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Serotonin and depression by Dr Healey in BMJ


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http://www.bmj.com/content/350/bmj.h1771

 British Medical Journal

 

 

 

The marketing of a myth

The serotonin reuptake inhibiting (SSRI) group of drugs came on stream in the late 1980s, nearly two decades after first being mooted. The delay centred on finding an indication. They did not have hoped for lucrative antihypertensive or antiobesity profiles. A 1960s idea that serotonin concentrations might be lowered in depression1 had been rejected,2 and in clinical trials the SSRIs lost out to the older tricyclic antidepressants as a treatment for severe depression (melancholia).3 4 5

When concerns emerged about tranquilliser dependence in the early 1980s, an attempt was made to supplant benzodiazepines with a serotonergic drug, buspirone, marketed as a non-dependence producing anxiolytic. This flopped.6 The lessons seemed to be that patients expected tranquillisers to have an immediate effect and doctors expected them to produce dependence. It was not possible to detoxify the tranquilliser brand.

Instead, drug companies marketed SSRIs for depression, even though they were weaker than older tricyclic antidepressants, and sold the idea that depression was the deeper illness behind the superficial manifestations of anxiety. The approach was an astonishing success, central to which was the notion that SSRIs restored serotonin levels to normal, a notion that later transmuted into the idea that they remedied a chemical imbalance. The tricyclics did not have a comparable narrative.

Serotonin myth

In the 1990s, no academic could sell a message about lowered serotonin. There was no correlation between serotonin reuptake inhibiting potency and antidepressant efficacy. No one knew if SSRIs raised or lowered serotonin levels; they still don’t know. There was no evidence that treatment corrected anything.7

The role of persuading people to restore their serotonin levels to “normal” fell to the newly obligatory patient representatives and patient groups. The lowered serotonin story took root in the public domain rather than in psychopharmacology. This public serotonin was like Freud’s notion of libido—vague, amorphous, and incapable of exploration—a piece of biobabble.8 If researchers used this language it was in the form of a symbol referring to some physiological abnormality that most still presume will be found to underpin melancholia—although not necessarily primary care “depression.”

The myth co-opted the complementary health market. Materials from this source routinely encourage people to eat foods or engage in activities that will enhance their serotonin levels and in so doing they confirm the validity of using an antidepressant.9 The myth co-opts psychologists and others, who for instance attempt to explain the evolutionary importance of depression in terms of the function of the serotonin system.10 Journals and publishers take books and articles expounding such theories because of a misconception that lowered serotonin levels in depression are an established fact, and in so doing they sell antidepressants.

Above all the myth co-opted doctors and patients. For doctors it provided an easy short hand for communication with patients. For patients, the idea of correcting an abnormality has a moral force that can be expected to overcome the scruples some might have had about taking a tranquilliser, especially when packaged in the appealing form that distress is not a weakness.

Costly distraction

Meanwhile more effective and less costly treatments were marginalised. The success of the SSRIs pushed older tricyclic antidepressants out of the market. This is a problem because SSRIs have never been shown to work for the depressions associated with a greatly increased risk of suicide (melancholia). The nervous states that SSRIs do treat are not associated with increased risk of suicide.11 The focus on SSRIs also coincided with the abandonment of the pursuit of research into established biological disturbances linked to melancholia (raised cortisol); the SSRIs are ineffective in mood disorders with raised cortisol.12

Over two decades later, the number of antidepressant prescriptions a year is slightly more than the number of people in the Western world. Most (nine out of 10) prescriptions are for patients who faced difficulties on stopping, equating to about a tenth of the population.13 14 These patients are often advised to continue treatment because their difficulties indicate they need ongoing treatment, just as a person with diabetes needs insulin.

Meanwhile studies suggesting that ketamine, a drug acting on glutamate systems, is a more effective antidepressant than SSRIs for melancholia cast doubt on the link between serotonin and depression.15 16 17

Serotonin is not irrelevant. Just as with noradrenaline, dopamine, and other neurotransmitters, we can expect it to vary among individuals and expect some correlation with temperament and personality.18 There were pointers to a dimensional role for serotonin from the 1970s onwards, with research correlating lowered serotonin metabolite levels with impulsivity leading to suicidality, aggression, and alcoholism.19 As with the eclipse of cortisol, this research strand also ran into the sand; SSRIs lower serotonin metabolite levels in at least some people, and they are particularly ineffective in patient groups characterised by impulsivity (those with borderline personality traits).20

This history raises a question about the weight doctors and others put on biological and epidemiological plausibility. Does a plausible (but mythical) account of biology and treatment let everyone put aside clinical trial data that show no evidence of lives saved or restored function? Do clinical trial data marketed as evidence of effectiveness make it easier to adopt a mythical account of biology? There are no published studies on this topic.

These questions are important. In other areas of life the products we use, from computers to microwaves, improve year on year, but this is not the case for medicines, where this year’s treatments may achieve blockbuster sales despite being less effective and less safe than yesterday’s models. The emerging sciences of the brain offer enormous scope to deploy any amount of neurobabble.21 We need to understand the language we use. Until then, so long, and thanks for all the serotonin.

Notes

Cite this as: BMJ 2015;350:h1771

**I am not a medical professional, if in doubt please consult a doctor with withdrawal knowledge.

 

 

Different drugs occasionally (mostly benzos) 1976 - 1981 (no problem)

1993 - 2002 in and out of hospital. every type of drug + ECT. Staring with seroxat

2002  effexor. 

Tapered  March 2012 to March 2013, ending with 5 beads.

Withdrawal April 2013 . Reinstated 5 beads reduced to 4 beads May 2013

Restarted taper  Nov 2013  

OFF EFFEXOR Feb 2015    :D 

Tapered atenolol and omeprazole Dec 2013 - May 2014

 

Tapering tramadol, Feb 2015 100mg , March 2015 50mg  

 July 2017 30mg.  May 15 2018 25mg

Taking fish oil, magnesium, B12, folic acid, bilberry eyebright for eye pressure. 

 

My story http://survivingantidepressants.org/index.php?/topic/4199-hello-mammap-checking-in/page-33

 

Lesson learned, slow down taper at lower doses. Taper no more than 10% of CURRENT dose if possible

 

 

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I liked it.

2009: Cancer hospital said I had adjustment disorder because I thought they were doing it wrong. Their headshrinker prescribed Effexor, and my life set on a new course. I didn't know what was ahead, like a passenger on Disneyland's Matterhorn, smiling and waving as it climbs...clink, clink, clink.

2010: Post surgical accidental Effexor discontinuation by nurses, masked by intravenous Dilaudid. (The car is balanced at the top of the track.) I get home, pop a Vicodin, and ...

Whooosh...down, down, down, down, down...goes the trajectory of my life, up goes my mood and tendency to think everything is a good idea.
2012: After the bipolar jig was up, now a walking bag of unrelated symptoms, I went crazy on Daytrana (the Ritalin skin patch by Noven), because ADHD was a perfect fit for a bag of unrelated symptoms. I was prescribed Effexor for the nervousness of it, and things got neurological. An EEG showed enough activity to warrant an epilepsy diagnosis rather than non-epileptic ("psychogenic") seizures.

:o 2013-2014: Quit everything and got worse. I probably went through DAWS: dopamine agonist withdrawal syndrome. I drank to not feel, but I felt a lot: dread, fear, regret, grief: an utter sense of total loss of everything worth breathing about, for almost two years.

I was not suicidal but I wanted to be dead, at least dead to the experience of my own brain and body.

2015: I  began to recover after adding virgin coconut oil and organic grass-fed fed butter to a cup of instant coffee in the morning.

I did it hoping for mental acuity and better memory. After ten days of that, I was much better, mood-wise. Approximately neutral.

And, I experienced drowsiness. I could sleep. Not exactly happy, I did 30 days on Wellbutrin, because it had done me no harm in the past. 

I don't have the DAWS mood or state of mind. It never feel like doing anything if it means standing up.

In fact, I don't especially like moving. I'm a brain with a beanbag body.   :unsure:

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