Table 1.

Summary of the clinical studies.

Author (Year)	Year	Groups Studied and Intervention	Results and Findings	Side Effects	Conclusions
Bray et al. [29]	2003	Randomized, double-blind, placebo-controlled, dose-ranging trial on the efficacy of TPM for weight loss in subjects aged 18–75 years with BMI ≥ 30 to <50 kg/m2 (n = 385). The subjects received either placebo, 64, 96, 192, or 384 mg of TPM daily.	All doses of TPM produced significant weight loss in comparison with placebo. Higher doses of TPM correspond to greater weight loss.	Side effects were most often CNS- and PNS-related. The most common side effects were paresthesia, memory difficulty, and fatigue. Side effect incidence was generally correlated to higher doses of TPM.	All studied TPM doses effectively reduced subjects’ body weights compared to placebo. Lower doses (64 mg and 96 mg) were better tolerated while still producing statistically significant reductions in the weight of the subjects.
Moradi et al. [30]	2013	Randomized, double-blind, placebo-controlled, parallel-group study on the efficacy of TPM for weight loss in subjects with documented DM2, a BMI between 27 and 50 kg/m2, and aged 18–75 years (n = 69). Subjects were treated with either a placebo or 150 mg of TPM per day.	The TPM treatment group achieved statistically significant decreases in weight compared to the placebo group. The treatment group’s systolic blood pressure and HbA1c significantly decreased compared to the placebo group, and diastolic blood pressure showed no significant difference.	Twenty-four of the thirty-nine subjects in the treatment group reported side effects, the most common being paresthesia and memory problems.	TPM 150 mg/day can effectively reduce weight loss by around 5% in obese patients with DM2. Measurements of metabolic parameters related to obesity and DM2 also show improvement when treating subjects with TPM.
Toplak et al. [31]	2007	Randomized, double-blind, placebo-controlled multicenter trial on the efficacy of TPM for weight loss and HbA1c reduction in subjects with DM2 on metformin monotherapy, a BMI ≥ 27 to <50 kg/m2, and aged 18–75 years (n = 646). Subjects were treated with a placebo, 96 mg/day of TPM, or 192 mg/day of TPM.	The 96 mg/day and 192 mg/day TPM treatment groups had statistically significant reductions in baseline bodyweight (4.5% and 6.5%, respectively) compared to placebo. TPM groups also had significant reductions in HbA1c compared to the placebo.	Side effects were significantly more common in the treatment group. A total of 32% of subjects treated with TPM experienced paresthesia.	The addition of TPM to subjects with DM2 treated with metformin is effective in reducing body weight. Improved glycemic control was also observed in subjects taking TPM; side effects are common.
Ben-Menachem et al. [32]	2003	Uncontrolled, prospective trial of 38 in which topiramate was added to patient medication regimens who were also taking anticonvulsants for partial-onset seizure and monitored for 1 year.	Patients’ baseline weights and mean body weights were reduced. After 1 year for all patients, 3 months correlated to stronger reductions in caloric intake.	This study reported only fatigue and anxiousness—concentration/attention trouble, depression, paresthesia, language impairments, and dizziness. The study had no major adverse events or deaths. Seven patients discontinued topiramate due to treatment-emergent adverse effects. Nervousness, fatigue, and depression were the most common symptoms after topiramate discontinuation.	Topiramate caused significant weight loss and was sustainable for 1 year with treatment.
Astrup et al. [33]	2004	Randomized, double-blind, placebo-controlled, parallel-group study on the efficacy of TPM on maintaining weight loss after 8 weeks of a low-calorie diet. Obese subjects aged 18–75 years who lost ≥8% of their body weight received a placebo, 96 mg/day of TPM, or 192 mg/day of TPM (n = 701).	After weight loss of ≥8% across 8 weeks from diet, subjects treated with 96 mg/day or 192 mg/day of TPM had further weight decreases of 5.2 and 6.4%, respectively. These results were statistically significant compared to the weight gain of 1.8% experienced by the placebo group.	Paresthesia and fatigue were common side effects, but the effects were mainly mild to moderate.	TPM was effective for weight loss maintenance achieved previously by dieting in obese subjects. TPM also produced significant weight loss, while the placebo group experienced weight gain.
Tonstad et al. [34]	2005	Randomized, placebo-controlled study on TPM’s efficacy for weight and blood pressure reduction in obese subjects with documented hypertension (n = 531). Subjects were treated with a placebo, 96 mg/day of TPM, or 192 mg/day of TPM.	The 96 mg/day and 192 mg/day treatment groups had significant weight decreases compared to placebo. Diastolic blood pressure decreased in both treatment groups, but systolic blood pressure did not in comparison to the placebo.	Common adverse effects included paresthesia, fatigue, and concentration difficulty.	TPM 96 mg/day and 192 mg/day were effective for reducing weight in obese subjects compared to the placebo.
Wilding J. et al. [35]	2004	Randomized, double-blind, placebo-controlled, parallel-group study on the efficacy of TPM for weight loss in obese subjects without comorbidities. Subjects with hypertension and/or dyslipidemia were included. Subjects were treated with a placebo, 96 mg/day of TPM, 192 mg/day of TPM, or 256 mg/day of TPM (n = 1289) for 1 year.	Subjects in the groups treated with 96 mg/day, 192 mg/day, and 256 mg/day achieved a mean weight decrease of 7.0, 9.1, and 9.7%, respectively. These results were statistically significant compared to the placebo group.	The most common side effects are related to CNS, PNS, and psychiatric disorders. Paresthesia was reported by most subjects treated with TPM; however, it was generally well-tolerated.	TPM produced significant weight loss in obese subjects. Weight loss continued to week 60.

Key: Topiramate (TPM); body mass index (BMI); central nervous system (CNS); peripheral nervous system (PNS); hemoglobin A_1c (HbA_1c); type II diabetes mellitus (DM2); controlled-release topiramate (CR-TPM).