Doxepin 3 mg or Zolpidem 5 mg for insomnia?

From the Guidelines

Doxepin 3 mg is the preferred option for treating insomnia due to its favorable safety profile and effectiveness for sleep maintenance, as supported by recent clinical guidelines 1. When considering the treatment of insomnia, it's essential to weigh the benefits and risks of different medications. Doxepin 3 mg and zolpidem 5 mg are two commonly used options, but they have distinct differences in their mechanisms of action, efficacy, and safety profiles.

• Doxepin 3 mg works by blocking histamine receptors in the brain, making it particularly helpful for people who wake up during the night.
• Zolpidem 5 mg, on the other hand, is better for sleep onset insomnia (difficulty falling asleep) as it works more quickly. However, zolpidem 5 mg carries more risks, including potential dependence, next-day impairment, and should be used for shorter periods (typically 7-10 days) 1.
• A systematic review found that nonbenzodiazepine BZRAs, such as zolpidem, improved sleep efficiency and other important outcomes compared with placebo, but also carried risks of adverse events and withdrawal symptoms 1.
• In contrast, doxepin 3 mg has a more favorable safety profile, with no black box warning for suicide risk, and its incidence of adverse events seemed to increase with longer treatment, but none of the RCTs found statistically significant differences in adverse event rates between low-dose doxepin and placebo 1. The choice between doxepin 3 mg and zolpidem 5 mg ultimately depends on the individual's specific sleep problem, age, other medications, and medical conditions, and consulting with a healthcare provider is essential for personalized advice 1.

From the FDA Drug Label

14.1 Transient Insomnia ... Normal elderly adults (mean age 68) experiencing transient insomnia (n=35) during the first two nights in a sleep laboratory were evaluated in a double-blind, crossover, 2-night trial comparing four doses of zolpidem (5,10,15 and 20 mg) and placebo All zolpidem doses were superior to placebo on the two primary PSG parameters (sleep latency and efficiency) and all four subjective outcome measures (sleep duration, sleep latency, number of awakenings, and sleep quality).

• Doxepin 3 mg is not mentioned in the provided drug label.
• Zolpidem 5 mg is mentioned as a dose that was superior to placebo on the two primary PSG parameters and all four subjective outcome measures in a study of normal elderly adults with transient insomnia 2. The FDA drug label does not provide a direct comparison between Doxepin 3 mg and Zolpidem 5 mg for insomnia.

From the Research

Comparison of Doxepin and Zolpidem for Insomnia

• Doxepin 3 mg and Zolpidem 5 mg are two medications used to treat insomnia, with different mechanisms of action and side effect profiles 3, 4.
• A study comparing the effects of doxepin and zolpidem on sleep structure and executive function in patients with insomnia disorder found that doxepin improved executive function more effectively than zolpidem 4.
• Doxepin 3 mg has been shown to be effective in improving sleep maintenance and duration in adults with primary insomnia, with a safety profile comparable to placebo 5, 6.
• Zolpidem 5 mg, on the other hand, has been associated with a range of adverse effects, including an increased risk of falls, hip fractures, and complex behaviors such as sleepwalking and driving while asleep 3.
• The choice between doxepin 3 mg and zolpidem 5 mg for insomnia should be made on a case-by-case basis, considering the individual patient's needs and medical history 3, 4.

Efficacy and Safety of Doxepin

• Doxepin 3 mg and 6 mg have been shown to be effective in improving sleep quality and reducing wake time after sleep onset in adults with primary insomnia 5, 6.
• Doxepin has a unique profile of sleep maintenance efficacy and safety, with no evidence of rebound insomnia or withdrawal effects upon discontinuation 6.
• The safety profile of doxepin is comparable to placebo, with no reported anticholinergic effects, no memory impairment, and no significant hangover/next-day residual effects 5, 6.

Considerations for Treatment

• The treatment of insomnia should involve a multi-disciplinary approach, focusing on implementing behavioral interventions, improving sleep hygiene, managing psychological stressors, hypnotic treatment, and pharmacological therapy 3.
• Antidepressants, such as doxepin, may be considered for the treatment of insomnia, particularly in patients with concomitant depressive symptomology or a history of depression 7.
• The dose of doxepin should be as low as possible, with 3 mg being a commonly used dose for the treatment of insomnia 5, 6.