Joanna Moncrieff is Professor of Critical and Social Psychiatry at University College London, a consultant psychiatrist for the NHS, and the author of the book, Chemically Imbalanced: The Making and Unmaking of the Serotonin Myth. Joanna explains how the widely accepted belief that depression is caused by a chemical imbalance or serotonin deficiency has little scientific evidence to support it and the concerning side effects of SSRIs that are typically prescribed.
Challenging the Serotonin Deficiency Theory of Depression
- The widely believed theory that depression is caused by a chemical imbalance or serotonin deficiency is not supported by evidence. It is a speculation or a theory with weak, inconsistent, and uncompelling evidence.
- The chemical imbalance theory was first constructed by psychiatrists and researchers in the 1960s to justify drug treatment for depression. However, it gained widespread popularity and became accepted as fact due to massive advertising campaigns by the pharmaceutical industry starting in the 1990s, when they began promoting their new range of SSRIs (selective serotonin reuptake inhibitors).
- A large project in the 1980s set up to test for differences in brain chemicals between people with and without depression came up with nothing, indicating the theory was not progressing.
- It is essential to discuss the lack of evidence because the principle upon which SSRIs are prescribed is built on sand, and these drugs have a ton of significant side effects. Many clinicians and the general public have been persuaded this theory is true.
Limited Efficacy of Antidepressants in Clinical Trials
- The justification for prescribing antidepressants, beyond the chemical imbalance theory, lies in clinical trials that show they perform "a little bit better than a placebo tablet".
- The measured difference between the antidepressant and the placebo in these trials is very small—a two-point difference on a common depression rating scale with a maximum score of 54 points.
- This difference is generally not large enough to register as a clinically significant difference when measuring people's function using other scales, such as the clinical global rating scale.
- The benefit observed in trials may not even be a pharmacological effect because the trials are often not fully double-blind. People can guess they are on the actual drug due to the side effects they experience.
- This leads to an amplified placebo effect for those taking the real drug and a potential negative placebo effect for those on the dummy pill. In one study, the effect of thinking one was taking the real drug (five or six points difference) was much bigger than the effect of actually getting the drug (two points difference).
- Most trials are conducted for 8 weeks or less, with very few lasting more than three months. This is remarkable given that the majority of people on SSRIs take them for much longer periods, often receiving repeat prescriptions for 18 months or more.
Significant Side Effects and Risks of SSRIs
- SSRIs are mind-altering drugs that change the normal state of brain chemistry and modify biology, leading to changes in thinking and feeling processes. They are not just incidental but are part of weighing up whether the drug is a good idea.
- Emotional Numbing/Blunting: A consistently reported effect is the suppression or restriction of the intensity of emotions, making people feel they cannot feel happy, cannot cry, and sometimes feel "nothing anymore". This state is often found to be unpleasant after the initial crisis has passed.
- Sexual Dysfunction: This is a very common side effect, affecting 60% or more of people taking SSRIs. SSRIs cause sexual dysfunction on top of any reduced libido caused by depression. A specific effect is the anesthesia of the genitals, dialing down sensitivity.
- Persistent Sexual Dysfunction: Most worryingly, emotional numbness and sexual dysfunction can persist after people stop taking the drug, potentially going on for years. This post-withdrawal sexual dysfunction is seen as a catastrophe by those affected.
- Increased Risk of Suicidal Ideation: Though documented as a rare side effect, there is an increased risk of suicidal ideation, particularly in young people, which seems counterintuitive for a drug prescribed for low mood.
- Dependence and Withdrawal: SSRIs can lead to physical adaptations and withdrawal effects when stopped, similar to alcohol, caffeine, or opiates. Withdrawal symptoms (e.g., anxiety, irritability, emotional changeability, and tearfulness) can be misinterpreted as a relapse into depression, leading doctors to recommend going back on the drug or increasing the dose.
- Other Side Effects: These can include lethargy, brain fog, feeling worse in the long run, and personality changes. Higher serotonin activity (which SSRIs temporarily increase) is involved in impairing sexual functioning.
The Subjective Nature of Depression Diagnosis
- The diagnosis of depression is very subjective and is not based on objective measures like a blood test.
- Official criteria for diagnosis include having a low mood for at least two weeks, but this two-week cutoff is arbitrary and "completely made up" by psychiatrists.
- The way doctors ask questions (e.g., "Have you had a low mood?") is prone to inherent bias, as the interpretation of these terms varies between individuals and cultures.
- The patient's presentation, such as being expressive or tearful, or the language they use (explicitly saying they are depressed), can influence their score on depression rating scales and the severity of the diagnosis.
Marketing, Medicalization, and Societal Impact
- The high prevalence of SSRI use (about 17% of the UK adult population, and 23% of women) is driven by the power of marketing and the confluence of interests.
- Pharmaceutical companies actively influenced doctors through advertising, providing lunches, and subsidizing lavish conferences, which embedded the message of the chemical imbalance theory within the medical profession.
- In the early 1990s, most people thought depression was a meaningful reaction to life circumstances (e.g., divorce, loneliness, unemployment, or abuse) and were wary of drugs that might numb feelings or cause dependence. The pharmaceutical industry, sometimes with the help of medical institutions (like the Royal College of Psychiatrists), actively set out to change this intuitive view to frame depression as a medical condition requiring medication.
- The mass medical treatment of depression is not proven to be working; long-term outcomes for people with depression who received medical treatment are no better than those who did not, and the number of people on disability benefits for depression and anxiety has risen dramatically since the 1990s, mirroring the increased use of antidepressants.
- Medicalization of emotion can be negative because it ceases to see the individual and their unique problems, instead treating a "label". Furthermore, giving a pill in this situation can be seen as giving false hope.
- Cultural Viewpoints: Many non-Western cultures (e.g., traditional Indian medicine or the Hatsa tribe) naturally view low mood as a signal that something needs to be addressed in the person's life, rather than a medical diagnosis.
Pathways to Recovery and Doctor Responsibility
- Reframing Emotion as a Signal: It is helpful to view low mood as a signal that the body and mind are reacting to stress or circumstances, prompting necessary lifestyle changes (e.g., better sleep, relaxation, changes in work).
- For struggling individuals, advice includes working out what the mood is signaling, making necessary life changes, seeking psychotherapy (like NHS talking therapist services), and prioritizing physical health, exercise, and mindfulness. If they choose to take antidepressants, they should aim for the shortest time possible.
- The majority of people with depression will improve naturally anyway, and coming to the doctor can be a "wakeup call" that galvanizes action and support from friends and family, contributing to improvement.
- When considering treatment, doctors should guide patients toward alternatives listed in guidelines (like NICE), including exercise, mindfulness, problem-solving therapy, and CBT. The four pillars of health (food, movement, sleep, and relaxation) are also suggested as having a profound impact on well-being.
- Withdrawal Management: Patients currently on SSRIs should never stop suddenly, as this can worsen withdrawal symptoms and prolong them. Reduction must be slow and careful, especially at the lowest doses (due to the hyperbolic relationship between drug dose and effect). Resources like the Royal College of Psychiatrists' advice on stopping antidepressants and the Maudsley deprescribing guidelines are available.