What are the rankings of ramelteon, Dayvigo (lemborexant), hydroxyzine, clonazepam, doxepin, and suvorexant for their potential to cause weight loss, weight gain, nightmares, and next-day tiredness?

Comparative Rankings of Sleep Medications by Side Effect Profile

1. Most Likely to Cause Weight Loss (Ranked)

None of these medications are associated with weight loss. All six agents are either weight-neutral or potentially weight-promoting, with the evidence base showing no sleep medications in this class promote weight reduction 1.

1. Ramelteon - Most weight-neutral (melatonin receptor agonist with minimal metabolic effects) 1, 2
2. Suvorexant - Weight-neutral orexin antagonist 1, 2
3. Dayvigo (lemborexant) - Weight-neutral orexin antagonist 3, 4
4. Doxepin - Low-dose formulations (3-6 mg) appear weight-neutral 1, 2
5. Hydroxyzine - Antihistamines show dose-dependent weight gain potential; more potent antihistamines carry greater risk 1
6. Clonazepam - Benzodiazepines associated with weight gain through multiple mechanisms including increased appetite and sedation-related decreased activity 1

2. Most Likely to Cause Weight Gain (Ranked)

Clonazepam and hydroxyzine carry the highest weight gain risk among these agents.

1. Clonazepam - Benzodiazepines consistently associated with weight gain through appetite stimulation and activity reduction 1
2. Hydroxyzine - Potent H1 antihistamine antagonism strongly linked to weight gain; more potent antihistamines show greater weight gain potential 1
3. Doxepin - At higher doses (typical antidepressant range), tricyclic antidepressants cause significant weight gain, though low-dose formulations (3-6 mg) for insomnia appear more weight-neutral 1, 2
4. Dayvigo (lemborexant) - Minimal weight impact as orexin antagonist 3, 4
5. Suvorexant - Minimal weight impact as orexin antagonist 1, 2
6. Ramelteon - Most weight-neutral option; melatonin receptor agonism not associated with metabolic effects 1, 2

3. Least Likely to Cause Nightmares (Ranked)

Ramelteon and the orexin antagonists have the lowest nightmare risk due to their mechanisms preserving normal sleep architecture.

1. Ramelteon - Melatonin receptor agonist that promotes natural sleep-wake regulation without REM suppression 1, 2
2. Dayvigo (lemborexant) - Orexin antagonist that preserves REM sleep architecture; Phase II studies show improved sleep maintenance without REM disruption 3, 2
3. Suvorexant - Orexin antagonist that actually increases REM sleep time compared to other hypnotics, particularly versus zolpidem; longer REM sleep associated with reduced nightmare frequency 5, 2
4. Doxepin - Low-dose H1 antagonism for sleep maintenance; limited nightmare data but no REM suppression at 3-6 mg doses 1, 2
5. Hydroxyzine - Antihistamine sedation may suppress REM sleep, potentially increasing REM rebound nightmares 2
6. Clonazepam - Benzodiazepines suppress REM sleep and cause REM rebound upon discontinuation, significantly increasing nightmare risk, particularly problematic in PTSD populations 6, 2

Clinical caveat: Suvorexant demonstrated significantly longer REM sleep time than zolpidem and placebo in elderly subjects, suggesting better preservation of normal sleep architecture that may reduce nightmare occurrence 5.

4. Least Likely to Cause Next-Day Tiredness (Ranked)

Ramelteon has the cleanest next-day profile, followed by the short-acting orexin antagonists.

1. Ramelteon - No next-day residual effects; works through circadian regulation rather than sedation; elderly subjects showed no remarkable changes in physical or cognitive function the following day 5, 2
2. Dayvigo (lemborexant) - Minimal next-day impairment; orexin antagonists designed to avoid morning sedation 3, 2
3. Suvorexant - Low-dose (10 mg) showed minimal next-day effects in elderly subjects; body sway testing revealed better performance than some comparators, though slightly more effect than zolpidem in closed-eye balance testing 5, 2
4. Doxepin - Low doses (3-6 mg) for sleep maintenance have shorter half-life effects than traditional antidepressant doses, but H1 antagonism can cause morning grogginess 1, 2
5. Hydroxyzine - Antihistamine with significant next-day sedation and anticholinergic effects causing morning drowsiness and cognitive impairment 2
6. Clonazepam - Long-acting benzodiazepine (half-life 30-40 hours) causes substantial next-day sedation, cognitive impairment, and fall risk, particularly problematic in elderly patients 2

Critical distinction: In elderly subjects receiving single low-dose administration, all three agents (suvorexant 10 mg, ramelteon 4 mg, zolpidem 5 mg) showed minimal next-day physical and cognitive impairment, making them appropriate for elderly populations, but ramelteon had the cleanest profile overall 5.