Antipsychotic agents

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Information about Antipsychotic agents

Psychotic disorders include schizophrenia, the manic phase of manic-depressive illness (bipolar disease), acute psychosis and other conditions marked by acute, severe agitation. The antipsychotic medications are invaluable adjuncts to the treatment of psychosis and bipolar illness and have revolutionized management of these conditions.

History of Antipsychotic agents

The antipsychotic agents in clinical use include the phenothiazines and structurally similar compounds such as thioxanthenes, benazepines, butyrophenones, diphenylbutylpiperidines and miscellaneous similar heterocyclic compounds. The antipsychotic medications are usually classified into conventional and atypical agents, based upon relative risks for extrapyramidal side effects that are greater with the older, conventional agents. They are also referred to as first and second generation antipscyhotic agents.

Early antipsychotics

The initial antipsychotic medications introduced into clinical practice were the phenothiazines, but they have been largely replaced in recent years by the atypical agents. Phenothiazines in current use (with initial brand names and date of first approval) include chlorpromazine (Thorazine: 1957, the initial prototype antipsychotic agent), fluphenazine (Prolixin: 1972), perphenazine (Trilafon: 1957), prochlorperazine (Compazine: 1956, used mostly as therapy of nausea rather than psychosis), thioridazine (Mellaril: 1978), and trifluoperazine (Stelazine: 1959). Miscellaneous conventional antipsychotic medications include haloperidol (Haldol: 1967), loxapine (Loxitane: 1976), molindone (Moban: 1974) and pimozide (Orap: 1984, used largely for Tourette syndrome). Lithium is also frequently discussed in the context of antipsychotic therapies, although its major use is for stabilization of bipolar illness.

Atypical antipsychotic agents

The atypical antipsychotic agents are more recently introduced drugs that generally have greater potency and fewer extrapyramidal side effects. Currently, these are the most commonly used antipsychotic agents. They include aripiprazole (Abilify: 2002), asenapine (Saphris: 2007), brexpiprazole (Rexulti: 2015), cariprazine (Vraylar: 2016), clozapine (Clozaril: 1975-79, 1989), iloperidone (Fanapt: 2010), lurasidone (Latuda: 2010), olanzapine (Zyprexa: 1996), paliperidone (Invega: 2006), pimavanserin (Nuplazid: 2016), quetiapine (Seroquel: 1997), risperidone (Risperdal: 1993) and ziprasidone (Geodon: 2001). Some of these agents are also used to treat bipolar illness and major depression.

Phenothiazines

The phenothiazines are well established causes of drug induced liver disease and typically cause a cholestatic injury arising within 1 to 4 weeks of starting treatment. Indeed, during the 1960s and early 1970s, chlorpromazine was one of the most common causes of drug induced liver disease ("Thorazine jaundice"). The other phenothiazines were found to cause a similar cholestatic hepatitis, although much less frequently than chlorpromazine. The other conventional antipsychotic medications have been linked to liver injury only rarely, if at all, and do not exhibit a characteristic signature pattern of injury.

Liver safety of Antipsychotic agents

Many but not all of the atypical antipsychotic medications have been linked to serum enzyme elevations during therapy, but clinically apparent liver injury with jaundice from these agents is very rare.

Antipsychotic agents

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Second Generation (Atypicals)

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