Fewer than one in four depressed patients are in remission after a minimum of six weeks’ treatment with antidepressants, a UK primary care cross-sectional study has found.

The data were collected during the initial stage of the CoBalT study, a randomised controlled trial of CBT augmentation for treatment-resistant depression.1 A total of 2,129 participants were recruited from 73 general practices. Eligible patients were those aged 18-75 who had been prescribed an adequate dose of antidepressant medication for at least six weeks.

Depressive symptoms were measured using the Beck depression inventory (BDI-II), a 21-item questionnaire. Adherence to treatment was assessed using the Morisky scale. Treatment-resistant depression was defined as a BDI-II score ≥ 14 despite adherence to treatment.

Just over half the participants (55%) had treatment-resistant depression (95% CI:53-58%). A further 22% had a BDI score ≥ 14 but had not adhered to their antidepressant treatment (95% CI:19-24%). Only 23% were in remission (95% CI: 21-26%).

Less than a quarter of those invited to participate did so. The authors acknowledge that this low response rate may have biased the results e.g. patients who were still depressed may have been less motivated to respond.

The goal of depression treatment should be remission rather than response. Remission is the complete resolution of depression symptoms plus the return of normal social and occupational functioning. Response is a substantial improvement, usually defined as a 50% or greater reduction in scores on the Hamilton Rating Scale for Depression (HDRS).2 Failure to achieve remission is associated with:

• Persistent functional impairment

• Increased risk of relapse

• A long-term chronic course

• Suicide attempts

• Worse outcomes from comorbid medical conditions.³

Researchers define remission as a score below the cut-off on a rating scale or questionnaire: a widely accepted definition is an HDRS score of 7 or less.² The present study identified depressive symptoms using the BDI-II questionnaire, using the recommended cut-off score of < 14 to define remission.⁴ However, a cut-off score is arbitrary and the ranges for different rating scales and questionnaires do not correspond. The American Psychiatric Association and NICE recommend that a BDI II score of < 10 should be regarded as equivalent to an HDRS score of < 8 and indicative of remission. According to NICE, a score of 10-16 indicates subthreshold symptoms.⁵ This would suggest that an even smaller number of the participants were actually in remission.

It has been suggested that remission indicates the temporary abatement of symptoms while receiving treatment and is not the same as recovery. To be deemed to have recovered, patients should remain in full remission despite discontinuation of treatment, they should have no residual symptoms that impair functioning and they should satisfy a test of psychological wellbeing.6 According to this definition, none of the participants had yet recovered!

More than two-thirds of the participants had been taking their current antidepressant medication for more than 12 months. The cross-sectional design of this study meant that it was biased towards those with chronic resistant depression and was unable to detect those who had recovered and no longer needed to take antidepressant medication.

The authors acknowledge that a longitudinal study would have given a more accurate picture.

Nevertheless, the findings are comparable with those of a large prospective study of sequential treatment outcomes which found that only 37% of patients achieved remission with citalopram. Stepwise treatment (switching or augmentation) was provided to non-responders but with a diminishing chance of response at each step (cumulative remission rates of 56% at step 2, 62% at step 3 and 67% at step 4).⁷

The first important lesson from this study is that most patients will not respond fully to acute antidepressant treatment, either because they do not take it or because the treatment is at least partially ineffective.

We should encourage adherence and provide active follow-up in the expectation that many patients will need adjustment of their management plans at 6-8 weeks’ follow-up. Options include increasing the dose, switching to another antidepressant, addition of CBT1 and combination treatment.

The second lesson is that we need to review our patients on long-term antidepressant treatment regularly, screen for significant residual symptoms and offer alternative treatments to those who are not in remission.

Dr Phillip Bland