Combining pharmacotherapy and CBT is a popular strategy for treating anxiety disorders; between 55% and 95% of patients are estimated to receive such combination treatment (Wardle, 1990
; Westra & Stewart, 1998
). In order to examine whether CBT plus pharmacotherapy is more effective than CBT plus placebo for adult anxiety disorders, we performed a comprehensive literature review of randomized controlled trials. Our comprehensive search yielded 11 studies, including trials on panic disorder (n
= 4), social anxiety disorder (n
= 3), obsessive-compulsive disorder (n
= 2), and generalized anxiety disorder (n
= 2). The total number of patients for the analyses ranged between 236 (response rate analyses at follow-up) and 471 (response rate analyses at post-acute) participants. Our analyses had to be limited to completer data due to the very small sample of studies (n
= 2) that reported intent-to-treat data.
Despite the relatively small total number of studies with completer data, the fail-safe N for the post-treatment completer analysis was 82, suggesting that the results are reliable. Furthermore, the majority of studies were of high quality as suggested by the Jadad scores. However, the lack of intent-to-treat data calls for an urgent need for more high-quality trials examining combination strategies.
Based on the available evidence, combined therapy appears to be effective among completers in the short term. The pooled effect size for the main outcome measures at the post-acute assessment for anxiety disorder severity was Hedges’ g = .59, and the pooled OR was 1.95, indicating that CBT plus pharmacotherapy is more effective than CBT plus placebo in the short-term. However, a publication bias analysis suggests that the effect size may only be considered robust for continuous measures. No difference was observed in the effect sizes of the self-report measures and the clinician-administered measures. Finally, we detected a significant publication year bias, suggesting that more recent studies reported smaller effects than older studies. This latter finding might be due to more rigorous assessment methods in more recent studies.
Although the overall effect of combined CBT and pharmacotherapy over CBT and placebo was medium at post-acute treatment, no difference between these two treatment modalities was found at 6-month follow-up. Moreover, combined therapy was not equally effective for all anxiety disorders. Large average effects were found for panic disorder (Hedges’ g = .99) and medium to large effects were found for generalized anxiety disorder (Hedges’ g = .81), but only small and non-significant effect-sizes were found for obsessive-compulsive disorder and social anxiety disorder. Finally, we observed that the effect size for CBT combined with benzodiazepines was significantly greater than CBT combined with SSRIs, tricyclics, or rMAOIs. However, the number of trials included in these analyses is too small to draw any firm conclusions.
Previous meta-analyses have either been limited to only one disorder or have generally employed more liberal inclusion criteria (Furukawa, Watanabe, & Churchill, 2006
; Mitte, Noack, & Hautzinger, 2005
; Abramowitz, 1997
; Rodebaugh, Holaway, & Heimberg, 2004
; Bandelow, Seidler-Brandler, Becker, Wedekind, & Ruther, 2007
). Accordingly, it is difficult to compare our findings to those reported in these previous studies. A recent meta-analytic review of randomized placebo controlled studies of CBT for adult anxiety disorders indicated that CBT was the least effective for treating generalized anxiety disorder and panic disorder with average effect sizes of Hedges’ g
= 0.51 and Hedges’ g
= 0.35, respectively (Hofmann & Smits, 2008
). Therefore, it is perhaps not surprising to see that the greatest efficacy for combination interventions was observed for these two anxiety disorders.
Several additional limitations deserve mention. First, the sample of studies included in this meta-analysis was of high quality, but relatively small. The fail-safe analysis suggests that the results are reliable for the continuous measures. Nevertheless, the data have to be interpreted with caution. Second, most of the studies included in the analyses failed to report intent-to-treat analyses. We consider this to be the most puzzling result, given the long tradition of randomized controlled trials with CBT. Consequently, the findings had to be limited to completer data. It is certainly possible that the intent-to-treat effect sizes are significantly smaller. Third, few studies reported follow-up data for patients who had not received post-study treatment. Therefore, the follow-up responder rate analyses included data both from patients who received subsequent treatment as well as from those who did not. Given the confounding influence that treatment after the acute study phase may have on follow-up results, the results of this analysis should be interpreted with caution.
In sum, we conclude that medication may be a useful strategy for enhancing acute-phase CBT outcomes, especially for panic disorder and generalized anxiety disorder. Less support exists for combination therapy for obsessive-compulsive disorder and social anxiety disorder. Furthermore, the findings to date do not support the use of this strategy for maximizing long-term CBT outcomes. In addition to a need for more clinical trials examining the efficacy of combination strategies across the different anxiety disorders, our study supports the examination of novel combination strategies that specifically target the mechanisms underlying the effects of CBT which may be more likely to improve long-term outcomes (Hofmann, 2007
; Hofmann, Pollack, & Otto, 2006