Which is more potent for insomnia, Atarax (hydroxyzine) or Unisom (doxylamine)?

Hydroxyzine (Atarax) vs Doxylamine (Unisom) for Insomnia

Doxylamine (Unisom) is more potent for insomnia than hydroxyzine (Atarax), with evidence supporting its effectiveness for short-term use up to four weeks, though neither medication is recommended as a first-line treatment for insomnia. 1

Efficacy Comparison

• Doxylamine succinate:

  • Effective for short-term insomnia treatment (up to four weeks) 1
  • Acts as a histamine H1 inverse agonist with specific benefits for maintenance insomnia (sleep in the last third of the night) 2
  • Available over-the-counter at doses of 12.5mg and 25mg 3
  • Shows dose-proportional effects with linear increases in plasma concentration between 12.5mg and 25mg doses 3

• Hydroxyzine (Atarax):

  • Not specifically mentioned in the provided guidelines for insomnia management
  • Falls under the general category of antihistamines, which are not recommended for sleep in elderly patients due to anticholinergic effects 4

Guideline Recommendations

The American Academy of Sleep Medicine and American Geriatrics Society do not recommend antihistamines like doxylamine or hydroxyzine as preferred treatments for insomnia:

• Diphenhydramine and other antihistamines are specifically not recommended for sleep in elderly patients due to anticholinergic effects 4
• Evidence for antihistamine use in insomnia is generally lacking, though doxylamine shows some effectiveness for up to four weeks 1
• Guidelines prioritize non-pharmacological approaches and other medication classes when pharmacotherapy is necessary 4

Potential Risks and Concerns

• Addiction potential: Case reports document doxylamine addiction with escalating doses (from 25mg/day to 125mg/day) 5
• Antihistamines generally have anticholinergic effects that can be problematic, especially in elderly patients 4
• Routine use of over-the-counter antihistamines for sleep should be discouraged according to clinical guidance 6

Recommended Approach to Insomnia Treatment

1. First-line: Non-pharmacological interventions

   • Cognitive Behavioral Therapy for Insomnia (CBT-I) 4, 1
   • Sleep hygiene education
   • Sleep restriction
   • Stimulus control
   • Regular exercise 4

2. If pharmacotherapy is necessary, preferred options include:

   • For sleep onset insomnia:

     • Ramelteon (8mg)
     • Zolpidem (10mg adults, 5mg elderly)
     • Zaleplon (10mg) 4

   • For sleep maintenance insomnia:

     • Low-dose doxepin (3-6mg)
     • Eszopiclone (2-3mg)
     • Suvorexant (10-20mg) 4

Important Caveats

• Both medications should be used for the shortest duration possible
• Neither medication is recommended for long-term use
• Elderly patients are particularly susceptible to anticholinergic side effects
• The better safety profile of newer-generation sleep medications makes them preferable for chronic insomnia 6
• Always assess for underlying causes of insomnia before initiating any pharmacological treatment 4

While doxylamine appears more potent for insomnia based on available evidence, clinicians should consider safer alternatives with better evidence profiles for managing insomnia, particularly for anything beyond very short-term use.