New research by scientists at the Sanford-Burnham Medical Research Institute in the United States into the connection between antipsychotic medications and insulin has found that some antipsychotics can cause the metabolic side effects of diabetes and obesity.
The study, published in the journal Molecular Psychiatry, showed how antipsychotic drugs can impede normal metabolism through the activation of a protein called SMAD3, which plays a key role in the transforming growth factor beta (TGFbeta) pathway. The TGFbeta pathway works to regulate a range of biological processes, such as insulin signalling, cell growth and inflammation.
The researchers highlighted that all antipsychotic drugs that result in metabolic side effects activated the SMAD3, but that antipsychotics free from such side effects did not. In addition, the SMAD3 activation was wholly independent from their neurological effects, which means that there is the potential for antipsychotics to be designed that are able to retain beneficial therapeutic effects in the brain but do not have the metabolic side effects, and therefore be safer for patients suffering from conditions such as bipolar disorder and schizophrenia.
Senior author Fred Levine commented “We now believe that many antipsychotics cause obesity and diabetes because they trigger the TGFbeta pathway. Of all the drugs we tested, the only two that didn’t activate the pathway were the ones that are known not to cause metabolic side effects.”

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