Despite these side effects, the patient chose to continue using midodrine for 1 more week since he felt the symptoms were decreasing with time. Seven days later, checking his dysgeusia and dysosmia status, he stated how he no longer experienced dysosmia and, although he still had dysgeusia, it was not as bothersome. The patient decided to continue with the treatment but stated that he would consider a lower dosage if these adverse effects did not completely subside.

The onset and duration of the patient’s dysosmia and dysgeusia symptoms are consistent with the pharmacokinetic profile of the medication; the reported timeframe matches the onset and dissipation of midodrine after each dose. Upon evaluation using the Naranjo probability score, the authors say the adverse events can be considered definite (score = 9).

One such instance of dysgeusia and dysosmia related to midodrine was reported by a 64-year old male, detailed in a 2004 case study (published in the Annals of Pharmacotherapy). Following a dose increase to 12.5mg daily the patient began to experience abnormal taste and smell disturbance. When this patient’s dosage was again lowered, the adverse effects ceased.


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The authors are unsure as to the cause of this mechanism, but speculate that as midodrine acts on the alpha-1 receptors, there is a chance that the medication may be activating the G-protein-coupled receptors (GPCRs) on the specific taste receptors. Although not a human study, taste aversion has been shown in rats exposed to cirazoline, another alpha-1 receptor agonist.2  Other medications that have been linked to olfactory perception changes, however not being used by this patient, include beta-blockers, dihydropyridine calcium channel blockers, diltiazem, enalapril, doxycycline, ciprofloxacin, lovastatin, methotrexate, and terbinafine.

Conclusion:

This case illustrates the likelihood of smell and taste disturbance adverse effects with midodrine use. The authors note how both effects may lessen or resolve over time with the use of the medication. This patient’s symptoms lessened over time and he was able to function but a sustained level of such symptoms could lead to serious health concerns such as weight loss, nutritional deficits, and impact on mental health. These findings suggest further tests to investigate the adverse effects of midodrine should be conducted.

References:

1. Mitka M. FDA takes slow road toward withdrawal of drug approved with fast-track process. JAMA. 2011;305(10): 982-984.

2. McMahon LR, Morien A, Davies BT, et al. Conditioned taste aversion in rats induced by the alpha-1 adrenoceptor agonist cirazoline. Pharmacol Biochem Behav. 1994;48(3):601-604