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Office of Mental Health

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:

What clinical guidance do we have?

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.