Table 1 Evidence for pharmacological complementary medicines
RemedyEffectiveness at RCT/meta-analysis (META) level in placebo (PLB) or equivalence (EQU) studiesReceptor targets/mechanism of actionSelected safety concerns
Affective disorders
    St John’s wortMETA PLB (n = 26): marginally effective in major depression5HTCYP 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 acidsRCT: no effect on mild to moderate depression (8)Modification of 2nd messenger systemsToxicity 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-tryptophanPreliminary5HTSerotonergic side effects as above
Association with eosinophilic myalgic syndrome remains unclear
    Folic acidPreliminary re augmentation strategyPrecursor to SAMeCaution in patients with cancer
    InositolInconclusive re treatment or augmentation strategyModification of 2nd messenger systemsInduction of mania?
Carbamazepine, valproate and lithium ↓ inositol
    SeleniumNone availableAntioxidantNarrow therapeutic index
↑ T4→T3 conversion
Anxiety and related disorders and insomnia
    ValerianMETA PLB (n = 6) and RCTs EQU (n = 2): improves insomnia (11–13)GABALiver toxicity may depend on extract (valepotriates)
Anxiety: insufficient evidence available
    Passion flowerPreliminary for reduction in anxietyGABASome extracts contain cyanogenic components
    ChamomileNone availableGABA
    Kava kavaMETA PLB (n = 7): effective in the reduction in anxiety (14)GABASignificant liver toxicity possible (may be extract-dependent)
DA antagonist
    Star flower/borageNone availableUnclearMay ↓ seizure threshold, potentially liver toxic
    Lemon balmNone availableGABA?
    HopsNo single-component trials availableUnclear
    OatsNone available5HT? (a source of tryptophan)
    LavenderNone availableUnclear, also purported to have antidepressive and pain-reducing properties
    Melatonin (N-acetyl-S-metoxy tryptamine)InconclusiveRegulates circadian rhythm
    Bach flower remediesNot effectiveUnclear
Psychosis and schizophrenia
    RauwolfiaEvidence dating back to 1950s/60s. No current evidence available.Facilitates degradation of monoaminesDepression, cardiac effects
    n-3 fatty acidsInconclusiveCf aboveCf above
Tardive dykinesia
    Vitamin EInconclusiveAntioxidantMay ↑ all-cause mortality
    n-3 fatty acidsNot effectiveCf aboveCf 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.