Phentermine Use in Patients with Seizures on Antiepileptic Medications
Phentermine should generally be avoided in patients with seizure disorders, even when seizures are controlled with antiepileptic medications, due to concerns about lowering seizure threshold and precipitating seizures. 1
Primary Contraindication
The 2022 AGA Clinical Practice Guideline explicitly states that phentermine-containing medications should not be used in patients with untreated hyperthyroidism "due to concerns for arrhythmias and seizures." 1 While this statement specifically addresses untreated hyperthyroidism, the underlying concern about seizure risk is relevant to all patients with seizure susceptibility.
Evidence of Seizure Risk
Case series data demonstrates an association between fenfluramine-phentermine combination therapy and seizure occurrence, including recrudescence of previously controlled idiopathic generalized epilepsy and new-onset seizures in midlife. 2
The mechanism appears to involve lowering of seizure threshold, with seizures persisting even after discontinuation of therapy in some cases. 2
When discontinuing phentermine-topiramate ER, the guideline specifically recommends gradual dose tapering "to minimize the risk of precipitating a seizure," indicating recognized seizure risk even during withdrawal. 1
Alternative Weight Loss Medications
For patients with seizure disorders requiring obesity pharmacotherapy, naltrexone-bupropion ER is explicitly contraindicated and should be avoided. 1 This leaves limited options:
Liraglutide 3 mg or semaglutide 2.4 mg (GLP-1 receptor agonists) are safer alternatives with no specific seizure-related contraindications. 1
Orlistat has no seizure-related concerns but has gastrointestinal side effects and lower efficacy. 1
Clinical Decision Framework
If phentermine is being considered despite seizure history:
Absolute avoidance is recommended for patients with active or poorly controlled seizures. 1
For patients with remote seizure history (childhood epilepsy in long-term remission), the risk-benefit calculation remains unfavorable given available safer alternatives. 2
Never use phentermine in combination with other medications that lower seizure threshold or in patients with risk factors including young age, mental retardation, antiepileptic polytherapy, or prominent epileptic activity on EEG. 3
Common Pitfalls
Do not assume that well-controlled seizures on antiepileptic medications eliminate the risk—phentermine may still lower seizure threshold sufficiently to overcome medication protection. 2
Avoid the misconception that short-term use (FDA-approved 12-week duration) reduces seizure risk—case reports show seizures can occur during treatment course. 2
Do not overlook drug interactions between phentermine and enzyme-inducing antiepileptics (carbamazepine, phenytoin, phenobarbital) that may alter medication levels. 4, 5