Back in August, I reviewed a recent meta-analysis that suggested combined treatment enhances recovery across a range of common mental health difficulties. Its limitation? In many ways, words like ‘psychotherapy’ are a little broad, but the results were nonetheless encouraging (Kennedy-Williams, 2014).

So to this month, and a new randomised controlled trial (RCT) published in JAMA Psychiatry (Hollon et al, 2014) investigating the effects of combining cognitive therapy (CT) with antidepressant medication (ADM) in assisting the rate of recovery in major depressive disorder (MDD).

Methods

Participants (N=452) were recruited from a number of clinics across North America. They were randomised to receive either CT plus ADM, or ADM alone. They were stratified according to sex, MDD chronicity, recurrence, severity and marital status. The latter of which is particularly encouraging to see, given the reduced risk of MDD in those who are married.

Blind evaluations of recovery were conducted using a modified version of the Hamilton Rating Scale for Depression (HRSD) and the Longitudinal Interval Follow-up Evaluation (LIFE).

Inclusion criteria:

• Meeting DSM-IV criteria for MDD which is either chronic (duration >2 years) or recurrent (>1 episode in previous 3 years)
• A score of 14 or more on the HRSD
• Aged 18 years or over
• English speaking
• Able to provide informed consent

Exclusion criteria:

• A history of bipolar disorder or non-affective psychosis
• Substance dependence in the past 3 months
• DSM-IV axis I disorders requiring non-protocol treatment
• DSM-IV axis II disorders poorly suited to study treatments (i.e. borderline, schizotypal or antisocial personality disorder)
• Medical conditions precluding participants from receiving ADM
• Current medications known to induce depression
• Mandated treatment, or compensation issues

There are two attention-grabbing elements here:

1. The first is the emphasis on ‘personalised medicine’, essentially continuing treatment until the desired result is achieved. Such a result, in this case, is recovery.
2. Which leads to the second headline; that treatment would continue beyond mere remission (which they defined as 4 consecutive weeks of minimal symptoms), into recovery (which was defined as 6 months without relapse following remission).

Cognitive therapy

For those psychologists out there; the CT treatment followed the ‘Beckian’ manual (Beck et al, 1979) for depression, and was delivered primarily by doctoral-level psychologists (N=12), plus one psychiatrist, and one nurse specialist. Interestingly, where co-morbid axis II problems were present (but not meeting criteria for exclusion), the treatment was augmented by elements of CT for personality disorders (Beck, Freeman, & Davis, 2003). Sessions were 50 minutes in length, and frequency was at the discrepancy of the practitioner.

Antidepressant medication

Several different classes of ADM were used. Participants were initially prescribed the most easily tolerated SSRI class, at the maximum tolerated dose. For those who showed poor response, these were switched to tricyclic, or monoamine oxidase inhibitor class ADMs, known to be harder to tolerate. As with CT, practitioners were free to alter dosages as required.

Results

• Recovery rates were higher in the CT plus ADM group versus ADM alone (72.6% vs 62.5%; t(451) = 2.45; P = .01; hazard ratio [HR], 1.33; 95% CI, 1.06 to 1.68; number needed to treat [NNT], 10; 95% CI, 5 to 72)
• This was, however, limited to more severe, non-chronic MDD (81.3% vs 51.7%; n = 146; t145 = 3.96; P = .001; HR, 2.34; 95% CI, 1.54 to 3.57; NNT, 3; 95% CI, 2 to 5)
• Also, attrition rates were significantly lower in the CT plus ADM group versus ADM alone (18.9% vs 26.8%; t(451) = −2.04; P = .04; HR, 0.66; 95% CI, 0.45 to 0.98)
• Despite augmented CT treatment, participants with comorbid axis II disorders, which represented 49.8% of the study population, were significantly less likely to recover irrespective of treatment condition versus those without (61.2% vs 73.5%; t(451)=2.81; p=.01; HR, 1.40; 95% CI, 1.11 to 1.77)
• They were also more likely to drop out, again irrespective of treatment condition (27,4% vs 18.4%; t(451)=2.09; p=.04)
• Finally, patients in the combined condition experienced fewer serious adverse events than those in the ADM condition (49 vs 71; P=.02)

Conclusions

The authors concluded that:

Cognitive therapy combined with medication treatment enhanced rates of recovery relative to medications alone, with the effect limited to patients with severe non-chronic depressions.

With regard to the relative effects of CT and ADM, they highlighted that their results suggest:

CT engages different mechanisms than ADM but that it likely only does so in some patients.

Finally, regarding those with Axis II disorders, the authors acknowledged that, despite a modified version of CT, they:

…evidenced higher rates of attrition and lower rates of recovery than did those without comorbid axis II disorders irrespective of treatment condition. 

Limitations

• The study was undertaken on a North American, predominantly White (85.8%) population
• As the authors acknowledged, there was no ‘psychotherapy only’ condition, or any psychotherapy comparison group, to explore CT versus other psychological interventions
• There was no economic evaluation conducted, to explore any cost-saving benefits of combining treatments

Summary

The editorial accompanying the article hails it as one of the most important single studies into the combined effects of ADM and psychotherapy of all time (Thase, 2014). It certainly operates on a large scale. And it’s true too, that a single study with a large number of participants reduces the likelihood of a type II error (finding false negative results), over meta-analyses including several smaller studies.

The idea of personalised medicine in research seems a complex one. On the one hand, this study may be hard to replicate, due to the personalisation of dosages, therapy frequency, and so forth. However, allowing practitioners and participants to alter treatments not only encourages patients a more active role in their treatment, in research terms, it better emulates routine clinical practice, rather than a rigorous research protocol with little bearing on the real world.

In the UK context though, the ‘personalised medicine’ concept is slightly more problematic, particularly in psychological services, where time-limited treatments are required to meet the over-demand. Rarely, it would seem, would practitioners be afforded the luxury of such an approach, although clearly, it seems efficacious.

Similarly, from a UK perspective, an evaluation of the economic benefit of combining treatments, particularly with such a rigorous follow-up procedure, would have added further weight to the argument that, at least in severe, non-chronic cases, combined treatment does indeed work well in supporting recovery from MDD.

Links

Hollon SD, DeRubeis RJ, Fawcett J, et al. Effect of Cognitive Therapy With Antidepressant Medications vs Antidepressants Alone on the Rate of Recovery in Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2014;71(10):1157-1164. doi:10.1001/jamapsychiatry.2014.1054. [Abstract]

Thase ME. (2014). Large-Scale Study Suggests Specific Indicators for Combined Cognitive Therapy and Pharmacotherapy in Major Depressive Disorder (Editorial). JAMA Psychiatry. Published online August 20, 2014. doi:10.1001/jamapsychiatry.2014.1524. [Abstract]

Beck AT, Rush AJ, Shaw BF, Emery G. (1979). Cognitive therapy of depression. Guilford Press, New York.

Beck AT, Freeman A, Davis DD. (2003). Cognitive Therapy of Personality Disorders. Guilford Press, New York.

Kennedy-Williams, P. (2014) Combining Psychotherapy and Antidepressants is best for Common Mental Illnesses. The Mental Elf, 19 Aug 2014.