What is the recommended dosing of doxepin (Sinequan) for insomnia?

From the Guidelines

Doxepin is recommended for insomnia at a dose of 3-6 mg taken orally once daily, about 30 minutes before bedtime, as it has been shown to improve sleep maintenance insomnia with minimal anticholinergic effects and less next-day impairment compared to higher antidepressant doses 1. The recommended starting dose is 3-6 mg, with some patients benefiting from doses as low as 3 mg, while others might require up to 6 mg.

• The maximum recommended dose for insomnia is 6 mg daily.
• It's essential to take doxepin consistently at the same time each night and allow for 7-8 hours of sleep after taking it to avoid morning drowsiness.
• Patients should avoid alcohol while taking doxepin as it can increase sedation and other side effects.
• Common side effects include drowsiness, dry mouth, and dizziness. Doxepin works for insomnia by blocking histamine H1 receptors in the brain, which promotes sleep without the tolerance and dependence issues associated with some other sleep medications, as supported by a systematic review that included 6 industry-sponsored RCTs, which found that low-dose doxepin (1,3, and 6 mg) improved scores on the ISI and subjective sleep latency, total sleep time, and sleep quality outcomes in older and younger adults 1.

From the Research

Doxepin Dosing for Insomnia

• Doxepin is a tricyclic compound that has been used to treat insomnia, with low-dose formulations (3-6 mg) showing efficacy in improving sleep maintenance and duration 2, 3, 4, 5.
• The low-dose formulation of doxepin selectively antagonizes H1 receptors, which is believed to promote the initiation and maintenance of sleep 2, 6.
• Clinical trials have demonstrated that low-dose doxepin (3-6 mg) is effective in reducing wake time after sleep onset, improving total sleep time, and enhancing sleep efficiency in adults with primary insomnia 2, 4, 5.
• The efficacy of low-dose doxepin has been maintained for up to 12 weeks of administration, with no evidence of physical dependence or worsening insomnia after discontinuation 2, 5.
• Common side effects of low-dose doxepin include headache and somnolence, with no significant next-day residual effects or anticholinergic effects reported 3, 4, 5.

Dosage and Administration

• The recommended dosage of doxepin for insomnia is 3-6 mg once daily, taken orally 2, 3, 4, 5.
• The 3 mg and 6 mg doses have been shown to be effective in improving sleep maintenance and duration, with the 6 mg dose also reducing subjective latency to sleep onset 4.
• The safety profile of low-dose doxepin is comparable to placebo, with no significant differences in next-day residual sedation or sleep architecture reported 4, 5.

Efficacy and Safety

• Low-dose doxepin has been shown to be effective in improving sleep maintenance and duration in adults with primary insomnia, with a small to medium effect size against placebo 3.
• The efficacy of low-dose doxepin has been demonstrated in both immediate and short-term posttreatment assessments, with no significant next-day residual effects reported 3, 5.
• The safety profile of low-dose doxepin is favorable, with no significant differences in adverse events or discontinuation rates compared to placebo 3, 4, 5.