Eight RCTs that randomized a total of 439 patients were included. So, each RCT included a relatively small number of patients.
Open-label (un-blinded) studies with a control group were included, but were used to evaluate adverse effects only and not to assess efficacy.
The duration of treatment was a mean of 14 weeks, with a standard deviation of 5 weeks.
Patients were randomized to receive topiramate (100 to 400 mg/day) versus placebo (seven RCTs) OR topiramate versus antipsychotic alone (one RCT).
Topiramate was efficacious for total psychopathology. The Standardized Mean Difference, a measure of the magnitude of effect, was 0.57, which indicates a moderate degree of effect.
Topiramate was efficacious for positive symptoms (Standardized Mean Difference 0.56), negative symptoms (Standardized Mean Difference 0.62), and for general psychopathology (Standardized Mean Difference 0.69).
Body weight and Body Mass Index (BMI) were reduced in persons treated with topiramate. The measure of magnitude of effect used for reduction in body weight was Weighted Mean Difference (no pun intended), and it was a reduction of 3.1 Kg (6.8 lbs).
The investigators also tried to see if certain clinical characteristics could predict the benefit of topiramate for reducing total psychopathology and for weight reduction. However, they could not identify any effect of duration of treatment, dose of topiramate, gender, age, baseline Positive and Negative Syndrome Scale score, or baseline BMI.
What about when topiramate is combined with clozapine? When combining topiramate with clozapine was compared to combining topiramate with other antipsychotics, the clozapine-topiramate combination led to greater efficacy than other antipsychotic-topiramate combinations. However, when combined with clozapine, topiramate was not efficacious for weight loss.
The only adverse effect that statistically trended towards being more common on topiramate than on the comparator was paresthesia.
Only one study assessed cognitive effects using formal testing and, surprisingly, found no cognitive adverse effects of topiramate. The reason for this is not known but the authors speculated that one reason could be that the study did not have enough power to find this effect with statistical confidence. Alternatively, these patients with schizophrenia spectrum disorders may already have significant cognitive impairment that may have masked any additional impairment due to topiramate.