What doctors think about antidepressants and the ‘serotonin theory’

Filip Vukasin

29/07/2022 4:14:56 PM

Two GPs and two psychiatrists provide reactions from the mental health coalface to a new systematic umbrella review that questions the role ‘chemical imbalance’ plays in depression.

Woman taking pill
Experts are concerned a recent study could cause doctors and patients to question SSRIs unnecessarily.

Last week, psychiatrists published a piece in the aftermath of their study, questioning the role of a ‘chemical imbalance’ in depression and concluding that ‘it is impossible to say that taking SSRIs [selective serotonin reuptake inhibitors] is worthwhile, or even completely safe’.
newsGP spoke to four clinicians who work in this space daily to gather their thoughts on a chemical role for depression and their reactions to the study:

  • Dr Nicholas Burgess, a psychiatrist who works exclusively in the public sector in the areas of consultation-liaison, neuropsychiatry and suicide prevention
  • Dr Jacqueline Rakov, a specialist clinical and forensic psychiatrist who has worked extensively in the court and correctional systems, and also works privately
  • Dr Jelena Radosavljevic, a GP and palliative care physician who runs a large inner-city practice with special interests in mental health, particularly relating to women
  • Dr Cathy Andronis, a GP with special interest in mental health and psychological therapy, who is the current Chair of RACGP Specific Interests Psychological Medicine
Biopsychosocial model
The monoamine theory refers to depression caused by an imbalance of neurotransmitters, such as serotonin, dopamine and norepinephrine.
The article in question challenged this theory and in doing so, produced a large mainstream media reaction, including within the medical community.
However, among the experts we spoke to there was some confusion at the attention it has generated.
‘This is not particularly new news,’ Dr Burgess told newsGP.
‘I would challenge you to find a single GP or psychiatrist worth their salt who subscribes to the concept that the experience of symptoms of depression are caused essentially by a lack of, or disturbance to monoaminergic tone.’
Dr Rakov formed a similar view, telling newsGP that she does not think the paper is ‘the scientific bombshell that people think or fear it is’.
‘We know that antidepressants are helpful for many people. We have extensive research that shows, compared to placebo, these medications work to help,’ she said.
‘However, unlike our physical medicine colleagues, we lack biochemical testing to support the presence of disease.’
There was a trend to contextualise depression as a chemical imbalance in the late 20th century, which has continually been researched and re-evaluated within the psychiatric community.
Some considered it a way of destigmatising depression; however, it may have led to oversimplification.
‘The fact that, according to the review, over 80% of the general population believe depression is caused by a “chemical imbalance” is a scourge on our profession, [with] primary care and untrained public figures either promulgating the idea or doing nothing to dispel it,’ Dr Rakov said.
‘Why the simple theory has persisted is interesting to consider – there may be comfort in having an external explanation for one’s malady.’
She believes barriers to psychotherapy, such as access and costs, could be one reason why antidepressants are so widely used.
‘A huge drawback in accessing effective treatment for depression is the unavailability of psychologists and psychiatrists to provide good psychotherapy,’ Dr Rakov said.
‘Waitlists are heaving, books are closed and psychotherapy takes time.
‘Psychotherapy can and should, in my view, be confronting and won’t have you feeling great instantly, making it unfortunately, a less attractive option.’
Another issue is the time pressure and workload faced by GPs, who are at the coalface of treating the public, particularly when accessing psychiatrists and psychologists is troublesome.
‘The medicine we practiced over the last 20 years could have contributed to the increased use of SSRIs and some patients wanting “something quick”,’ Dr Radosavljevic told newsGP.
‘High turnover of patients and a pressure on doctors to see more patients may have something to do with it.’
All the clinicians newsGP spoke to agreed there is a role for SSRIs in treating depression, but not at the expense of other modalities.
Dr Burgess said depression should be considered as a symptom or experience that can arise from a number of causes, being influenced multi-directionally by environmental, social, psychological and biological factors.
Meanwhile, Dr Rakov describes depression as heterogenous, pointing out that it needs to be treated as such.
‘We know that even SSRIs – which are just one class of antidepressant – have mechanisms far beyond serotonin,’ she said.
‘The neurobiological field of psychiatry has been moving away from this theory for some time, with a landmark study being published and leaning towards a brain-derived neurotrophic factor-based model.’
In Dr Andronis’ experience, SSRIs can reduce anxiety symptoms and therefore mental distress quite generally, but they don’t ‘fix specific problems’ that are usually related to situational and/or concurrent life events.
‘We know that acting on and improving your life circumstances is more beneficial and resilience building, compared with relying on tolerating distress better as a medication effect,’ she told newsGP.
‘Self confidence and self-esteem improve with action whereas dependence on medications can foster passivity.’
Criticisms and concerns
The clinicians newsGP spoke to also had some concerns with the article.
‘I think the paper only … [confuses] the public about what depression is and is not,’ Dr Rakov said.
‘It is no surprise that there is a chasm between what health professionals know and the view the public holds, as these exist everywhere in medicine.
‘I don’t think the average person could, nor should have to, explain the mechanism of action of general anaesthetic, antihypertensives, or even coffee.’
Dr Radosavljevic believes the article could cause both doctors and patients to question SSRIs, thereby undermining them.
‘We already have clusters of patients that don’t want “chemical treatment” who may or may not believe in psychotherapy,’ she said.
Dr Burgess also reflected that the piece runs the risk of conflating the issue of the causative underpinnings of depression with the effectiveness of treatment.
‘I am particularly concerned with the implications of statements such as “we conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe”.’
‘I am not the first to point out that symptomatic relief does not necessarily come from a restoration of normal physiological homeostasis.’
Dr Burgess recalled an analogy when discussing the psychopharmacology of antidepressants.
‘We accept that the symptoms of a headache are reduced by taking ibuprofen, but not that the headache is caused by a lack of ibuprofen,’ he said.
‘I would view antidepressants similarly – that they can be helpful in treating the symptoms of depression, even if their absence is not the causative problem.’
Like all medications, SSRIs come with risks and this study gives an opportunity to discuss and reflect on them.
‘Many patients describe the effect of the SSRI as an “emotional numbing” and this reduced range of emotional expression may therefore be experienced as less distress or less worry about problems,’ Dr Andronis said.
‘While this reduced emotional reactivity is welcome for some people, for others it can feel like blunting or dulling of emotions and can paradoxically result in reduced interest or creativity in making lifestyle changes and this is a problem if beneficial habit changes are not made.’
Another issue is overprescribing. More than three million Australian adults take antidepressants daily, making Australia the second highest consumer of antidepressants of all OECD countries.
‘We know far too many are prescribed SSRIs and other antidepressants – nearly 15% of Australians are taking one,’ Dr Rakov said.
She also has concerns about the rates of psychopharmacological prescribing in young people.
‘[They] are an especially over-prescribed group, with service providers or families failing to recognise the child doesn’t exist as an island but rather part of a complex sociofamilial unit that all needs “fixing”,’ she said.
‘The message this sends to young people is especially harmful – something is “wrong” with them.’
Another issue can be weaning and ceasing SSRIs.
‘Many of my patients have been on SSRIs for a long time and sometimes getting them off is a problem,’ Dr Radosavljevic said.
Holistic care
All four doctors agree that depression is a complex condition that requires nuance and multinodal treatment, as opposed to expecting SSRIs to be the single saviour.
‘Whilst antidepressants can and do play an important role in the treatment of depression, they are not silver bullets – they do not change reality,’ Dr Burgess said.
‘Medication cannot replace key determinants of psychological wellbeing such as good physical health, social connectedness, safety from violence and trauma, and security from poverty.
‘A thorough consideration of the patient and their context should always be key in our approach to the formulation and treatment of symptoms of depression.’
Dr Andronis concurs.
‘The most important message for GPs from this finding regarding serotonin is that we should be discussing this uncertainty with our patients and outlining the risks and benefits of SSRIs,’ she said.
‘[In doing so] we empower them to decide how they wish to manage their anxiety and depression, holistically and collaboratively.’
This approach is supported by Dr Rakov.
‘The way I describe depression to patients is as spokes on a wheel. If one is missing, the wheel clunks along ineffectively,’ she said.
‘The spokes include factors like psychotherapy, sleep, nutrition, movement, personal/professional connectedness, as well as medication.
‘We absolutely cannot afford to stigmatise treatment of depression with medication. For some people it is lifesaving.
‘But we should be judicious about their use, too, as they are not without harm. We should focus our efforts on the heterogenous disease that is depression and not become overly zealous about one mere hypothesis.’
Dr Radosavljevic also considers this study a welcome catalyst for better guidelines and support for GPs treating depression, as she finds citing evidence helps in discussions with patients, particularly those that are reticent to treatments.
‘Medicine is an art, but we need better guidelines and support, particularly when controversial science can complicate our frontline battle,’ she said.
‘This article may be a good trigger.’
And with mental health continuing to be the number reason why people present to their GP, many continue to upskill in psychotherapy, such as through online training offered by the RACGP.
‘A number of GPs are honing their skills formally in both lifestyle medicine and psychotherapies which is really wonderful given depression is one of the world’s leading disease burdens,’ Dr Rakov said.
This new study adds to an ongoing, long-term conversation about the role of SSRIs in treating depression.
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Dr Rama Krishnan   30/07/2022 9:27:51 AM

So, we really don’t know the cause of depression. Experience by GPS with relation to SSRIs are essentially anecdotal. Probably SSRI are MOSTLY doing the job of placebos. There are studies now which implicates gut bacteria as the cause of anxiety depressive symptoms. More research is needed before we recommend ANY chemicals for depression as we at this stage do not know the real causes of this condition. Non pharmaceutical treatment is the way to go at present.

Dr Harold George Burkitt   30/07/2022 9:41:03 AM

I welcome the robust discussion that has been unleashed. We must completely consider the biological purpose of discomfort which is absolutely central to homeostasis. The capacity to sense and experience discomfort, chemical, physical or emotional, is the mechanism which instigates integrative/restorative responses in all organisms. See my recent blog for Critical and Ethical Mental Health

Rodney Jones   30/07/2022 10:13:58 AM

In the risk-benefit trade-off are they any better than grog ?

Dr Mary Emeleus   30/07/2022 10:26:47 AM

I want to highlight that conflating psychotherapy with something offered only by "psychologists and psychiatrists" is incorrect. Many generalist doctors do specific training and are excellent therapists, like my colleagues in the Australian Society for Psychological Medicine and many others. All kinds of people can train in psychotherapy and the evidence is clear that one's original profession does not determine the outcome: it's the ability to build a strong therapeutic alliance with people and a number of other factors. Many psychiatrists are not specifically trained in psychotherapy. Our current system does not fund many excellent professional psychotherapists who could be helping our patients, including Credentialed mental health nurses. This is very unfortunate given the current system pressures which are well described in this article.

Dr Michael Sosnin   30/07/2022 10:38:12 AM

I wonder if the high rate of antidepressant prescription in Australia may be partly explained by their use for other conditions such as chronic pain and migraine, particularly as we try and move away from opioids.

Dr Nay Lin Tun   30/07/2022 8:16:15 PM

Good review.

Dr Philip Ian Dawson   31/07/2022 12:56:22 PM

Association does not prove causation. Chemical changes in the brains of depressed people may either be a result of depression or a part of the cause. This study does nothing to answer that. Depression used to be classified as endogenous or reactive(exogenous). The former often responds well to pills, the latter to psychotherapy especially behaviour change and CBT.