Comparative efficacy and safety of Crocus sativus L. for treating mild to moderate major depressive disorder in adults: a meta-analysis of randomized controlled trials

Figures & data

Figure 1 Flow diagram indicating the process of selecting literature for meta-analysis.

Figure 2 Quality assessments for each included study.

Notes: “+” means “low bias”, “−” means “high bias”, and “?” means “unclear bias”.

Table 1 Characteristics of the seven included studies

Study	Country	Study design	Na	Age, years (mean ± SD)	Females (%)	Disease	Severity	Diagnostic criteria	Treatment, dosage, duration	Outcome measures	Changed scores
Akhondzadeh Basti et al (2007)^Citation43	Iran	RCT	40	34.8±6.9	52.5	MDD	Mild to moderate	DSM-IV	Petal of saffron, 30 mg/day, 8 weeks Fluoxetine, 20 mg/day, 8 weeks	HAMD-17	−12.00±4.1 vs −13.50±4.91
Akhondzadeh et al (2004)^Citation44	Iran	RCT	30	34.0±9.2	56.7	MDD	Mild to moderate	DSM-IV	Commercial saffron, 30 mg/day, 6 weeks Imipramine, 100 mg/day, 6 weeks	HAMD-17	−11.2±1.39 vs −10.41±1.38
Akhondzadeh et al (2005)^Citation45	Iran	RCT	40	36.3±7.4	45.0	MDD	Mild to moderate	DSM-IV	Commercial saffron, 30 mg/day, 6 weeks Placebo, 30 mg/day, 6 weeks	HAMD-17	−12.2±4.67 vs −5.1±4.71
Ghajar et al (2017)^Citation46	Iran	RCT	66	36.0±11.1	43.3	MDD with anxiety	Mild to moderate	DSM-V	Saffron, 15–30 mg/day, 6 weeks Citalopram, 20–40 mg/day, 6 weeks	HAMD-14	−10.13±5.96 vs −11.27±3.67
Mazidi et al (2016)^Citation47	Iran	RCT	60	43.2±9.7	70.0	MDD with anxiety	Mild to moderate	DSM-IV	Commercial saffron, 100 mg/day, 12 weeks Placebo, 100 mg/day, 12 weeks	BDI	−6.69±2.73 vs −4.35±4.6
Moshiri et al (2006)^Citation48	Iran	RCT	40	35.7±6.9	42.5	MDD	Mild to moderate	DSM-IV	Petal of saffron, 30 mg/day, 6 weeks Placebo, 30 mg/day, 6 weeks	HAMD-17	−14.01±5.53 vs −5.05±4.63
Noorbala et al (2005)^Citation49	Iran	RCT	40	36.9±7.9	50.0	MDD	Mild to moderate	DSM-IV	Commercial saffron, 30 mg/day, 6 weeks Fluoxetine, 20 mg/day, 6 weeks	HAMD-17	−12.20±4.67 vs −15.00±5.88

Note:

a The number of patients who were assigned randomly.

Abbreviations: BDI, Beck Depression Inventory; DSM, Diagnostic and Statistical Manual of Mental Disorders; HAMD, Hamilton Depression Rating Scale; MDD, major depressive disorder; RCT, randomized controlled trial.

Figure 3 Meta-analyses of primary outcomes: (A) improvement of depression symptoms compared with placebo; (B) improvement of depression symptoms compared with synthetic antidepressants.

Abbreviations: CI, confidence interval; IV, inverse variation; SD, standard deviation; Std, standard.

Figure 4 Results for subgroup analyses of primary outcomes: (A) subgroup analysis in studies compared with placebo, stratified by treatment dosage, duration, and outcome measures; (B) subgroup analysis in studies compared with synthetic antidepressants, stratified by type of antidepressants.

Abbreviations: BDI, Beck Depression Inventory; CI, confidence interval; HAMD, Hamilton Depression Rating Scale; IV, inverse variation; SD, standard deviation; SSRIs, selective serotonin reuptake inhibitors; Std, standard; TCAs, tricyclic antidepressants.

Table 2 Meta-analyses of secondary outcomes

Secondary outcomes	Comparison	Studies	Effect size		Heterogeneity
			SMD (95% CI)	P-value	I^2 (%)	P-value
Remission rate^Citation43,Citation46	Antidepressants	2	0.54 (0.21, 1.41)	0.21	17	0.27
Response rate^Citation43,Citation46	Antidepressants	2	0.47 (0.19, 1.19)	0.11	0	0.86
Drop-out rate^Citation45,Citation47,Citation48	Placebo	3	0.87 (0.07, 10.64)	0.91	67	0.05
Drop-out rate^Citation43,Citation44,Citation46,Citation49	Antidepressants	4	1.00 (0.28, 3.63)	1.00	0	1.00

Abbreviations: CI, confidence interval; SMD, standardized mean difference.

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