Experts proclaim that approximately 14.4 million Americans take an antipsychotic medication. The drugs are typically prescribed for bipolar disorder, schizophrenia, or a number of other behavioral disorders — making them among the most prescribed drugs in the U.S.
Unfortunately, despite their widespread use, most of the medications are known to cause the metabolic side effects of obesity and diabetes.
Naturally this presents a significant dilemma to individuals as they weigh a choice between improving their mental health and damaging their physical health.
A new paper in the journal Molecular Psychiatry, discusses the biochemical changes triggered by the antipsychotic drugs.
The medications interfere with normal metabolism by activating a protein called SMAD3. The SMAD3 protein, in turn, is an important component of a cellular conduit termed the transforming growth factor beta (TGFbeta) pathway.
The TGFbeta pathway regulates many biological processes, including cell growth, inflammation, and insulin signaling.
In the current study, all antipsychotics that cause metabolic side effects activated SMAD3, while antipsychotics free from these side effects did not.
What’s more, SMAD3 activation by antipsychotics was completely independent from their neurological effects, raising the possibility that antipsychotics could be designed that retain beneficial therapeutic effects in the brain, but lack the negative metabolic side effects.
“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,” said Fred Levine, M.D., Ph.D., senior author of the study.
The TGFbeta pathway also plays an important role in metabolic disease in people who don’t take antipsychotic medications.
“It’s known that people who have elevated TGFbeta levels are more prone to diabetes. So having a dysregulated TGFbeta pathway — whether caused by antipsychotics or through some other mechanism — is clearly a very bad thing,” said Dr. Levine.
“The fact that antipsychotics activate this pathway should be a big concern to pharmaceutical companies. We hope this new information will lead to the development of improved drugs.”