Recent thinking on Depression- Causes and Treatment

[redsturgeon]

For many years the chemical imbalance theory of depression has been at the forefront of medical thinking and treatment of depression. This being that depression is caused by lack of serotonin (5HT) in the brain and can thus be effectively treated with drugs which increase circulating 5HT within the brain.

This has resulted in widespread prescribing of 5HT re-uptake inhibitors that work by stopping the body breaking down serotonin thus increasing levels of the neurotransmitter within the brain. The upshot being that in both the UK and the US about one in six adults are prescribed antidepressants having been told by doctors that they will fix the underlying chemical imbalance responsible for their condition. These drugs come with side effects and with problems concerning long term use and difficulties in withdrawal.

The latest review of the evidence for the role of serotonin in depression is here:

https://www.nature.com/articles/s41380-022-01661-0

a review looking at 17 studies including over 160,000 subjects. The conclusion being

The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.

To be clear this review does not argue that antidepressants do not work, merely that the mode of action is not that which was previously thought.
While antidepressants do work, it is now clear that they do not do so in the way that clinicians have been led to believe. This may have led to significant over treatment with these drugs in the past in a similar way that led to drugs such as Valium being over prescribed decades previously.

This paper from over a decade ago gives an alternative view of how these drugs might work:

https://www.bmj.com/content/338/bmj.b1963

Drugs for psychiatric problems are prescribed on the assumption that they mostly act against neurochemical substrates of disorders or symptoms. In this article we question that assumption, proposing that drugs’ action be viewed rather as producing altered, drug induced states, a view we have called the drug centred model of action.

Evidence shows that the effect of external events is also likely to be significant so that the number of stressful external events will have a significant impact on how likely an individual is to suffer from depression.

This recent article covers the topic in more detail

https://theconversation.com/chemical-im ... ons-188921

Note that bipolar depression is a separate condition and it is not referred to in any of these articles.

I hope this is of interest to some.

John

[Lootman]

Evidence shows that the effect of external events is also likely to be significant so that the number of stressful external events will have a significant impact on how likely an individual is to suffer from depression.

My completely amateur thought would be that much depression is situational. The people I have known who have had bouts of depression were usually people who went through a period of stress, caused by divorce, loss of job, legal, medical or financial troubles etc.

So whilst there might be a correlation between feeling depressed and there being an imbalance of chemicals, it doesn't make much sense to me to suggest that the chemicals caused depression. Rather that the imbalance reflects the mental and emotional state of the person - both change because of external pressures.

Of course there may be some people who are structurally depressed, due to physiological factors. But for many depression is temporary, situational and even useful: Like physical pain, depression can be a sign that some aspect of your life is wrong and needs to be fixed. In which case masking the symptoms can cause harm as it prevents the person from addressing the root cause of the problem.

That said, the desire to be prescribed a pill to feel better is tempting, both for the patient and for the doctor. Valium is a little different because that addresses anxiety rather than depression. 60 or so years after it was developed, it is still in wide use today, including by my dentist. But again for occasional use, not persistent use.

Non-scientist here, if that isn't obvious.

[redsturgeon]

That said, the desire to be prescribed a pill to feel better is tempting, both for the patient and for the doctor. Valium is a little different because that addresses anxiety rather than depression. 60 or so years after it was developed, it is still in wide use today, including by my dentist. But again for occasional use, not persistent use.

Non-scientist here, if that isn't obvious.

Just to clarify I was using Valium as an example of over prescribing and not suggesting it was ever used as an anti depressant. In addition to its anxiolytic properties it is also useful as a muscle relaxant and sedative. It is indeed still used today but not long term as it was often prescribed in the past and not really recommended for longer than a month. When the Rolling Stones sang about it as "mother's little helper", it was probably the most widely prescribed drug in the western world. Nowadays Valium (diazepam) is still widely used and abused but not prescribed quite as much as 40 years ago.

As a non-scientist your overall description of depression contains a lot of common sense although I would make the point that a clinical definition would require a persistent, longer term alteration of mood rather than a short term or temporary event. Best practice would be to engage in non pharmaceutical interventions initially but things like counselling are more expensive for the NHS to provide so the prescription pad is often the default.

John