Never Forget the Fine Print: From Fertility Rites to “Miracle Med”

PSYCHIATRISTS ARE PHYSICIANS FIRST

When the email from “Sam” arrived asking about adding a natural weight loss product to his more mainstream prescription medications, I was not surprised. Binge eating was his bête noire. A onetime college athlete who lost his scholarship because of an ankle injury, he had since sat around eating while watching sports on TV and lamenting his lost career. He desperately wanted to shed unwanted weight, but treatments that control bingeing do not guarantee weight loss. He had tried hoodia with no success. So, when he heard about a new natural weight loss concoction, he was understandably excited yet skeptical because he knew of the government’s crackdown on hoodia.

Sam forwarded me a laundry list of ingredients without hoodia but with yohimbine (Pausinystalia yohimbe). Years had passed since I had seen that word in print.

“Was it safe?” was all he wanted to know. Whether it worked seemed to be a secondary concern. My short answer was no, and I promised a longer explanation at his next appointment. In the interim, flashbacks of another patient from long ago popped up. Although psychopharmacology has quickly evolved in the decades since the emergency department (ED) consult, that related case was too dramatic to forget.

I remember the frantic call from the ED staff, begging me to see their patient posthaste.

“Maybe you can prescribe lithium or haloperidol or something like that. We cannot contain him here, but we have nowhere to send him,” said the pressured voice on the phone. “He saw a psychiatrist, but that is all we know.”

It was Sunday midmorning, late summer, when many Manhattanites escape town leaving side streets empty and opening tables at New York City’s unending array of eateries. Uninterrupted by impatient New Yorkers demanding seats, out-of-towners could enjoy unhurried brunches, fussed over by glamorous waitstaff who were patiently anticipating their Broadway debuts. The tidy townhouses lined side by side behind the hospital conveyed an extra sense of calm that contrasted with rowdy Saturday nights.

Taking a shortcut, I quickly arrived at the ED, which was nearly abandoned. I peered through the window of the make-do quiet room and could see that the doctor who called the consult was not exaggerating. A tanned, middle-aged man stood a few feet behind the door. He looked to be 50-something, but he jumped and hopped like a child, in sync to the beat of an invisible drum. His thinning silver hair swung wildly. Most strikingly, his suit jacket was draped around his waist, hiding his backside and little else. Empty sleeves looped across the front, dangling like a loincloth, albeit one with a shiny—probably pricey—silk lining. Where he left his pants, shoes, socks, and shirt was anyone’s guess. All I knew is that he wore nothing else.

Per protocol, I checked the chart before walking into the room, not just for safety’s sake but to learn a little about the patient by skimming the demographics. He was, in fact, middle-aged, married, and, in hindsight, possibly a vestige of the Mad Men generation, although Mad Men had not aired yet. For that matter, sildenafil had not been invented, nor had the now-ubiquitous second-generation antipsychotics that are often used to treat bipolar disorder. Per the intake sheet, “Mr Smith” was a senior vice president at a name-brand advertising firm, even if his present posture suggested otherwise.

The history mentioned that his private psychiatrist, who had retreated to the Hamptons for the summer, referred all emergencies to the hospital, as per his answering machine message. Before leaving, said psychiatrist started him on lithium, then carbamazepine, maybe even valproate, but now everything spiraled out of control. Experience told me that advertising executives with bipolar disorder tendencies are not uncommon, because advertising takes high energy, unabashed enthusiasm, and lots of chutzpah, which are abundant in hypomanic states. Yet it was also unlikely that someone with uncontrolled bipolar disorder could rise so high through the corporate ranks, even if his prescriptions screamed bipolar. It was also unlikely that this behavior represented garden-variety bipolar disorder, because the nurse noted that he was disoriented to time and place, distracted, and responding to unseen stimuli. His rapid, jerky movements put me on high alert for impending seizures, even though a cursory neurological exam had cleared him.

I scrolled through the medication list, checked the charted vital signs, scanned all labs listed, and looked for clues to explain this seemingly sudden deterioration. Even the toxicology screens were negative. The medications included several antihypertensives, which opened the possibility of a recent cerebrovascular accident secondary to hypertension, but he was moving all 4 limbs without restrictions, and his frenetic, dancelike activity functioned as a makeshift cardiac stress test, making it unlikely (but not impossible) that his strange symptoms followed hypoperfusion. There was only 1 odd entry, a little, nearly illegible word: Yocon.

In those days, we checked prescription pharmaceuticals through big, bulky Physicians’ Desk Reference editions with thin pages and small print. And that was where I found the culprit: that little word was the trade name for yohimbine, a reputed (but disputed) aphrodisiac used in fertility rituals in Cameroon, Central Africa, according to a memorable medical school ethnopharmacology lecture. I called the man’s internist, who had hospital privileges and even made rounds on weekends. The internist checked his chart and confirmed that a urologist had started the man on prescription yohimbine a few weeks earlier. The doctor noted that he added more antihypertensive medications soon after, which made sense, given that this herb can increase blood pressure and interfere with the efficacy of blood pressure medications.

The nurses crowded outside the room, eager for an explanation, and appreciative of the colorful story behind this mystery. Yohimbine was an α1-adrenergic agonist, a product of an East African tree with a similar name. It was marketed as an antidote to erectile dysfunction and subsequently approved for this purpose, despite equivocal evidence. Whether yohimbine helped in this regard was unclear, but its psychoactive properties were apparent. I wondered whether prescriptive yohimbine (or nonmedicinal yohimbe bark) directly increased libido as advertised, or whether it simply induced manic states in susceptible individuals, with the attendant hypersexuality of mania.

That theory was within the realm of possibility, especially because recent reports confirm that the stimulant especially affects individuals who are predisposed to bipolar disorder, as well as schizophrenia, panic disorder, and posttraumatic stress disorder. Even popular online consumer medical websites warn against its use in cases of depression because it can precipitate manic reactions.¹ The National Institute of Health’s National Center for Complementary and Alternative Medicine, now the National Center for Complementary and Integrative Health, has since taken a harsher stance, warning against its use in individuals with any psychiatric history.²

Over time, we learned much about yohimbine and its positive and negative effects. Although it fell into disuse after the invention of the much more predictable PDE5 inhibitors indicated for erectile dysfunction, online marketers still promote it for a wide range of problems, including appetite suppression and obesity. Yohimbine gained greatest use as a veterinary antidote to animal tranquilizers. It has been misused by some humans, as was the case with ketamine, a onetime animal tranquilizer turned club drug that has recently been repurposed as a treatment for depression. No comparable success stories have been reported for yohimbine, although bodybuilders cite anecdotal evidence that the herb enhances exercise endurance. In contrast, forensic medicine journals report tragic deaths among young bodybuilders,³ and note that yohimbine can cause delirium, hallucinosis, seizures, and sometimes deaths. An article in American Journal of Psychiatry confirms that it can switch depression into mania.¹

Importantly, dangerous interactions can occur with phenothiazines—so it was fortunate that the patient quieted down with a dark, soundless room and intravenous diazepam, prescribed by the neurologist to stop seizures should they occur. Aided by the tincture of time, and a short stay upstairs once a bed opened, he reportedly returned to baseline. When I checked on him a few days later, he did not recall this episode.

In hindsight, our mystery man escaped easily. Who knows what tragedies could have occurred had strong psychotropics been added to his medication mix without stopping the clandestine culprit? At worst, lethal medication interactions could have followed. And, at best, he would have been condemned to a lifetime’s treatment for a condition that might not have emerged without this botanical boost.

Fortunately, psychiatrists are physicians first, and we must consider the big picture, without reflexive and thoughtless prescriptions for psychotropics—even if the general public, as well as other medical professionals, assume that is all we do. As for Sam, I expect him to appreciate this warning story about yohimbine, even if the negative studies about its efficacy for weight loss disappoint him.

Dr Packer is assistant clinical professor of psychiatry and behavioral sciences at Icahn School of Medicine at Mount Sinai, New York, NY.

References

1. Price LH, Charney DS, Heninger GR. Three cases of manic symptoms following yohimbine administration. Am J Psychiatry. 1984;141(10):1267-1268.

2. Yohimbe. National Center for Complementary and Integrative Health. Updated November 2020. Accessed December 21, 2020. https://www.nccih.nih.gov/health/yohimbe

3. Anderson C, Anderson D, Harre N, Wade N. Case study: two fatal case reports of acute yohimbine intoxication. J Anal Toxicol. 2013;37(8):611-614.❒