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Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis

BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h6019 (Published 08 December 2015) Cite this as: BMJ 2015;351:h6019

Re: Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis

Antidepressants are addictive and increase the risk of relapse

In their systematic review, Amick et al. write that reasons for preferring psychotherapy over drugs for depression include concerns about side effects and ‘perceived “addictiveness”’ of drugs (1). This addictiveness is not hypothetical, it is very real (2,3) and affects about half of those treated with antidepressants (3,4).

The authors do not discuss what might be their most important finding, that psychotherapy leads to fewer relapses than drug therapy, which was expected, as it is related to the drugs’ addictiveness. It is tricky that withdrawal symptoms and disease symptoms can be the same, but there are clear differences. Withdrawal-induced, depression-like symptoms usually come rather quickly and disappear within hours when the full dose is resumed, whereas it takes weeks before the patients get better if they have a true depression (3).

A large trial of patients with remitted depression illustrates this (5). After the patients had become well, they continued with open maintenance drug therapy for 4-24 months. They then suddenly had their therapy changed to a double-blind placebo for 5-8 days at a time that was unknown to the patients and clinicians. Forty of 122 patients (33 %) on sertraline or paroxetine had an increase in their Hamilton depression score of at least eight, which is a clinically relevant increase. This study illustrates why most doctors get it wrong when they think the disease has come back upon lowering or stopping the dose. In a group of 122 patients whose depression has been in remission for 4-24 months, likely only one or none would get a true relapse of the depression during 5-8 random days.

Antidepressants trap people into what often becomes life-long treatment. Of 260,322 persons in Finland who were on such a drug in 2008, 45 % were on an antidepressant drug five years later (3).

1 Amick HR, Gartlehner G, Gaynes BN, et al. Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis. BMJ 2015;351:h6019.

2 Nielsen M, Hansen EH, Gøtzsche PC. What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors. Addiction 2012;107:900–8.

3 Gøtzsche PC. Deadly psychiatry and organised denial. Copenhagen: People’s Press; 2015.

4 Kessing L, Hansen HV, Demyttenaere K, et al. Depressive and bipolar disorders: patients’ attitudes and beliefs towards depression and antidepressants. Psycho¬logical Medicine 2005;35:1205-13.

5 Rosenbaum JF, Fava M, Hoog SL, et al. Selective serotonin reuptake inhibi¬tor discontinuation syndrome: a randomised clincial trial. Biol Psychiatry 1998;44:77-87.

Competing interests: No competing interests

21 December 2015
Peter C Gøtzsche
Professor
Nordic Cochrane Centre
Rigshospitalet, Copenhagen