Selective serotonin reuptake inhibitors (drug interactions)
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed medications for managing severe and mild to moderate depression, as well as other conditions. While SSRIs are effective, they can interact with various substances, leading to potential health risks or benefits. Certain herbal supplements, such as St. John's wort, should be avoided with SSRIs due to the risk of serotonin syndrome, a potentially life-threatening condition caused by excessive serotonin levels. Conversely, compounds like S-adenosyl-methionine (SAMe) and Bupleurum chinense may enhance the effectiveness of SSRIs and reduce depressive symptoms, though caution is still advised.
Other interactions with SSRIs can involve herbal remedies like kava and valerian, which may increase side effects such as dizziness and confusion. Additionally, the effectiveness of supplements like fish oil, ginkgo, and folate in enhancing SSRIs remains inconclusive, with mixed results in clinical studies. Notably, the impact of folate may vary between genders, with some evidence suggesting it could benefit women more than men in conjunction with SSRIs. Understanding these interactions is crucial for anyone taking SSRIs, as they can significantly affect treatment outcomes and overall safety.
Selective serotonin reuptake inhibitors (drug interactions)
DEFINITION: Medications used for severe and mild to moderate depression and for a variety of other conditions.
- INTERACTIONS:Bupleurum chinense, ephedra, fish oil, 5-HTP, folate, ginkgo, kava, St. John’s wort, SAMe (S-adenosylmethionine), valerian
- DRUGS IN THIS FAMILY: Citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil, Pexeva), sertraline (Zoloft), vilazodone (Viibryd), vortioxetine (Trintellix)
5-hydroxytryptophan (5-HTP)
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 migraines. 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.
Based on the latest knowledge about how it works, 5-HTP should not be taken with SSRIs, as it 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, profuse sweating, and rapid heartbeat. In severe cases, life-threatening fever, arrhythmia, loss of consciousness, or seizure can occur.
S-adenosyl-methionine (SAMe)
Effect: Possible Helpful Interaction
S-adenosyl-methionine, more commonly known as 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. SAMe appears to have antidepressant effects and may in some way increase serotonin activity.
One randomized clinical trial published in the American Journal of Psychiatry in 2010 found that SAM-e supplementation could enhance SSRI efficacy among those whose major depression had not previously responded to SSRI medication. Seventy-three patients were randomized to 800 milligrams of SAM-e twice daily or a placebo for six weeks. One-quarter of participants dropped out; among the remainder, reduced depressive symptoms and remission occurred more frequently among those taking the combination therapy than receiving the placebo.
Bupleurum chinense
Effect: Possible Helpful Interaction
A 2019 systematic review in the Journal of Alternative and Complementary Medicine reported that twenty-four randomized clinical trials found the combination of Bupleurum chinense, an herb used in traditional Chinese medicine, along with SSRIs led to a reduction of depressive symptoms at one to three months. Eight trials reported fewer adverse events than with SSRIs alone.
St. John’s Wort
Effect: Likely 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.
Kava and Valerian
Effect: Possible Harmful Interaction
Kava and valerian are herbal remedies that act on the central nervous system. Kava may have some benefit for anxiety, but its use for depression has not been clinically proven. Similarly, valerian may be effective for treating insomnia, but it is unclear whether useful for mood disorders. When used alongside SSRIs, kava or valerian may increase side effects such as confusion, dizziness, drowsiness, and difficulty concentrating, and also impair thinking, judgment, and motor coordination.
Folate
Effect: Supplementation Possibly Not Helpful
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. Folate, which is involved in serotonin production, might also help SSRI antidepressants work better. In one 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.
A 2014 trial involving 475 patients with moderate to severe depression, most of whom were on SSRIs, found that no statistically significant differences among those who received 5-milligram folate supplements daily for three months and those who received a placebo. The treatment and placebo were compared for symptom severity, suicidality, and mental or physical health.
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.
In 2019, a British Journal of Psychiatry systematic review of thirty-one randomized clinical trials reported that increased intake of long-chain omega-3 fatty acids did little to nothing to prevent or treat depression and anxiety.
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 the 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.
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