DOPAMINE AND THE USE OF SSRIS FOR CONDITIONS OTHER THAN DEPRESSION

Serotonin reuptake inhibitors (SSRIs) have been used as adjunctive age nts in open and recently double blind studies of the treatment of pati ents with schizophrenia, showing improvements in negative symptoms ove r 6 months. Extrapyramidal symptoms (EPS) were not exacerbated. Seroto nergic blockade is one mechanism advocated for the apparent efficacy o f many atypical neuroleptics in the treatment of negative schizophreni c symptoms and also for the low rate of EPS. SSRIs undoubtedly cause E PS in some patients, perhaps linked to the modification both of dopami ne and acetylcholine release. Recent PET studies show that SSRIs diffe r in their effects on striatal dopamine concentration and receptor bin ding. Both serotonin and dopamine have been implicated in the pathophy siology of OCD and use of combined neuroleptic and SSRI treatment has also been described in cases refractory to an SSRI along with disorder s related to OCD, such as Tourette's syndrome and trichotillomania. It has also been suggested that the anorectic effects of SSRIs are media ted by dopaminergic mechanisms. The dopamine reuptake blocker bupropio n has been used to treat sexual dysfunction secondary fluoxetine, impl icating dopamine in these side-effects. Animal studies suggest a dopam inergic mechanism for anhedonia, a core feature of major depression. D opamine receptor blockade has been shown to reverse improvement seen w ith a range of antidepressants, including drugs selective for serotoni n or noradrenaline, in animal models. This must be reconciled with the adjunctive effect of dopamine blockers added to antidepressants, incl uding SSRIs, in psychotic depression.