Side Effects and Adverse Drug Reactions

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Side effects of antipsychotics are a major consideration in physician prescribing. Patients who cannot bear the side effects of medications are noncompli-ant and suffer greater rates of relapse and recurrence. Certain side effects such as sedation can be useful to a patient with insomnia or severe agitation but can also limit functioning. A comparison of side-effect profiles for commonly used antipsychotics is provided in Table 11-1. Common side effects are described below. Further discussion of neurologic side effects is found in Chapter 16.

Anticholinergic Side Effects

Low-potency antipsychotics have the greatest anticholinergic side effects such as dry mouth, constipation, urinary retention, and blurred vision. The anticholinergic properties, however, counter the EPS. In some cases, anticholinergic delirium may occur, especially in the elderly, those with organic brain syndromes, or patients on other anticholinergic agents.

Reduced Seizure Threshold

Low-potency typical antipsychotics and clozapine are associated with lowering seizure threshold. Seizures resulting from antipsychotic therapy are treated by changing medications, lowering the dose, or adding an antiseizure medication.

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62 • Blueprints Psychiatry Hypotension

Orthostatic hypotension is particularly common with low-potency agents and risperidone. The hypotensive effect of antipsychotics is generally due to alpha-receptor blockade.


Agranulocytosis has been associated most commonly with clozapine. Because of the potentially fatal nature of this adverse effect, clozapine distribution is regulated and requires a weekly complete blood count with differential to monitor for neutropenia.

Cardiac Side Effects

Ziprasidone, low-potency antipsychotics (particularly thioridazine), and risperidone may cause QT prolongation (with risk of torsade de pointes). Nonspecific electrocardiographic changes may also occur with certain antipsychotic medications (particularly with clozapine and olanzapine).

Metabolic Effects

Although patients with psychotic disorders are known to have higher rates of obesity and diabetes mellitus independent of medication therapy, studies have indicated that certain atypical antipsychotic medications (particualarly olanzapine and clozapine) are associated with high rates of weight gain, dys-

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lipidemia, and may be associated with adult-onset diabetes. All patients taking these medications should have regular metabolic indices checked including lipid levels, fasting blood sugar, and body mass index.

Movement Disorders

Movement disorders such as dystonia, EPS, akathisia, NMS, and tardive dyskinesia may occur and are discussed further in Chapter 16.

Other Side Effects

Skin and ocular pigmentation are common side effects of neuroleptics, as is increased photosensitivity. Thioridazine can cause pigmentary retinopathy at high doses. Increased prolactin levels (and sequela) may also occur. Quetiapine may increase the risk of developing cataracts.

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