Taking Ambien And Xanax: Which To Stop First?

In our latest question and answer, the pharmacist discusses tapering options for those on both a benzodiazepine, like Xanax, and Ambien.

Jul 05, 2019

Mar asked

I have been on Xanax 0.5 mg for 4 and 1/2 years, and Ambien 10 mg/day for 15+ years. The Xanax is no longer really helping, but I am sleeping with the zolpidem. In order to get off of these drugs, which should I taper off of first? It is my understanding that both of these meds affect the GABA-A receptors. Some people say to taper the Xanax first, but then others say the zolpidem will impede the recovery of the GABA receptors. I know to taper these medications very slowly and I can do that, I just don't know which to taper first. My doctor is of no help in this and refuses to switch me to a longer-acting benzodiazepine such as diazepam.

At a glance

  • Ambien (zolpidem) and Xanax (alprazolam) have similar pharmacologic actions, but the overall effect and receptor interaction of Xanax is more wide-ranging. There is currently no recommendation regarding which to taper first if you are taking both of them. There are many factors to consider and you should discuss a tapering protocol with your doctor that best suits your situation.


Two Pill Bottles With White Pills Spilling Out

You are correct that both Ambien (zolpidem) and Xanax (alprazolam) work in a similar manner, and therefore, it can be tricky to find a conclusive recommendation on which to taper first if you are taking both of them.

In fact, there are no definitive guidelines on how to taper either drug, even if you are taking them alone. The fact you are taking them together is an added wrinkle.

Tapering protocols, in general, are highly patient-specific, and have to account for a variety of factors, including:

  • Patient age
  • How long you have been taking the medication to be tapered
  • Concomitant medications
  • Concomitant disease states

In your situation, being on both zolpidem and alprazolam, again, there is no recommendation that states you should taper one before the other. An appropriate tapering protocol could be devised by you and your doctor that involves either medication being discontinued first.

It is incredibly important to work up a tapering protocol with your doctor, as they have your complete medical history and are in the best position to give you guidance.

Nevertheless, if we are following the general medication tapering mantra of 'start low and go slow' (meaning to start your dose reduction from your current dose and incrementally decrease slowly over time), it would make sense to work down on your zolpidem first.

I say this because while zolpidem and alprazolam work on the some of the same receptors (i.e. GABA-A), alprazolam has a wider range of activity. The actions of zolpidem are directed to a smaller number of these receptors (I discuss this in more detail in the next section).

Stopping a medication that has a narrower mechanism of action than the other (assuming they work in a similar manner overall) first makes intuitive sense. It would be like going on a diet and stopping the consumption of a single unhealthy item, like donuts, first, as opposed to stopping all unhealthy food immediately. It's essentially a step-down approach.

Having said the above, there certainly are cases where stopping alprazolam first would make sense too, like if your main concern is that you have trouble sleeping at night.

Studies show that alprazolam (and other benzodiazepines) can significantly affect several stages of deep sleep (e.g. stages 3 and 4) but zolpidem doesn't appear to alter these, at least not to a significant degree.

Therefore, in order to better manage a healthy and consistent sleep schedule, having zolpidem as your sole drug to taper (as opposed to tapering a benzodiazepine like Xanax on top of it) may make it easier to successfully manage and monitor your sleep.

An additional reason to potentially decrease alprazolam first is that benzodiazepines overall are well-documented to be difficult to discontinue and some patients can experience moderate to severe withdrawal symptoms.

Zolpidem, on the other hand, is generally associated with less severe withdrawal symptoms, which occur at a much lower rate than with benzodiazepine withdrawal. In fact, the prescribing information for Ambien states the following:

  1. Xanax Monograph. AccessFDA
  2. Ivadal Monograph. Sanofi-aventis
  3. Ambien Monograph. AccessFDA
  4. Alprazolam Monograph. NIH Bookshelf
  5. Detoxification from high-dose zolpidem using diazepam. PubMed
  6. Deprescribing benzodiazepine receptor agonists. PubMed
  7. Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research. PubMed
  8. Management of benzodiazepine misuse and dependence. PubMed

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