The research undermines the basis for prescribing SSRI antidepressants. Other research faults the psychiatric profession for promoting the unproven theory.

A comprehensive new study has found no scientific evidence to support the theory that depression is due to a chemical imbalance in the brain.  Some 45 million Americans taking antidepressants on the basis of this debunked notion are now in a position to question their physician or other prescriber about taking the drugs and, if they decide to stop taking them, to ask for help in slowly tapering off the drugs because of the substantial risk of withdrawal symptoms.

The theory of a chemical imbalance, particularly a low level of serotonin, causing depression, while never proven, has been widely promoted since the late 1980s in drug advertising by pharmaceutical companies marketing selective serotonin reuptake inhibitor (SSRI) antidepressants.  The result is today’s $15.6 billion in annual global sales of antidepressants.

Given that the rationale for prescribing SSRI antidepressants is to correct a chemical imbalance in the brain, a team of researchers from the U.K., Spain and Switzerland, led by Joanna Moncrieff, a psychiatrist and professor at University College London, looked for proof of that imbalance.  The researchers conducted a comprehensive review, which for the first time integrated all relevant research, to evaluate whether scientific evidence supported the serotonin theory of depression.    

Their conclusion, published in Molecular Psychiatry: “Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity.”

“The serotonin theory of depression has been one of the most influential and extensively researched biological theories of the origins of depression,” the researchers wrote.  “Our study shows that this view is not supported by scientific evidence.  It also calls into question the basis for the use of antidepressants.”

The researchers expressed concern that the general public’s acceptance of the chemical imbalance theory of depression has had the adverse effect of causing depressed individuals to believe they have less control over their moods, leading them “to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood.”

“Our study shows that [the serotonin theory of depression] is not supported by scientific evidence.  It also calls into question the basis for the use of antidepressants.”
– Joanna Moncrieff, psychiatrist and professor at University College London

Being told depression is caused by a chemical imbalance in the brain may lead people to feel that taking an antidepressant to correct a serotonin deficit is a health requirement, similar to a diabetic’s need for insulin.  The researchers noted: “The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue antidepressant medication and may discourage people from discontinuing treatment, potentially leading to lifelong dependence on these drugs.”

In an interview with the Daily Mail, Moncrieff said, “The popularity of the ‘chemical imbalance’ theory has coincided with a huge increase in the use of antidepressants.  Thousands suffer from side effects of antidepressants, including severe withdrawal effects that can occur when people try to stop them, yet prescription rates continue to rise.”

“We can safely say that after a vast amount of research conducted over several decades, there is no convincing evidence that depression is caused by serotonin abnormalities,” she added.

This conclusion confirms what the Citizens Commission on Human Rights (CCHR) has been warning since the late 1980s: the theory of a chemical imbalance of the brain has no basis in science.  Psychiatrists and other health care providers prescribing antidepressants have ignored this inconvenient truth.

In crediting CCHR for its role as a mental health watchdog in exposing the lack of science in the chemical imbalance theory, the European Times wrote: “And so, this is the very uncomfortable moment for all those who ignored it or attempted to ridicule the warnings, in which the mental health watchdog that has been warning on the issue for at least 33 years could tell them ‘I told you so.’”

The psychiatric profession bears responsibility for promoting the chemical imbalance theory

Psychiatrists and other prescribers have dispensed antidepressants for decades without any proof of a chemical imbalance in the brain.  As this unproven assertion has been increasingly questioned amid the lack of evidence to support it, leading psychiatrists have claimed that the serotonin theory of depression was never taken seriously by the psychiatric profession.

This claim was investigated in an earlier study in which Moncrieff participated.  Researchers in the psychiatry department of University College London examined the coverage of the serotonin theory of depression in a sample of highly cited and influential academic literature starting in 1990, when the serotonin theory was first popularized.  They found that the theory of a chemical imbalance causing depression was, in fact, endorsed by the professional and academic community and to claim it was not “is patently false.”

“On the contrary, from our research it is clear that during the period 1990-2010 there was considerable coverage of and support for the serotonin hypothesis of depression in the psychiatric and psychopharmacological literature,” the researchers wrote, publishing their findings earlier this year in SSM – Mental Health.

“The analysis suggests that, despite protestations to the contrary, the profession bears some responsibility for the propagation of a theory that has little empirical support and the mass antidepressant prescribing it has inspired.” 

Those who want to stop taking antidepressants should do so only under a doctor’s supervision because of the risk of serious withdrawal symptoms, but doctors still have no clear guidance for how to taper patients off the drugs.

In a recent assessment of clinical practice guidelines on tapering and discontinuing antidepressants issued by the national health authorities and major national or international professional organizations in the U.S., U.K., Canada, Australia, Singapore, Ireland and New Zealand, researchers found that none provided guidance on dose reductions, how to distinguish withdrawal symptoms from relapse or how to manage withdrawal symptoms.  The researchers called for further research to determine more effective guidelines for reducing the risk, severity and duration of antidepressant withdrawal symptoms.

That research followed a study of the incidence, severity and duration of antidepressant withdrawal effects that concluded more than 56% of people who attempt to come off antidepressants experience withdrawal symptoms, with nearly half (46%) of them rating those symptoms as “severe.”

The Citizens Commission on Human Rights continues to raise public awareness of the lack of scientific proof of the chemical imbalance theory and the known harms of antidepressants and other psychiatric drugs, so that consumers and their physicians can make fully informed decisions about starting and stopping the drugs.

CCHR also recommends a complete physical examination with lab tests and nutritional and allergy screenings to identify any underlying physical causes of depression or other unwanted mental and emotional symptoms. 

WARNING: Anyone wishing to discontinue or change the dose of an antidepressant or other behavioral drug is cautioned to do so only under the supervision of a physician because of potentially dangerous withdrawal symptoms.