A patient with a history of migraines, currently taking phentermine (phentermine) 37.5mg and topiramate (topiramate) 25mg, presents with numbness in their lip, left side of their face, fingertips, and feet, as well as speech difficulties, after starting phentermine, what is the cause of their symptoms and how should they be managed?

Likely Diagnosis: Drug-Induced Paresthesias from Topiramate

The patient's symptoms—numbness of the lip, left face, fingertips, and feet, along with speech difficulties—are classic adverse effects of topiramate, which they are taking for migraine prevention. These neurological symptoms (paresthesias and cognitive/speech impairment) are well-documented side effects of topiramate and represent the most likely cause of their presentation 1.

Understanding the Clinical Picture

The temporal relationship is critical here: symptoms began after one month of topiramate 25 mg, which coincides with the typical timeframe for topiramate-related adverse effects to manifest. The FDA label explicitly warns that topiramate may cause:

• Paresthesias (tingling of arms and legs) as a common side effect 1
• Effects on thinking and alertness, including confusion, problems with concentration, attention, memory, and/or speech 1
• Speech disturbances as documented in overdose cases, though can occur at therapeutic doses 1

The combination of phentermine 37.5 mg with topiramate 25 mg is noteworthy. While this combination is used therapeutically for weight management (at different doses), the patient appears to be taking these medications separately—phentermine for weight loss and topiramate for migraine prevention 2. The phentermine is less likely to be the culprit for these specific neurological symptoms, as paresthesias and speech difficulties are characteristic of topiramate, not sympathomimetic agents.

Differential Diagnosis to Exclude

While topiramate adverse effects are most likely, the following must be ruled out given the stroke-like presentation:

• Hemiplegic migraine with aura: The unilateral facial numbness and speech difficulties could represent migraine aura, though the persistent nature and involvement of extremities makes this less likely 3
• Transient ischemic attack (TIA): Despite negative MRI, TIA remains in the differential for transient focal neurological symptoms, particularly with left-sided facial and speech involvement 3
• Topiramate-induced metabolic acidosis: Can cause altered mental status and neurological symptoms, though typically presents with tiredness, loss of appetite, and irregular heartbeat 1
• Medication overuse headache (MOH): If the patient is using acute migraine medications frequently, this could complicate the clinical picture 3

Further Testing Required

Immediate Laboratory Evaluation

• Serum bicarbonate level to assess for topiramate-induced metabolic acidosis, as recommended for all patients on topiramate 1
• Basic metabolic panel including electrolytes, BUN, creatinine to evaluate renal function and acid-base status 1
• Complete blood count to rule out other systemic causes

Neurological Assessment

• Detailed neurological examination focusing on cranial nerves, motor strength, sensory testing, and speech evaluation to document the extent of deficits 3
• Cognitive screening to assess for topiramate-related cognitive impairment beyond speech difficulties 1

Cardiovascular Evaluation (if not already completed)

• Carotid duplex ultrasonography to detect carotid stenosis, given the focal neurological symptoms corresponding to left internal carotid territory 3
• Echocardiography if extracranial cerebrovascular disease does not account for symptoms, to search for cardioembolic source 3

Ophthalmologic Evaluation

• Urgent ophthalmologic examination if any visual symptoms develop, as topiramate can cause acute myopia and secondary angle closure glaucoma 1

Treatment Plan

Immediate Management

Discontinue or significantly reduce topiramate dose. The FDA label clearly states that if serious adverse effects occur, the healthcare professional will probably stop topiramate 1. Given the severity of symptoms (speech difficulties that made the patient think they were having a heart attack), this warrants immediate action.

• Gradual taper is preferred to avoid seizure risk in patients taking topiramate for epilepsy, though for migraine prevention, more rapid discontinuation may be appropriate 1
• Do not abruptly stop without medical supervision—the patient should be instructed on how to slowly stop taking topiramate 1

Alternative Migraine Prevention

Since the patient requires migraine prevention (they were prescribed topiramate 25 mg for this indication), alternative preventive therapy should be initiated:

• First-line alternatives: Propranolol 80-240 mg/day or other beta-blockers without intrinsic sympathomimetic activity 3
• Second-line options: Amitriptyline 30-150 mg/day, particularly if the patient has mixed migraine and tension-type headache 3
• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) if two or three other preventive medications have failed, though cost and insurance restrictions may limit access 3

Addressing the Phentermine

Reassess the need for phentermine 37.5 mg. While phentermine is less likely causing the neurological symptoms, it should be evaluated:

• If used for weight management: Consider whether the benefits outweigh risks, particularly given the patient's recent frightening neurological symptoms 2
• If weight loss is needed: Discuss alternative approaches including lifestyle modifications, as phentermine is approved only for short-term use 2
• Monitor for cardiovascular effects: Phentermine can cause hypertension and tachycardia, which could complicate the clinical picture 2

Critical Pitfalls to Avoid

• Do not dismiss paresthesias as benign: While paresthesias are common with topiramate (occurring in 28.8% of patients), they can be distressing and may indicate the need for dose reduction or discontinuation 4
• Do not continue topiramate at the same dose hoping symptoms will resolve: The FDA label warns that effects on thinking, alertness, and speech require immediate medical attention 1
• Do not overlook metabolic acidosis: This can develop insidiously and cause serious complications if untreated 1
• Do not assume all symptoms are drug-related without proper workup: The stroke-like presentation warrants thorough evaluation to exclude true cerebrovascular disease 3

Follow-Up Plan

• Reassess symptoms within 1-2 weeks after topiramate discontinuation or dose reduction to confirm resolution of paresthesias and speech difficulties
• Monitor serum bicarbonate if continuing topiramate at any dose 1
• Establish effective migraine prevention with alternative agent, allowing 2-3 months to assess efficacy 3
• Educate on migraine triggers and lifestyle modifications to reduce migraine frequency 3
• Limit acute migraine medication use to no more than twice weekly to prevent medication overuse headache 3