Is there a cheaper alternative to pregabalin (Lyrica) with equal anxiolytic effect?/nThe questioner

Fråga: Is there a cheaper alternative to pregabalin (Lyrica) with equal anxiolytic effect? The questioner has special interest in gabapentin.

Sammanfattning: Pregabalin has been shown to have a modest anxiolytic activity similar to that of lorazepam, alprazolam and venlafaxine in a few, short-term RCTs with some methodological problems.

There is only weak documentation on the anxiolytic properties of gabapentin. Comparative studies are lacking.

Svar: Equality is statistically impossible to prove, and there are not even any published non-inferiority studies on pregabalin compared to other anxiolytic agents.

Pregabalin has been compared in doses from 150 to 600 mg/day in 2-3 divided doses to lorazepam (2 mg x 3), alprazolam (0.5 mg x 3) and venlafaxine (32.5 mg x 2), respectively, for the treatment of generalised anxiety disorder in four different published randomised, placebo-controlled studies. All these studies were short-term studies (4-6 weeks) with 60-100 patients in each treatment arm. In all of these studies all active treatments showed similar decreases (-10 to -14 points; placebo -7 to -11) on the Hamilton Anxiety Rating Scale (HAM-A; maximum score 56) (1,2,3,4). Bensodiazepines were associated with withdrawal symptoms, which was not the case with pregabalin (1,2). Dropout rates were 15-30% and, when described, intention-to-treat analyses were performed as last observation carried forward (LOCF) analyses (3,4). Interestingly, the withdrawal rates were greatest (30%) in the venlafaxine treated patients (4).

Also interesting is that the EMEA Scientific discussion describes two other pregabalin studies with lorazepam as active comparator that has not been published, both equally sized or larger than the published ones. One study failed to show statistical significant changes in any group compared to placebo and the other failed to show a dose-effect relationship of pregabalin (5).

Gabapentin 600-3600 mg/day has been studied in a randomised controlled trial on social phobia. This study used the Panic and Agoraphobia Scale (PAS) as well as HAM-A. HAM-A results are not published. Withdrawal rate was more than 25% during the 8-week study and is insufficiently presented. Only the permitted dose range of gabapentin is presented, not what doses were actually given (6). No comparative studies have been published.

Other reports of gabapentin in anxiety disorders are mainly case reports.

Gabapentin is not approved for any anxiety disorder (7).

Comparative prices in May 2008 are: Lorazepam 6 mg/day: SEK 6/day, Alprazolam 1.5 mg/day: SEK 3.60/day, Venlafaxine 75 mg/day: SEK 11/day, Pregabalin 150-600 mg/day: SEK 16-32/day, gabapentin 600-3600 mg/day: SEK 6-79/day (7).