Hypersexuality

Bipolar mania sometimes includes hypersexuality, traditionally stigmatized and moralized as hedonistic. A more objective approach might hypothesize excessive or uncomfortable physiologic engorgement looking for relief.

What little is known about sexual engorgement is that treatments intended to increase engorgement strongly resemble the purine inosine and inhibit the purine enzyme PDE5 to increase the guanosine-derivative cGMP.

Zaprinast is a lab-reagent PDE5 inhibitor with a striking resemblance to inosine.

Inosine-derivatives are likely physiologic inhibitors of PDE5 and likely cause physiologic engorgement.

One scenario that causes decreased adenosine with compensatory increases in I,X,G derivatives (presenting as bipolar mania) is decreased adenylosuccinate synthase activity, impairing the sole adenosine synthesis pathway and causing buildup of inosine-derivatives, which in turn cause excessive engorgement and likely present with hypersexuality.

Hypersexual bipolar mania identifies a particular biochemistry, which predicts particular treatment response and non-response.

I recently attended a case with hypersexual psychotic mania after receiving full doses of two (SGA) antipsychotics, consistent with treatment guidelines, without response.

662 mg aripiprazole lauroxil long-acting injectable
5 days prior to admission (sufficient for absorption)
2 mg risperidone x four doses in <24 hr prior to intake

Dopamine hypothesis does not explain non-response.

Lack of response is predictable with purine mechanisms of antipsychotics, since inhibiting IMP/XMP conversion will not result in less IMP.

PDE5 is selectively expressed in sexually responsive tissues and in the retina. This innate physiology is recreated in film as mild visual blurring to suggest infatuation.

Inosine-similar PDE5 inhibitors commonly cause blurred vision: priapism (pathologic engorgement) is a listed adverse event.

Inosine-similar risperidone and paliperidone commonly cause blurred vision (mechanism of action unknown) and priapism is a listed adverse event.

Correlations between chemical structures and known side-effects may clarify underlying mechanisms.

Statins worsen bipolar symptoms XXXX and increase activity of PDE5 inhibitors 16490024, potentially having anti-ED activity on their own 24628781. IMG