From the Guidelines
St. John's Wort (Hypericum perforatum) treats depression through multiple mechanisms affecting neurotransmitter systems in the brain, primarily by inhibiting the reuptake of serotonin, dopamine, norepinephrine, GABA, and glutamate, and may also reduce the activity of monoamine oxidase (MAO) and modulate cytokine production. The herb's active compounds, primarily hyperforin and hypericin, are responsible for these effects.
Mechanism of Action
- Inhibition of neurotransmitter reuptake: Hyperforin and hypericin inhibit the reuptake of several neurotransmitters, including serotonin, dopamine, norepinephrine, GABA, and glutamate, allowing these mood-regulating chemicals to remain active in the brain for longer periods.
- Reduction of monoamine oxidase (MAO) activity: St. John's Wort may reduce the activity of MAO, an enzyme that breaks down neurotransmitters.
- Modulation of cytokine production: St. John's Wort may modulate cytokine production, potentially addressing the inflammatory component of depression.
Dosage and Administration
- Typical dosage: 300 mg three times daily of a standardized extract containing 0.3% hypericin or 3-5% hyperforin.
- Patients should be aware of potential interactions with other medications, including oral contraceptives, anticoagulants, immunosuppressants, and some HIV medications, as St. John's Wort can induce liver enzymes that metabolize drugs, potentially reducing their effectiveness.
Efficacy and Safety
- Meta-analyses of 9 trials (1513 participants) indicated similar response rates for patients treated with second-generation antidepressants or St. John's Wort (52% vs. 54%) after 6 to 12 weeks of treatment 1.
- Patients treated with antidepressants had a significantly higher risk for treatment discontinuation (16% vs. 12%) and discontinuation due to adverse events (7% vs. 4%) than those on St. John's Wort 1.
Important Considerations
- St. John's Wort is not currently regulated by the U.S. Food and Drug Administration, and there is no current standard in place about the contents and potency of the medication.
- Adverse effects associated with St. John's Wort may include mild gastrointestinal symptoms, skin reactions, fatigue, sedation, restlessness, dizziness, headache, and dry mouth.
- St. John's Wort is contraindicated in patients receiving monoamine oxidase or serotonin reuptake inhibitors.
From the Research
Mechanism of Action of St. John's Wort
The mechanism of action of St. John's Wort (Hypericum perforatum) in treating depression involves several key components:
- Inhibition of the neuronal uptake of serotonin, noradrenaline, dopamine, gamma-aminobutyric acid (GABA), and L-glutamate 2
- Hyperforin, a constituent of St. John's Wort, inhibits the re-uptake of neurotransmitters by affecting the sodium gradient, leading to an inhibition of uptake 2
- St. John's Wort extract has a broad spectrum of action, characterized by its ability to inhibit the uptake of multiple neurotransmitters, which is unique among antidepressants 2
Key Constituents and Their Effects
- Hyperforin: plays a crucial role in the antidepressant effects of St. John's Wort, inhibiting the re-uptake of neurotransmitters and affecting the sodium gradient 2, 3
- Hypericin: a naphthodianthrone with potential antidepressant effects, although its exact mechanism is not fully understood 3
- Flavonoids: may contribute to the antidepressant effects of St. John's Wort, although their exact role is not fully understood 3
Pharmacological Activity and Therapeutic Efficacy
- St. John's Wort extract has been shown to be effective in treating mild to moderate depression, with a good tolerability profile and low frequency of adverse events 2, 4, 5
- The efficacy of St. John's Wort is comparable to that of standard antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants, in some studies 4, 5
- However, the safety profile of St. John's Wort is complicated by its potential for drug interactions, particularly with serotonergic agents and CYP 450 drugs 6, 4, 5