Don asked
Ambien CR is approved for long term use but not so for regular Ambien. Please explain the difference.
Answer
The reason Ambien and Ambien CR have two different indications is due to a few factors.It's important to note that the difference isn't really due to how the medications work in our bodies, but due how to manufacturer went about their clinical trials and research. While the FDA can change labeling requirements for medications, the manufacturer is the party responsible for stating the indication of use for the drug they are submitting for approval. When Ambien was approved, Sanofi (the manufacturer) submitted the drug for short term use and that is how the FDA evaluated it. When they submitted Ambien CR to the FDA, they did not submit it for short term use and the FDA evaluated it as such.
Let's look at the exact wording for each drug in respect to their indication.
Ambien: Ambien (zolpidem tartrate) is indicated for the short-term treatment of insomnia characterized by difficulties with sleep initiation. Ambien has been shown to decrease sleep latency for up to 35 days in controlled clinical studies [see Clinical Studies (14)]. The clinical trials performed in support of efficacy were 4-5 weeks in duration with the final formal assessments of sleep latency performed at the end of treatment
Ambien CR: Ambien CR (zolpidem tartrate extended-release tablets) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance (as measured by wake time after sleep onset). The clinical trials performed in support of efficacy were up to 3 weeks (using polysomnography measurement up to 2 weeks in both adult and elderly patients) and 24 weeks (using patient-reported assessment in adult patients only) in duration
We can see that the indication for Ambien clearly states that it is for short term treatment of insomnia, however ambiguous that statement is while Ambien CR does not that have statement. The main reason for this is the clinical trial length that was conducted for Ambien. The clinical trial for Ambien was only 4 weeks and therefore the company didn't have any data to submit for use lasting longer than 4 weeks. There is no way Ambien would be approved if they submitted the drug for continuous use.
While commonly stated as fact, Ambien is not actually INDICATED for only 7-10 days of treatment. The actual wording is "short term use". The 7-10 days comes from a warning in the package insert that reads:
"Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with sedative/hypnotic drugs, including zolpidem"
In terms of Ambien CR, there were multiple clinical trials performed, one of which was for 24 weeks, significantly longer than the initial trials for immediate release Ambien. Ambien CR does in fact contain the same 7-10 warning as Ambien however which is pretty much a blanket statement for any sedative medication. Due to the extended length of the clinical trail, Ambien CR was submitted without the short term use qualifier and was subsequently approved.
