What are the medication recommendations for insomnia in a patient taking benzodiazepines (Benzodiazepine)

From the Guidelines

For a patient already taking a benzodiazepine who is experiencing insomnia, the primary recommendation is to avoid adding another benzodiazepine medication due to risk of tolerance, dependence, and additive sedative effects. Instead, consider non-benzodiazepine options like cognitive behavioral therapy for insomnia (CBT-I) as first-line treatment, as suggested by the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guidelines 1. If medication is necessary, low-dose trazodone (25-100mg at bedtime) or non-benzodiazepine hypnotics like zolpidem (5-10mg), eszopiclone (1-3mg), or zaleplon (5-10mg) at bedtime may be appropriate alternatives, as they have been shown to improve sleep efficiency and reduce sleep onset latency compared to placebo 1. Melatonin (1-5mg) or extended-release melatonin can also be considered for milder cases. Some key points to consider when treating insomnia in patients taking benzodiazepines include:

• Avoiding the use of benzodiazepines or trazodone for treatment of chronic insomnia disorder due to their potential harms and adverse effects 1
• Using nonbenzodiazepine BZRAs at the lowest effective dose and for the shortest possible duration to minimize adverse events 1
• Counseling patients on the potential risks associated with nonbenzodiazepine BZRAs, including the risk for serious injuries caused by sleep behaviors 1
• Implementing sleep hygiene measures, including maintaining a regular sleep schedule, avoiding stimulants before bedtime, creating a comfortable sleep environment, and limiting screen time before bed. It's also important to address the underlying cause of insomnia and develop a plan to gradually taper the current benzodiazepine if possible, as long-term use can actually worsen sleep architecture and lead to rebound insomnia. The goal should be to treat insomnia while minimizing polypharmacy and addressing the potential contribution of the current benzodiazepine to the sleep disturbance.

From the FDA Drug Label

2.3 Use with CNS Depressants Dosage adjustment may be necessary when zolpidem tartrate tablets are combined with other CNS-depressant drugs because of the potentially additive effects [see WARNINGS AND PRECAUTIONS (5.2)].

When a patient is taking benzodiazepine, which is a CNS depressant, and is prescribed zolpidem, dosage adjustment may be necessary due to the potentially additive effects of these drugs.

• The patient should be closely monitored for signs of excessive sedation or respiratory depression.
• The lowest effective dose of zolpidem should be used, and the patient should be cautioned about the risks of combining CNS depressants.
• The recommended initial dose of zolpidem is 5 mg for women and either 5 or 10 mg for men, but this may need to be adjusted based on the patient's response to the medication and the presence of other CNS depressants 2.

From the Research

Medication Recommendations for Insomnia in Patients Taking Benzodiazepines

When considering medication recommendations for insomnia in patients who are already taking benzodiazepines, several factors must be taken into account, including the potential for dependence, tolerance, and adverse effects associated with long-term benzodiazepine use 3, 4.

• Alternative Therapies: Non-benzodiazepine hypnotics such as zolpidem, zaleplon, and eszopiclone are generally well-tolerated and have favorable safety profiles compared to older benzodiazepines and barbiturates 5.
• Melatonin Receptor Agonists: Ramelteon, a melatonin receptor agonist, has a minimal adverse effect profile and is effective for sleep-onset latency and increasing total sleep time, making it a valuable first-line option 6, 7.
• Dual Orexin Receptor Antagonists: Suvorexant is recommended for sleep maintenance insomnia due to its efficacy and relatively mild adverse effects 7.
• Low-Dose Sedating Antidepressants: Low-dose doxepin is recommended for sleep maintenance insomnia, with evidence supporting its use 7.
• Gabapentin and Pregabalin: These may be useful in patients with restless leg syndrome or chronic neuropathic pain and insomnia, although their use in insomnia treatment is not extensively studied 6, 7.

Considerations for Patients on Benzodiazepines

For patients already taking benzodiazepines, the goal should be to minimize the duration of use and to use the lowest effective dose, due to the risks of dependence, cognitive impairment, and other adverse effects 3, 4.

• Gradual Tapering: For patients who have been taking benzodiazepines for a long time, a gradual and carefully monitored taper is recommended to reduce the risk of withdrawal symptoms and to minimize potential harm 3.
• Cognitive Behavioral Therapy: This should always be considered as a first-line treatment for insomnia, given its efficacy and lack of adverse effects 6.

Safety and Efficacy

The safety and efficacy of medications used to treat insomnia, especially in older adults, must be carefully evaluated, considering the potential for adverse effects such as dementia, serious injury, and fractures 6.

• Non-Pharmacologic Interventions: There should be an emphasis on non-pharmacologic interventions and treating comorbid conditions, with benzodiazepines and non-benzodiazepine receptor agonists used as last resorts 6.