How Effective Are Contemporary Antidepressants? – Prof Malcolm Hopwood

Posted on July 24, 2016

Prof. Hopwood is the Ramsay Health Care Professor of Psychiatry at the University of Melbourne. His research areas of interest include psychopharmacology, clinical aspects of mood and anxiety disorders and psychiatry aspects of acquired brain injury and other neuropsychiatric disorders.

The most recent meta-analysis looking at remission rates and antidepressants found that there was a 53.8% improvement with an antidepressant and a 37.3% improvement with the placebo. (Papakostas  et al., 2006).

What does this mean?

Are we are making better placebo’s than we used to? – I doubt it

The response rate is approximately 50-50. This implies a few things according to Prof. Hopwood:

  • We have had an evolution of antidepressants – initially, they were tested within inpatient populations, where the placebo rate is possibly 10-15%. Nowadays most trials are done in outpatient settings where placebo rates can be higher. ‘Mild MDD has a significant spontaneous remission rate’ which can impact on trial results.
  • Recruitment biases and sampling errors –

We’re probably not measuring the proper disease state that we actually want to know about.

  • The rise of the active comparator –

This is not a true head to head trial.

  • The Data is ‘unhelpful’ in differentiating compounds

The most convincing evidence for the efficacy of Antidepressants is not in acute treatment but in relapse prevention.

John Geddes meta-analysis found that in trials extending 12 months or more post reaching remission; relapse occurs in around 40% of people taking the placebo and about 15% on an antidepressant.

This is a significant difference and well worth having.

However, it is worth noting that this result may be enhanced by an enriched sampling effect.

The big question in treatment therefore is: 

Is response (i.e. 50%) adequate?’…The answer is clearly and absolutely no. Full remission should be the goal.

Even the presence of one symptom (asymptomatic recovery) decreases the median relapse time significantly.


  1. Papakostas, G. I., Perlis, R. H., Scalia, M. J., Petersen, T. J., & Fava, M. (2006). A meta-analysis of early sustained response rates between antidepressants and placebo for the treatment of major depressive disorder. Journal of clinical psychopharmacology, 26(1), 56-60.
  2. Geddes, J. R., Carney, S. M., Davies, C., Furukawa, T. A., Kupfer, D. J., Frank, E., & Goodwin, G. M. (2003). Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. The Lancet, 361(9358), 653-661.
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