Does pregabalin cause weight gain

Pregabalin has to prove itself


epilepsyby Conny Becker, Berlin

With pregabalin, a new anti-epileptic drug has been on the German market since the beginning of September that, like its structurally related gabapentin, also relieves peripheral neuropathic pain. Experts see some advantages in the new substance: It works quickly, is easy to use, well tolerated and can be combined.

“About a third of patients with epilepsy show remission only under therapy. For many patients, one must therefore assume that they will have to take a drug for 20, 30 or 40 years, ”informed Professor Dr. Christian Elger from the Clinic for Epileptology at the University of Bonn at the Pfizer-supported introductory press conference in Berlin. It is therefore important to use substances with few side effects in long-term therapy. Valproic acid and carbamazepine are still the gold standard. Newer anti-epileptic drugs like levetiracetam would often be combined to make more patients seizure-free. Even if pregabalin, which is approved as Lyrica® for the additional therapy of partial seizures with and without secondary generalization in adults, does not work significantly better than other anti-epileptic drugs, it does have favorable pharmacokinetics: it is not bound to protein in the plasma Excreted almost completely via the kidneys and not metabolized, shows no enzyme induction and therefore no interaction with the hormonal system, other anti-epileptic drugs or medication.

"New anti-epileptic drugs should offer advantages outside of seizure control, also in the group of difficult-to-treat epilepsy sufferers," said the neurologist. Pregabalin does not affect cognitive abilities (as known from carbamazepine) and also has an antidepressant or anxiolytic effect, as unpublished studies have shown. Since, according to estimates, around half of all patients with severe forms of epilepsy suffer from depression, such a side effect could increase the success of the therapy. Compliance also increases because patients only have to take one hard capsule (available with 25, 50, 75, 100, 150, 200 or 300 mg of active ingredient) twice a day. “We have a large number of patients who take 2 or 3 grams of gabapentin daily. That's a handful of tablets, which means that compliance drops, ”says Elger. Compared to the older GABA analogue, pregabalin only needs a fifth of the amount of substance because it has a higher binding affinity for the receptor.

Dose-dependent weight gain

"At a dose of 150 mg per day, pregabalin is already clearly effective," explained Professor Dr. Dieter Schmidt, resident neurologist from Berlin. If this starting dose was doubled, studies showed that the frequency of partial seizures decreased by a further 10 percent, and with 600 mg per day by another 10 percentage points. The additional therapy with 600 mg of pregabalin was able to reduce the seizures by around 54 percent.

The substance is well tolerated. The side effects of the additional therapy, such as drowsiness (29 percent), fatigue (21 percent), ataxia (13 percent) and general weakness (11 percent), were mostly mild to moderate and usually dose-dependent. However, 10 percent of patients gained at least 7 percent of their body weight within three months. The weight gain was particularly pronounced with the maximum dose (16 percent), whereas only 5 percent of those treated with 150 mg were affected. Schmidt therefore advises starting with daily doses of 75 mg twice.

Neuropathic pain alleviated

The new anticonvulsant is also effective in the treatment of patients with peripheral neuropathic pain, that is, especially in diabetic neuropathy and postherpetic neuralgia, reported Professor Dr. Thomas Tölle from the Neurological Clinic of the Technical University of Munich. In Germany, around four million patients suffer from pain caused by lesions or dysfunction of the peripheral nervous system. In addition to antidepressants such as amitriptyline or venlafaxine, opiates and lidocaine, anticonvulsants are also used - above all gabapentin and the sodium channel blockers carbamazepine and oxcarbazepine.

“We have ten randomized controlled trials of pregabalin in neuropathic pain, all of which are positive. Otherwise there can be no substance, ”said Professor Dr. Ralf Baron from the Department of Neurology at the University of Kiel. In the three published placebo-controlled studies with more than 650 patients, the substance was effective and very well tolerated. Here, the weight gain with only 3 percent does not play a significant role, however edema did occur, which disappeared again in the course of the therapy. Since pregabalin has not shown any interactions with other drugs, it is a good alternative, especially for older, multimorbid patients. In addition, the substance was able to improve patients' disturbed sleep, which is a problem in people with neuropathic pain.

"We have a very quick onset of action," said Baron, describing another advantage of the substance. It works significantly better than placebo after only a few days, with no slow titration necessary as with gabapentin. At a dose of 150 to 600 mg, pregabalin halved the pain in around half of the patients within twelve weeks (placebo 25 percent). He therefore initially plans to combine pregabalin with tramadol or tilidine and possibly amitriptyline.

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