Are all Antipsychotics Equal, or are some more Equal Than Others?
By Dr. Flowers, Medical Director of the Anne Sippi Clinic Treatment Facilities and a Diplomat of the American Board of Psychiatry and Neurology

Schizophrenia became a medically treatable illness since the introduction of chlorpromazine (Thorazine) in 1952. With anti psychotic medications came the ability to provide significant relief from the acute symptoms of schizophrenia while conferring substantial relapse prevention. In fact, few medical therapies are more thoroughly demonstrated in all of medicine than the effectiveness of anti psychotic medication. In 1964, one of the largest double blind, placebo-controlled studies of anti psychotic medications was completed by the National Institute of Mental Health. In this study, more than 300 patients diagnosed with schizophrenia were randomly assigned to one of three standard anti psychotic medications or to a placebo. Seventy-five percent of the patients taking active medication were considered to have either moderate to marked improvement. In fact, countless subsequent studies have shown similar outcomes. Together, they demonstrate that patients improve with medication, and this improvement is not a chance occurrence!

Despite this remarkably effective treatment, significant clinical difficulties remain. First, depending on operational criteria and patient characteristics, some 30% to 50% of patients with the signs and symptoms of schizophrenia do not respond to a trial of standard anti psychotic medication. Second, anti psychotic medications are not without troublesome side effects both neurologic (tardive dyskinesia) and metabolic (weight gain). In addition, standard anti psychotic medications have minimal or at best only partial effects on the negative symptoms, cognitive symptoms and mood symptoms of schizophrenia. Finally, with the current availability of over a dozen different medications, including both older conventional and newer atypicals, the issue of which medication to use is raised. Even more important: are all medications equal with regard to effectiveness or efficacy?

In most clinical practice situations, if a given patient in the midst of an acute episode of schizophrenia is treated with a standard anti psychotic medication and fails to demonstrate response, one of three alternatives is chosen. First, continue the current medication at the same dose for a longer period of time. Second, increase the dosage of the current medication.
Third, switch to a different standard anti psychotic medication.

Unfortunately, researchers have shown that chronic patients who have failed to respond to an adequate anti psychotic dosage given for an adequate duration are unlikely to respond to higher doses, longer trials or trials of other standard anti psychotic treatments. This situation changes considerably with the addition of clozapine (Clozaril). Most research indicates that response rates with clozapine in treatment resistant patients ranges from 30% to 60% for treatment periods of 6 weeks to 1 year. Given this clearly superior effectiveness, trying one standard anti psychotic after another, raising the dosage, or waiting longer, are likely to cost the patient an increased length of psychosis and an ultimately reduced chance for remission or a favorable outcome.

A more reasonable approach to the pharmacotherapy of schizophrenia would be as follows: acute psychotic episodes should be treated with a single standard anti psychotic agent at an adequate dosage for an adequate duration.
For treatment failures, when compliance is not an issue and side effects do not limit treatment, a trial or a clozapine-like medication is indicated. For treatment failures related to questionable compliance a depot anti psychotic medication is indicated.

The treatment algorithm for schizophrenia continues to gradually develop as more research is completed with the newer medications. However, to us, a basic questions remains: Do older standard anti psychotic medications continue to have a place in the modern therapy of psychosis?