TUCSON, ARIZ. – Clozapine is widely viewed as a last-resort antipsychotic agent, but it ought to be considered something more, Dr. Henry A. Nasrallah asserted at a psychopharmacology conference sponsored by the University of Arizona.
"I really urge you, if a patient doesn’t respond to two or three very adequate courses of monotherapy with drugs chosen from among the other nine atypical antipsychotic agents on the market – and that means 12 weeks at the highest tolerated dose – [to] go to clozapine and save the patient a lot of grief," said Dr. Nasrallah, professor of psychiatry and neuroscience at the University of Cincinnati.
Clozapine (Clozaril) is approved for patients with treatment-refractory schizophrenia, but Dr. Nasrallah also advocates its use in treatment-resistant patients (that is, partial responders who get only 20%-30% improvement, and continue to have low-grade delusions and hallucinations that never really seem to get better despite adequate monotherapy trials of several other atypical antipsychotic agents).
"It’ll bring big improvements in 60%-70% of those patients," the psychiatrist said. "Stay with clozapine. It can take 3, 6, even 12 months, during which I think gene expression takes place and we capture more and more patients. They respond beautifully. I have patients going back to college after being homeless for 7 years – I mean, that’s how good clozapine can be. Why should we settle for 20%-30%? Clozapine is a little more labor intensive, but your patients have a life that they’re losing. We owe it to our patients to give it a shot."
Switching to clozapine is a better option for treatment-refractory or -resistant patients than is turning to combination therapy with multiple atypical antipsychotics, Dr. Nasrallah continued.
"Combination therapies have never been shown to work, even though 40% of patients [in the United States] are taking two, three, four, and even five antipsychotics at a time," he said. "That doesn’t make any sense, because we don’t have any evidence that adding two antipsychotics works when one doesn’t."
Dr. Nasrallah disclosed that he serves as a consultant for AstraZeneca, Janssen, Pfizer, Merck, Dainippon Sumitomo Pharma, and Novartis. He receives research grant support from numerous pharmaceutical companies as well as the National Institute of Mental Health.