A Narrative Review: Phentermine and Topiramate for the Treatment of Pediatric Obesity

Figures & data

Table 1 Summary of Trials of Phentermine, Topiramate, and PHEN/TPM for Obesity Management in Pediatrics

Study	Design	Sample Size (n)	Age (yr)	Main Inclusion Criteria	Dose	Duration	Efficacy	Safety	Quality of Evidence
Phentermine
Lorber et al (1966)^Citation46	3-parallel-arm (Phenmetrazine vs Phentermine vs Placebo) RCT Outcome measure: Weight change (kg)	68	3–15	BMI>95th%	Phenmetrazine 12.5 mg daily Phentermine 15 mg daily	12-wk	Phentermine vs placebo: ‒0.1 kg	Phentermine Arm: Insomnia (n=1)	Low
Rauh et al (1968)^Citation48	2-parallel-arm (Chlorphentermine vs Placebo) RCT Outcome measure: Weight change (kg)	30	12–18	BMI>95th%	Chlorphentermine 65 mg daily	12-wk	Phentermine vs placebo: ‒6.7 kg	No SAEs	Low
Ryder et al (2017)^Citation47	Retrospective chart review Outcome measure: %BMI change	25	12–18	BMI>95th%	Phentermine 15 mg/day	24-wk	Phentermine vs placebo: ‒4.1%BMI	Phentermine arm: Increased blood pressure, heart rate	Moderate
Ali Ibrahim et al (2022)^Citation45	Retrospective chart review Outcome measure: %BMIp95 change	30	12–18	BMI>95th%	Phentermine 8–37.5 mg/day	24-mo	Youth taking phentermine had mean reduction in %BMIp95 of ‒15%	AE (n=6): agitation, sleep disturbances, increased blood pressure, anxiety, photophobia, dehydration	Low
Topiramate
Fox et al (2015)^Citation49	Retrospective chart review Outcome measure: %BMI change	28	14–18	BMI>95th%	Topiramate 25 to 125 mg/day	24-wk	Topiramate vs lifestyle modification: ‒4.9%BMI	No SAEs	Low
Fox et al (2016)^Citation50	2-parallel-arm (Topiramate + meal replacement vs placebo) RCT Outcome measure: %BMI change	21	14–18	BMI>120% of the 95th%	Topiramate 75 mg/day	24-wk	Topiramate vs placebo: ‒1.9%BMI	No SAEs	Low
Consoli et al (2019)^Citation51	2-parallel-arm (topiramate vs Placebo) RCT Outcome measure: %BMI change	62	15–45	Prader Willi Syndrome Youth: BMI>95th% Adult: BMI > 30 kg/m^2	Topiramate 50–200 mg/day	8-wk	%BMI Change: Topiramate vs Placebo: No difference Hyperphagia scores: Topiramate vs Placebo: significant reduction in topiramate group	No SAEs	Low
Berman et al (2023)^Citation52	Case series Outcome measure: %BMIp95 change	5	8–12	BMI>95th% Developmental delay	Topiramate 100 mg/day	16-wk	Topiramate group mean reduction in %BMIp95 ‒12%	4/5 No SAEs 1/5 drowsiness	Low
PHEN/TPM
Kelly et al (2022)^Citation53	3-parallel-arm (PHEN/TPM 7.5 mg/46 mg, vs PHEN/TPM 15 mg/92 mg vs Placebo) RCT Outcome measure: %BMI change	223	14–18	BMI>95th%	PHEN/TPM 7.5 mg/46 mg PHEN/TPM 15 mg/92 mg	56-wk	High Dose PHEN/TPM: ‒10.44%BMI vs Low Dose PHEN/TPM: ‒8.11% vs +0.1% Placebo	3 SAEs: bile duct stone, depression, suicidal ideation	High

Abbreviations: %BMI_p95, BMI in excess of the 95th percentile; BMI>95th%, body mass index greater than the 95th percentile; RCT, randomized controlled trial; AE, adverse event, SAE, serious adverse event; HbA1c, hemoglobin A1c; BMI, body mass index; GI, gastrointestinal.; GI, gastrointestinal; LDL, low density lipoprotein, PHEN/TPM, Phentermine/topiramate extended release product; TG, triglycerides.

Table 2 Overview of Phentermine, Topiramate, and PHEN/TPM

Agent	Phentermine	Topiramate	PHEN/TPM
Obesity Approval Status	Yes ≥16yo for short-term use	No ≥ 2 years old for seizures ≥ 12 years old for migraine prophylaxis	Yes ≥ 12 years old
Weight Loss Mechanism of Action	Norepinephrine reuptake inhibition Increases the release of norepinephrine in the central nervous system by releasing norepinephrine from presynaptic vesicles in the lateral hypothalamus Stimulates release of serotonin and dopamine, from nerve terminals Monoamine oxidase and serotonin reuptake inhibitor Inhibits neuropeptide Y	Modulation of GABA Antagonizes alpha-amino-3-hydroxyl-4-isoxazole-propionic acid kainite receptors Carbonic-anhydrase inhibition	Combination of phentermine and topiramate mechanism of action
Mode of Administration and Dose	Oral 8 mg, 15 mg, 30 mg, 37.5 mg Daily in morning	Oral Up to 200 mg twice daily (obesity dosing varies widely); extended release formulation	Oral Oral Mid-dose (phentermine 7.5mg/topiramate extended release 46mg) High-dose (phentermine 15mg/topiramate extended release 92mg) Once daily in the morning
Controlled Substance	Yes Schedule IV	No	Yes Schedule IV
Summary of Adult Weight Loss Efficacy	No RCTs Data from small, uncontrolled studies: 3–4% reduction in body weight in short-term trials	No RCTs Data from small, uncontrolled studies: 5–8% reduction in body weight for doses ranging from 96mg to 256mg	7% for mid-dose and 9% for high- dose in 1 year
Summary of Pediatric Weight Loss Efficacy	No RCTs Data from small, uncontrolled studies: 4% reduction in BMI in short-term trials	Limited Data	8% for mid-dose and 10% for high- dose in 1 year
Effects on Co- Morbidities and Risk Factors	Limited data	Limited Data	Pediatrics: Improved lipid profile; no effect on quality of life
Side Effect Profile	Hypertension, tachycardia, palpitations, pulmonary hypertension agitation, restlessness, insomnia, anxiety, euphoria/dysphoria, tremor	Headache, paresthesia, dizziness, dysgeusia, cognitive impairment potential seizure with abrupt discontinuation, dry mouth, diarrhea, constipation, fetal toxicity, acute onset of decreased visual acuity, worsening depression or suicidal thoughts, metabolic acidosis, elevation of creatinine, nephrolithiasis;	Hypertension, tachycardia, palpitations, pulmonary hypertension agitation, restlessness, insomnia, anxiety, dysphoria, tremor headache, paresthesia, dizziness, dysgeusia, cognitive impairment potential seizure with abrupt discontinuation, dry mouth, diarrhea, constipation, fetal toxicity, acute onset of decreased visual acuity, worsening depression or suicidal thoughts, metabolic acidosis, elevation of creatinine, nephrolithiasis
Contraindications	History of CVD or drug use; MAOI use; hyperthyroidism; glaucoma; agitated states; pregnancy	Pregnancy, glaucoma	Same contraindications recommended for phentermine and topiramate monotherapy
Use Cautions	High blood pressure, congenital heart disease, use of SSRIs, SNRIs, insulin, or valproic acid, renal disease, metabolic acidosis, history of kidney stones, depression, suicidal ideation, high risk for pregnancy	Kidney stones, glaucoma, high risk for pregnancy due to fetal toxicity, metabolic acidosis, active suicidal ideation, poor cognitive function	Same use cautions recommended for phentermine and topiramate monotherapy
Cost	Low	Low	Moderate
Patient Selection	Strong hunger; low energy	Poor satiety, food cravings, binge eating disorder, weight gain due to atypical antipsychotic medications, headaches,seizures, mood dysregulation	Dual therapy Insurance Coverage Desire for synergist effect with daily dosing

Abbreviations: %BMI_p95, BMI in excess of the 95th percentile; BMI>95th%, body mass index greater than the 95th percentile; CVD, Cardiovascular disease; RCT, randomized controlled trial; AE, adverse event, SAE, serious adverse event; HbA1c, hemoglobin A1c; BMI, body mass index; GI, gastrointestinal.; GI, gastrointestinal; LDL, low density lipoprotein, PHEN/TPM, Phentermine/topiramate extended release product; TG, triglycerides.

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