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Fluoxetine and Side Effects

Ross J. Baldessarini, MD
Arch Gen Psychiatry. 1990;47(2):191-192. doi:10.1001/archpsyc.1990.01810140091015.
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To the Editor.—  Bouchard and colleagues1 recently reported an increased risk of extrapyramidal signs and symptoms during treatment with fluoxetine or other potent and selective inhibitors of neuronal uptake of serotonin. Others have noted such symptoms when this new antidepressant was combined with a neuroleptic agent,2 leading to the question of whether a pharmacodynamic effect or a pharmacokinetic drug interaction was at work, as may occur with increased plasma concentrations of tricyclic antidepressants.3 Bouchard et al suggested that such reactions with fluoxetine or similar agents alone might arise through the ability of serotonin uptake blockers to potentiate putative inhibitory effects of serotonin on the metabolic production or release of dopamine by neurons of the basal ganglia.We tested this prediction in a laboratory model by measuring the accumulation of dopa after pretreating with a centrally active inhibitor of its decarboxylation (NSD-1015, 150 mg/kg intraperitoneally, 45 minutes before

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