Managing Negative Symptoms of Schizophrenia: How Far Have We Come?

The specific efficacy of antipsychotics on negative symptoms is questionable, suggesting an urgent need for specific treatments for negative symptoms. This review includes studies published since 2014 with a primary or secondary focus on treating negative symptoms in schizophrenia. Special emphasis is given to recently published meta-analyses. Topics include novel pharmacological approaches, including glutamatergic-based and nicotinic-acetylcholinergic treatments, treatments approved for other indications by the US FDA (or other regulatory bodies) (antipsychotics, antidepressants, and mood stabilizers), brain stimulation, and behavioral- and activity-based approaches, including physical exercise. Potential complications regarding the design of current negative symptom trials are discussed and include inconsistent placebo effects, lack of reliable biomarkers, negative symptom scale and inclusion criteria variability, attempts to distinguish between primary and secondary negative symptoms, lack of focus on early psychosis, and the potential iatrogenic bias of clinical trials.