Intracranial hemorrhage after a single dose of Yohimbine in a chronic user of clonidine

Abstract

Introduction: Yohimbine, an alpha-2 adrenoreceptor antagonist found in a variety of supplements, has been historically used to treat libido, erectile dysfunction, xerostomia, and as a weight loss enhancement. Yohimbine toxicity causes a sympathomimetic syndrome as demonstrated by the case below of a female who developed an intracranial hemorrhage (ICH) following an ingestion of yohimbine.

Case: This case follows a 39-year-old female who presented to the emergency department (ED) with complaints of nausea, emesis, and flushing following the ingestion of a female sexual enhancement supplement labeled to contain yohimbine (BioXgenic Nature's Desire) one hour prior. The patient took her prescribed 0.1 mg clonidine when the symptoms commenced. Upon arrival, the patient's blood pressure was 198/93. She developed neurological sequelae including a left-sided facial droop and weakness of her right extremities. A computed tomography scan demonstrated an acute basal ganglia hemorrhage with mild mass effect and mild subarachnoid hemorrhage. She was transferred to a regional referral hospital and discharged 16 days later to a rehabilitation center with persistent neurological sequelae.

Discussion: This patient exhibited sympathetic toxicity temporally associated with yohimbine ingestion. Our patient also had a variety of risk factors that increased the likelihood of a poor outcome with yohimbine. Chronic use of clonidine is known to down-regulate alpha-2 receptors. This leads to dependence of clonidine to maintain adrenergic homeostasis and could potentiate the effects of yohimbine. To compound effects, our patient was also taking bupropion and desvenlafaxine, which inhibit norepinephrine reuptake, likely worsening our patient's sympathomimetic response. Despite the temporal relationship of our patient's ICH and ingestion of yohimbine, a definitive relationship cannot be inferred due to our lack of confirmatory testing of yohimbine content and possibility of adulterants. The U.S. Food and Drug Administration (FDA) does not regulate the supplement market strictly, with multiple studies illustrating variation among ingredients of supplements despite stated quantities on the labels.

Conclusion: Dietary supplements are not required by the FDA to undergo efficacy or safety testing, necessitating clear post-marketing communication regarding potential adverse events from various supplements. Users should be aware of yohimbine-containing products and the possible side effects of toxicity. It is crucial that physicians and patients be aware of possible drug-supplement interactions of yohimbine and the presentation of sympathomimetic syndromes.

Keywords: Clonidine; Hypertensive emergency; Intracranial hemorrhage; Yohimbine.