The highs and lows of the serotonin theory of depression

A British Medical Journal editorial on serotonin and depression, which made the claim that newer SSRI antidepressants are less effective than older tricyclic drugs, has been met with criticism from psychologists and psychiatrists. The article by Professor David Healy, which appeared in the BMJ, also said SSRIs had led to the marginalisation of cheaper and more effective treatments.

Professor Healy wrote that ‘In the 1990s, no academic could sell a message about lowered serotonin. There was no correlation between serotonin reuptake inhibiting potency and antidepressant efficacy. No one knew if SSRIs raised or lowered serotonin levels; they still don’t know. There was no evidence that treatment corrected anything.’

According to Healy, the lowered serotonin story ‘took root in the public domain rather than in psychopharmacology. This public serotonin was like Freud’s notion of libido – vague, amorphous, and incapable of exploration – a piece of biobabble.’ Healy suggested this ‘myth’ has been reinforced across the general public and in the complementary health market, where people are encouraged to eat foods which ‘boost’ the neurotransmitter.

Many academics commented on the editorial, including Professor Simon Wessely (President of the Royal College of Psychiatrists). He said that while it was unclear how antidepressants helped depression, it was established that such drugs – along with psychological treatments – were helpful in depression. He added: ‘Most important of all, the newer drugs (the SSRIs) are safer if taken in overdose than the older tricyclics. People should not change their current medication on the basis of this editorial alone.’

Dr Clare Stanford, Reader in Experimental Psychopharmacology, UCL, said: ‘Prof David Healy’s article treads a path that is well-worn but out of date. He argues that selective serotonin re-uptake inhibitors (SSRI) antidepressants are used because of a pervasive myth that they boost serotonin levels, but this is something of a straw man. He makes the mistake of assuming that antidepressants reverse a functional abnormality in the brain that causes depression. Actually, the theory that low ‘levels’ of serotonin in the brain (whatever that means, functionally) causes depression died many years ago, in spite of the fact that a deficit in the synthesis of serotonin in the brain can trigger relapse of depression in some patients who are in remission: a fact which he also fails to mention. By contrast, the monoamine theory of ‘anti-depression’ is alive and kicking. There is plenty of evidence that SSRIs increase communication from neurones that release serotonin, as well as other monoamine transmitters, and that the ensuing downstream changes, such as creation of new neurons (neurogenesis) or modification of gene expression, can ameliorate depression. In short, SSRIs probably switch-on anti-depression, rather than switch-off depression (which could explain the rapid efficacy of ketamine).’

Professor Trevor Robbins (University of Cambridge) told the British Psychological Society that a more objective view of the evidence would be that changes in serotonin function likely contribute to many symptoms of, and forms of, depression, but are obviously often not the primary causal factor. He continued: ‘SSRIs appear to help some, but not all depressed people, also their mechanisms of action are not completely understood but almost certainly do so via affecting serotonin function. It is naive to think of levels of serotonin as being the crucial element; the system works in a more complicated way which is gradually becoming better understood.’