The serotonin paradox: Negative symptoms and SSRI augmentation

Negative symptoms of schizophrenia are often difficult to treat and may be associated with poorer long-term outcome. As depressive and negative symptoms show some overlap, augmentation of neuroleptics by antidepressants has repeatedly been investigated for efficacy against negative symptoms in schizophrenic patients. Studies on SSRI augmentation of neuroleptic medication reveal some evidence for increased efficacy of conventional antipsychotics in negative symptoms after addition of SSRIs. Since no correlation could be found between improvement of negative symptoms on the one hand and positive, depressive or extrapyramidal motor symptoms on the other, a direct effect seems likely. SSRIs may therefore be an alternative to clozapine, especially in patients for whom there are contraindications against clozapine treatment. As yet, there is no convincing rationalization for the paradox that both serotonergic and antiserotonergic substances, e.g. atypical antipsychotics, may improve negative symptoms.