"Dopamine-Dependent" Side Effects of Selective Serotonin Reuptake Inhibitors: A Clinical Review

Objective: Neurophysiologic findings indicate an inhibition of dopaminergic neurotransmission by selective serotonin reuptake inhibitors (SSRIs). This article highlights the relationships between changes in dopaminergic neurotransmission induced by SSRIs and the occurrence of certain side effects such as hyperprolactinemia, extrapyramidal symptoms, sexual and cognitive dysfunction, galactorrhea, mammary hypertrophy, and, more rarely, gynecomastia.

Data Sources and Selection: A systematic search of the literature in English, French, and German from 1980 to 2004 was performed in MEDLINE, EMBASE, and the Cochrane Library using the keywords SSRI, dopamine, serotonin, side effects, antidepressants, citalopram, escitalopram, sertraline, paroxetine, fluoxetine, fluvoxamine, and nefazodone. References cited in all trials were searched iteratively to identify missing studies. All studies concerning inhibition of dopaminergic neurotransmission by SSRIs and SSRI-related side effects were considered. We retained 62 significant articles debating the subject.

Data Extraction and Synthesis: We critically reviewed the studies, depending on the methodologies (case reports, clinical reports, randomized studies), and assessed the pertinence of “dopamine-dependent” SSRI-related side effects. The analytic review of these articles suggests that some specific SSRI-related side effects be classified as dopamine-dependent.

Conclusions: At a clinical level, it could be useful to underline dopamine-dependent characteristics of some SSRI-related side effects. This approach would allow clinicians the opportunity to search other dopamine-dependent side effects systematically. At a pharmacologic level, this approach could stimulate the development of molecules with a “corrective” function on dopamine-dependent side effects of SSRIs by facilitating dopaminergic neurotransmission.