page_title: Zolpidem
section_title: Tolerance, dependence, and withdrawal
hierarchical_section_title: Zolpidem / Adverse effects / Tolerance, dependence, and withdrawal
caption_attribution_description: Stillnox
context_page_description: Zolpidem, sold under the brand name Ambien, among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and behavioral changes, such as sleep hygiene, have been tried. It decreases the time to sleep onset by about fifteen minutes and at larger doses helps people stay asleep longer. It is taken by mouth and is available in conventional tablets, sublingual tablets, or oral spray.
  Common side effects include daytime sleepiness, headache, nausea, and diarrhea. Other side effects include memory problems, hallucinations, and substance abuse. The previously recommended dose was decreased in 2013, by the US Food and Drug Administration, to the immediate-release 10 mg for men, and 5 mg for women, in an attempt to reduce next-day somnolence. Newer extended-release formulations include the 6.25 mg for women, and 12.5 mg or 6.25 mg for men, which also cause next-day somnolence when used in higher doses. Additionally, driving the next morning is not recommended with either higher doses or the long-acting formulation.
context_section_description: As zolpidem is associated with drug tolerance and substance dependence, its prescription guidelines are only for severe insomnia and short periods of use at the lowest effective dose. Tolerance to the effects of zolpidem can develop in some people in just a few weeks. Abrupt withdrawal may cause delirium, seizures, or other adverse effects, especially if used for prolonged periods and at high doses. When drug tolerance and physical dependence to zolpidem develop, treatment usually entails a gradual dose reduction over a period of months to minimize withdrawal symptoms, which can resemble those seen during benzodiazepine withdrawal. Failing that, an alternative method may be necessary for some people, such as a switch to a benzodiazepine equivalent dose of a longer-acting benzodiazepine drug, as for diazepam or chlordiazepoxide, followed by a gradual reduction in dose of the long-acting benzodiazepine. In people who are difficult to treat, an inpatient flumazenil administration allows for rapid competitive binding of flumazenil to GABAA–receptor as an antagonist, thus stopping (a effectively detoxifying) zolpidem from being able to bind as an agonist on GABAA–receptor; slowly drug dependence or addiction to zolpidem will wane.
  Alcohol has cross tolerance with GABAA receptor positive allosteric modulators, such as the benzodiazepines and the nonbenzodiazepine drugs. For this reason, alcoholics or recovering alcoholics may be at increased risk of physical dependency or abuse of zolpidem. It is not typically prescribed in people with a history of alcoholism, recreational drug use, physical dependency, or psychological dependency on sedative-hypnotic drugs. A 2014 review found evidence of drug-seeking behavior, with prescriptions for zolpidem making up 20% of falsified or forged prescriptions.
  Rodent studies of the tolerance-inducing properties have shown that zolpidem has less tolerance-producing potential than benzodiazepines, but in primates, the tolerance-producing potential of zolpidem was the same as seen with benzodiazepines.
caption: Ambien tablets
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