Comments on: New antidepressants all bark and no bite?

By: Jennifer R. Ewing

Jennifer R. Ewing — Wed, 27 Feb 2008 02:49:39 +0000

The following paragraph is very telling:
This study focused on the drugs fluoxetine (Prozac), venlafaxine (Effexor), nefazodone (Serzone), and paroxetine (Seroxat or Paxil) and used the US Freedom of Information Act to request data on (mainly) negative trials that haven’t been published to complement the data set from published trials.
To me, this smacks of someone deliberately going out of their way to find reasons to look down on the pharmaceutical industry’s attempts to help the people suffering the worst types of depression. There is, and always has been, a very large segment of the population who believe that depression is merely self pity, and labeling such as “depression” merely “validates” those feelings. It’s unfortunately true that some people claim to have clinical depression when they don’t, because they’re drug-seekers looking for an easy high. Those reprehensible people, and the doctors who enable them, should in no way be lumped in with the same people who genuinely suffer from a diagnosable, treatable and very real mental illness. They should, however, be lumped in with the ivory-tower “researchers” who glibly pronounce that “depression meds don’t work”.

By: Mike

Mike — Tue, 26 Feb 2008 20:31:10 +0000

Yeah i think it may not be the best thing to lump every single study together. Some of the studies are just not constructed well enough to be able to distinguish the drug response from the placebo response. Some of the studies enroll patients who barely meet the criteria for major depression and other studies use antidepressant doses which are too low to get any effect. So I don’t think you can treat all those studies with equal weight. Trials to treat depression are notoriously difficult to run due to the large placebo effect.
Also, antidepressants (like SSRI’s) have a non-selective effect on the brain. These drugs increase serotonin at multiple serotonin receptors. A lot of the side effects of the drugs can actually show up as a worsening of depression on certain depression rating scales (sexual dysfunction, anxiety, insomnia). So the “right” depression rating scale also has to be used. If a depression rating scale has too many items that load on sexual dysfunction, apathy, insomnia etc. then an SSRI might not be able to seperate from a placebo response. A pharmaceutical company has to manipulate the variables of a trial to get a specified outcome (efficacy) and they won’t always be successful at doing it.
Its basically the same thing with transcranial magnetic stimulation (TMS) and depression. If you looked at all the earlier trials, there wasn’t much evidence of efficacy. However, that’s because they didn’t know the exact area of the brain to target, the amount of sessions needed, the intensity of the TMS needed, the symptoms that would be improved by targeting that specific area of the brain etc. Now, though, newer TMS trials are having much more success in distinguishing the real TMS from the sham TMS.

By: PJ

PJ — Tue, 26 Feb 2008 17:32:04 +0000

I think that by saying “this was no different from placebo” you are being misleading. Strictly speaking it was statistically different from placebo but did not reach the NICE criteria for a clinically significant difference:
“a three-point difference in Hamilton Rating Scale of Depression (HRSD)scores or a standardized mean difference (d) of 0.50″
While discussion of what does and does not constitute a clinically significant difference is valuable I think it is a mistake on the part of the (majority) of commentators on this study to accept without question the claim that there is no real difference between the drugs and placebo without further discussion.
Also I’m at a loss to know what the claim that the benefit in severe depression is due to reduced placebo rather than increased efficacy of the drugs means given that any efficacy of the drugs must be over and above the placebo effect. If there is less response to placebo in severe depression there there must be relatively more ‘real’ effect over and above that placebo effect in severe depression.