Which medication, doxepin (Sinequan) or suvorexant (Belsomra), is least likely to cause nightmares and next-day somnolence?

Comparative Safety Profile: Doxepin vs Suvorexant for Nightmares and Next-Day Tiredness

For minimizing nightmares, doxepin is the safer choice as it has no documented association with nightmares in clinical trials, whereas suvorexant's FDA labeling explicitly warns of abnormal dreams as a reported side effect. 1

Nightmare Risk

Doxepin (3-6 mg) has no evidence of causing nightmares in the comprehensive American Academy of Sleep Medicine meta-analyses, which evaluated headache, somnolence, diarrhea, and upper respiratory infections as adverse events but did not identify nightmares or abnormal dreams as a concern. 2

Suvorexant carries documented risk of abnormal dreams. The FDA drug labeling for suvorexant (Belsomra) specifically lists "abnormal dreams" as an additional side effect beyond the most common adverse reactions. 1 The FDA labeling also warns of complex sleep behaviors and potential neuropsychiatric symptoms including hallucinations, which could manifest as disturbing dream content. 1

Next-Day Somnolence Risk

Both medications show comparable low risk for next-day tiredness, but doxepin has slightly better evidence:

Doxepin Next-Day Effects

• At 3 mg: No significant increase in somnolence versus placebo (risk difference +0.01). 2
• At 6 mg: Small increased risk (risk difference +0.04). 2
• No difference from placebo on objective next-day performance measures including DSST (Digit Symbol Substitution Test), Symbol Copying Test, or visual analogue scales for morning sleepiness at either 3 mg or 6 mg doses. 2
• Multiple studies confirm no significant next-day residual sedation effects with low-dose doxepin. 3, 4, 5

Suvorexant Next-Day Effects

• Somnolence is the most common adverse effect, occurring in approximately 7% of patients (versus 3% for placebo). 6, 1
• At therapeutic doses (15/20 mg), somnolence rates ranged from 5.1% to 8.4% compared to 3.1-3.4% for placebo. 2
• The FDA labeling explicitly warns patients not to drive or operate machinery the next day until fully awake, as drowsiness may persist. 1
• Somnolence frequency increases in a dose-dependent manner at higher doses. 2

Clinical Decision Algorithm

For patients prioritizing nightmare avoidance:

• Choose doxepin 3-6 mg as first-line, as it has no documented nightmare risk. 2
• Avoid suvorexant if the patient has history of vivid dreams, nightmares, or neuropsychiatric symptoms. 1

For patients prioritizing minimal next-day tiredness:

• Doxepin 3 mg is optimal, with essentially no difference from placebo in somnolence risk and objective performance measures. 2
• If using doxepin 6 mg, counsel about the small (4%) increased somnolence risk. 2
• Suvorexant carries higher next-day somnolence risk (7% vs 3% placebo), particularly problematic for patients who must drive or operate machinery. 6, 1

Important Caveats

Doxepin is specifically indicated for sleep maintenance insomnia, not sleep onset difficulties, so it should be reserved for patients with wake after sleep onset problems. 7, 8

Suvorexant requires at least 7 hours of sleep opportunity to minimize next-day effects, and should not be taken with alcohol or after meals (which delays onset). 1

Both medications are recommended by the American Academy of Sleep Medicine for sleep maintenance insomnia, but doxepin has the advantage of lower cost and no controlled substance classification. 2, 7