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Antipsychotic drugs are effective for psychotic symptoms but of limited utility for negative symptoms and general psychopathology (e.g., depression, anxiety, stress). Some patients with schizophrenia are thought to experience an exacerbation of symptoms caused by an imbalance of pro- and anti-inflammatory cytokines and elevated levels of inflammatory proteins. These immune-inflammatory alterations may adversely impact dopaminergic, glutamatergic, and cholinergic neurotransmission, which may be linked to the positive, negative, and cognitive symptoms in schizophrenia. Withania sominfera (WSE), a medicinal herb with known anti-inflammatory and immunomodulating properties, has proven beneficial for treating anxiety, stress, and depression in separate clinical trials. Professor of Psychiatry K.N. Roy Chengappa, MD wondered if adding WSE as an adjunctive treatment for individuals with schizophrenia might produce similar benefits. He collaborated with colleagues Jaspreet Brar, MD, PhD, Jessica Gannon, MD and Patricia Schlicht, RN, MA, to conduct a randomized, double-blind, placebo-controlled clinical trial to examine the effects of WSE when added to antipsychotic medications. Their findings appear in an article published in the Journal of Clinical Psychiatry.

Sixty-six patients with schizophrenia experiencing an exacerbation of symptoms (n = 33 per group) participated in the study. In addition to their antipsychotic medication, one group received WSE while the other group received a placebo during the 12-week trial. Primary outcomes were assessed using the Positive and Negative Symptom Scale (PANSS) (e.g., total and positive, negative, and general symptoms)  and secondary outcomes were based on scores from the Perceived Stress Scale (PSS) and the Clinical Global Impressions (CGI) scale. Beginning at four weeks and continuing to the end of treatment, participants receiving WSE experienced significant reductions in negative, general, and total symptoms, but no change in positive symptoms. The investigators used PSS data to evaluate stress and inflammatory indices and found that scores improved significantly with WSE compared to placebo. Adverse events were mild to moderate and transient among participants in the WSE treatment arm; however, sleepiness and upper abdominal discomfort were more common in this group. No significant between-treatment differences were noted in body weight, vital signs, or laboratory measures, suggesting good tolerability of WSE. Overall, the study suggests that for patients who continue to experience mild to moderate positive symptoms as well as negative, general, and stress symptoms despite ongoing antipsychotic treatment, adding a standardized extract of WSE may help reduce these symptoms. 

Dr. Chengappa, the study’s first author, noted some limitations with the study; for example, they did not select patients to participate who had evidence of pre-existing inflammation. Moreover, it is not known whether higher or lower doses of the standardized extract of Withania somnifera may be just as effective. “Basic pharmacokinetic and pharmacodynamic studies are needed to learn more about absorption, distribution, and elimination characteristics of this agent,” he added, “It will also be important to assess which of the many bioactive constituent(s) of this herbal extract might be responsible for the beneficial effects. 

Adjunctive Use of a Standardized Extract of Withania somnifera (Ashwagandha) to Treat Symptom Exacerbation in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study
Chengappa KNR, Brar JS, Gannon JM and Schlicht PJ
J Clin Psychiatry. 2018 79(5). pii: 17m11826. doi: 10.4088/JCP.17m11826