What medications are effective for treating insomnia?

From the Guidelines

Benzodiazepines like temazepam (15-30mg) or non-benzodiazepine "Z-drugs" such as zolpidem (5-10mg), eszopiclone (1-3mg), and zaleplon (5-20mg) are commonly prescribed for short-term insomnia management, while low-dose doxepin (3-6mg) or the melatonin receptor agonist ramelteon (8mg) may be used for longer-term management, as suggested by the American College of Physicians guideline 1. When considering treatment options for insomnia, it's essential to weigh the benefits and risks of each medication.

• Benzodiazepines and Z-drugs can be effective for short-term use but may lead to dependence, morning grogginess, or rebound insomnia.
• Low-dose doxepin and ramelteon are alternatives for longer-term management, with a more favorable side effect profile.
• Over-the-counter options like diphenhydramine (25-50mg) or doxylamine (25mg) should be used sparingly due to potential side effects.
• Melatonin supplements (0.5-5mg) can help regulate sleep cycles, particularly for circadian rhythm disorders. It's crucial to use these medications at the lowest effective dose for the shortest duration possible and to avoid alcohol consumption, which can increase side effects, as recommended by the American Academy of Sleep Medicine 1. Additionally, cognitive behavioral therapy for insomnia (CBT-I) is a recommended first-line treatment for adults with chronic insomnia disorder, as it can improve sleep outcomes and reduce symptoms of insomnia, according to the American College of Physicians guideline 1.

From the FDA Drug Label

Eszopiclone tablets are indicated for the treatment of insomnia. In controlled outpatient and sleep laboratory studies, eszopiclone tablets administered at bedtime decreased sleep latency and improved sleep maintenance. Zolpidem tartrate tablets are indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. Zolpidem tartrate tablets have been shown to decrease sleep latency for up to 35 days in controlled clinical studies

The medications eszopiclone and zolpidem are effective for treating insomnia, as they have been shown to decrease sleep latency and improve sleep maintenance in clinical studies 2, 3, and 3.

• Eszopiclone is indicated for the treatment of insomnia, with clinical trials performed up to 6 months in duration.
• Zolpidem is indicated for the short-term treatment of insomnia, with clinical trials performed up to 5 weeks in duration.

From the Research

Medications for Insomnia

• Nonbenzodiazepine hypnotic medications, such as zolpidem, zaleplon, and eszopiclone, have been shown to be effective in treating insomnia, with a lower risk of tolerance and abuse compared to traditional benzodiazepines 4.
• Melatonin receptor agonists, such as ramelteon, have also been found to be helpful in treating sleep initiation difficulties, with no abuse liability and no limitation on prescription duration 4, 5.
• Low-dose doxepin has been demonstrated to be effective in treating sleep maintenance insomnia, with minimal anticholinergic effects 4.
• The z-drugs (zolpidem, eszopiclone, and zaleplon) are recommended as first-line agents for the general population with difficulty falling asleep, while low-dose doxepin and the z-drugs are recommended for those who have difficulty staying asleep 6.
• Benzodiazepines are not recommended due to their high abuse potential and the availability of better alternatives 6.

Comparative Efficacy of Insomnia Medications

• A systematic review and network meta-analysis found that benzodiazepines, doxylamine, eszopiclone, lemborexant, seltorexant, zolpidem, and zopiclone were more efficacious than placebo in acute treatment, while eszopiclone and lemborexant were more effective than placebo in long-term treatment 7.
• The same study found that eszopiclone and lemborexant had a favorable profile, but eszopiclone might cause substantial adverse events, and safety data on lemborexant were inconclusive 7.
• Doxepin, seltorexant, and zaleplon were found to be well-tolerated, but data on efficacy and other important outcomes were scarce 7.

Safety and Tolerability of Insomnia Medications

• The non-benzodiazepine hypnotics, such as zolpidem and zopiclone, have been associated with some risk for dependence and abuse, but concerns regarding such risks appear to be greater than warranted by empirical evidence 8.
• Rare but serious adverse events, such as anaphylaxis, angio-oedema, and complex sleep-related behaviors, have been identified in postmarketing surveillance of hypnotics, including zolpidem and zopiclone 8.
• Benzodiazepines, eszopiclone, zolpidem, and zopiclone were found to cause more dropouts due to adverse events than placebo, while doxepin, seltorexant, and zaleplon were found to be well-tolerated 7.