To sweat or not to sweat? A hypothesis on the effects of venlafaxine and SSRIs

Summary The hypothesis put forward here attempts to explain how the efficacy of venlafaxine against climacteric symptoms, including sweating, can be reconciled with the fact that this medication is known to cause sweating as an adverse side-effect. Peripherally, the sweating function is regulated noradrenergically by the sympathetic nervous system, central noradrenergic signal transmission being subject partly to inhibitory, partly to excitatory influences by serotonin (5-HT). Theoretically, sweating can be both initiated and inhibited by the activity of selective 5-HT reuptake inhibitors (SSRIs), so that the noradrenergic “tone” resulting from the interaction of noradrenergic and serotonergic neurons in the various regions of the brain probably determines the degree of sweating. Venlafaxine can counteract sweating at low doses as a result of its serotonergic effect, while it can increase sweating at higher doses with an increasing noradrenergic active component. At daily doses of up to 75 mg venlafaxine, sweating is largely avoided as a concomitant effect.