fluvoxamine and Seizures

Anti-depressants are among the most widely-prescribed medications. It is unknown whether the risk of seizure during therapeutic use differs by drug. We ranked the seizure risk of popular anti-depressants.. We conducted a population-based case-control study between April 2002 and March 2015 in Ontario, Canada. Cases were Ontario residents aged ≥65 years hospitalized for a first-ever seizure within 60 d of filling a prescription for one of nine second-generation anti-depressants, each dispensed more than 1 million times (range: 1,196,810 [fluvoxamine] to 19,849,930 [citalopram]) during the study period. For each case, we identified up to four seizure-free controls receiving a similar anti-depressant, and matched on age, sex, date and a pre-defined seizure-specific disease risk index.. We identified 5701 patients hospitalized with a first-ever seizure and matched them with 21,872 controls. Relative to bupropion, the risk of new-onset seizure during therapeutic use was highest for escitalopram (adjusted odds ratio [OR] 1.79; 95% confidence interval [CI] 1.42-2.25) and citalopram (OR 1.67; 95% CI 1.35-2.07), while no incremental risk was found for fluoxetine (OR 1.02; 95%CI 0.78-1.33) and duloxetine (OR 0.94; 95%CI 0.75-1.22). Other anti-depressants were associated with modest increase in seizure risk.. The risk of seizure during therapeutic use among elderly patients varies among second-generation anti-depressants. Escitalopram and citalopram are associated with the highest risk. Prescribers should consider the seizure risk of individual anti-depressants and use discretion when selecting an anti-depressant, especially for patients with other risk factors for seizure. Frontline clinicians should be cognizant of this differential risk.

Topics: Aged; Aged, 80 and over; Antidepressive Agents, Second-Generation; Bupropion; Case-Control Studies; Citalopram; Duloxetine Hydrochloride; Female; Fluvoxamine; Humans; Male; Odds Ratio; Ontario; Population; Seizures

Unintentional ingestion of selective serotonin reuptake inhibitor (SSRI) medications is common amongst children <6 years of age. Current evidence-based management guidelines are based on a low incidence of significant medical outcomes in these children.. To describe and compare outcomes of pediatric exposures to vilazodone with other SSRIs.. A retrospective observational case series analysis of both single and polysubstance SSRI exposures amongst children <6 years old reported to the National Poison Data System (NPDS).. 11,384 SSRI exposures in children <6 years of age reported to NPDS between January 2012 and June 2016 were assessed. Vilazodone only accounted for 5.9% of all exposures, but resulted in the highest proportion of health care facility admission compared to other SSRIs, both in single substance (165 of 531 (31.1%); OR 9.0 [7.3-11.2]) and polysubstance (57 of 107 (53.3%); OR 4.1 [2.7-6.2]) exposures. Children exposed to vilazodone also have higher odds of experiencing a major or moderate outcome in single (134 of 531 (25.2%); OR 20.5 [15.5-27.1]) and polysubstance (37 of 107 (35.6%); OR 5.9 [3.7-9.0]) exposures compared to other SSRIs. Several severe clinical outcomes, such as seizure and coma, were more common among the vilazodone exposures.. Exposure to vilazodone in this age group results in an increased rate of hospitalization as well as more severe clinical effects as compared to other SSRIs. Current evidence-based SSRI exposure management guidelines may not be appropriate for the management of vilazodone ingestion in this age group.

Topics: Child; Child, Preschool; Citalopram; Coma; Dose-Response Relationship, Drug; Evidence-Based Medicine; Female; Fluoxetine; Fluvoxamine; Follow-Up Studies; Hospitalization; Humans; Infant; Male; Paroxetine; Poison Control Centers; Retrospective Studies; Seizures; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Vilazodone Hydrochloride

Epilepsy has been documented to lead to many changes in the nervous system including cell loss and mossy fiber sprouting. Neuronal loss and aberrant neuroplastic changes in the dentate gyrus of the hippocampus have been identified in the pentylenetetrazole (PTZ) kindling model. Antiseizure activity of selective serotonin reuptake inhibitors has been reported in several studies. In the current study, the protective effect of fluvoxamine against PTZ-kindling was investigated in terms of seizure scores, neuronal loss, and regulation of hippocampal neuroplasticity. Further, the role of 5-HT3 receptors was determined. Kindling was induced by repeated injections of PTZ (35 mg/kg) thrice weekly, for a total of 13 injections. One hundred male albino mice were allocated into 10 groups: (1) saline, (2) PTZ, (3) diazepam (1 mg/kg)+PTZ, (4-6) fluvoxamine (5, 10 or 20 mg/kg)+PTZ, (7) ondansetron+fluvoxamine (20 mg/kg)+PTZ, (8) ondansetron+PTZ group, (9) ondansetron (2 mg/kg, i.p.)+saline, and (10) fluvoxamine (20 mg/kg)+saline. PTZ-kindled mice showed high seizure activity, hippocampal neuronal loss, and expression of growth-associated phosphoprotein (GAP-43) compared with saline-treated mice. Repeated administration of fluvoxamine (20 mg/kg) in PTZ-kindled mice suppressed seizure scores, protected against hippocampal neuronal loss, and downregulated GAP-43 expression, without producing any signs of the 5-HT syndrome in healthy rats. Importantly, pretreatment with a selective 5-HT3 receptor blocker (ondansetron) attenuated the aforementioned effects of fluvoxamine. In conclusion, the ameliorating effect of fluvoxamine on hippocampal neurons and neuroplasticity in PTZ-kindled mice was, at least in part, dependent on enhancement of hippocampal serotoninergic transmission at 5-HT3 receptors.

Topics: Animals; Anticonvulsants; Cell Death; Disease Models, Animal; Fluvoxamine; GAP-43 Protein; Hippocampus; Kindling, Neurologic; Male; Mice; Neurons; Ondansetron; Pentylenetetrazole; Random Allocation; Receptors, Serotonin, 5-HT3; Seizures; Serotonin 5-HT3 Receptor Antagonists

Topics: Adolescent; Amphetamine-Related Disorders; Antidepressive Agents; Antitussive Agents; Anxiety Disorders; Child; Dextromethorphan; Diagnosis, Differential; Drug Interactions; Female; Fluvoxamine; Hallucinogens; Humans; Male; N-Methyl-3,4-methylenedioxyamphetamine; Obsessive-Compulsive Disorder; Seizures; Selective Serotonin Reuptake Inhibitors; Serotonin Agents; Serotonin Syndrome; Sertraline

To inform clinicians of the possibility that seizures due to therapeutic doses of fluvoxamine may not be as rare as previously considered.. A 49-year-old white man with schizoaffective disorder and a past history of seizures secondary to head trauma had been seizure-free for approximately 10 years. Fluvoxamine therapy was begun due to increasing obsessive-compulsive behavior. Despite receiving anticonvulsants for his mood disorder, the patient had a breakthrough seizure. There were no underlying medical conditions that might have induced this seizure. No further seizures occurred after he was placed on a higher dosage of the anticonvulsants. The obsessive-compulsive behavior improved considerably as a result of fluvoxamine treatment.. The patient presented here developed a seizure with a therapeutic dosage of fluvoxamine; seizures associated with this agent have occurred more often with overdose. Multiple factors such as a prior history of seizures, head trauma, and concurrent treatment with other psychotropic agents are considered in this case report.. Despite the relatively safe and benign adverse effect profile of the selective serotonin-reuptake inhibitors such as fluvoxamine, clinicians should be cautious about seizures as an adverse effect, especially when the patient has even a remote history of seizure or head trauma.

Topics: Dose-Response Relationship, Drug; Fluvoxamine; Humans; Male; Middle Aged; Psychotic Disorders; Seizures; Selective Serotonin Reuptake Inhibitors

A 38-year-old patient with severe obsessive-compulsive disorder received fluvoxamine in a clinical study. Psychometric ratings showed marked clinical improvement in the third week of fluvoxamine administration, but after 8 weeks, at a dose of 300 mg per day, he suffered a grand mal seizure after drinking a glass of beer (0.2 liter). He had no history of previous epileptic seizures. Careful neurological evaluation including computer tomography and magnetic resonance imaging of the brain revealed no signs of acute disease. EEG before the fit did not show epileptiform activity; after the fit, spikes and spike-wave complexes appeared, which disappeared upon discontinuation of fluvoxamine. Since his obsessive-compulsive symptoms had responded well to fluvoxamine and worsened after its discontinuation, the drug was cautiously reintroduced. Improvement of the obsessive-compulsive symptoms was observed again, but spikes and spike-wave complexes reappeared at a dose of 50 mg per day. Under anticonvulsant treatment with carbamazepine, fluvoxamine was increased to 100 mg per day. No seizures occurred during a follow-up to two years.

Topics: Adult; Alcohol Drinking; Antidepressive Agents; Beer; Electroencephalography; Fluvoxamine; Humans; Male; Obsessive-Compulsive Disorder; Psychiatric Status Rating Scales; Seizures

Topics: Adult; Ambulatory Surgical Procedures; Female; Fluvoxamine; Humans; Seizures

Topics: Antidepressive Agents; Depressive Disorder; Fluvoxamine; Humans; Oximes; Seizures; Serotonin Antagonists

Freely moving rats were implanted with cortical, caudal, thalamic, and reticular electrodes. Drugs were infused intravenously at a constant rate up to a final cumulative dose of 40, 50, or 60 mg/kg. Doses of 10 mg/kg imipramine, viloxazine, desmethylimipramine, mianserin, and maprotiline produced spike-wave complexes, spikes, and increased spindling. General sustained discharges occurred after 20 mg/kg of mianserin, viloxazine, imipramine, desmethylimipramine and amitriptyline, and after 30 mg/kg of maprotiline. An abnormal high-amplitude pattern was evident after mianserin, amitriptyline, imipramine, and desmethylimipramine. On the average, seizures were observed at 40 mg/kg and were seen after desmethylimipramine (50 mg/kg), mianserin (30 mg/kg), amitriptyline (20 mg/kg), imipramine (40 mg/kg), maprotiline (40 mg/kg), and zimelidine (50 mg/kg). Ranking the tested antidepressants in decreasing order in accordance with their relative (pro)convulsive properties gives: amitriptyline greater than mianserin much greater than imipramine greater than desmethylimipramine greater than viloxazine much greater than maprotiline much greater than zimelidine greater than clovoxamine greater than nomifensine = fluvoxamine.

Topics: Amitriptyline; Animals; Antidepressive Agents; Desipramine; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Epilepsy; Fluvoxamine; Imipramine; Male; Maprotiline; Mianserin; Oximes; Rats; Rats, Inbred Strains; Seizures; Viloxazine