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#216 Anxiously Awaiting Evidence: Pregabalin in generalized anxiety disorder


CLINICAL QUESTION
QUESTION CLINIQUE
Is pregabalin effective for generalized anxiety disorder (GAD)?


BOTTOM LINE
RÉSULTAT FINAL
Evidence for pregabalin in GAD is inconsistent and at high-risk of bias (industry-written, short-term, poorly described methods, high drop-outs, and run-in periods that overinflate benefit). If real, an additional one in 6-8 people may respond to pregabalin compared to placebo at 4-8 weeks. However, the change in anxiety scales was not clinically meaningfully different than placebo for the average patient.   



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EVIDENCE
DONNÉES PROBANTES
  • All Randomized Controlled Trials (RCTs) written by industry. 
  • One systematic review, four RCTs:1 
    • Versus placebo (one RCT, n=271):  
      • Response: 59% versus 44% placebo, not statistically different. 
      • Changes in anxiety scale: ~3-4 points out of 56, not always statistically significant, likely not clinically meaningful 
    • Versus benzodiazepines:  
      • Response (one RCT, n=454): 300 mg statistically better than alprazolam (61% versus 43%) but higher doses no difference.1,2 
      • Change in anxiety scale (one RCT, n=271)No difference. 
    • Overall adverse effects: 67% placebo, 73% pregabalin 50 mg, 89% pregabalin 200 mg, 91% lorazepam.1 
  • Four other RCTs (273-374 patients each): 
    • Change in anxiety scale: ~3 points out of 56. Statistically differentnot clinically meaningful.3-6 
    • Response rates 50-60% versus 27-46% placebo. Statistically different in ¾ studies.3,5,6 Number Needed to Treat (NNT)=6-8. 
    • Trend to higher response rates with lorazepam (61% versus 46%).6  
  • Other systematic reviews provided standard mean differences (clinically uninterpretable).7,8 
  • RCT versus sertraline:9 No difference anxiety scale or adverse effects.   
  • As adjunct: RCT of 356 patients.10 
    • If inadequate response to antidepressant, randomized to pregabalin 150-600 mg/day or placebo. At eight weeks: 
      • Mean change in anxiety scale: 1.2 (statistically, but not clinically different). 
      • Response (anxiety scale): 48% versus 35%, NNT=8. 
      • Response (global improvement scale) or remission: No difference. 
    • Stopped due to adverse effects: 4% versus 2%, Number Needed to Harm=47. 
  • Limitations: <80% completed study;3-6 short-term (4-8 weeks);1-6 selective reporting;6 quality markers inadequately described;3-6 run-in which can overinflate benefit.2,4-6
Context: 
  • Several studies show lower anxiety scores within one week, but usually not a clinically meaningful difference.3,4,6  
  • Weight gain at one year (all indications): 17% gained >7% of their body weight and mean gain=2.2kg.11 
  • Canadian guidelines recommend pregabalin or antidepressants first-line or as adjunct.12 


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Author(s)
Auteur(s)
  • Adrienne J Lindblad BSP ACPR PharmD
  • Lisa K. Freeman BSc(Hon) MD CCFP MPH FRCPC

1. Gale CK, Millichamp J. Clin Evid. 2011; 10:1002.

2. Rickels K, Pollack MH, Feltner DE, et al. Arch Gen Psychiatry. 2005; 62:1022-30.

3. Kasper S, Herman B, Nivoli G, et al. Int Clin Psychopharmacol. 2009; 24:87-96.

4. Montgomery S, Chatamra K, Pauer L, et al. Br J Psychiatry. 2008; 193(5):389-94.

5. Pohl RB, Feltner DE, Fieve RR, et al. J Clin Psychopharmacol. 2005; 25(2):151-8.

6. Pande AC, Crockatt JG, Feltner DE, et al. Am J Psych. 2003; 160:533-40.

7. Generoso MB, Trevizol AP, Kasper S, et al. Int Clin Psychopharmacol. 2016; 32:49-55.

8. Boschen MJ. Can J Psychiatry. 2011; 56(9):558-66.

9. Cvjetkovic-Bosnjak M, Soldatovic-Stajic B, Babovic SS, et al. Eur Rev Med Pharmacol Sci. 2015; 19(11):2120-4.

10. Rickels K, Shiovitz TM, Ramey TS, et al. Int Clin Psychopharmacol. 2012; 27:142-50.

11. Cabrera J, Emir B, Dills D, et al. Curr Med Res Opin. 2012; 28(6):1027-37.

12. Katzman MA, Bleau P, Blier P, et al. BMC Psychiatry. 2014; 14(suppl 1):S1.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.