What is the efficacy of promethazine (Phenergan) as a hypnotic for insomnia?

Promethazine is NOT Effective as a Hypnotic and Should Not Be Used for Insomnia

Promethazine should not be prescribed for insomnia treatment due to lack of efficacy evidence, significant safety concerns, interference with evidence-based therapies, and potential for dependence. 1, 2

Why Promethazine Fails as a Sleep Aid

Lack of Evidence for Efficacy

• The American Academy of Sleep Medicine explicitly states that over-the-counter antihistamine sleeping aids (including promethazine) are not recommended due to lack of demonstrated efficacy and safety concerns 1
• Evidence for antihistamine efficacy and safety is "very limited, with very few available studies from the past 10 years using contemporary study designs and outcomes" 1
• Recent analysis confirms promethazine "has no good evidence base" for improving sleep quality 2

Significant Safety Concerns

• Anticholinergic toxicity: Promethazine has serious side effects from its anticholinergic properties, including cognitive impairment, confusion, urinary retention, constipation, and increased fall risk (particularly dangerous in elderly patients) 1, 3
• CNS depression: The FDA label warns of marked drowsiness and impaired mental/physical abilities, with enhanced impairment when combined with other CNS depressants 3
• Underappreciated addiction potential: Promethazine has recreational use and addictive potential that is often overlooked by prescribers 2
• Cardiovascular risks: Should be used cautiously in patients with cardiovascular disease 3

Interference with Effective Treatment

• Promethazine actively impedes cognitive-behavioral therapy for insomnia (CBT-I), which is the evidence-based first-line treatment 2
• Patients using promethazine are less likely to engage with or benefit from psychological and behavioral techniques that actually improve sleep in the medium-to-long term 2

What Should Be Used Instead

First-Line Treatment

• Cognitive Behavioral Therapy for Insomnia (CBT-I) is the standard of care and should be offered before or alongside any pharmacotherapy 1, 4

Appropriate Pharmacotherapy When Needed

For sleep onset difficulty:

• Short-acting benzodiazepine receptor agonists (BzRAs): zaleplon, zolpidem (very short half-lives, minimal residual sedation) 1
• Ramelteon (melatonin receptor agonist, no DEA scheduling, appropriate for patients with substance use history) 1, 4

For sleep maintenance difficulty:

• Low-dose doxepin (3-6 mg) - improved sleep efficiency with favorable safety profile in older adults 1, 4
• Eszopiclone or temazepam (longer half-lives for sleep maintenance) 1

Second-line options (when comorbidities present):

• Sedating antidepressants: trazodone, mirtazapine, low-dose doxepin (particularly when treating comorbid depression/anxiety) 1, 4

Critical Prescribing Principles

• Use the lowest effective dose and shortest possible duration 1, 4
• Provide patient education on treatment goals, safety concerns, and potential side effects 1, 4
• Regular follow-up to assess efficacy and monitor for adverse effects 4
• Gradual tapering when discontinuing to minimize rebound insomnia 1

Common Pitfall to Avoid

The most dangerous pitfall is prescribing promethazine because it's "non-scheduled" or perceived as "safer" than controlled substances. This is false. 2 Promethazine lacks efficacy evidence, has significant anticholinergic and CNS side effects, interferes with effective behavioral treatments, and has underrecognized abuse potential. If a non-scheduled medication is required, low-dose doxepin (3-6 mg) has actual evidence supporting its use and a more favorable safety profile. 1, 4