering. Psychiatry needs a surge in pharmacologic innovations to advance from decades-old, serendipitously discovered, partially effective drugs to highly specific and effective biologic interventions.

Where will these desired breakthroughs come from? The National Institute of Mental Health (NIMH) does not have the budget to develop new drugs for psychiatry. The pharmaceutical industry—on which psychiatry is almost entirely dependent for new medications—seems to have stalled. Drug companies are complex, for-profit enterprises that employ tens of thousands of researchers to discover, test, and develop new drugs under an increasingly stifling web of regulatory controls.

Although drug companies have made progress against disease, the public has a rather negative view of them. Americans seem to appreciate that drug discovery is arduous, time-consuming, and costly, but they hold pharmaceutical companies to a different standard than other corporations. Practically everyone applauds when a high-tech or apparel company makes huge profits, yet when a pharmaceutical company does so there is outrage. Like it or not, creating new medications requires massive investment, and—other than taxes—profits are the only way to provide the resources for psychopharmacology research and development (R&D).

Perhaps the lull in new psychopharmacologics reflects escalating pressures on drug companies:

• Patent life is limited.
• Product development takes years and significant financial risk (only 1 in 10,000 new molecular entities makes it to market).
• Liability costs are skyrocketing because of unrealistic public expectations for new medications: high efficacy and no side effects.

Drug companies compound their problems by overspending on marketing and lobbying, and they often merge with one another to create behemoths that stifle innovation. No wonder we see so many reformulations of existing products and “me-too” drugs instead of high-risk, high-cost novel approaches to disease management.

What practical solutions could rejuvenate drug discovery? The answers are not simple, but consider these ideas:

• Extend by several years the patents on breakthrough (novel mechanism, first-in-class) drugs, and during this extension earmark a good chunk of profits for R&D.
• Limit punitive damages from lawsuits related to breakthrough medications to remove this impediment to innovation.
• Create incentives for drug companies to collaborate with NIMH researchers to translate neurobiologic and molecular genetics discoveries into innovative, biologically specific agents for psychiatric brain diseases.

Forging private-public collaborations may be a winning formula for all, with seriously afflicted patients as the ultimate beneficiaries of new drugs for their unmet needs.

Clinical psychiatry, like other medical specialties, eagerly awaits treatment breakthroughs. Despite the availability of many pharmacotherapies, even common illnesses such as diabetes, hypertension, and bipolar disorder cannot be cured.

Until investigators unravel a disease’s pathophysiology, treatments tend to remain symptomatic. Molecular genetics research ultimately may revolutionize the treatment of serious body and mind disorders, but how long must we wait?

As naïve medical students in the 1970s, my friends and I believed cures certainly would be discovered before the new millennium for cancer, arthritis, Alzheimer’s dementia, schizophrenia, diabetes, major depression, and anxiety. Although progress has been made, the pace of developing effective new treatments has been much slower than we expected.

As a researcher, I understand why brave new treatments are elusive. Even so, I keep hoping to see “disruptive” discoveries that will bring solutions to our patients’ suffering. Psychiatry needs a surge in pharmacologic innovations to advance from decades-old, serendipitously discovered, partially effective drugs to highly specific and effective biologic interventions.

Where will these desired breakthroughs come from? The National Institute of Mental Health (NIMH) does not have the budget to develop new drugs for psychiatry. The pharmaceutical industry—on which psychiatry is almost entirely dependent for new medications—seems to have stalled. Drug companies are complex, for-profit enterprises that employ tens of thousands of researchers to discover, test, and develop new drugs under an increasingly stifling web of regulatory controls.

Although drug companies have made progress against disease, the public has a rather negative view of them. Americans seem to appreciate that drug discovery is arduous, time-consuming, and costly, but they hold pharmaceutical companies to a different standard than other corporations. Practically everyone applauds when a high-tech or apparel company makes huge profits, yet when a pharmaceutical company does so there is outrage. Like it or not, creating new medications requires massive investment, and—other than taxes—profits are the only way to provide the resources for psychopharmacology research and development (R&D).

Perhaps the lull in new psychopharmacologics reflects escalating pressures on drug companies:

• Patent life is limited.
• Product development takes years and significant financial risk (only 1 in 10,000 new molecular entities makes it to market).
• Liability costs are skyrocketing because of unrealistic public expectations for new medications: high efficacy and no side effects.

Drug companies compound their problems by overspending on marketing and lobbying, and they often merge with one another to create behemoths that stifle innovation. No wonder we see so many reformulations of existing products and “me-too” drugs instead of high-risk, high-cost novel approaches to disease management.

What practical solutions could rejuvenate drug discovery? The answers are not simple, but consider these ideas:

• Extend by several years the patents on breakthrough (novel mechanism, first-in-class) drugs, and during this extension earmark a good chunk of profits for R&D.
• Limit punitive damages from lawsuits related to breakthrough medications to remove this impediment to innovation.
• Create incentives for drug companies to collaborate with NIMH researchers to translate neurobiologic and molecular genetics discoveries into innovative, biologically specific agents for psychiatric brain diseases.

Forging private-public collaborations may be a winning formula for all, with seriously afflicted patients as the ultimate beneficiaries of new drugs for their unmet needs.

Clinical psychiatry, like other medical specialties, eagerly awaits treatment breakthroughs. Despite the availability of many pharmacotherapies, even common illnesses such as diabetes, hypertension, and bipolar disorder cannot be cured.

Until investigators unravel a disease’s pathophysiology, treatments tend to remain symptomatic. Molecular genetics research ultimately may revolutionize the treatment of serious body and mind disorders, but how long must we wait?

As naïve medical students in the 1970s, my friends and I believed cures certainly would be discovered before the new millennium for cancer, arthritis, Alzheimer’s dementia, schizophrenia, diabetes, major depression, and anxiety. Although progress has been made, the pace of developing effective new treatments has been much slower than we expected.

As a researcher, I understand why brave new treatments are elusive. Even so, I keep hoping to see “disruptive” discoveries that will bring solutions to our patients’ suffering. Psychiatry needs a surge in pharmacologic innovations to advance from decades-old, serendipitously discovered, partially effective drugs to highly specific and effective biologic interventions.

Where will these desired breakthroughs come from? The National Institute of Mental Health (NIMH) does not have the budget to develop new drugs for psychiatry. The pharmaceutical industry—on which psychiatry is almost entirely dependent for new medications—seems to have stalled. Drug companies are complex, for-profit enterprises that employ tens of thousands of researchers to discover, test, and develop new drugs under an increasingly stifling web of regulatory controls.

Although drug companies have made progress against disease, the public has a rather negative view of them. Americans seem to appreciate that drug discovery is arduous, time-consuming, and costly, but they hold pharmaceutical companies to a different standard than other corporations. Practically everyone applauds when a high-tech or apparel company makes huge profits, yet when a pharmaceutical company does so there is outrage. Like it or not, creating new medications requires massive investment, and—other than taxes—profits are the only way to provide the resources for psychopharmacology research and development (R&D).

Perhaps the lull in new psychopharmacologics reflects escalating pressures on drug companies:

• Patent life is limited.
• Product development takes years and significant financial risk (only 1 in 10,000 new molecular entities makes it to market).
• Liability costs are skyrocketing because of unrealistic public expectations for new medications: high efficacy and no side effects.

Drug companies compound their problems by overspending on marketing and lobbying, and they often merge with one another to create behemoths that stifle innovation. No wonder we see so many reformulations of existing products and “me-too” drugs instead of high-risk, high-cost novel approaches to disease management.

What practical solutions could rejuvenate drug discovery? The answers are not simple, but consider these ideas:

• Extend by several years the patents on breakthrough (novel mechanism, first-in-class) drugs, and during this extension earmark a good chunk of profits for R&D.
• Limit punitive damages from lawsuits related to breakthrough medications to remove this impediment to innovation.
• Create incentives for drug companies to collaborate with NIMH researchers to translate neurobiologic and molecular genetics discoveries into innovative, biologically specific agents for psychiatric brain diseases.

Forging private-public collaborations may be a winning formula for all, with seriously afflicted patients as the ultimate beneficiaries of new drugs for their unmet needs.

Psychiatric practitioners often are urged to practice evidence-based medicine (EBM), but some clinicians prefer to follow expert consensus guidelines—Eminence-Based Medicine. Still others uphold their own practice observations—Experience-Based Medicine. Which form of EBM do you practice?

Pros and cons of each. The most scientifically credible EBM is based on evidence from double-blind, randomized controlled clinical trials, such as those conducted by pharmaceutical companies seeking FDA approval of a new drug or indication. Critics point out, however, that this form of EBM does not reflect real-world practice because patients in FDA pivotal trials often are “too clean”—they’re frequently treatment-responsive and not drug-dependent, medically ill, or receiving other medications.

Eminence-based medicine—usually disseminated in practice guidelines—is respected because it reflects recommendations of some 30 to 50 experts on a set of psychiatric disorders (usually prominent clinical researchers with a critical approach to data). However, many practice guideline algorithms are based on educated opinions and extrapolations from narrow evidence-based data that are extended to various manifestations of a specific disorder.

Experience-based medicine, which combines evidence-based principles with a hefty dose of personal clinical observations in a heterogeneous patient population over time, is a prevalent source of information for clinical practitioners. Research purists often brush aside this form of EBM as too subjective, or because they feel using it can lead to risky conclusions about how to use a particular therapy. A common criticism of experience-based medicine is that a placebo response, which can occur in up to one-third of psychiatric patients (as can be seen in most FDA registration trials) may masquerade as a positive outcome.

A role for all three. In my opinion, research-driven, evidence-based medicine is the indispensable foundation for medical decision-making, but expert opinion and personal experience legitimately belong in a clinician’s toolbox as well. Treatments for psychiatric disorders have been evaluated in randomized controlled trials (first-tier evidence) for only a small proportion of DSM-IV diagnoses. What’s a clinician to do when faced with a disorder for which evidence-based medicine has proven no treatment to be effective? This is where the art of medicine comes into play.

Combining art and science. A clinician can try an intervention that may be supported by weaker evidence, such as from single-blind studies (second-tier evidence) or several published case series or reports. When nothing else has worked, such as in treatment-resistant patients or those with complex comorbidities, a clinician may boldly go where no one has gone before and try a novel but untested combination. Such a therapeutic foray is high-risk exploration that may fail dismally—or it may serendipitously usher in a radical yet effective new approach to alleviating the symptoms of a serious disease.

Clinicians who stumble upon a new approach should publish their observations in a letter to the editor or case report to stimulate replications, rebuttals, or additional personal observations. Subjecting unexpected findings to critique and refinement in the dynamic market of ideas can increase their value.

Eminence-based practice guidelines—through a reasonably calibrated amalgam of evidence and experience—provide clinicians with a series of steps and an acceptable risk–to-benefit ratio to manage patients who do not respond adequately to evidence-based treatment. Consensus-driven expert opinion integrates the art and science of medicine and commands greater credibility than the opinion of a single clinician.

Using every tool. Each of us implements all three types of EBM when managing our patients. We need to, and we have to. That is the reality of the medical practice of psychiatry.

Psychiatric practitioners often are urged to practice evidence-based medicine (EBM), but some clinicians prefer to follow expert consensus guidelines—Eminence-Based Medicine. Still others uphold their own practice observations—Experience-Based Medicine. Which form of EBM do you practice?

Pros and cons of each. The most scientifically credible EBM is based on evidence from double-blind, randomized controlled clinical trials, such as those conducted by pharmaceutical companies seeking FDA approval of a new drug or indication. Critics point out, however, that this form of EBM does not reflect real-world practice because patients in FDA pivotal trials often are “too clean”—they’re frequently treatment-responsive and not drug-dependent, medically ill, or receiving other medications.

Eminence-based medicine—usually disseminated in practice guidelines—is respected because it reflects recommendations of some 30 to 50 experts on a set of psychiatric disorders (usually prominent clinical researchers with a critical approach to data). However, many practice guideline algorithms are based on educated opinions and extrapolations from narrow evidence-based data that are extended to various manifestations of a specific disorder.

Experience-based medicine, which combines evidence-based principles with a hefty dose of personal clinical observations in a heterogeneous patient population over time, is a prevalent source of information for clinical practitioners. Research purists often brush aside this form of EBM as too subjective, or because they feel using it can lead to risky conclusions about how to use a particular therapy. A common criticism of experience-based medicine is that a placebo response, which can occur in up to one-third of psychiatric patients (as can be seen in most FDA registration trials) may masquerade as a positive outcome.

A role for all three. In my opinion, research-driven, evidence-based medicine is the indispensable foundation for medical decision-making, but expert opinion and personal experience legitimately belong in a clinician’s toolbox as well. Treatments for psychiatric disorders have been evaluated in randomized controlled trials (first-tier evidence) for only a small proportion of DSM-IV diagnoses. What’s a clinician to do when faced with a disorder for which evidence-based medicine has proven no treatment to be effective? This is where the art of medicine comes into play.

Combining art and science. A clinician can try an intervention that may be supported by weaker evidence, such as from single-blind studies (second-tier evidence) or several published case series or reports. When nothing else has worked, such as in treatment-resistant patients or those with complex comorbidities, a clinician may boldly go where no one has gone before and try a novel but untested combination. Such a therapeutic foray is high-risk exploration that may fail dismally—or it may serendipitously usher in a radical yet effective new approach to alleviating the symptoms of a serious disease.

Clinicians who stumble upon a new approach should publish their observations in a letter to the editor or case report to stimulate replications, rebuttals, or additional personal observations. Subjecting unexpected findings to critique and refinement in the dynamic market of ideas can increase their value.

Eminence-based practice guidelines—through a reasonably calibrated amalgam of evidence and experience—provide clinicians with a series of steps and an acceptable risk–to-benefit ratio to manage patients who do not respond adequately to evidence-based treatment. Consensus-driven expert opinion integrates the art and science of medicine and commands greater credibility than the opinion of a single clinician.

Using every tool. Each of us implements all three types of EBM when managing our patients. We need to, and we have to. That is the reality of the medical practice of psychiatry.

Psychiatric practitioners often are urged to practice evidence-based medicine (EBM), but some clinicians prefer to follow expert consensus guidelines—Eminence-Based Medicine. Still others uphold their own practice observations—Experience-Based Medicine. Which form of EBM do you practice?

Pros and cons of each. The most scientifically credible EBM is based on evidence from double-blind, randomized controlled clinical trials, such as those conducted by pharmaceutical companies seeking FDA approval of a new drug or indication. Critics point out, however, that this form of EBM does not reflect real-world practice because patients in FDA pivotal trials often are “too clean”—they’re frequently treatment-responsive and not drug-dependent, medically ill, or receiving other medications.

Eminence-based medicine—usually disseminated in practice guidelines—is respected because it reflects recommendations of some 30 to 50 experts on a set of psychiatric disorders (usually prominent clinical researchers with a critical approach to data). However, many practice guideline algorithms are based on educated opinions and extrapolations from narrow evidence-based data that are extended to various manifestations of a specific disorder.

Experience-based medicine, which combines evidence-based principles with a hefty dose of personal clinical observations in a heterogeneous patient population over time, is a prevalent source of information for clinical practitioners. Research purists often brush aside this form of EBM as too subjective, or because they feel using it can lead to risky conclusions about how to use a particular therapy. A common criticism of experience-based medicine is that a placebo response, which can occur in up to one-third of psychiatric patients (as can be seen in most FDA registration trials) may masquerade as a positive outcome.

A role for all three. In my opinion, research-driven, evidence-based medicine is the indispensable foundation for medical decision-making, but expert opinion and personal experience legitimately belong in a clinician’s toolbox as well. Treatments for psychiatric disorders have been evaluated in randomized controlled trials (first-tier evidence) for only a small proportion of DSM-IV diagnoses. What’s a clinician to do when faced with a disorder for which evidence-based medicine has proven no treatment to be effective? This is where the art of medicine comes into play.

Combining art and science. A clinician can try an intervention that may be supported by weaker evidence, such as from single-blind studies (second-tier evidence) or several published case series or reports. When nothing else has worked, such as in treatment-resistant patients or those with complex comorbidities, a clinician may boldly go where no one has gone before and try a novel but untested combination. Such a therapeutic foray is high-risk exploration that may fail dismally—or it may serendipitously usher in a radical yet effective new approach to alleviating the symptoms of a serious disease.

Clinicians who stumble upon a new approach should publish their observations in a letter to the editor or case report to stimulate replications, rebuttals, or additional personal observations. Subjecting unexpected findings to critique and refinement in the dynamic market of ideas can increase their value.

Eminence-based practice guidelines—through a reasonably calibrated amalgam of evidence and experience—provide clinicians with a series of steps and an acceptable risk–to-benefit ratio to manage patients who do not respond adequately to evidence-based treatment. Consensus-driven expert opinion integrates the art and science of medicine and commands greater credibility than the opinion of a single clinician.

Using every tool. Each of us implements all three types of EBM when managing our patients. We need to, and we have to. That is the reality of the medical practice of psychiatry.

“Off-label” may evoke an uncomfortable sense of therapeutic mischief, yet the term describes a vital evolution of scientific discovery in pharmacotherapy. Because no FDA-approved drugs are available for many psychiatric disorders, patients would suffer needlessly if psychotropics were not used off-label.

The Agency for Healthcare Research and Quality recently reported on the “Efficacy and comparative effectiveness of off-label use of atypical antipsychotics.”¹ Its findings confirm other published studies of the wide-spread off-label uses of second-generation antipsychotics (SGAs). In Georgia’s Medicaid system, for example, a large proportion of antipsychotics, antidepressants, and mood stabilizers are prescribed off-label.²

Clinicians, in fact, use psychotropics off-label for many legitimate reasons, including:

No other options. In a recent study,³ we found that only 12% of DSM-IV-TR categories have an approved drug, leaving 88% of psychiatric disorders with no “official” pharmacologic treatment. Obviously, compassionate practitioners use whatever is available to alleviate the suffering of the many psychiatric patients for whom no drug has been approved.

Through trial and error over time, clinicians have found multiple uses for SGAs and other psychotropics in many symptoms or diagnoses. Clinicians have engaged in this necessary innovative process for years—even decades—before some diagnostic categories eventually obtained an FDA-approved drug.

In my opinion, this process is vital to the scientific “discovery” process that precedes controlled clinical trials that ultimately confirm what clinicians have collectively observed. It also is a vital scientific partnership between clinicians who generate hypotheses about additional drug efficacies and researchers who test these hypotheses to produce evidence-based findings.

‘Real-world’ clinical issues. On-label psychotropic use is supported by short-term studies of very “clean” samples of patients, who often are not representative of community-based practice. When the drug is launched in the “real world,” however, it is used in much more complicated patients who may be treatment-resistant and have comorbid medical or psychiatric disorders or substance abuse.

Clinicians often find that a higher (off-label) dose can be more effective for real-world patients than the lower doses that worked in FDA-required pre-approval trials. Thus, off-label use of a high-dose SGA may have better efficacy in some patients than the narrow range of approved dosages.

Maintenance therapy dilemmas. Years may pass before we see maintenance studies for an antipsychotic that has been approved for acute treatment of schizophrenia or mania. But clinicians are highly unlikely to discontinue that drug after a patient successfully responds within a few weeks. Thus, we essentially practice off-label psychopharmacology whenever we maintain a patient on a drug approved only for acute uses.

Combination therapies. No antipsychotic combinations are approved for schizophrenia, yet more than one-third of chronic schizophrenia patients in the United States are concurrently receiving 2 or more concurrent SGAs.⁴ Combining antipsychotics is often regarded as dubious off-label polypharmacy, yet clinicians stand by their observations that patients who do not improve with 1 drug may respond when another is added.

Although combination pharmacotherapy is not supported by credible evidence—controlled trials of 2 SGAs vs 1 combined with a placebo—clinicians again might be discovering options for treatment-resistant or refractory patients before FDA trials are conducted.

Simpler dosing for better adherence. A drug may be approved for twice-daily (bid) administration, yet clinicians might soon discover that prescribing it once daily (qd) is equally or even more effective because of improved patient adherence. Off-label dosing may be rational and even better than the official dose schedule, yet a drug company might never go through the costly process of repeating its clinical trial to demonstrate that bid and qd dosing are equivalent. Thus, practitioners will continue to use the drug off-label based on clinical experience, not on research data.

Scientific implications. Aside from advancing psychopharmacologic practices and discovering new treatments, off-label data also could shed light on a potential shared neurobiology among psychiatric disorders. Off-label prescribing ultimately might help us reconceptualize the overlapping neural pathways of several axis I and axis II disorders, all of which appear to be improved by the same pharmacologic agent such as an atypical antipsychotic. It might even prompt us to coin a new name for antipsychotics, such as “neurostabilizers.”

Write and tell me what term you would coin for a class of drugs with multiple psychiatric uses.

“Off-label” may evoke an uncomfortable sense of therapeutic mischief, yet the term describes a vital evolution of scientific discovery in pharmacotherapy. Because no FDA-approved drugs are available for many psychiatric disorders, patients would suffer needlessly if psychotropics were not used off-label.

The Agency for Healthcare Research and Quality recently reported on the “Efficacy and comparative effectiveness of off-label use of atypical antipsychotics.”¹ Its findings confirm other published studies of the wide-spread off-label uses of second-generation antipsychotics (SGAs). In Georgia’s Medicaid system, for example, a large proportion of antipsychotics, antidepressants, and mood stabilizers are prescribed off-label.²

Clinicians, in fact, use psychotropics off-label for many legitimate reasons, including:

No other options. In a recent study,³ we found that only 12% of DSM-IV-TR categories have an approved drug, leaving 88% of psychiatric disorders with no “official” pharmacologic treatment. Obviously, compassionate practitioners use whatever is available to alleviate the suffering of the many psychiatric patients for whom no drug has been approved.

Through trial and error over time, clinicians have found multiple uses for SGAs and other psychotropics in many symptoms or diagnoses. Clinicians have engaged in this necessary innovative process for years—even decades—before some diagnostic categories eventually obtained an FDA-approved drug.

In my opinion, this process is vital to the scientific “discovery” process that precedes controlled clinical trials that ultimately confirm what clinicians have collectively observed. It also is a vital scientific partnership between clinicians who generate hypotheses about additional drug efficacies and researchers who test these hypotheses to produce evidence-based findings.

‘Real-world’ clinical issues. On-label psychotropic use is supported by short-term studies of very “clean” samples of patients, who often are not representative of community-based practice. When the drug is launched in the “real world,” however, it is used in much more complicated patients who may be treatment-resistant and have comorbid medical or psychiatric disorders or substance abuse.

Clinicians often find that a higher (off-label) dose can be more effective for real-world patients than the lower doses that worked in FDA-required pre-approval trials. Thus, off-label use of a high-dose SGA may have better efficacy in some patients than the narrow range of approved dosages.

Maintenance therapy dilemmas. Years may pass before we see maintenance studies for an antipsychotic that has been approved for acute treatment of schizophrenia or mania. But clinicians are highly unlikely to discontinue that drug after a patient successfully responds within a few weeks. Thus, we essentially practice off-label psychopharmacology whenever we maintain a patient on a drug approved only for acute uses.

Combination therapies. No antipsychotic combinations are approved for schizophrenia, yet more than one-third of chronic schizophrenia patients in the United States are concurrently receiving 2 or more concurrent SGAs.⁴ Combining antipsychotics is often regarded as dubious off-label polypharmacy, yet clinicians stand by their observations that patients who do not improve with 1 drug may respond when another is added.

Although combination pharmacotherapy is not supported by credible evidence—controlled trials of 2 SGAs vs 1 combined with a placebo—clinicians again might be discovering options for treatment-resistant or refractory patients before FDA trials are conducted.

Simpler dosing for better adherence. A drug may be approved for twice-daily (bid) administration, yet clinicians might soon discover that prescribing it once daily (qd) is equally or even more effective because of improved patient adherence. Off-label dosing may be rational and even better than the official dose schedule, yet a drug company might never go through the costly process of repeating its clinical trial to demonstrate that bid and qd dosing are equivalent. Thus, practitioners will continue to use the drug off-label based on clinical experience, not on research data.

Scientific implications. Aside from advancing psychopharmacologic practices and discovering new treatments, off-label data also could shed light on a potential shared neurobiology among psychiatric disorders. Off-label prescribing ultimately might help us reconceptualize the overlapping neural pathways of several axis I and axis II disorders, all of which appear to be improved by the same pharmacologic agent such as an atypical antipsychotic. It might even prompt us to coin a new name for antipsychotics, such as “neurostabilizers.”

Write and tell me what term you would coin for a class of drugs with multiple psychiatric uses.

“Off-label” may evoke an uncomfortable sense of therapeutic mischief, yet the term describes a vital evolution of scientific discovery in pharmacotherapy. Because no FDA-approved drugs are available for many psychiatric disorders, patients would suffer needlessly if psychotropics were not used off-label.

The Agency for Healthcare Research and Quality recently reported on the “Efficacy and comparative effectiveness of off-label use of atypical antipsychotics.”¹ Its findings confirm other published studies of the wide-spread off-label uses of second-generation antipsychotics (SGAs). In Georgia’s Medicaid system, for example, a large proportion of antipsychotics, antidepressants, and mood stabilizers are prescribed off-label.²

Clinicians, in fact, use psychotropics off-label for many legitimate reasons, including:

No other options. In a recent study,³ we found that only 12% of DSM-IV-TR categories have an approved drug, leaving 88% of psychiatric disorders with no “official” pharmacologic treatment. Obviously, compassionate practitioners use whatever is available to alleviate the suffering of the many psychiatric patients for whom no drug has been approved.

Through trial and error over time, clinicians have found multiple uses for SGAs and other psychotropics in many symptoms or diagnoses. Clinicians have engaged in this necessary innovative process for years—even decades—before some diagnostic categories eventually obtained an FDA-approved drug.

In my opinion, this process is vital to the scientific “discovery” process that precedes controlled clinical trials that ultimately confirm what clinicians have collectively observed. It also is a vital scientific partnership between clinicians who generate hypotheses about additional drug efficacies and researchers who test these hypotheses to produce evidence-based findings.

‘Real-world’ clinical issues. On-label psychotropic use is supported by short-term studies of very “clean” samples of patients, who often are not representative of community-based practice. When the drug is launched in the “real world,” however, it is used in much more complicated patients who may be treatment-resistant and have comorbid medical or psychiatric disorders or substance abuse.

Clinicians often find that a higher (off-label) dose can be more effective for real-world patients than the lower doses that worked in FDA-required pre-approval trials. Thus, off-label use of a high-dose SGA may have better efficacy in some patients than the narrow range of approved dosages.

Maintenance therapy dilemmas. Years may pass before we see maintenance studies for an antipsychotic that has been approved for acute treatment of schizophrenia or mania. But clinicians are highly unlikely to discontinue that drug after a patient successfully responds within a few weeks. Thus, we essentially practice off-label psychopharmacology whenever we maintain a patient on a drug approved only for acute uses.

Combination therapies. No antipsychotic combinations are approved for schizophrenia, yet more than one-third of chronic schizophrenia patients in the United States are concurrently receiving 2 or more concurrent SGAs.⁴ Combining antipsychotics is often regarded as dubious off-label polypharmacy, yet clinicians stand by their observations that patients who do not improve with 1 drug may respond when another is added.

Although combination pharmacotherapy is not supported by credible evidence—controlled trials of 2 SGAs vs 1 combined with a placebo—clinicians again might be discovering options for treatment-resistant or refractory patients before FDA trials are conducted.

Simpler dosing for better adherence. A drug may be approved for twice-daily (bid) administration, yet clinicians might soon discover that prescribing it once daily (qd) is equally or even more effective because of improved patient adherence. Off-label dosing may be rational and even better than the official dose schedule, yet a drug company might never go through the costly process of repeating its clinical trial to demonstrate that bid and qd dosing are equivalent. Thus, practitioners will continue to use the drug off-label based on clinical experience, not on research data.

Scientific implications. Aside from advancing psychopharmacologic practices and discovering new treatments, off-label data also could shed light on a potential shared neurobiology among psychiatric disorders. Off-label prescribing ultimately might help us reconceptualize the overlapping neural pathways of several axis I and axis II disorders, all of which appear to be improved by the same pharmacologic agent such as an atypical antipsychotic. It might even prompt us to coin a new name for antipsychotics, such as “neurostabilizers.”

Write and tell me what term you would coin for a class of drugs with multiple psychiatric uses.

The human brain’s ability to think is a dramatic evolutionary leap above all other living creatures. But this cognitive power has a down side: our brains appear to be wired to generate and harbor false beliefs. Severe cases are pejoratively labeled “delusions” and usually lead to psychiatric care. But what about less-severe false and irrational beliefs that are common in the “normal” population?

Consider superstitions. How many of your friends expect the worst after seeing a black cat cross their path, adamantly avoid a hotel room on the 13th floor, knock on wood to ward off evil, or are convinced that breaking a mirror brings bad luck?

Let’s keep going. How many of your coworkers believe astrology determines their destiny or that clairvoyance and reincarnation are real? I’ll bet you know dozens of ordinary, “healthy” people who tenaciously believe in ghosts, the devil, and angels.

You certainly have met people who are convinced objects can be levitated through mental forces. What about the many who believe dreams provide information about the future or that fortune-tellers can predict the future by palm-reading, tarot cards, or gazing into a crystal ball?

Take athletes. Many have odd beliefs that shape their behavior before, during, and after games to help them win. They may wear a lucky item of clothing at every game, wear their socks inside out, bounce the ball a specific number of times before a free throw, or slap the goalie’s pad for good luck. Some believe they will play better if they force themselves to eat a certain number of candy bars or vomit before each game or tuck their shirts in on the right side but not on the left.

How about college students who insist on using a specific “lucky pen” during an exam or believe that singing a certain song before a test will help get them a good grade? Ask gamblers what they believe can make them win at poker, craps, roulette, or slot machines, and you will hear a flurry of bizarre beliefs. And denying the potential for harm or death is a common false belief among persons who engage in high-risk and dangerous sports or behaviors.

Suspicious theories or religious beliefs proliferate when humans feel helpless. We accept “conspiracy theories” whenever a major event (such as landing on the moon) or a calamity (assassination of a President, terrorist attack, or massive flooding after a hurricane) occurs. Many people believe in UFOs or that aliens abduct innocent people, molest them aboard a space ship, then return them to Earth to tell others about their traumatic memories.

Finally, various nonpsychotic disorders are associated with illogical, irrational, or false beliefs:

• Individuals with anxiety disorders may firmly believe that a plane will crash if they board it or that a bridge will collapse if they drive over it.
• Successful people who become clinically depressed often express the (false) belief that they are stupid, failures, worthless, or bankrupt.
• Pretty women with body dysmorphic disorder are convinced they are ugly.
• Anorexic adults who have shriveled to 75 pounds firmly believe they are fat.
• A person with obsessive-compulsive disorder is convinced that something terrible will happen if he does not flush the toilet 9 times every time he uses it.

What does it all mean? Overwhelming evidence shows that odd, irrational, false, or bizarre beliefs are ubiquitous among people regarded as ordinary and sane.

Does generating false beliefs have a useful or adaptive evolutionary value? Could the magical belief in miracles have evolved in the human brain to instill hope during dark hours or to help us confront the inevitability of death? Could this “mental software”—designed to cope with inevitable existential tribulations—have mutated into unwarranted superstitious and supernatural beliefs in everyday life?

Until neuroscience research untangles the enigmas of human thoughts and beliefs, let us remember that patients with schizophrenia’s implausible delusions, mania’s grandiose delusions, or psychotic depression’s somatic delusions are merely extreme variants on a continuum of irrational beliefs on which all of us “sane” individuals also belong.

The human brain’s ability to think is a dramatic evolutionary leap above all other living creatures. But this cognitive power has a down side: our brains appear to be wired to generate and harbor false beliefs. Severe cases are pejoratively labeled “delusions” and usually lead to psychiatric care. But what about less-severe false and irrational beliefs that are common in the “normal” population?

Consider superstitions. How many of your friends expect the worst after seeing a black cat cross their path, adamantly avoid a hotel room on the 13th floor, knock on wood to ward off evil, or are convinced that breaking a mirror brings bad luck?

Let’s keep going. How many of your coworkers believe astrology determines their destiny or that clairvoyance and reincarnation are real? I’ll bet you know dozens of ordinary, “healthy” people who tenaciously believe in ghosts, the devil, and angels.

You certainly have met people who are convinced objects can be levitated through mental forces. What about the many who believe dreams provide information about the future or that fortune-tellers can predict the future by palm-reading, tarot cards, or gazing into a crystal ball?

Take athletes. Many have odd beliefs that shape their behavior before, during, and after games to help them win. They may wear a lucky item of clothing at every game, wear their socks inside out, bounce the ball a specific number of times before a free throw, or slap the goalie’s pad for good luck. Some believe they will play better if they force themselves to eat a certain number of candy bars or vomit before each game or tuck their shirts in on the right side but not on the left.

How about college students who insist on using a specific “lucky pen” during an exam or believe that singing a certain song before a test will help get them a good grade? Ask gamblers what they believe can make them win at poker, craps, roulette, or slot machines, and you will hear a flurry of bizarre beliefs. And denying the potential for harm or death is a common false belief among persons who engage in high-risk and dangerous sports or behaviors.

Suspicious theories or religious beliefs proliferate when humans feel helpless. We accept “conspiracy theories” whenever a major event (such as landing on the moon) or a calamity (assassination of a President, terrorist attack, or massive flooding after a hurricane) occurs. Many people believe in UFOs or that aliens abduct innocent people, molest them aboard a space ship, then return them to Earth to tell others about their traumatic memories.

Finally, various nonpsychotic disorders are associated with illogical, irrational, or false beliefs:

• Individuals with anxiety disorders may firmly believe that a plane will crash if they board it or that a bridge will collapse if they drive over it.
• Successful people who become clinically depressed often express the (false) belief that they are stupid, failures, worthless, or bankrupt.
• Pretty women with body dysmorphic disorder are convinced they are ugly.
• Anorexic adults who have shriveled to 75 pounds firmly believe they are fat.
• A person with obsessive-compulsive disorder is convinced that something terrible will happen if he does not flush the toilet 9 times every time he uses it.

What does it all mean? Overwhelming evidence shows that odd, irrational, false, or bizarre beliefs are ubiquitous among people regarded as ordinary and sane.

Does generating false beliefs have a useful or adaptive evolutionary value? Could the magical belief in miracles have evolved in the human brain to instill hope during dark hours or to help us confront the inevitability of death? Could this “mental software”—designed to cope with inevitable existential tribulations—have mutated into unwarranted superstitious and supernatural beliefs in everyday life?

Until neuroscience research untangles the enigmas of human thoughts and beliefs, let us remember that patients with schizophrenia’s implausible delusions, mania’s grandiose delusions, or psychotic depression’s somatic delusions are merely extreme variants on a continuum of irrational beliefs on which all of us “sane” individuals also belong.

The human brain’s ability to think is a dramatic evolutionary leap above all other living creatures. But this cognitive power has a down side: our brains appear to be wired to generate and harbor false beliefs. Severe cases are pejoratively labeled “delusions” and usually lead to psychiatric care. But what about less-severe false and irrational beliefs that are common in the “normal” population?

Consider superstitions. How many of your friends expect the worst after seeing a black cat cross their path, adamantly avoid a hotel room on the 13th floor, knock on wood to ward off evil, or are convinced that breaking a mirror brings bad luck?

Let’s keep going. How many of your coworkers believe astrology determines their destiny or that clairvoyance and reincarnation are real? I’ll bet you know dozens of ordinary, “healthy” people who tenaciously believe in ghosts, the devil, and angels.

You certainly have met people who are convinced objects can be levitated through mental forces. What about the many who believe dreams provide information about the future or that fortune-tellers can predict the future by palm-reading, tarot cards, or gazing into a crystal ball?

Take athletes. Many have odd beliefs that shape their behavior before, during, and after games to help them win. They may wear a lucky item of clothing at every game, wear their socks inside out, bounce the ball a specific number of times before a free throw, or slap the goalie’s pad for good luck. Some believe they will play better if they force themselves to eat a certain number of candy bars or vomit before each game or tuck their shirts in on the right side but not on the left.

How about college students who insist on using a specific “lucky pen” during an exam or believe that singing a certain song before a test will help get them a good grade? Ask gamblers what they believe can make them win at poker, craps, roulette, or slot machines, and you will hear a flurry of bizarre beliefs. And denying the potential for harm or death is a common false belief among persons who engage in high-risk and dangerous sports or behaviors.

Suspicious theories or religious beliefs proliferate when humans feel helpless. We accept “conspiracy theories” whenever a major event (such as landing on the moon) or a calamity (assassination of a President, terrorist attack, or massive flooding after a hurricane) occurs. Many people believe in UFOs or that aliens abduct innocent people, molest them aboard a space ship, then return them to Earth to tell others about their traumatic memories.

Finally, various nonpsychotic disorders are associated with illogical, irrational, or false beliefs:

• Individuals with anxiety disorders may firmly believe that a plane will crash if they board it or that a bridge will collapse if they drive over it.
• Successful people who become clinically depressed often express the (false) belief that they are stupid, failures, worthless, or bankrupt.
• Pretty women with body dysmorphic disorder are convinced they are ugly.
• Anorexic adults who have shriveled to 75 pounds firmly believe they are fat.
• A person with obsessive-compulsive disorder is convinced that something terrible will happen if he does not flush the toilet 9 times every time he uses it.

What does it all mean? Overwhelming evidence shows that odd, irrational, false, or bizarre beliefs are ubiquitous among people regarded as ordinary and sane.

Does generating false beliefs have a useful or adaptive evolutionary value? Could the magical belief in miracles have evolved in the human brain to instill hope during dark hours or to help us confront the inevitability of death? Could this “mental software”—designed to cope with inevitable existential tribulations—have mutated into unwarranted superstitious and supernatural beliefs in everyday life?

Until neuroscience research untangles the enigmas of human thoughts and beliefs, let us remember that patients with schizophrenia’s implausible delusions, mania’s grandiose delusions, or psychotic depression’s somatic delusions are merely extreme variants on a continuum of irrational beliefs on which all of us “sane” individuals also belong.

The life span of the seriously mentally ill is even shorter than we had thought. Earlier studies showed a loss of 20% of the average life span or 15 to 16 years.¹ Recent figures are alarmingly higher, however, and vary from state to state.

Virginia has the "best" mortality rate among the seriously mentally ill with a loss of "only" 13.5 years of potential life, according to the Center for Mental Health Services (CMHS) and the Centers for Disease Control and Prevention (CDC).² Perhaps persons who suffer from schizophrenia should move to Virgina because the loss of potential life years in other states is much worse:   
   • Arizona: 31.8 years   
   • Texas: 29.3 years   
   • Missouri: 27.9 years   
   • Utah: 26.9 years   
   • Oklahoma: 26.3 years.

A recent Ohio study of mortality and medical illness found an average loss of 32 years of life among persons with schizophrenia.³

Why is the life span of mentally ill persons so short? Apart from their high rates of death from unnatural causes (suicide, homicide, and accidents), the most frequent killer is cardiovascular disease. High mortality rates are well-documented in schizophrenia from various ailments but especially heart disease.⁴ Bipolar disorder and major depression are also associated with high death rates from cardiovascular disease.⁵

The sad truth is that a “dual neglect” contributes to premature mortality of the seriously mentally ill: the system fails to provide ongoing basic primary healthcare, and patients neglect to seek or adhere to medical care.

Persons with serious mental illness often have risk factors associated with preventable causes of heart disease and stroke, including smoking, obesity, sedentary life styles, and poor nutrition. In addition, the metabolic syndrome—obesity, hypertension, hyperglycemia, and dyslipidemia—is highly associated with schizophrenia,⁶ bipolar disorder,⁷ and unipolar depression.⁸

Cardiovascular risk associated with metabolic syndrome requires ongoing medical follow-up, which many mentally ill patients do not receive. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) found shockingly low treatment rates for diabetes, hypertension, and hyperglycemia among outpatients with schizophrenia around the country.⁹

Let us mobilize to correct this shameful health disparity, one patient at a time. The message to mental health professionals is clear:
   • In addition to controlling symptoms of psychosis, mania, depression, or anxiety, routinely screen patients for weight gain, hypertension, high fasting serum glucose, and elevated lipid levels.
   • Refer overweight and obese patients to primary care providers, dietitians, and exercise counselors to reduce their cardiovascular risks.

Psychiatrists and nurse practitioners must address both mental and medical health needs when formulating assessments, treatment plans, and patient education. For practical recommendations on managing medical comorbidities, see “7-point checkup for stable schizophrenia outpatients,” by Britton Ashley Arey, MD, and Stephen R. Marder, MD. The public mental health system also could help the seriously mentally ill by integrating primary healthcare with mental healthcare in community settings across the nation. There are no excuses to do anything less.

The life span of the seriously mentally ill is even shorter than we had thought. Earlier studies showed a loss of 20% of the average life span or 15 to 16 years.¹ Recent figures are alarmingly higher, however, and vary from state to state.

Virginia has the "best" mortality rate among the seriously mentally ill with a loss of "only" 13.5 years of potential life, according to the Center for Mental Health Services (CMHS) and the Centers for Disease Control and Prevention (CDC).² Perhaps persons who suffer from schizophrenia should move to Virgina because the loss of potential life years in other states is much worse:   
   • Arizona: 31.8 years   
   • Texas: 29.3 years   
   • Missouri: 27.9 years   
   • Utah: 26.9 years   
   • Oklahoma: 26.3 years.

A recent Ohio study of mortality and medical illness found an average loss of 32 years of life among persons with schizophrenia.³

Why is the life span of mentally ill persons so short? Apart from their high rates of death from unnatural causes (suicide, homicide, and accidents), the most frequent killer is cardiovascular disease. High mortality rates are well-documented in schizophrenia from various ailments but especially heart disease.⁴ Bipolar disorder and major depression are also associated with high death rates from cardiovascular disease.⁵

The sad truth is that a “dual neglect” contributes to premature mortality of the seriously mentally ill: the system fails to provide ongoing basic primary healthcare, and patients neglect to seek or adhere to medical care.

Persons with serious mental illness often have risk factors associated with preventable causes of heart disease and stroke, including smoking, obesity, sedentary life styles, and poor nutrition. In addition, the metabolic syndrome—obesity, hypertension, hyperglycemia, and dyslipidemia—is highly associated with schizophrenia,⁶ bipolar disorder,⁷ and unipolar depression.⁸

Cardiovascular risk associated with metabolic syndrome requires ongoing medical follow-up, which many mentally ill patients do not receive. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) found shockingly low treatment rates for diabetes, hypertension, and hyperglycemia among outpatients with schizophrenia around the country.⁹

Let us mobilize to correct this shameful health disparity, one patient at a time. The message to mental health professionals is clear:
   • In addition to controlling symptoms of psychosis, mania, depression, or anxiety, routinely screen patients for weight gain, hypertension, high fasting serum glucose, and elevated lipid levels.
   • Refer overweight and obese patients to primary care providers, dietitians, and exercise counselors to reduce their cardiovascular risks.

Psychiatrists and nurse practitioners must address both mental and medical health needs when formulating assessments, treatment plans, and patient education. For practical recommendations on managing medical comorbidities, see “7-point checkup for stable schizophrenia outpatients,” by Britton Ashley Arey, MD, and Stephen R. Marder, MD. The public mental health system also could help the seriously mentally ill by integrating primary healthcare with mental healthcare in community settings across the nation. There are no excuses to do anything less.

The life span of the seriously mentally ill is even shorter than we had thought. Earlier studies showed a loss of 20% of the average life span or 15 to 16 years.¹ Recent figures are alarmingly higher, however, and vary from state to state.

Virginia has the "best" mortality rate among the seriously mentally ill with a loss of "only" 13.5 years of potential life, according to the Center for Mental Health Services (CMHS) and the Centers for Disease Control and Prevention (CDC).² Perhaps persons who suffer from schizophrenia should move to Virgina because the loss of potential life years in other states is much worse:   
   • Arizona: 31.8 years   
   • Texas: 29.3 years   
   • Missouri: 27.9 years   
   • Utah: 26.9 years   
   • Oklahoma: 26.3 years.

A recent Ohio study of mortality and medical illness found an average loss of 32 years of life among persons with schizophrenia.³

Why is the life span of mentally ill persons so short? Apart from their high rates of death from unnatural causes (suicide, homicide, and accidents), the most frequent killer is cardiovascular disease. High mortality rates are well-documented in schizophrenia from various ailments but especially heart disease.⁴ Bipolar disorder and major depression are also associated with high death rates from cardiovascular disease.⁵

The sad truth is that a “dual neglect” contributes to premature mortality of the seriously mentally ill: the system fails to provide ongoing basic primary healthcare, and patients neglect to seek or adhere to medical care.

Persons with serious mental illness often have risk factors associated with preventable causes of heart disease and stroke, including smoking, obesity, sedentary life styles, and poor nutrition. In addition, the metabolic syndrome—obesity, hypertension, hyperglycemia, and dyslipidemia—is highly associated with schizophrenia,⁶ bipolar disorder,⁷ and unipolar depression.⁸

Cardiovascular risk associated with metabolic syndrome requires ongoing medical follow-up, which many mentally ill patients do not receive. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) found shockingly low treatment rates for diabetes, hypertension, and hyperglycemia among outpatients with schizophrenia around the country.⁹

Let us mobilize to correct this shameful health disparity, one patient at a time. The message to mental health professionals is clear:
   • In addition to controlling symptoms of psychosis, mania, depression, or anxiety, routinely screen patients for weight gain, hypertension, high fasting serum glucose, and elevated lipid levels.
   • Refer overweight and obese patients to primary care providers, dietitians, and exercise counselors to reduce their cardiovascular risks.

Psychiatrists and nurse practitioners must address both mental and medical health needs when formulating assessments, treatment plans, and patient education. For practical recommendations on managing medical comorbidities, see “7-point checkup for stable schizophrenia outpatients,” by Britton Ashley Arey, MD, and Stephen R. Marder, MD. The public mental health system also could help the seriously mentally ill by integrating primary healthcare with mental healthcare in community settings across the nation. There are no excuses to do anything less.

A distinguished speaker at a recent national conference was describing his classification of bipolar disorder, and his slides listed subtypes I, II, II½, III, IV, and IV½. During the question-and-answer session, a perplexed attendee announced—with tongue in cheek—that he had 4½ questions and 2½ comments about the bipolar presentation….

Let’s face it, bipolar disorder is a fascinating neuropsychiatric condition that tests every clinician’s diagnostic acumen and treatment skills. Many questions about its diagnosis and treatment remain unanswered.

Diagnosis. Bipolar disorder can present with many different symptoms and with phases that cycle spontaneously or in response to treatment. And with its many mood states and multiple comorbidities, bipolar disorder is replete with red herrings. Many of its sufferers are misdiagnosed with alcoholism, anxiety, borderline personality disorder, attention-deficit/hyperactivity disorder (child or adult), or—the most frequent misdiagnosis—major depression.

Treatment. Despite a rich literature, astonishingly few large controlled clinical trials have been conducted to guide bipolar disorder pharmacotherapy. Long-term follow-up studies indicate that depression dominates in >75% of bipolar patients’ symptomatic days. Even so, (inexplicably) 8 drugs are approved in monotherapy for bipolar mania and only 1 for bipolar depression. (Quetiapine monotherapy was FDA-approved in October, joining the combination of olanzapine/fluoxetine with this labeling.)

No antidepressants are indicated for bipolar depression, yet they have been widely used despite their inherent risk of inducing switches to mania, hypomania, mixed states, and rapid cycling.

Winging it. Most clinicians improvise when treating rapid cycling, hypomania, cyclothymia, or bipolar II. No medications have been approved for these bipolar states, which commonly are seen in outpatient settings.

Three mood stabilizers and five atypical antipsychotics are approved for mania in bipolar I disorder, but hardly a shred of controlled evidence exists to help you decide which drug to try first. Without controlled head-to-head trials, clinicians must choose treatment based on available data:

• Some may use quetiapine as first-line therapy because of evidence showing efficacy in both bipolar mania and bipolar depression.
• Others may select ziprasidone or valproate ER, the only agents approved for all three types of mania (euphoric, mixed, and psychotic).
• Still others—cognizant of high nonadherence and the relapse-inducing risk of substance abuse in bipolar patients—may choose parenteral long-acting risperidone for long-term maintenance.

Combination therapy. Most bipolar disorder patients eventually receive two or more medications, but the evidence is anemic (at best) for combination therapy as well.

What is the optimal combination for mania with severe anxiety or for bipolar II disorder with mixed features or irritable depression? Dozens of iterations are possible, with nothing for prescribers to rely on except “expert consensus” guidelines based on opinion or clinical experience. No controlled clinical trials have compared various combinations, and little is known about:

• optimal dosing of agents in combinations
• which combinations are safest in patients with coexisting medical conditions.

Much remains to be learned about diagnosis and treatment of bipolar disorder’s subtypes. Our talented and productive patients with bipolar disorder look to us to provide the safest, most effective treatments that improve functioning without compromising quality of life. For this, we need a National Institute of Mental Health-sponsored study of bipolar disorder, similar to the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) studies of schizophrenia and Alzheimer’s disease (see Will CATIE-AD change dementia treatment?).

In the meantime, good luck managing the next bipolar II½ patient you see!

A distinguished speaker at a recent national conference was describing his classification of bipolar disorder, and his slides listed subtypes I, II, II½, III, IV, and IV½. During the question-and-answer session, a perplexed attendee announced—with tongue in cheek—that he had 4½ questions and 2½ comments about the bipolar presentation….

Let’s face it, bipolar disorder is a fascinating neuropsychiatric condition that tests every clinician’s diagnostic acumen and treatment skills. Many questions about its diagnosis and treatment remain unanswered.

Diagnosis. Bipolar disorder can present with many different symptoms and with phases that cycle spontaneously or in response to treatment. And with its many mood states and multiple comorbidities, bipolar disorder is replete with red herrings. Many of its sufferers are misdiagnosed with alcoholism, anxiety, borderline personality disorder, attention-deficit/hyperactivity disorder (child or adult), or—the most frequent misdiagnosis—major depression.

Treatment. Despite a rich literature, astonishingly few large controlled clinical trials have been conducted to guide bipolar disorder pharmacotherapy. Long-term follow-up studies indicate that depression dominates in >75% of bipolar patients’ symptomatic days. Even so, (inexplicably) 8 drugs are approved in monotherapy for bipolar mania and only 1 for bipolar depression. (Quetiapine monotherapy was FDA-approved in October, joining the combination of olanzapine/fluoxetine with this labeling.)

No antidepressants are indicated for bipolar depression, yet they have been widely used despite their inherent risk of inducing switches to mania, hypomania, mixed states, and rapid cycling.

Winging it. Most clinicians improvise when treating rapid cycling, hypomania, cyclothymia, or bipolar II. No medications have been approved for these bipolar states, which commonly are seen in outpatient settings.

Three mood stabilizers and five atypical antipsychotics are approved for mania in bipolar I disorder, but hardly a shred of controlled evidence exists to help you decide which drug to try first. Without controlled head-to-head trials, clinicians must choose treatment based on available data:

• Some may use quetiapine as first-line therapy because of evidence showing efficacy in both bipolar mania and bipolar depression.
• Others may select ziprasidone or valproate ER, the only agents approved for all three types of mania (euphoric, mixed, and psychotic).
• Still others—cognizant of high nonadherence and the relapse-inducing risk of substance abuse in bipolar patients—may choose parenteral long-acting risperidone for long-term maintenance.

Combination therapy. Most bipolar disorder patients eventually receive two or more medications, but the evidence is anemic (at best) for combination therapy as well.

What is the optimal combination for mania with severe anxiety or for bipolar II disorder with mixed features or irritable depression? Dozens of iterations are possible, with nothing for prescribers to rely on except “expert consensus” guidelines based on opinion or clinical experience. No controlled clinical trials have compared various combinations, and little is known about:

• optimal dosing of agents in combinations
• which combinations are safest in patients with coexisting medical conditions.

Much remains to be learned about diagnosis and treatment of bipolar disorder’s subtypes. Our talented and productive patients with bipolar disorder look to us to provide the safest, most effective treatments that improve functioning without compromising quality of life. For this, we need a National Institute of Mental Health-sponsored study of bipolar disorder, similar to the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) studies of schizophrenia and Alzheimer’s disease (see Will CATIE-AD change dementia treatment?).

In the meantime, good luck managing the next bipolar II½ patient you see!

A distinguished speaker at a recent national conference was describing his classification of bipolar disorder, and his slides listed subtypes I, II, II½, III, IV, and IV½. During the question-and-answer session, a perplexed attendee announced—with tongue in cheek—that he had 4½ questions and 2½ comments about the bipolar presentation….

Let’s face it, bipolar disorder is a fascinating neuropsychiatric condition that tests every clinician’s diagnostic acumen and treatment skills. Many questions about its diagnosis and treatment remain unanswered.

Diagnosis. Bipolar disorder can present with many different symptoms and with phases that cycle spontaneously or in response to treatment. And with its many mood states and multiple comorbidities, bipolar disorder is replete with red herrings. Many of its sufferers are misdiagnosed with alcoholism, anxiety, borderline personality disorder, attention-deficit/hyperactivity disorder (child or adult), or—the most frequent misdiagnosis—major depression.

Treatment. Despite a rich literature, astonishingly few large controlled clinical trials have been conducted to guide bipolar disorder pharmacotherapy. Long-term follow-up studies indicate that depression dominates in >75% of bipolar patients’ symptomatic days. Even so, (inexplicably) 8 drugs are approved in monotherapy for bipolar mania and only 1 for bipolar depression. (Quetiapine monotherapy was FDA-approved in October, joining the combination of olanzapine/fluoxetine with this labeling.)

No antidepressants are indicated for bipolar depression, yet they have been widely used despite their inherent risk of inducing switches to mania, hypomania, mixed states, and rapid cycling.

Winging it. Most clinicians improvise when treating rapid cycling, hypomania, cyclothymia, or bipolar II. No medications have been approved for these bipolar states, which commonly are seen in outpatient settings.

Three mood stabilizers and five atypical antipsychotics are approved for mania in bipolar I disorder, but hardly a shred of controlled evidence exists to help you decide which drug to try first. Without controlled head-to-head trials, clinicians must choose treatment based on available data:

• Some may use quetiapine as first-line therapy because of evidence showing efficacy in both bipolar mania and bipolar depression.
• Others may select ziprasidone or valproate ER, the only agents approved for all three types of mania (euphoric, mixed, and psychotic).
• Still others—cognizant of high nonadherence and the relapse-inducing risk of substance abuse in bipolar patients—may choose parenteral long-acting risperidone for long-term maintenance.

Combination therapy. Most bipolar disorder patients eventually receive two or more medications, but the evidence is anemic (at best) for combination therapy as well.

What is the optimal combination for mania with severe anxiety or for bipolar II disorder with mixed features or irritable depression? Dozens of iterations are possible, with nothing for prescribers to rely on except “expert consensus” guidelines based on opinion or clinical experience. No controlled clinical trials have compared various combinations, and little is known about:

• optimal dosing of agents in combinations
• which combinations are safest in patients with coexisting medical conditions.

Much remains to be learned about diagnosis and treatment of bipolar disorder’s subtypes. Our talented and productive patients with bipolar disorder look to us to provide the safest, most effective treatments that improve functioning without compromising quality of life. For this, we need a National Institute of Mental Health-sponsored study of bipolar disorder, similar to the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) studies of schizophrenia and Alzheimer’s disease (see Will CATIE-AD change dementia treatment?).

In the meantime, good luck managing the next bipolar II½ patient you see!

There is much more to dopamine than schizophrenia and Parkinson’s disease. Research has discovered a fascinating array of dopamine functions, some as triggers for neuropsychiatric disorders and others critical for healthy living.

Here’s a quiz; how many of the following functions of dopamine’s six receptors and four pathways do you know?

Motor coordination. Most of us take for granted moving or handling objects, thanks to normal dopamine levels in our nigrostriatal tracts. However, one look at a person afflicted with Parkinson’s disease trying to walk or hold a cup of coffee should make us grateful to dopamine for freedom of movement.

Abnormal vs. reality testing. Normal dopamine activity in the mesolimbic tract is vital to maintaining a healthy, adaptive awareness of our surroundings. Persons with abnormally heightened dopamine activity in the medial temporal region—for example, abusers of dopamine agonists such as methamphetamine (see "The 'meth' epidemic")—can be tormented by ideas of reference and delusions about neutral environmental stimuli.

Reward and pleasure. It is hard to imagine life without experiencing fun doing pleasurable activities. So give credit to dopamine in the ventral striatum for all the activities you enjoy, such as playing golf, watching an opera, or socializing with good friends. The dopamine receptor gene has been referred to as “the reward gene.”

Cognition and decision-making. Critical cognitive tasks such as memory, attention, and executive functions depend on an intact mesocortical dopamine pathway. Going to school or holding a job is impossible if mesocortical dopamine is deficient, which is why persons with schizophrenia become disabled.

Placebo effect. Psychiatrists appreciate the high placebo response rates associated with treating depression, anxiety, insomnia, or pain. Research implicates the release of dopamine in the reward pathways that probably are involved in alleviating psychiatric and physical symptoms. Even patients with Parkinson’s disease receiving sham deep brain stimulation or striatal tissue transplants in controlled clinical trials may improve initially because of dopamine release.

Depression. Dopamine is a monoamine that modulates mood, and a decrement in dopamine leads to dysphoria or major depression. Dopamine deficiency states such as Parkinson’s disease are frequently associated with depression and can be treated with dopaminergic antidepressants.

Social defeat. People—and animals as well—can develop permanent aversion to social contact if exposed to unrelenting abuse and violence. Mesolimbic dopamine pathways are implicated in this syndrome of “social defeat,” which can be reversed by chronic administration of antidepressants.

Alcohol dependence. Dopamine receptor dysfunction has been linked with a propensity to abuse alcohol and to reduced sensitivity to reward. The mesolimbic dopamine pathway appears to be critical for experiencing pleasure from abused drugs and is thought to be a common denominator for addictions and drug-seeking behavior.

Hypersexuality. When levodopa [L-dopa] was first used to treat Parkinson’s disease, one of its earliest side effects was increased sexual drive. This effect has been observed with other dopamine agonists and is attributed to potentiation of reward pathways that reinforce pleasurable activities. Other factors also may be involved, as in impulse control disorders.

Pathologic gambling. Treating Parkinson’s disease with dopamine agonists has been associated with an increase in pathologic gambling, an impulse control disorder. The incidence approaches 10%.

Compulsive shopping. Excessive, inappropriate buying is another impulse control disorder that emerges during dopamine agonist therapy.

ADHD. A cortical/frontal dopamine deficit is believed important in the pathophysiology of attention-deficit/hyperactivity disorder. ADHD symptoms can be alleviated with dopamine agonists (stimulants).

Dopamine can enhance health but also disrupt movement, mood, and behavior and lead to neuropsychiatric disorders. This neurotransmitter can reward or torment us. I invite you to send me e-mail ([email protected]) to comment on the 12 functions I’ve listed above or on other disorders you have observed that result from excessive or deficient dopamine activity.

P.S. Three days after I wrote this editorial, researchers announced another potential role for dopamine: regulating the sleep-wake cycle.¹ Excess dopamine in mice allowed rapid-eye movement (REM) sleep (i.e., dreaming) to intrude on wakefulness! This may explain the dreamlike hallucinations in schizophrenia or L-dopa psychosis. Mice with depleted dopamine stopped having REM, even during sleep, but injecting them with D2 receptor agonists restored REM.

There is much more to dopamine than schizophrenia and Parkinson’s disease. Research has discovered a fascinating array of dopamine functions, some as triggers for neuropsychiatric disorders and others critical for healthy living.

Here’s a quiz; how many of the following functions of dopamine’s six receptors and four pathways do you know?

Motor coordination. Most of us take for granted moving or handling objects, thanks to normal dopamine levels in our nigrostriatal tracts. However, one look at a person afflicted with Parkinson’s disease trying to walk or hold a cup of coffee should make us grateful to dopamine for freedom of movement.

Abnormal vs. reality testing. Normal dopamine activity in the mesolimbic tract is vital to maintaining a healthy, adaptive awareness of our surroundings. Persons with abnormally heightened dopamine activity in the medial temporal region—for example, abusers of dopamine agonists such as methamphetamine (see "The 'meth' epidemic")—can be tormented by ideas of reference and delusions about neutral environmental stimuli.

Reward and pleasure. It is hard to imagine life without experiencing fun doing pleasurable activities. So give credit to dopamine in the ventral striatum for all the activities you enjoy, such as playing golf, watching an opera, or socializing with good friends. The dopamine receptor gene has been referred to as “the reward gene.”

Cognition and decision-making. Critical cognitive tasks such as memory, attention, and executive functions depend on an intact mesocortical dopamine pathway. Going to school or holding a job is impossible if mesocortical dopamine is deficient, which is why persons with schizophrenia become disabled.

Placebo effect. Psychiatrists appreciate the high placebo response rates associated with treating depression, anxiety, insomnia, or pain. Research implicates the release of dopamine in the reward pathways that probably are involved in alleviating psychiatric and physical symptoms. Even patients with Parkinson’s disease receiving sham deep brain stimulation or striatal tissue transplants in controlled clinical trials may improve initially because of dopamine release.

Depression. Dopamine is a monoamine that modulates mood, and a decrement in dopamine leads to dysphoria or major depression. Dopamine deficiency states such as Parkinson’s disease are frequently associated with depression and can be treated with dopaminergic antidepressants.

Social defeat. People—and animals as well—can develop permanent aversion to social contact if exposed to unrelenting abuse and violence. Mesolimbic dopamine pathways are implicated in this syndrome of “social defeat,” which can be reversed by chronic administration of antidepressants.

Alcohol dependence. Dopamine receptor dysfunction has been linked with a propensity to abuse alcohol and to reduced sensitivity to reward. The mesolimbic dopamine pathway appears to be critical for experiencing pleasure from abused drugs and is thought to be a common denominator for addictions and drug-seeking behavior.

Hypersexuality. When levodopa [L-dopa] was first used to treat Parkinson’s disease, one of its earliest side effects was increased sexual drive. This effect has been observed with other dopamine agonists and is attributed to potentiation of reward pathways that reinforce pleasurable activities. Other factors also may be involved, as in impulse control disorders.

Pathologic gambling. Treating Parkinson’s disease with dopamine agonists has been associated with an increase in pathologic gambling, an impulse control disorder. The incidence approaches 10%.

Compulsive shopping. Excessive, inappropriate buying is another impulse control disorder that emerges during dopamine agonist therapy.

ADHD. A cortical/frontal dopamine deficit is believed important in the pathophysiology of attention-deficit/hyperactivity disorder. ADHD symptoms can be alleviated with dopamine agonists (stimulants).

Dopamine can enhance health but also disrupt movement, mood, and behavior and lead to neuropsychiatric disorders. This neurotransmitter can reward or torment us. I invite you to send me e-mail ([email protected]) to comment on the 12 functions I’ve listed above or on other disorders you have observed that result from excessive or deficient dopamine activity.

P.S. Three days after I wrote this editorial, researchers announced another potential role for dopamine: regulating the sleep-wake cycle.¹ Excess dopamine in mice allowed rapid-eye movement (REM) sleep (i.e., dreaming) to intrude on wakefulness! This may explain the dreamlike hallucinations in schizophrenia or L-dopa psychosis. Mice with depleted dopamine stopped having REM, even during sleep, but injecting them with D2 receptor agonists restored REM.

There is much more to dopamine than schizophrenia and Parkinson’s disease. Research has discovered a fascinating array of dopamine functions, some as triggers for neuropsychiatric disorders and others critical for healthy living.

Here’s a quiz; how many of the following functions of dopamine’s six receptors and four pathways do you know?

Motor coordination. Most of us take for granted moving or handling objects, thanks to normal dopamine levels in our nigrostriatal tracts. However, one look at a person afflicted with Parkinson’s disease trying to walk or hold a cup of coffee should make us grateful to dopamine for freedom of movement.

Abnormal vs. reality testing. Normal dopamine activity in the mesolimbic tract is vital to maintaining a healthy, adaptive awareness of our surroundings. Persons with abnormally heightened dopamine activity in the medial temporal region—for example, abusers of dopamine agonists such as methamphetamine (see "The 'meth' epidemic")—can be tormented by ideas of reference and delusions about neutral environmental stimuli.

Reward and pleasure. It is hard to imagine life without experiencing fun doing pleasurable activities. So give credit to dopamine in the ventral striatum for all the activities you enjoy, such as playing golf, watching an opera, or socializing with good friends. The dopamine receptor gene has been referred to as “the reward gene.”

Cognition and decision-making. Critical cognitive tasks such as memory, attention, and executive functions depend on an intact mesocortical dopamine pathway. Going to school or holding a job is impossible if mesocortical dopamine is deficient, which is why persons with schizophrenia become disabled.

Placebo effect. Psychiatrists appreciate the high placebo response rates associated with treating depression, anxiety, insomnia, or pain. Research implicates the release of dopamine in the reward pathways that probably are involved in alleviating psychiatric and physical symptoms. Even patients with Parkinson’s disease receiving sham deep brain stimulation or striatal tissue transplants in controlled clinical trials may improve initially because of dopamine release.

Depression. Dopamine is a monoamine that modulates mood, and a decrement in dopamine leads to dysphoria or major depression. Dopamine deficiency states such as Parkinson’s disease are frequently associated with depression and can be treated with dopaminergic antidepressants.

Social defeat. People—and animals as well—can develop permanent aversion to social contact if exposed to unrelenting abuse and violence. Mesolimbic dopamine pathways are implicated in this syndrome of “social defeat,” which can be reversed by chronic administration of antidepressants.

Alcohol dependence. Dopamine receptor dysfunction has been linked with a propensity to abuse alcohol and to reduced sensitivity to reward. The mesolimbic dopamine pathway appears to be critical for experiencing pleasure from abused drugs and is thought to be a common denominator for addictions and drug-seeking behavior.

Hypersexuality. When levodopa [L-dopa] was first used to treat Parkinson’s disease, one of its earliest side effects was increased sexual drive. This effect has been observed with other dopamine agonists and is attributed to potentiation of reward pathways that reinforce pleasurable activities. Other factors also may be involved, as in impulse control disorders.

Pathologic gambling. Treating Parkinson’s disease with dopamine agonists has been associated with an increase in pathologic gambling, an impulse control disorder. The incidence approaches 10%.

Compulsive shopping. Excessive, inappropriate buying is another impulse control disorder that emerges during dopamine agonist therapy.

ADHD. A cortical/frontal dopamine deficit is believed important in the pathophysiology of attention-deficit/hyperactivity disorder. ADHD symptoms can be alleviated with dopamine agonists (stimulants).

Dopamine can enhance health but also disrupt movement, mood, and behavior and lead to neuropsychiatric disorders. This neurotransmitter can reward or torment us. I invite you to send me e-mail ([email protected]) to comment on the 12 functions I’ve listed above or on other disorders you have observed that result from excessive or deficient dopamine activity.

P.S. Three days after I wrote this editorial, researchers announced another potential role for dopamine: regulating the sleep-wake cycle.¹ Excess dopamine in mice allowed rapid-eye movement (REM) sleep (i.e., dreaming) to intrude on wakefulness! This may explain the dreamlike hallucinations in schizophrenia or L-dopa psychosis. Mice with depleted dopamine stopped having REM, even during sleep, but injecting them with D2 receptor agonists restored REM.

Pharmacotherapy works for psychiatric disorders, and so does psychotherapy. That’s why I provide both to each of my patients and why Current Psychiatry articles address combination therapy (for example, see “Treating psychiatric reactions to medical illness,”). Many studies have concluded that combining pharmacotherapy and psychotherapy produces better outcomes than either treatment alone.

The apparent synergy between verbal therapy and medications is often observed but rarely investigated. Does it occur because two different mechanisms of action work better than one, such as when we combine a dopamine blocker (antipsychotic) with a GABA agonist (mood stabilizer) in a patient with bipolar mania? Or do drug therapy and psychotherapy share a common pathway that is enhanced when they are administered together, such as when we combine two antidepressants to manage a patient with treatment-resistant depression?

What is psychotherapy’s mechanism of action anyway, and do various modalities—cognitive-behavioral, interpersonal, or supportive—have the same psychobiological mechanism of action?

Psychotherapy’s mechanism

Given the limited evidence and lack of clear answers in this area, it is reasonable to use recent advances in neuroscience to speculate on how two ostensibly different treatment modalities improve clinical manifestations—the mood, thought, and behavior alterations—of psychiatric brain disorders.

Emerging discoveries over the past few years suggest the common pathway of psychotherapy and pharmacotherapy may be neuroplasticity—synaptogenesis, dendritic spines, and neurogenesis. In other words, talking to a person or giving that person a psychotropic are both likely to modify that person’s brain structure.

Unlike any other organ, the brain changes continuously in response to external and internal stimuli, such as verbal, visual, tactile, and olfactory perceptions as well as chemical stimuli. Neural tissue also changes in response to experiences—stressful or pleasurable, real or imagined, emotional or cognitive. Psychotherapy represents a targeted, strategic, and tactical approach to stimulate specific feelings, recollections, and insights. These are encoded into the recipient’s neurobiological pathways and ultimately translate into a change in behavior or symptoms.

Every therapeutic encounter produces neuroplasticity, and—as with drug therapy—the cumulative effect of repeated doses of psychotherapy consolidates the improvement. One way to conceptualize this mechanism is that psychotherapy refurbishes the patient’s brain structure at the molecular level, restoring resilience to a brain/mind system that was compromised by genetic factors or environmental stress.

‘Re-Wiring’ the brain

Where does pharmacotherapy fit into this model? Here, too, evidence is emerging that psychotropics may exert their therapeutic effect not only through neurochemical pathways but also by stimulating neurotropic factors and inducing beneficial neuroplastic changes.

Antidepressants, mood stabilizers, and atypical antipsychotics (but not conventional neuroleptics) have been shown to induce synaptogenesis, neurite extension, and neurogenesis. These actions result in “re-wiring” and “re-sculpting” brain regions such as the hippocampus and subventricular zone.

Psychotropics are known to trigger gene expression within hours for some genes and after days or weeks for others (which may explain short-term alleviation of some symptoms but delayed response of others). Psychotropics’ neuroprotective and neuroplastic effects also appear to help “replenish” brain tissue destroyed by the neurotoxic effects of repetitive psychotic, manic, or depressive relapses. Increases in nerve growth factor, brain-derived neurotropic factor, and fibroblast growth factor have been implicated in brain tissue regeneration in serious psychiatric disorders. Animal and human studies support this model, but more research is needed.

Accelerating Neuroplasticity

Using this neuroplasticity model, we can reasonably postulate that the convergence of psychotherapy with pharmacotherapy may accelerate and expedite the clinical improvement that hinges on “therapeutic restructuring” of certain neural pathways. I find it intriguing to think that by repairing brain tissue with two different stimuli—talking and medicating—we can mend the fractured mind of an ailing brain.

As neuroscientists explore more deeply this area of research, we clinicians will continue to use concomitant pharmacotherapy and psychotherapy to help our patients navigate the road to recovery.

Pharmacotherapy works for psychiatric disorders, and so does psychotherapy. That’s why I provide both to each of my patients and why Current Psychiatry articles address combination therapy (for example, see “Treating psychiatric reactions to medical illness,”). Many studies have concluded that combining pharmacotherapy and psychotherapy produces better outcomes than either treatment alone.

The apparent synergy between verbal therapy and medications is often observed but rarely investigated. Does it occur because two different mechanisms of action work better than one, such as when we combine a dopamine blocker (antipsychotic) with a GABA agonist (mood stabilizer) in a patient with bipolar mania? Or do drug therapy and psychotherapy share a common pathway that is enhanced when they are administered together, such as when we combine two antidepressants to manage a patient with treatment-resistant depression?

What is psychotherapy’s mechanism of action anyway, and do various modalities—cognitive-behavioral, interpersonal, or supportive—have the same psychobiological mechanism of action?

Psychotherapy’s mechanism

Given the limited evidence and lack of clear answers in this area, it is reasonable to use recent advances in neuroscience to speculate on how two ostensibly different treatment modalities improve clinical manifestations—the mood, thought, and behavior alterations—of psychiatric brain disorders.

Emerging discoveries over the past few years suggest the common pathway of psychotherapy and pharmacotherapy may be neuroplasticity—synaptogenesis, dendritic spines, and neurogenesis. In other words, talking to a person or giving that person a psychotropic are both likely to modify that person’s brain structure.

Unlike any other organ, the brain changes continuously in response to external and internal stimuli, such as verbal, visual, tactile, and olfactory perceptions as well as chemical stimuli. Neural tissue also changes in response to experiences—stressful or pleasurable, real or imagined, emotional or cognitive. Psychotherapy represents a targeted, strategic, and tactical approach to stimulate specific feelings, recollections, and insights. These are encoded into the recipient’s neurobiological pathways and ultimately translate into a change in behavior or symptoms.

Every therapeutic encounter produces neuroplasticity, and—as with drug therapy—the cumulative effect of repeated doses of psychotherapy consolidates the improvement. One way to conceptualize this mechanism is that psychotherapy refurbishes the patient’s brain structure at the molecular level, restoring resilience to a brain/mind system that was compromised by genetic factors or environmental stress.

‘Re-Wiring’ the brain

Where does pharmacotherapy fit into this model? Here, too, evidence is emerging that psychotropics may exert their therapeutic effect not only through neurochemical pathways but also by stimulating neurotropic factors and inducing beneficial neuroplastic changes.

Antidepressants, mood stabilizers, and atypical antipsychotics (but not conventional neuroleptics) have been shown to induce synaptogenesis, neurite extension, and neurogenesis. These actions result in “re-wiring” and “re-sculpting” brain regions such as the hippocampus and subventricular zone.

Psychotropics are known to trigger gene expression within hours for some genes and after days or weeks for others (which may explain short-term alleviation of some symptoms but delayed response of others). Psychotropics’ neuroprotective and neuroplastic effects also appear to help “replenish” brain tissue destroyed by the neurotoxic effects of repetitive psychotic, manic, or depressive relapses. Increases in nerve growth factor, brain-derived neurotropic factor, and fibroblast growth factor have been implicated in brain tissue regeneration in serious psychiatric disorders. Animal and human studies support this model, but more research is needed.

Accelerating Neuroplasticity

Using this neuroplasticity model, we can reasonably postulate that the convergence of psychotherapy with pharmacotherapy may accelerate and expedite the clinical improvement that hinges on “therapeutic restructuring” of certain neural pathways. I find it intriguing to think that by repairing brain tissue with two different stimuli—talking and medicating—we can mend the fractured mind of an ailing brain.

As neuroscientists explore more deeply this area of research, we clinicians will continue to use concomitant pharmacotherapy and psychotherapy to help our patients navigate the road to recovery.

Pharmacotherapy works for psychiatric disorders, and so does psychotherapy. That’s why I provide both to each of my patients and why Current Psychiatry articles address combination therapy (for example, see “Treating psychiatric reactions to medical illness,”). Many studies have concluded that combining pharmacotherapy and psychotherapy produces better outcomes than either treatment alone.

The apparent synergy between verbal therapy and medications is often observed but rarely investigated. Does it occur because two different mechanisms of action work better than one, such as when we combine a dopamine blocker (antipsychotic) with a GABA agonist (mood stabilizer) in a patient with bipolar mania? Or do drug therapy and psychotherapy share a common pathway that is enhanced when they are administered together, such as when we combine two antidepressants to manage a patient with treatment-resistant depression?

What is psychotherapy’s mechanism of action anyway, and do various modalities—cognitive-behavioral, interpersonal, or supportive—have the same psychobiological mechanism of action?

Psychotherapy’s mechanism

Given the limited evidence and lack of clear answers in this area, it is reasonable to use recent advances in neuroscience to speculate on how two ostensibly different treatment modalities improve clinical manifestations—the mood, thought, and behavior alterations—of psychiatric brain disorders.

Emerging discoveries over the past few years suggest the common pathway of psychotherapy and pharmacotherapy may be neuroplasticity—synaptogenesis, dendritic spines, and neurogenesis. In other words, talking to a person or giving that person a psychotropic are both likely to modify that person’s brain structure.

Unlike any other organ, the brain changes continuously in response to external and internal stimuli, such as verbal, visual, tactile, and olfactory perceptions as well as chemical stimuli. Neural tissue also changes in response to experiences—stressful or pleasurable, real or imagined, emotional or cognitive. Psychotherapy represents a targeted, strategic, and tactical approach to stimulate specific feelings, recollections, and insights. These are encoded into the recipient’s neurobiological pathways and ultimately translate into a change in behavior or symptoms.

Every therapeutic encounter produces neuroplasticity, and—as with drug therapy—the cumulative effect of repeated doses of psychotherapy consolidates the improvement. One way to conceptualize this mechanism is that psychotherapy refurbishes the patient’s brain structure at the molecular level, restoring resilience to a brain/mind system that was compromised by genetic factors or environmental stress.

‘Re-Wiring’ the brain

Where does pharmacotherapy fit into this model? Here, too, evidence is emerging that psychotropics may exert their therapeutic effect not only through neurochemical pathways but also by stimulating neurotropic factors and inducing beneficial neuroplastic changes.

Antidepressants, mood stabilizers, and atypical antipsychotics (but not conventional neuroleptics) have been shown to induce synaptogenesis, neurite extension, and neurogenesis. These actions result in “re-wiring” and “re-sculpting” brain regions such as the hippocampus and subventricular zone.

Psychotropics are known to trigger gene expression within hours for some genes and after days or weeks for others (which may explain short-term alleviation of some symptoms but delayed response of others). Psychotropics’ neuroprotective and neuroplastic effects also appear to help “replenish” brain tissue destroyed by the neurotoxic effects of repetitive psychotic, manic, or depressive relapses. Increases in nerve growth factor, brain-derived neurotropic factor, and fibroblast growth factor have been implicated in brain tissue regeneration in serious psychiatric disorders. Animal and human studies support this model, but more research is needed.

Accelerating Neuroplasticity

Using this neuroplasticity model, we can reasonably postulate that the convergence of psychotherapy with pharmacotherapy may accelerate and expedite the clinical improvement that hinges on “therapeutic restructuring” of certain neural pathways. I find it intriguing to think that by repairing brain tissue with two different stimuli—talking and medicating—we can mend the fractured mind of an ailing brain.

As neuroscientists explore more deeply this area of research, we clinicians will continue to use concomitant pharmacotherapy and psychotherapy to help our patients navigate the road to recovery.