What supplements can be used with antidepressants?

Supplements That Can Be Used with Antidepressants

Aerobic exercise is the most evidence-supported supplement to antidepressant therapy, showing significantly improved remission rates when combined with antidepressants (45% vs 81% in elderly patients), with minimal risk of adverse interactions. 1

Evidence-Based Supplements to Consider with Antidepressants

Strongly Supported Options:

1. Aerobic Exercise

   • Provides similar efficacy to antidepressants when used alone
   • Significantly improves outcomes when combined with antidepressants, especially in elderly patients
   • Has extremely low risk of adverse events (0.8% vs 6.2% with antidepressants alone)
   • Dosing: Supervised aerobic exercise program 1

2. Acupuncture

   • When combined with antidepressants, achieves higher remission rates than antidepressant monotherapy (35.7% vs 26.1%)
   • Higher response rates also observed with combination treatment
   • Note: Evidence primarily from Chinese studies where publication bias may exist 1

Supplements with Limited Evidence:

1. S-adenosyl-L-methionine (SAMe)

   • May have benefits when added to antidepressants
   • Evidence is limited by small sample sizes and methodological issues
   • Available as FDA-recognized supplement 1, 2

2. Omega-3 Fatty Acids

   • Some evidence suggests potential benefit
   • Current evidence insufficient to draw firm conclusions
   • Generally considered safe with antidepressants 1

3. Antioxidant Supplements

   • Recent meta-analysis shows improvement in depression and anxiety symptoms with:
     • Magnesium
     • Zinc
     • Selenium
     • CoQ10
   • May serve as adjunctive therapy to conventional antidepressants 3

Supplements to Avoid with Antidepressants

1. St. John's Wort

   • AVOID combining with antidepressants
   • Significant risk of serotonin syndrome when combined with SSRIs, SNRIs, or TCAs
   • All tertiary drug information resources identify this as a significant interaction 4, 5

2. Ginseng

   • Associated with significant adverse interactions with psychotropic medications
   • Can cause serotonin syndrome with SSRIs/SNRIs (11.8% of complications)
   • With antipsychotics, especially haloperidol, can cause ventricular arrhythmias
   • Can intensify sedative effects when combined with sedatives 6

3. Ginkgo Biloba

   • Most common effect when combined with SSRIs/SNRIs is hemorrhagic complications (27.45% of complications)
   • Significant risk of pharmacokinetic and pharmacodynamic interactions 6

4. Milk Thistle

   • Associated with pancreatitis when combined with certain antipsychotics
   • Significant risk of pharmacokinetic interactions 6

5. Rhodiola Rosea

   • Significant risk of interactions with psychotropic medications
   • Specific adverse effects vary by medication 6

Important Considerations

1. Pharmacokinetic Interactions

   • Newer antidepressants (SSRIs, SNRIs) have differential effects on CYP enzymes:
     • Fluoxetine and paroxetine: potent CYP2D6 inhibitors
     • Fluvoxamine: affects CYP1A2 and CYP2C19
     • Nefazodone: potent CYP3A4 inhibitor
     • Citalopram and sertraline: low inhibitory activity, safer options 5

2. Pharmacodynamic Interactions

   • Serotonin syndrome is a major risk when combining serotonergic agents
   • CNS-active supplements pose greatest risk with antidepressants 5, 7

3. Monitoring

   • When adding any supplement, monitor for:
     • Changes in mood, energy, and sleep
     • Signs of serotonin syndrome (confusion, agitation, muscle rigidity, hyperthermia)
     • Bleeding complications
     • Changes in blood pressure

4. Withdrawal of Problematic Supplements

   • In 132 documented cases of adverse reactions, withdrawal of the plant preparation resulted in decreased severity or complete resolution of symptoms 6

For optimal outcomes with minimal risk, aerobic exercise represents the safest and most effective "supplement" to antidepressant therapy, while acupuncture shows promising results as an adjunctive treatment. Conventional supplements should be approached with caution, particularly herbal preparations which carry significant interaction risks.