There’s something to please most people in a new meta-analysis by Cuijpers et al in World Psychiatry, regardless of where you sit on the psychology/psychiatry spectrum. Particularly though, it would seem, if you see value in both.

As the name suggests, common mental health disorders (CMHDs), namely depression and anxiety disorders, are prevalent. Although accurate data is hard to obtain, due in part to high numbers of people not seeking treatment, it is estimated that in the UK, CMHDs affect 15% of the population at any given time (see NICE, 2011).

Treatment often remains in primary care, up to 90% of cases in fact, which typically involves pharmacotherapy (antidepressants). Although in the UK, the Improving Access to Psychological Therapies (IAPT) initiative has dramatically increased access to evidence-based psychological interventions such as CBT for CMHDs in primary care, the majority of cases still either go untreated or with medication alone.

There is evidence that combined treatments work well for individual disorders such as depression, panic disorder, obsessive-compulsive disorder (OCD) or social anxiety disorder (SAD). However, the question of interest to Cuijpers et al regards the efficacy of combined treatment across CMHDs, versus pharmacotherapy alone, to build a wider picture of their clinical utility. The authors were also keen to examine the effect of combined treatment, as well as psychotherapy and pharmacotherapy alone, versus placebo.

Methods

The authors searched PubMed, PsycInfo, Embase and the Cochrane database of randomised trials for studies comparing combined antidepressant medications and psychological treatments, compared with antidepressants alone. The authors also checked the reference lists of earlier relevant meta-analyses.

After removing duplicates, a total of 14,903 abstracts were retrieved. Of these, 2,278 papers were given further consideration. 2,226 of these were excluded, leaving a total of 52 studies for the meta-analysis.

Inclusion criteria:

• Studies involving adults who met diagnostic criteria for a depressive disorder, panic with or without agoraphobia, generalised anxiety disorder (GAD), seasonal affective disorder (SAD), OCD or post-traumatic stress disorder (PTSD), as defined by a structured diagnostic interview
• Studies published in English, German, Spanish or Dutch

Exclusion criteria:

• Studies involving inpatients or anyone under the age of 18
• Maintenance studies involving participants whom had partially recovered from an earlier treatment

The Cochrane “Risk of bias” tool was used to assess potential bias in studies, with validity checked by two independent researchers.

Antidepressants were coded by type (e.g. SSRI, TCA, SNRI, MAOI), as were psychological treatments (CBT, IPT, or a mix of treatments, coded as ‘other’). Effect sizes of post-treatment differences between groups were calculated using Hedges’ g, and effect sizes were corrected for small sample bias. These values were then transformed for a number needed to treat (NNT), for better clinical meaningfulness.

A random effects pooling model was used due to predicted heterogeneity between studies.

Results

Combined treatment versus pharmacotherapy alone

• The overall mean effect size of the difference between combined treatment and pharmacotherapy alone was g=0.43 (95% CI: 0.31 to 0.56, NNT=4.20) in favour of combined treatment
• However, this was reduced to g=0.37 (95% CI: 0.27 to 0.47; NNT=4.85) when outliers with particularly high effect sizes were excluded
• For specific disorders, the effect sizes (all in favour of combined treatment) were as follows:
  • Major depression: g=0.43 (95% CI: 0.29 to 0.57; NNT=4.20)
  • Panic disorder: g=0.54 (95% CI: 0.25 to 0.82; NNT=3.36)
  • OCD: g=0.70 (95% CI: 0.14 to 1.25; NNT=2.63)
• Other disorders did less well:
  • SAD yielded some benefit of combined treatment, but this was non-significant
  • There was insufficient evidence for dysthymia, GAD and PTSD

Treatment versus placebo

• A total of 11 studies allowed comparison to placebo, with effect sizes as follows (again all in favour of treatment):
  • Combined treatment vs placebo: g=0.74 (95% CI: 0.48 to 1.01; NNT=2.50)
  • Pharmacotherapy vs placebo: g=0.35 (95% CI: 0.21 to 0.49)
  • Psychotherapy vs placebo: g=0.37 (95% CI: 0.11 to 0.64)

Long-term comparisons

• Long-term benefits of combined therapy versus pharmacotherapy alone were significantly greater, with a relative risk (RR) of 1.48 (95% CI: 1.23 to 1.78; NNT=4.29) up to a maximum follow-up of 24 months

Conclusions

As the authors concluded that their meta-analysis reveals:

Clear evidence that combined treatment with psychotherapy and antidepressant medication is more effective than treatment with antidepressant medication alone.

The benefits of combined treatment remain at follow-up. The authors do observe, however, that publication bias may have exaggerated the results.

Another interesting finding is that combined treatment is more beneficial than pill placebo, and approximately twice as effective as pharmacotherapy or psychotherapy alone.

Finally, the authors emphasise that previously, it had been hard to disentangle the effects of psychotherapy and pharmacotherapy in combined treatments, however, the results here suggest that:

The effects of psychotherapy and pharmacotherapy may be largely independent from each other and additive, not interfering with each other, and both contribute about equally to the effects of combined treatment.

Limitations

• Understandably, given the current trend regarding both psychological and pharmacological treatments, a large percentage of studies focussed on cognitive and/or behavioural interventions (63%) and SSRIs (42%)
• Also, a large proportion of studies focussed on depressive disorders (62%)
• Furthermore, as the authors acknowledge, the psychological treatments were pooled into broader categories than would perhaps exist in clinical practice
• Also, the quality of the included studies was variable. For example, only 37% reported independent allocation, and 25% did not report blinding. Indeed, only 25% of studies met all four quality criteria
• Analysis also indicated significant publication bias

Summary

This meta-analysis, although hampered at times by study quality and heterogeneity of data, provides useful insight into the clinical utility of combined treatments. In doing so, it provides a strong argument for a combined approach to supporting the needs of people with depression and anxiety. The challenge remains to improve access for those not seeking treatment, and to continue to improve psychological services in primary care to meet this clear clinical need.

Links

Cuijpers, P., Sijbrandij, M., Koole, S. L., Andersson, G., Beekman, A. T., & Reynolds, C. F. (2014). Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta‐analysis. World Psychiatry, 13 (1), 56-67.

NICE (2011). Common mental health disorders: Identification and pathways to care.  Retrieved from http://www.nice.org.uk/guidance/cg123