Melatonin for Depression?

Our states of mind are directly related to circadian rhythms. Clinical work has found that by synchronizing those rhythms through treatment with melatonin, people can feel some relief from the symptoms of depression.

Getting the circadian cycle in balance is one way – and not the only way – that melatonin can prevent or alleviate depression, anxiety, and strengthen other aspects of mood and well-being.

Naturally, if you’re getting better sleep, you’re going to feel more able to take things in stride and keep daily conflicts in perspective. But depression is more than that. It can be a chemical, inflammatory, and structural issue with how the brain responds and what habitual patterns it creates and retreats to. And melatonin is one important component in that big picture.

Melatonin can actually help change the way the brain is structured and how it learns new habits and emotional responses. In scientific terms, this is known as neuroplasticity – the ability of the brain to change, grow, and develop.

One way that melatonin does this is by helping preserve levels of a protein called brain derived neurotrophic factor, or BDNF. BDNF is critical to mental well-being, learning, and outlook. It is generated by the body – one way is through exercise – but it is generally lower in people suffering from depression.

BDNF helps create neurons, and is generally deficient in those with Alzheimer’s, Parkinson’s, and Huntington’s diseases as well as being a component of depression, anxiety, and memory deficits.

In some cases, there are variations in genes that simply reduce levels of natural melatonin production in the body. It’s been found that those with major depressive disorder (MDD) have lower plasma levels of melatonin, which is related to inflammatory proteins that have crossed the blood-brain barrier. In addition, the hippocampus of the brain – required for learning and memory – is actually reduced in volume in patients with MDD, which also reduces neuroplasticity. Fortunately, preclinical studies show melatonin can help.

Researchers have found that melatonin can overcome the reduced volume in the hippocampus of the brain by inducing the growth of dendrites – nerve cells that carry and receive signals in the brain. So in a very definite way, it may literally help reshape the brain.


Valdés-Tovar M, Estrada-Reyes R, Solís-Chagoyán H, et al. Circadian modulation of neuroplasticity by melatonin: a target in the treatment of depression. Br J Pharmacol. 2018 Aug;175(16):3200-3208.

Mood disorders are a spectrum of neuropsychiatric disorders characterized by changes in the emotional state. In particular, major depressive disorder is expected to have a worldwide prevalence of 20% in 2020, representing a huge socio-economic burden. Currently used antidepressant drugs have poor efficacy with only 30% of the patients in remission after the first line of treatment. Importantly, mood disorder patients present uncoupling of circadian rhythms. In this regard, melatonin (5-methoxy-N-acetyltryptamine), an indolamine synthesized by the pineal gland during the night, contributes to synchronization of body rhythms with the environmental light/dark cycle. In this review, we describe evidence supporting antidepressant-like actions of melatonin related to the circadian modulation of neuroplastic changes in the hippocampus. We also present evidence for the role of melatonin receptors and their signalling pathways underlying modulatory effects in neuroplasticity. Finally, we briefly discuss the detrimental consequences of circadian disruption on neuroplasticity and mood disorders, due to the modern human lifestyle. Together, data suggest that melatonin’s stimulation of neurogenesis and neuronal differentiation is beneficial to patients with mood disorders. LINKED ARTICLES: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit

Here is the link to the complete article: Circadian modulation of neuroplasticity by melatonin: a target in the treatment of depression