Since the introduction in the 1950s of the phenothiazine chlorpromazine as an anesthetic agent and the serendipitous discovery of its antipsychotic effect, a large number of antipsychotic drugs have been marketed for clinical use. No attempt is made here to describe or even list all of them. Some have had only an evanescent popularity and others have yet to prove their value. Chemically, these compounds form a heterogeneous group. Eight classes of them are of particular clinical importance: (1) the phenothiazines; (2) the thioxanthenes; (3) the butyrophenones; (4) the rauwolfias alkaloids; (5) an indole derivative, loxapine, and a unique dihydroindolone, molindone; (6) a diphenylbutylpiperidine, pimozide; (7) dibenzodiazepines, typified by clozapine and olanzapine; and (8) a benzisoxazole derivative, risperidone. Molindone and loxapine are about as effective as the phenothiazines in the management of schizophrenia and their side effects are similar, although claims have been made that they are less likely to induce tardive dyskinesias and seizures. Their main use is in patients who are not responsive to the older drugs or who suffer intolerable side effects from them.
The antipsychotic agents in the class of clozapine (which is less used than other agents in the class because of cases of aplastic anemia) have attracted great interest, because—as already mentioned—they are associated with relatively fewer extrapyramidal side effects. For this reason, they are particularly favored in controlling the confusion and psychosis of parkinsonian patients. The other new class of drugs, of which risperidone is the main example, also has fewer extrapyramidal side effects than the phenothiazines and a more rapid onset of action than the traditional antipsychotic medications. All of these newer medications produce the “metabolic syndrome” of weight gain, adverse lipid changes, and glucose intolerance. Pimozide may be useful in the treatment of haloperidol-refractory cases of Gilles de la Tourette syndrome (see Chap. 4); its main danger is its tendency to produce cardiac arrhythmias.
This group comprises chlorpromazine (Thorazine), promazine (Sparine), triflupromazine (Vesprin), prochlorperazine (Compazine), perphenazine (Trilafon), fluphenazine (Permitil, Prolixin), thioridazine (Mellaril), mesoridazine (Serentil), and trifluoperazine (Stelazine). In addition to their psychotherapeutic effects, these drugs have a number of other actions, so that certain members of this group are used as antiemetics (prochlorperazine) and antihistaminics (promethazine).
The phenothiazines have had their widest application in the treatment of the major psychoses, namely schizophrenia and, to a lesser extent, bipolar psychosis, but they are being replaced by newer agents with fewer side extrapyramidal effects (but with problematic issues of their own). Under the influence of these drugs, many patients who would otherwise have been hospitalized were able to live at home and even work productively. In the hospital, the use of these drugs has facilitated the care of hyperactive, delirious, and combative patients (see Chaps. 48 and 49 for details of this clinical use).