Antidepressents promote insulin resistance

Hope you missed me - I've been away for a few days attempting some hillwalking in the Scottish hills, but while most of the rest of the UK has been bathed in sunshine, the Northwest Highlands have been wet and windy with low cloud. Typical. I prepared a couple of post before I went, so this is being posted from beautiful Gairloch in Wester Ross. (Google it if you want to know more!)

This is related to the last post about exercise reducing the panic symptoms that some people experience.

This study looked at the effects of antidepressants on metabolism and found that they induce insulin resistance. This of course is generally thought to be a bad thing.

In the light of the last post, maybe instead of giving drugs to the depressed - which have all sorts of sorry side effects - we should get them active and exercising again? Prescribe tabata squats for the schizophrenic?


Antidepressants induce cellular insulin resistance by activation of IRS-1 kinases.



Certain selective serotonin reuptake inhibitors (SSRIs) induce the clinical and biochemical manifestations of a metabolic syndrome by as yet unknown mechanism. Here we demonstrate that incubation (1 h) of rat hepatoma Fao cells with the SSRIs paroxetine and sertraline, but not with the atypical antipsychotic drug olanzapine, inhibited the insulin-stimulated Tyr phosphorylation of the insulin receptor substrate-1 (IRS-1) with half-maximal effects at approximately 10 muM. This inhibition correlated with a rapid phosphorylation and activation of a number of Ser/Thr IRS-1 kinases including JNK, S6K1, ERK and p38 MAPK, but not PKB (Akt). JNK appears as a key player activated by SSRIs because specific JNK inhibitors partially eliminated the effects of these drugs. The SSRIs induced the phosphorylation of IRS-1 on S307 and S408, which inhibits IRS-1 function and insulin signaling. These results implicate selected SSRIs as inhibitors of insulin signaling and as potential inducers of cellular insulin resistance.