Mild-to-moderate depression
Depressive episode with mild or moderate symptom severity by DSM-5 or ICD-10. In mild forms, psychotherapy and watchful waiting may replace medication; in moderate forms, pharmacotherapy or combination with psychotherapy is used.
ICD-10 F32.09 drugs
Also known as: Mild depression, Moderate depression
Drugs used for this condition
- BHypericum perforatumSecond line · Antidepressants. Other antidepressants of herbal originSt. John's wort is one of the best-studied herbal options in depression. EMA HMPC in 2018 granted well-established-use status for mild to moderate depressive episodes. The Linde Cochrane review 2008 pooled 29 RCTs with 5489 patients: a standardised St. John's wort extract was more effective than placebo and as effective as SSRIs (fluoxetine, sertraline, citalopram) in mild to moderate depression. NICE NG222 (2022) permits St. John's wort in mild episodes but explicitly warns about multiple interactions. The effect builds over 4–6 weeks at 300 mg of standardised extract three times daily. In severe depression St. John's wort is not indicated – no efficacy data. If St. John's wort was prescribed and you take other medications, do not start before reviewing every pill with a doctor: the interaction list is long and clinically dangerous.
- CSaffron (Crocus sativus stigma extract)Add-on therapy · Herbal antidepressant supplement, standardised affron® and Safr'Inside® extractsSaffron is one of the few herbs with a series of meta-analyses in mild to moderate depression. Hausenblas 2013 pooled 5 RCTs with 142 patients, Lopresti 2014 covered 6 RCTs and Marx 2019 covered 11 RCTs. Conclusions converge: saffron is more effective than placebo and comparable to low-dose fluoxetine and imipramine in mild to moderate depression. Effect size is moderate, study duration 6–8 weeks, samples mostly Iranian. No EMA HMPC monograph for saffron exists, and well-established use has not been granted due to limited geography and small sample size. NICE NG222 (2022) does not mention saffron. Standardised affron® and Safr'Inside® extracts at 28–30 mg/day are the only form with reproducible clinical data. In severe depression saffron is not indicated. If saffron is considered as a replacement for standard treatment in moderate or severe depression, consider seeking a second opinion.
Marketing claims without evidence base
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
- D5-hydroxytryptophan (5-HTP)Not recommended · Direct serotonin precursor, supplement (not registered as medicine in EU or US)5-HTP is widely sold as a «natural antidepressant» promising a «safe SSRI alternative». Evidence base is weak: Cochrane 2002 (Shaw) reviewed 108 studies, of which only 2 RCTs met quality criteria – 64 patients total, ambiguous results. No large modern RCT has confirmed clinically meaningful 5-HTP efficacy in depression. NICE 2022 and SEP 2014 list CBT and SSRIs first-line for mild-to-moderate depression; 5-HTP is not included. Main risk: self-combination with an antidepressant or tramadol – serotonin syndrome (tachycardia, hyperthermia, myoclonus, rigidity, confusion). If 5-HTP was recommended for depression instead of a psychiatric consultation, consider seeking a second opinion.
- DCholine alfoscerateNot recommended · Other nervous system drugs. ParasympathomimeticsAlpha-GPC is sometimes recommended for depression in elderly patients with vascular cognitive dysfunction as «cholinergic mood support». No direct RCTs in depressive disorder: ASCEND-S and ASCOMALVA data recorded behavioural-scale changes in dementia patients, not in patients with primary depressive episode. NICE 2022 (NG222) for mild-to-moderate depression lists CBT and SSRIs (sertraline, escitalopram, fluoxetine) first-line; alpha-GPC is not in guidelines. SEP 2014 in Spain gives the same recommendation. If alpha-GPC was recommended for depression instead of a psychiatric consultation, CBT and adequate pharmacotherapy, consider seeking a second opinion.
- DCholine bitartrateNot recommended · Essential nutrient, dietary supplement. The basic choline form used in supplements. Not registered as a medicine in the EU or USA; sold as a supplement in RussiaCholine bitartrate is a source of choline, sold in supplements and promoted for mood and brain function, including mild to moderate depression. Convincing benefit for this use has not been shown – there is no evidence base supporting an antidepressant effect. For a mild to moderate depressive episode, psychotherapy and, when a doctor decides it fits, antidepressants are the approaches that help, so it is worth seeing a specialist.
- DLecithin (soy or sunflower phosphatidylcholine)Not recommended · Phospholipid mixture, dietary supplement. A mass OTC «memory drug» and «hepatoprotector» in Russia. Essentiale (Sanofi, essential phospholipids) is a separate regulated medicine, registered by AEMPS and in Russia for NAFLDLecithin (soy or sunflower phosphatidylcholine) is a dietary supplement and a source of phosphatidylcholine and choline. For mild to moderate depressive episodes it gets promoted as a mood and nervous-system support. There is no convincing evidence for this use: quality studies confirming an effect on depressive symptoms are lacking. What helps in mild to moderate depression are approaches with proven benefit, mainly psychotherapy and, when indicated, antidepressants chosen by a doctor. Lecithin is safe as a supplement, but it should not replace treatment with proven benefit, because that can mean losing the time and care a person actually needs.
- DRhodiola rosea (golden root)Not recommended · Plant adaptogen, supplement. In EU – traditional herbal medicinal product per EMA HMPC monographRhodiola is sold as a «natural antidepressant» promising a «safe SSRI alternative». Small RCTs in mild-to-moderate depression (Darbinyan 2007, Mao 2015) showed heterogeneous results with small samples. NICE 2022 and SEP 2014 list CBT and SSRIs first-line for mild-to-moderate depression; rhodiola is not included. If rhodiola was recommended for depression instead of a psychiatric consultation, consider seeking a second opinion.
- FL-tryptophanNot recommended · Essential amino acid, precursor of serotonin, melatonin and niacin. In the UK registered by MHRA as Optimax for resistant depressionL-tryptophan supplement is sold as a «natural antidepressant» promising a «safe SSRI alternative». Evidence base in mild-to-moderate depression is insufficient: Cochrane 2002 did not confirm clinically meaningful efficacy. NICE 2022 and SEP 2014 list CBT and SSRIs first-line for mild-to-moderate depression; L-tryptophan is not included. Main risk: self-combination with an antidepressant, tramadol or triptans – serotonin syndrome (tachycardia, hyperthermia, myoclonus, rigidity, confusion). A separate documented harm is the historical eosinophilia-myalgia syndrome epidemic with fatalities, after which the FDA removed L-tryptophan from over-the-counter sale. Unproven benefit against real harm is a net-minus, so it is not recommended. If L-tryptophan was recommended for depression instead of a psychiatric consultation, consider seeking a second opinion.
- FMucuna pruriens (velvet bean)Not recommended · Plant source of L-DOPA. Used in Ayurveda for Parkinson disease; in the West – biohacking supplementMucuna is sold in the biohacking segment as a «natural antidepressant» on the dopaminergic mood modulation hypothesis via L-DOPA. No evidence base in depression: no significant RCTs. NICE 2022 and SEP 2014 list CBT and SSRIs first-line for mild-to-moderate depression; mucuna is not mentioned. Main risk: mucuna contains L-DOPA and interacts with MAO-I, antipsychotics and antihypertensives – self-administration is unsafe. If mucuna was recommended for depression instead of a psychiatric consultation, consider seeking a second opinion.
How to read tiers A–F
Evidence tiers belong to the drug-indication pair, not to the drug as a whole: the same substance can be A for one condition and F for another.
- AStrong evidence – first or second line in international guidelines
- BRecommended in selected cases
- CStudy data contradict each other
- DBenefit not proven, no documented harm
- FDocumented harm, or risk without benefit