clozapine and Neuromuscular-Diseases

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).

Topics: Animals; Antipsychotic Agents; Body Temperature Regulation; Bone Diseases; Clozapine; Digestive System Diseases; Dose-Response Relationship, Drug; Humans; Metabolic Diseases; Neuromuscular Diseases; Risk Assessment; Risk Factors; Sexual Dysfunction, Physiological; Skin Diseases

Mild myopathy is a common manifestation of the X-linked McLeod neuroacanthocytosis syndrome. We present a patient with McLeod syndrome and a primarily subclinical myopathy, who developed severe rhabdomyolysis with renal insufficiency after a prolonged period of excessive motor restlessness due to an agitated psychotic state and a single dose of clozapine. Other possible causes for rhabdomyolysis such as prolonged immobility, trauma, hyperthermia, generalized seizures, toxin exposure, or metabolic changes were excluded. Clinical course was favorable, with persistent slight elevation of serum creatine kinase levels caused by the underlying myopathy. Our findings suggest that McLeod myopathy is a predisposing factor for severe rhabdomyolysis. This possibly life-threatening condition should be added to the clinical spectrum of McLeod syndrome, and serum creatine kinase levels should be carefully monitored in patients with this syndrome, particularly if a hyperkinetic movement disorder is present or neuroleptic medication is used.

Topics: Acanthocytes; Clozapine; GABA Antagonists; Humans; Hyperkinesis; Male; Middle Aged; Motor Activity; Neuromuscular Diseases; Rhabdomyolysis; X Chromosome