Adjunctive therapy with pregabalin in generalized anxiety disorder patients with partial response to SSRI or SNRI treatment

Abstract

This study evaluated the efficacy of adjunctive pregabalin versus placebo for treatment of patients with generalized anxiety disorder (GAD) who had not optimally responded to previous or prospective monotherapies. This was a phase 3, randomized, double-blind, placebo-controlled study. Patients diagnosed with GAD who had a historical and current lack of response to pharmacotherapy [Hamilton Anxiety Rating Scale (HAM-A) of ≥ 22 at screening] were randomized to adjunctive treatment with either pregabalin (150-600 mg/day) or placebo. The primary outcome measure was the change in HAM-A total scores after 8 weeks of combination treatment. Adverse events were regularly monitored. Randomized patients (N=356) were treated with pregabalin (n=180) or placebo (n=176). Mean baseline HAM-A scores were 20.7 and 21.4, respectively. After treatment, the mean change in HAM-A was significantly greater for pregabalin compared with placebo (-7.6 vs. -6.4, respectively; P<0.05). HAM-A responder rates (≥ 50% reduction) were significantly higher for pregabalin (47.5%) versus placebo (35.2%; P=0.0145). The time-to-sustained response favored pregabalin over placebo (P=0.014). Adverse events were consistent with previous studies and discontinuations were infrequent for pregabalin (4.4%) and placebo (2.3%). The study was discontinued early after an interim analysis. The results indicate that adjunctive pregabalin is an efficacious therapy for patients with GAD who experience an inadequate response to established treatments.

Pharmacological treatment for generalized anxiety disorder in adults: an update

“…All active groups had meaningful reductions in the psychic and somatic symptoms subscales [89]. Pregabalin has also been compared to venlafaxine XR 75 --225 mg and a treatment difference in favor of pregabalin occurred by day 4 and persisted until the end of the 8-week study [90].…”

Efficacy and safety of pregabalin in generalised anxiety disorder: A critical review of the literature

“…Incidence and number needed to harm (NNH) of adverse events for pregabalin. Comparison with venlafaxine-XR in a flexible-dose study PGB-150 mg, n=70 −1.62 7.1 PGB-600 mg, n=66 −3.90 b 19.7 Placebo, n=67 6.0 (Rickels et al, 2005) PGB-300 mg, n=91 −3.89 b 3.0 PGB-450 mg, n=90 −2.65 b 8.0 PGB-600 mg, n=89 −3.43 b 15.0 Placebo, n=91 9.9 (Pohl et al, 2005) PGB-200 mg, n=78 −3.10 b 9.0 PGB-400 mg, n=89 −3.60 b 11.2 PGB-450 mg, n=88 −3.10 b 12.5 Placebo, n=86 8.1 PGB-400 mg, n=97 −3.10 b 6.2 PGB-600 mg, n=110 −2.50 b 13.6 Placebo, n=101 9.9 (Montgomery et al, 2008) PGB-150-600 mg, n=177 −2.10 b 10.7 Placebo, n=96 9.4 PGB-300-600 mg, n=121 −2.80 b 12.4 n=125 placebo, n=128 5.5 (Rickels et al, 2012) PGB-150-600 mg, n=180 −1.20 b 4.4 Placebo, n=176…”

“…Study sample Design Treatment, n Significant efficacy a (Pande et al, 2003) Adult GAD, HAM-A ⩾20 DB-RCT, 4 weeks PGB-150 mg, n=69 Y PGB-600 mg, n=70 Y Lorazepam-6 mg, n=68 Y Placebo, n=69 Adult GAD, HAM-A ⩾20 DB-RCT, 4 weeks PGB-150 mg, n=70 N PGB-600 mg, n=66 Y Lorazepam-6 mg, n=68 Y Placebo, n=67 (Bandelow et al, 2007) Adult GAD, HAM-A ⩾20 DB-RCT, 4 weeks PGB-150 mg, n=71 N PGB-600 mg, n=71 N Lorazepam-6 mg, n=70 N Placebo, n=70 (Rickels et al, 2005) Adult GAD, HAM-A ⩾20 DB-RCT, 4 weeks PGB-300 mg, n=91 Y PGB-450 mg, n=90 Y PGB-600 mg, n=89 Y Alprazolam-1.5 mg, n=93 Y Placebo, n=91 (Pohl et al, 2005) Adult GAD, HAM-A ⩾20 DB-RCT, 6 weeks PGB-200 mg, n=78 Y PGB-400 mg, n=89 Y PGB-450 mg, n=88 Y Placebo, n=86 Adult GAD, HAM-A ⩾20 DB-RCT, 6 weeks PGB-400 mg, n=97 PGB-Y 600 mg, n=110 Venla-IR-Y 75 mg, n=113 Placebo, n=101 Y (Montgomery et al, 2008) Elderly ( in GAD with HAM-A total score as the primary outcome measure, one in elderly patients (Montgomery et al, 2008) and one in younger adults ); (c) two open-label, flexibledose studies in adults with GAD, one a short-term (four weeks) trial (Moller et al, 2009), and one a long-term (12 months) trial (Montgomery et al, 2012); (d) one randomised, double-blind, placebo-controlled, long-term (six months), fixed-dose relapse prevention study in chronic GAD (Feltner et al, 2008); (e) one double-blind, short-term (eight weeks), flexible-dose trial, in which patients with treatment-refractory GAD currently being treated with either an SSRI or SNRI antidepressant were randomised to receive either adjunctive pregabalin or placebo (Rickels et al, 2012); and (f) a switch study in which patients with GAD and currently receiving long-term therapy with a benzodiazepine were randomised to 12 weeks of double-blind treatment with either flexible-dose pregabalin or placebo while undergoing a gradual benzodiazepine taper at a rate of 25% per week, followed by a six-week benzodiazepine-free phase (Hadley et al, 2012). In addition, we identified five pooled analyses (all industrysponsored) that reported additional secondary efficacy outcomes based on the primary, randomised clinical trials summarised in Table 1.…”

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders

“…Second-line adjunctive therapies: Adjunctive pregabalin demonstrated good efficacy in a large RCT in patients with GAD who had an inadequate response to prior treatments (Level 2) [617]. …”