Clozapine with insulin

Smoking cessation, with or without nicotine substitutes, may alter response to concomitant medication in ex-smokers. Smoking may affect alcohol, benzodiazepines, beta-adrenergic blockers, caffeine, clozapine, fluvoxamine, olanzapine, tacrine, theophylline, clorazepate, lidocaine (oral), estradiol, flecanide, imipramine, heparin, insulin, mexiletine, opioids, propranolol, catecholamines, and cortisol. 

Weight gain is very common, especially with clozapine and olanzapine, and requires monitoring of food intake, especially carbohydrates. Hyperglycemia may develop, but whether secondary to weight gain-associated insulin resistance or to other potential mechanisms remains to be clarified. 

Severe insulin resistance with ketoacidosis (pH 6.9) has been reported with clozapine (292). After withdrawal, insulin requirements fell. Reinstitution of clozapine induced an identical increase in insulin need. 

Diabetes was also more common in 63 patients taking clozapine than in 67 receiving typical depot neuroleptic drugs (299). The percentages of type 2 diabetes mellitus were 12% and 6% respectively. Nevertheless, the mechanism is not known. In six patients with schizophrenia, clozapine increased mean concentrations of blood glucose, insulin, and C peptide (300). The authors concluded that the glucose intolerance was due to increased insulin resistance. 

Insulin resistance is a major but not necessary risk factor for type 2 diabetes. Glucose metabolism in 36 out-patients with schizophrenia aged 18-65 years taking clozapine (n — 12), olanzapine (n — 12), or risperidone (n = 12) has been examined in a cross-sectional study... 

The hormone leptin is synthesized by adipocytes and is important in controlling body weight plasma leptin concentrations correlate with fat mass and insulin resistance. Leptin could be a link between obesity, insulin resistance syndrome, and treatment with some neuroleptic drugs. Plasma leptin concentrations are raised, regardless of weight, in patients taking clozapine (793). 

As well as their effects on the brain, neuroleptics commonly produce other potentially lethal effects. They are all toxic to the heart, inducing conduction defects and arrhythmias. Olanzapine and clozapine also interfere with normal metabolism, causing what is known as metabolic syndrome. This syndrome has only recently been described and is defined as the occurrence of obesity, diabetes, hypertension and dyslipidaemia6 (Shirzadi Ghaemi 2006). The underlying cause of the syndrome is thought to be resistance to insulin. All these effects... 

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