Boosting Your Serotonin or Exploiting Your Depression?

February 1, 2010 at 9:11 pm (Bad Science, Big Pharma, Homeopathy, Patrick Holford) (, , , , , , , , )

What do Big Pharma, Patrick Holford, and Homeopaths all have in common? Well, apart from any other similarities, they all claim to be able to “boost your serotonin”, “remedy your neurotransmitter imbalance”, or help you to “overcome depression.”

Patrick Holford recommends, in his book Optimum Nutrition For The Mind, “keeping your crucial neurotransmitters in balance.” He goes on to write something which I found rather interesting:

Most prescription drugs aim to correct these imbalances, but have undesirable side-effects. Instead, I recommend supplementing the amino acid 5-hydroxy tryptophan (5-HTP) 100mg up to 300mg, twice a day, to boost your serotonin levels.

The section of the book is headed “Overcoming Depression.” Patrick Holford seems to believe that “boosting your serotonin levels” will help you overcome depression, that prescription drugs for depression work (and, notably, that they work by “boosting” your serotonin), that 5-HTP has the same effect, and that 5-HTP is not associated with side-effects in the same way that SSRI drugs are.

The idea that both 5-HTP and SSRI drugs increase serotonin levels and help with depression, but only one has side-effects is one that I find odd. Holford does not support his comment with any references, so I can only assume that this comment is based on opinion rather than anything factual.

[Note: Holford also calls St John’s Wort “the happiness herb” in the same chapter, and claims that it is “one of the most thoroughly researched of all natural remedies.” It’s worth pointing out that this thorough research has revealed that St John’s Wort has some undesirable side-effects: St John’s wort and depression: slight efficacy at best, many drug interactions]

While SSRI drugs do seem to have some effect on depression, it is far from clear that this effect is due to a simple “more serotonin = better mood” equation. As Ben Goldacre writes here, the serotonin hypothesis:

was always shaky, and the evidence now is hugely contradictory. I’m not giving that lecture here, but as a brief illustration, there is a drug called tianeptine – a selective serotonin reuptake enhancer, not an inhibitor – and yet research shows this drug is a pretty effective treatment for depression too.

The excellent Mind Hacks blog has a fascinating post on ‘depression as a brain disease’:

If depression is nothing more than low serotonin, drugs that specifically lower serotonin levels in the brain should lead to depression or at least low mood. Studies which have tried this in both healthy participants and depressed patients show remarkably little effect on mood, with a mild dysphoria being the only occasional effect.

The post concludes:

It is clear from the scientific literature that a purely biological theory of mental illness is not sufficient to explain and treat the experience of mental distress. Furthermore, simplified theories, that argue, for example, that depression is ’caused by low serotonin’ are lacking in support and best avoided.

Both Vaughan Bell of Mind Hacks and Ben Goldacre of Bad Science link to a paper in Nature titled Is mood chemistry?

recent evidence indicates that problems in information processing within neural networks, rather than changes in chemical balance, might underlie depression, and that antidepressant drugs induce plastic changes in neuronal connectivity, which gradually lead to improvements in neuronal information processing and recovery of mood.

It would suit pharmaceutical companies, and supplement manufacturers, if there were a simple narrative that would help to sell their pills.

It seems the reality is that it’s a bit more complicated than “low serotonin causes depression”, or “boost your serotonin levels and overcome depression.” I suspect, however, that it is now the case that, whether true or not, “everyone ‘knows’ now that boosting serotonin ‘cures’ depression.”

For nutritionists and supplement manufacturers pushing 5-HTP as a serotonin booster, or something that will help overcome depression, this Cochrane review might make for uncomfortable reading:

A large number of studies appear to address the research questions, but few are of sufficient quality to be reliable. Available evidence does suggest these substances are better than placebo at alleviating depression. Further studies are needed to evaluate the efficacy and safety of 5-HTP and tryptophan before their widespread use can be recommended. The possible association between these substances and the potentially fatal Eosinophilia-Myalgia Syndrome has not been elucidated. Because alternative antidepressants exist which have been proven to be effective and safe the clinical usefulness of 5-HTP and tryptophan is limited at present.

In the case of Big Pharma, Ben Goldacre has described the “dodgy behaviour”, the “$600 billion pharma industry”, and the publication bias made clear by a paper in the New England Journal of Medicine. He’s also written that “in popular culture the depression/serotonin theory is proven and absolute.”

This meta analysis of ‘Efficacy and Tolerability of Tricyclic Antidepressants and SSRIs Compared With Placebo for Treatment of Depression in Primary Care‘ notes that all the SSRI vs placebo studies included in their review had some commercial involvement – but, more importantly, it tells us that: “Many studies reviewed were of low methodological quality, and nearly all studies were of short duration.”

It is unfortunate that so many published studies in this are are apparently of low methodological quality – and this is a situation that needs to be addressed. “More research” is a line almost invariably included in academic papers. Perhaps it should come with a qualifier along these lines: “…unless it’s as badly-designed as the crap we’ve just trawled through.”

And now, if you will follow me, we shall move from bad behaviour, marketing pills, and the poor quality of some research to homeopathy. Don’t worry – it’s not far.

ABC Homeopathy offer “suggestions of homeopathic remedies for Seratonin Imbalance” and have helpfully grouped the symptoms experienced by a previous vistor to their homeopathic remedy finder.*

I ticked the little box next to the symptoms “mind; emotions, feelings, attitude, disposition; indifference, apathy, etc.” I clicked the “find remedies” button and the next page came up:

The homeopathic remedy which best matches your symptoms is Sepia […] For potency information, please see our potency guide. […] If you need to buy this remedy, please support the remedy finder by buying through our online shop.

I checked the potency guide, which told me:

Not all homeopaths agree on dosage and potency, but as a general rule, Chronic illnesses (i.e. those that you’ve had for a long time) should be treated with high potencies (i.e. 30x – 200c.) and Acute conditions (i.e. those that are relatively new) with low potencies (i.e. 6x or 6C)

I clicked on the “add to shopping basket” option and found that, if I wished to purchase their suggested remedy for chronic depression, they could sell me “Tablets- off the shelf; 30C; 125 tablets; £6.50” I know – it’s not very holistic, is it? More ‘simplistic’ than ‘holistic’, I would say.

You might think I’ve been unfair to homeopaths by using an online remedy finder rather than the words of a homeopath. Well, the Society of Homeopaths themselves say, on a page titled “Stress, anxiety and depression”, that:

It is not only counselling that has a role to play in preventing serious mental illness. In a national survey conducted by The Society of Homeopaths, 87% of patients who complained of mental and emotional problems reported positive change.

30C of Sepia – or 30C of any other homeopathic remedy – would in all likelihood contain not a single molecule of the active ingredient. I would be relying on vibrational energies left by the ingredient that they had diluted out of existence, or the memory of water. Well, to be more precise I suppose I would be relying on the memory of sugar (remembering something that the water had been remembering when it was dripped onto the sugar pills).

SSRIs might help with depression. St John’s Wort* or 5-HTP might help, but are is not recommended. The only way that homeopathy might help with depression is either through the placebo effect, or perhaps by providing someone with a bloody good laugh when you describe to them the process of manufacturing magic water and dripping it onto sugar pills.

EDIT 02/02/2010

*For further comment on St John’s Wort, please see the comment by Silphion in the thread below.

This Cochrane review concludes:

The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.

The note of caution in this conclusion seems to relate to the research carried out in Germany being more favourable to hypericum. This remedy is popular in Germany and Neuroskeptic discusses the possible effect that its popularity may have on the research conducted into it. There are also some interesting comments from pj in the thread that follows Neuroskeptic’s post.

EDIT 08/02/2010

* I’ve noticed this odd spelling of serotonin before. Today I spotted a couple of other oddities – serotonine and seratonine.

10 Comments

  1. silphion said,

    While totally agreeing with you about the nonsense of equating depression with a simple and linear neurotrasmitter imbalance, and with the idea that molecules of natural origin might, in principle, act without side effects, I would challenge the picture you gave of Hypericum perforatum extracts (SJW).
    Firstly, the main problem with the use of SJW does not lie in side effects. Any clinical trial done on it has showed that side effects associated with SJW use are in percentage much less and less severe that those associated with standard treatment. The main problem lies in its demonstrated pharmacological interactions (not many: cyclosporin; SSRI; oral contraceptives; antiretrovirals (e.g., indinavir, nevirapine) and anticancer drugs (i.e., irinotecan, imatinib)) and in it s potential (albeit not showed in clinical trials but only in vitro) side effects with many more drugs. Although this is a very important issue, it must be emphasised that the risk profile is very different from one of severe side effects: if a subject is not taking drugs with which the interaction is demonstrated or suspected, the risk simply disappears, while in the case of drugs with severe side effects, these side effects are not eliminable.
    Secondly, there were many more possible articles to cite in relations to SJW, why choosing that one and saying it is a thorough research? Are more recent meta analyses or clinical trials or reviews less thorough? In which sense exactly? It seems to me that we could say that SJW seems a very interesting substitute for standard antidepressants in case of mild to moderate depression, because it has comparable efficacy and fewer side effects. Its efficacy profile in case of major depression is less clear, and that its use should not be considered without specialistic consult.
    Thirdly, it seems to me that SJW is interesting exactly because it does not seem to act via a single mechanism or a single molecule, but can be described as a pleiotropic agent, which seems preferable in view of a non reductionistic description of what depression is.

    Cheers
    Marco

    1. Cochrane analysis 2008 (http://www.ncbi.nlm.nih.gov/pubmed/18843608?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_SingleItemSupl.Pubmed_Discovery_RA&linkpos=1&log$=relatedreviews&logdbfrom=pubmed)
    AUTHORS’ CONCLUSIONS: The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.

  2. Heather said,

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  3. More Serotonin Stuff, Patrick Holford and Depression « Stuff And Nonsense said,

    […] EDIT 02/02/2010: new post on boosting serotonin. […]

  4. Serotonin Pills in the Media « Stuff And Nonsense said,

    […] EDIT 02/02/2010: new post on boosting serotonin. […]

  5. jdc325 said,

    @silphion Thank you for commenting. My point in writing that note was to draw attention to the fact that the remedies that Partick Holford recommends most certainly do have side-effects. Holford seems to refer to the side-effects of SSRI drugs and to ignore those of herbal or “food supplement” remedies. My point was that the “thorough research” that Holford refers to has uncovered side-effects of St John’s Wort that Holford does not refer to. I found this a little ironic.

    I agree that St John’s Wort is not as bad as I seem to have implied in my post. The best available evidence relating to St John’s Wort that I could find on searching Pubmed was in fact the Cochrane review that you link to. I also found an interesting paper on SJW in major depressive disorder: http://www.ncbi.nlm.nih.gov/pubmed/19028540

    Hypericum does not differ from SSRIs according to efficacy and adverse events in MDD. Lower withdrawal from study due to adverse events by Hypericum is an advantage in management of MDD.

    Having looked again at the literature on St John’s Wort, I think that (while the rest of my comments on SJW are probably reasonable and relevant) the comment in my concluding paragraph is unfair. I shall amend this paragraph (and mark up the changes) to better reflect the best available evidence on this remedy.

    Once again – thank you for commenting.

  6. Cultural Bias in Scientific Research « Stuff And Nonsense said,

    […] days ago, I wrote a post about ‘boosting serotonin‘ and included some comment on St John’s Wort. This review of St John’s wort for […]

  7. silphion said,

    @jdc325
    thanks for the prompt reply. I realized SIW was not your main focus, just an example for your primary argument. One of the problems when talking about non conventional remedies is that nonsense and uncritical thinking abounds, and people working in the field of herbal medicine research/education finds themselves in a defensive position because of the biased writings of supposed experts in the field like Holford. Maybe that’s why I felt like intervening on SJW :-), which, quite apart from its role as an antidepressant, is an intriguing plant exactly because of its meta activity on detoxifying mechanisms (nuclear pregnane receptor X, etc.)
    Cheers
    PS: the point about possible bias in German RCT is appropriate, the source of the possible bias is however IMHO still very difficult to pinpoint. I would dare say that in this case cross-cultural observational studies could offer a new vantage point

  8. jdc325 said,

    One of the problems when talking about non conventional remedies is that nonsense and uncritical thinking abounds, and people working in the field of herbal medicine research/education finds themselves in a defensive position because of the biased writings of supposed experts in the field like Holford.

    Yes, I think that’s what some people call “poisoning the well” – people abusing or misrepresnting the science in a particular area can make it difficult for serious researchers to discuss that area.

    the point about possible bias in German RCT is appropriate, the source of the possible bias is however IMHO still very difficult to pinpoint. I would dare say that in this case cross-cultural observational studies could offer a new vantage point

    You might find my post on cultural bias in scientific research interesting: link.

  9. Holford, Burne and Serotonin Pills « Stuff And Nonsense said,

    […] Holford’s website. Recent discussion of serotonin over at the 21st floor, a blog post about boosting your serotonin, Bad Science on serotonin, and PJ on […]

  10. Astounding Article : Is Big Pharma abandoning psychiatry? « GSK : Licence To (K) ill said,

    […] article is astounding and insightful on so many levels. It not only raises the questionable ‘science‘ that surrounds psychiatric diagnoses but is also examines the ‘profitability‘ […]

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