Bupropion. Treatment of nicotine addiction.

Originally developed and sold as an antidepressant, bupropion was soon proven effective in the treatment of nicotine addiction. In 2007 he was appointed more than 20 million times, making it the fourth most frequently prescribed antidepressant on the USA market after sertraline, ESCITALOPRAM and fluoxetine. Bupropion is registered in the Russian Federation as a drug. Bupropion lowers the threshold of convulsive readiness of the brain. Potential ability to induce an epileptic seizure became widely known soon after the release of bupropion on the market. However, the risk of a seizure while observing the prescribed dosage of bupropion is comparable to other antidepressants. Bupropion is an effective antidepressant by itself and as an additional remedy in cases of insufficient efficacy of first-line antidepressants (SSRIs). Unlike many other antidepressants, bupropion does not cause weight gain and sexual dysfunction.



History Bupropion was invented by Nariman in Meta Burroughs Wellcome company (now GlaxoSmithKline) in 1969, and in 1974 received a U.S. patent. Bupropion is approved by the FDA (USA) for use as an antidepressant 30 December 1985 and entered the market under the proprietary name of Wellbutrin (Wellbutrin). However, after numerous cases of seizures caused by manufacturer's recommended dose (400-600 mg), the drug was withdrawn from the market in 1986. Subsequently it was established that the risk of a seizure depends on the dose of the drug, after which bupropion was again approved for use in 1989 with a maximum recommended dose of 450 mg per day. In 1996 the FDA approved the extended formula of bupropion Wellbutrin SR, intended for reception twice a day (unlike a triple reception of the original Wellbutrin). In 2003, FDA approved an even more prolonged formula, called Wellbutrin XL, intended for receiving a single day. Wellbutrin SR and XL are available as generics in the U.S., and in Canada in the form of a generic option applies only SR. In 1997, bupropion was approved by the FDA for use as drugs in the treatment of nicotine addiction brand Zyban (Zyban). In 2006, Wellbutrin XL was approved for the treatment of seasonal depression. Therapeutic use Depression



Clinical studies double-blind method with the use of placebo confirmed the efficacy of bupropion in the treatment of clinical depression. Comparative clinical studies demonstrated the equivalency of bupropion and sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil) and ESCITALOPRAM (Lexapro) as antidepressants. Recent studies have shown a significantly higher rate of remission for bupropion than for venlafaxine (Effexor). Unlike other antidepressants, except mirtazapine (Remeron), maprotiline (Ludiomil) and tianeptine (Stablon), bupropion does not cause sexual dysfunction and the likelihood of sexual side effects is not different from placebo. Treatment with bupropion is not accompanied by an increase in the weight of the patient; on the contrary, by the end of every clinical trials that have compared the effect of bupropion with placebo or other antidepressants, the group of bupropion had a lower average weight. Bupropion is more effective than SSRIs at improving symptoms of hypersomnia and fatigue in patients suffering from depression. In a comparative meta-studies showed a moderate advantage of SSRIs over bupropion in the treatment of depression with high anxiety, while in the treatment of depression with medium and low anxiety medications equivalent.According to some polls, a joint appointment of an SSRI with bupropion is the preferred strategy for the treatment of patients not responsive to SSRIs. For example, the combination of bupropion and citalopram (Celexa) was more effective than switching to another antidepressant. The addition of bupropion to an SSRI (primarily fluoxetine or sertraline) resulted in a significant improvement in 70-80% of patients who had incomplete susceptibility to first line antidepressants. Bupropion improved "energy" patients, oppressed by SSRI; improved mood and motivation, as well as some improvement of cognitive and sexual functions. Sleep quality and level of anxiety in most cases has not changed. In the study, STAR*D patients, immune to citalopram (Celexa) were randomly assigned with bupropion or buspirone



(Buspar). About 30% of patients in both groups achieved remission. However, the combination with bupropion gave the best results in assessing the patients themselves and better their tolerated. The authors concluded that "...these data suggest that the combination of bupropion prolonged action with citalopram has provided a more favorable outcome than the combination of buspirone with citalopram." In the same study noted a higher probability of remission in the case of appointment to the resistive citalopram patients of the combination of citalopram with bupropion, compared with simple switching to bupropion (30 % vs. 20 %). Anxiety Bupropion has shown some success in the treatment of social phobia and anxiety accompanying depression, but not panic disorder with agoraphobia[28]. Its anxiolytic (calming) effect is comparable to sertraline and doxepine. However, in some patients, bupropion can cause agitation, especially at high doses, and often as ritalin, — anxiety. Nicotine addiction Bupropion reduces the severity of the rejection of nicotine and the associated withdrawal syndrome. After a 7-week treatment, 27% of patients taking bupropion reported that Smoking cessation is a problem for them. In the placebo group and 56% of patients. In the same study, 21% of patients who are taking bupropion, noted mood swings, versus 32% of the placebo group[31]. Taking bupropion lasted from 7 to 12 weeks, during which time the patient should not smoke for 10 days. Bupropion almost doubled the probability of quitting after three months. One year after taking the drug resistant Smoking cessation in a group of bupropion was one and a half times higher than in the placebo group. The combined intake of bupropion and nicotine does not increase the degree of Smoking cessation. In direct comparison, varenicline (Chantix) and bupropion latter showed high efficacy: after one year, the level of persistent refusal of Smoking was 10 % for placebo 15% for bupropion, and 23 % for varenicline. Bupropion slows the weight gain that often occurs during the first weeks of quitting (after 7 weeks in the placebo group the mean increase in weight was 2.7 kg, compared to 1.5 kg in the group of bupropion). Over time, however, this effect disappeared (after 26 weeks in both groups the mean weight gain was 4.8 kg). Sexual dysfunction Wellbutrin XL Bupropion is one of few antidepressants that do not cause sexual dysfunction[34]. As shown by the survey of psychiatrists, it is the preferred drug for treating sexual dysfunction caused by SSRI, although such preference is not svidetelstvuet on obtaining FDA approval. Thirty-six percent of psychiatrists prefer the transfer of patients with sexual dysfunction caused by SSRI, bupropion, and 43 % prescribe bupropion in addition to already taking the drug[35]. There is some research supporting the efficacy of both approaches; the most often improvements in sexual functions marked sexual desire and orgasm. In the case of adjuvant therapy, to achieve the improvement of the patient's condition, to take SSRIs, you need to add at least 200 mg of bupropion per day, since the addition of 150 mg per day has not been achieved statistically significant results compared to placebo. Some studies have shown that bupropion is also improved sexual function in people not suffering from depression. In opposite-sex double-blind study of 12-week course of bupropion 63 % of the subjects rated their condition as "improved" or "significant improvement", against only 3% of patients in the placebo group[42]. Two studies, one of which was conducted using a placebo, demonstrated the efficacy of bupropion for women with hypoactive sexual attraction, with a significant improvement of arousal, orgasm and overall satisfaction. Also, bupropion has shown itself to be very promising in treating sexual dysfunction caused by chemotherapy for breast cancer, and dysfunction of orgasm. Also, as in the case of the treatment of sexual function disorders caused by SSRI treatment, it is necessary to use higher doses of the drug (300 mg): a randomized study using a low dose (150 mg) did not detect a significant difference between bupropion, sexual therapy or combined treatment. Bupropion has no effect on sexual function in healthy males.