Few data are available on cognitive and psychiatric effects of topiramate (TPM) monotherapy in migraine. Twenty patients affected by migraine were treated with TPM monotherapy. At the same time, twenty control subjects were selected. A comprehensive neuropsychological and behavioural battery of tests were performed at baseline (T0), at titration (T1) and in maintenance period (T2). Topiramate serum levels were also investigated at T1 and T2. On comparison with the control group, no cognitive and psychiatric differences were detected at baseline. A significant reduction of word fluency score (P < 0.05) was evident after TPM treatment, both at T1 and T2. No patient developed psychiatric adverse events. TPM induced an impairment of verbal fluency and no psychiatric adverse events, demonstrating selective negative cognitive profile in migraine therapy. Slow titration, low doses, lack of previous psychiatric disorders and/or familial history may explain our data.