MHM Magazine

10 | MENTAL HEALTH MATTERS | 2025 | Issue 4 MHM rather than the exception, with many individuals presenting with additional psychiatric diagnoses such as depression, anxiety disorders, ADHD, substance use disorders, and psychosis – all of which also associated with sleep disturbances. There is compelling evidence for an association between circadian rhythm disturbances and OCD, with studies showing that between 17% and 42% of OCD patients in inpatient programmes meet criteria for delayed sleep phase disorder (DSPD). Evening chronotype (eveningness), or the tendency to prefer a later sleep/ wake schedule and engagement in activities later in the day, has also been associated with increased OCD symptoms. Melatonin and its possible role in psychiatry The word ‘melatonin’ is derived from Greek, ‘melas’ meaning ‘dark’ and ‘tonos’ meaning ‘hormone of darkness’. First discovered by Lerner in 1958 melatonin (N-acetyl-5-methoxy-tryptamine or C13H16N2O2) is a ubiquitous molecule with a wide distribution in nature and produced by many living organisms, including plants. In humans, melatonin is a hormone produced by the pineal gland in response to darkness, closely regulating sleep and circadian rhythms. It has been shown that abnormal melatonin functions are associated with sleep disorders in schizophrenia and mood disorders such as bipolar and major depressive disorder. Despite its widespread use, surprisingly little information is available regarding the pharmacokinetic properties of melatonin in humans. Nevertheless, a key physiochemical and pharmacokinetic limitation is its comparatively short half-life in its physiological microenvironment following administration. Emerging evidence supports the therapeutic potential of melatonin in a range of neuropsychiatric and neurodegenerative conditions associated with sleep problems, including Parkinson’s disease. Further investigations in clinical populations including OCD are necessary to establish optimal dosing strategies and administration routes to minimize potential adverse effects. Tryptophan, serotonin, melatonin and OCD In the brain, an essential amino acid, tryptophan, is converted into serotonin, which is one of the key neurotransmitters involved in OCD. Within the pineal gland, serotonin undergoes further enzymatic conversion into melatonin, primarily under the influence of the circadian rhythm and darkness. Thus, there is a direct biochemical link: tryptophan  serotonin  melatonin, with the pineal glan d acting as the central site for melatonin production (Figure 1). Interestingly, lower serum melatonin levels have been reported in OCD patients while a recent MRI study reported smaller pineal gland volumes in OCD patients compared to healthy controls. Whether the smaller pineal volume in OCD plays a role in the lower serum melatonin levels reported in OCD patients, and whether decreased melatonin functions are implicated in the pathogenesis of OCD, remain to be established. Figure 1. The Melatonin synthesis pathway Exogenous melatonin is typically synthesised in a laboratory and mimics the effects of endogenous melatonin, which is naturally produced by the pineal gland and several other organs. It’s classified as a pharmaceutical agent in the United Kingdom, Europe, and South Africa, where its distribution is regulated and requires a medical prescription for legal purchase and use. The recommended melatonin dosage falls within the range of 0.5 to 10 mg per dose. Clearly, clinical studies using varying dose ranges are urgently needed to provide information on the optimal dose of melatonin for human use. In general, human and animal studies documented that short- term use of melatonin is safe, even in extreme doses. Mild adverse effects such as agitation, dizziness, headache, nausea, and daytime sleepiness may occur. Despite this, melatonin use has increased substantially in the last 15 years, with a notable rise in youth who frequently have several years of continuous exposure. Final conclusions concerning long-term safety of melatonin use are limited amongst other reasons by a lack of randomised, double blind, placebo-controlled studies. Due to a lack of studies, pregnant and breast-feeding women are still advised not to take exogenous melatonin. Melatonin: potential beneficial effects in OCD As noted above, many patients experience only partial relief with SSRIs/CBT emphasising the need for innovative alternative treatments. In view of the sleep disturbances observed in OCD patients and in some of the comorbidities associated with the condition, it seems logical to ask whether interventions addressing disruptions in sleep timing, circadian rhythms and melatonin therapy would be beneficial. The possibility of melatonin mediating the therapeutic effects of SSRIs in OCD was first explored in the nineties. Interestingly, a Figure 1. MHM | 2025 | Volume 12 | Issue 4 | Melatonin: A brief review of its role and therapeutic potential in obsessive-compulsive disorder (OCD) H