5-hydroxytryptophan (5-HTP) and S-adenosylmethionine (SAMe)
Effect: Possible Harmful Interaction
The body uses the natural substance 5-HTP to manufacture serotonin, and
supplemental forms have been used for treating depression and migraine headaches.
SAMe is a naturally occurring compound derived from the
amino acid methionine and the energy molecule adenosine triphosphate. SAMe is
widely used as a supplement for treating osteoarthritis and depression.
Based on one case report and the latest knowledge about how they work, SAMe and
5-HTP should not be taken with SSRIs, as they might increase the risk of serotonin
syndrome. This syndrome is a toxic reaction brought on by too much serotonin
activity. The condition requires immediate medical attention, with symptoms
including anxiety, restlessness, confusion, weakness, tremor, muscle twitching or
spasm, high fever, profuse sweating, and rapid heartbeat.
The report describes a case of apparent serotonin syndrome in a person taking SAMe
with clomipramine, a tricyclic antidepressant that increases serotonin
activity.
Although SAMe is not currently known to affect serotonin, it does appear to have
antidepressant effects and may in some way increase serotonin activity. Because
SSRIs increase serotonin activity even more than clomipramine, a similar problem
might occur if one combines SAMe with an SSRI. The supplement 5-HTP is used by the
body to manufacture serotonin, so it could also increase the risk of serotonin
syndrome when combined with an SSRI.
St. John’s Wort
Effect: Possible Harmful Interaction
The herb St.
John’s wort (Hypericum perforatum) is
primarily used to treat mild to moderate depression. One of its actions appears to
be increasing the activity of serotonin in the brain.
Persons taking an SSRI medication should not take the herb St. John’s wort at the same time. It is possible that serotonin levels might be raised too high, causing a dangerous condition called serotonin syndrome.
Several case reports appear to bear this out. Serotonin syndrome was reported in five elderly persons who began using St. John’s wort while taking sertraline (four reports) or nefazodone (one report). One person had symptoms resembling serotonin syndrome after combining paroxetine (50 milligrams [mg] daily) and St. John’s wort (600 mg daily). Another person taking St. John’s wort with two other serotonin-enhancing drugs was reported to experience serotonin syndrome.
Furthermore, persons wishing to switch from an SSRI to St. John’s wort may need to wait a few weeks for the SSRI to be cleansed from the body before it is safe to start taking the herb. The waiting time required depends on which SSRI is being taken.
Folate
Effect: Possible Helpful Interaction
Folate is a B vitamin that offers many important health
benefits. It helps prevent birth defects and disorders and possibly reduces the
risk of heart disease. A recent study suggests that folate can also help SSRI
antidepressants work better. In this double-blind, placebo-controlled trial, 127
persons with severe depression were given either Prozac plus
folate (500 micrograms [mcg] daily) or Prozac alone. Researchers wanted to see
whether the vitamin would increase the medication’s effectiveness.
The results were different for men and women. Female participants definitely benefited from receiving folate along with the medication. While just under 50 percent of the women taking Prozac alone fully recovered from their depression, combination treatment produced a recovery rate of nearly 75 percent. This is a marked difference, and one that makes a strong case for combining folate with antidepressant therapy.
Men, however, did not do any better on combination treatment than on Prozac alone. Researchers found evidence that a higher dose would have been necessary for male participants, perhaps 800 to 1,000 mcg daily. However, for dosages this high, medical supervision is necessary.
Fish Oil
Effect: Supplementation Probably Not Helpful
Fish
oil contains essential fatty acids in the omega-3 family.
Fish oil, its constituents, and a slightly modified fish oil constituent called
ethyl-EPA have all been tested for treatment of depression. While a few small
studies have suggested that these substances might enhance the effectiveness of
antidepressant drugs, the results of larger and better-designed studies have been
mostly negative.
Ginkgo
Effect: Supplementation Probably Not Helpful
SSRIs can cause many sexual side effects, including inability to achieve orgasm
(in women) and impotence (in men). Case reports and open studies raised hopes that
the herb ginkgo could help reverse these problems. However, only
double-blind, placebo-controlled studies can truly establish efficacy of a
treatment, and when studies of this type were finally performed to evaluate
ginkgo’s potential effectiveness for this purpose, no benefits were seen.
Ephedra
Effect: Supplementation Probably Not Helpful
Like ginkgo, ephedrine (extracted from the herb ephedra) does not appear
any more effective than placebo for treatment of female sexual dysfunction caused
by SSRIs.
Bibliography
Frangou, S., et al. “Efficacy of Ethyl-Eicosapentaenoic Acid in Bipolar Depression.” British Journal of Psychiatry 188 (2006): 46-50.
Grenyer, B. F., et al. “Fish Oil Supplementation in the Treatment of Major Depression.” Progress in Neuro-Psychopharmacology and Biological Psychiatry 1, no. 31 (2007): 1393-1396.
Hallahan, B., et al. “Omega-3 Fatty Acid Supplementation in Patients with Recurrent Self-Harm.” British Journal of Psychiatry 190 (2007): 118-122.
Jazayeri, S., et al. “Comparison of Therapeutic Effects of Omega-3 Fatty Acid Eicosapentaenoic Acid and Fluoxetine, Separately and in Combination, in Major Depressive Disorder.” Australian and New Zealand Journal of Psychiatry 42 (2008): 192-198.
Kang, B. H., et al. “A Placebo-Controlled, Double-Blind Trial of Ginkgo biloba for Antidepressant-Induced Sexual Dysfunction.” Human Psychopharmacology: Clinical and Experimental 17 (2002): 279-284.
Lin, P. Y., and K. P. Su. “A Meta-analytic Review of Double-Blind, Placebo-Controlled Trials of Antidepressant Efficacy of Omega-3 Fatty Acids.” Journal of Clinical Psychiatry 68 (2007): 1056-1061.
Marangell, L. B., et al. “A Double-Blind, Placebo-Controlled Study of the Omega-3 Fatty Acid Docosahexaenoic Acid in the Treatment of Major Depression.” American Journal of Psychiatry 160 (2003): 996-998.
Meston, C. M. “A Randomized, Placebo-Controlled, Crossover Study of Ephedrine for SSR-Induced Female Sexual Dysfunction.” Journal of Sex and Marital Therapy 30 (2004): 57-68.
Rogers, P. J., et al. “No Effect of N-3 Long-Chain Polyunsaturated Fatty Acid (EPA and DHA) Supplementation on Depressed Mood and Cognitive Function.” British Journal of Nutrition 99, no. 2 (2008): 421-431.
Wheatley, D. “Triple-Blind, Placebo-Controlled Trial of Ginkgo biloba in Sexual Dysfunction Due to Antidepressant Drugs.” Human Psychopharmacology 19, no. 8 (2004): 545-548.
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