Discontinuing "Z drugs"
"Z drugs" refers to a class of drugs typically used to treat insomnia. They include zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). Technically, these drugs are known as "benzodiazepine receptor agonists (BZRA)." Below are links to expert guidance for physicians on how to help patients discontinue use of these drugs.
Croke L. (2019). Deprescribing Benzodiazepine Receptor Agonists for Insomnia in Adults. American Family Physician, 99, 1, 57-58. [PDF]
Pottie, K., Thompson, W., Davies, S, et al. (2018). Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guideline. Canadian Family Physician, 64, 5, 339-351. [PDF]
Deprescribing.org: Guidelines and algorithms
Benzodiazepine Receptor Agonist deprescribing guideline (published in Canadian Family Physician) (13 pages)
Benzodiazepine Receptor Agonist deprescribing algorithm (2 pages)
Benzodiazepine and Z-Drug deprescribing guideline information pamphlet (2 pages)
Benzodiazepine and Z-Drug deprescribing infographic (1 page)
Whiteboard video on using the Benzodiazepine Receptor Agonist deprescribing algorithm (12 minutes)
Kaiser Permanente: Benzodiazepine and Z Drug Safety Guideline [PDF]
American Family Physician - Deprescribing Benzodiazepine Receptor Agonists for Insomnia in Adults
Croke L. (2019). Deprescribing Benzodiazepine Receptor Agonists for Insomnia in Adults. American Family Physician, 99, 1, 57-58. [PDF]
Key points of this article
• Although BZRAs are beneficial for short-term improvement in sleep onset latency and duration, they also have associated harms, including problems with dependence. Evidence suggests that the benefits of BZRAs for insomnia wane after four weeks, whereas harms can continue, especially for older persons, including a greater risk of falls, motor vehicle collisions, problems with memory, and daytime sedation.
• A slow taper of BZRAs is recommended in patients 18 to 64 years of age who use these most days of the week for more than four weeks.
• Patients 65 years and older taking a BZRA for any duration should be recommended to taper off slowly.
• A slow taper with a 25% dose reduction every two weeks and medication-free days at the end of the taper is suggested.
• It should be noted that switching to a long-acting BZRA does not improve cessation rates or reduce withdrawal symptoms compared with tapering short-acting BZRAs.
• Options include 50% reduction and switching to lorazepam (Ativan)... during final tapering if the patient's current dosage does not allow tapering in 25% increments.
Canadian Family Physician - Deprescribing benzodiazepine receptor agonists
Pottie, K., Thompson, W., Davies, S, et al. (2018). Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guideline. Canadian Family Physician, 64, 5, 339-351. [PDF]
Benzodiazepine receptor agonists are associated with harms, and therapeutic effects might be short term.
Taper the BZRA dose slowly
Adding CBT to the tapering intervention improves cessation rates versus tapering alone
risks of ongoing BZRA use (eg, falls, memory impairment, motor vehicle accidents) and potential benefits of discontinuation (eg, reduced fall risk, less daytime sedation, improvement in thinking and memory);
therapeutic effect of BZRAs might be lost within 4 weeks owing to receptor changes (but amnestic effects persist)5; and
mild, short-term (a few days to weeks) adverse drug withdrawal effects can be expected during tapering.39
Very gradual dose reductions to lowest available doses (eg, 25% reduction every 2 weeks and a slower taper of 12.5% every 2 weeks near the end of stopping), followed by periodic drug-free days were used successfully in clinical trials (Table 2).28,30–38 Switching to long-acting BZRAs (eg, diazepam) has not been shown to reduce incidence of withdrawal symptoms or improve cessation rates more than tapering shorter-acting BZRAs does.
When deciding on tapering doses and rates, consider using a slower rate with those more likely to have a higher risk of relapse (eg, long-term use or history of psychological distress). Some clinicians would recommend tapering over several months. Such patients might require closer monitoring and support.
What withdrawal symptoms can be expected and how should they be dealt with?
The tapering group reported more trouble sleeping at 3 months compared with continuation of BZRAs
In many cases, when withdrawal symptoms occur they are mild and short term (lasting a few days and up to approximately 4 weeks).39 In studies detailing benzodiazepine withdrawal symptoms, such symptoms tend to appear and peak more quickly (1 to 2 days) and be more severe with abruptly stopping short-acting benzodiazepines compared with after tapering long-acting benzodiazepines (4 to 10 days).64,65 Gradual taper of short-acting agents does not eliminate withdrawal symptoms but ameliorates their severity, with symptoms beginning to appear once doses are reduced to about 25% of baseline.55 While common, resulting insomnia is typically mild, and patients should be assured that there is no difference in insomnia compared with usual care or continuation of BZRAs at 12 months.
Other common withdrawal symptoms reported in the literature include irritability, sweating, gastrointestinal symptoms, and anxiety.39 Patients should be reassured that if these symptoms occur they are typically mild and short term (lasting days to weeks), and that discomfort is usually temporary.39 Severe withdrawal symptoms (eg, seizures) do not appear to occur with tapering but have been reported rarely in patients stopping very high doses without tapering39 or who have underlying seizure disorders.
What monitoring needs to be done, how often, and by whom?
Tapering will reduce, but might not eliminate, withdrawal symptoms.28,34 A monitoring plan should be developed in conjunction with the patient. At each step in the taper (approximately every 1 to 2 weeks for the duration) monitor for severity and frequency of adverse drug withdrawal symptoms (anxiety, irritability, sweating, gastrointestinal symptoms, insomnia), potential benefits (eg, less daytime sedation, improved cognition, fewer falls), and mood, sleep quality, and changes in sleep. This can be done at a scheduled appointment or through a telephone call (by physician, psychologist, pharmacist, or nurse). If desired, withdrawal symptoms can be monitored using the types of scales used in clinical trials (eg, benzodiazepine withdrawal symptom questionnaire or Clinical Institute Withdrawal Assessment for Benzodiazepines scale)73 or via clinical assessment. If withdrawal symptoms occur at a severity and frequency that is bothersome for a patient, consider maintaining the current BZRA dose for 1 to 2 weeks before attempting the next dose reduction; then continue to taper at a slower rate.
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609131/
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01562-3/fulltext