Clozapine seizures caused

B. Severe intoxication may cause coma, seizures, and respiratory arrest. The ECG may show QTc interval prolongation and occasionally QRS prolongation (particularly with thioridazine [Mellaril]). Hypothennia or hyperthennia may occur. Clozapine can cause a prolong confusional state and rarely cardiac toxicity. 

The answer is c. (Hardman7 p 408.) Clozapine differs from other neuroleptic agents in that it can induce seizures in nonepileptic patients In patients with a history of epileptic seizures for which they are not receiving treatment, stimulation of seizures can occur following the administration of neuroleptic agents because they lower seizure threshold and cause brain discharge patterns reminiscent of epileptic seizure disorders. 

Clozapine causes virtually no extrapyramidal side effects and can actually relieve tardive dyskinesia. Nevertheless, it is a difficult medication to tolerate. Its common side effects include drowsiness, weight gain, dizziness, constipation, and drooling (sialorrhea). Clozapine also increases the risk that vulnerable individuals may have seizures. 

Quetiapine (Seroquel). Another atypical antipsychotic, quetiapine has also been approved by the FDA for the treatment of acute mania. It is usually administered twice daily at doses of 150-750mg/day. Like its counterparts, quetiapine is a well-tolerated medication. Its common side effects are drowsiness, dizziness, and headache. It causes less weight gain than olanzapine or clozapine but more than ziprasidone or aripiprazole. Quetiapine also does not cause agranulocytosis nor does it increase the risk of seizures. It can occasionally cause mild changes in liver function tests, but these usually return to normal even if the patient continues taking quetiapine. 

Seizures Seizures have been associated with the use of clozapine. Dose appears to be an important predictor of seizure, with a greater likelihood at higher clozapine doses. Use caution when administering clozapine to patients having a history of seizures or other predisposing factors. Advise patients not to engage in any activity where sudden loss of consciousness could cause serious risk to themselves or others. 

Dibenzodiazepine Clozapine May benefit treatment-resistant patients little extrapyramidal toxicity May cause agranulocytosis in up to 2% of patients dose-related lowering of seizure threshold... 

Clozapine causes a particularly high rate of grand mal seizures, estimated at 4% to 5% in the first year. This is a very serious hazard. The drug frequently produces severe low blood pressure and increased heart rate, potentially resulting in cardiovascular collapse. It can also cause hypertension. It can cause fever and a flulike syndrome. Respiratory arrest... 

However, they are more common with clozapine (SEDA-22, 57) and are said to occur in 0.9% of patients taking olanzapine (SEDA-24, 67). Olanzapine has been reported to cause a lowered seizure threshold (173). 

In a 12-week, double-blind, randomized, placebo-controlled study in 40 patients with treatment-resistant schizophrenia (funded by Johnson Johnson Pharmaceutical Research Development), the addition of risperidone to clozapine improved overall symptoms and positive and negative symptoms (49). The adverse events profile of clozapine + risperidone was similar to that of clozapine + placebo. Clozapine + risperidone did not cause additional weight gain, agranulocytosis, or seizures compared with clozapine + placebo. All the patients completed 12 weeks of treatment however, the small sample size precluded definitive conclusions. 

Clozapine has a very low incidence of extrapyramidal side effects and very few cases of tardive dyskinesia. It is very sedating and has some anticholinergic and an-tiadrenergic side effects (see Fig. 17-B). Sedation is the most troublesome side effect. Clozapine lowers the seizure threshold and can cause hepatitis. The most serious side effect, however, is a severe blood disorder, aplastic anemia, which has caused several deaths in the United States. These deaths have occurred despite the mandatory weekly monitoring of white blood cell count. Clozapine can cost as much as 10,000 per year because of the need for weekly blood tests, although this cost is offset by reduced hospitalizations. Also, there have been a few sudden deaths associated with clozapine, presumably cardiac in nature. 

Antidepressants are commonly used in combination with antipsychotics to treat depressive symptoms in individuals with schizophrenia. Different antidepressants have been reported to inhibit metabolism of different P450 pathways. Table 66-10 summarizes the potential metabolic drug interactions between antidepressants and SGAs. Potential enzyme inhibitor interactions with clozapine are the most clinically significant. Increased clozapine serum concentrations with a CYP 1A2 inhibitor such as fluvoxamine may precipitate seizures. With the newer atypical antipsychotics, enzyme inhibitors are more likely to cause side effects such as increased sedation, orthostatic hypotension, or increased risk of akathisia and other extrapyramidal side effects. 

Clozapine, which is associated with higher risk of agranulocytosis and seizures, is indicated (25 mg once or twice daily) only in the management of schizophrenic patients who fail to respond adequately to standard antipsychotic drug treatment. On the other hand, it is relatively free from extrapyramidal side effects such as parkinsonism. Approximately 50% of the administered dose is excreted in the urine and 30% in the feces as inactive demethylated, hydroxylated, and N-oxide derivatives. Clozapine has anticholinergic properties and causes tachycardia, and hence poses a serious risk for a patient with compromised cardiovascular function (see also Table 23). 

Bupropion, clozapine, low-potency phenothiazines, maprotiline, TCAs (all have the capacity to significantly decrease seizure threshold and may cause prolonged seizure activity)... 

Miscellaneous toxidties Visual impairment caused by retinal deposits has occurred with thioridazine at high doses, this drug may also cause severe conduction defects in the heart that result in fatal ventricular arrhythmias. Sertindole prolongs the QT interval of the ECG the underlying myocardial effect may lead to cardiac arrhythmias. Clozapine causes a small but important (1—2%) incidence of agranulocytosis and at high doses has caused seizures. 

Urinary tract Urinary system adverse reactions, especially enuresis, have been associated with clozapine [SED-15, 832] with an estimated incidence greater than 6%. The mechanisms include overflow incontinence after urinary retention due to the anti-muscarinic action of clozapine or a cholinomimetic activity, and reduced internal urethral sphincter tone caused by aj adrenoceptor blockade enuresis has also been attributed to a non-specific action of clozapine such as excessive sedation, lowering of the seizure threshold, and constipation exacerbating urinary retention and over-fiow. Secondary enuresis in a 21-year man with schizophrenia settled with resolution of his psychotic symptoms but later remerged after starting clozapine [SS ]. 

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