Seizure with antipsychotics

Most conventional antipsychotics are associated with a dose-depen-dent risk of a lowered seizure threshold, although the incidence of seizures with most of these drugs is quite small (Devinsky et al. 1991). Of all the conventional antipsychotics, molindone and fluphenazine have been shown most consistently to have the lowest potential for this side effect (ltd and Soldatos 1980 Ohver et al. 1982). The atypical antipsychotic clozapine is associated with a dose-dependent risk of seizure. 

The incidence of seizures with olanzapine, which has been estimated at 0.9% of treated patients, is probably comparable to that with other antipsychotic drugs. 

ANTIPSYCHOTICS BUPROPION t risk of seizures. This risk is marked in elderly people, in patients with a history of seizures, with addiction to opiates/cocaine/ stimulants, and in diabetics treated with oral hypoglycaemics or insulin Bupropion is associated with a dose-related risk of seizures. These drugs, which lower seizure threshold, are individually epileptogenic. Additive effects occur when they are combined Extreme caution. The dose of bupropion should not exceed 450 mg/day (or 150 mg/day in patients with severe hepatic cirrhosis)... 

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. 

There is an increased risk of drug-induced seizures in all patients treated with antipsychotics. The highest risk for antipsychotic-induced seizures is with the use of CPZ or clozapine. Seizures are more likely with initiation of treatment and with the use of higher doses and rapid dose increases. 

Molindone (Moban). Molindone is another of the medinm potency antipsychotics. There are two featnres that set it apart. First, it is less prone to cansing weight gain than other antipsychotics. As a result, it is sometimes preferred for obese schizophrenia patients. Second, although typical antipsychotics do not necessarily cause seizures, they may make them more likely to occur in people who are already prone to seizures. There is some evidence to suggest that molindone may be the least likely antipsychotic to increase the vulnerability to seizures. For this reason, molindone is frequently used to treat patients with schizophrenia who also have epilepsy. 

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. 

Largactil is a proprietary preparation of chlorpromazine, an aliphatic antipsychotic with marked sedation and moderate antimuscarinic and extrapyramidal side-effects. Serenace is a proprietary preparation of haloperidol, a butyrophenone antipsychotic with marked extrapyramidal side-effects, moderate sedation but not very likely to cause hypotension. Tegretol is a proprietary preparation of carbamazepine, an anti-epileptic drug indicated in partial and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic seizures, trigeminal neuralgia and in the prophylaxis of bipolar disorder unresponsive to lithium. 

Seizures Bupropion is associated with a dose-related risk of seizures. Discontinue bupropion and do not restart in patients who experience a seizure while on treatment. Use extreme caution when bupropion is administered to patients with a history of seizure, cranial trauma, or other predisposition(s) toward seizure, or prescribed with other agents (eg, antipsychotics, other antidepressants, theophylline, systemic steroids) that lower seizure threshold. 

Use with caution in older patients with Parkinson s Disease (an atypical antipsychotic is recommended), seizure disorders, cardiovascular disease with conduction disturbance, hepatic encephalopathy, narrow-angleglaucoma, congenital prolonged O-T syndrome or drugs which prolong O-T interval. 

The risk of agranulocytosis and seizures limits use to patients who have failed to respond or were unable to tolerate treatment with appropriate courses of standard antipsychotics. 

The use of electrical stimulation to induce therapeutic seizures is the safest and most efficient form of convulsive therapy (e.g., as compared with pharmacoconvulsive therapy). In 1938, Cerletti and Bini ( 3) were the first to attempt this approach, and until the introduction of effective pharmacotherapy, ECT remained the primary treatment for more severe mood and psychotic episodes. Since then, however, this somatic therapy has been relegated to a secondary role, usually attempted after trials with standard psychotropics (e.g., antidepressants, antipsychotics, lithium, and other mood stabilizers, often in multiple combinations) have proved inadequate. 

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