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Hi! David Rosenberg here for the Psychopharmacology Institute. In this CAP—or Child and Adolescent Psychiatry—Smart Take, we will closely examine melatonin use in children and adolescents and whether it can decrease the risk of suicidality, bodily injuries, falls, and accidents. Sleep disorders in children and adolescents are associated with a significantly increased risk of injury and suicidality. The first-line treatment for children and adolescents with sleep disturbances is behavioral interventions, such as cognitive–behavioral therapy (CBT) and sleep hygiene. In Sweden, where this study was conducted, melatonin is the most commonly prescribed medication for sleep in youth. This study took advantage of the fact that although melatonin is commonly available over the counter in many countries, in Sweden it was only available by prescription until 2020. In this study, the authors examined over 25,000 children and adolescents 6–18 years of age treated with melatonin, so a very large sample. What did they find?
There was a significantly decreased risk of self-harm following the initiation of treatment with melatonin in female youth with depression and anxiety. So, this raises the intriguing possibility that sleep interventions, such as melatonin, might have a role in reducing the risk of self-harm, particularly in female adolescents with depression and anxiety. On the other hand, bodily injuries, falls, and accidents did not decrease in youth who initiated melatonin. Despite how commonly melatonin is used, prescribed or not, or taken over the counter, this is the first study examining the risk of intentional self-harm, unintentional injuries, and accidents in youth treated with melatonin. Unintentional accidents were comparable to the year before and after melatonin treatment. However, the risk of self-harm and poisoning was highest in the month immediately prior to melatonin initiation and decreased right after that. Poisoning and self-harm overlap, so the comparability and risk patterns with self-harm and poisoning are unsurprising.
Not surprisingly, psychiatric comorbidity was very high in this sample, with nearly 90% of youth prescribed melatonin having at least 1 psychiatric disorder. ADHD, by far, was the most common psychiatric comorbidity accounting for over 50% of new melatonin users. ADHD being highly comorbid in youth prescribed melatonin is not surprising because ADHD is frequently associated with sleep disturbances independent of medication status. Sleep disturbance is also often reported as a side effect of the medication treatment of ADHD. The risk of self-harm and poisoning was driven most by adolescents suffering from depression and/or anxiety, which was most pronounced in female adolescents. What is especially interesting is that when the investigators controlled for patients on antidepressants, there was a similar pattern of decrease in intentional self-harm rates following melatonin initiation in females. So, this suggests that antidepressant use did not entirely explain these results. I should note that the authors did not comment on patients who have received nonmedication therapy—CBT, psychotherapy, sleep hygiene, and nonmedication interventions—for their depression or anxiety and how this may have impacted or not their results.
Something else that is interesting is that in this study, females were significantly older than males, so this also might in part account for the self-harm findings in females being more pronounced than in males. Diagnostic differences may also account for sex differences in the age of initiation of melatonin. There were far more males than females with ADHD in this sample, which is not unexpected given the higher prevalence of ADHD in boys than girls. This is also consistent with clinical practice and prior reports that melatonin is initiated earlier in males than in females, who more often combine melatonin with ADHD medications because both ADHD and medications used to treat it have been reported to be associated with sleep disturbance. So, males and females are often prescribed melatonin for entirely different reasons, so this is not an apple vs apple comparison, more apples vs oranges.
It is also important to point out that although the risk of self-harm and poisoning among female adolescents was decreased after melatonin initiation, risks were still higher compared with the risk 1 year before melatonin initiation. In other words, the risk appeared to decrease with melatonin initiation, but it did not vanish. So, it still merits close monitoring of suicidality, poisoning, and risk of self-harm whether or not a patient is treated with melatonin. Moreover, this might reflect that previous self-harm events increase the risk for subsequent self-harm events.
So, what is the bottom line? Treating sleep disturbances associated with depression and anxiety in youth could decrease suicidality, intentional self-harm, and poisoning. The risk is still present even in those treated; close monitoring is always indicated in this population. This study also has some significant limitations, namely that this analysis could not exclude or compare patients who were prescribed other sleep medications or took other over-the-counter medications. The authors also did not investigate nonpharmacologic interventions, such as CBT. Also, several authors have significant ties to the industry, including being employees of the industry that produce melatonin and having stock options in the industry and companies manufacturing melatonin and other psychotropic medications. Nonetheless, this is a promising lead; further controlled investigation is warranted.
Abstract
Melatonin Use and the Risk of Self-Harm and Unintentional Injuries in Youths With and Without Psychiatric Disorders
Marica Leone, Ralf Kuja-Halkola, Tyra Lagerberg, Johan Bjureberg, Agnieszka Butwicka, Zheng Chang, Henrik Larsson, Brian M D’Onofrio, Amy Leval, Sarah E Bergen
Background: Sleep disorders in youth have been associated with increased risks of injury, including suicidal behavior. This study investigated whether melatonin, which is the most common medication for sleep disturbances in youth in Sweden, is associated with a decreased risk of injury.
Methods: This population-based cohort study included 25,575 youths who initiated melatonin treatment between ages 6 and 18. Poisson regression was used to estimate rate of injuries in the year prior to and following melatonin treatment initiation. A within-individual design was used to estimate relative risks by comparing injury risk in the last unmedicated month with injury risks in the 12 months after medication initiation. Analyses were stratified by sex, injury type, psychiatric comorbidities and age at melatonin-treatment initiation.
Results: While body injuries, falls and transport accident rates were comparable in the year before and after melatonin-treatment initiation, the risk of self-harm was highest in the months immediately prior to medication, and decreased thereafter. This was particularly prominent among adolescents with depression and/or anxiety, with females displaying greater absolute risks than males. Compared to the last unmedicated month, the 12 months post medication initiation had decreased relative risks for self-harm, with an IRR [95% CI] in the month following melatonin-treatment initiation of 0.46 [0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.
Conclusions: Decreased risk of intentional self-harm was observed following melatonin-treatment initiation among females with depression and anxiety, suggesting that sleep interventions could be considered in an effort to reduce risk of self-harm in this population.
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Reference
Leone, M., Kuja‐Halkola, R., Lagerberg, T., Bjureberg, J., Butwicka, A., Chang, Z., Larsson, H., D’Onofrio, B. M., Leval, A., & Bergen, S. E. (2023). Melatonin use and the risk of self‐harm and unintentional injuries in youths with and without psychiatric disorders. Journal of Child Psychology and Psychiatry
