Psoriasis

Psoriasis has recognized association with cAMP: cAMP metabolism inhibition is the accepted mechanism of action of apremilast, one of the primary treatments for psoriasis PMID 26481941.  PDE4 returns cAMP to AMP: inhibition will tend to increase available cAMP, but decrease adenosine. This decrease in adenosine has been observed in sensitive individuals: insomnia and suicidal ideation PMID 35576125. IMG

Topiramate chemical structure resembles cAMP vs cGMP and has shown early evidence of benefit in treating psoriasis 12100195.

Sertraline shares chemical structure with apremilast. Taking an SSRI is associated with decreased risk of psoriasis PMID 33257042 and decreased need for primary treatment for psoriasis PMID 23711088. This may be attributable to sertraline primarily, or it may be more broadly shared. IMG

Psoriasis is associated with an increased risk of incidental suicidal ideation PMID 9892952.

Diphenhydramine also shares the 6-amino-methyl structure seen in apremilast, and is recommended for treatment of sleep difficulty and/or itching related to psoriasis: PMID 9507561. Hydroxyzine does not share this structure, but benztropine does.

Lithium has long been known to be a adenylate cyclase inhibitor, decreasing cAMP production PMID 4191451. Decreased epidermal cAMP production has been implicated in this unfortunately common (2-6%) side-effect PMID 19287551. IMG

Beta-blockers increase risk for psoriasis, with the mechanism being hypothesized as related to blocking epinephrine-based activation of adenylate cyclase PMID 32766006. Beta-blocker inhibition of epinephrine's cAMP induction has been directly observed in animal model PMID 4501130. Using this information to address mania, beta-blockers are thus expected to augment the long-recognized adenylate cyclase inhibition effect of lithium, with corresponding increase in ATP, addressing the root cause of mania. In cases where lithium alone is insufficient to increase ATP/ resolve mania, beta-blockers may augment the response at the same location: adenylate cyclase inhibition. IMG

Bupropion is associated with a fulminant, rapid-onset psoriasis that can be life-threatening PMID 34745784. Bupropion inhibition of norepinephrine's adenylate cyclase activation has been directly observed in animal models: PMID 6320035, 6312356.

Despite the expectation that bupropion, as a stimulant, would increase blood pressure, my clinical observations have been more consistent with adrenergic blockade. A recent case of pheochromocytoma I attended had found bupropion to be a particularly helpful treatment prior to his diagnosis. Does bupropion have beta-blocker activity? IMG

Psoriasis has been correlated with Parkinson's disease PMID 27057013, with worsening psoriasis predicting worsening Parkinson's PMID 35870136. Parkinson's has been associated with a decrease in adenosine derivatives, including cAMP in Parkinson's disease model PMID 8821058, 18717735. 

I have observed an unusually high frequency of psoriasis among patients with catatonia, resolving with resolution of catatonia, another type of dystonia, suggesting common etiology.  IMG

Allopurinol has been used to treat psoriasis 4274726, apparently inhibiting PDE 4,7,8

BZD, being xanthine-similar, may prevent xanthine from acting as a physiologic PDE 147 inhibitor, decreasing available cAMP and therefore aggravating psoriasis.