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Antidepressants ~ chemical intervention or placebo?

The chemical imbalance theory of depression came about by accident; a serendipitous discovery in the search for drugs to treat completely different disorders. How reliable is this theory of depression, and is this really what antidepressant medications are affecting?

The accidental birth of a billion dollar industry

In 1952, scientists isolated a drug called reserpine from the dried Indian snakeroot plant (which had been used for centuries in India for the treatment of fever and snakebites). It was found to reduce levels of the monoamines in the body (serotonin, dopamine and noradrenalin) and to be pretty good at controlling high blood pressure – the only problem was that it had a tendency to make people sad.

In the same year, researchers noted that a drug given to patients for TB increased the levels of monoamines in the body and made people “inappropriately happy”.

Following this, a hypothesis was formed that depression is therefore due to decreased levels of neural monoamines; particularly serotonin. In the 60 years that followed, the idea that a chemical imbalance causes depression has been repeated like a mantra by public health authorities and become ingrained in popular culture. Pharmaceutical corporations have spent billions of dollars on researching, marketing and advertising medications that promise to cure depression by increasing neural serotonin: but are they selling us a false narrative?

Post hoc, ergo propter hoc: After it, therefore because of it

The immediate and glaring problem with the assumption underlying the development of antidepressants is that of logic: it operates on ex juvantibus reasoning (whereby an inference is made about disease causation from an observed response of the disease to a treatment): just as headaches are not caused by a lack of aspirin, the efficacy of serotonergic drugs is not in itself proof that depression is caused by a lack of serotonin.

The insidious jump was made from an association with increased positive mood, to an inference of causation of increased positive mood. These two relations are in no way the same: we cannot infer causation from correlation.

More to medication than chemicals

The chemical content of antidepressants is not their only potentially relevant variable, for they are also in themselves placebos: many people are prescribed them under the promise that they will improve their symptoms: prescribing physicians say so, the media says so, pop psychology says so… Is simply believing you are taking something which will make you happier enough to make you happier? Is this what pharmaceutical companies are actually selling us?

Kirsch et al (2002) suggest that this may be the case. They found, through analysis of all antidepressant clinical trials submitted to the FDA for approval, that the antidepressant response was matched by 80% of the placebos used. Similarly, Turner et al (2008) reviewed all published literature concerning 12 antidepressants from 1987 to 2004 and showed a 94% success rate, but in the withheld literature there was below 50% success.

Combined, all studies showed 51% efficacy; only 1% above chance, and only 2 points above placebo. There seems to be a publishing bias in which the studies that conform to the predictions of the chemical imbalance theory are most likely to be published: but what we see in journals may not be the full story.

So, the fact that ‘traditional’ antidepressants act to increase levels of serotonin in the brain may just be an accidental property, epiphenomenal to their placebo function. This is supported by several other findings:

  • The latency of their chemical effects to be translated into increased positive mood (average 6 weeks): surely if depression was due to not having enough neural serotonin, we would all be happier as soon as we took an antidepressant pill, as they increase serotonin levels within minutes.
  • They are not universally effective: if a chemical imbalance was the true proximal cause of depression, we would expect antidepressant efficacy to be higher than chance, which it doesn’t seem to be.
  • Spontaneous remission (improvement of a condition without intervention) occurs in many diseases, including depression: how do we know that any improvements we see after antidepressant administration aren’t a result of this?
  • Tianeptine, which actually reduces available neural serotonin, is clinically efficacious in the treatment of depression, with few side-effects (even alleviating comorbid anxiety without sedation). Based on the pharmaceutical industry’s story about depression, this drug should actually accentuate depressive symptoms.
  • St. John’s Wort, a herbal intervention, has performed as well as or even better than antidepressants in randomised controlled studies.
  • CBT: Butler et al (2006) summarised recent meta-analysis literature, demonstrating that CBT efficacy is moderately superior to that of antidepressants for the treatment of depression. Dimidjian (2006) further found that the behavioural activation component of CBT alone is as effective as antidepressant medication. CBT and antidepressants are associated with similar rates of recovery, but evidence suggests that CBT has far fewer cases of relapse.
  • Group therapy: Leff (2000) found that, for people with depression living with a ‘critical partner’, couples therapy is ‘more acceptable’ than antidepressant drugs and is at least as efficacious if not more so, both in treatment and maintenance phases, and is no more expensive overall.
  • Mindfulness: Kuyken et al (2008) found mindfulness to be as effective as antidepressants in preventing relapse of depression, and more effective in improving quality of life. It was also proved to be as cost-effective in helping to stay well in the long term.

Taken together, this evidence seems to suggest that, not only are antidepressants not as effective as the pharmaceutical industry would have us believe, but they may even be less effective than non-pharmaceutical interventions. Their chemical content may be secondary to the placebo effects of the industry constructed around them, which tells us that taking certain pills will make us happier. Perhaps that’s all we ever needed to hear.

The House Partnership, 3rd April 2016


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