Co-occurring depression was common in this sample of primary care patients with anxiety disorders, with nearly two-thirds of patients meeting criteria for MDD at baseline. This comorbidity rate is consistent with the extensive literature showing a strong association between anxiety and mood disorders, particularly in clinical samples.5
Depressed participants had higher rates of GAD, PTSD, and medical comorbidity than non-depressed participants and endorsed more severe anxiety symptoms and anxiety-related disability at baseline. Socio-demographically, participants with co-occurring MDD were more likely to identify as Hispanic and African-American, to endorse a low educational level, and to qualify for Medicaid. These baseline findings suggest that primary care patients with co-occurring anxiety disorders and MDD often present with additional clinical complexities (e.g., co-occurring medical problems, social challenges related to lower education/financial resources) that may play a role in their anxiety and mood symptoms.
Despite the more severe and complex baseline presentation of depressed participants, co-occurring MDD did not significantly moderate the effects of the CALM intervention (relative to UC) on anxiety symptoms, anxiety-related disability, or treatment response and remission rates. This finding converges with results of prior studies with smaller samples showing no prescriptive effects of depression on treatment outcomes following behavioral treatment for anxiety disorders.7,8
In contrast, co-occurring MDD was prognostic of outcomes over the 18 months of follow-up, predicting both magnitude of improvement and absolute levels of anxiety symptoms and anxiety-related disability at each assessment point. Irrespective of treatment assignment, depressed participants improved more yet still appeared worse than non-depressed participants at all follow-up assessments. The higher absolute levels of symptoms and disability (and hence lower remission rates) in the depressed group appeared to be a byproduct of their baseline elevations, which were not fully compensated for by their larger improvements on the anxiety outcome measures.
The analyses of remission rates merit comment, as the results were striking yet not significant at the a priori threshold of p < .01. For depressed patients, the 6-month remission rate in CALM was twice that of UC (41% versus 20%). The corresponding difference in the non-depressed group was less dramatic (48% versus 39%). This pattern persisted at subsequent follow-ups, and it is noteworthy that at the final assessment (18 months), depressed patients who received UC displayed particularly low remission rates (28%) compared to all other patients (50%–55%; see and ). These data suggest that UC may have particularly low efficacy for patients with co-occurring depression; whereas higher-intensity interventions such as CALM may improve likelihood of remission in this subgroup.
As noted in previous reports,4, 22
the CALM intervention is superior to UC in reducing anxiety symptoms and anxiety-related disability in primary care patients with anxiety disorders. The current findings support the use of CALM and similar empirically supported interventions for anxiety disorders in patients with co-occurring depression. The lack of moderation of the CALM intervention effect by MDD suggests that, contrary to some clinical opinion, the potency of empirically supported treatments for anxiety is not generally compromised by co-occurring depression. On the contrary, improvements in anxiety symptoms and anxiety-related disability associated with CALM and UC were larger for the depressed versus the non-depressed participants. These improvements were not only statistically but clinically significant; collapsing across CALM and UC, the average anxiety symptom score for depressed participants was in the “mild” range at all follow-up assessments.
Factors Contributing to the Effect of Depression on Degree of Clinical Improvement
To our knowledge, co-occurring depression has not been associated with larger improvements in previous studies examining prognostic effects of depression on anxiety treatment outcomes. Prior studies found either less clinical improvement10–14
or equivalent degrees of change15–21
in depressed patients relative to comparison groups. We therefore consider potential factors that may have contributed to this discrepant finding.
First, the more naturalistic design of CALM (compared to efficacy trials) may partly explain the larger improvements observed in the depressed participants. Rather than prescribing a set number of sessions, the CALM intervention allowed clinicians and patients to work flexibly toward a goal of clinical remission. Primary care providers and any specialist clinicians who treated patients assigned to UC were presumably working toward a similar goal. Within this context, it is not entirely surprising that depressed participants displayed greater clinical change; because they started with more severe symptoms, larger decreases would be required for them to approach the goal of remission. Study clinicians had a range of options available for targeting the symptoms of patients with more complicated presentations, including “stepping up” by adding more of the initial treatment modality or “stepping over” to the alternative treatment modality.
To investigate this further, we conducted post-hoc
analyses to explore whether the more severe initial presentations of depressed participants prompted clinicians to deliver treatment differently. For patients assigned to CALM, data were available from the study’s web-based tracking system (see Supplementary Table
). We found that depressed and non-depressed patients assigned to CALM did not differ significantly in terms of proportions who received CBT only, medication management only, and combination treatment. There also were no significant between-groups differences in the number of contacts with study clinicians, regardless of the type of contact (in-person vs. phone; medication management vs. CBT; active treatment vs. relapse prevention). The only difference that approached statistical significance was in the direction of non
-depressed patients receiving more CBT contacts; on average they received approximately one more CBT contact than depressed patients (p
= .013; all other differences were non-significant at p
For the full sample, data were limited to patients’ self-reports of treatment from the baseline, 6, 12, and 18 month assessments. Rates of depressed and non-depressed patients who reported receiving key elements of CBT during treatment sessions did not differ significantly at any of the follow-ups. Not surprisingly, depressed participants were more likely to report using antidepressant or antianxiety medication of adequate type, length, and dose (see34
for the study’s operational definitions of adequate pharmacotherapy); however, the advantage that depressed patients had on this indicator of treatment quality was greater at baseline (33.0% vs. 23.7%) than at the study follow-ups . While clear implications cannot be deduced from this pattern, it is possible that the difference in rate of adequate pharmacotherapy or other aspects of medication treatment (e.g., more aggressive regimens) could have contributed to the larger improvements observed in the depressed group.
In addition to differences in treatment delivery, patient factors influencing outcome should also be considered as a potential explanation for the larger improvements in depressed patients. It is possible that participants who were more impaired at baseline (as the depressed participants were) may have been more motivated to comply with treatment recommendations than those whose symptoms were less disabling. Again, this type of effect could be more apparent in an effectiveness study conducted in a “real-world” setting than in an efficacy trial conducted in a research setting (where there may be less variability in treatment adherence due to more stringent controls in subject selection and treatment delivery).
Finally and importantly, it may have been more difficult to demonstrate change in the non-depressed participants because they endorsed relatively low anxiety symptom and anxiety-related disability scores at baseline. Conversely, the more severe baseline symptoms and disability of the depressed patients may have allowed more room for improvement on the outcome measures. This basic measurement issue could have contributed to the different magnitudes of improvement observed in the depressed and non-depressed groups.
The current study elucidates the effects of depression on treatment for anxiety in a mixed anxiety disorder sample. Due to statistical power considerations, the study was not designed to evaluate further interactions involving specific anxiety disorder diagnoses (i.e., 4-way interactions among Principal Anxiety Diagnosis, MDD, Treatment Assignment, and Time). The results reported here cannot be assumed to apply uniformly to each individual anxiety disorder.
In addition, the CALM study evaluated a multifaceted intervention involving CBT, medication management, or their combination. Our results pertain specifically to the effects of depression on the CALM package compared to UC. Design considerations preclude us from drawing conclusions regarding the influence of depression on the effectiveness of specific components of CALM. While participants were randomly assigned to CALM or UC, the components of CALM they received (CBT, medication management) were not randomly assigned but dictated by patient and provider choice. Future investigations should evaluate potential prescriptive effects of depression on the specific modalities of CBT and pharmacotherapy, as this could aid in selection of an optimal empirically supported intervention for anxiety.
Conclusions and Future Directions
Co-occurring depression did not moderate the effects of CALM on anxiety symptoms, anxiety-related disability, or response/remission rates. Improvements in anxiety symptoms and anxiety-related disability were clearly demonstrated for depressed participants. These results support the use of interventions such as CALM for patients with co-occurring depression, especially when considered in conjunction with findings that depressive symptoms often improve with effective treatment of anxiety disorders.4, 35
Clinicians implementing such interventions in primary care settings can expect higher absolute levels of anxiety-related symptoms and disability (as well as additional complexities such as medical comorbidity and challenges related to social conditions) in depressed patients relative to non-depressed patients referred for similar interventions. However, the magnitude of improvement also may be greater for the depressed patients. Some noteworthy findings that did not meet the a priori
threshold for statistical significance suggested the possibility of a stronger advantage of CALM over UC in producing remission of anxiety symptoms in the depressed participants. Future research should continue to explore the issue of whether higher-intensity interventions such as CALM are even more strongly indicated in anxiety patients with more complicated initial presentations involving co-occurring depression.