CMAJ • April 22, 2008; 178 (9). doi:10.1503/cmaj.1080028.
© 2008 Canadian Medical Association or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
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Letters

Effectiveness of selective serotonin reuptake inhibitors

Corrado Barbui, MD*, Toshiaki A. Furukawa, MD PhD{dagger} and Andrea Cipriani, MD*

*Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, World Health Organization Collaborating Centre for Research and Training in Mental Health, University of Verona, Verona, Italy; {dagger}Department of Psychiatry and Cognitive-Behavioral Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

[The authors respond:]

We selected leaving the study early for any reason as the primary outcome for our systematic review1 because patients frequently stop taking or change their antidepressant medication. In Italy, for example, a recent survey showed that of more than 2800 adults observed for 6 months after receiving their first antidepressant prescription, 60% received only occasional prescriptions after their first one.2 We therefore reasoned that treatment adherence might represent a clinically useful outcome measure in meta-analyses of randomized controlled trials, as we thought that under experimental conditions this outcome might integrate patients' and clinicians' judgments of efficacy, safety and tolerability into a global measure of effectiveness and acceptability. Similar reasoning was recently used in a clinical trial of antipsychotic drugs.3

We acknowledge that this outcome measure may only offer a "down-to-earth" evaluation of a drug's effectiveness and acceptability, but this limitation can be seen as a strength in a field of research where efficacy is typically quantified as a score on a rating scale: in clinical practice, physicians seldom define patient improvement with rating scales.

For patients with moderate to severe major depression, one of the first goals is to keep them on treatment. Therefore, the main clinical question of our systematic review was whether paroxetine is better than placebo at keeping patients on treatment. Staying on treatment can also be seen as a hard measure with little measurement error. In addition, we investigated the effectiveness of paroxetine in those who actually took it and we also used standard measures of depression.

The main clinical message of our analysis is that the effect of antidepressants in patients with moderate to severe depression is modest. Physicians should consider combining pharmacologic and nonpharmacologic treatments such as psychological and psychosocial interventions backed by scientific evidence.4,5 Similarly, patients should not receive the message that modifications of thought, mood and behaviour can be achieved by pharmacologic means only.

Footnotes

Competing interests: None declared for Corrado Barbui and Andrea Cipriani. Toshiaki Furukawa has received research funds and speaker's fees from Asahi Kasei, Astellas, Dai-Nippon, Sumitomo, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Kyowa Hakko, Meiji, Nikken Kagaku, Organon, Otsuka, Pfizer and Yoshitomi. He is on the research advisory boards of Sekisui Chemicals, Pfizer, Janssen and Mochida. His research has also been funded by the Japanese Ministry of Education, Science and Technology and by the Japanese Ministry of Health Labor and Welfare.


REFERENCES

  1. Barbui C, Furukawa TA, Cipriani A. Effectiveness of paroxetine in the treatment of acute major depression in adults: a systematic re-examination of published and unpublished data from randomized trials. CMAJ 2008;178:296-305.[Abstract/Free Full Text]
  2. Poluzzi E, Motola D, Silvani C, et al. Prescriptions of antidepressants in primary care in Italy: pattern of use after admission of selective serotonin reuptake inhibitors for reimbursement. Eur J Clin Pharmacol 2004;59:825-31.[CrossRef][Medline]
  3. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005;353:1209-23.[Abstract/Free Full Text]
  4. Ebmeier KP, Donaghey C, Steele JD. Recent developments and current controversies in depression. Lancet 2006;367:153-67.[CrossRef][Medline]
  5. Timonen M, Liukkonen T. Management of depression in adults. BMJ 2008;336:435-9.[Free Full Text]




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