First-Generation Antipsychotic Drugs
This table lists selected first-generation antipsychotic drugs. For a table of atypical agents, click here. For a table of the next generation of medications, click here.
| Prochlorperazine | October 1956 | Severe nausea and vomiting; schizophrenia; non-psychotic anxiety | D2 receptor blockade | N/A | Contraindicated for comatose states or in the presence of large doses of CNS depressants, pediatric surgery and children under two years old or under 20 pounds; extrapyramidal symptoms, TD, NMS, cholestatic jaundice, leukopenia, agranulocytosis | IM, IV | ||
| Perphenazine | February 1957 | Schizophrenia; severe nausea and vomiting in adults | D2 receptor blockade | $17.30, (8 mg/day) | Contraindicated in the presence of existing blood dyscrasias, bone marrow depression, or liver damage, and for patients who are comatose, greatly obtunded, on large doses of CNS depressants, or with subcortical brain damage; TD, NMS, extrapyramidal symptoms, EEG abnormalities, hypotension, hypertension | The lead investigators of the CATIE study, which compared four atypical antipsychotics to perphenazine, made the controversial conclusion that "the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone and ziprasidone" (
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| Chlorpromazine hydrochloride | Thorazine | November 1957 | Manic phase of manic-depressive disorder; schizophrenia; anxiety and restlessness prior to surgery; adjunct in treatment of tetanus; acute intermittent porphyria and severe behavioral and conduct disorders in children 1 to 12 years of age; nausea and vomiting; intractable hiccoughs | D2 receptor blockade | $40.99, (400 mg/day) | Contraindicated for comatose or severely depressed states; hypotension, hypertension, extrapyramidal adverse reactions, NMS, increase in weight, TD | IM | French surgeons discovered the antipsychotic affects of chlorpromazine during World War II. The first antipsychotic medication, chlorpromazine is among the "low-potency" conventional drugs, which also include thioridazine and mesoridazine. |
| Trifluoperazine hydrochloride | Stelazine (now available as a generic)(GlaxoSmithKline) | April 1959 | Schizophrenia; short-term treatment of nonpsychotic anxiety | D2 receptor blockade | $53.81, (17 mg/day) | NMS, TD, CNS depression (somnolence to coma), hypotension, extrapyramidal symptoms, agitation, restlessness, seizures, fever, hypothermia, hyperthermia, autonomic reactions, ECG changes, cardiac arrhythmias | ||
| Fluphenazine | August 1960 | Psychotic disorders; long-acting parenteral depot products for long-term neuroleptic therapy | D2 receptor blockade | $29.12, (12.5 mg/day) | Contraindicated for comatose or severely depressed states, use of large doses of other CNS depressants, bone marrow depression or blood dyscrasias, liver damage, cerebral arteriosclerosis, coronary artery disease, severe hypotension or hypertension, subcortical brain damage, children younger than 12 years of age; TD, NMS, hypotension, hypertension, pseudoparkinsonism | Fluphenazine is one of the "high-potency" conventional antipsychotics, including haloperidol and perphenazine, that were purposefully developed to block D2 receptors (as opposed to chance discovery). These remained the primary treatment until the release of clozapine in 1989. | ||
| Thioridazine HCl | Thioridazine HCl (now available as a generic) (Mylan) | March 1962 | Treatment-resistant schizophrenia | D2 receptor blockade | $55.95, (500 mg/day) | Prolongation of the QTc interval--Torsade de Pointes-type arrhythmias and sudden death, proarrhythmic effects, TD, NMS, agranulocytosis, akathisia, agitation, menstrual irregularities, altered libido, gynecomastia, lactation, weight gain, edema | ||
| Haloperidol | April 1967 | Schizophrenia; tics and vocal utterances of Tourette's Disorder | D2 receptor blockade | $33.50, (5 mg/day) | Contraindicated in severe toxic central nervous system depression or comatose states and in individuals who have Parkinson's disease; QT prolongation, NMS, TD, extrapyramidal symptoms, hypotension, hypertension | IM | Haloperidol, as well as other first-generation antipsychotics, has a higher risk of extrapyramidal side effects compared to second-generation drugs, according to conventional research, although investigators from the CATIE study question this presumption. | |
| Thiothixene | Generic | July 1967 | Schizophrenia | D2 receptor blockade | $34.90, (25 mg/day) | Contraindicated for comatose or severely depressed states, circulatory collapse, CNS depression from any cause, bone marrow depression, blood dyscrasias; orthostatic hypotension, ECG changes, TD, NMS, extrapyramidal symptoms (e.g., pseudoparkinsonism, akathisia, dystonias), seizures, paradoxical exacerbation of psychotic symptoms, anorexia, increase in appetite and weight | ||
| Molindone Hydrochloride | Moban (Endo Pharmaceuticals) | January 1974 | Schizophrenia | D2 receptor blockade | $245.18 (75 mg/day) | Contraindicated in severe central nervous system depression; TD, NMS, drowsiness, depression, hyperactivity, euphoria, akathisia, akinesia | ||
| Loxapine | Loxitane (Watson Labs) | February 1975 | Schizophrenia | D2 receptor blockade | $95.50, (75 mg/day) | Contraindicated for comatose or severe drug-induced depressed states and hypersensitivity to dibenzoxazepines; TD, NMS, hypotension, hypertension, weight gain, weight loss, dry mouth, nausea, vomiting | IM | In 2000, the Cochrane Database of Systematic Reviews (2:CD001943, 2000) noted that "Loxapine is antipsychotic but its effects are under researched. It is not clearly different from typical drugs in either its positive or adverse effects." |
* Dosages reflect typical figures from the Physician's Desk Reference. Costs reflect what Medicare typically pays per month's supply.