Selective serotonin reuptake inhibitors, or SSRIs, are second-generation antidepressant drugs that are linked to an increase in the mood-enhancing neurotransmitter serotonin. Some SSRIs can give rise to elevated melatonin levels in the brain. Taking melatonin supplements with these antidepressants could exaggerate the side effects of melatonin. Other SSRIs can lower brain levels of melatonin. Taking extra melatonin to avoid this side effect may suppress the antidepressant effects of the SSRIs.
SSRIs
SSRIs are a class of second-generation antidepressants that historically succeeded first-generation antidepressants, such as tricyclics and MAO inhibitors. SSRIs raise the extracellular levels of serotonin in the brain by blocking the serotonin transporters. Serotonin transporters transport serotonin back into the cells, which decreases the amount of serotonin available for binding to cell receptors on the neurons.
Melatonin
Melatonin is a neurotransmitter secreted by the pineal gland. Melatonin controls the circadian rhythm, your 24-hour cycle. Melatonin is also a potent antioxidant and can help prevent cell damage from oxidative stress, a kind of cell dysfunction that can occur when oxygen reacts with molecules in the cells. People use melatonin for a variety of purposes, most commonly to treat jetlag, delayed sleep phase syndrome and insomnia. Melatonin is relatively safe for adults. Its side effects include short-term feelings of depression, irritability, daytime sleepiness, dizziness, headaches and stomach cramps.
SSRIs and Increased Melatonin Levels
Serotonin converts into melatonin in the pineal gland. So, in theory, elevated levels of serotonin should lead to elevated levels of melatonin. However, different SSRIs may have different effects on melatonin levels. A study published in the May 2000 Issue of “European Journal of Clinical Pharmachology" showed that the SSRI fluvoxamine raises melatonin levels, whereas the SSRI citalopram has no effect on blood levels of serotonin. The study was limited to the immediate effects of the SSRIs on melatonin, however. It is consistent with the study that both SSRIs have positive long-term effects on melatonin levels. Since fluvoxamine can raise melatonin levels, taking a melatonin supplement with fluvoxamine may increase the effects and side effects of melatonin.
SSRIs and Decreased Melatonin Levels
Unlike fluvoxamine and citalopram, the SSRI fluoxetine can lower the levels of melatonin in the short term. Taking extra melatonin supplements to counteract this effect of the antidepressant may reduce its antidepressant effect. While short-term use of fluoxetine lowers melatonin levels, repeated use of fluoxetine can increase the day-time levels of melatonin. Long-term use of both fluoxetine and melatonin may increase day-time sleepiness and other side effects of melatonin.
References
- "Acta Biochimica Polonica"; Melatonin as an Antioxidant: Biochemical Mechanisms and Pathophysiological Implications in Humans; R. J. Reiter; 2003
- University of Maryland Medical Center: Melatonin
- "Clinical Pharmacology: Advances and Applications"; Chronic Fluoxetine Treatment Increases Daytime Melatonin Synthesis in the Rodent; G. W. Reierson et al.; September 2009
- "British Journal of Psychiatry"; Effect of Fluoxetine on Melatonin in Patients with Seasonal Affective Disorder and Matched Controls; P. A. Childs et al.; February 1995
- "European Journal of Clinical Pharmacology"; Fluvoxamine but Not Citalopram Increases Serum Melatonin in Healthy Subjects -- An Indication that Cytochrome P450 CYP1A2 and CYP2C19 Hydroxylate Melatonin; C. von Bahr; May 2000
- "Life Sciences"; Influence of the Antidepressants Desipramine and Fluoxetine on Tryptophan-2,3-Dioxygenase in the Presence of Exogenous Melatonin; H. A. Walsh et al.; 1998
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