When the Heart and the Mind Collide: Cardiovascular Risk Factors and Antipsychotic Use in the Schizophrenic Population

From Thorazine to Abilify: The Role of Pharmacotherapy in the Treatment of Schizophrenia For millions of people, 1954 was the year voices stopped. It was during this year that the pharmaceutical company Smith Kline & French (known today as GlaxoSmithKline) began US distribution of the first antipsychotic, chlorpromazine, better known by its trade name, Thorazine. For many, chlorpromazine was a wonder drug—a quick fix for the debilitating and frightening symptoms of schizophrenia. Indeed, more than 100 million patients were treated with chlorpromazine and other drugs in the phenothiazine class before these drugs fell out of favor due to their pronounced adverse effects. These adverse effects, often referred to as extrapyramidal symptoms (EPSs), included movement abnormalities, ranging from mild tremor to severe involuntary facial grimacing and eye rolling, and tardive dyskinesia. Chlorpromazine and other similar drugs that played on the subtleties of the dopaminergic system, are now known as firstgeneration, or typical, antipsychotics. This nomenclature came into use in the decades that followed with the introduction of novel antipsychotic drugs, known as atypicals, that tinkered not only with dopamine but with its sister neurotransmitter, serotonin, in what seemed to be a successful effort to avoid the untoward effects of the earlier drugs. Clozapine, the first of these atypical or second-generation antipsychotics (SGAs), was used in Europe as early as the mid 1970s. While it was initially welcomed as an alternative to the EPSinducing typicals, reports of fatal agranulocytosis associated with its use quickly dampened this initial excitement. Ultimately, clozapine was approved in the United States, but not until 1989 and with the US Food and Drug Administration’s (FDA’s) stipulation that it be used only to treat ‘‘refractory schizophrenia’’ (for which it had been shown to be particularly efficacious). Clozapine aside, the true heyday of the atypicals began in the mid 1990s with the introduction of olanzapine. Olanzapine and other atypical antipsychotics like quetiapine, aripiprazole, risperidone, and ziprasidone, now in widespread use, have transformed the pharmacotherapy of schizophrenic patients. But at what cost? In recent years, this question has received a lot of attention. Both in the lay press and in the medical literature, one theme has emerged as dominant: The patient population using these drugs has been shown to have abnormally high rates of obesity, diabetes, dyslipidemia, and cardiovascular disease (CVD).