Side effects of clozapine

Rietschel, M., Naber, D., Fimmers, R. et al. (1997). Efficacy and side effects of clozapine not associated with variation in the 5-HT2C receptor. NeuroReport, 8, 1999-2003. 

The most talked about and concerning side effect of clozapine is a potentially dangerous reduction in the number of white blood cells. This side effect, called agranulocytosis, occurs in about 1% of patients treated with clozapine. Although we... 

Another serious side effect of clozapine is a risk of seizures. This mainly occurs at higher doses of the drug, and having a seizure is not necessarily a sufficient reason to stop clozapine permanently. If the clozapine has been especially helpful, an anticonvulsant can be added to protect against further seizures. Valproate (Depakote) may be best in this regard because it not only provides protection from seizures but also may help to relieve some of the symptoms of schizophrenia. Recently, it has become clear that two atypical antipsychotic drugs, clozapine and olanzapine, are associated with an increased risk for the development of type II diabetes. 

Clozapine is an atypical antipsychotic that is usually used in patients who are inadequately controlled with other antipsychotics. The reason is that clozapine is associated with a risk of potentially fatal agranulocytosis. As with other atypicals, side-effects of clozapine include occurrence of hyperglycaemia and diabetes. 

Sedation. Sedation is the most common side effect of clozapine, and it is particularly prominent early in treatment. Sedation generally attenuates when the dose is reduced, when tolerance to this side effect develops, or when a disproportionate amount is given at bedtime. 

Because patients with galactosemia need to avoid weight loss as a result of restrictive dietary measures, the authors suggested that this is an interesting example of weight gain as a positive side effect of clozapine, not necessarily associated with increased appetite and higher caloric intake. 

Rietschel M, Naber D, Oberlander H, Holzbach R, Fimmers R, Eggermann K, Moller HJ, Propping P, Nothen MM. Efficacy and side-effects of clozapine testing for association with allelic variation in the dopamine D4 receptor gene. Neuropsychopharmacology 1996 15(5) 491-6. 

Rietschel M, Naber D, Fimmers R, Moller HJ, Propping P, Nothen MM. Efficacy and side-effects of clozapine not... 

In spite of these advantages, clozapine use was accompanied by many disturbing side effects and dangerous adverse reactions, notably an increased risk of potentially fatal agranulocytosis (a severe drop in white blood cell count). This potential risk (which occurs in 1-1.5% of cases) requires patients to take weekly blood tests for the first 6 months of treatment, with a decreased frequency thereafter, for as long as they are on clozapine it is easy to understand why so few patients were willing to continue long-term treatment, in spite of the benefits obtained. Other side effects of clozapine that further limit its use are listed in Table 5.14. 

TABLE 5.14. Some Potential Side Effects of Clozapine (Clozaril)... 

CALCIUM CHANNEL BLOCKERS CLOZAPINE Plasma concentrations of clozapine may be t by diltiazem and verapamil Diltiazem and verapamil inhibit CYP1 A2-mediated metabolism of clozapine Watch for side-effects of clozapine... 

Since the release of clozapine, researchers have sought to develop an atypical antipsychotic without the side effects of clozapine (especially aplastic anemia). As of this writing, two other atypical agents have been released risperidone and olanzapine, and several others may soon be released, including sertindole and quetiapine. These agents vary somewhat in their pharmacological profile and, as a group, may... 

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