Fenfluramine–Phentermine (Fen-Phen) and Seizures: Evidence for an Association

Spencer, David C.; Hwang, Jane; Morrell, Martha J.

doi:10.1006/ebeh.2000.0132

Cited by 4 publications

(4 citation statements)

References 25 publications

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“…Fenfluramine is an amphetamine‐like drug that was part of the popular “Fen–Phen” combination antiobesity medication (Spencer et al., 2000). Following the general use of this combination, serious adverse effects were described, especially heart valve disease and pulmonary hypertension (McCann et al., 1997; Dahl et al., 2008; Connolly et al., 2009).…”

Section: Methodsmentioning

confidence: 99%

Successful use of fenfluramine as an add‐on treatment for Dravet syndrome

et al. 2012

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Summary Purpose: Despite the development of new antiepileptic drugs, Dravet syndrome frequently remains therapy resistant and is a catastrophic epilepsy syndrome. Fenfluramine is an amphetamine‐like drug that has been used in the past as a part of antiobesity treatments. Because of the possible cardiac adverse effects (valve thickening, pulmonary hypertension) associated with use of fenfluramine, it was withdrawn from the market in 2001. In Belgium, a Royal Decree permitted examination of the potential anticonvulsive effects of fenfluramine in a clinical trial consisting of a small group of patients diagnosed with Dravet syndrome. Methods: Herein, we report 12 patients, 7 female and 5 male, with a genetically proven (11 of 12) diagnosis of Dravet syndrome who received fenfluramine as add‐on therapy. Key Findings: Their ages at their last evaluation ranged from 3–35 years. The mean dosage of fenfluramine was 0.34 (0.12–0.90) mg/kg/day. Exposure duration to fenfluramine ranged from 1–19 years. Seven of the patients who were still receiving the fenfluramine treatment at the time of the last visit had been seizure‐free for at least 1 year. In total, patients had been seizure‐free for a mean of 6 (1–19) years. In seven patients, the fenfluramine treatment was interrupted once during the follow‐up; seizures reappeared in three of the seizure‐free patients. Subsequent reintroduction of fenfluramine controlled the seizures in these three patients again. Only two patients exhibited a mild thickening of one or two cardiac valves without clinical significance. Significance: Compared with a recent long‐term follow‐up series in which a maximum of 16% of patients with Dravet syndrome were seizure‐free, our result of 70% of patients with Dravet syndrome remaining seizure‐free is noteworthy. Given the limitations of this observational study, a larger prospective study should be undertaken to confirm these promising results.

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Section: Methodsmentioning

confidence: 99%

Successful use of fenfluramine as an add‐on treatment for Dravet syndrome

et al. 2012

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“…Thus, our patient's negative UDS and blood phentermine level could be explained by its short half-life and a history of drug discontinuation about two months ago. Although the acute, sympathomimetic adverse effects of phentermine are well-known, there appears to be a paucity of publications that delve into the repercussions of long-term use [10][11][12].…”

Section: Discussionmentioning

confidence: 99%

“…Initial discontinuation of phentermine improved cardiac function, followed by worsening ventricular function on spontaneous re-initiation of the medication three months later [ 14 ]. Phentermine has been associated with valvular abnormalities, atrial fibrillation, and more so when combined with fenfluramine or dexfenfluramine, resulting in market withdrawal [ 11 , 15 ]. Conversely, a recent study using electronic health record data showed that long-term phentermine use (>12 months) was associated with minimal risk (0.3%) of cardiovascular disease [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

A Rare Case of Phentermine-Induced Nonischemic Cardiomyopathy

Damani¹,

Hassan²,

Mahapatra³

et al. 2022

Cureus

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Obesity is a global epidemic with steadily increasing prevalence in most countries. Weight loss is generally challenging for patients to tackle in the face of the temptation to overeat and avoid physical activity. Hence, clinicians and patients alike are likely to steer toward the use of anorexigens. We report the case of a 33-yearold female with no significant cardiac history who presented with dyspnea, productive cough, and chest pressure for one month and was diagnosed with new-onset heart failure with a reduced ejection fraction secondary to prolonged phentermine use. The authors aim to highlight phentermine's potential for precipitating heart failure, even in a young, relatively healthy person, especially with a growing obese population. Ultimately, healthy weight loss can be achieved by implementing dietary changes and encouraging adequate physical activity, as the World Health Organization (WHO) recommended. Anorectic drugs may be employed for short-term use. Further research concerning the long-term side effects of phentermine may avert the prescriber and patient from abusing this drug.

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“…A few substituted amphetamines, including MDMA, have also been associated with fibrosis and VHD. One such derivative is norfenfluramine, a metabolite of fenfluramine ( Vickers et al, 2001 ), which was frequently used as an anorexic agent in combination with phentermine, another anti-obesity medication ( Spencer et al, 2000 ). One study found 24 cases of VHD after using the fenfluramine-phentermine combination for an average of 12.3 months ( Connolly et al, 1997 ).…”

Section: Drug-induced Cardiac Valvulopathiesmentioning

confidence: 99%

Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins

Rouaud,

Calder,

Hasler

2024

J Psychopharmacol

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Though microdosing psychedelics has become increasingly popular, its long-term effects on cardiac health remain unknown. Microdosing most commonly involves ingesting sub-threshold doses of lysergic acid diethylamide (LSD), psilocybin, or other psychedelic drugs 2–4 times a week for at least several weeks, but potentially months or years. Concerningly, both LSD and psilocybin share structural similarities with medications which raise the risk of cardiac fibrosis and valvulopathy when taken regularly, including methysergide, pergolide, and fenfluramine. 3,4-Methylenedioxymethamphetamine, which is also reportedly used for microdosing, is likewise associated with heart valve damage when taken chronically. In this review, we evaluate the evidence that microdosing LSD, psilocybin, and other psychedelics for several months or more could raise the risk of cardiac fibrosis. We discuss the relationship between drug-induced cardiac fibrosis and the 5-HT2B receptor, and we make recommendations for evaluating the safety of microdosing psychedelics in future studies.

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Fenfluramine–Phentermine (Fen-Phen) and Seizures: Evidence for an Association

Cited by 4 publications

References 25 publications

Successful use of fenfluramine as an add‐on treatment for Dravet syndrome

Successful use of fenfluramine as an add‐on treatment for Dravet syndrome

A Rare Case of Phentermine-Induced Nonischemic Cardiomyopathy

Microdosing psychedelics and the risk of cardiac fibrosis and valvulopathy: Comparison to known cardiotoxins

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