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What Is the Difference between Diazepam and Zolpidem?

By Susan Abe
Updated Jan 25, 2024
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Diazepam and zolpidem are commonly available medications that have some similar sedating effects. The two medicines also share some of the same pathways or means of changing brain chemistry. They can both be habit-forming when used for long periods of time and should not be discontinued abruptly; they are therefore regulated by prescription in some countries. Diazepam and zolpidem are, however, two entirely different types of drugs. They are used for different purposes, have different chemical structures, are metabolized differently in the body, and are excreted by different methods.

These medications utilize some of the same neurotransmitters and the same neurotransmitter receptors in the brain. Zolpidem, however, only uses those receptors that produce the sedative qualities common to both drugs. Hence, its use as a sleep accelerator is reasonable and expected. Diazepam, on the other hand, works on all the usual neurotransmitters and receptors associated with the gamma-amino-butylric acid (GABA) system. Due to the greater variety of its effects, diazepam is used an anti-anxiety agent, an anticonvulsant, a treatment for muscle spasms, and as a treatment during alcohol detoxification.

The two drugs have different routes of administration. While both medications can be administered orally, diazepam can also be administered intravenously (IV), intramuscularly (IM) or via a rectal gel (PR). Zolpidem is also available in a fast-dissolving sublingual form and also a nasal spray.

Diazepam and zolpidem are both metabolized by the liver, although through different enzymatic systems. A long-acting benzodiazepine, diazepam reaches its peak level one to two hours after oral administration. Zolpidem is meant to be taken on an empty stomach and its effects are designed to happen very quickly — as soon as it is absorbed into the bloodstream. Diazepam remains in the body for a much, much longer period of time than does zolpidem. The half-life of diazepam averages 100 hours while that of zolpidem is only around three and a half hours.

Taken together, both diazepam and zolpidem can potentiate — or intensify — each other's effects. Both can cause respiratory depression, difficulties with balance and other signs that mimic intoxication because of their shared mode of action on the central nervous system. Diazepam and zolpidem should never be taken with alcohol or other medications that can cause respiratory depression. Either drug should be given cautiously to patients with liver or kidney disease as they are both metabolized by the liver and primarily excreted renally.

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