Melatonin is a naturally occurring hormone and a widely available over-the-counter supplement. It is synthesized primarily in the brain and signals the onset of biological night. Depression is a mood disorder characterized by persistent sadness and loss of interest. The use of melatonin supplements in people experiencing depression raises a safety question: can this hormone, intended to promote sleep, actually worsen depressive symptoms? Evidence suggests that while melatonin does not typically induce major depression, its interaction with brain chemistry, individual sensitivity, and existing medications requires careful examination.
Melatonin’s Function in Sleep and Circadian Rhythm
The body’s production of melatonin is controlled by the suprachiasmatic nucleus, often called the body’s master clock. This hormone is released by the pineal gland following the environmental light-dark cycle. Melatonin levels rise in the evening darkness, signaling the body to prepare for sleep. This process regulates the sleep-wake cycle, known as the circadian rhythm.
Melatonin supplementation is commonly used to correct issues like jet lag, shift work disorder, or delayed sleep phase syndrome. Since sleep disturbances are frequently associated with depressive disorders, people often use melatonin to address this co-occurring issue. The supplement is considered a “chronobiotic,” meaning it helps synchronize the timing of the internal biological clock.
Evaluating the Direct Link to Worsened Depression
Research does not indicate that melatonin supplementation causes major depressive disorder in previously healthy individuals. However, temporary adverse mood reactions are possible in certain people, especially those with pre-existing mood vulnerabilities. Some individuals report short-term symptoms like irritability, confusion, or a brief worsening of depressive feelings after taking the supplement. The mechanism is not fully clear, but it may relate to individual brain chemistry differences or how the hormone interacts with neurotransmitter systems.
Melatonin’s primary function is to reduce energy in preparation for sleep. This resulting increase in tiredness and low energy is also a common symptom of depression, meaning melatonin can potentially exacerbate feelings of lethargy and fatigue. Improper timing of the supplement can also disrupt the circadian rhythm, which is frequently misaligned in individuals with depression. Taking the supplement too early or too late can further confuse the body’s internal clock, which may indirectly affect mood stability.
The American Psychiatric Association advises caution for individuals with a personal or family history of psychiatric disorders, as increased depressive symptoms have been reported in some cases. Melatonin use is often discouraged entirely in specific populations, such as older adults with dementia, due to observed detrimental effects on mood and daytime functioning. Clinical studies generally find that while melatonin may not improve core mood symptoms of depression, it also does not significantly worsen them when used correctly for sleep problems.
Interaction with Antidepressant Medications
A concern involves combining melatonin with certain antidepressant drugs, particularly those that increase serotonin levels. Melatonin is produced from serotonin, and both compounds share pathways affected by medication. Combining melatonin with serotonergic drugs, such as selective serotonin reuptake inhibitors (SSRIs) like sertraline or fluoxetine, may increase the risk of Serotonin Syndrome.
Serotonin Syndrome is a rare but serious adverse reaction caused by excessive serotonin activity in the central nervous system. Symptoms range from mild (shivering and diarrhea) to severe (muscle rigidity, fever, and seizures). The risk is elevated because both the supplement and the medication contribute to overall serotonergic activity.
Melatonin also interacts with the liver’s cytochrome P450 (CYP) enzyme system, which metabolizes many medications. Melatonin is primarily metabolized by the CYP1A2 enzyme. Certain antidepressants, such as fluvoxamine, are potent inhibitors of the CYP1A2 enzyme. When an inhibitor like fluvoxamine is taken with melatonin, it can dramatically slow the breakdown of melatonin, leading to much higher concentrations in the bloodstream. This increased exposure may heighten side effects like excessive sedation or confusion. Conversely, melatonin has been shown to potentially reduce the effectiveness of some antidepressant medications in animal studies, though this effect is not well-established in humans.
Safe Use and Medical Consultation Guidelines
Consulting a healthcare provider before starting melatonin is recommended, especially if depression is diagnosed or if psychiatric medications are being used. A physician can assess the individual risk profile, considering all existing medications and health conditions.
If approved, the starting dose should be kept low, typically 0.5 to 3 milligrams, as higher doses are not necessarily more effective and may increase adverse effects. The timing of the dose is important; it should be taken strategically to align with the desired sleep schedule. If a person experiences warning signs such as increased daytime drowsiness, confusion, unusual irritability, or worsening depressive thoughts, they should immediately discontinue the supplement and seek medical advice.