Melatonin and Mood
Melatonin is known mostly for its effects on the sleep-wake cycle and as a treatment for insomnia. However, there is plenty of evidence to suggest benefits for everything from migraines and dementia to heart disease and cancer. One of the less well-studied benefits of melatonin may be its effects on mood.
The first published study of melatonin and depression was small (Carman 1976). It included just eight patients. In the placebo-controlled study, melatonin increased depression, anxiety, anger and psychotic symptoms. However, the study should be viewed cautiously, as they used extremely high doses of melatonin, in most cases over 1000 mg, that were given throughout the day, not just at bedtime. By way of comparison, most recent studies use doses of melatonin between 3 and 25 mg given at bedtime. This study, however, may have created the negative stigma that still exists around the use of melatonin for mood symptoms.
Seasonal Affective Disorder
For seasonal affective disorder, where patients have depression over winter, overproduction of melatonin has long been suspected as a potential cause. In the winter, reduced levels of daylight would increase melatonin production in the brain. However, a meta-analysis on the data from 1997 concluded that melatonin was not the likely cause of seasonal affective disorder (Lee 1997). More recently, some researchers have considered that melatonin may help in the treatment of seasonal affective disorder. Unfortunately, the current research is insufficient to draw conclusions either way (Nussbaumer-Streit 2019). Even so, I wouldn’t be afraid to try melatonin to help with sleep and mood in patients struggling with seasonal affective disorder.
Sleep Problems and Depression
A small study on melatonin for sleep problems in depression did not find the same problems as the earlier study that utilized 1000 mg doses (Dolberg 1990). The study used between 5 and 10 mg of slow-release melatonin at 9:00 PM. The dosing was effective for improving sleep, but was not found to influence mood.
For patients with depression and delayed sleep phase, a condition where individuals usually fall asleep a few hours later than normal and wake up a few hours later than normal, melatonin was helpful (Rahman 2010). It improved sleep and mood over four weeks of supplementation. A similar trial in depressed patients with sleep problems found that melatonin improved mood without adverse side effects, although the results didn’t reach full statistical significance (Serfaty 2010).
A study in depressed patients treated them with standard medication with melatonin or medication with placebo (Chojnacki 2015). Sleep problems were reduced better with melatonin, although anxiety and depression symptom improvements were equivalent between the two groups.
Melatonin and Mood in Mid-Life and Later
A separate small trial in patients with cognitive decline, a precursor to dementia, found that melatonin at night improved some aspects of sleep, cognition and mood symptoms (Jean-Louis 1998). In a separate trial of patients 65 and older, melatonin supplementation improved sleep, depression and anxiety symptoms (Garzón 2009).
For women after menopause, a meta-analysis found that melatonin supplementation was helpful for numerous symptoms, including both anxiety and depression (Kayacik 2024). Melatonin was also typically devoid of serious side effects.
Melatonin, Mood and Cancer
Studies in breast cancer have been mixed, with one study finding improvements with 6 mg over three months and a separate trial finding sleep benefits but no change in mood with lower doses between 1 and 3 mg (Hansen 2014, Chen 2014). A separate trial that gave melatonin during breast cancer chemotherapy also showed brain protective effects with improved mood (Palmer 2020). A meta-analysis of studies on melatonin in cancer patients found a small but significant impact of melatonin on depression when used longer than two weeks (Fan 2022).
Depression, Melatonin and Other Health Conditions
For patients with a history of opioid addiction who were on methadone to control opioid use, the addition of melatonin significantly reduced depression and anxiety symptoms (Ghaderi 2019).
For women with polycystic ovarian syndrome (PCOS), a condition that often includes mood symptoms, melatonin improved a number of the contributing factors to the condition. In addition, sleep quality, mood and anxiety also showed significant benefits (Shabani 2019). A study in patients with heart disease that used a higher dose of 25 mg did not find benefits on mood (Madsen 2019).
A study from Russia on Parkinson’s disease patients found improvements in sleep, energy, anxiety and quality of life, but no change in mood symptoms (Datieva 2013). However, a study out of Iran did find significant benefits for Parkinson’s disease patients, including on mood (Khakhaki 2020).
Studies in patients with kidney disease have shown benefits for mood. A trial using 10 mg and a trial using 3 mg both found mood benefits in patients on dialysis for kidney disease (Ostadmohammadi 2020, Yousef 2022).
Conclusion
While the studies are somewhat mixed, overall, melatonin appears to be quite safe, and when taken before bedtime, it may significantly reduce depression and other mood symptoms for some patients. Evidence is probably strongest for individuals with associated sleep problems and postmenopausal women, among other conditions.
