Serotonin reuptake inhibitors (SSRIs) have been used as adjunctive agents in open and recently double blind studies of the treatment of patients with schizophrenia, showing improvements in negative symptoms over 6 months. Extrapyramidal symptoms (EPS) were not exacerbated. Serotonergic blockade is one mechanism advocated for the apparent efficacy of many atypical neuroleptics in the treatment of negative schizophrenic symptoms and also for the low rate of EPS. SSRIs undoubtedly cause EPS in some patients, perhaps linked to the modification both of dopamine and acetylcholine release. Recent PET studies show that SSRIs differ in their effects on striatal dopamine concentration and receptor binding. Both serotonin and dopamine have been implicated in the pathophysiology of OCD and use of combined neuroleptic and SSRI treatment has also been described in cases refractory to an SSRI along with disorders related to OCD, such as Tourette's syndrome and trichotillomania. It has also been suggested that the anorectic effects of SSRIs are mediated by dopaminergic mechanisms. The dopamine reuptake blocker bupropion has been used to treat sexual dysfunction secondary fluoxetine, implicating dopamine in these side-effects. Animal studies suggest a dopaminergic mechanism for anhedonia, a core feature of major depression. Dopamine receptor blockade has been shown to reverse improvement seen with a range of antidepressants, including drugs selective for serotonin or noradrenaline, in animal models. This must be reconciled with the adjunctive effect of dopamine blockers added to antidepressants, including SSRIs, in psychotic depression.