Seizures antipsychotics causing

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. 

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. 

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. 

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. 

Antipsychotic drugs include the older phenothiazines and butyrophenones, as well as newer atypical drugs. All of these can cause CNS depression, seizures, and hypotension. Some can cause QT prolongation. The potent dopamine D2 blockers are... 

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. 

Tricyclic antidepressants resemble the phenothiazine antipsychotics such as chlorpromazine in structure and function. Like the phenothiazine derivatives (e.g., chlorpromazine), tricyclic antidepressants (e.g., amitriptyline) may reduce the seizure threshold and precipitate seizures in epileptic patients, cause cholestatic jaundice, movement disorders, and hematologic side effects. Unlike the phenothiazine derivatives, the tricyclic antidepressants may increase motor activity, have a very slow onset and long duration of action, a relatively narrow margin of safety, and a strong anticholinergic effect. In fact, dry mouth is the most common side effect, and other anticholinergic effects such as tachycardia, loss of accommodation, constipation, urinary retention, and paralytic ileus have been reported following amitriptyline. 

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. 

Mesoridazine, a metabolite of thioridazine, is thought to exert its antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thereby inhibiting dopamine-mediated effects. Mesoridazine has many other central and peripheral affects it produces both alpha and ganglionic blockade and counteracts histamine- and serotonin-mediated activities. Mesoridazine and thioridazine cause fewer movement disorders (see Phenotheazine Derivatives). Mesoridazine is metabolized to inactive metabolites, which are excreted by the kidneys. Overdosage of mesoridazine causes CNS depression characterized by deep, unarousable sleep, convulsive seizures, and cardiac arrhythmias (see also Table 2). 

Overdosage toxidty Poisoning with antipsychotics other than thioridazine is not usually fatal. Hypotension often responds to fluid replacement. Neuroleptics lower the convulsive threshold and may cause seizures, which are usually managed with diazepam or phenytoin. Thioridazine overdose, because of cardiotoxicity, is more difficult to treat. 

Serum levels of clonazepam are decreased by the enzyme-inducing properties of phenobarbitai, phenytoin, and CBZ. Concurrent administration of amphetamines, methylphenidate, ethanol, antianxiety drugs, or antipsychotics may cause CNS depression or altered respiration. The combined administration of clonazepam and valproate may cause absence status, and in patients displaying a mixed seizure pattern, clonazepam may precipitate grand mal seizures. 

A report briefly mentions a diabetic girl who had an episode of minor hypotension with chlorpromazine that appeared to have been exacerbated by sotalol. A schizophrenic patient taking chlorpromazine and tiotixene experienced delirium, grand mal seizures and skin photosensitivity, attributed to a rise in the serum levels of the antipsychotic drugs caused by increasing doses of propranolol (up to a total of 1200 mg daily). ... 

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