Crocus sativus (saffron) adjunct to risperidone for negative symptoms of schizophrenia: a randomized, double-blind, placebo-controlled trial.

Current treatments for schizophrenia encounter resistance, limited efficacy, and limiting complications, necessitating novel approaches. The effects of saffron on negative symptoms were investigated as it has shown neuroprotective and antipsychotic properties. Fifty-six clinically stable chronic schizophrenic outpatients were equally assigned to saffron 15 mg q12hr or placebo groups while continuing risperidone. The Positive and Negative Syndrome Scale (PANSS) was used to assess schizophrenia-related symptoms in weeks 4 and 8. Also, the patients were assessed for the Hamilton depression rating scale (HDRS) and adverse effects. The baseline characteristics of the groups were comparable (Ps > 0.05). There were significant time-treatment interaction effects on negative ( = 0.137), general psychopathology ( = 0.193), and total ( = 0.113) PANSS scores. Affirmatively, their reductions were significantly greater in the saffron group until weeks 4 (Cohen's ds = 0.922, 0.898, and 0.759, respectively) and 8 (Cohen's ds = 0.850, 1.047, and 0.705, respectively). Regarding the negative symptoms, a better 25% response rate was obtained in the saffron group until the endpoint (P = 0.003). The HDRS scores, extrapyramidal symptom rating scale scores, and side effect frequencies were comparable between the groups (Ps > 0.05). Saffron was beneficial for primary negative symptoms of chronic schizophrenia in a safe and tolerable manner. It also outperformed placebo in improving general psychopathology and total symptoms.