This is the first study to investigate moderators and predictors of treatment outcome using data from a large randomized controlled trial of CBT augmentation (EX/RP vs. SMT) of SRI pharmacotherapy in OCD. Significant moderators of treatment outcome included pre-treatment OCD severity and gender. Significant predictors of poorer outcome included having more comorbid axis I disorders, more lifetime SRI trials, and lower QoL at baseline. Together, these moderators and predictors accounted for an additional 37.2% of the total variance in post-treatment OCD severity, a large and clinically important effect, beyond the 30.5% of the variance explained by treatment type alone.
The finding that pre-treatment severity predicted post-treatment outcome among patients receiving SMT but not EX/RP is consistent with the only other study examining predictors of EX/RP augmentation (Tolin et al., 2004
). This finding is also consistent with a review of EX/RP studies (of medicated and unmedicated patients) that found pre-treatment severity failed to predict outcome in 4 of 6 studies (Steketee and Shapiro, 1995
); in two other studies pre-treatment severity predicted EX/RP outcome but patients continued to improve with additional EX/RP treatment (Keijsers et al., 1994
, de Haan et al., 1997
). Thus, greater OCD severity alone should not prevent patients from benefiting from EX/RP, although patients with severe OCD may need additional sessions. Moreover, our data suggest that SRI therapy augmented with EX/RP may attenuate the impact of OCD severity on outcome. In contrast, pre-treatment severity had a major impact on SMT outcome: patients with high severity before treatment were more likely to have high severity after treatment. This makes sense since SMT is not an efficacious treatment for OCD (Simpson et al., 2008
Gender also moderated the effect of treatment type on outcome, such that the benefit of EX/RP over SMT was larger for males than females although EX/RP was still superior to SMT for females. This finding contrasts with findings from one naturalistic in-patient study providing combination therapy that found that females had a better post-treatment outcome to EX/RP than males (Stewart et al., 2006
). Two studies that mixed medicated and unmedicated patients found no gender difference in EX/RP outcome (Foa et al., 1983a
, Steketee et al., 2001
). It is not entirely clear what drove the relationship between gender and EX/RP outcome in our sample. It was not explained by other variables in the model nor by post-hoc exploration of comorbid disorders. However, we note that 26.3% of females receiving EX/RP had prominent hoarding symptoms compared with just 5.7% of males. This is noteworthy since those with hoarding symptoms experienced on average only half of the post-treatment YBOCS reduction achieved by those without hoarding symptoms. The fact that we had more females with prominent hoarding symptoms then males may in part explain the relationship between gender and EX/RP outcome in our sample. Future research should further examine the relationship between gender and outcome.
The number of comorbid Axis I conditions a patient had at baseline predicted poorer treatment outcome. Each additional axis I disorder resulted in a 2.06 point increase in patients’ post-treatment YBOCS score. The relationship between number of Axis I conditions and EX/RP outcome is consistent with one study that included both medicated and unmedicated children and adolescents (Storch et al., 2008
). Another study that included both medicated and unmedicated adults found a trend for the number of comorbid conditions predicting EX/RP outcome (Steketee et al., 2001
). Although 44% of patients in our study had a comorbid disorder, there were too few cases of individual disorders (e.g., major depressive disorder, n=4; PTSD, n=4) to examine whether any were driving this effect. However, our data indicate that neither severity of anxiety nor depression were responsible for the relationship between number of Axis I disorders and treatment outcome. Comorbidity might result in poorer outcome for many different reasons including higher anxiety sensitivity, greater pessimism, lower distress tolerance, and lower motivation and adherence with treatment. If future research points towards these factors, interventions such as dialectical behavioral therapy for emotional regulation, motivational interviewing to improve adherence, and cognitive therapy for pessimism could all be valuable ways of targeting the relationship between comorbidity and EX/RP outcome.
Little attention has been paid to the number of prior SRI trials as a predictor of post-treatment outcome to EX/RP. Our finding that the number of past SRI trials predicted poorer outcome is consistent with studies examining predictors of medication response (Denys et al., 2003
) and with one small open trial of EX/RP augmentation (Tolin et al., 2004
), based on individual analyses of predictors. In our study, each additional past SRI trial resulted in a 1.20 point increase in patients’ post-treatment YBOCS score. It is worth noting that the number of past SRI trials is not a substitute for patient’s comorbidity or OCD severity as both of these factors were controlled in the analysis. This finding may reflect a psychological cause, such that patients who perceive a lack of benefit from past medication trials could have less optimism about EX/RP, reducing the degree to which they engage in treatment. Psycho-education about the efficacy of EX/RP augmentation might benefit these patients. Alternatively, resistance to medications (as measured by proxy here as the number of prior SRI trials) could represent a neurobiological resistance to treatment since some evidence points to a shared neurobiological substrate of treatment response (Baxter et al., 1992
). Thus, resistance to medications may be associated with resistance to any treatment.
This is the first randomized trial to examine the relationship between pre-treatment QoL and post-treatment EX/RP outcome.. Higher QoL predicted a better treatment response whereas global measures of functioning did not. Every standard deviation decrease in QoL resulted in a 1.79 increase in patients’ post-treatment YBOCS score. Patients’ mean QoL score at baseline (55.77, SD 16.52) was significantly lower on the QLESQ than that observed in healthy controls (78.91, SD 13.04) based on Huppert et al. (2009)
. It might be that patients reporting higher QoL are more motivated to manage their OCD symptoms because they experience satisfaction from their lives in other domains. Future research should confirm this relationship between QoL and EX/RP outcome.
Several variables were not associated with treatment outcome. The number of Axis II disorders did not predict outcome, consistent with prior studies of EX/RP that included medicated and unmedicated patients (de Haan et al., 1997
, Steketee et al., 2001
) and another that focused on EX/RP augmentation of SRI pharmacotherapy (Tolin et al., 2004
). It remains possible that only certain Axis II disorders, such as schizotypal and borderline personality disorders, are associated with poor outcome to EX/RP (Steketee et al., 2000
), a question we could not explore due to the small number of patients with these disorders. Insight did not predict outcome, which is consistent with one study of combination therapy (Stewart et al., 2006
) and two EX/RP studies that included medicated and unmedicated patients (Hoogduin and Duivenvoorden, 1988
, Lelliott et al., 1988
); insight did predict outcome in two smaller studies, one of EX/RP augmentation with medication (Tolin et al., 2004
) and another of EX/RP monotherapy (Foa et al., 1999
). Each study measured insight differently, making it difficult to interpret the findings. Insight may need to be very poor before it affects EX/RP outcome (Foa et al., 1999
) since insight itself improves with treatment (Foa et al., 1999
, Cottraux et al., 2001
). Few patients in our study had poor insight (i.e., mean insight= 0.7, based on a scale of 0–4; no patient was rated as 4 and only 5% were rated as 3 = poor insight).
Finally, the presence of prominent hoarding symptoms were not significantly related to outcome in our sample, in contrast with most prior studies (Black et al., 1998
, Mataix-Cols et al., 2002
, Saxena et al., 2002
, Abramowitz et al., 2003
). However, only seven people who received EX/RP (6.5% of the total sample) reported the presence of prominent hoarding symptoms; thus, our result had a large confidence interval and cannot be considered definitive. Moreover, all seven also had other OCD symptoms, which may have resulted in declines in their OCD severity. Of note, these seven experienced much less reduction on average in their post-treatment YBOCS score than those without hoarding symptoms (5.0 vs. 10.4). If these seven were representative, a larger group of patients with hoarding symptoms might well have replicated findings from other EX/RP studies.
This study has several limitations. First, as in most predictor studies, the analyses were exploratory, since patients were not randomized based on potential predictors of interest. Second, although one of the largest randomized samples of EX/RP outcome, it contained too few cases of specific Axis I and Axis II disorders of interest to examine their individual effects. Third, we were not able to address the impact of severe depression on EX/RP augmentation because patients were already receiving a SRI medication at study entry. Thus, few patients had severe depression (HAM-D > 24) at initial evaluation, and they were excluded from entering if they did.
Conclusions and Clinical Implications
In sum, significant moderators of a poorer outcome included gender (affecting EX/RP) and pre-treatment severity (affecting SMT). Significant predictors of a poorer outcome (adjusting for treatment type and pre-treatment severity) were more comorbid Axis I conditions, past SRI trails and lower QoL at baseline. Our approach of examining a range of risk factors (versus searching for individual effects) begins to address an important gap in the OCD literature around predictors of combination therapy and EX/RP augmentation of pharmacotherapy in particular.
Findings for the EX/RP subgroup were consistent with the full model. The combined variance of female gender, more comorbid conditions, more past SRI trials and lower QoL for EX/RP was large (R2
=55.2%). Yet the effect sizes for these individual factors were small to medium. This may explain the inconsistency between prior studies where the range of possible predictors examined was not as broad. Our results suggest that monitoring for a combination of risk factors is required to identify OCD patients at risk for poor EX/RP outcome. For example, patients with one comorbid condition, one past SRI-trial, and the mean score on QoL (QLESQ=55.77 vs. 78.91 for healthy controls (Huppert et al., 2009
) had on average a post-treatment YBOCS score over 5 points higher (a clinically meaningful increase) than patients without these risk factors. Many patients in this study had several past SRI trials, comorbid conditions, and lower than average QoL, putting them at significant risk for poor EX/RP outcomes.
Future research will need to replicate these findings and should consider whether patients with multiple risk factors can benefit from a multi-modular intervention to target each risk factor impeding EX/RP outcome. Our data suggest that such an intervention should include evidence-based treatments targeting comorbidity, interventions to enhance QoL, and psycho-education regarding the effectiveness of EX/RP for medication non-responders.