It's rare for a journal article to trigger the intensity of debate as that provoked by psychologist Professor Irving Kirsch's meta-analysis, published earlier this year, which purported to show that for the majority of patients with depression, anti-depressant medication is clinically no more effective than placebo.

For the 36th Maudsley debate, held at the Institute of Psychiatry, Kirsch, with psychiatrist Dr Joannah Moncrief in support, defended the conclusions of his research findings. Arguing against Kirsch and Moncrief's motion - that anti-depressants are no more effective than placebo - were psychiatrist and expert on the psychopharmacology of depression Professor Guy Goodwin and biology Professor Lewis Wolpert, who has written a book about his own experience of depression.

Kirsch's meta-analysis used the freedom of information act in America to access all drug trial data, published and unpublished, submitted to the Food and Drug Administration by pharmacological companies seeking approval for their anti-depressants. Taking all the trials together showed that while drugs are statistically more efficacious than placebo, their advantage, for all but the most extremely ill patients, is not clinically significant (using the National Institute of Health and Clinical Excellence threshold of a three point score difference on the Hamilton Depression Rating Scale).

Commentators have criticised the quality of these trials, Kirsch explained, but they are all the evidence we have for the efficacy of anti-depressants. Either you trust these randomly controlled trials, which show drugs are rarely more effective than placebo, or you reject the validity of these trials, in which case we are still left with zero scientific evidence for the effectiveness of anti-depressant drugs.

Next up, Guy Goodwin took issue with the idea that it is easy for drugs to do well in the kind of clinical trials described by Kirsch. Merck, for example, invested heavily in Aprepitant as a possible anti-depressant only to find over several trials that it was no more effective, statistically and clinically, than placebo, whereas the same trials found the established anti-depressant Paroxetine was more effective. 'These trials have real consequences, they aren't just intellectual games,' he said. 'The idea that you just have to do a study, chuck in anything and you'll get a response is not a myth that you must carry away from this lecture.'

Goodwin said some of the strongest evidence for anti-depressant drug efficacy comes from so-called continuation trials. For example, one study looked at patients who had responded positively to the drug Agomelatine, switching half the sample onto placebo after eight or ten weeks, but ensuring the patients were unaware of whether they had been switched or not. Twelve weeks after the switch, 21 per cent of the patients still on Agomelatine had relapsed compared with 47 per cent of the patients switched to placebo.

None of this persuaded Joannah Moncrief, who argued the idea that we have truly 'anti-depressant' drugs is a myth. What we traditionally think of as anti-depressants are merely psychoactive drugs, with a variety of non-specific effects, including sedation and stimulation. Any such drugs are likely to have an impact in placebo-controlled trials, she said, but they aren't actually treating the disease process. They cut people off from their emotions, they overlay the depression rather than replacing it. Perhaps the most compelling evidence for the ineffectiveness of anti-depressants, she argued, comes from the fact that levels of depression are not decreasing, as you would expect them to if we had an effective drug treatment.

'The last speaker has clearly never suffered from depression herself,' Lewis Wolpert began in characteristically pugnacious fashion. 'When you enter into a depressed state, it's unlike anything ever experienced before.' Wolpert emphasised the biological basis of depression: it's inherited; post-mortem studies show brain abnormalities in the depressed; and treatment with interferon alpha for hepatitis triggers depression, unless the patient is also prescribed an anti-depressant. Also, macaque monkeys and mice with induced depression-like states benefit from anti-depressants, in a way that can't be dismissed as placebo.

Wolpert also drew on his own personal experiences. He had switched anti-depressants several times before finding an effective drug, a fact he felt cast doubt on the idea he was only responding to a placebo effect. 'This article of yours has done enormous damage to people with depression,' Wolpert said, addressing Kirsch. 'Such people rarely want medical help as it is. Please vote against this absurd motion,' he asked the audience.

In the minute they were given to round-up their cases, the speakers moved no closer to a consensus. Kirsch pointed to research showing that serotonin depletion in healthy people fails to trigger depression, thus undermining the popular idea that drugs work by correcting such an imbalance. Goodwin said Moncrief reminded him of famed anti-psychiatrist Thomas Szasz, but without the conviction to go all the way. Moncrief simply re-stated her belief that all placebo-controlled trials are invalid because they fail to take account of the psychoactive effects of the drugs. Wolpert agreed good new clinical trials were needed, but he maintained that the efficacy of drugs for severe depression was clearly established. 'If you're taking an anti-depressant, for goodness sake, don't stop now!' he said.