Topiramate for weight loss

Topiramate is an anticonvulsant drug approved for the treatment of epilepsy and in the prophylaxis of some forms of migraine. It is a neuromodulatory drug, whose anticonvulsant activity is presumably due to the inhibition of the voltage-dependent sodium channels, to the increase of the currents evoked by GABA, to the inhibition of the currents evoked by the kainate, to the inhibition of high channels calcium activated voltage, and carbonic anhydrase inhibition.

The various side effects of topiramate include weight loss and appetite loss (anorectic effect), potentially useful in the treatment of obesity. In this sense, topiramate has been the subject of intense experimentation, both on animal models and in clinical settings, which has even led to the design of a specific drug, which never entered the market due to the FDA's lack of authorization. It is Qnexa, a drug based on topiramate and phentermine (another active with anorectic action), designed for the treatment of obesity and related conditions (diabetes, hypertension and hypercholesterolemia); the lack of trade authorization was motivated by the risk of important side effects, such as palpitations, suicidal thoughts, memory lapses and birth defects.

The exact mechanism of action with which topiramate helps you lose weight has not yet been outlined; however, various mechanisms have been hypothesized: 1) increase in energy expenditure in the face of a reduced caloric intake linked to the anorectic effect; 2) reduction of the activity of salivary enzymes, important for the perception of food taste; 3) reduction of leptin and corticosteroid concentrations; 4) reduction of glycaemia and insulinemia.

The topiramate proved effective for slimming purposes even in monotherapy, as evidenced by the results of some clinical studies conducted on patients suffering from obesity unrelated to complications, on patients with weight gain induced by psychotropic drugs, and on patients suffering from the syndrome of binge eating disorder. The most commonly reported adverse effects during these studies include paraesthesia, memory impairment, taste distortion, fatigue, drowsiness, insomnia, difficulty concentrating and dizziness. To reduce these side effects, attempts have been made to experiment with new formulations of slow-release topiramate, which however do not seem to bring significant benefits. In general, monotherapy with topiramate is well tolerated, and although paresthesias are common during use, their intensity is usually mild or moderate, rarely of an intensity that requires suspension of therapy.

The doses of monotherapy topiramate tested in the aforementioned clinical trials in the treatment of obesity ranged from 32 to 384 mg per day, included in the context of a broader therapy that involved behavioral changes for weight loss, including the adoption of a low-calorie diet; these doses guaranteed an average weight loss of 5-15% higher than in the control group. The most effective topiramate dose in the treatment of obesity appears to be between 100 and 200 mg a day. Although the short and long term efficacy is comparable to that of sibutramine and orlistat, further studies are needed to better define the safety profile of the treatment.

See also: Topiramate for Quitting Smoking