What are the side effects of Ramelteon (rozerem)?

Ramelteon Side Effects

Ramelteon has a relatively benign side effect profile with most adverse events occurring at rates similar to placebo, though it can cause somnolence, fatigue, dizziness, nausea, and headache in a small percentage of patients. 1, 2

Common Side Effects

• The most frequently reported adverse events with ramelteon include:
  • Somnolence (3% vs 2% with placebo) 2
  • Fatigue (3% vs 2% with placebo) 2
  • Dizziness (4% vs 3% with placebo) 2
  • Nausea (3% vs 2% with placebo) 2
  • Headache (7% vs placebo) 3
  • Exacerbation of insomnia (3% vs 2% with placebo) 2

Serious Side Effects

• Rare but serious adverse reactions include:
  • Severe anaphylactic and anaphylactoid reactions including angioedema involving the tongue, glottis, or larynx 2
  • Symptoms such as dyspnea, throat closing, nausea, and vomiting suggesting anaphylaxis 2
  • These reactions may require emergency medical treatment and can be fatal if airway obstruction occurs 2

Neuropsychiatric Effects

• Cognitive and behavioral changes have been reported with ramelteon use:
  • Abnormal thinking and behavioral changes 2
  • Hallucinations, bizarre behavior, agitation, and mania 2
  • Amnesia and anxiety 2
  • Complex behaviors such as "sleep-driving" and other activities with amnesia for the event 2
  • Worsening of depression including suicidal ideation in primarily depressed patients 2

Next-Day Effects

• Unlike many other sleep medications, ramelteon generally does not cause significant next-day impairment:
  • Three clinical studies specifically assessed next-day effects and found no consistent evidence of residual impairment 1, 4
  • Roth and colleagues reported no significant residual effects on cognitive function, recall, alertness, or concentration in older adults 4
  • Zammitt et al. found only isolated, transient impairments that were not consistent across the study period 4
  • Mayer found no consistent evidence of next-day impairment in alertness, recall, or cognition 4

Endocrine Effects

• Ramelteon has been associated with effects on reproductive hormones:
  • Decreased testosterone levels 2
  • Increased prolactin levels 2
  • The long-term impact of these hormonal changes on developing humans is unknown 2
  • Assessment of prolactin and testosterone levels should be considered for patients presenting with unexplained amenorrhea, galactorrhea, decreased libido, or fertility problems 2

Drug Interactions and Precautions

• Patients should avoid:
  • Engaging in hazardous activities requiring concentration after taking ramelteon 2
  • Consuming alcohol in combination with ramelteon due to potential additive effects 2
  • Using ramelteon if they have severe hepatic impairment 2
  • Using ramelteon if they have severe sleep apnea 2

Advantages Over Other Hypnotics

• Unlike benzodiazepines and non-benzodiazepine hypnotics, ramelteon:
  • Has no abuse potential and is not classified as a controlled substance 4, 5
  • Shows no evidence of rebound insomnia or withdrawal effects following discontinuation 1
  • Has not been associated with significant next-day cognitive or motor impairment 4
  • May be preferable for elderly patients due to minimal next-day effects and low risk of falls 4

Monitoring Recommendations

• No standard laboratory monitoring is required for patients taking ramelteon 2
• Patients should be monitored for:
  • Development of abnormal thinking or behavioral changes 2
  • Signs of anaphylactic or anaphylactoid reactions 2
  • Hormonal effects in patients with relevant symptoms 2

Ramelteon's unique mechanism as a melatonin receptor agonist contributes to its favorable side effect profile compared to other hypnotics, making it a suitable option for patients with insomnia characterized by difficulty falling asleep, particularly when there are concerns about next-day impairment or potential for abuse 4, 6.