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Down-titrate or discontinue antipsychotic doses slowly to decrease risk of relapse or symptom exacerbation.

ATYPICAL ANTIPSYCHOTICS: Each atypical antipsychotic has a distinct pharmacologic profile. Unlike conventional antipsychotics, atypical antipsychotics exert their therapeutic effects by antagonizing both the dopamine (D₂) and serotonin (5HT₂) receptors. Aripiprazole, however, functions as a partial agonist at the dopamine D₂ and serotonin 5HT_1A receptors, and as an antagonist at the serotonin 5HT_2A receptor.

Antagonism at other receptors may explain some of the other therapeutic and adverse effects associated with these agents. For example, antagonism of muscarinic receptors (eg, clozapine, olanzapine) may produce anticholinergic-like effects. Antagonism of histamine receptors may cause somnolence and adrenergic α₁ receptor antagonism produces orthostatic hypotension (eg, aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone).

Atypical antipsychotics have a lower risk of extrapyramidal effects, tardive dyskinesia and prolactin elevation than conventional drugs. However, weight gain, hyperlipidemia, and increased risk of type 2 diabetes are major side effects of this class. Among the atypical antipsychotics, mean weight gain is greatest with clozapine and olanzapine, less with quetiapine, even less with risperidone, and is very low with ziprasidone; all patients should be monitored prior to and during therapy.

Due to the risk of agranulocytosis, clozapine is reserved for patients who can not tolerate or are unresponsive to other antipsychotics.

CONVENTIONAL ANTIPSYCHOTICS: Conventional antipsychotics are dopamine receptor antagonists with a high affinity for dopamine D₂ receptors. They are associated with a high incidence of adverse extrapyramidal effects, tardive dyskinesia, sedation, and hyperprolactinemia that may result in galactorrhea, amenorrhea, or gynecomastia. Among the conventional antipsychotics, mean weight gain is greatest with chlorpromazine and thioridazine.

The conventional antipsychotics can be divided into three groups of phenothiazines on the basis of a variable side chain:
Aliphatic phenothiazines (eg, chlorpromazine) are low in potency and more likely to produce sedation, hypotension and anticholinergic effects.
Piperidine phenothiazines (eg, thioridazine) produce fewer adverse extrapyramidal effects, which may be attributed to increased antimuscarinic acitivity in the CNS, but can cause depression of cardiac conduction and repolarization.
Piperazine phenothiazines (eg, prochlorperazine, fluphenazine, trifluoperazine) have limited antimuscarinic activity, a higher risk of adverse extrapyramidal effects, but a lower incidence of sedation or autonomic side effects.

In general, most phenothiazines have relatively flat dose-response profiles, therefore lower dosages may be as effective and produce less side effects than higher dosages.