From the Guidelines
Benzodiazepines and Z-drugs (non-benzodiazepine hypnotics) are typically considered last-line interventions for treating insomnia, due to their potential for dependence, tolerance, and withdrawal, as well as other significant concerns such as physical dependence, cognitive impairment, and increased fall risk 1.
Key Considerations
- These medications should be used at the lowest effective dose for the shortest duration possible, ideally less than 2-4 weeks.
- Examples of benzodiazepines include temazepam (15-30 mg), lorazepam (0.5-2 mg), and clonazepam (0.5-2 mg).
- Examples of Z-drugs include zolpidem (5-10 mg), eszopiclone (1-3 mg), and zaleplon (5-20 mg).
Mechanism of Action
- These medications work by enhancing the effect of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, which promotes sleep by reducing neuronal excitability.
Prior to Consideration
- Patients should try cognitive behavioral therapy for insomnia (CBT-I), sleep hygiene improvements, and possibly other pharmacological options like melatonin, doxepin, or trazodone, which have better safety profiles for long-term use 1.
Important Notes
- The choice of a specific pharmacological agent within a class should be directed by symptom pattern, treatment goals, past treatment responses, patient preference, cost, availability of other treatments, comorbid conditions, contraindications, concurrent medication interactions, and side effects 1.
- Over-the-counter antihistamine or antihistamine/analgesic type drugs (OTC “sleep aids”) as well as herbal and nutritional substances (e.g., valerian and melatonin) are not recommended in the treatment of chronic insomnia due to the relative lack of efficacy and safety data 1.
From the Research
Last Line Intervention for Insomnia Treatment
The last line of intervention for insomnia treatment often involves the use of certain drug classes when other treatments have failed.
- Benzodiazepines are not recommended due to their high abuse potential and availability of better alternatives 2.
- Sedating antihistamines, antiepileptics, and atypical antipsychotics are not recommended unless used primarily to treat another condition 2.
- Orexin receptor antagonists like suvorexant may be considered, but they are no more effective than z-drugs and are more expensive 2, 3.
- Off-label drugs such as trazodone, an antidepressant, have been shown to be effective for insomnia treatment, particularly for primary and secondary insomnia 4, 3, 5.
- Other off-label options include low-dose doxepin, which is recommended for sleep maintenance insomnia 2, 3.
Drug Classes Used
Some of the drug classes used as last line intervention for insomnia treatment include: