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Re: weight gain on SSRIs - continued

Posted by Adam on August 15, 1999, at 16:20:11

In reply to weight gain on SSRIs - continued, posted by Elizabeth on August 15, 1999, at 1:32:51

Accusations of naivite or unethical behavior are ones I certainly never wanted to make or insinuate. Having seen grant money in action, all I can say is that where it comes from
can have an influence. I think, in general, all parties are aware of this and do their best to behave impartially. Research is conducted by human beings. A healthy dose of
skepticism is always warranted, which does not mean one should be paranoid or dismiss everything that a party with a certain vested interest has to say. I've seen brilliant
competitors in academia hurl various ideological and philosophical spitwads at one another, produce totally contradictory results in attempts to repeat the other's experiments,
accuse one another of being idiots, shitheads, what have you. I've yet to hear these diametrically opposed individuals refer to one another as liars, or try to sick the ORI on
each other (though I guess this happens sometimes). Science is just full of this stuff though. Everyone tries to do the right thing, and they mostly succeed. You take the
true love of the scientific process and throw money and egos and dogma into the mix, and it gets complicated. I still and always will have faith in the process, mostly because
of the necessity of reproducibility in science as a condition for acceptance. I take one paper, lots of anecdotal information, and my own experience and conclude that the truth is
out there, and I hope someone finds it. My assumption is that SSRI-induced weight gain is real and could be teased out as a bona fide side effect in some individuals, including me.

Tegretol use has been associated with agranulocytosis and aplastic anaemia. If I were to conduct a tegretol study and monitor 1000 individuals for a year I might never see
these terrible side effects and conclude they do not occur. Of course, these conditions are exceedingly rare and can't be equated with something as mundane as putting on weight. I
think because of the severity of such side effects few physicians would be prepared to dismiss the Tegretol connection. There is certainly a higher incidence of, say, agranulocytosis
among Tegretol users than among the general population. For good resons, the association is considered real despite the fact that there might be little justification for such a
conclusion on the grounds of certain statistical tests. This is a hypothetical situation, I know, but I think a plausible one.

Perhaps real SSRI-induced weight gain is rare. I should think, though, that there might be a number of exceptonal cases one could focus on that could help separate the signal
from the noise. Certainly weight gain is common. Is 20% weight gain in six months with no change in diet or activity common? If not, how uncommon is it? Does this sort of thing
happen in individuals who don't take psycotropic medications? If so, how often? I don't do experiments on people, and perhaps I am suggesting a study that would be unfeasibly large
and complex. But such a study could help one, perhaps, identify a subtype with a specific sensitivity to SSRIs that is manifested as weight gain. Maybe one could gain valuable
information from such individuals that could be used to design better drugs, or at the very least teach us some fundimentals about the mechanisms of weight gain. Perhaps we could
learn more about this serotonin/carbohydrate association I keep hearing about. Personally, using the assumption that increased carbohydrate intake somehow increases serotonin levels
or mimicks this in some way, I would think that everybody ought to lose weight on an SSRI. This doesn't happen. Perhaps it's not serotonergic mechanisms that are involved but the non-
specific receptor binding that does occur to a greater or lesser degree with all these drugs.

Sometimes it's the rare cases, perhaps the results of uncommon genetic polymorphisms, that yield the most information. I hope that, based on studies such as the one Elizabeth has cited,
people do not ignore the SSRI/weight gain connection or write it off. I think it still deserves further study, and I have the utmost sympathy for anyone who has experienced it. It's
not a fun thing.

> I don't take kindly to being called "naive" just because I bring up professional ethics as though it were a real issue for some researchers. Please try to be more considerate. Thanks.
> > David Michelson (lead author) works for Lilly.
> A number of the other authors work for universities. So? I think before you accuse people of twisting their results around, you should have some evidence. If studies funded by other sources (say, NIMH) showed differently, then I'd be more convinced by accusations that Lilly fixed this one. As it is, I don't doubt their results. I think they are plausible.
> > Also of note are the previous studies involving Prozac in which some of the authors have been involved. All that I have read were funded by Lilly. They also had results favorable to Lilly.
> Post hoc, ergo propter hoc...?
> > The study does not say there is no weight gain on Prozac. It says the weight gain on Prozac was equal to the placebo group weight gain.
> Right; meaning that Prozac does not appear to "cause" weight gain any more often than an inactive placebo "causes" it. That is, people didn't gain weight on Prozac that they wouldn't have gained off it.
> > On Prozac 25.4% of the participants had 7% or more increase in weight. In placebo it was 26.7%. The weight gain in the Prozac group was attributed to improvement in appetite after recovery while it was poor nutrition for the unfortunate placebo group.
> Weight gain was associated with initial appetite loss. I don't see where it says that it was caused by poor nutrition in the placebo group. As far as I can tell, they attribute it to recovery from depression in *both* groups.
> See, they only looked at people whose depression was remitted, whether they were on Prozac or placebo...that's why there were so many placebo dropouts by week 50, because most of the people on placebo relapsed. So they were comparing Prozac responders to placebo responders. IOW, they were controlling for the presence of depression. A study that compared Prozac to placebo without controlling for depression would probably make it appear that Prozac was causing weight gain because more of the placebo group would remain depressed (depressed people weigh less, as a whole, than nondepressed ones, though there are individuals who gain weight while depressed). That would be a design flaw.
> > Their statement that "the number of fluoxetine-treated patients with a 7% or greater increase in weight never exceeded that of patients in the placebo group" loses some impact when you consider that only 15 placebo participants were able to finish the study.( It will be a great sound bite though) The results of all participants, whether they completed or not, were a little different.
> > Prozac- 13.2% had 7% or greater weight increase.
> > Placebo- 7.4% had 7% or greater weight increase.
> This isn't very impressive. The placebo dropouts had less time to gain weight because they left the study early; of *course* fewer of them are going to. You'd have to look at when they dropped out, and how much weight they gained per unit time, in order to make this meaningful.
> Note that they also said: "Weight change did not vary among patients assigned to receive placebo who dropped out before completing 26 total weeks (12 weeks of acute treatment and 14 weeks of continuation therapy) compared with patients receiving placebo who completed 26 total weeks."
> > I could go on and on ripping this apart but I think you get the picture. You can make numbers mean whatever you want.
> You haven't made them mean what you want, though. You haven't ripped anything apart. Adam's "I know my body" argument is far more convincing.
> Look, all I'm saying is, this weight gain phenomenon doesn't seem to be well validated. Yes, it probably happens occasionally, but not enough to show up as statistically significant even in large trials. I think it's probably overreported by people who just fear the normal weight gain that comes with recovery. This is unfortunate indeed.




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