The trace amine theory of spontaneous hypertension as induced by classic monoamine oxidase inhibitors

Abstract

The classic monoamine oxidase inhibitors (MAOIs) tranylcypromine (TCP) and phenelzine (PLZ) are powerful antidepressants that come with an equally powerful stigma, and are thus rarely prescribed-despite their well-established effectiveness. Some of these preconceptions appear to stem from unclarity, as the etiology of a rare but important side effect, 'spontaneous hypertension' (SH)-a significant increase in blood pressure absent dietary tyramine ingestion-remains improperly elucidated. This paper aims at uprooting some of the stigma surrounding MAOIs by advancing the trace amine (TA) theory as the causative underpinning of SH. This theory posits that SH results from the considerable influx of TAs observed following TCP-or PLZ-administration. TAs are known, albeit at greatly supraphysiological levels, to raise blood pressure on account of their propensity to exert potent indirect sympathomimetic effects; additionally, some research posits that TAs may induce vasoconstrictive effects partly or wholly separate therefrom, which would then constitute a second hypertensive mechanism. TAs are endogenous to the human body in low quantities. Both TCP and PLZ cause marked elevations of 2-phenylethylamine (PEA), meta-and para-tyramine (m-/p-TYR), octopamine (OA), and tryptamine (TRYP), following both acute and (sub) chronic administration. This paper holds that TYR plays a pivotal role in causing SH, due to its strong pressor effect. Cautious treatment of SH is advised, given its typically self-limiting nature. The risk of hypotensive overshoots must be taken into account. For severe cases, this paper urges reconsideration, following suitable confirmation trials, of antipsychotics (notably risperidone) as these agents may reduce striatal p-TYR levels.

The prescriber’s guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression

“…In the event of a transient BP increase 4.5.1 This side effect can arise shortly after MAOI dosing (mostly with tranylcypromine). 32 A rise in BP is then observed for a couple of hours (the rise in BP is often limited, although in extreme cases it can reach 180 to 200 mmHg systolic). Considering the limited duration of this BP increase, the risk is most often limited; therefore, treatment is typically not indicatedalthough it may still be advisable in more severe cases.…”

“…The cessation of MAOI treatment is only rarely necessary. Note: Several clinician members of the Workgroup mention the successful treatment of exercise-induced hypotension in MAOI patients with propranolol. This is a novel treatment strategy in expert clinical practice; there is no relevant literature at present (this means confirmatory research is required; implement with care). In the event of a transient BP increase This side effect can arise shortly after MAOI dosing (mostly with tranylcypromine) 32 . A rise in BP is then observed for a couple of hours (the rise in BP is often limited, although in extreme cases it can reach 180 to 200 mmHg systolic).…”

“…In the event of a transient BP increase This side effect can arise shortly after MAOI dosing (mostly with tranylcypromine) 32 . A rise in BP is then observed for a couple of hours (the rise in BP is often limited, although in extreme cases it can reach 180 to 200 mmHg systolic).…”

A Scoping Review to Assess Risk of Fracture Associated with Anxiolytic Medications

“…All members in the class of anxiolytics are utilized to mitigate anxiety-provoking stimuli, but the pharmacologic effects could be accompanied by side effects such as blood pressure fluctuations, cognitive impairment, and delirium, which can lead to falls. [13][14][15] In the geriatric population, falls cause 95% of hip fractures which may result in decreased long term mobility and nursing home admission. 16 While some psychotrophic medications have been associated with an increased risk of fracture, anxiolytics, which are prescribed more commonly, have not been evaluated systematically.…”

Fast and Sensitive Quantification of AccQ-Tag Derivatized Amino Acids and Biogenic Amines by UHPLC-UV Analysis from Complex Biological Samples

“…Tryptamine, tyramine and 2-phenethyl amine are called trace amines and have roles in neural and vascular functions [ 13 ], while cadaverine and putrescine are important molecules for cell division [ 14 ]. In addition to their physiological roles, biogenic amines also play a role in the pathomechanism of several diseases such as hypertension [ 15 ], schizophrenia [ 16 ] and cancer development [ 17 ]. Ethylamine represents an organic compound that was found to be negatively associated with the risk of the development of type 2 diabetes mellitus in a Japanese population [ 18 ].…”