Melatonin

• Sleep onset insomnia: Strong evidence from meta-analyses indicates melatonin (especially immediate-release) modestly reduces sleep-onset latency and may slightly increase total sleep time compared with placebo. Effects are generally small-to-moderate and more pronounced in older adults and those with delayed sleep timing.
• Jet lag: Strong evidence from systematic reviews shows melatonin taken near local bedtime at destination helps prevent and reduce symptoms of jet lag and realigns circadian rhythm after eastward or transmeridian travel.
• Delayed sleep–wake phase disorder (DSWPD): Strong-to-moderate evidence and clinical guidelines support timed, low-dose melatonin several hours before desired bedtime to advance circadian phase and improve sleep timing, often combined with morning light therapy.
• Shift work–related sleep disturbance: Moderate evidence (mixed across trials) suggests melatonin can improve daytime sleep duration after night shifts and reduce sleepiness in some individuals; benefits are variable.
• Pediatric insomnia in neurodevelopmental conditions (e.g., autism spectrum disorder): Moderate evidence (including RCTs of prolonged-release formulations) suggests improvements in sleep onset and total sleep time; use should be clinician-directed.
• Preoperative anxiety and sedation: Moderate evidence from small RCTs suggests melatonin may reduce preoperative anxiety and provide mild sedation without major psychomotor impairment compared with some benzodiazepines.
• Blood pressure (nocturnal): Emerging-to-moderate evidence indicates controlled-release melatonin may modestly lower nocturnal blood pressure in some hypertensive patients; results vary and immediate-release formulations may not have this effect.
• Antioxidant/anti-inflammatory effects: Emerging human evidence (more robust preclinical data) shows improvements in oxidative stress markers; clinical outcome benefits remain uncertain.

Common (generally mild, 1–10%): daytime drowsiness/somnolence, headache, dizziness, nausea, vivid dreams or nightmares, morning grogginess. These are often dose- and timing-dependent and may lessen with lower doses or earlier evening timing. Less common: irritability, short-term mood changes (including low mood), confusion/disorientation, tremor, gastrointestinal discomfort, dry mouth, decreased body temperature, transient blood pressure changes. Rare but serious: allergic reactions, hallucinations, paradoxical agitation, potential blood pressure elevation in some when combined with certain antihypertensives (e.g., immediate-release with nifedipine in limited reports), arrhythmia, potential worsening of seizure frequency in susceptible individuals (data mixed), abnormal bleeding (theoretical/rare reports), and daytime psychomotor impairment leading to increased accident risk. Dependence/withdrawal: Not typically associated with dependence; rebound insomnia is uncommon. Next-day impairment is possible, especially with higher doses, extended-release forms near morning hours, or co-use of CNS depressants.

Commonly used ranges in studies (not medical advice; optimal dosing varies by individual, indication, and formulation):

• General insomnia/sleep onset: 0.5–5 mg immediate-release taken about 30–60 minutes before desired bedtime; lower doses (e.g., 0.3–1 mg) may be as effective and reduce next-day effects in some adults and older adults.
• Jet lag: 0.5–5 mg at local bedtime at destination for 2–5 days (some protocols begin 1–2 days pre-travel for eastward flights). Timing relative to light exposure is important.
• Delayed sleep–wake phase disorder (DSWPD): 0.3–3 mg taken approximately 3–5 hours before the current spontaneous sleep onset or desired bedtime, typically combined with morning bright light; precise timing is critical for phase advancement.
• Shift work sleep issues: 1–3 mg after night shifts to consolidate daytime sleep, with avoidance of bright light during post-shift commute.
• Pediatric neurodevelopmental insomnia (e.g., ASD): Prolonged-release 2–5 mg in the evening has been used in trials under medical supervision.
• Preoperative anxiolysis: 3–10 mg given 60–90 minutes pre-procedure in clinical studies. Formulation notes: Immediate-release favors sleep initiation; prolonged-release may aid sleep maintenance. Avoid taking too late at night to reduce next-day grogginess. Light management (dim evening light; morning bright light) enhances circadian benefits.

• Pregnancy and breastfeeding: Insufficient safety data; generally avoided unless specifically recommended by a clinician.
• Bleeding disorders or use of anticoagulant/antiplatelet therapy: Potential antiplatelet effects may increase bleeding risk.
• Autoimmune diseases or transplant recipients on immunosuppression: Melatonin has immunomodulatory properties that could theoretically counteract immunosuppressive therapy; use only with medical supervision.
• Epilepsy/seizure disorders: Mixed data; case reports suggest possible seizure provocation in susceptible individuals, while others show benefit—specialist guidance advised.
• Major depressive disorder or bipolar disorder: Possible mood effects or induction of depressive symptoms in some; monitor closely and consult a clinician.
• Uncontrolled hypertension or significant cardiovascular disease: Mixed hemodynamic effects (formulation-dependent); monitor blood pressure if used.
• Diabetes or impaired glucose tolerance: Melatonin may affect glucose metabolism and insulin sensitivity; monitor glucose if used.
• Hepatic impairment: Melatonin is primarily metabolized in the liver (CYP1A2); use caution and consider lower doses.
• Pre-surgical patients: Due to potential bleeding risk and additive sedation with anesthetics, many clinicians advise discontinuation 1–2 weeks before elective surgery unless directed otherwise by the surgical team.
• Children and adolescents: Use only under pediatric guidance, particularly outside of neurodevelopmental indications.