Treatment of negative symptoms: Where do we stand, and where do we go?

Negative symptoms, e.g. social withdrawal, reduced initiative, anhedonia and affective flattening, are notoriously difficult to treat. In this review, we take stock of recent research into treatment of negative symptoms by summarizing psychosocial as well as pharmacological and other biological treatment strategies. Major psychosocial approaches concern social skills training, cognitive behavior therapy for psychosis, cognitive remediation and family intervention. Some positive findings have been reported, with the most robust improvements observed for social skills training. Although cognitive behavior therapy shows significant effects for negative symptoms as a secondary outcome measure, there is a lack of data to allow for definite conclusions of its effectiveness for patients with predominant negative symptoms. With regard to pharmacological interventions, antipsychotics have been shown to improve negative symptoms, but this seems to be limited to secondary negative symptoms in acute patients. It has also been suggested that antipsychotics may aggravate negative symptoms. Recent studies have investigated glutamatergic compounds, e.g. glycine receptor inhibitors and drugs that target the NMDA receptor or metabotropic glutamate 2/3 (mGlu2/3) receptor, but no consistent evidence of improvement of negative symptoms was found. Finally, some small studies have suggested improvement of negative symptoms after non-invasive electromagnetic neurostimulation, but this has only been partly replicated and it is still unclear whether these are robust improvements. We address methodological issues, in particular the heterogeneity of negative symptoms and treatment response, and suggest avenues for future research. There is a need for more detailed studies that focus on different dimensions of negative symptoms.