Lee KC, Finley PR, Alldredge BK. Risk of seizures associated with psychotropic medications: emphasis on new drugs and new findings. Expert Opin Drug Saf 2: 233-247

University of California, San Francisco, 521 Parnassus Avenue, C-152, Box 0622, San Francisco, CA 94143-0622, USA.
Expert Opinion on Drug Safety (Impact Factor: 2.91). 06/2003; 2(3):233-47. DOI: 10.1517/14740338.2.3.233
Source: PubMed

ABSTRACT Psychotropic medications in the classes of antidepressants, antipsychotics and mood stabilisers have been recognised in the literature and clinical settings as having high epileptogenic potential. Among these three classes, clozapine, tricyclic antidepressants (TCAs) and lithium are agents that clinicians have historically recognised as precipitants of drug-induced seizures. There are few reports that review the epileptogenic risk of newer psychotropic agents; in this qualitative review, the authors provide an update on the most recently published reports on seizures associated with antidepressants, antipsychotics, mood stabilisers, anxiolytics and sedative-hypnotics. In general, the epileptogenic risks of the newer psychotropic agents appear to be quite low as long as dosing strategies are consistent with recommended guidelines. Whilst newer psychotropic medications appear to be safe in patients with epilepsy, few studies have specifically addressed this population. In addition, the potential for drug interactions between antiepileptic drugs and psychotropics may be substantial with certain agents. For example, many psychotropes are both substrates and inhibitors of cytochrome P450 (CYP450) isoenzymes, whilst many antiepileptic drugs are both substrates and inducers of CYP450 activity. Every attempt should be made to minimise potential interactions when these agents are concomitantly administered.

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Available from: Kelly Lee, Feb 04, 2015
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    • "These generic statements are applied equally to agents that might differ with respect to their effects on seizure incidence, for example olanzapine versus the serotonin reuptake inhibitor (SRI) antidepressants. Olanzapine, which is structurally similar to clozapine, has been reported to be associated with electroencephalogram (EEG) slowing or epileptiform abnormalities (Amann et al. 2003; Centorrino et al. 2002; Lee et al. 2003; Pillmann et al. 2000; Woolley and Smith 2001) and is viewed by some authors as being associated with higher seizure risk (Camacho et al. 2005; Lee et al. 1999; Lee et al. 2003; Woolley and Smith 2001). On the other hand, fluoxetine (Favale et al. 1995) and citalopram (Favale et al. 2003; Specchio et al. 2004) have been reported to produce antiepileptic effects in open label studies of nondepressed epileptic patients, which is also consistent with research utilizing animal models indicating an anticonvulsant effect of SRI antidepressants (Borowicz et al. 2006; Dailey et al. 1992; Kabuto et al. 1994; Kecskemeti et al. 2005; Leander 1992; Pasini et al. 1992; Pericic et al. 2005; Pisani et al. 1999; Prendiville and Gale 1993; Sparks and Buckholtz 1985; Ugale et al. 2004; Wada et al. 1999). "
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    ABSTRACT: Clinical trial data provide an approach to the investigation of the effects of psychopharmacological agents, and psychiatric disorders themselves, on seizure threshold. We accessed public domain data from Food and Drug Administration (FDA) Phase II and III clinical trials as Summary Basis of Approval (SBA) reports that noted seizure incidence in trials of psychotropic drugs approved in the United States between 1985 and 2004, involving a total of 75,873 patients. We compared seizure incidence among active drug and placebo groups in psychopharmacological clinical trials and the published rates of unprovoked seizures in the general population. Increased seizure incidence was observed with antipsychotics that was accounted for by clozapine and olanzapine, and with drugs indicated for the treatment of OCD that was accounted for by clomipramine. Alprazolam, bupropion immediate release (IR) form, and quetiapine were also associated with higher seizure incidence. The incidence of seizures was significantly lower among patients assigned to antidepressants compared to placebo (standardized incidence ratio = .48; 95% CI, .36- .61). In patients assigned to placebo, seizure incidence was greater than the published incidence of unprovoked seizures in community nonpatient samples. Proconvulsant effects are associated with a subgroup of psychotropic drugs. Second-generation antidepressants other than bupropion have an apparent anticonvulsant effect. Depression, psychotic disorders, and OCD are associated with reduced seizure threshold.
    Biological Psychiatry 09/2007; 62(4):345-54. DOI:10.1016/j.biopsych.2006.09.023 · 10.26 Impact Factor
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    • "Treating comorbid individuals can be problematic; some anticonvulsants exacerbate depressive symptoms (Brent et al, 1987; Wiegartz et al, 1999; Kanner and Balabanov, 2002), and some antidepressants (eg bupropion, clomipramine) are reported to increase seizure susceptibility. Many of the newer antidepressants (eg sertraline, venlafaxine) appear safer but have not been systematically tested (Kanner et al, 2000; Kanner and Balabanov, 2002; Lee et al, 2003). The neurotransmitter norepinephrine (NE) has both antidepressant and anticonvulsant properties. "
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    ABSTRACT: Epilepsy and depression are comorbid disorders, but the mechanisms underlying their relationship have not been identified. Traditionally, many antidepressants have been thought to increase seizure incidence, although this remains controversial, and it is unclear which medications should be used to treat individuals suffering from both epilepsy and depression. Since the neurotransmitter norepinephrine (NE) has both antidepressant and anticonvulsant properties, we speculated that NE transporter (NET) inhibitor antidepressants might be therapeutic candidates for comorbid individuals. To test this idea, we assessed the effects of chronic administration (via osmotic minipump) of the selective NET inhibitor reboxetine on flurothyl-induced seizures in mice. We found that reboxetine had both proconvulsant and anticonvulsant properties; it lowered both seizure threshold and maximal seizure severity. NET knockout (NET KO) mice essentially phenocopied the effects of reboxetine on flurothyl-induced seizures, and the trends were extended to pentylenetetrazole and maximal electroshock seizures (MES). Furthermore, reboxetine had no further effect in NET KO mice, demonstrating the specificity of reboxetine for the NET. We next tested the chronic and acute effects of other classes of antidepressants (desipramine, imipramine, sertraline, bupropion, and venlafaxine) on seizure susceptibility. Only venlafaxine was devoid of proconvulsant activity, and retained some anticonvulsant activity. These results suggest that chronic antidepressant drug treatment has both proconvulsant and anticonvulsant effects, and that venlafaxine is a good candidate for the treatment of epilepsy and depression comorbidity.
    Neuropsychopharmacology 05/2006; 31(4):730-8. DOI:10.1038/sj.npp.1300847 · 7.05 Impact Factor
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    • "The first-generation antipsychotic agents (eg, chlorpromazine ) may lower the seizure threshold. Of the ''novel'' antipsychotic agents, clozapine and olanzapine have been associated with seizures [81] [82]. In general, novel antipsychotic agents antagonize serotonin, dopamine, muscarinic, H 1 , and a 1 receptors [73]. "
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    ABSTRACT: Drug- and toxin-associated seizures may result from exposure to a wide variety of agents. Obtaining a comprehensive history behind the exposure is generally more helpful than diagnostic testing. Most DTS may be managed with supportive care, including benzodiazepines, except in the case of agents that require a specific intervention or antidote.
    Medical Clinics of North America 12/2005; 89(6):1297-321. DOI:10.1016/j.mcna.2005.06.004 · 2.61 Impact Factor
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