The Truth About Insomnia and Melatonin: Natural Does Not Always Mean Harmless

I have been lucky I have never struggled with sleep. But as a psychiatrist, I have treated countless patients who do struggle. Insomnia is not just about feeling tired, and it affects nearly every domain of mental and physical health.

Chronic insomnia impairs attention, working memory, and executive functioning and worsens mood and anxiety disorders by disrupting emotional regulation.^1,2 It is also linked to poor physical health: higher rates of hypertension, coronary artery disease, heart failure, and stroke.^3-5 Insomnia alters appetite-regulating hormones leptin and ghrelin, leading to cravings for calorie-dense foods and carbohydrates, weight gain, insulin resistance, and metabolic syndrome.^6,7 It even weakens immune defense by reducing cytokine production and promoting chronic inflammation.⁸

In psychiatry, much of our work begins with helping patients sleep naturally and restoratively. Yet most hypnotic medications modestly reduce sleep-onset latency while disturbing normal architecture and risking dependence, withdrawal, and even falls in older adults.^9,10 It is no surprise many turn to supposedly natural options like melatonin, a hormone secreted by the pineal gland that regulates circadian rhythm.

What the Evidence Really Says About Melatonin

For delayed sleep–wake phase disorder, melatonin has consistent, strong evidence and is first-line in American Academy of Sleep Medicine (AASM) guidelines.¹¹ For primary insomnia, however, results are mixed: melatonin may shorten sleep-onset latency by only 5 to 7 minutes, a difference often not clinically meaningful.^12,13 Its utility for sleep maintenance is limited immediate-release forms are cleared quickly, though prolonged-release versions show modest benefits in older adults (≥ 55 years), in whom endogenous production declines.¹⁴ Placebo response is high, dosing ranges widely (0.3–10 mg), and over the counter products vary substantially in purity and potency.¹⁵

Accordingly, the AASM does not recommend melatonin as a first-line option for chronic insomnia due to limited and low-quality evidence compared to Cognitive Behavioral Therapy for Insomnia (CBT-I).¹⁶

Safety Signals: A Wake-Up Call

A 2025 analysis presented at the American Heart Association Scientific Sessions used the TriNetX Global Research Network to review 5 years of health records for over 130,000 adults with insomnia. Those with documented long-term melatonin use (≥ 12 months) had ~90 % higher incidence of new heart failure (4.6 % vs 2.7 %), were 3.5 times more likely to be hospitalized for heart failure (19 % vs 6.6 %), and nearly twice as likely to die of any cause (7.8 % vs 4.3 %).¹⁷

While this observational abstract cannot prove causation and confounding by insomnia severity or comorbid disease is likely it challenges the perception that natural equals safe.¹⁸ Melatonin is unregulated in the United States, often taken nightly for months or years without medical supervision.

Evidence-Based Treatment Hierarchy

First-line: CBT-I.
Cognitive restructuring, stimulus control, and sleep-restriction therapy are the most evidence-based interventions for chronic insomnia, each receiving strong AASM recommendations.¹⁶

Adjunctive pharmacotherapy.
When indicated, medication should be short-term, lowest effective dose, combined with CBT-I, and used in shared decision-making.
AASM 2017 recommendations include:¹⁹

• Strong/Standard: low-dose doxepin (sleep maintenance), eszopiclone (onset/maintenance), ramelteon (onset), suvorexant (onset/maintenance), zaleplon (onset), zolpidem (onset/maintenance).
• Suvorexant: An orexin receptor antagonist, effective for sleep onset and maintenance.
• Moderate: temazepam (with caution re tolerance/dependence).
• Not Recommended: antihistamines (eg, diphenhydramine), trazodone (off-label use with limited evidence), and melatonin (OTC, unregulated).

The Takeaway

Melatonin has a role but a narrow one, primarily for circadian-phase adjustment. For chronic insomnia, it is weakly backed by modest data and growing questions about long-term safety.
Not everything natural is harmless, and not every sleepless night should be medicated. Start with behavior, then tailor pharmacology as needed.

Dr Rossi is an inpatient and consultation liaison psychiatrist who also performs electroconvulsive therapy services at AtlantiCare Regional Medical Center in Pomona, New Jersey. He currently serves on the board of the New Jersey Psychiatric Association, where he has worked on advocacy projects, including enhancing access to collaborative care in the state.

References

1. Fortier-Brochu E, Morin CM. Cognitive impairment in individuals with insomnia: clinical significance and correlates. Sleep. 2012;35(6):913-923.

2. Baglioni C, Battagliese G, Feige B, et al. Insomnia as a predictor of depression: a meta-analytic evaluation. J Affective Disorders. 2016;186:10-19.

3. Sofi F, Cesari F, Casini A, et al. Insomnia and risk of cardiovascular disease: a meta-analysis. Eur J Prev Cardiol. 2014;21(1):57-64.

4. Laugsand LE, Vatten LJ, Platou C, et al. Insomnia and risk of acute myocardial infarction. Circulation. 2011;124(19):2073-2081.

5. Javaheri S, Redline S. Insomnia and cardiovascular disease. Chest. 2017;152(2):435-444.

6. Spiegel K, Tasali E, Penev P, et al. Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med. 2004;141(11):846-850.

7. Buxton OM, Marcelli E. Short and long sleep are positively associated with obesity, diabetes, hypertension, and cardiovascular disease among adults in the United States. J Clin Endocrinol Metab. 2010;95(5):2050-2059.

8. Irwin MR. Sleep and inflammation: partners in sickness and health. Nat Rev Immunol. 2019;19(11):702-715.

9. Glass J, Lanctôt KL, Herrmann N, et al. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331(7526):1169.

10. Holbrook AM, Crowther R, Lotter A, et al. Meta-analysis of benzodiazepine use in the treatment of insomnia. CMAJ. 2000;162(2):225-233.

11. Auger RR, Burgess HJ, Emens JS, et al. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: Advanced SleepWake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD): an update for 2015. J Clin Sleep Med. 2015;11(10):1199-1236.

12. Choi K, Lee YJ, Park S, et al. Efficacy of melatonin for insomnia: systematic review and meta-analysis. Sleep Med Rev. 2020;52:101303.

13. Brzezinski A, Vangel MG, Wurtman RJ, et al. Effects of exogenous melatonin on sleep: meta-analysis. Sleep Med Rev. 2005;9(1):41-50.

14. Wade AG, Ford I, Crawford G, et al. Efficacy of prolonged release melatonin in insomnia patients aged 55-80 years: quality of sleep and next-day alertness outcomes. Curr Med Res Opin. 2011;27(5):871-885.

15. Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275-281.

16. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med. 2017;13(2):307-349.

17. American Heart Association. Long-term use of melatonin supplements to support sleep may have negative health effects. News release. November 3, 2025. Accessed November 14, 2025. https://newsroom.heart.org

18. Science Media Centre. Expert reaction to conference abstract on melatonin and heart failure. 2025. Accessed November 14, 2025. https://www.sciencemediacentre.org

19. American Academy of Sleep Medicine. Clinical Practice Guideline for the pharmacologic treatment of chronic insomnia in adults. 2017. Accessed November 14, 2025. https://aasm.org/resources/pdf/pharmacologictreatmentofinsomnia.pdf