Most antidepressant drugs are safe for patients with epilepsy at therapeutic doses: A review of the evidence (original) (raw)
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Neurologia i Neurochirurgia Polska, 2018
People with epilepsy (PWE) frequently suffer from comorbid mood and anxiety disorders. Depression is one of the major psychiatric comorbidities having a negative impact on the quality of life in people with epilepsy. A review of the literature indicates that the majority of antidepressant-related seizures have been associated with either ultra-high doses or overdosing and, generally, the risk of antidepressant-associated seizures is low. Correspondingly, there is some evidence indicating that antidepressants of most widely used groups may additionally lower the risk of triggering seizures. Four antidepressants are not recommended for patients with epilepsy, i.e.: amoxapine, bupropion, clomipramine and maprotiline. Clinicians applying first line of depression treatment in patients with epilepsy should consider use of SSRIs or SNRIs, particularly sertraline, citalopram, mirtazapine, reboxetine, paroxetine, fluoxetine, escitalopram, fluvoxamine, venlafaxine, duloxetine. Implementation of anticonvulsive drugs in depressed patients should include valproate, carbamazepine, lamotrigine, gabapentin, pregabalin. The paper reviews the evidence for the clinical use of antidepressants in PWE.
Epilepsy & Behavior, 2013
For a long time, there has been a misconception that all antidepressant drugs have proconvulsant effects. Yet, antidepressants of the selective serotonin reuptake inhibitor (SSRI) family not only have been shown to be safe when used in patients with epilepsy (PWE) but also have been found to possess antiepileptic properties in animal models of epilepsy. In humans randomized to SSRIs vs. placebo for the treatment of major depressive episodes, the incidence of epileptic seizures was significantly lower among those treated with the antidepressants. These data raise the question of whether there is enough evidence that would support a randomized placebo-controlled trial to test antiepileptic effect of SSRIs in PWE. This article reviews the preclinical and clinical data to address this question.
Antidepressant therapy in epilepsy: can treating the comorbidities affect the underlying disorder?
British Journal of Pharmacology, 2013
There is a high incidence of psychiatric comorbidity in people with epilepsy (PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, a growing body of evidence suggests that newer ('second generation') antidepressants, such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. Although a great deal is known about how antidepressants affect excitability on short time scales in experimental models, little is known about the effects of chronic antidepressant exposure on the underlying processes subsumed under the term 'epileptogenesis': the progressive neurobiological processes by which the non-epileptic brain changes so that it generates spontaneous, recurrent seizures. This paper reviews the literature concerning the influences of antidepressants in PWE and in animal models. The second section describes neurobiological mechanisms implicated in both antidepressant actions and in epileptogenesis, highlighting potential substrates that may mediate any effects of antidepressants on the development and progression of epilepsy. Although much indirect evidence suggests the overall clinical effects of antidepressants on epilepsy itself are beneficial, there are reasons for caution and the need for further research, discussed in the concluding section.
Journal of epilepsy research, 2017
Depression is one of the major psychiatric comorbidities associated with epilepsy. The inconclusive results of antidepressants (ADs) regarding their safety in regard to convulsions have strongly contributed towards under treatment of depression in people with epilepsy (PWE). Thus, the present study was envisaged to assess the relative safety of four different classes of ADs regarding their convulsive potential in kindled/epileptic animals. Kindling (an animal model to induce chronic epilepsy) was induced in male Swiss albino mice by administration of pentylenetetrazole subconvulsive doses (35 mg/kg, i.p.) at an interval of 48 ± 2 h for 42 days. The epileptic animals were treated with saline; imipramine (20 mg/kg/day i.p.); fluoxetine (20 mg/kg/day i.p.); venlafaxine (10 mg/kg/day i.p.) and mirtazapine (10 mg/kg/day i.p.) for 15 days. Except naive, animals were challenged with pentylenetetrazole subconvulsive dose (35 mg/kg, i.p.) on every 5(th) day to determine convulsion severity s...
Seizures with neuroleptics and antidepressants
General Hospital Psychiatry, 1987
Seizures remain among the most serious side effects of psychotropic drugs. The authors review the literature associating neuroleptic and antidepressant medications with seizures, discussing the relative "seizurogenicity" of different medications, risk factors for seizures, and drugs of choice for high-risk patients. Case histories are presented. Available evidence suggests that molindone, fluphenazine, and haloperidol areamong the least seizurogenic neuroleptics and fhat doxepin, monoamine oxidase inhibitors, or electroconvulsive therapy may be safest in treating the depressed patient at risk for seizures.
British journal of pharmacology, 2015
Two of the most relevant unmet needs in epilepsy are represented by the development of disease-modifying drugs able to affect epileptogenesis and/or the study of related neuropsychiatric comorbidities. No systematic studies have investigated the effects of chronic treatment with antipsychotics or antidepressants on epileptogenesis. However, such drugs are known to influence seizure threshold. We evaluated the effects of an early long-term treatment (ELTT; 17 weeks), started before seizure onset (P45), with fluoxetine (selective serotonin-reuptake inhibitor), duloxetine (dual-acting serotonin-noradrenaline reuptake inhibitor), haloperidol (typical antipsychotic drug), risperidone and quetiapine (atypical antipsychotic drugs) on the development of absence seizures and comorbid depressive-like behavior in the WAG/Rij rat model. Furthermore, we studied the effects of these drugs on established absence seizures in adult (6 month old) rats after a chronic 7 weeks treatment. ELTT with all ...