30 Years of Progress - Antipsychotic Therapy

Last week I posted about the progress in the treatment of depression over the last 30 years. Today I’m going to discuss what I think is an even more dramatic improvement in pharmacologic management of psychiatric disease. The treatment of major psychosis, especially schizophrenia, but also bipolar disorder, has had revolutionary breakthroughs with the new generation of antipsychotics. Although these diagnoses are far less common than depression, they are a devastating problem for the individuals and families they affect. When I was in training, and really until the last 15-20 years, the antipsychotic medications were also called “major tranquilizers.” This is because when taking them patients were essentially tranquilized. Examples of these medications were thorazine, haloperidol and others. Patients taking these medications were sedated, slowed in their thinking, and very dull. (Think of scenes from “One Flew Over the Cuckoo’s Nest”) In addition to these poorly tolerated side effects the medications often led to irreversible involuntary movement disorders called tardive dyskinesias. This is when patients would develop lip smacking, twitching of muscles, and other involuntary muscle movements that sometimes did not go away on stopping the medications. As primary care physicians we were very reluctant to prescribe these medications, and psychiatrists had to closely monitor patients to try to balance the horrors of untreated major psychosis with the risk of development or worsening of very difficult and sometimes irreversible side effects. When treated with these meds patients may not have been psychotic, but they were rarely very functional.

In about 1990 a group of meds known as second generation antipsychotics were developed. The first of these was clozapine which is difficult to use because of the potential to cause agranulocytosis. It was followed shortly by risperidol, olanzapine and others. These were a huge improvement in our arsenal of antipsychotic meds, since they are much less sedating, often leave patients able to function in society, be fairly alert, and feel better on the meds than off. Many schizophrenic patients are now stable on long term antipsychotics and function in society far better than was possible on the older medications. Also the tardive dyskinesias are almost unheard of with these medications. Now we have to watch for other side effects like weight gain with some, and an increased risk of developing diabetes, but these are relatively tame side effects compared to treating a patient with a drug that made them nearly a walking zombie. With these drugs many patients are treated successfully by primary care physicians, and function out of institutions free of the intrusive and destructive psychotic problems of their disease. Even newer drugs continue to be developed and give us more options to fine tune treatment of major psychosis.