Antipsychotic

But he did find that the Levo amphetamines seemed to be more closely associated with psychosis.

No, for Solomon Snyder, his main question, once he had come to this conclusion that amphetamines could trigger psychosis by flooding the brain with dopamine, That led him to his next question, which was, okay, how do antipsychotic drugs work? Because he had this picture in his mind, something like this.

Suppose that antipsychotic drugs like chlorpromazine and Haldol, suppose they work by blocking dopamine receptors.

Then I have this simple, beautiful picture where if I flood your brain with dopamine, I can induce schizophrenia or a schizophrenia-like state.

If I block dopamine activity, I can alleviate this schizophrenia state.

And so by turning dopamine on and off, it's almost as if I can turn psychosis on and off.

And so after the amphetamine research, A lot of his research was focused on understanding exactly what antipsychotic drugs did to the brain, which, interestingly enough, even in 1970 was not entirely known.

People did theorize that there was some connection between drugs like chlorpromazine and antipsychotic.

Imagine that a 26-year-old man on risperidone for six months comes to your office for a follow-up appointment, and he mentions that he's been having trouble in the bedroom.

He didn't bring it up sooner because he was embarrassed by his erectile dysfunction, but as clinicians we should remember that sexual side effects are one of the most common reasons that young people stop taking antipsychotics.

So why does this happen? While there are several possible mechanisms, dopaminergic blockade causing prolactin elevations is common.

As you know, dopamine doesn't just regulate mood, motivation, and psychosis.

It also acts as the body's brake on prolactin release, which itself gets released when we treat psychosis with dopamine-blocking antipsychotics.

As prolactin rises, it causes adverse effects in both sexes, including menstrual irregularities, galactorrhea, erectile dysfunction, and decreased libido.

Today's episode dives deep into antipsychotics and sexual side effects with Dr. Freudenreich, who's a professor of psychiatry at Harvard Medical School and a psychiatrist at the Massachusetts General Hospital, where he co-directs the MGH Psychosis Clinical and Research Program and also directs the MGH Fellowship in Public and Community Psychiatry.

We'll discuss which antipsychotics are the worst offenders when it comes to prolactin elevation.

Today, we're discussing a study conducted as a collaboration between Origin, the University of Melbourne, and Monash University that tackled this very question, studying people experiencing their very first episode of psychosis who had never taken antipsychotic medication before.

The results challenge some widely held assumptions and offer a new perspective on what's really driving brain changes and early psychosis.

Joining me is Dr. Sid Chopra from Origin and the University of Melbourne, first and corresponding author of a recent paper in biological psychiatry titled Differential Effects of Illness and Antipsychotics on Cortical Thinning in First Episode Psychosis.

Dr. Chopra, welcome to the Biological Psychiatry Podcast.

Thank you.

Like people who have more severe illness symptoms will be given more medications, well, I guess high doses of medications for longer.

And this kind of confounds illness severity and medication dose.

And Antipsychotics remain the first-line treatment, and they kind of have since maybe the 50s.