Ginkgo biloba extract (GBE) may reduce the side effects experienced by some persons taking SSRIs such as fluoxetine or Reference sertraline. An open-label study with elderly, depressed persons found that 200–240 mg of GBE daily was effective in alleviating sexual side effects in both men and women taking SSRIs.¹ One case study reported that 180–240 mg of GBE daily reduced genital anesthesia and sexual side effects secondary to fluoxetine use in a 37-year-old woman.²

DHEA (Dehydroepiandrosterone) supplementation (50 mg per day) has been shown to restore the response of beta-endorphin, a brain chemical involved in pain and pleasure sensations, to fluoxetine.³ Further research is needed to determine if this drug combination is safe for long-term use.

Low blood levels of folic acid have been correlated to poor response to fluoxetine.⁴ Furthermore, the addition of folic acid to fluoxetine appears to enhance the effectiveness of the drug. A double-blind trial found that Reference depressed women receiving 500 mcg of folic acid per day in addition to fluoxetine experienced significant improvement in their symptoms, as well as fewer side effects, compared with women receiving only fluoxetine.⁵ Similar results were not observed in men; however, men appear to have a higher requirement for folic acid than do women, so a higher intake may be necessary.

Fluoxetine works by increasing serotonin activity in the brain. 5-HTP is converted to serotonin in the brain, and taking it with fluoxetine may increase fluoxetine-induced side effects. Until more is known, 5-HTP should not be taken with any SSRI drug, including fluoxetine.

L-tryptophan is an amino acid found in protein-rich foods. Foods rich in L-tryptophan are not believed to cause any problems during fluoxetine use. However, dietary supplements of L-tryptophan taken during fluoxetine treatment have been reported to cause headache, sweating, dizziness, agitation, restlessness, nausea, vomiting, and other symptoms.⁶

There have been no published reports about negative consequences of combining St. John’s wort (Hypericum perforatum)  (Hypericum perforatum)  (Hypericum perforatum) and fluoxetine. One case has been reported of an interaction between St. John’s wort and a weak serotonin reuptake inhibitor drug known as Reference trazodone that is vaguely similar to fluoxetine.⁷ In another case, a patient experienced grogginess, lethargy, nausea, weakness, and fatigue after taking one dose of Reference paroxetine (Paxil®, another SSRI drug) after ten days of St. John’s wort use.⁸ Nevertheless, some doctors are concerned about the possibility of an interaction between St. John’s wort and fluoxetine causing side effects (e.g., mental confusion, muscle twitching, sweating, flushing) known collectively as serotonin syndrome.^{9 , 10} Until more is known about interactions and adverse actions, people taking any SSRI drugs, including fluoxetine, should avoid St. John’s wort, unless they are being closely monitored by a doctor.

Administration of fluoxetine for six weeks significantly lowered melatonin levels in people with Reference seasonal affective disorder (SAD) and in healthy persons as well.¹¹ Further study is needed to determine if this might interfere with sleeping or whether melatonin supplementation might be appropriate.