This article by Correll et al. aims to provide useful information for physicians about treating negative symptoms in schizophrenia. A multistep PubMed and Google Scholar literature search on the phrase “negative symptoms schizophrenia” was used to find review articles and metanalyses published from 2009–2019. Also, to find articles outside of the computerized search, a manual search of reference lists of relevant reviews and primary studies were conducted. The article summarizes the definitions and terms that surround negative symptoms and expresses that schizophrenia patients have poor functional outcomes and long-term disability because negative symptoms are a central component of the illness.

The article explains that “to date, no agent is approved by the FDA for the treatment of negative symptoms” and points out that “to date, the only prospective, large-scale, randomized, double-blind evidence demonstrating the superiority of one approved antipsychotic over another in the treatment of negative symptoms comes from a rigorously designed 26- week study comparing the effects of fixed-dose cariprazine (3 mg/d, 4.5 mg/d [target dose], or 6 mg/d) and risperidone (3 mg/d, 4 mg/d [target dose], or 6 mg/d) on predominant negative symptoms in patients with stable and limited positive symptoms, and without relevant depression or extrapyramidal symptoms.” The study showed that cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, has significant differences and clinically relevant improvement in both negative symptoms and functional impairment compared to risperidone. Cariprazine also showed significant advantages over risperidone on the Clinical Global Impressions-Improvement Scale (CGI-I) and the Personal and Social Performance Scale (PSP), further demonstrating that it can be a clinically meaningful treatment for negative symptoms.

Other adjunctive treatments against negative symptoms, such as glutamatergic compounds (e.g., glycine, D-serine, D-cycloserine), minocycline, dopamine agonists (e.g., selegiline, modafinil), and cholinergics, have shown limited evidence thus far. The article calls for higher-quality trials and patient-based meta-analyses to examine whether patients might benefit from combination treatment, as there is currently no single co-treatment strategy with sufficient evidence to treat negative symptoms. Agents acting on NMDA receptors, alpha 7 nicotinic receptors, and 5-HT2A and sigma-2 receptors, antidepressants, deep transcranial magnetic stimulation and transcranial direct current stimulation are all under investigation for negative symptoms treatment.

Some strategies that have shown some benefits in improving negative symptoms:

Even though the results from these psychosocial treatments are mixed and inconsistent, the article maintains that these may be an “important way for clinicians to support patients and their families as they cope with negative symptoms and attempt to improve outcomes and quality of life.” To help patients reach improved outcomes, negative symptoms need to be recognized, assessed and management as best as possible.

Negative symptoms occur in most schizophrenia patients and often remain unrecognized by clinicians. Even if recognized, there is only limited evidence-based treatment against negative symptoms, causing poor patient functionality, low productivity and a decline in quality of life. Monotherapy agents tested in well-designed clinical trials (i.e. cariprazine) have shown promise in improving negative symptoms.