This is the first study to show the superiority of a combined treatment over medication, psychotherapy, and placebo in the acute treatment of SAD. In addition, we found that phenelzine, but not CBGT alone, was superior to placebo. These results were consistent across several outcome measures and analytic strategies and maintained over the 12-week continuation phase.
Supporting our main hypothesis, combined treatment was superior to both monotherapies and to placebo. Two mechanisms could explain the higher efficacy of combined treatment: 1) distinct groups of SAD patients could respond only to phenelzine or to CBGT. By receiving both, patients in the combined treatment group would have increased their chances of receiving at least one treatment that was efficacious for them; 2) combined treatment may exert a truly additive or synergistic effect in the treatment of SAD, beyond the effects of either monotherapy delivered alone.
If only the first mechanism was at work, responders in the combined group would not have had larger average improvement than responders in the monotherapy groups. However, individuals receiving combined treatment had larger average improvements than those receiving phenelzine or CBGT alone. This finding suggests an additive or synergistic effect of these treatment modalities, possibly due to their different mechanism of action or by mutually facilitating the other’s effect. For example, phenelzine may reduce anxiety and increase the chances of successful exposures to feared situations, whereas the skills learned through CBGT may help those on phenelzine profit more from their exposures.
Our findings of the superiority of combined treatment are at variance with previous studies of combination treatment of SAD,15, 17, 18
but in accord with some other studies and meta-analyses that have shown the superiority of combined treatment over monotherapies in other mood and anxiety disorders.45–48
Discrepancies in the SAD results may be due in some cases to the use of medications with a mixed15
or poor record of efficacy in the treatment of SAD.17, 18
The findings of Blomhoff and colleagues19
are more difficult to interpret. Although the study failed to find an additional benefit of combined treatment over sertraline monotherapy, this result may have been due to the use of pairwise comparisons, rather than tests for ordered responses implied in the design. We reanalyzed the rates of response from that study assuming a gradation of response from placebo to monotherapies to combined treatment using a linear-by-linear test, which yielded a χ2
= 8.0, df=1, p=.005. An even more significant result was obtained when the gradation was assumed to be placebo, exposure therapy, sertraline, and combined treatment (χ2
= 9.9, df=1, p=0.002). More recent work by the same group, although not formally tested for ordered responses, also suggest a gradient of efficacy in the acute treatment of SAD with placebo having the lowest degree of response, followed by monotherapies (exposure therapy and sertraline) and combined treatment having the highest efficacy at week 24.49
Taken together, the available evidence appears to support the superiority of combined treatment over medication or exposure/CBT alone for the treatment of SAD.
Consistent with prior reports,10, 50–52
we found that phenelzine was superior to placebo on most measures, providing additional documentation of its efficacy. Both phenelzine and CBGT, however, were less efficacious than in previous reports,10
and CBGT was generally not superior to placebo in pairwise comparisons, although it was superior to placebo in the analyses using tests of constrained statistical inference, was not different from phenelzine monotherapy in any pairwise comparisons at week 12, and achieved the same efficacy as phenelzine at week 24. The lower efficacy of CBGT in this study is surprising to us and may be due to sample differences (R.G. H. moved from Albany, NY, to Philadelphia, PA, between the time of the previous trial10
and the present one). However, there were no site-by-treatment interactions in either study, making this explanation less likely. Furthermore, in another two-site trial conducted by our group since the time of the study reported here, CBT proved highly efficacious.53
and qualitative reviews57
continue to support the efficacy of CBT for SAD.
Our study has the limitations common to most efficacy trials. First, treatments were provided by experts and may show lower efficacy in less specialized settings. Second, participants had to be willing to be randomized to any of the four treatment cells. Individuals who dropped out of the study postrandomization but prior to receiving any treatment could not be included in the analyses. Our results may not generalize to them. Similarly, because individuals were recruited from advertisements and word of mouth, the results may not be generalizable to all patients with SAD. Third, because the study lacked a CBGT plus pill placebo group, the non-specific effects of phenelzine in the combined treatment cannot be ruled out. Fourth, because self-exposure was neither assessed nor explicitly discouraged in the pill-only groups, it is possible that more spontaneous exposure occurred in the phenelzine group which may have contributed to their improvement. Fifth, our study examined only one medication, one psychotherapy, and their combination, rather than a broader array of treatments. Thus, our findings may not extend to individuals treated with SSRIs or SNRIs. However, both our reanalysis of the Blomhoff et al.19
study and the findings of Haug et al.49
suggest that a gradation of response from placebo to monotherapy to combined treatment may extend to other medications and empirically-supported psychotherapies. Further research is needed to confirm those findings. Sixth, there were some baseline differences across treatment groups and sites. However, the results remained significant after appropriate statistical adjustments, suggesting the robustness of our findings.
In summary, our study is the first one to provide an empirical rationale for the use of combined treatment for SAD. Future studies should prospectively examine whether the combination of an SSRI plus behavior therapy or CBT is superior to either treatment alone, as well as the acceptability, efficacy and cost-effectiveness of combined versus sequentially administered or augmented treatments.