Most central nervous system (CNS) adverse effects of melatonin appear to be infrequent and mild in most patients with a few days of use. Much less is known regarding side effects occurring during the long term melatonin administration. Most clinical trials have involved <= 6 months of daily melatonin use. The most commonly reported adverse reactions are headache and somnolence. Prolonged sedation and drowsiness during waking hours have been noted; patients experiencing excessive drowsiness during waking hours following melatonin use at bedtime may need to consume a lower bedtime dosage. One study reported that subjective drowsiness from melatonin may affect attention and concentration while driving; patients should determine how melatonin affects them before participating in activities requiring alertness. Other CNS and psychiatric adverse reactions include dizziness, abnormal dreams, unspecified sleep disturbances, nightmares, and seizures in the published literature.(20)In primarily depressed patients, worsening of depression (including suicidal ideation) have been reported. Hallucinations, as well as behavioral changes such as bizarre behavior, anxiety, agitation, and mania have been reported with the use of melatonin analogs.(19) Neuro-psychiatric symptoms may occur unpredictably. Complex sleep-related behaviors such as “sleep-driving” (i.e., driving while not fully awake after ingestion of a hypnotic) and other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex), with amnesia for the event, have been reported in association with hypnotic use, including melatonin analogs.(19) The use of alcohol and other hypnotics should be avoided when possible since these may increase the risk of such symptoms. Somnambulism (sleep walking) has been reported when melatonin was used in conjunction with zolpidem. As with other melatonin analogs, the emergence of any new changes in mood, cognition, or behavior requires further evaluation of the patient. Discontinuation of melatonin should be considered for patients who report any complex sleep behavior, worsening depression, or any other unusual changes in moods or behaviors. During excessive melatonin dosage (e.g., 24 to 30 mg of ingestion), impaired cognition, lethargy, disorientation, short-term amnesia, acute psychosis and confusion have been reported.(23)(24) In these cases, the temporal association of melatonin ingestion to the clinical course of the patients supported melatonin as the causative agent.
Gastrointestinal (GI) adverse effects of melatonin appear to be infrequent with a few days of use. Much less is known regarding the long term administration of this hormone. Most clinical trials have involved <= 6 months of daily melatonin administration. Infrequent or rare GI adverse reactions reported in the published literature include abdominal pain, dyspepsia, pyrosis (heartburn), nausea, vomiting, constipation, flatulence, and difficulty swallowing.(20)
Melatonin may rarely cause allergic or dermatologic reactions. Rash (unspecified), including fixed drug eruptions and exanthema, with or without pruritus, have been reported after melatonin administration. Other reported dermatologic effects include hyperhidrosis (increased sweating) and hot flashes. Rarely, angioedema and anaphylactoid reactions have been reported with the melatonin analog, ramelteon; however, no reports of such reactions to melatonin are found in the published literature.(19) A report of “difficulty swallowing and breathing” was reported in one clinical study of melatonin for jet lag; this might have represented an allergic response. Patients experiencing a serious allergic reaction to melatonin should discontinue the agent and not be rechallenged.
Cardiovascular (CV) adverse effects of melatonin appear to be infrequent or rare with a few days of use. Much less is known regarding the long term administration of this hormone. Most clinical trials have involved <= 6 months of daily melatonin administration. Infrequent or rare CV reactions reported in the published literature include palpitations and sinus tachycardia.
One case report exists in the literature describing a temporal association of melatonin use for insomnia with the development of autoimmune hepatitis confirmed by liver biopsy. Discontinuation of the melatonin and the administration of corticosteroid therapy resulted in symptomatic and clinical improvements.(25) A case of autoimmune hepatitis has been reported in the literature due to ramelteon, a melatonin agonist.(26)
Adverse events reported with melatonin appear to be infrequent or rare with a few days of use. Much less is known regarding the long term administration of this hormone. Most clinical trials have involved <= 6 months of daily melatonin administration. Infrequent or rare general adverse reactions reported in the published literature include naso-pharyngitis, arthralgia, and swelling of the arms/legs (fluid retention) following air travel.
Leave a Reply