Anti-depressants have been around since the 1950’s, but it
wasn’t until SSRIs (Selective Serotonin Reuptake Inhibitors), the first being
Prozac, came on the market in the 1980’s that things really took off. The safer
profile meant that primary care physicians could start prescribing, and Prozac
itself became a blockbuster drug (over $US1 billion in annual sales) and a
household name. Others followed and by 2005, anti-depressants were the most
prescribed drugs in the USA. For most patients, however, they are no better
than placebo. That doesn’t mean that they don’t’ work, they just don’t work any
better than placebo.
The studies
The actual effect (here)
of these drugs over placebo drugs is not that great: about 2 points on the 62
point Hamilton Depression Scale – a difference not deemed clinically important.
Further, this more
recent meta-analysis showed that the effect of anti-depressants over placebo
was negligible for those with mild, moderate or severe depression – it was only
significant for those with very severe depression.
This
study showed that selective (biased) reporting of SSRI trials led to
favourable studies being over-reported, and in those published, the results were
reported with a bias towards a positive result.
This
study further explores this bias. Instead of reviewing all of the published
trials, like we normally do, they looked at all of the trials that were
submitted to the FDA (as part of the requirement for getting the drugs approved,
accessed via Freedom of Information Act). They found that of the trials that
were not published, 22 out of 23 were negative (showed the drug to be
ineffective), and that 11 of the published trials that were negative (according
to the FDA) were published in a way that made them look positive. If you
summarised the published trials, you came up with 94% of the trials being
positive, making anti-depressants look very good. If you summarised all of the
trials that were done (including the unpublished trials) you only get 51%
positive, and remember, some of those positive ones are really negative. Our
decisions should be based on the totality of evidence. It appears that we may
be basing many of our decisions on a biased selection of the evidence.
But even the Cochrane reviews (of published studies) show very small effects for anti-depressant use (primary
care, the
elderly, post-natal
depression) and their review of anti-depressants versus active (therefore
better) placebos also showed minor differences, and concluded: “This suggests that the effects of antidepressants
may generally be overestimated and their placebo effects may be underestimated”.
In fact, the Cochrane reviews of exercise
and St
John’s wort for depression showed similar effectiveness to
anti-depressants, but with fewer side effects. They even show that music
therapy, or relaxation
therapy are effective treatments.
The downside
The use of SSRIs was extended to adolescents, but reports of
an increase in the rate of suicide
and suicide
ideation in children and adolescents taking SSRIs put a dampener on that
practice. SSRIs have also been linked to birth defects (here).
This is beyond their standard
side effects, which are too numerous to list here.
The punch line
The biological mechanism for most anti-depressants (SSRIs,
TCAs, MAOIs) is based on the ‘serotonin hypothesis’
that low levels of serotonin make you sad. However, this hypothesis is based on
the fact that these drugs, which happen to increase the serotonin levels around
the neurons, are anti-depressants, making for fairly circular reasoning. How
then do we explain why newer anti-depressants, called SSREs
(Selective Serotonin Reuptake Enhancers),
which have the exact opposite effect
of SSRIs, seem to work just as well? My simple explanation is that they both
work by the placebo effect, and that the serotonin hypothesis is simplistic and
wrong. Don’t worry, I am sure that some clever doctors out there are working
out a contorted biological explanation of this paradox.
The bottom line
Anti-depressants are regularly used as punching bags for those who want to highlight the role of Big Pharma, conflicts of interests amongst psychiatrists, problems with advisory bodies, medicalisation, over-treatment, over-diagnosis, and the social construction of 'diseases'. My point is simple, and I think it is the issue at the core of all of the problems mentioned: these drugs either don't work or barely work at all, beyond the placebo effect.
Addit 11 Sept 2012: See this link for a review on antidepressants, balancing harm vs good on an evolutionary basis.
The bottom line
Anti-depressants are regularly used as punching bags for those who want to highlight the role of Big Pharma, conflicts of interests amongst psychiatrists, problems with advisory bodies, medicalisation, over-treatment, over-diagnosis, and the social construction of 'diseases'. My point is simple, and I think it is the issue at the core of all of the problems mentioned: these drugs either don't work or barely work at all, beyond the placebo effect.
Addit 11 Sept 2012: See this link for a review on antidepressants, balancing harm vs good on an evolutionary basis.
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