Seizures from antipsychotics

Tramadol, phenothiazine antipsychotics and the majority of antidepressants, as well as a number of other drugs, can lower the seiznre threshold and are associated with an increased risk of convnlsions [6]. Again, these drugs may accumulate in patients with liver impairment such as cirrhosis or acute liver failure, and care must be taken if choosing to use them. This is especially important in alcoholics, who have an increased risk of seizures from acute alcohol withdrawal [7]. Examples of drugs that can lower the seizure threshold and should be used with caution/avoided are ... 

Other sedative-hypnotic medications, such as barbiturates, may play a useful role in severe withdrawal from this group of drugs. For example, in a case series of GBL withdrawal, use of intravenous pentobarbital in the range of 1-2 mg/kg/hour lowered the total requirement for intravenous lorazepam (Sivilotti et al. 2001). Antipsychotic medications are often used to reduce psychotic agitation. However, because antipsychotic medications lower the seizure threshold and may contribute to loss of central control of temperature leading to hyperthermia or neuroleptic malignant syndrome (NMS), they are not indicated as first-line medications for GHB withdrawal delirium (Dyer and Roth 2001 McDaniel and Miotto 2001 Sharma et al. 2001). If anti-... 

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. 

Clonazepam. Clonazepam is marketed primarily for petit mal variant, myoclonic, and akinetic seizures. It also has had wide psychiatric application, including the treatment of acute mania or other agitated psychotic conditions, usually in combination with lithium or antipsychotics. The literature on clonazepam s efficacy for acute mania is based on the work of Chouinard (120) and coworkers who compared this agent with placebo or standard treatments for acute mania. As noted earlier, however, another group from Montreal found that comparable doses of lorazepam were more effective than clonazepam for acute mania (119). 

Seizures, muscular hyperactivity, and rigidity may result in death. Seizures may cause pulmonary aspiration, hypoxia, and brain damage. Hyperthermia may result from sustained muscular hyperactivity and can lead to muscle breakdown and myoglobinuria, renal failure, lactic acidosis, and hyperkalemia. Drugs and poisons that often cause seizures include antidepressants, theophylline, isoniazid (INH), diphenhydramine, antipsychotics, cocaine, and amphetamines. 

All basic and advanced life-support measures should be implemented. Gastric decontamination should be performed. Butyrophenones are readily absorbed by activated charcoal. Aggressive supportive care should be instituted. Dystonic reactions respond well to intravenous benztropine or diphenhydramine. Oral therapy with diphenhydramine or benztropine should be continued for 2 days to prevent recurrence of the dystonic reaction. For patients suffering from neuroleptic malignant syndrome, a potentially fatal condition associated with the administration of antipsychotic drugs, dantrolene sodium, and bromocriptine have been used in conjunction with cooling and other supportive measures. Arrhythmias should be treated with lidocaine or phenytoin. Diazepam is the drug of choice for seizures phenytoin is used to prevent recurrence. Hemodialysis and hemoperfu-sion have not been shown to be effective. 

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). 

The pharmacology of benzodiazepine derivatives differs significantly from that of the neuroleptics, in that the benzodiazepines have no psychoplegic (antipsychotic) activity and cause no extrapyramidal, autonomic, or endocrine side effects. In addition, unlike the neuroleptics, which lower the seizure threshold, these substances are anticonvulsants. In addition, they are anxiolytics, muscle relaxants, and mild sedatives. Although the benzodiazepine derivatives do not produce pronounced autonomic or CV side effects, they can reduce or block the emotionally induced changes in cardiovascular functions, probably through actions on the limbic system. 

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