Side Effects of Clozapine and Some Other Psychoactive Drugs

The recognition, management, and if possible prevention, of major cardiovascular, central nervous system, haematological, and metabolic adverse effects, including diabetes mellitus and weight gain, of antipsychotics and some other drugs used to treat mental illness is a topic of much debate. However, a wide range of other adverse effects, some of which may be life-threatening, may also be encountered. Side-effects reviewed here include: gastrointestinal-associated effects (constipation, hypersalivation, oropharyngeal lesions, nasal congestion, nausea, nocturnal enuresis, and urinary retention), metabolic effects (obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, and hypertension), neuromuscular effects (extrapyramidal side effects, myoclonus, and neuroleptic malignant syndrome, and pleurothotonus), thermoregulatory effects, effects on the liver, pancreas, and kidney, sexual side effects, and effects on skin and bone. Metabolic factors affecting the incidence of adverse effects to clozapine especially are also discussed. The increasing use of atypical (second generation) antipsychotics and indeed of selective serotonin reuptake inhibitors has led to a greater appreciation of not only the benefits of these drugs, but also of the spectrum of toxicity that may occur in clinical practice. The adverse effects of antipsychotics are a major factor in promoting poor adherence to, and even discontinuation of, antipsychotic treatment on the one hand, and increasing the risk of cardiovascular and metabolic disease on the other. As such they merit recognition and either harm minimization strategies (use of the minimum effective dose, or use of lower doses of combinations of antipsychotics), or in extreme cases discontinuation of the offending drug(s).