title: The serotonergic and noradrenergic effects of antidepressant drugs are anticonvulsant, not proconvulsant.
abstract: Contrary to existing evidence, convulsant liability of the antidepressants has been attributed to noradrenergic and serotonergic increments. This is a classic case of confusing treatment effects with the manifestations of illness. In fact, the remarkable anticonvulsant effectiveness of antidepressant-induced noradrenergic and serotonergic activation has been ignored. Some antidepressant drugs such as the specific serotonin reuptake inhibitor (SSRI) fluoxetine may be devoid of convulsant liability entirely, while having distinct anticonvulsant properties. Some authorities advance the notion that the seizure predisposition of patients with epilepsy increases risks for antidepressant-induced seizures. However, evidence does not support this contention. Instead, data increasingly support the concept that noradrenergic and serotonergic deficiencies contribute to seizure predisposition. Indeed, the antidepressants have the potential to overcome seizure predisposition in epilepsy. Whereas therapeutic doses of antidepressants elevate noradrenergic and serotonergic transmission, larger doses can activate other biological processes that may be convulsant.
authors.affiliation: University of Illinois College of Medicine, Peoria, IL, USA. jobe252@insightbb.com
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Jobe
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Browning
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000494:pharmacology*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D015897:Comorbidity; D003292:Convulsants / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D008959:Models, Neurological; D019964:Mood Disorders / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D009638:Norepinephrine / Q000172:deficiency / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D003292:Convulsants; D012701:Serotonin; D009638:Norepinephrine