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Underground > Laboratory >

The drugs don't work?

16:19 / 29.02.08

The Independent recently reported that antidepressant drugs have no clinical significance. A group of exprerts including Professor Kirsch of Hull University conducted a 'meta-analysis' of all of the evidence available for six of the most commonly prescribed SSRI's and concluded they were, in effect, no better than a sugar pill.

Several news reports suggested that Kirsch had concluded SSRI's were only helpful in a small group of the most severely depressed people, but in fact even this was generous. Kirsch said in interview that antidepressants had only appeared to work better for this group because their placebo had probably stopped being effectual.

Is there something fundamentally wrong with conventional treatments for depression? Is the report scaremongering? Or are the drugs repeatedly failing to treat depression at the physical level?

Poke it with a stick

20:54 / 29.02.08

Speaking from well-informed second-hand experience, fluoxetine does seem to work, at least for a while. The drug did seem to stabilise the user's mood, though at the expense of creativity and sense of humour.

Now, it's suspected by doctors that it's been bringing on spasms and blackouts of which the user is now suffering. Not sure that's such a ringing endorsement of SSRIs, mind.

04:37 / 01.03.08

There was some discussion of this over on reddit, but I don't remember seeing any conclusive evidence one way or the other. Many were treating the report with skepticism.

I think the placebo effect is going to seriously skew results either way, because one can't really correct for it.

09:21 / 02.03.08

I think it's probably quite a dangerous conclusion to draw based on what seems like no more research than any other study. It's been widely covered because it's an interesting story and makes good headlines, but there was a Psychiatrist dude on Radio 4 saying the result of news coverage like this is that some people currenly doing really well on these tablets will suddenly stop taking them - which is bad news if they do work, and then if that person feels awful enough they might think suicide is the only option. So a person doing well and recovering from depression is now dead, possibly only because shock headlines sell papers.

11:12 / 02.03.08

I think it's probably quite a dangerous conclusion to draw based on what seems like no more research than any other study.

It's not "no more research than any other study", though; it's a meta-analysis of - if I remember right - 47 studies, which is quite a lot. No study has ever concluded that any anti-depressant has hugely signficant results; the reasons that any anti-depressants have been licenced is because drug companies have the capacity to run lots of studies and then only release those which reach a level of clinical significance (a rather paltry 3 points on a 51-point scale; the average improvement found across the studies being just short of this at 2 points).

Obviously it's pretty bad if people suddenly stop taking medications which are helping them, but a) it seems unlikely anyone would stop taking them if they actually thought they were helping, and if you can't tell if a drug is doing anything it's probably not having a brilliant effect, and b) it's also pretty bad if people are taking unnecessary medications which do them no good at all, and which have lists of awful potential side-effects - which also include suicide.

I'm not anti-psychiatry/anti-psychiatric drugs, but I've always been astounded by how little evidence there is that anti-depressants do anything helpful at all. Given that there are companies with a vested interest in making sure huge quantities of the things are prescribed (I can't quite believe that a privately owned capitalist system can really be considered a good way to run anything to do with healthcare. Well, anything at all really, but particularly healthcare), I'm not sure that an assumption that they are helpful, given this absence of scientific evidence, is a particularly good starting point.

16:39 / 02.03.08

I'd agree with pretty much everything you've said, Pringles. There seems to be little space to acknowledge that the drugs might be ineffective from a client point of view, as the treatment appears to be to shift patients from one drug to the next if the antidepressant has no effect.

At the same time, no claims that any kind of essential mineral/vitamin supplement are effective antidepressants can be validated. Their manufacturers do not have the overheads to fund clinical trials.

That said, the FDA is planning to regulate all vitamin supplements in America.

Closed for Business Time

12:28 / 03.03.08

J. Moncrieff at University College London has been publishing findings critical of the standard model of psychiatric illnesses (illness = chemical imbalances in brain = can be cured by drugs) for a long time. Below is a link to an essay she wrote with a David Cohen which argues for a rather different take on what psychiatric drugs really do to us.

Link

The abstract reads:

The term antidepressant refers to a drug that helps to rectify specific biological abnormalities that give rise to the symptoms of depression. This exemplifies what we have called the “disease-centred” model of psychotropic drug action [1]. Modelled on paradigmatic situations in general medicine—such as the use of insulin in diabetes, antibiotics in infectious disease, chemotherapy in cancer—the disease-centred model suggests that antidepressants help restore normal functioning by acting on the neuropathology of depression or of depressive symptoms.

In contrast, we propose in this Essay that an alternative “drug-centred” model can better explain observed drug effects in psychiatric conditions. This drug-centred model suggests that instead of relieving a hypothetical biochemical abnormality, drugs themselves cause abnormal states, which may coincidentally relieve psychiatric symptoms (Table 1). Alcohol's disinhibiting effects may relieve symptoms of social phobia, but that does not imply that alcohol corrects a chemical imbalance underlying social phobia. Sedation may lessen high arousal, present in many acute psychiatric situations. Drugs that induce indifference, such as neuroleptics or opiates, may help reduce the distress of acute psychotic symptoms. Low-dose stimulants may help improve attention and concentration in the short term.

Do read it, it's quite intriguing.

16:40 / 03.03.08

Thanks for posting that Nolte. I found it very interesting. I would summarise the conclusions in terms of:

1) Drugs which appear to have an antidepressant effect really create an abnormal brain state which has an incidental effect of relieving certain symptoms of depression
2) 'Antidepressant drugs' do not exist as a discrete clinical concept, as other drugs such as opiates and stimulants may produce short term anti-depressant effect
3) No drug termed 'antidepressant' has shown to have a longterm mood elevating effect, because of the development of tolerance.

Poke it with a stick

09:11 / 06.03.08

Again, research indicates that they can have an effect - just not a positive one - Seroxat makes GSK supposedly knew about the higher risk of suicide amongst young users but kept it quiet:
BBC article here

14:24 / 10.03.08

I must point out that my comment relates broadly to anti-depressants and not specifically SSRIs.

I have read the original article and it certainly seems to me that this story has been sensationalised by the media.

The paper itself does show that anti-depressants have an effect, but only in those patients who score highly on a scale of depression to begin with. Interestingly, the effect was apparent largely due to a reduced response to placebo in those patients with high baseline depression scores.

Now, it is important to note that depression is not like diseases such as cancer, heart disease or arthritis - it is particularly difficult to decide who is depressed and who is not. I would suggest that the lack of an effect in patients with low b.line scores is due to the increased likelihood of including people who do not "really" have depression... ie, their depression is more likely to be psychological (primarly due to current stress) than biological (due to chemical imbalances resulting from some essential quality of the patient e.g. genetic profile).

Furthermore, the authors themselves: a) accept that these drugs do have an effect on those patients with higher b.line depression scores but; b) claim that the effect is not significant based on an arbitrary definition of a "clinically significant" effect. There is a brilliant BMJ editorial on the second point here: http://tiny.cc/o8Hq7

[Unfortunately, this is not freely available so if you are interested I can copy-paste the important comments in this editorial - if you trust me :P]

Now, I am not qualified to give medical advice and it would be irresponsible for me to suggest otherwise. However, if I were taking one of the anti-depressants included in the meta-analysis and they were working for me, I would continue taking them on the basis of this study and a few BMJ editorials (in my case acting in proxy as medical advice).

J.

14:34 / 10.03.08

I think the placebo effect is going to seriously skew results either way, because one can't really correct for it.

Most clinical trials (the good ones anyway) specifically include a control group which are randomised to receive a placebo or (more commonly these days) "treatment as usual". The whole point is that if one can show that the response in the treatment group is significantly (positively) different to that of the control (placebo/TAU) group, then the treatment clearly works better than the comparison.

I would guess you are saying that the size of the effect seen in the treatment group is, in part, a placebo effect and we cannot tease this out... well, maybe not, but it seems logical to suggest that if 30% of the placebo group get better, and 50% of the treatment group get better, the effect of the drug is 20%.

J.

16:29 / 10.03.08

Yeah, I'm partly saying that placebo effects would kind of cancel each other out on either side, but I'm also saying that there's something really hard to quantify about placebo effects to begin with, which is part of the reason why double-blind studies are important (so testers don't know if it's a placebo or not).

And there's also something about placebos and depression to begin with - since placebos are essentially psychological things with physical effects, I imagine it'd be really hard to tell the difference between effects if a brain-altering chemical did one thing without being a placebo, and a placebo did something similar (but not identical) without the necessary chemical ingredients. If that makes sense.

08:54 / 11.03.08

Grant, I think I understand now. It is amazing how little research there is into how placebos work. In the case of depression it seems quite logical that if the subject *believes* they are taking a drug that has an effect, they are more likely to report a benefit simply as a result of the relatively subjective nature of the outcome variable (depression scale). A similar thing seems to apply to studies of drugs to relieve pain or conditions such as chronic fatigue or irritable bowel syndrome. Unless there are objective physical measures established which identify the presence or at least severity of conditions like these, it will be very difficult to tease out the placebo effect itself...

An interesting point was raised in the paper recommended by Surrah; if a simple sugar pill is used in trials of anti-depressant efficacy, the trial is likely to become unblinded as those assigned to treatment will be more likely to believe they are being treated as a result of the side-effects such drugs tend to have (compared to none resulting from sugar tablets!) For me, this point has thrown an awful lot of clinical trials for psychiatry into doubt...

Now, what the hell is happening when a patient's cancer goes into remission whilst being "treated" with a placebo? I think the answer is pretty obvious when the outcome is based on clinical interpretation and the study isn't double-blinded (as the expectation of a specific effect will skew the clinician's judgement one way or the other). Fortunately, clinical trials without double-blinding are much less common in recent times. In the case of such double-blind experiments it is less clear. I find it very tempting to accept that belief in the efficacy of the dummy treatment has a positive effect on the progression of the disease. Unfortunately, I have not had much luck tracking down evidence to support this hypothesis (that thought can influence disease progression/prognosis) other than the placebo effect itself...

If anyone on this board could offer such evidence I would be greatful! I have started a new topic here.