Office of Mental Health

Office of Mental Health

Commissioner Michael F. Hogan, PhD

Governor David A. Paterson

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OMH Advisory on Antipsychotic Medications

November 21, 2008
Lloyd I. Sederer, MD
Lewis A. Opler, MD, PhD
Jeffrey A. Lieberman, MD

Antipsychotic medications (APs) are an essential component of the treatment of schizophrenia, schizoaffective disorders, and other serious and persistent mental illnesses when individuals suffer with psychotic symptoms such as hallucinations and delusions, as well as agitated or strange behaviors. There is very good evidence that people with schizophrenia who do not remain on APs will have over twice the rate of relapse into acute psychosis resulting in loss of social and occupational functioning as well as increased risk for hospitalization, incarceration and homelessness. There is a range of old and new AP's with variable effectiveness and side effects for each individua l– many serious, including significant weight gain, effects on the heart and metabolism, and neurological problems. Therefore consumers, families and physicians await development of medicines that offer better relief from symptoms and loss of functioning along with fewer side effects – and face complex decisions together about how to use antipsychotic medications.

As researchers have explored the effects of APs on the brain, two divergent findings have emerged: the neuroprotective and neurotoxic effects of these medications. Neuroprotective means an effect of a medication (or other intervention) that is beneficial to the brain. Neurotoxic means an effect that is damaging to the brain. To complicate matters, they are not mutually exclusive of one another, which is to say both can exist with the same medications in the same person. APs may have direct positive or negative effects on the cells in the brain; or may impart their effects indirectly by preventing progression of a disease that itself damages the brain (as schizophrenia can) or by limiting brain activity that may be necessary for the health and responsiveness of brain tissue (for example by decreasing brain activity needed for cell maintenance or development). As with other areas of schizophrenia treatment, we generally do not have definitive scientific information about either the protective or toxic impact of AP's. At the same time, there is considerable evidence but no conclusive proof that prolonged psychosis itself damages the brain.

While researchers explore these critical questions, what can we say and what clinical course can we pursue today?

We can say:

Psychosis is a deeply unsettling illness that causes great suffering and burden for the person affected and his or her loved ones
Individuals with serious and persistent mental illnesses with psychotic symptoms are at far greater risk for relapse into psychosis if they do not take APs
APs are far more effective when combined with illness management and recovery, family psychoeducation, school or work, recognition and treatment of any co-occurring drug or alcohol problem, and reliable and safe housing
Repeated episodes of psychosis are bad for people in that they are disruptive to people's lives and associated with poorer functioning and quality of life
Both older and newer AP's vary in their effectiveness and side effects, generally and also in terms of how an individual will respond. Medication treatment is thus best a long-term collaboration between patient and prescriber to find the treatment that works best with the least and most tolerable side effects.
The time between becoming psychotically ill and beginning an antipsychotic medication (untreated psychosis) is crucial since the longer the delay the more likely there will be poorer long term functional outcomes
There is not good evidence to support the use of APs before the onset of psychotic symptoms (e.g. as a preventive measure); because of the risks and side effects of AP treatment this is considered ill-advised
Because of the substantial side effects of AP treatment as well as uncertainty about the full long term impact of medication use, treatment at the minimum effective dosage of a chosen medication is medically appropriate
Research findings on APs can vary substantially or not pertain to all people affected by a disease as a result of
different MRI or other imaging machines and techniques that are used
individual functioning prior to developing a psychotic illness (so called “pre-morbid” functioning is a strong predictor of long term outcome)
greater severity of illness that may be associated with more delays or interruptions in treatment for some or the use of higher doses of APs for others
those individuals studied may represent a limited group of people (e.g., those hospitalized at academic centers)

What clinical guidance do we have?

Careful assessment is the foundation for all treatment considerations. We have to ask and answer is there a psychotic illness and what we know about its nature (e.g., is it drug or endocrine induced, is it a bipolar illness, is it schizophrenia?)
Treatment of psychosis protects people from long term loss of functioning
Early intervention is essential: delays cause suffering, increased burden and poorer long term outcomes
APs alone are not sufficient treatment for a persistent psychotic illness: a comprehensive approach that combines medications with family work, rehabilitation and recovery is always needed
Sharing information and decision-making with clients and their families builds alliances, enhances engagement and retention in care, and builds responsibility in recipients of care
The choice of which antipsychotic agent to use must include explicit attention to minimizing its side-effects, recognizing that all agents produce side-effects but that these problems differ widely by drug and by individual
The first generation APs (now unfortunately very underutilized) offer a choice based on their effects on weight gain, sedation, libido and neurologic side effects like rigidity, tremor and akathisia (restlessness) and involuntary movement problems like tardive dyskinesia
The second generation APs offer a choice based on their effects on weight gain, sedation, insulin, lipids and libido
For all medications the lowest dose needed to achieve benefits is the desired dose
While some patients may benefit from the use of more than one antipsychotic medication, the research literature does not support the effectiveness of AP polypharmacy

In summary, recipients, families and clinicians continue every day to make decisions about optimal care for the treatment of psychotic illness. Research on the possible protective and toxic effects of antipsychotic medications remains inconclusive. But we do know that psychotic illness is bad for people and that early intervention, comprehensive care and conservative use of medications chosen together with recipients and supported by their families remain the mainstays of good clinical care.