Henry A. Nasrallah, MD

A widespread and enduring notion about schizophrenia is that it is a hopeless brain disease associated with progressive clinical, cognitive, social, and vocational deterioration. After all, community mental health centers are replete with profoundly disabled persons who carry a schizophrenia diagnosis. Most have no friends, spouses, or significant others and have not been employed for years. So can one argue that persons with schizophrenia ever recover?

How you define “recovery,” as discussed in this issue (page 40), certainly influences how you would answer that question. As a long-time schizophrenia researcher who has treated thousands of patients and conducted dozens of research projects into schizophrenia, I respond with a “definite maybe.”

Odds of recovery: 1 in 5?

The severity and outcome of any illness—including schizophrenia—falls into a bell-shaped curve, from very mild to very severe. Observations can be misleading, however. Kraepelin, for example, based his deteriorative description of schizophrenia on severely ill, long-term hospitalized patients. This biased sample did not include patients who remained in the community with their families, doing well enough not to need hospitalization.

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study¹ provides a good example of schizophrenia’s heterogeneity. At enrollment, the 1,460 outpatients ranged from no symptoms to severely ill. Schizophrenia outcome is similarly distributed.

The landmark Iowa 500 study² in the 1970s was one of the most thorough examinations of long-term schizophrenia outcomes, including recovery. With funding from the National Institute of Mental Health, researchers tracked down and interviewed hundreds of persons admitted 30 to 40 years earlier to the Iowa State Psychopathic Hospital and who met rigorous Research Diagnostic Criteria for schizophrenia. They found that:

Table

Expert consensus proposed criteria for schizophrenia remission

• 20% had recovered completely and resumed normal life
• 80% remained ill, with variable degrees of severity.

The best prognosis was for paranoid schizophrenia and the worst for non-paranoid schizophrenia; hebephrenia (“disorganized”) and undifferentiated schizophrenia had similarly poor outcomes.

A major confound for recovery from schizophrenia is that patients with psychotic bipolar disorder sometimes are misdiagnosed as having schizophrenia. Patients with bipolar disorder can achieve remission for a while, only to relapse again. If mis-diagnosed, they may be reported as “recovered” schizophrenia cases when they cycle out of a severe bipolar episode.

Treatment adherence: A key to recovery

Features associated with better outcome and possible recovery in schizophrenia include female gender, sudden onset of psychosis, paranoid subtype, high IQ, minimal negative symptoms, presence of an affective component, having a supportive family, good insight, continuity of care, and—very important—optimal treatment adherence.

Discontinuing treatment in schizophrenia leads to psychotic relapses and a lower probability of recovering. Therefore, I find it puzzling that injectable, long-acting antipsychotics are used infrequently in the United States, despite the high rate of treatment discontinuation in schizophrenia. In Europe, the rate of use of injectable antipsychotics is 3 times higher.

I have obtained extremely good outcomes—including recovery in patients who were regarded as hopelessly deteriorated—with long-acting injectable second-generation antipsychotics (SGAs) and dramatic functional recovery after giving patients injectable SGA treatment continuously for 2 years or more. My experience with depot first-generation antipsychotics (FGAs) was that they helped prevent relapse but did not help patients return to functioning. A possible explanation is that SGAs have been found to induce neurotropic factors and stimulate neurogenesis, whereas FGAs may lead to a decline in neurotropic factors and apoptotic loss of brain tissue.³

A useful remission measure

To measure clinically meaningful improvement (remission), I recommend criteria developed by schizophrenia experts (Table).⁴ These research criteria define remission based on core items in the Positive and Negative Syndrome Scale (PANSS). If symptoms remain in remission >6 months, social and vocational rehabilitation is more likely to restore a patient’s functional capacity. That functional improvement—not just symptomatic remission—would constitute true recovery.

Recovery is possible but appears to occur in a minority of patients.² Many patients can achieve remission, which enables them to gradually regain various degrees of functioning. Just as a stroke patient may need rehabilitation to learn to talk and walk again, individuals with schizophrenia can reclaim their lives with a balanced regimen of effective antipsychotic medication, coupled with personalized social, cognitive, and vocational rehabilitation.

A widespread and enduring notion about schizophrenia is that it is a hopeless brain disease associated with progressive clinical, cognitive, social, and vocational deterioration. After all, community mental health centers are replete with profoundly disabled persons who carry a schizophrenia diagnosis. Most have no friends, spouses, or significant others and have not been employed for years. So can one argue that persons with schizophrenia ever recover?

How you define “recovery,” as discussed in this issue (page 40), certainly influences how you would answer that question. As a long-time schizophrenia researcher who has treated thousands of patients and conducted dozens of research projects into schizophrenia, I respond with a “definite maybe.”

Odds of recovery: 1 in 5?

The severity and outcome of any illness—including schizophrenia—falls into a bell-shaped curve, from very mild to very severe. Observations can be misleading, however. Kraepelin, for example, based his deteriorative description of schizophrenia on severely ill, long-term hospitalized patients. This biased sample did not include patients who remained in the community with their families, doing well enough not to need hospitalization.

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study¹ provides a good example of schizophrenia’s heterogeneity. At enrollment, the 1,460 outpatients ranged from no symptoms to severely ill. Schizophrenia outcome is similarly distributed.

The landmark Iowa 500 study² in the 1970s was one of the most thorough examinations of long-term schizophrenia outcomes, including recovery. With funding from the National Institute of Mental Health, researchers tracked down and interviewed hundreds of persons admitted 30 to 40 years earlier to the Iowa State Psychopathic Hospital and who met rigorous Research Diagnostic Criteria for schizophrenia. They found that:

Table

Expert consensus proposed criteria for schizophrenia remission

• 20% had recovered completely and resumed normal life
• 80% remained ill, with variable degrees of severity.

The best prognosis was for paranoid schizophrenia and the worst for non-paranoid schizophrenia; hebephrenia (“disorganized”) and undifferentiated schizophrenia had similarly poor outcomes.

A major confound for recovery from schizophrenia is that patients with psychotic bipolar disorder sometimes are misdiagnosed as having schizophrenia. Patients with bipolar disorder can achieve remission for a while, only to relapse again. If mis-diagnosed, they may be reported as “recovered” schizophrenia cases when they cycle out of a severe bipolar episode.

Treatment adherence: A key to recovery

Features associated with better outcome and possible recovery in schizophrenia include female gender, sudden onset of psychosis, paranoid subtype, high IQ, minimal negative symptoms, presence of an affective component, having a supportive family, good insight, continuity of care, and—very important—optimal treatment adherence.

Discontinuing treatment in schizophrenia leads to psychotic relapses and a lower probability of recovering. Therefore, I find it puzzling that injectable, long-acting antipsychotics are used infrequently in the United States, despite the high rate of treatment discontinuation in schizophrenia. In Europe, the rate of use of injectable antipsychotics is 3 times higher.

I have obtained extremely good outcomes—including recovery in patients who were regarded as hopelessly deteriorated—with long-acting injectable second-generation antipsychotics (SGAs) and dramatic functional recovery after giving patients injectable SGA treatment continuously for 2 years or more. My experience with depot first-generation antipsychotics (FGAs) was that they helped prevent relapse but did not help patients return to functioning. A possible explanation is that SGAs have been found to induce neurotropic factors and stimulate neurogenesis, whereas FGAs may lead to a decline in neurotropic factors and apoptotic loss of brain tissue.³

A useful remission measure

To measure clinically meaningful improvement (remission), I recommend criteria developed by schizophrenia experts (Table).⁴ These research criteria define remission based on core items in the Positive and Negative Syndrome Scale (PANSS). If symptoms remain in remission >6 months, social and vocational rehabilitation is more likely to restore a patient’s functional capacity. That functional improvement—not just symptomatic remission—would constitute true recovery.

Recovery is possible but appears to occur in a minority of patients.² Many patients can achieve remission, which enables them to gradually regain various degrees of functioning. Just as a stroke patient may need rehabilitation to learn to talk and walk again, individuals with schizophrenia can reclaim their lives with a balanced regimen of effective antipsychotic medication, coupled with personalized social, cognitive, and vocational rehabilitation.

A widespread and enduring notion about schizophrenia is that it is a hopeless brain disease associated with progressive clinical, cognitive, social, and vocational deterioration. After all, community mental health centers are replete with profoundly disabled persons who carry a schizophrenia diagnosis. Most have no friends, spouses, or significant others and have not been employed for years. So can one argue that persons with schizophrenia ever recover?

How you define “recovery,” as discussed in this issue (page 40), certainly influences how you would answer that question. As a long-time schizophrenia researcher who has treated thousands of patients and conducted dozens of research projects into schizophrenia, I respond with a “definite maybe.”

Odds of recovery: 1 in 5?

The severity and outcome of any illness—including schizophrenia—falls into a bell-shaped curve, from very mild to very severe. Observations can be misleading, however. Kraepelin, for example, based his deteriorative description of schizophrenia on severely ill, long-term hospitalized patients. This biased sample did not include patients who remained in the community with their families, doing well enough not to need hospitalization.

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study¹ provides a good example of schizophrenia’s heterogeneity. At enrollment, the 1,460 outpatients ranged from no symptoms to severely ill. Schizophrenia outcome is similarly distributed.

The landmark Iowa 500 study² in the 1970s was one of the most thorough examinations of long-term schizophrenia outcomes, including recovery. With funding from the National Institute of Mental Health, researchers tracked down and interviewed hundreds of persons admitted 30 to 40 years earlier to the Iowa State Psychopathic Hospital and who met rigorous Research Diagnostic Criteria for schizophrenia. They found that:

Table

Expert consensus proposed criteria for schizophrenia remission

• 20% had recovered completely and resumed normal life
• 80% remained ill, with variable degrees of severity.

The best prognosis was for paranoid schizophrenia and the worst for non-paranoid schizophrenia; hebephrenia (“disorganized”) and undifferentiated schizophrenia had similarly poor outcomes.

A major confound for recovery from schizophrenia is that patients with psychotic bipolar disorder sometimes are misdiagnosed as having schizophrenia. Patients with bipolar disorder can achieve remission for a while, only to relapse again. If mis-diagnosed, they may be reported as “recovered” schizophrenia cases when they cycle out of a severe bipolar episode.

Treatment adherence: A key to recovery

Features associated with better outcome and possible recovery in schizophrenia include female gender, sudden onset of psychosis, paranoid subtype, high IQ, minimal negative symptoms, presence of an affective component, having a supportive family, good insight, continuity of care, and—very important—optimal treatment adherence.

Discontinuing treatment in schizophrenia leads to psychotic relapses and a lower probability of recovering. Therefore, I find it puzzling that injectable, long-acting antipsychotics are used infrequently in the United States, despite the high rate of treatment discontinuation in schizophrenia. In Europe, the rate of use of injectable antipsychotics is 3 times higher.

I have obtained extremely good outcomes—including recovery in patients who were regarded as hopelessly deteriorated—with long-acting injectable second-generation antipsychotics (SGAs) and dramatic functional recovery after giving patients injectable SGA treatment continuously for 2 years or more. My experience with depot first-generation antipsychotics (FGAs) was that they helped prevent relapse but did not help patients return to functioning. A possible explanation is that SGAs have been found to induce neurotropic factors and stimulate neurogenesis, whereas FGAs may lead to a decline in neurotropic factors and apoptotic loss of brain tissue.³

A useful remission measure

To measure clinically meaningful improvement (remission), I recommend criteria developed by schizophrenia experts (Table).⁴ These research criteria define remission based on core items in the Positive and Negative Syndrome Scale (PANSS). If symptoms remain in remission >6 months, social and vocational rehabilitation is more likely to restore a patient’s functional capacity. That functional improvement—not just symptomatic remission—would constitute true recovery.

Recovery is possible but appears to occur in a minority of patients.² Many patients can achieve remission, which enables them to gradually regain various degrees of functioning. Just as a stroke patient may need rehabilitation to learn to talk and walk again, individuals with schizophrenia can reclaim their lives with a balanced regimen of effective antipsychotic medication, coupled with personalized social, cognitive, and vocational rehabilitation.

The FDA, with its complex and challenging mission, is constantly caught between Congress’ scrutiny and the public’s demands. It does not need nagging about doing more, but I’d like to suggest how the FDA could stimulate psychiatric drug discovery and encourage continuing medical education (CME). I propose 2 creative ideas as a long-time researcher with thorough knowledge of controlled clinical trials and an educator with extensive CME involvement.

Reward innovation in drug discovery

Like all psychiatric clinicians, I am painfully aware that many DSM-IVTR disorders have no FDA-approved medications. Within each of the existing classes of approved psychotropics—antipsychotics, antidepressants, and mood stabilizers—drugs tend to have similar mechanisms of action. Further, most available psychotropics are of limited effectiveness, and hardly any major therapeutic breakthroughs in psychiatry have been achieved in the past 50 years. Pharmaceutical companies seem content to settle for the safety of developing “me too” drugs and yet more formulations of existing agents.

Incentives can be powerful motivators for individuals and organizations to excel. So, to spur innovation by the pharmaceutical industry, I urge the FDA to extend the patent lives of breakthrough drugs (only those with completely new mechanisms of action) from the current 17 years to 25 years. I believe this very lucrative “carrot” will motivate every drug company to mobilize its resources and invest heavily in financially risky but innovative research and development.

Excellence deserves to be differentially rewarded, and outstanding drug discovery should be no exception. Promising an 8-year patent “bonus” extension could generate a tsunami of first-in-class drugs and cures for diseases that today’s medications treat inadequately or not at all. Yes, the pharmaceutical companies would make higher profits, but the ultimate winners would be patients whose lives are improved and extended by these novel medications.

Support CME collaboratively

A second idea occurred to me after I read the Josiah Macy, Jr. Foundation’s November 2007 report recommending the unthinkable: that CME be completely divorced from the financial life-blood of pharmaceutical sponsorship! More than 60% of financial support for accredited CME activities in medicine comes from pharmaceutical and medical device companies ($1.45 billion of a total $2.4 billion in 2006).¹

The Macy Foundation’s report acknowledges that “abrupt cessation of all such support would impose unacceptable hardship” on many professional organizations and institutions, and it proposes a 5-year phase-out period.¹ This ban on commercial support would include grand rounds and symposia organized by medical schools, which provide almost no funds for CME in their limited budgets.

How can the FDA help? I propose that the FDA support CME nationwide by pooling pharmaceutical company contributions in a not-for-profit independent fund and appoint the Accreditation Council for Continuing Medical Education (ACCME) as overseer. The ACCME would evaluate applications from all specialties and allocate funds to support meritorious CME programs.

For each year that a pharmaceutical company contributes to the CME fund, the FDA would grant a 3-month patent extension on all of the company’s drugs. This extension could yield drug companies more than $1 billion in additional sales for blockbusters such as atypical antipsychotics.

CME could be adequately funded, but without today’s perceived tarnish—whether deserved or not—of pharmaceutical influence. Pharmaceutical companies would no longer directly sponsor CME programs but would continue to be important philanthropic partners. Contributions from dozens of companies would fund the vital activities by which physicians and nurses keep pace with advances in the diagnosis and treatment of disease.

Your comments?

My suggestions are intended to start a dialogue about financial support for two critical needs in psychiatry: research to develop new psychiatric medications and support for continuing education. To advance, we must break with stale models and exploit reasonable solutions. I invite you to send your comments to me at [email protected]

The FDA, with its complex and challenging mission, is constantly caught between Congress’ scrutiny and the public’s demands. It does not need nagging about doing more, but I’d like to suggest how the FDA could stimulate psychiatric drug discovery and encourage continuing medical education (CME). I propose 2 creative ideas as a long-time researcher with thorough knowledge of controlled clinical trials and an educator with extensive CME involvement.

Reward innovation in drug discovery

Like all psychiatric clinicians, I am painfully aware that many DSM-IVTR disorders have no FDA-approved medications. Within each of the existing classes of approved psychotropics—antipsychotics, antidepressants, and mood stabilizers—drugs tend to have similar mechanisms of action. Further, most available psychotropics are of limited effectiveness, and hardly any major therapeutic breakthroughs in psychiatry have been achieved in the past 50 years. Pharmaceutical companies seem content to settle for the safety of developing “me too” drugs and yet more formulations of existing agents.

Incentives can be powerful motivators for individuals and organizations to excel. So, to spur innovation by the pharmaceutical industry, I urge the FDA to extend the patent lives of breakthrough drugs (only those with completely new mechanisms of action) from the current 17 years to 25 years. I believe this very lucrative “carrot” will motivate every drug company to mobilize its resources and invest heavily in financially risky but innovative research and development.

Excellence deserves to be differentially rewarded, and outstanding drug discovery should be no exception. Promising an 8-year patent “bonus” extension could generate a tsunami of first-in-class drugs and cures for diseases that today’s medications treat inadequately or not at all. Yes, the pharmaceutical companies would make higher profits, but the ultimate winners would be patients whose lives are improved and extended by these novel medications.

Support CME collaboratively

A second idea occurred to me after I read the Josiah Macy, Jr. Foundation’s November 2007 report recommending the unthinkable: that CME be completely divorced from the financial life-blood of pharmaceutical sponsorship! More than 60% of financial support for accredited CME activities in medicine comes from pharmaceutical and medical device companies ($1.45 billion of a total $2.4 billion in 2006).¹

The Macy Foundation’s report acknowledges that “abrupt cessation of all such support would impose unacceptable hardship” on many professional organizations and institutions, and it proposes a 5-year phase-out period.¹ This ban on commercial support would include grand rounds and symposia organized by medical schools, which provide almost no funds for CME in their limited budgets.

How can the FDA help? I propose that the FDA support CME nationwide by pooling pharmaceutical company contributions in a not-for-profit independent fund and appoint the Accreditation Council for Continuing Medical Education (ACCME) as overseer. The ACCME would evaluate applications from all specialties and allocate funds to support meritorious CME programs.

For each year that a pharmaceutical company contributes to the CME fund, the FDA would grant a 3-month patent extension on all of the company’s drugs. This extension could yield drug companies more than $1 billion in additional sales for blockbusters such as atypical antipsychotics.

CME could be adequately funded, but without today’s perceived tarnish—whether deserved or not—of pharmaceutical influence. Pharmaceutical companies would no longer directly sponsor CME programs but would continue to be important philanthropic partners. Contributions from dozens of companies would fund the vital activities by which physicians and nurses keep pace with advances in the diagnosis and treatment of disease.

Your comments?

My suggestions are intended to start a dialogue about financial support for two critical needs in psychiatry: research to develop new psychiatric medications and support for continuing education. To advance, we must break with stale models and exploit reasonable solutions. I invite you to send your comments to me at [email protected]

The FDA, with its complex and challenging mission, is constantly caught between Congress’ scrutiny and the public’s demands. It does not need nagging about doing more, but I’d like to suggest how the FDA could stimulate psychiatric drug discovery and encourage continuing medical education (CME). I propose 2 creative ideas as a long-time researcher with thorough knowledge of controlled clinical trials and an educator with extensive CME involvement.

Reward innovation in drug discovery

Like all psychiatric clinicians, I am painfully aware that many DSM-IVTR disorders have no FDA-approved medications. Within each of the existing classes of approved psychotropics—antipsychotics, antidepressants, and mood stabilizers—drugs tend to have similar mechanisms of action. Further, most available psychotropics are of limited effectiveness, and hardly any major therapeutic breakthroughs in psychiatry have been achieved in the past 50 years. Pharmaceutical companies seem content to settle for the safety of developing “me too” drugs and yet more formulations of existing agents.

Incentives can be powerful motivators for individuals and organizations to excel. So, to spur innovation by the pharmaceutical industry, I urge the FDA to extend the patent lives of breakthrough drugs (only those with completely new mechanisms of action) from the current 17 years to 25 years. I believe this very lucrative “carrot” will motivate every drug company to mobilize its resources and invest heavily in financially risky but innovative research and development.

Excellence deserves to be differentially rewarded, and outstanding drug discovery should be no exception. Promising an 8-year patent “bonus” extension could generate a tsunami of first-in-class drugs and cures for diseases that today’s medications treat inadequately or not at all. Yes, the pharmaceutical companies would make higher profits, but the ultimate winners would be patients whose lives are improved and extended by these novel medications.

Support CME collaboratively

A second idea occurred to me after I read the Josiah Macy, Jr. Foundation’s November 2007 report recommending the unthinkable: that CME be completely divorced from the financial life-blood of pharmaceutical sponsorship! More than 60% of financial support for accredited CME activities in medicine comes from pharmaceutical and medical device companies ($1.45 billion of a total $2.4 billion in 2006).¹

The Macy Foundation’s report acknowledges that “abrupt cessation of all such support would impose unacceptable hardship” on many professional organizations and institutions, and it proposes a 5-year phase-out period.¹ This ban on commercial support would include grand rounds and symposia organized by medical schools, which provide almost no funds for CME in their limited budgets.

How can the FDA help? I propose that the FDA support CME nationwide by pooling pharmaceutical company contributions in a not-for-profit independent fund and appoint the Accreditation Council for Continuing Medical Education (ACCME) as overseer. The ACCME would evaluate applications from all specialties and allocate funds to support meritorious CME programs.

For each year that a pharmaceutical company contributes to the CME fund, the FDA would grant a 3-month patent extension on all of the company’s drugs. This extension could yield drug companies more than $1 billion in additional sales for blockbusters such as atypical antipsychotics.

CME could be adequately funded, but without today’s perceived tarnish—whether deserved or not—of pharmaceutical influence. Pharmaceutical companies would no longer directly sponsor CME programs but would continue to be important philanthropic partners. Contributions from dozens of companies would fund the vital activities by which physicians and nurses keep pace with advances in the diagnosis and treatment of disease.

Your comments?

My suggestions are intended to start a dialogue about financial support for two critical needs in psychiatry: research to develop new psychiatric medications and support for continuing education. To advance, we must break with stale models and exploit reasonable solutions. I invite you to send your comments to me at [email protected]

One of psychiatry’s so-called triumphs was the discovery of antipsychotics (starting with chlorpromazine in the 1950s) and the ensuing release of the seriously mentally ill into the community. State hospitals were rapidly evacuated, and patients supplied with the new “miracle drugs” were relabeled as “clients” or “consumers” as if they did not have severe medical illnesses. Asylums that had off ered medical care, refuge, and safety were condemned to the trash heap of psychohistory.

How naïve we were! As we discovered, antipsychotics are so limited in effi cacy and tolerability that most patients eventually stop taking them and relapse, leading to recurrent hospitalizations. Little did we know—although Kraepelin had warned us—that schizophrenia’s dis-ability is caused not by psychosis but by severe cognitive defi cits and negative symptoms that neuroleptics fail to reverse.

We now know that persons with schizophrenia are unable to navigate the complexities of community living because they have frontal lobe pathology, poor executive function, severe memory defi cits, and impaired social cognition. They may have regained their civil rights when they left the institutions, but they could not effectively exercise those rights. Left to their own devices, they were expected to become independent and autonomous, but many were too cognitively disabled to do so.

The results—in my opinion—have been tragic, inhumane, and disastrous for the 3 million Americans who have schizophrenia. Yet I’m perplexed that there is no public outrage about the misery of these seriously mentally ill individuals. Consider deinstitutionalization’s unintended consequences:

Homelessness has risen dramatically since the demise of state hospitals, which had housed persons with psychiatric brain diseases.

Incarceration. Yesterday’s state hospitals have morphed into today’s jails and prisons. Correctional facilities are bulging with mentally ill inmates, and don’t think they are receiving better care than in the old asylums. Their illness behaviors have been criminalized and deemed “illegal” because they live in the community, not in a medical facility.

Poverty. In most cases, the seriously mentally ill live below the poverty level and barely meet their subsistence needs.

Substance abuse has burgeoned among the mentally ill, creating a more severe form of mental illness euphemistically labeled “dual diagnosis.” Alcohol and drug abuse worsens psychosis and bipolar mania and leads to treatment resistance and further deterioration.

Crime. Though the mentally ill are perceived as crime perpetrators, they are more likely to be crime victims.

Medical illness. Persons with serious mental illness suffer high rates of infection, obesity, diabetes, hyper-lipidemia, and hypertension—all of which require intensive and ongoing medical care.

Poor access to primary care. Although at high risk for cardiovascular disease, most persons with schizophrenia do not receive the most basic medical care because they do not have a primary care provider.

Early mortality. Individuals with serious mental illness die much younger than persons in the general population, forfeiting about 28 years of potential life. Interestingly, my colleagues in countries that still have psychiatric institutions tell me their chronically mentally ill patients often live to old age.

Lack of stable or signi?cant relationships. Most of the seriously mentally ill live an isolated life of quiet desperation and loneliness. They do not know how to make friends. State hospitals offered access to social and recreational activities where patients could regularly meet others, make friends, and maybe even find a sexual partner.

Social and vocational disability and stigma. The seriously mentally ill are stigmatized in many ways and have little chance of employment. In state hospitals, supervised work therapy enabled many to work in the bakery, laundry, wood shop, or on the farm and provided the dignity of being part of a work community.

Deinstitutionalization failed because society’s good intentions were guided by legalisms and sociologic notions, rather than scientific principles. Serious mental disorders are neurobiologic diseases that severely limit independent functioning. Until effective treatments are found for schizophrenia’s cognitive deficits and negative symptoms, we should seek a more humane model of care. We should be bold enough to restore comprehensive long-term health care facilities where patients’ mental and physical illnesses can be stabilized and they can achieve supervised autonomy through evidence-based biopsychosocial and rehabilitative therapies.

An institutional model of care is rational for at least some persons with schizophrenia who are suffering under a politically correct system of care. Without medically driven care, the misery will continue.

One of psychiatry’s so-called triumphs was the discovery of antipsychotics (starting with chlorpromazine in the 1950s) and the ensuing release of the seriously mentally ill into the community. State hospitals were rapidly evacuated, and patients supplied with the new “miracle drugs” were relabeled as “clients” or “consumers” as if they did not have severe medical illnesses. Asylums that had off ered medical care, refuge, and safety were condemned to the trash heap of psychohistory.

How naïve we were! As we discovered, antipsychotics are so limited in effi cacy and tolerability that most patients eventually stop taking them and relapse, leading to recurrent hospitalizations. Little did we know—although Kraepelin had warned us—that schizophrenia’s dis-ability is caused not by psychosis but by severe cognitive defi cits and negative symptoms that neuroleptics fail to reverse.

We now know that persons with schizophrenia are unable to navigate the complexities of community living because they have frontal lobe pathology, poor executive function, severe memory defi cits, and impaired social cognition. They may have regained their civil rights when they left the institutions, but they could not effectively exercise those rights. Left to their own devices, they were expected to become independent and autonomous, but many were too cognitively disabled to do so.

The results—in my opinion—have been tragic, inhumane, and disastrous for the 3 million Americans who have schizophrenia. Yet I’m perplexed that there is no public outrage about the misery of these seriously mentally ill individuals. Consider deinstitutionalization’s unintended consequences:

Homelessness has risen dramatically since the demise of state hospitals, which had housed persons with psychiatric brain diseases.

Incarceration. Yesterday’s state hospitals have morphed into today’s jails and prisons. Correctional facilities are bulging with mentally ill inmates, and don’t think they are receiving better care than in the old asylums. Their illness behaviors have been criminalized and deemed “illegal” because they live in the community, not in a medical facility.

Poverty. In most cases, the seriously mentally ill live below the poverty level and barely meet their subsistence needs.

Substance abuse has burgeoned among the mentally ill, creating a more severe form of mental illness euphemistically labeled “dual diagnosis.” Alcohol and drug abuse worsens psychosis and bipolar mania and leads to treatment resistance and further deterioration.

Crime. Though the mentally ill are perceived as crime perpetrators, they are more likely to be crime victims.

Medical illness. Persons with serious mental illness suffer high rates of infection, obesity, diabetes, hyper-lipidemia, and hypertension—all of which require intensive and ongoing medical care.

Poor access to primary care. Although at high risk for cardiovascular disease, most persons with schizophrenia do not receive the most basic medical care because they do not have a primary care provider.

Early mortality. Individuals with serious mental illness die much younger than persons in the general population, forfeiting about 28 years of potential life. Interestingly, my colleagues in countries that still have psychiatric institutions tell me their chronically mentally ill patients often live to old age.

Lack of stable or signi?cant relationships. Most of the seriously mentally ill live an isolated life of quiet desperation and loneliness. They do not know how to make friends. State hospitals offered access to social and recreational activities where patients could regularly meet others, make friends, and maybe even find a sexual partner.

Social and vocational disability and stigma. The seriously mentally ill are stigmatized in many ways and have little chance of employment. In state hospitals, supervised work therapy enabled many to work in the bakery, laundry, wood shop, or on the farm and provided the dignity of being part of a work community.

Deinstitutionalization failed because society’s good intentions were guided by legalisms and sociologic notions, rather than scientific principles. Serious mental disorders are neurobiologic diseases that severely limit independent functioning. Until effective treatments are found for schizophrenia’s cognitive deficits and negative symptoms, we should seek a more humane model of care. We should be bold enough to restore comprehensive long-term health care facilities where patients’ mental and physical illnesses can be stabilized and they can achieve supervised autonomy through evidence-based biopsychosocial and rehabilitative therapies.

An institutional model of care is rational for at least some persons with schizophrenia who are suffering under a politically correct system of care. Without medically driven care, the misery will continue.

One of psychiatry’s so-called triumphs was the discovery of antipsychotics (starting with chlorpromazine in the 1950s) and the ensuing release of the seriously mentally ill into the community. State hospitals were rapidly evacuated, and patients supplied with the new “miracle drugs” were relabeled as “clients” or “consumers” as if they did not have severe medical illnesses. Asylums that had off ered medical care, refuge, and safety were condemned to the trash heap of psychohistory.

How naïve we were! As we discovered, antipsychotics are so limited in effi cacy and tolerability that most patients eventually stop taking them and relapse, leading to recurrent hospitalizations. Little did we know—although Kraepelin had warned us—that schizophrenia’s dis-ability is caused not by psychosis but by severe cognitive defi cits and negative symptoms that neuroleptics fail to reverse.

We now know that persons with schizophrenia are unable to navigate the complexities of community living because they have frontal lobe pathology, poor executive function, severe memory defi cits, and impaired social cognition. They may have regained their civil rights when they left the institutions, but they could not effectively exercise those rights. Left to their own devices, they were expected to become independent and autonomous, but many were too cognitively disabled to do so.

The results—in my opinion—have been tragic, inhumane, and disastrous for the 3 million Americans who have schizophrenia. Yet I’m perplexed that there is no public outrage about the misery of these seriously mentally ill individuals. Consider deinstitutionalization’s unintended consequences:

Homelessness has risen dramatically since the demise of state hospitals, which had housed persons with psychiatric brain diseases.

Incarceration. Yesterday’s state hospitals have morphed into today’s jails and prisons. Correctional facilities are bulging with mentally ill inmates, and don’t think they are receiving better care than in the old asylums. Their illness behaviors have been criminalized and deemed “illegal” because they live in the community, not in a medical facility.

Poverty. In most cases, the seriously mentally ill live below the poverty level and barely meet their subsistence needs.

Substance abuse has burgeoned among the mentally ill, creating a more severe form of mental illness euphemistically labeled “dual diagnosis.” Alcohol and drug abuse worsens psychosis and bipolar mania and leads to treatment resistance and further deterioration.

Crime. Though the mentally ill are perceived as crime perpetrators, they are more likely to be crime victims.

Medical illness. Persons with serious mental illness suffer high rates of infection, obesity, diabetes, hyper-lipidemia, and hypertension—all of which require intensive and ongoing medical care.

Poor access to primary care. Although at high risk for cardiovascular disease, most persons with schizophrenia do not receive the most basic medical care because they do not have a primary care provider.

Early mortality. Individuals with serious mental illness die much younger than persons in the general population, forfeiting about 28 years of potential life. Interestingly, my colleagues in countries that still have psychiatric institutions tell me their chronically mentally ill patients often live to old age.

Lack of stable or signi?cant relationships. Most of the seriously mentally ill live an isolated life of quiet desperation and loneliness. They do not know how to make friends. State hospitals offered access to social and recreational activities where patients could regularly meet others, make friends, and maybe even find a sexual partner.

Social and vocational disability and stigma. The seriously mentally ill are stigmatized in many ways and have little chance of employment. In state hospitals, supervised work therapy enabled many to work in the bakery, laundry, wood shop, or on the farm and provided the dignity of being part of a work community.

Deinstitutionalization failed because society’s good intentions were guided by legalisms and sociologic notions, rather than scientific principles. Serious mental disorders are neurobiologic diseases that severely limit independent functioning. Until effective treatments are found for schizophrenia’s cognitive deficits and negative symptoms, we should seek a more humane model of care. We should be bold enough to restore comprehensive long-term health care facilities where patients’ mental and physical illnesses can be stabilized and they can achieve supervised autonomy through evidence-based biopsychosocial and rehabilitative therapies.

An institutional model of care is rational for at least some persons with schizophrenia who are suffering under a politically correct system of care. Without medically driven care, the misery will continue.

Life in the womb is fraught with hazards. Any deviation from a healthy pregnancy can damage a major organ system (first trimester), impair brain structural/functional development (second trimester), or cause prematurity and low birth weight (third trimester).

So many things can go wrong in the intrauterine environment that it is miraculous most babies are born with no apparent physical malformations. But behavioral teratogenesis is more subtle than physical defects and might not manifest until years later. Numerous studies have linked prenatal and obstetric complications to serious psychiatric disorders later in childhood or adulthood.

No wonder, then, that the pharmacologic management of mentally ill pregnant women is a high-stakes challenge. Consider the article in this issue by Louann Brizendine et al on treating anxiety during pregnancy with selective serotonin reuptake inhibitors vs benzodiazepines (page 38).

Risk vs benefit. Psychotropics can have unpredictable, serious effects on fetal growth and development, but fetal repercussions may be equally devastating if we do not stabilize the mentally ill mother and guard her against self-neglect, nonadherence to prenatal care, suicide, or infanticide. Thus, the benefit: risk ratio is sufficiently high to justify pharmacologic intervention during pregnancy—with the requisite caution this treatment deserves.

The greatest risk to the fetus is teratogenicity, which 1 review article¹ defined as “the dysgenesis of fetal organs as evidenced either structurally or functionally (eg, brain functions). The typical manifestations of teratogenesis are restricted growth or death of the fetus, carcinogenesis, and malformations, defined as defects in organ structure or function. These abnormalities vary in severity (eg, hypospadias that is mild and may be missed, or is severe, necessitating several corrective operations). Major malformations may be life-threatening and require major surgery or may have serious cosmetic or functional effects.”

Because of teratogenicity concerns, pregnant women are excluded from clinical trials of investigational drugs. Thus, new drugs are not approved for use in these patients, and FDA rankings of drugs’ teratogenic potential (Table) are guided by nonblinded, noncontrolled, naturalistic, after-the-fact observations—the lowest tier of evidence-based medicine.

Table

FDA classification of medications’ teratogenic potential

Proceed with caution. Against this background, I follow these principles when treating pregnant patients:

• Counsel all mentally ill women about the potential risks of conceiving while receiving a psychotropic before they consider pregnancy. Counseling should include all prescription and nonprescription drugs.
• Obtain a family history of psychiatric disorders from all pregnant patients.
• Make an accurate psychiatric diagnosis in pregnant patients, and assess the risks of providing vs withholding needed pharmacotherapy.
• Use nondrug treatments (if evidence-based) before medications. Options include behavioral therapies, interpersonal therapy, supportive therapy, and somatic treatments such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and light therapy.
• When using psychotropics, select the lowest-risk agents (Category A) first, and use the lowest efficacious dose.
• Collaborate with the patient’s obstetrician. I coined the term “psychiatric dystocia” to describe the complicating potential of mental illness on pregnancy.
• Completely avoid drugs with established teratogenicity, and educate the patient not to take these drugs if another physician prescribes them to her.
• Prescribe high-dose folate (4 to 5 mg/d) for psychotic, bipolar, or depressed pregnant patients to protect against neural tube defects and enhance fetal CNS development.
• Regularly check the patient’s nutrition, sleep hygiene, substance use (smoking, alcohol, coffee, illicit drugs), and use of over-the-counter supplements.
• Use stress-reduction techniques to reduce potential deleterious effects of stress-induced hypercortisolemia on the fetus, and involve the patient’s partner.
• See the mentally ill pregnant patient frequently for check-ups on response and/or side effects.
• Arrange for a child psychiatrist to examine the infant of a seriously mentally ill patient shortly after birth. A newborn’s irritability, crankiness, or insomnia may be perceived as withdrawal symptoms or behavioral teratogenesis, whereas it could very well be a genetically inherited temperament instability from a mother suffering from anxiety, depression, or psychosis.

Helping the mother without harming the child is like walking a tightrope: it calls upon all our skills, experience, and sound judgment.

P.S. To help you manage potential medico-legal issues such as prescribing during pregnancy, Current Psychiatry welcomes Douglas Mossman, MD, as editor of Malpractice Rx. This month, Dr. Mossman discusses documentation and invites you to submit questions about liability.

Life in the womb is fraught with hazards. Any deviation from a healthy pregnancy can damage a major organ system (first trimester), impair brain structural/functional development (second trimester), or cause prematurity and low birth weight (third trimester).

So many things can go wrong in the intrauterine environment that it is miraculous most babies are born with no apparent physical malformations. But behavioral teratogenesis is more subtle than physical defects and might not manifest until years later. Numerous studies have linked prenatal and obstetric complications to serious psychiatric disorders later in childhood or adulthood.

No wonder, then, that the pharmacologic management of mentally ill pregnant women is a high-stakes challenge. Consider the article in this issue by Louann Brizendine et al on treating anxiety during pregnancy with selective serotonin reuptake inhibitors vs benzodiazepines (page 38).

Risk vs benefit. Psychotropics can have unpredictable, serious effects on fetal growth and development, but fetal repercussions may be equally devastating if we do not stabilize the mentally ill mother and guard her against self-neglect, nonadherence to prenatal care, suicide, or infanticide. Thus, the benefit: risk ratio is sufficiently high to justify pharmacologic intervention during pregnancy—with the requisite caution this treatment deserves.

The greatest risk to the fetus is teratogenicity, which 1 review article¹ defined as “the dysgenesis of fetal organs as evidenced either structurally or functionally (eg, brain functions). The typical manifestations of teratogenesis are restricted growth or death of the fetus, carcinogenesis, and malformations, defined as defects in organ structure or function. These abnormalities vary in severity (eg, hypospadias that is mild and may be missed, or is severe, necessitating several corrective operations). Major malformations may be life-threatening and require major surgery or may have serious cosmetic or functional effects.”

Because of teratogenicity concerns, pregnant women are excluded from clinical trials of investigational drugs. Thus, new drugs are not approved for use in these patients, and FDA rankings of drugs’ teratogenic potential (Table) are guided by nonblinded, noncontrolled, naturalistic, after-the-fact observations—the lowest tier of evidence-based medicine.

Table

FDA classification of medications’ teratogenic potential

Proceed with caution. Against this background, I follow these principles when treating pregnant patients:

• Counsel all mentally ill women about the potential risks of conceiving while receiving a psychotropic before they consider pregnancy. Counseling should include all prescription and nonprescription drugs.
• Obtain a family history of psychiatric disorders from all pregnant patients.
• Make an accurate psychiatric diagnosis in pregnant patients, and assess the risks of providing vs withholding needed pharmacotherapy.
• Use nondrug treatments (if evidence-based) before medications. Options include behavioral therapies, interpersonal therapy, supportive therapy, and somatic treatments such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and light therapy.
• When using psychotropics, select the lowest-risk agents (Category A) first, and use the lowest efficacious dose.
• Collaborate with the patient’s obstetrician. I coined the term “psychiatric dystocia” to describe the complicating potential of mental illness on pregnancy.
• Completely avoid drugs with established teratogenicity, and educate the patient not to take these drugs if another physician prescribes them to her.
• Prescribe high-dose folate (4 to 5 mg/d) for psychotic, bipolar, or depressed pregnant patients to protect against neural tube defects and enhance fetal CNS development.
• Regularly check the patient’s nutrition, sleep hygiene, substance use (smoking, alcohol, coffee, illicit drugs), and use of over-the-counter supplements.
• Use stress-reduction techniques to reduce potential deleterious effects of stress-induced hypercortisolemia on the fetus, and involve the patient’s partner.
• See the mentally ill pregnant patient frequently for check-ups on response and/or side effects.
• Arrange for a child psychiatrist to examine the infant of a seriously mentally ill patient shortly after birth. A newborn’s irritability, crankiness, or insomnia may be perceived as withdrawal symptoms or behavioral teratogenesis, whereas it could very well be a genetically inherited temperament instability from a mother suffering from anxiety, depression, or psychosis.

Helping the mother without harming the child is like walking a tightrope: it calls upon all our skills, experience, and sound judgment.

P.S. To help you manage potential medico-legal issues such as prescribing during pregnancy, Current Psychiatry welcomes Douglas Mossman, MD, as editor of Malpractice Rx. This month, Dr. Mossman discusses documentation and invites you to submit questions about liability.

Life in the womb is fraught with hazards. Any deviation from a healthy pregnancy can damage a major organ system (first trimester), impair brain structural/functional development (second trimester), or cause prematurity and low birth weight (third trimester).

So many things can go wrong in the intrauterine environment that it is miraculous most babies are born with no apparent physical malformations. But behavioral teratogenesis is more subtle than physical defects and might not manifest until years later. Numerous studies have linked prenatal and obstetric complications to serious psychiatric disorders later in childhood or adulthood.

No wonder, then, that the pharmacologic management of mentally ill pregnant women is a high-stakes challenge. Consider the article in this issue by Louann Brizendine et al on treating anxiety during pregnancy with selective serotonin reuptake inhibitors vs benzodiazepines (page 38).

Risk vs benefit. Psychotropics can have unpredictable, serious effects on fetal growth and development, but fetal repercussions may be equally devastating if we do not stabilize the mentally ill mother and guard her against self-neglect, nonadherence to prenatal care, suicide, or infanticide. Thus, the benefit: risk ratio is sufficiently high to justify pharmacologic intervention during pregnancy—with the requisite caution this treatment deserves.

The greatest risk to the fetus is teratogenicity, which 1 review article¹ defined as “the dysgenesis of fetal organs as evidenced either structurally or functionally (eg, brain functions). The typical manifestations of teratogenesis are restricted growth or death of the fetus, carcinogenesis, and malformations, defined as defects in organ structure or function. These abnormalities vary in severity (eg, hypospadias that is mild and may be missed, or is severe, necessitating several corrective operations). Major malformations may be life-threatening and require major surgery or may have serious cosmetic or functional effects.”

Because of teratogenicity concerns, pregnant women are excluded from clinical trials of investigational drugs. Thus, new drugs are not approved for use in these patients, and FDA rankings of drugs’ teratogenic potential (Table) are guided by nonblinded, noncontrolled, naturalistic, after-the-fact observations—the lowest tier of evidence-based medicine.

Table

FDA classification of medications’ teratogenic potential

Proceed with caution. Against this background, I follow these principles when treating pregnant patients:

• Counsel all mentally ill women about the potential risks of conceiving while receiving a psychotropic before they consider pregnancy. Counseling should include all prescription and nonprescription drugs.
• Obtain a family history of psychiatric disorders from all pregnant patients.
• Make an accurate psychiatric diagnosis in pregnant patients, and assess the risks of providing vs withholding needed pharmacotherapy.
• Use nondrug treatments (if evidence-based) before medications. Options include behavioral therapies, interpersonal therapy, supportive therapy, and somatic treatments such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and light therapy.
• When using psychotropics, select the lowest-risk agents (Category A) first, and use the lowest efficacious dose.
• Collaborate with the patient’s obstetrician. I coined the term “psychiatric dystocia” to describe the complicating potential of mental illness on pregnancy.
• Completely avoid drugs with established teratogenicity, and educate the patient not to take these drugs if another physician prescribes them to her.
• Prescribe high-dose folate (4 to 5 mg/d) for psychotic, bipolar, or depressed pregnant patients to protect against neural tube defects and enhance fetal CNS development.
• Regularly check the patient’s nutrition, sleep hygiene, substance use (smoking, alcohol, coffee, illicit drugs), and use of over-the-counter supplements.
• Use stress-reduction techniques to reduce potential deleterious effects of stress-induced hypercortisolemia on the fetus, and involve the patient’s partner.
• See the mentally ill pregnant patient frequently for check-ups on response and/or side effects.
• Arrange for a child psychiatrist to examine the infant of a seriously mentally ill patient shortly after birth. A newborn’s irritability, crankiness, or insomnia may be perceived as withdrawal symptoms or behavioral teratogenesis, whereas it could very well be a genetically inherited temperament instability from a mother suffering from anxiety, depression, or psychosis.

Helping the mother without harming the child is like walking a tightrope: it calls upon all our skills, experience, and sound judgment.

P.S. To help you manage potential medico-legal issues such as prescribing during pregnancy, Current Psychiatry welcomes Douglas Mossman, MD, as editor of Malpractice Rx. This month, Dr. Mossman discusses documentation and invites you to submit questions about liability.

Might it resolve to spend far more money on innovative research and development than on marketing?

Making New Year’s resolutions is a time-honored tradition. Whether we resolve to lose a few pounds, exercise regularly, or quit a harmful habit, we all partake in self-improvement as the new year dawns.

What would a large corporation resolve to do in the new year? We can only imagine, but a corporation that discovers and manufactures CNS pharmaceuticals might resolve to:

1. Test new drugs in patients who resemble “real world” patients, not just in patients with no medical problems, no substance abuse, and no history of treatment resistance.

2. Develop drugs with new mechanisms, not just another “me too” agent.

3. Publish all data (positive and negative), not just favorable results.

4. Develop drugs for children, rather than following the tradition of developing drugs for adults and then waiting many years (during which practitioners use those drugs off-label in children) before finally conducting trials to secure FDA approval of pediatric indications.

5. Conduct studies to guide practitioners about the safety of new drugs in pregnant women with mental illness.

6. Spend far more money on innovative research and development than on marketing.

7. Kick the habit of direct-to-consumer marketing, so that physicians can prescribe the best agent in their clinical judgment, not the drug the patient demands because she saw it on TV.

8. Accelerate the discovery of pharmacogenomic biomarkers to help match drug and patient, maximize efficacy, and minimize serious side effects.

9. Be more transparent about the fact that many clinical trials are being conducted in developing countries because U.S.-based trials have become too expensive and pose other “disadvantages” (such as a higher placebo response rate and more side effect complaints).

10. Establish mutually beneficial partnerships with the National Institutes of Health and academic research institutes to translate neurobiological discoveries into new and physiology-driven pharmacotherapeutic interventions.

11. Pool grants with competitors so that continuing medical education (CME) programs are no longer sponsored by a single company and are designed without real or perceived influence by an industry sponsor.

12. Better inform the public about the pharmaceutical industry’s positive aspects, such as being the only U.S. industry that: a) develops new medications for disabling psychiatric disorders; b) donates billions of dollars worth of drug samples to indigent or uninsured community patients; and c) provides hundreds of thousands of well-paying jobs for scientists, managers, and sales representatives.

13. Remind the world that hundreds of disabling and fatal diseases still have no available treatments, and a huge financial investment and years of basic and clinic research are needed to discover the needed treatments for them.

14. Justify the high cost of new drugs by demonstrating how profits are ploughed into discovering new drugs (in other words, show convincingly that the pharmaceutical industry works for the public good, not just for shareholders).

15. Stop buying lunches for doctors who attend speaker programs, and instead make donations to their designated charities.

I cannot vouch that this fictional account of a pharmaceutical company’s New Year’s resolutions reflects reality. But if it does, I wonder if such resolutions—like those of almost all of us—would falter soon after the new year starts… .

Might it resolve to spend far more money on innovative research and development than on marketing?

Making New Year’s resolutions is a time-honored tradition. Whether we resolve to lose a few pounds, exercise regularly, or quit a harmful habit, we all partake in self-improvement as the new year dawns.

What would a large corporation resolve to do in the new year? We can only imagine, but a corporation that discovers and manufactures CNS pharmaceuticals might resolve to:

1. Test new drugs in patients who resemble “real world” patients, not just in patients with no medical problems, no substance abuse, and no history of treatment resistance.

2. Develop drugs with new mechanisms, not just another “me too” agent.

3. Publish all data (positive and negative), not just favorable results.

4. Develop drugs for children, rather than following the tradition of developing drugs for adults and then waiting many years (during which practitioners use those drugs off-label in children) before finally conducting trials to secure FDA approval of pediatric indications.

5. Conduct studies to guide practitioners about the safety of new drugs in pregnant women with mental illness.

6. Spend far more money on innovative research and development than on marketing.

7. Kick the habit of direct-to-consumer marketing, so that physicians can prescribe the best agent in their clinical judgment, not the drug the patient demands because she saw it on TV.

8. Accelerate the discovery of pharmacogenomic biomarkers to help match drug and patient, maximize efficacy, and minimize serious side effects.

9. Be more transparent about the fact that many clinical trials are being conducted in developing countries because U.S.-based trials have become too expensive and pose other “disadvantages” (such as a higher placebo response rate and more side effect complaints).

10. Establish mutually beneficial partnerships with the National Institutes of Health and academic research institutes to translate neurobiological discoveries into new and physiology-driven pharmacotherapeutic interventions.

11. Pool grants with competitors so that continuing medical education (CME) programs are no longer sponsored by a single company and are designed without real or perceived influence by an industry sponsor.

12. Better inform the public about the pharmaceutical industry’s positive aspects, such as being the only U.S. industry that: a) develops new medications for disabling psychiatric disorders; b) donates billions of dollars worth of drug samples to indigent or uninsured community patients; and c) provides hundreds of thousands of well-paying jobs for scientists, managers, and sales representatives.

13. Remind the world that hundreds of disabling and fatal diseases still have no available treatments, and a huge financial investment and years of basic and clinic research are needed to discover the needed treatments for them.

14. Justify the high cost of new drugs by demonstrating how profits are ploughed into discovering new drugs (in other words, show convincingly that the pharmaceutical industry works for the public good, not just for shareholders).

15. Stop buying lunches for doctors who attend speaker programs, and instead make donations to their designated charities.

I cannot vouch that this fictional account of a pharmaceutical company’s New Year’s resolutions reflects reality. But if it does, I wonder if such resolutions—like those of almost all of us—would falter soon after the new year starts… .

Might it resolve to spend far more money on innovative research and development than on marketing?

Making New Year’s resolutions is a time-honored tradition. Whether we resolve to lose a few pounds, exercise regularly, or quit a harmful habit, we all partake in self-improvement as the new year dawns.

What would a large corporation resolve to do in the new year? We can only imagine, but a corporation that discovers and manufactures CNS pharmaceuticals might resolve to:

1. Test new drugs in patients who resemble “real world” patients, not just in patients with no medical problems, no substance abuse, and no history of treatment resistance.

2. Develop drugs with new mechanisms, not just another “me too” agent.

3. Publish all data (positive and negative), not just favorable results.

4. Develop drugs for children, rather than following the tradition of developing drugs for adults and then waiting many years (during which practitioners use those drugs off-label in children) before finally conducting trials to secure FDA approval of pediatric indications.

5. Conduct studies to guide practitioners about the safety of new drugs in pregnant women with mental illness.

6. Spend far more money on innovative research and development than on marketing.

7. Kick the habit of direct-to-consumer marketing, so that physicians can prescribe the best agent in their clinical judgment, not the drug the patient demands because she saw it on TV.

8. Accelerate the discovery of pharmacogenomic biomarkers to help match drug and patient, maximize efficacy, and minimize serious side effects.

9. Be more transparent about the fact that many clinical trials are being conducted in developing countries because U.S.-based trials have become too expensive and pose other “disadvantages” (such as a higher placebo response rate and more side effect complaints).

10. Establish mutually beneficial partnerships with the National Institutes of Health and academic research institutes to translate neurobiological discoveries into new and physiology-driven pharmacotherapeutic interventions.

11. Pool grants with competitors so that continuing medical education (CME) programs are no longer sponsored by a single company and are designed without real or perceived influence by an industry sponsor.

12. Better inform the public about the pharmaceutical industry’s positive aspects, such as being the only U.S. industry that: a) develops new medications for disabling psychiatric disorders; b) donates billions of dollars worth of drug samples to indigent or uninsured community patients; and c) provides hundreds of thousands of well-paying jobs for scientists, managers, and sales representatives.

13. Remind the world that hundreds of disabling and fatal diseases still have no available treatments, and a huge financial investment and years of basic and clinic research are needed to discover the needed treatments for them.

14. Justify the high cost of new drugs by demonstrating how profits are ploughed into discovering new drugs (in other words, show convincingly that the pharmaceutical industry works for the public good, not just for shareholders).

15. Stop buying lunches for doctors who attend speaker programs, and instead make donations to their designated charities.

I cannot vouch that this fictional account of a pharmaceutical company’s New Year’s resolutions reflects reality. But if it does, I wonder if such resolutions—like those of almost all of us—would falter soon after the new year starts… .

Ask any mental health professional to give an example of a major psychotic disorder, and the most likely answer would be schizophrenia. But is schizophrenia really a psychotic disorder? And if not, then what is it, and how do you explain the psychotic symptoms associated with the disorder?

Research and clinical observation tell us that psychosis is a secondary feature of schizophrenia. This brain disease’s enduring and most disabling components are cognitive deficits and negative symptoms, both of which have been shown to precede the onset of psychotic symptoms. Because the core deficit is cognition—especially short-term memory and executive functions—individuals with schizophrenia are unable to return to the classroom or hold a job even when medications have suppressed their psychotic symptoms. Impaired social cognition can:

• masquerade as negative symptoms, such as poor social skills
• result in positive symptoms, such as ideas of reference or paranoid delusions, when the individual with schizophrenia misperceives ordinary social cues as “threats.”

Cognitive aberrations, including perceptual distortion, also contribute to delusions and hallucinations. Persons with schizophrenia are rarely identified as “ill” or hospitalized for acute psychiatric care until their behavior becomes bizarre with the appearance of psychotic symptoms. In fact, most practitioners do not apply the diagnostic label of schizophrenia until the individual manifests delusions, hallucinations, and bizarre behavior, and rarely—if ever—are cognitive functions assessed during initial evaluations (except in research settings). It may be that psychosis emerges as a consequence of cognitive deficits caused by adverse neurodevelopment and neurodegenerative and neurochemical changes.

Psychosis in medical disorders. Many genetically transmitted medical disorders can manifest with psychotic symptoms but are never labeled “psychotic disorders.” Examples include albinism, congenital adrenal hyperplasia, erythropoietic protoporphyria, Fabry’s disease, familial basal ganglia calcification, G6PD deficiency, Gaucher’s disease, hemochromatosis, Huntington’s chorea, hyperasparaginism, ichthyosis vulgaris, Kartagener’s syndrome, Klinefelter’s syndrome (karyotype 47,XXY), metachromatic leukodystrophy, Niemann-Pick disease, phenylketonuria, acute intermittent porphyria, Turner’s syndrome, and Wilson’s disease.

Medical disorders that include occasional psychotic symptoms may share neurobiologic features with schizophrenia and could provide clues about the neural pathways that generate delusions or hallucinations. But few of these disorders share schizophrenia’s core features of adverse neuroplastic changes and clusters of cognitive dysfunction and negative symptoms.

Targeting cognitive dysfunction in schizophrenia. Researchers are seeking ways to improve short-term memory and executive function in persons with schizophrenia, whose scores on these cognitive measures fall 1 to 3 standard deviations below the average of the general population. The National Institute of Mental Health, for example, has funded the MATRICS initiative (Measurement and Treatment Research to prove Cognition in Schizophrenia). Several candidate drugs that may serve as possible “cognitive enhancers” are being tested—for use in combination with antipsychotics—to help individuals with schizophrenia function better in social and employment settings.

Will negative symptoms—and even some positive symptoms—be ameliorated when cognition is improved? We’ll have to wait and see.

Perhaps DSM-V—planned to appear around 2012— should reconceptualize schizophrenia as a neurodevelopmental/neurodegenerative disorder characterized by a deficit syndrome and cognitive dysfunction, with intermittent secondary psychotic episodes. Or maybe we can go back to Kraepelin’s prescient nomenclature: dementia praecox!

Ask any mental health professional to give an example of a major psychotic disorder, and the most likely answer would be schizophrenia. But is schizophrenia really a psychotic disorder? And if not, then what is it, and how do you explain the psychotic symptoms associated with the disorder?

Research and clinical observation tell us that psychosis is a secondary feature of schizophrenia. This brain disease’s enduring and most disabling components are cognitive deficits and negative symptoms, both of which have been shown to precede the onset of psychotic symptoms. Because the core deficit is cognition—especially short-term memory and executive functions—individuals with schizophrenia are unable to return to the classroom or hold a job even when medications have suppressed their psychotic symptoms. Impaired social cognition can:

• masquerade as negative symptoms, such as poor social skills
• result in positive symptoms, such as ideas of reference or paranoid delusions, when the individual with schizophrenia misperceives ordinary social cues as “threats.”

Cognitive aberrations, including perceptual distortion, also contribute to delusions and hallucinations. Persons with schizophrenia are rarely identified as “ill” or hospitalized for acute psychiatric care until their behavior becomes bizarre with the appearance of psychotic symptoms. In fact, most practitioners do not apply the diagnostic label of schizophrenia until the individual manifests delusions, hallucinations, and bizarre behavior, and rarely—if ever—are cognitive functions assessed during initial evaluations (except in research settings). It may be that psychosis emerges as a consequence of cognitive deficits caused by adverse neurodevelopment and neurodegenerative and neurochemical changes.

Psychosis in medical disorders. Many genetically transmitted medical disorders can manifest with psychotic symptoms but are never labeled “psychotic disorders.” Examples include albinism, congenital adrenal hyperplasia, erythropoietic protoporphyria, Fabry’s disease, familial basal ganglia calcification, G6PD deficiency, Gaucher’s disease, hemochromatosis, Huntington’s chorea, hyperasparaginism, ichthyosis vulgaris, Kartagener’s syndrome, Klinefelter’s syndrome (karyotype 47,XXY), metachromatic leukodystrophy, Niemann-Pick disease, phenylketonuria, acute intermittent porphyria, Turner’s syndrome, and Wilson’s disease.

Medical disorders that include occasional psychotic symptoms may share neurobiologic features with schizophrenia and could provide clues about the neural pathways that generate delusions or hallucinations. But few of these disorders share schizophrenia’s core features of adverse neuroplastic changes and clusters of cognitive dysfunction and negative symptoms.

Targeting cognitive dysfunction in schizophrenia. Researchers are seeking ways to improve short-term memory and executive function in persons with schizophrenia, whose scores on these cognitive measures fall 1 to 3 standard deviations below the average of the general population. The National Institute of Mental Health, for example, has funded the MATRICS initiative (Measurement and Treatment Research to prove Cognition in Schizophrenia). Several candidate drugs that may serve as possible “cognitive enhancers” are being tested—for use in combination with antipsychotics—to help individuals with schizophrenia function better in social and employment settings.

Will negative symptoms—and even some positive symptoms—be ameliorated when cognition is improved? We’ll have to wait and see.

Perhaps DSM-V—planned to appear around 2012— should reconceptualize schizophrenia as a neurodevelopmental/neurodegenerative disorder characterized by a deficit syndrome and cognitive dysfunction, with intermittent secondary psychotic episodes. Or maybe we can go back to Kraepelin’s prescient nomenclature: dementia praecox!

Ask any mental health professional to give an example of a major psychotic disorder, and the most likely answer would be schizophrenia. But is schizophrenia really a psychotic disorder? And if not, then what is it, and how do you explain the psychotic symptoms associated with the disorder?

Research and clinical observation tell us that psychosis is a secondary feature of schizophrenia. This brain disease’s enduring and most disabling components are cognitive deficits and negative symptoms, both of which have been shown to precede the onset of psychotic symptoms. Because the core deficit is cognition—especially short-term memory and executive functions—individuals with schizophrenia are unable to return to the classroom or hold a job even when medications have suppressed their psychotic symptoms. Impaired social cognition can:

• masquerade as negative symptoms, such as poor social skills
• result in positive symptoms, such as ideas of reference or paranoid delusions, when the individual with schizophrenia misperceives ordinary social cues as “threats.”

Cognitive aberrations, including perceptual distortion, also contribute to delusions and hallucinations. Persons with schizophrenia are rarely identified as “ill” or hospitalized for acute psychiatric care until their behavior becomes bizarre with the appearance of psychotic symptoms. In fact, most practitioners do not apply the diagnostic label of schizophrenia until the individual manifests delusions, hallucinations, and bizarre behavior, and rarely—if ever—are cognitive functions assessed during initial evaluations (except in research settings). It may be that psychosis emerges as a consequence of cognitive deficits caused by adverse neurodevelopment and neurodegenerative and neurochemical changes.

Psychosis in medical disorders. Many genetically transmitted medical disorders can manifest with psychotic symptoms but are never labeled “psychotic disorders.” Examples include albinism, congenital adrenal hyperplasia, erythropoietic protoporphyria, Fabry’s disease, familial basal ganglia calcification, G6PD deficiency, Gaucher’s disease, hemochromatosis, Huntington’s chorea, hyperasparaginism, ichthyosis vulgaris, Kartagener’s syndrome, Klinefelter’s syndrome (karyotype 47,XXY), metachromatic leukodystrophy, Niemann-Pick disease, phenylketonuria, acute intermittent porphyria, Turner’s syndrome, and Wilson’s disease.

Medical disorders that include occasional psychotic symptoms may share neurobiologic features with schizophrenia and could provide clues about the neural pathways that generate delusions or hallucinations. But few of these disorders share schizophrenia’s core features of adverse neuroplastic changes and clusters of cognitive dysfunction and negative symptoms.

Targeting cognitive dysfunction in schizophrenia. Researchers are seeking ways to improve short-term memory and executive function in persons with schizophrenia, whose scores on these cognitive measures fall 1 to 3 standard deviations below the average of the general population. The National Institute of Mental Health, for example, has funded the MATRICS initiative (Measurement and Treatment Research to prove Cognition in Schizophrenia). Several candidate drugs that may serve as possible “cognitive enhancers” are being tested—for use in combination with antipsychotics—to help individuals with schizophrenia function better in social and employment settings.

Will negative symptoms—and even some positive symptoms—be ameliorated when cognition is improved? We’ll have to wait and see.

Perhaps DSM-V—planned to appear around 2012— should reconceptualize schizophrenia as a neurodevelopmental/neurodegenerative disorder characterized by a deficit syndrome and cognitive dysfunction, with intermittent secondary psychotic episodes. Or maybe we can go back to Kraepelin’s prescient nomenclature: dementia praecox!

Polypharmacy has been a 4-letter word for a long time in schizophrenia management. Prescribing more than 1 antipsychotic to a patient with refractory symptoms has evoked images of a potentially harmful, nonevidence-based cocktail with no proven advantage over monotherapy.

Compare schizophrenia with bipolar disorder, for which combination therapy—an antipsychotic plus a mood stabilizer plus an antidepressant/ antianxiety agent—is the standard of care. Similarly, augmentation therapy is viewed as necessary for difficult cases of unipolar depression.

In the United States, approximately 40% of schizophrenia patients receive 2 or more concomitant antipsychotics (atypical and conventional agents).¹ Clearly, many clinicians resort to antipsychotic polypharmacy in a desperate attempt to manage chronic, treatment-resistant illness, even though no published data support this practice.

This situation may be changing, however, because of evolving under-standings of schizophrenia’s neurobiology. Before long, clinicians may employ concomitant agents with different mechanisms in novel approaches to improve outcomes in patients with schizophrenia.

Novel polypharmacy. The dopamine pathways approach is inadequate for achieving true remission across all of chronic schizophrenia’s symptom domains. Positive and negative symptoms and cognitive impairment that persist despite antipsychotic therapy call for new treatment approaches. Here are some of my speculations—suggested by emerging data about schizophrenia’s pathophysiology—about “futuristic” adjuncts to antipsychotics:

Add a glutamate modulator (such as lamotrigine). This combination has shown benefit in patients who have not responded to clozapine.² Many lines of evidence show that the glutamate system is impaired in schizophrenia, and this approach is promising.

Add a GABA agonist (such as valproate or benzodiazepines). Recent findings of a GABA deficit in frontal lobe chandelier cells in schizophrenia gives this combination legitimacy.³

Add an anti-inflammatory agent (such as a COX-2 inhibitor). Several studies report increased inflammatory cytokines in patients with schizophrenia. Others have found an antipsychotic/anti-inflammatory combination more efficacious than an antipsychotic alone.⁴

Add a cognitive enhancing agent. Antipsychotics as monotherapy fail to reverse schizophrenia’s severe cognitive deficits (~2 standard deviations below healthy individuals’ cognition).The National Institute of Mental Health-sponsored MATRICS initiative (Measurement and Treatment Research to Improve Cognition in Schizophrenia)⁵ is testing potential neuro-protective and myelin-repair agents to improve deficits in memory, attention, and executive function in schizophrenia. Potential mechanisms include alpha 7 nicotinic receptor agonists, D1 receptor agonists, or AMPA glutamatergic receptor agonists. These agents might become available in a few years.

Add a neuroprotective agent. As a neurodegenerative disorder, schizophrenia could benefit from induction of neurotrophic factors (such as nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], or vascular endothelial growth factor [VEGF]) and neurogenesis stimulation. Atypical antipsychotics —but not typical agents—have shown neurotrophic activity,⁶ but combining them with other neurotrophic agents such as lithium or selective serotonin reuptake inhibitors⁷ might expedite brain tissue regeneration and improve patients’ function.

Add a myelin repair agent. Many schizophrenia studies suggest impaired myelin (white-matter) structure, which may explain the “disconnection” among brain regions that results in thought disorder. A recent report indicates that citalopram restored white-matter integrity in patients with obsessive-compulsive disorder after a few weeks of use.⁸ If these results are replicated in schizophrenia, antipsychotic-myelin repair agent combinations may become a rational polypharmacy.

What lies ahead. Future schizophrenia treatment almost certainly will include drug combinations that:

• address clinical domains not managed with current antipsychotic monotherapy
• help override treatment resistance or refractoriness (hallucinations or delusions).

Combinations of 3 or more drugs often are used to treat serious medical disorders such as cancer, HIV, or malignant hypertension. Management of a severe, disabling psychiatric disorder such as schizophrenia should be no less aggressive.

Polypharmacy has been a 4-letter word for a long time in schizophrenia management. Prescribing more than 1 antipsychotic to a patient with refractory symptoms has evoked images of a potentially harmful, nonevidence-based cocktail with no proven advantage over monotherapy.

Compare schizophrenia with bipolar disorder, for which combination therapy—an antipsychotic plus a mood stabilizer plus an antidepressant/ antianxiety agent—is the standard of care. Similarly, augmentation therapy is viewed as necessary for difficult cases of unipolar depression.

In the United States, approximately 40% of schizophrenia patients receive 2 or more concomitant antipsychotics (atypical and conventional agents).¹ Clearly, many clinicians resort to antipsychotic polypharmacy in a desperate attempt to manage chronic, treatment-resistant illness, even though no published data support this practice.

This situation may be changing, however, because of evolving under-standings of schizophrenia’s neurobiology. Before long, clinicians may employ concomitant agents with different mechanisms in novel approaches to improve outcomes in patients with schizophrenia.

Novel polypharmacy. The dopamine pathways approach is inadequate for achieving true remission across all of chronic schizophrenia’s symptom domains. Positive and negative symptoms and cognitive impairment that persist despite antipsychotic therapy call for new treatment approaches. Here are some of my speculations—suggested by emerging data about schizophrenia’s pathophysiology—about “futuristic” adjuncts to antipsychotics:

Add a glutamate modulator (such as lamotrigine). This combination has shown benefit in patients who have not responded to clozapine.² Many lines of evidence show that the glutamate system is impaired in schizophrenia, and this approach is promising.

Add a GABA agonist (such as valproate or benzodiazepines). Recent findings of a GABA deficit in frontal lobe chandelier cells in schizophrenia gives this combination legitimacy.³

Add an anti-inflammatory agent (such as a COX-2 inhibitor). Several studies report increased inflammatory cytokines in patients with schizophrenia. Others have found an antipsychotic/anti-inflammatory combination more efficacious than an antipsychotic alone.⁴

Add a cognitive enhancing agent. Antipsychotics as monotherapy fail to reverse schizophrenia’s severe cognitive deficits (~2 standard deviations below healthy individuals’ cognition).The National Institute of Mental Health-sponsored MATRICS initiative (Measurement and Treatment Research to Improve Cognition in Schizophrenia)⁵ is testing potential neuro-protective and myelin-repair agents to improve deficits in memory, attention, and executive function in schizophrenia. Potential mechanisms include alpha 7 nicotinic receptor agonists, D1 receptor agonists, or AMPA glutamatergic receptor agonists. These agents might become available in a few years.

Add a neuroprotective agent. As a neurodegenerative disorder, schizophrenia could benefit from induction of neurotrophic factors (such as nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], or vascular endothelial growth factor [VEGF]) and neurogenesis stimulation. Atypical antipsychotics —but not typical agents—have shown neurotrophic activity,⁶ but combining them with other neurotrophic agents such as lithium or selective serotonin reuptake inhibitors⁷ might expedite brain tissue regeneration and improve patients’ function.

Add a myelin repair agent. Many schizophrenia studies suggest impaired myelin (white-matter) structure, which may explain the “disconnection” among brain regions that results in thought disorder. A recent report indicates that citalopram restored white-matter integrity in patients with obsessive-compulsive disorder after a few weeks of use.⁸ If these results are replicated in schizophrenia, antipsychotic-myelin repair agent combinations may become a rational polypharmacy.

What lies ahead. Future schizophrenia treatment almost certainly will include drug combinations that:

• address clinical domains not managed with current antipsychotic monotherapy
• help override treatment resistance or refractoriness (hallucinations or delusions).

Combinations of 3 or more drugs often are used to treat serious medical disorders such as cancer, HIV, or malignant hypertension. Management of a severe, disabling psychiatric disorder such as schizophrenia should be no less aggressive.

Polypharmacy has been a 4-letter word for a long time in schizophrenia management. Prescribing more than 1 antipsychotic to a patient with refractory symptoms has evoked images of a potentially harmful, nonevidence-based cocktail with no proven advantage over monotherapy.

Compare schizophrenia with bipolar disorder, for which combination therapy—an antipsychotic plus a mood stabilizer plus an antidepressant/ antianxiety agent—is the standard of care. Similarly, augmentation therapy is viewed as necessary for difficult cases of unipolar depression.

In the United States, approximately 40% of schizophrenia patients receive 2 or more concomitant antipsychotics (atypical and conventional agents).¹ Clearly, many clinicians resort to antipsychotic polypharmacy in a desperate attempt to manage chronic, treatment-resistant illness, even though no published data support this practice.

This situation may be changing, however, because of evolving under-standings of schizophrenia’s neurobiology. Before long, clinicians may employ concomitant agents with different mechanisms in novel approaches to improve outcomes in patients with schizophrenia.

Novel polypharmacy. The dopamine pathways approach is inadequate for achieving true remission across all of chronic schizophrenia’s symptom domains. Positive and negative symptoms and cognitive impairment that persist despite antipsychotic therapy call for new treatment approaches. Here are some of my speculations—suggested by emerging data about schizophrenia’s pathophysiology—about “futuristic” adjuncts to antipsychotics:

Add a glutamate modulator (such as lamotrigine). This combination has shown benefit in patients who have not responded to clozapine.² Many lines of evidence show that the glutamate system is impaired in schizophrenia, and this approach is promising.

Add a GABA agonist (such as valproate or benzodiazepines). Recent findings of a GABA deficit in frontal lobe chandelier cells in schizophrenia gives this combination legitimacy.³

Add an anti-inflammatory agent (such as a COX-2 inhibitor). Several studies report increased inflammatory cytokines in patients with schizophrenia. Others have found an antipsychotic/anti-inflammatory combination more efficacious than an antipsychotic alone.⁴

Add a cognitive enhancing agent. Antipsychotics as monotherapy fail to reverse schizophrenia’s severe cognitive deficits (~2 standard deviations below healthy individuals’ cognition).The National Institute of Mental Health-sponsored MATRICS initiative (Measurement and Treatment Research to Improve Cognition in Schizophrenia)⁵ is testing potential neuro-protective and myelin-repair agents to improve deficits in memory, attention, and executive function in schizophrenia. Potential mechanisms include alpha 7 nicotinic receptor agonists, D1 receptor agonists, or AMPA glutamatergic receptor agonists. These agents might become available in a few years.

Add a neuroprotective agent. As a neurodegenerative disorder, schizophrenia could benefit from induction of neurotrophic factors (such as nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], or vascular endothelial growth factor [VEGF]) and neurogenesis stimulation. Atypical antipsychotics —but not typical agents—have shown neurotrophic activity,⁶ but combining them with other neurotrophic agents such as lithium or selective serotonin reuptake inhibitors⁷ might expedite brain tissue regeneration and improve patients’ function.

Add a myelin repair agent. Many schizophrenia studies suggest impaired myelin (white-matter) structure, which may explain the “disconnection” among brain regions that results in thought disorder. A recent report indicates that citalopram restored white-matter integrity in patients with obsessive-compulsive disorder after a few weeks of use.⁸ If these results are replicated in schizophrenia, antipsychotic-myelin repair agent combinations may become a rational polypharmacy.

What lies ahead. Future schizophrenia treatment almost certainly will include drug combinations that:

• address clinical domains not managed with current antipsychotic monotherapy
• help override treatment resistance or refractoriness (hallucinations or delusions).

Combinations of 3 or more drugs often are used to treat serious medical disorders such as cancer, HIV, or malignant hypertension. Management of a severe, disabling psychiatric disorder such as schizophrenia should be no less aggressive.

What part of the brain incorporates our moment-to-moment experiences, weaves them into coherent and interconnected verbal, spatial, and emotional memories, and enables us to be aware of our entire ‘life story’?

It’s the hippocampus, of course. Damage to this portion of the brain—as in seriously mentally ill individuals—severely impairs the ability to form new memories, with subsequent social and vocational impairment.

Interestingly, the hippocampus also is the “regeneration center” of the brain, continuously producing progenitor cells that can differentiate into neurons and glia that migrate to brain regions that need replenishment.

What does that have to do with psychiatry? A lot. It is now well established that the hippocampus is structurally and functionally impaired in several severe neuropsychiatric disorders. The hippocampus:

• fails to develop adequately in schizophrenia
• shows progressive atrophy in persons with recurrent unipolar or bipolar depression
• shrivels in severe stress disorders such as posttraumatic stress disorder (PTSD)
• is damaged by the toxicity of alcohol addiction
• is rapidly devastated in Alzheimer’s dementia.

It’s no wonder that cognitive functions—especially memory and learning—are seriously impaired in persons suffering from these disorders.

Regeneration and repair

What can psychiatrists do about our patients’ hippocampal dysfunction? There is good news on that front.

Abstinence from alcohol will reverse hippocampal damage within 6 to 12 months. Antidepressants have been found to stimulate production of new brain cells (neurogenesis) and to gradually rebuild the structure of the hippocampus in depressed individuals. Ditto for atypical (but not conventional) antipsychotics, which induce neurotrophic growth factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). NGF and BDNF facilitate survival and maturation of new neurons produced in the hippocampus. Some atypicals have been shown to prevent or reverse stress-induced suppression of neurogenesis in the hippocampus and, theoretically, prevent PTSD.

Recent studies demonstrate that antidepressants lose their clinical efficacy if neurogenesis is inhibited. This suggests that hippocampal neurogenesis—rather than neurotransmitters—may be the mechanism by which depression is lifted. Only dementia still defies efforts to halt its ruthless destruction of the hippocampus, with severe cognitive decline and a faded sense of self and the world.

Flexing the memory center

Besides medication, other practical tools can keep the hippocampus healthy (prevention) or restore its health (intervention), whether in psychiatric patients or in mentally healthy but aging individuals. These include:

• physical exercise, which stimulates neurogenesis
• stress management to reduce the neurotoxic effects of cortisol on the hippocampus
• mental exercises—such as memorizing a poem or a list of words or numbers, reading, writing, or retrieving vocabulary—all activate the hippocampus
• deep breathing several times a day to oxygenate the brain adequately (the hippocampus is the most vascularized brain region and the first to suffer from low oxygen).

We clinicians also should keep our hippocampi healthy through prevention and intervention so we can take good care of our patients.

What part of the brain incorporates our moment-to-moment experiences, weaves them into coherent and interconnected verbal, spatial, and emotional memories, and enables us to be aware of our entire ‘life story’?

It’s the hippocampus, of course. Damage to this portion of the brain—as in seriously mentally ill individuals—severely impairs the ability to form new memories, with subsequent social and vocational impairment.

Interestingly, the hippocampus also is the “regeneration center” of the brain, continuously producing progenitor cells that can differentiate into neurons and glia that migrate to brain regions that need replenishment.

What does that have to do with psychiatry? A lot. It is now well established that the hippocampus is structurally and functionally impaired in several severe neuropsychiatric disorders. The hippocampus:

• fails to develop adequately in schizophrenia
• shows progressive atrophy in persons with recurrent unipolar or bipolar depression
• shrivels in severe stress disorders such as posttraumatic stress disorder (PTSD)
• is damaged by the toxicity of alcohol addiction
• is rapidly devastated in Alzheimer’s dementia.

It’s no wonder that cognitive functions—especially memory and learning—are seriously impaired in persons suffering from these disorders.

Regeneration and repair

What can psychiatrists do about our patients’ hippocampal dysfunction? There is good news on that front.

Abstinence from alcohol will reverse hippocampal damage within 6 to 12 months. Antidepressants have been found to stimulate production of new brain cells (neurogenesis) and to gradually rebuild the structure of the hippocampus in depressed individuals. Ditto for atypical (but not conventional) antipsychotics, which induce neurotrophic growth factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). NGF and BDNF facilitate survival and maturation of new neurons produced in the hippocampus. Some atypicals have been shown to prevent or reverse stress-induced suppression of neurogenesis in the hippocampus and, theoretically, prevent PTSD.

Recent studies demonstrate that antidepressants lose their clinical efficacy if neurogenesis is inhibited. This suggests that hippocampal neurogenesis—rather than neurotransmitters—may be the mechanism by which depression is lifted. Only dementia still defies efforts to halt its ruthless destruction of the hippocampus, with severe cognitive decline and a faded sense of self and the world.

Flexing the memory center

Besides medication, other practical tools can keep the hippocampus healthy (prevention) or restore its health (intervention), whether in psychiatric patients or in mentally healthy but aging individuals. These include:

• physical exercise, which stimulates neurogenesis
• stress management to reduce the neurotoxic effects of cortisol on the hippocampus
• mental exercises—such as memorizing a poem or a list of words or numbers, reading, writing, or retrieving vocabulary—all activate the hippocampus
• deep breathing several times a day to oxygenate the brain adequately (the hippocampus is the most vascularized brain region and the first to suffer from low oxygen).

We clinicians also should keep our hippocampi healthy through prevention and intervention so we can take good care of our patients.

What part of the brain incorporates our moment-to-moment experiences, weaves them into coherent and interconnected verbal, spatial, and emotional memories, and enables us to be aware of our entire ‘life story’?

It’s the hippocampus, of course. Damage to this portion of the brain—as in seriously mentally ill individuals—severely impairs the ability to form new memories, with subsequent social and vocational impairment.

Interestingly, the hippocampus also is the “regeneration center” of the brain, continuously producing progenitor cells that can differentiate into neurons and glia that migrate to brain regions that need replenishment.

What does that have to do with psychiatry? A lot. It is now well established that the hippocampus is structurally and functionally impaired in several severe neuropsychiatric disorders. The hippocampus:

• fails to develop adequately in schizophrenia
• shows progressive atrophy in persons with recurrent unipolar or bipolar depression
• shrivels in severe stress disorders such as posttraumatic stress disorder (PTSD)
• is damaged by the toxicity of alcohol addiction
• is rapidly devastated in Alzheimer’s dementia.

It’s no wonder that cognitive functions—especially memory and learning—are seriously impaired in persons suffering from these disorders.

Regeneration and repair

What can psychiatrists do about our patients’ hippocampal dysfunction? There is good news on that front.

Abstinence from alcohol will reverse hippocampal damage within 6 to 12 months. Antidepressants have been found to stimulate production of new brain cells (neurogenesis) and to gradually rebuild the structure of the hippocampus in depressed individuals. Ditto for atypical (but not conventional) antipsychotics, which induce neurotrophic growth factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). NGF and BDNF facilitate survival and maturation of new neurons produced in the hippocampus. Some atypicals have been shown to prevent or reverse stress-induced suppression of neurogenesis in the hippocampus and, theoretically, prevent PTSD.

Recent studies demonstrate that antidepressants lose their clinical efficacy if neurogenesis is inhibited. This suggests that hippocampal neurogenesis—rather than neurotransmitters—may be the mechanism by which depression is lifted. Only dementia still defies efforts to halt its ruthless destruction of the hippocampus, with severe cognitive decline and a faded sense of self and the world.

Flexing the memory center

Besides medication, other practical tools can keep the hippocampus healthy (prevention) or restore its health (intervention), whether in psychiatric patients or in mentally healthy but aging individuals. These include:

• physical exercise, which stimulates neurogenesis
• stress management to reduce the neurotoxic effects of cortisol on the hippocampus
• mental exercises—such as memorizing a poem or a list of words or numbers, reading, writing, or retrieving vocabulary—all activate the hippocampus
• deep breathing several times a day to oxygenate the brain adequately (the hippocampus is the most vascularized brain region and the first to suffer from low oxygen).

We clinicians also should keep our hippocampi healthy through prevention and intervention so we can take good care of our patients.

Many—if not most—psychiatrists treating dementia-related psychosis in geriatric patients use second-generation antipsychotics (SGAs), a practice not approved by the FDA. Consider the following 2 emergency consultation cases:

• Mrs. A, age 76, has exhibited serious memory difficulties for >1 year. She can no longer find her way home or take care of personal needs. This morning her husband brings her to the ER after she struck him on the head with a frying pan and threatened to kill a 72-year-old widowed neighbor with whom she accused him of having an affair.
• Mr. J, age 82, was diagnosed with Alzheimer’s disease 3 years ago and resides in a nursing home. You receive a call from staff that Mr. J has become very agitated, accused his roommate of stealing his belongings, and screamed at the roommate and staff to give him his “stuff” back.

These 2 vignettes describe classic cases of psychotic symptoms occurring in the context of dementia. Both patients clearly need an antipsychotic to control their delusions and prevent them from endangering themselves and others.

SGAs vs FGAs vs placebo. Late-life dementia is associated with a 50% incidence of psychosis. These patients are extremely susceptible to neurologic movement disorders (acute parkinsonism and subsequent tardive dyskinesia [TD]) when given first-generation antipsychotics (FGAs) and far less so with SGAs. After 9 months’ exposure, geriatric patients with psychotic symptoms have been shown to be 10 times more likely to develop TD with FGAs (28%) than with SGAs (2.5%).¹

Even so, in 2005 the FDA imposed a “black-box” warning on the use of SGAs for psychosis related to dementia because the mortality rate in 17 pooled placebo-controlled dementia studies was approximately 1.7 times higher with SGAs (4.5%) compared with placebo (2.5%).² Causes of death were mostly heart-related or pneumonia.

When treating psychosis in the elderly, however, we don’t choose between an SGA and placebo but between SGAs and FGAs. Thus, the relative mortality risk of these 2 drug classes is what really matters to clinicians who prefer to use SGAs but feel inhibited by the black-box warning.

New evidence. Many practitioners might not be aware that 4 studies published since 2004 of elderly patients receiving antipsychotics have addressed the relative risk of mortality with SGAs vs FGAs. In patients age ≥65 with dementia, these studies found:

• In a 2-year U.S. retrospective review, the mortality rate was 21% among those receiving haloperidol vs approximately 5% among those receiving risperidone or olanzapine.³
• In a retrospective U.S. study of 2,890 patients who started FGAs or SGAs between 1994 and 2003, FGAs were at least as likely as SGAs to increase the risk of death. The greatest increases in risk were seen soon after patients started antipsychotic therapy and with higher dosages of FGAs.⁴
• In a 2-year prospective study of 254 very frail patients (mean age 86) in Finnish hospitals or nursing homes, neither the use of FGAs nor SGAs increased the risk of death or hospital admission. The use of restraints, however, doubled the risk of death.⁵
• In a population-based, retrospective Canadian study of 27,259 matched pairs, a statistically significant increase in mortality was seen with SGAs compared with no antipsychotic use, whether patients lived at home or in long-term-care facilities. This difference was seen 30 days after treatment started and seemed to persist to 180 days. By comparison, the mortality risk appeared to be higher with FGAs than with SGAs at all measured time points.⁶

The black-box warning on SGAs does not guide clinicians in the use of antipsychotics; it simply compares a class of drugs with placebo, and sugar pills are not an option for managing psychosis. The 4 published studies represent a more useful guide about the relative mortality risk of FGAs and SGAs. They also provide evidence that supports clinical practice in managing patients with psychosis in late-life dementia.

Many—if not most—psychiatrists treating dementia-related psychosis in geriatric patients use second-generation antipsychotics (SGAs), a practice not approved by the FDA. Consider the following 2 emergency consultation cases:

• Mrs. A, age 76, has exhibited serious memory difficulties for >1 year. She can no longer find her way home or take care of personal needs. This morning her husband brings her to the ER after she struck him on the head with a frying pan and threatened to kill a 72-year-old widowed neighbor with whom she accused him of having an affair.
• Mr. J, age 82, was diagnosed with Alzheimer’s disease 3 years ago and resides in a nursing home. You receive a call from staff that Mr. J has become very agitated, accused his roommate of stealing his belongings, and screamed at the roommate and staff to give him his “stuff” back.

These 2 vignettes describe classic cases of psychotic symptoms occurring in the context of dementia. Both patients clearly need an antipsychotic to control their delusions and prevent them from endangering themselves and others.

SGAs vs FGAs vs placebo. Late-life dementia is associated with a 50% incidence of psychosis. These patients are extremely susceptible to neurologic movement disorders (acute parkinsonism and subsequent tardive dyskinesia [TD]) when given first-generation antipsychotics (FGAs) and far less so with SGAs. After 9 months’ exposure, geriatric patients with psychotic symptoms have been shown to be 10 times more likely to develop TD with FGAs (28%) than with SGAs (2.5%).¹

Even so, in 2005 the FDA imposed a “black-box” warning on the use of SGAs for psychosis related to dementia because the mortality rate in 17 pooled placebo-controlled dementia studies was approximately 1.7 times higher with SGAs (4.5%) compared with placebo (2.5%).² Causes of death were mostly heart-related or pneumonia.

When treating psychosis in the elderly, however, we don’t choose between an SGA and placebo but between SGAs and FGAs. Thus, the relative mortality risk of these 2 drug classes is what really matters to clinicians who prefer to use SGAs but feel inhibited by the black-box warning.

New evidence. Many practitioners might not be aware that 4 studies published since 2004 of elderly patients receiving antipsychotics have addressed the relative risk of mortality with SGAs vs FGAs. In patients age ≥65 with dementia, these studies found:

• In a 2-year U.S. retrospective review, the mortality rate was 21% among those receiving haloperidol vs approximately 5% among those receiving risperidone or olanzapine.³
• In a retrospective U.S. study of 2,890 patients who started FGAs or SGAs between 1994 and 2003, FGAs were at least as likely as SGAs to increase the risk of death. The greatest increases in risk were seen soon after patients started antipsychotic therapy and with higher dosages of FGAs.⁴
• In a 2-year prospective study of 254 very frail patients (mean age 86) in Finnish hospitals or nursing homes, neither the use of FGAs nor SGAs increased the risk of death or hospital admission. The use of restraints, however, doubled the risk of death.⁵
• In a population-based, retrospective Canadian study of 27,259 matched pairs, a statistically significant increase in mortality was seen with SGAs compared with no antipsychotic use, whether patients lived at home or in long-term-care facilities. This difference was seen 30 days after treatment started and seemed to persist to 180 days. By comparison, the mortality risk appeared to be higher with FGAs than with SGAs at all measured time points.⁶

The black-box warning on SGAs does not guide clinicians in the use of antipsychotics; it simply compares a class of drugs with placebo, and sugar pills are not an option for managing psychosis. The 4 published studies represent a more useful guide about the relative mortality risk of FGAs and SGAs. They also provide evidence that supports clinical practice in managing patients with psychosis in late-life dementia.

Many—if not most—psychiatrists treating dementia-related psychosis in geriatric patients use second-generation antipsychotics (SGAs), a practice not approved by the FDA. Consider the following 2 emergency consultation cases:

• Mrs. A, age 76, has exhibited serious memory difficulties for >1 year. She can no longer find her way home or take care of personal needs. This morning her husband brings her to the ER after she struck him on the head with a frying pan and threatened to kill a 72-year-old widowed neighbor with whom she accused him of having an affair.
• Mr. J, age 82, was diagnosed with Alzheimer’s disease 3 years ago and resides in a nursing home. You receive a call from staff that Mr. J has become very agitated, accused his roommate of stealing his belongings, and screamed at the roommate and staff to give him his “stuff” back.

These 2 vignettes describe classic cases of psychotic symptoms occurring in the context of dementia. Both patients clearly need an antipsychotic to control their delusions and prevent them from endangering themselves and others.

SGAs vs FGAs vs placebo. Late-life dementia is associated with a 50% incidence of psychosis. These patients are extremely susceptible to neurologic movement disorders (acute parkinsonism and subsequent tardive dyskinesia [TD]) when given first-generation antipsychotics (FGAs) and far less so with SGAs. After 9 months’ exposure, geriatric patients with psychotic symptoms have been shown to be 10 times more likely to develop TD with FGAs (28%) than with SGAs (2.5%).¹

Even so, in 2005 the FDA imposed a “black-box” warning on the use of SGAs for psychosis related to dementia because the mortality rate in 17 pooled placebo-controlled dementia studies was approximately 1.7 times higher with SGAs (4.5%) compared with placebo (2.5%).² Causes of death were mostly heart-related or pneumonia.

When treating psychosis in the elderly, however, we don’t choose between an SGA and placebo but between SGAs and FGAs. Thus, the relative mortality risk of these 2 drug classes is what really matters to clinicians who prefer to use SGAs but feel inhibited by the black-box warning.

New evidence. Many practitioners might not be aware that 4 studies published since 2004 of elderly patients receiving antipsychotics have addressed the relative risk of mortality with SGAs vs FGAs. In patients age ≥65 with dementia, these studies found:

• In a 2-year U.S. retrospective review, the mortality rate was 21% among those receiving haloperidol vs approximately 5% among those receiving risperidone or olanzapine.³
• In a retrospective U.S. study of 2,890 patients who started FGAs or SGAs between 1994 and 2003, FGAs were at least as likely as SGAs to increase the risk of death. The greatest increases in risk were seen soon after patients started antipsychotic therapy and with higher dosages of FGAs.⁴
• In a 2-year prospective study of 254 very frail patients (mean age 86) in Finnish hospitals or nursing homes, neither the use of FGAs nor SGAs increased the risk of death or hospital admission. The use of restraints, however, doubled the risk of death.⁵
• In a population-based, retrospective Canadian study of 27,259 matched pairs, a statistically significant increase in mortality was seen with SGAs compared with no antipsychotic use, whether patients lived at home or in long-term-care facilities. This difference was seen 30 days after treatment started and seemed to persist to 180 days. By comparison, the mortality risk appeared to be higher with FGAs than with SGAs at all measured time points.⁶

The black-box warning on SGAs does not guide clinicians in the use of antipsychotics; it simply compares a class of drugs with placebo, and sugar pills are not an option for managing psychosis. The 4 published studies represent a more useful guide about the relative mortality risk of FGAs and SGAs. They also provide evidence that supports clinical practice in managing patients with psychosis in late-life dementia.

Continuing medical education (CME) has grown into a thriving educational ‘business’ whose success is highly dependent on educational grants.

The notion of a “quid pro quo” has grown among observers because the pharmaceutical industry provides most funding for CME programs in psychiatry and other specialties. Evaluations completed at that end of CME programs sometimes reflect attendees’ perception that the content has been “slanted” in favor of the sponsor’s proprietary drug(s).

Congress weighs in. The issue of potential influence by pharmaceutical industry sponsors on the content of CME programs is heating up. Congress has decided to hold hearings to investigate allegations that drug companies may be using CME programs to skew doctors’ treatment decisions or to circumvent laws against promoting off-label uses of medications. Congress wants to investigate whether a conflict of interest exists when pharmaceutical companies sponsor CME programs, especially when the speakers have received research grants, speaking honoraria, or consulting fees from the pharmaceutical sponsors.

Realities of CME. CME is required for the license renewal of physicians and nurses in all states. It is rigorously regulated by the Accreditation Council for Continuing Medical Education (ACCME), whose parent is the American Medical Association. Several thousand CME providers (including all medical schools) solicit educational grants from sponsors and offer programs in the form of grand rounds at teaching institutions, symposia, or dinner programs, etc.

Most teaching institutions have practically no internal funds to cover CME program costs, such as administrative expenses, speakers’ travel and honoraria, refreshments and meals, venue charges, printing, parking, etc. Without grants from external sponsors, CME programs would shrink drastically, and the cost of CME credits for licensure renewal would skyrocket.

‘Hands-off’ policies. Over the past 3 years, the ACCME has tightened procedures for CME content development, and drug companies are complying with these “hands-off” requirements. All have adopted a similar process whereby a grants committee reviews applications and makes decisions devoid of marketing influences. As an applicant for CME grants, I find the process to have become more elaborate and the rate of funding lower than in the past.

Expert speakers. Most CME speakers are experts in psychopharmacology and have financial relationships with more than one pharmaceutical company. Because these companies produce drugs that are in vigorous competition, it would be difficult for the speakers to assume a conflict of interest. Only good science will stand the test of competing interests.

CME programs’ depth and scope might decline and learning objectives might not be met if the speakers were not researchers or experts in the published literature of psychopharmacology.

Balance, not bias. Many CME symposia are sponsored jointly by several competing pharmaceutical companies, which reduces the likelihood that content could be skewed in favor of any particular one. At the University of Cincinnati department of psychiatry, for example, no specific drug company ever sponsors our grand rounds, and no sponsor recommends any speaker. Rather, every week we simply express our appreciation for the support of several industry grant providers listed on a slide at the beginning of each grand rounds program. In post-meeting evaluations, attendees’ perception of bias in the presentations has been close to zero since we moved to multiple sponsorship.

Ongoing evaluation of educational content for balance is absolutely essential and is required of all major CME providers. Physicians and nurses would lose a valuable component of CME programs if excessive restrictions were to shackle the free exchange of the latest basic, clinical, and translational research data. That may include controversial issues such as emerging uses of drugs for other than their approved indications.

Discussions about off-label uses of FDA-approved medications are highly relevant to medical practice and can lead to a more critical, evidence-based approach to patient care—the ultimate goal of CME programs.

Continuing medical education (CME) has grown into a thriving educational ‘business’ whose success is highly dependent on educational grants.

The notion of a “quid pro quo” has grown among observers because the pharmaceutical industry provides most funding for CME programs in psychiatry and other specialties. Evaluations completed at that end of CME programs sometimes reflect attendees’ perception that the content has been “slanted” in favor of the sponsor’s proprietary drug(s).

Congress weighs in. The issue of potential influence by pharmaceutical industry sponsors on the content of CME programs is heating up. Congress has decided to hold hearings to investigate allegations that drug companies may be using CME programs to skew doctors’ treatment decisions or to circumvent laws against promoting off-label uses of medications. Congress wants to investigate whether a conflict of interest exists when pharmaceutical companies sponsor CME programs, especially when the speakers have received research grants, speaking honoraria, or consulting fees from the pharmaceutical sponsors.

Realities of CME. CME is required for the license renewal of physicians and nurses in all states. It is rigorously regulated by the Accreditation Council for Continuing Medical Education (ACCME), whose parent is the American Medical Association. Several thousand CME providers (including all medical schools) solicit educational grants from sponsors and offer programs in the form of grand rounds at teaching institutions, symposia, or dinner programs, etc.

Most teaching institutions have practically no internal funds to cover CME program costs, such as administrative expenses, speakers’ travel and honoraria, refreshments and meals, venue charges, printing, parking, etc. Without grants from external sponsors, CME programs would shrink drastically, and the cost of CME credits for licensure renewal would skyrocket.

‘Hands-off’ policies. Over the past 3 years, the ACCME has tightened procedures for CME content development, and drug companies are complying with these “hands-off” requirements. All have adopted a similar process whereby a grants committee reviews applications and makes decisions devoid of marketing influences. As an applicant for CME grants, I find the process to have become more elaborate and the rate of funding lower than in the past.

Expert speakers. Most CME speakers are experts in psychopharmacology and have financial relationships with more than one pharmaceutical company. Because these companies produce drugs that are in vigorous competition, it would be difficult for the speakers to assume a conflict of interest. Only good science will stand the test of competing interests.

CME programs’ depth and scope might decline and learning objectives might not be met if the speakers were not researchers or experts in the published literature of psychopharmacology.

Balance, not bias. Many CME symposia are sponsored jointly by several competing pharmaceutical companies, which reduces the likelihood that content could be skewed in favor of any particular one. At the University of Cincinnati department of psychiatry, for example, no specific drug company ever sponsors our grand rounds, and no sponsor recommends any speaker. Rather, every week we simply express our appreciation for the support of several industry grant providers listed on a slide at the beginning of each grand rounds program. In post-meeting evaluations, attendees’ perception of bias in the presentations has been close to zero since we moved to multiple sponsorship.

Ongoing evaluation of educational content for balance is absolutely essential and is required of all major CME providers. Physicians and nurses would lose a valuable component of CME programs if excessive restrictions were to shackle the free exchange of the latest basic, clinical, and translational research data. That may include controversial issues such as emerging uses of drugs for other than their approved indications.

Discussions about off-label uses of FDA-approved medications are highly relevant to medical practice and can lead to a more critical, evidence-based approach to patient care—the ultimate goal of CME programs.

Continuing medical education (CME) has grown into a thriving educational ‘business’ whose success is highly dependent on educational grants.

The notion of a “quid pro quo” has grown among observers because the pharmaceutical industry provides most funding for CME programs in psychiatry and other specialties. Evaluations completed at that end of CME programs sometimes reflect attendees’ perception that the content has been “slanted” in favor of the sponsor’s proprietary drug(s).

Congress weighs in. The issue of potential influence by pharmaceutical industry sponsors on the content of CME programs is heating up. Congress has decided to hold hearings to investigate allegations that drug companies may be using CME programs to skew doctors’ treatment decisions or to circumvent laws against promoting off-label uses of medications. Congress wants to investigate whether a conflict of interest exists when pharmaceutical companies sponsor CME programs, especially when the speakers have received research grants, speaking honoraria, or consulting fees from the pharmaceutical sponsors.

Realities of CME. CME is required for the license renewal of physicians and nurses in all states. It is rigorously regulated by the Accreditation Council for Continuing Medical Education (ACCME), whose parent is the American Medical Association. Several thousand CME providers (including all medical schools) solicit educational grants from sponsors and offer programs in the form of grand rounds at teaching institutions, symposia, or dinner programs, etc.

Most teaching institutions have practically no internal funds to cover CME program costs, such as administrative expenses, speakers’ travel and honoraria, refreshments and meals, venue charges, printing, parking, etc. Without grants from external sponsors, CME programs would shrink drastically, and the cost of CME credits for licensure renewal would skyrocket.

‘Hands-off’ policies. Over the past 3 years, the ACCME has tightened procedures for CME content development, and drug companies are complying with these “hands-off” requirements. All have adopted a similar process whereby a grants committee reviews applications and makes decisions devoid of marketing influences. As an applicant for CME grants, I find the process to have become more elaborate and the rate of funding lower than in the past.

Expert speakers. Most CME speakers are experts in psychopharmacology and have financial relationships with more than one pharmaceutical company. Because these companies produce drugs that are in vigorous competition, it would be difficult for the speakers to assume a conflict of interest. Only good science will stand the test of competing interests.

CME programs’ depth and scope might decline and learning objectives might not be met if the speakers were not researchers or experts in the published literature of psychopharmacology.

Balance, not bias. Many CME symposia are sponsored jointly by several competing pharmaceutical companies, which reduces the likelihood that content could be skewed in favor of any particular one. At the University of Cincinnati department of psychiatry, for example, no specific drug company ever sponsors our grand rounds, and no sponsor recommends any speaker. Rather, every week we simply express our appreciation for the support of several industry grant providers listed on a slide at the beginning of each grand rounds program. In post-meeting evaluations, attendees’ perception of bias in the presentations has been close to zero since we moved to multiple sponsorship.

Ongoing evaluation of educational content for balance is absolutely essential and is required of all major CME providers. Physicians and nurses would lose a valuable component of CME programs if excessive restrictions were to shackle the free exchange of the latest basic, clinical, and translational research data. That may include controversial issues such as emerging uses of drugs for other than their approved indications.

Discussions about off-label uses of FDA-approved medications are highly relevant to medical practice and can lead to a more critical, evidence-based approach to patient care—the ultimate goal of CME programs.