Discontinuation of Benzodiazepine

Discontinuation of sedatives and hypnotics, including the benzodiazepines, can be divided into three categories: (1) long-term low-dose benzodiazepine use, (2) high-dose benzodiazepine abuse and multiple drug abuse, and (3) high-dose abuse of nonbenzodiazepine sedatives and hypnotics (especially intermediate-acting barbiturates). The first group of patients can usually be discontinued on an outpatient basis. Some of the second and even the third group can be treated as outpatients, but most will require inpatient care. Inpatient discontinuation today with managed care is generally reserved for patients who fail at outpatient discontinuation and for those who demonstrate acutely life-threatening loss of control over their drug use. The pharmacological management of inpatient benzodiazepine withdrawal from nontherapeutically high doses of these medicines is covered in standard texts dealing with inpatient detoxification (Wesson et al., 2003).

With respect to withdrawal from benzodiazepines in the context of addiction treatment, the most common problem that addiction treatment professionals experience is that some of their patients who take benzodiazepines also suffer from underlying anxiety disorders and panic attacks. When these patients stop taking a benzodiazepine, they experience a short-term rebound increase in these distressing symptoms. These rebound symptoms, including panic attacks, are difficult for the patients and their physicians to separate from withdrawal symptoms, because they are similar and the time course is also similar, with both types of symptoms occurring at low benzodiazepine doses and peaking during the first or second drug-free week.

There is evidence that most patients who take benzodiazepines at prescribed dose levels can discontinue using them with quite moderate symptoms if the dose reduction is gradual (Busto, Simpkins, & Sellers, 1983; Rickels, Schweizer, Csanalosi, Case, & Chung, 1988). One study found that about half of long-term benzodiazepine users could stop with no withdrawal symptoms (Tyrer, Rutherford, & Huggett, 1981). However, some patients who stop benzodiazepine use, especially after use for many years, do have either prolonged or severe withdrawal symptoms (Noyes, Garvey, Cook, & Perry, 1988). About one in three medical patients with long-term use of a benzodiazepine have clinically significant withdrawal symptoms, even after gradual tapering, and about one in eight patients stopping a benzodiazepine will have prolonged and/or severe symptoms (DuPont, 1988). In any case, discontinuation symptoms (except for abrupt cessation, which can produce seizures and is not indicated) from benzodiazepines are "distressing but not dangerous" (DuPont et al., 1992; Sellers et al., 1993).

There are a number of useful publications on the diagnosis and treatment of chronic anxiety (Davidson, 2003; DuPont, Spencer, & DuPont, 2004; Ross, 1994; Spencer, DuPont, & DuPont, 2004). The benzodiazepines can be used to treat either acute or chronic anxiety, as well as the panic attacks that are commonly associated with anxiety disorders. The benzodiazepines can be used either as needed or every day, and they can be used either alone or with other medicines, most often with antidepressants (Davidson, 1997).

Although all of the benzodiazepines are now off patent, there has been a recent interest in the development of new delivery mechanisms for the two most widely used benzodiazepines (Stahl, 2003). Alprazolam is now available in an extended release formulation, Xanax XR. It has the advantage of slower onset of action, which reduces initial sedation in the hour or two after administration. Slower onset of action also lowers the abuse potential of Xanax XR, since it is the rapid onset of action that triggers the brain reward that addicts seek. This new formulation of alprazolam permits once-a-day, or at most twice-a-day, dosing and reduces the risk of "clock watching," which may be seen with frequent dosing throughout the day. This new formulation of alprazolam may be a significant improvement over the three to four times a day dosing required for the immediate release alprazolam.

Clonazepam has been reformulated for sublingual administration for easy administration without swallowing a pill. This new product is called Klonopin Wafers. In the new formulations of these two benzodiazepines, the manufactur ers have moved in opposite directions to maximize two different therapeutic effects. Xanax XR has a slower onset and longer duration of action to smooth the brain level of alprazolam for 24-hour-a-day effectiveness. Sublingual clo-nazepam has been reformulated to overcome the problems some patients have swallowing pills.

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