The antidepressant Prozac and related drugs are no better than placebo in treating all but the most severely depressed patients, according to a damaging assessment of the latest generation of antidepressants.

SSRIs, or selective serotonin reuptake inhibitors, were supposed to revolutionise care of depression – by treating symptoms without the side effects of older drugs, such as tricyclics.

But despite selling in vast quantities, a new meta-analysis of these drugs, from data presented to the US Food and Drug Administration (FDA), appears to suggest that for most patients they do not work. A previous study had indicated that the benefits of antidepressants might be exaggerated.

UK and US researchers led by Irving Kirsch of Hull University, UK, studied all clinical trials submitted to the FDA for the licensing of the four SSRIs: fluoxetine (Prozac), venlafaxine, nefazodone, and paroxetine (Seroxat or Paxil), for which full datasets were available.


They conclude that, “compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression”.

Dishing out drugs

They did detect some benefits in the most severely depressed patients. But conclude that in this group the small effect is “due to decreased responsiveness to placebo, rather than increased responsiveness to medication”.

Given these results, they say that there is little reason to prescribe SSRI medications to any but the most severely depressed patients.

David Healy, a psychiatrist at Cardiff University, UK, specialising in the use of SSRI drugs, says the latest study confirms suspicions that the drugs’ effectiveness had been dramatically overstated.

“Most importantly this new study shows that the people who did respond to the drugs would have responded to placebo, anyway.

“It confirms that GPs should not be dishing these drugs out as first-line treatment for mild depression,” he told New Scientist. The drugs were, he notes, “routinely being given to people who would get better without them”.

Positive results

Eli Lilly, which manufactures Prozac, says that “extensive scientific and medical experience has demonstrated it is an effective antidepressant”. It adds that: “More than 50 million people with depression have been treated with Prozac since its launch.”

A spokesman for GlaxoSmithKline, which makes Seroxat, points out that the study only looked at a “small subset of the total data available”.

Healy notes however, that drug companies have tended to publish studies showing positive results of the SSRIs in mildly depressed patients.

He says too that there have been concerns that SSRI drugs, particularly paroxetine, may cause dependence in some patients, and this underlines the need to avoid their unnecessary prescription.

Placebo benefit

Healy warns however, that anyone taking SSRI antidepressants should not suddenly stop taking their medication and should consult their doctor before coming off the drugs.

David Nutt, a psychopharmacologist at Bristol University, UK, points out that if SSRIs provided some sort of placebo benefit, this should not be discounted. He notes that “the true drug effect is that of the drug added to that of placebo which is not the same as no treatment”.

Earlier this month, New Scientist reported claims by US lawyers that they had obtained documents suggesting that an inappropriate analysis of clinical trial data by researchers at GlaxoSmithKline had obscured suicide risks associated with paroxetine for 15 years.

Journal reference: PLoS Medicine (February 2008)

Mental Health – discover the latest research in our continuously updated special report.