What is already known on this topic

Antidepressant medications (ADM) and cognitive therapy (CT) are recommended as first-line treatments for major depressive disorder (MDD), on the basis of clinical trials of relatively brief duration.1 Real-world clinical practice, however, typically involves multiple medication trials and strategies for combining, augmenting or switching to other medications or CT until remission is reached. The present study addresses this limitation by examining a principle-driven algorithm for providing ADM alone versus ADM combined with CT (ADM plus CT) in a sample of adult outpatients treated for up to 42 months.

Methods of the study

This randomised study consisted of 452 outpatients (aged 18 years or over) with Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) chronic or recurrent MDD recruited at three US research centres. Patients with Axis I psychiatric comorbidity, imminent suicide risk, pregnancy, mandated treatment or compensation issues were excluded. Remission was defined as a 17-item Hamilton Rating Scale for Depression (HSRD) ≤8 or Longitudinal Interval Follow-up Evaluation (LIFE) ≤2 for four consecutive weeks. Recovery was defined as 6 months without relapse (two consecutive weeks of HRSD ≥16 or LIFE ≥5) following remission. The ADM treatment involved up to four different classes of antidepressants and any of the augmenting or adjunctive agents commonly used in clinical practice. CT was delivered based on manuals developed by Beck et al.2 ,3 Those in the ADM-only group did not receive any sham treatments or additional study visits to match the amount of time/attention provided in the ADM plus CT group. Patients in both groups who did not achieve remission by month 18 or recovery by month 36 were terminated from the study. Outcome assessments were conducted by trained interviewers who were blind to treatment condition, while participants and providers were unblinded.

What does this paper add

• This paper involves a much longer intervention period and more flexible treatment algorithms in order to more closely model/operationalise the strategies employed in clinical practice.

• Including flexible treatment algorithms and treating to the end points of remission in the acute phase and recovery in the continuation phase are important methodological contributions. The majority of prior studies have based end points on treatment duration, rather than on symptom remission/recovery. Full remission at 12 months did not differ between the ADM+CT (63.6%) and ADM alone (60.3%) groups.

• Recovery rates were higher with ADM+CT than ADM alone (72.6% vs 62.5%); however, overall recovery rates were lower for patients with comorbid Axis II irrespective of treatment conditions (61.2% vs 73.5%). Subgroup analyses indicated similar recovery rates in the two conditions for patients with low-severity MDD (72.9% vs 69.8%), whereas patients with high-severity MDD were more likely to benefit from ADM+CT (73.4% vs 54.3%). Participants with severe, non-chronic MDD received the most benefit from combined treatment (81.3% vs 51.7%).

Limitations

• Generalisability is limited to English-speaking outpatients with chronic or recurrent MDD. Patients with substance abuse, bipolar disorder and borderline personality disorder were excluded, as were pregnant women and those with certain unspecified Axis I conditions. The sample was 86% Caucasian and nearly 50% of participants were college graduates. Rates of specific Axis I and II comorbidities were not specified.

• The ADM and CT may have been of higher quality/integrity than interventions provided in the community. CT and medication management sessions were closely supervised and were conducted more frequently than is typical in general practice settings.

• Providers and participants were not blind to the treatment and there was no placebo or attention-control condition to account for passage of time or non-specific therapy effects.

• The authors do not describe the specific antidepressant agents used, which makes the results difficult to interpret clinically. They note that a forthcoming paper will provide more details on the medication management protocol.

What next in research

Additional research is still needed to achieve the goal of personalised medicine (ie, which treatment(s), for which patient, in what order).4 This may be best achieved through clinical trials that employ sequential, multiple assignment, randomised trial designs that can more closely match the type of decision-making that occurs in clinical practice.5 Subgroup analyses could then examine which sequence of interventions is most effective for patients with chronic and/or severe MDD, comorbid Axis II conditions, etc.

Do these results change your practices and why?

These results suggest that high-quality medication management may be sufficient to obtain recovery for patients with less severe and/or chronic MDD. The more time- and cost-intensive ADM plus CT strategy may be best suited for patients with severe, non-chronic MDD. Pending replication of these findings, I would be more likely to refer patients with severe depression of less than 2 years duration to receive combined treatment as a first-line intervention. For those with less severe depression of longer duration, I would wait to see if they respond to ADM prior to augmenting with psychotherapy.