Second generation antidepressants (i.e. antidepressants other than tricyclics and MAOIs), cognitive behaviour therapy (CBT) and combination therapy are equally effective as initial treatments for adult patients with major depression, a systematic review and meta-analysis has found.

Studies were identified by a search of electronic databases for the period Jan 1990-Jan 2015. Eleven randomised controlled trials involving 1,511 patients were included in the analysis.

Within these, there were ten trials comparing antidepressant treatment with CBT and three trials comparing antidepressant treatment with combination therapy. The median age in most trials was 35-45 years and the majority of patients were women. Meta-analysis was restricted to those trials rated as having a low or medium risk of bias.

Most participants had moderate to severe depression. Remission was defined as a Hamilton Rating Scale for Depression (HRSD) score of either < 7 or ≤ 7. Response was defined as a 50% or greater reduction from the baseline HRSD score.

There was no significant difference between second generation antidepressants and CBT for:

• Remission (three trials): risk ratio (RR) 0.98 (95% CI: 0.73-1.32)

• Response (five trials): RR 0.91

(95% CI: 0.77-1.07)

There was also no significant difference between antidepressants and combination therapy:

• Remission (two trials): RR 1.06

(95% CI: 0.82-1.38)

• Response (two trials): RR 1.03

(95% CI: 0.85-1.26)

For both comparisons, there were no significant differences in the rates of withdrawal from the study RR 0.90 (95% CI: 0.49-1.65).

The authors warn that the results should be interpreted with caution as the strength of evidence was low for most outcomes. They also advise that the results may not be applicable to patients with milder depression, and those with chronic medical conditions (i.e. most of the patients we see in general practice!).

NICE recommends combination treatment for both moderate and severe depression in the absence of a chronic condition.¹ This study does not support this recommendation.

A recent American study found that combination treatment was only superior to antidepressant treatment in patients with severe depression.²

There is also evidence from a recent UK study that adding CBT to antidepressant treatment is effective in treatment resistant depression.³

NICE recommends that we offer a choice of antidepressants or CBT to patients with persistent subthreshold symptoms or mild to moderate depression who have not responded to a low intensity psychosocial intervention.¹

The authors of the present study argue that their finding of therapeutic equivalence justifies giving patients a choice. However, most studies have not found that matching treatment to patient preference improves outcomes.^4,5

It has been suggested that CBT may be more effective than antidepressants in preventing depression relapse.

The present study lacked sufficient evidence to address this question but another recent meta-analysis concluded that patients treated with CBT were significantly less likely to relapse than those whose antidepressant treatment was withdrawn after the initial treatment period.⁶

Providing there is timely access to CBT, I think it is reasonable to offer a choice of either antidepressants or CBT to patients with moderate depression or persistent (> 8 weeks) subthreshold/mild depression. CBT may be the preferred option for those at greater risk of relapse. Patients with severe depression should be offered combination treatment and there may also be a role for combination treatment in patients with moderate depression who have not responded to an initial 6-8 week course of antidepressants.

Dr Phillip Bland