Image used from BBC website
BBC’s Panorama programme covered the use of SSRIs (Selective Serotonin Reuptake Inhibitors), a category of anti-depressants, in the treatment of depression.
Using a mix of patient stories and interviews with high-powered researchers and psychiatrists, the lack of evidence for SSRIs, the side effects and the risk of withdrawal symptoms were exposed. The final section of the programme showed the lack of evidence for the effectiveness of antidepressants (including SSRIs) more generally, by suppressing negative studies.
Serotonin is a neurotransmitter which is targeted by SSRIs. It works in the brain and influences mood, sleep, appetite and sex drive. This neurotransmitter is also found elsewhere in the body where it is involved in digestion, wound healing and blood clotting.
Examples of SSRIs include fluoxetine (Prozac); citalopram (Cipramil), sertraline (Zoloft) etc..
Lack of Evidence for SSRIs
SSRIs came to prominence in the 80s/90s on the back of the “chemical imbalance theory” and that depression was caused by low levels of serotonin in the brain. Panorama obtained an internal document from Pfizer from the 1980s. This showed that Pfizer was made aware it could not claim that there was evidence of chemical imbalance in marketing material for Sertraline, one of the most widely used antidepressants. Which demonstrated that there was only, at best, limited evidence for the chemical imbalance theory, which has underpinned the prevalence of SSRIs ever since.
Recent studies have backed this up, with Prof Joanna Moncrieff being interviewed about her research, released in 2022. Revealing that there was still, 40 years later, limited evidence for lowered serotonin and the chemical imbalance theory. Despite this, it is still referenced, according to Panorama, on 50% of antidepressant patient information leaflets. It is still also commonly referred to by GPs and psychiatrists.
Prof David Healy commenting on SSRIs said “Everybody thinks, because it is an antidepressant, that it is doing something to our brain, but in actual fact, it is much more likely to be doing something to our body”.
Prof Tony Kendrick of Southampton University said “There isn’t that much evidence for the deficiency of serotonin…. We don’t understand exactly how these drugs work…. In terms of what serotonin does to us, it is extraordinary, we understand so little.”
Panorama then dealt with one particular side effect, Post SSRI Sexual Dysfunction (PSSD), in detail. Side effects of SSRIs (and other antidepressants) are relatively common and can include weight gain, agitation, nausea, blurred vision, as well as sexual side effects.
Sexual side effects of antidepressants are common (lower libido, erectile dysfunction, impotence) with a third of patients experiencing these. However, PSSD is the failure of sexual function to return after stopping taking SSRIs. Multiple patients were interviewed who had experienced long-term “genital numbing” or “chemical castration”. While highlighting the plight of these sufferers, sadly there does not seem to be much that medicine or psychiatry can offer these patients. Although research is underway in this area. The risk of PSSD has not been quantified yet given that antidepressants are so commonly prescribed, the number of people suffering is likely to be large. There is now a risk warning in SSRI packaging.
A section of the programme about withdrawal symptoms was particularly powerful. Two contributors to this section were in very strong positions to describe their lived experiences and talked about the lesser-known aspect of SSRIs: it can be hard to stop taking them.
Dr Mark Horowitz, a trainee psychiatrist and researcher, experienced withdrawal symptoms himself as he stopped taking SSRIs. This surprised him given the training he had completed during his PhD on antidepressants. He advised: “If I had no understanding then the public surely had even less”.
Another contributor, Prof David Taylor Chief Pharmacist at the Maudsley Hospital, also had experienced withdrawal symptoms and was even better placed to comment on the current understanding of SSRIs. As a contributing author to The Maudsley Prescribing Guidelines in Psychiatry; the bible for psychiatrists on deciding on which drugs to prescribe for various conditions. He recalled his own experience of coming off SSRIs: “It was really quite an unpleasant experience and that is probably an understatement. I was quite shocked by it”.
Symptoms of SSRI withdrawal are similar to those of depression and/or anxiety. As a result, many people experiencing withdrawal symptoms are re-prescribed SSRIs, as it is believed they are relapsing. In order to stop taking SSRIs while reducing symptoms, very gradual tapering is often required in order to minimise the risk.
The programme’s final segment covered the poor efficacy of antidepressants, drawing on the research of Eric Turner, a former FDA Clinical Reviewer. His study revealed what proportion of clinical trials run by pharmaceutical companies are suppressed. Two trials are needed to show outperformance against a placebo. This is widely achieved by suppressing the negative trials and only publishing the positive ones.
Driving home the point in the interview with Prof Andrea Cipriani of Oxford. who reviewed a vast amount of research into the effectiveness of antidepressants. Published in 2018, this study concluded that antidepressants are only 15% more effective than a placebo. This needs to be caveated as the result disguises the fact that: “Some people don’t respond at all and other people respond a lot to the medication. This is why we need to get rid of the one size fits all approach”.
Bringing the programme to a close, Prof Kendrick shared the latest guidance to trainee doctors: “We now teach students and trainees to hold off on prescribing antidepressants if possible. For mild depression, most people get better whatever they do over a few months. So it can hold off, you don’t start people on antidepressants, then they are not going to get problems further down the line trying to come off them.”
Important advice from the panorama programme
- Review your medication with your doctor every 6 months
- Don’t come off your antidepressants without advice from your doctor
- If you experience withdrawal symptoms, share the Royal College of Psychiatrists guidance with your doctor: Stopping Antidepressants
Some shocking stats from the programme
- 23% of women are now taking antidepressants
- More than 8m people are on antidepressants, including SSRIs
- A third of patients on antidepressants experience sexual side effects
- More than 2m people have been taking antidepressants for over 5 years
- The number of antidepressant prescriptions has doubled in a decade
- In 2021, 101.9 prescriptions for antidepressants were issued
- 1 in 7 people take antidepressants
Smart TMS Commentary
Panorama’s powerful programme helped to illuminate the problems that an over-reliance on pharmaceutical treatments has caused for psychiatry. The benefits of antidepressants are undoubted but the side effects can be devastating for a minority.
As Prof David Taylor commented, referring to the introduction of SSRIs after the problems with addictive benzodiazepines: “In the mental health sphere, we are quite good at making the same mistake more than once and I suspect that people felt that we wouldn’t let that happen again. We wouldn’t allow an introduction of a group of drugs which seemed to work really well but then later find that it was difficult for people to stop them”. It is to be hoped that the apparent rush to ketamine, psilocybin and other psychedelics is not another mistake in the making!
More effective treatments, preferably non-pharmaceutical, with minimal side effects, are needed. Transcranial Magnetic Stimulation (TMS) is one such. It is much more effective than placebo (and antidepressants) and has very few side effects, none of which are serious or irreversible. You can find out more about TMS treatment, here.
Smart TMS CEO.