Alprazolam extended-release in panic disorder

Abstract

Alprazolam-XR is an extended-release formulation of alprazolam designed to deliver sustained therapeutic concentrations for 24 h after once-daily dosing. Plasma concentrations gradually decline as the time for the next dose approaches, but still remain above therapeutic minimum levels. The anti-panic efficacy of alprazolam-XR appears to be comparable to the original formulation of alprazolam. The main advantage of the new extended-release formulation appears to be its greater tolerability and safety. The speed with which high-potency benzodiazepines are absorbed, and rise to peak concentrations is correlated with both abuse potential and with the incidence and severity of common adverse events, such as sedation and cognitive and psychomotor impairment. Alprazolam-XR does not exhibit the sudden increases in plasma concentration characteristic of the original formulation of alprazolam. This pharmacokinetic difference appears to translate into a reduced liability of abuse and a reduced incidence of sedation and cognitive and psychomotor impairment during acute therapy. This would appear to give alprazolam-XR a more favourable benefit:risk profile than the original formulation of alprazolam. In addition, the once-daily dosing (as opposed to three or four times per day) reduces clock-watching, increases compliance and it eliminates the penalty of breakthrough anxiety and panic that many patients experience if they inadvertently miss a dose. It should be noted that long-term therapy with alprazolam-XR carries the same risk of dependence and withdrawal during discontinuation as the original formulation of alprazolam.

Cognitive, psychomotor and actual driving performance in healthy volunteers after immediate and extended release formulations of alprazolam 1 mg

“…Alprazolam XR produced fewer and less severe side effects than its IR equivalent. Moreover, it has been shown that cognitive and psychomotor performance is less impaired after alprazolam XR than after alprazolam IR (Busto et al 2000;Mumford et al 1995;Rickels 2004).…”

Physiologically based pharmacokinetic and pharmacodynamic modelling of alprazolam: Implications for anxiety and addiction

“…In a similar manner, the immediate‐release (IR) preparations of certain medications, including alprazolam, have greater misuse liability than the extended‐release (XR) forms 16,17 . The XR form of alprazolam, furthermore, has lengthier therapeutic durations and decreased cognitive adverse effects 18–20 …”

“…16,17 The XR form of alprazolam, furthermore, has lengthier therapeutic durations and decreased cognitive adverse effects. [18][19][20] To further clarify the mechanisms that underlie alprazolam therapeutic and potentially detrimental properties, this study utilized physiologically based pharmacokinetic (PBPK) and pharmacodynamic (PD) models, which incorporated putative unbound interstitial brain concentration-time profiles that regulate several clinical endpoints.…”

Rescuing the Hyperventilation Theory of Panic: Reply to Ley (2005).

“…However, this outcome was not predicted by any HVT of panic but, at least according to the authors, by Klein's (1993) suffocation false alarm theory. In another drug treatment study, subtyping by respiratory symptoms did not predict response (Rickels, Klee, Kremer, & Clary, 2003). A longer acting formulation of alprazolam produced equal improvement regardless of whether respiratory or autonomic symptoms predominated initially.…”