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

2024-12-12
International clinical psychopharmacology 40(6)
- Siamand Mazhar
- Ahmad Shamabadi
- Kimia Kazemzadeh
- Mohammad Aidin Farahvash
- Atiye Heidari Dalfard
- Bita Fallahpour
- Mohammad-Reza Khodaei Ardakani
- Shahin Akhondzadeh

PubMed: 39661337
DOI: 10.1097/yic.0000000000000575

Study Design

Type: Randomized Controlled Trial (RCT)
Population: 56 clinically stable chronic schizophrenic outpatients
Methods: Randomized, placebo-controlled, 8 weeks of saffron 15 mg twice daily while continuing risperidone
Duration: 8 weeks
Funding: Unclear

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 ( P s > 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 d s = 0.922, 0.898, and 0.759, respectively) and 8 (Cohen's d s = 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 ( P s > 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.

Research Insights

Saffron→Improved Negative Symptom Response Rate
Regarding the negative symptoms, a better 25% response rate was obtained in the saffron group until the endpoint ( P = 0.003)
Effect
Beneficial
Effect size
Large
Dose
15 mg q12hr (30 mg/day)
Saffron→Reduced Depression
The HDRS scores... were comparable between the groups ( P s > 0.05)
Effect
Neutral
Effect size
Small
Dose
15 mg q12hr (30 mg/day)
Saffron→Reduced Extrapyramidal Symptoms
The... extrapyramidal symptom rating scale scores... were comparable between the groups ( P s > 0.05)
Effect
Neutral
Effect size
Small
Dose
15 mg q12hr (30 mg/day)
Saffron→Reduced General Psychopathology
There were significant time-treatment interaction effects on... general psychopathology ( = 0.193)... their reductions were significantly greater in the saffron group until weeks 4 (Cohen's d s = 0.898) and 8 (Cohen's d s = 1.047)
Effect
Beneficial
Effect size
Large
Dose
15 mg q12hr (30 mg/day)
Saffron→Reduced Negative Symptoms
There were significant time-treatment interaction effects on negative ( = 0.137)... their reductions were significantly greater in the saffron group until weeks 4 (Cohen's d s = 0.922) and 8 (Cohen's d s = 0.850)
Effect
Beneficial
Effect size
Large
Dose
15 mg q12hr (30 mg/day)
Saffron→Reduced Total PANSS Score
There were significant time-treatment interaction effects on... total ( = 0.113) PANSS scores... their reductions were significantly greater in the saffron group until weeks 4 (Cohen's d s = 0.759) and 8 (Cohen's d s = 0.705)
Effect
Beneficial
Effect size
Large
Dose
15 mg q12hr (30 mg/day)

Adverse Events Reported

Saffron→extrapyramidal symptoms
The HDRS scores, extrapyramidal symptom rating scale scores, and side effect frequencies were comparable between the groups ( P s > 0.05).
Finding
No significant difference
Significant
No
Saffron→Overall tolerability
It also outperformed placebo in improving general psychopathology and total symptoms.
Finding
Reported