Table 1 Evidence for pharmacological complementary medicines

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.