THE CASE
A 49-year-old man with chronic insomnia was referred to the pharmacist authors (LF and DP) to initiate and manage the tapering of nightly zolpidem use. Per chart review, the patient had complaints of insomnia for more than 30 years. His care had been transferred to a Nebraska clinic 5 years earlier, with a medication list that included zolpidem controlled release (CR) 12.5 mg nightly. Since then, multiple interventions to achieve cessation had been tried, including counseling on sleep hygiene, adjunct antidepressant use, and abrupt discontinuation. Each of these methods was unsuccessful. So, his family physician (SS) reached out to the pharmacist authors (LF and DP).
THE APPROACH
Due to the patient’s long history of zolpidem use, a lack of literature on the topic, and worry for withdrawal symptoms, a taper schedule was designed utilizing various benzodiazepine taper resources for guidance. The proposed taper utilized 5-mg immediate release (IR) tablets to ensure ease of tapering. The taper ranged from 20% to 43% weekly reductions based on the ability to split the zolpidem tablet in half.
DISCUSSION
Zolpidem is a sedative-hypnotic medication indicated for the treatment of insomnia when used at therapeutic dosing (ie, 5 to 10 mg nightly). Anecdotal efficacy, accompanied by weak chronic insomnia guideline recommendations, has led prescribers to use zolpidem as a chronic medication to treat insomnia.1,2 There is evidence of dependence and possible seizures from supratherapeutic zolpidem doses in the hundreds of milligrams, raising safety concerns regarding abuse, dependence, and withdrawal seizures in chronic use.2,3
Additionally, there is limited evidence regarding the appropriate process of discontinuing zolpidem after chronic use.2 Often a taper schedule—similar to those used with benzodiazepine medications—is used as a reference for discontinuation.1 The hypothetical goal of a taper is to prevent withdrawal effects such as rebound insomnia, anxiety, palpitations, and seizures.3 However, an extended taper may not actually be necessary with chronic zolpidem patients.
Tapering with minimal adverse effects
Pharmacokinetic and pharmacodynamic studies have suggested minimal, if not complete, absence of rebound or withdrawal effects with short-term zolpidem use.4 The same appears to be true of patients with long-term use. In a study, Roehrs and colleagues5 explored whether long-term treatment (defined as 8 months) caused rebound insomnia upon abrupt withdrawal. The investigators concluded that people with primary insomnia do not experience rebound insomnia or withdrawal symptoms with chronic, therapeutic dosing.
Another study involving 92 elderly patients on long-term treatment of zolpidem (defined as > 1 month, with average around 9.9 ± 6.2 years) experienced only 1 or 2 nights of rebound insomnia during a month-long taper.1,6 Following that, they experienced improvements in initiation and staying asleep.
A possible explanation for the lack of dependence or withdrawal symptoms in patients chronically treated with zolpidem is the pharmacokinetic profile. While the selectivity of the binding sites differentiates this medication from benzodiazepines, the additional fact of a short half-life, and no repeated dosing throughout the day, likely limit the risk of experiencing withdrawal symptoms.1 The daily periods of minimal zolpidem exposure in the body may limit the amount of physical dependence.
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