Remedy | Effectiveness at RCT/meta-analysis (META) level in placebo (PLB) or equivalence (EQU) studies | Receptor targets/mechanism of action | Selected safety concerns | ||
Affective disorders | |||||
St John’s wort | META PLB (n = 26): marginally effective in major depression | 5HT | CYP 3A4 and p-glycoprotein induction may lead to significant pharmacological interactions, serotonergic side effects including serotonin syndrome and induction of mania possible | ||
META EQU (n = 14): effective (3) | GABA | ||||
META PLB (n = 18): trend towards reduction in effect size in meta-analysis, effect size inversely associated with sample size (4) | MAO inhibition | ||||
S-Adenosyl-methionine (SAMe) | META PLB (n = 6) EQU (n = 7) and RCTs EQU (n = 2): effective in major depression (5,6,7) | Facilitates monoamine synthesis (5HT, NA, DA) | Serotonergic side effects as above | ||
Modification of 2nd messenger systems | |||||
n-3 fatty acids | RCT: no effect on mild to moderate depression (8) | Modification of 2nd messenger systems | Toxicity possible if combined with other vitamin A preparations | ||
META PLB (n = 10): improves depressive symptoms in patients with clearly defined depression or bipolar affective disorder. Results heterogenous and subject to publication bias. Role of EPA and DHA requires further evaluation. High-dose EPA more effective? (9) | |||||
META PLB (n = 8) improves depression in patients with bipolar or unipolar depression either as augmentation or monotherapy. Ceiling effect of 1 g for EPA? (10) | |||||
l-Tryptophan, 5-hydroxy-tryptophan | Preliminary | 5HT | Serotonergic side effects as above | ||
Association with eosinophilic myalgic syndrome remains unclear | |||||
Folic acid | Preliminary re augmentation strategy | Precursor to SAMe | Caution in patients with cancer | ||
Inositol | Inconclusive re treatment or augmentation strategy | Modification of 2nd messenger systems | Induction of mania? | ||
Carbamazepine, valproate and lithium ↓ inositol | |||||
Selenium | None available | Antioxidant | Narrow therapeutic index | ||
↑ T4→T3 conversion | |||||
Anxiety and related disorders and insomnia | |||||
Valerian | META PLB (n = 6) and RCTs EQU (n = 2): improves insomnia (11–13) | GABA | Liver toxicity may depend on extract (valepotriates) | ||
Anxiety: insufficient evidence available | |||||
Passion flower | Preliminary for reduction in anxiety | GABA | Some extracts contain cyanogenic components | ||
Chamomile | None available | GABA | |||
Kava kava | META PLB (n = 7): effective in the reduction in anxiety (14) | GABA | Significant liver toxicity possible (may be extract-dependent) | ||
DA antagonist | |||||
Star flower/borage | None available | Unclear | May ↓ seizure threshold, potentially liver toxic | ||
Lemon balm | None available | GABA? | |||
Cholinergic? | |||||
Hops | No single-component trials available | Unclear | |||
Oats | None available | 5HT? (a source of tryptophan) | |||
Lavender | None available | Unclear, also purported to have antidepressive and pain-reducing properties | |||
Melatonin (N-acetyl-S-metoxy tryptamine) | Inconclusive | Regulates circadian rhythm | |||
GABA | |||||
Bach flower remedies | Not effective | Unclear | |||
Psychosis and schizophrenia | |||||
Rauwolfia | Evidence dating back to 1950s/60s. No current evidence available. | Facilitates degradation of monoamines | Depression, cardiac effects | ||
n-3 fatty acids | Inconclusive | Cf above | Cf above | ||
Tardive dykinesia | |||||
Vitamin E | Inconclusive | Antioxidant | May ↑ all-cause mortality | ||
Melatonin | Inconclusive | Antioxidant | |||
n-3 fatty acids | Not effective | Cf above | Cf above |
Updated and collated from references 1 and 2.
CYP, cytochrome P 450; DA, dopamine; GABA, gamma-aminobutyric acid; DHA, docosahexaonic aicd; EPA, eicosapentaenoic acid; EQU, equivalence studies; 5HT, 5-hydroxytryptophan (serotonin); MAO, monoaminoxidase; META, meta-analysis; n-3 fatty acids, omega-3 fatty acids; PLB, placebo controlled studies; RCT, randomised controlled trial.