Tools for Practice


#216 Anxiously Awaiting Evidence: Pregabalin in generalized anxiety disorder


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


BOTTOM LINE
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
  • 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):

  • 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.