Bupropion HCL benefit and side effects by Ray Sahelian, M.D.

April 20 2014

 

Bupropion is a norepinephrine and dopamine uptake inhibitor that has been available for several years for the treatment of depression and aiding smokers to quit. Bupropion is an antidepressant medication that affects chemicals within the brain that nerves use to send messages to each other. These chemical messengers are called neurotransmitters. The neurotransmitters that are released by nerves are taken up again by the nerves that release them for reuse. (This is referred to as reuptake.) Many experts believe that depression is partly caused by an imbalance among the amounts of neurotransmitters that are released. Bupropion is unrelated to other antidepressants. It works by inhibiting the reuptake of dopamine, and norepinephrine, an action which results in more dopamine, and norepinephrine to transmit messages to other nerves (its influence on serotonin is not very clear yet). Bupropion is unique in that its major effect is on dopamine, an effect which is not shared by the selective serotonin reuptake inhibitors or SSRIs (e.g. paroxetine, Paxil; fluoxetine, Prozac; sertraline, Zoloft) or the tricyclic antidepressants or TCAs (e.g. amitriptyline, Elavil; imipramine, Tofranil; desipramine, Norpramin). Bupropion hcl is available as sustained release bupropion SR.
   The high risk of smoking among young people with attention-deficit/hyperactivity disorder (ADHD) is not reduced by treatment with the antidepressant bupropion.

 

Bupropion side effects
Common bupropion side effects are nervousness and insomnia. Nausea is less common than with the SSRI drugs and sexual dysfunction is probably the least of any antidepressant. Bupropion overdose can lead to seizures.

 

History
Bupropion hcl became available to the public in the United States in 1989. Initially it was prescribed three times a day. Then, in 1996, a twice-daily sustained-release formulation was put on the market. In the year 2003, a once-daily extended-release bupropion sr was introduced.

 

Forms of buproprion, product names
This medication is available as three oral formulations: bupropion immediate release Wellbutrin administered three times daily; bupropion sustained release Wellbutrin SR administered twice daily; and bupropion extended/modified release Wellbutrin XL or Wellbutrin XR administered once daily. All three formulations are bioequivalent in terms of systemic exposure to bupropion.

 

Bupropion and sexuality

Since bupropion raises dopamine levels, it actually can enhance sexuality rather than depress libido as do many SSRIs. Bupropion has been shown to have a favorable effect on sexual dysfunction. Several reports and small, short-term trials have examined it as an adjunct or substitute for other antidepressants in sexually dysfunctional patients. Use of bupropion has also been studied in nondepressed patients. Bupropion may be a promising medication for treating sexual dysfunction. However, specific dosing is unclear. Long term sexual effects of bupropion treatment are not fully clear at this time.

 

A Double-blind Comparison Between Bupropion XL and Venlafaxine XR: Sexual Functioning, Antidepressant Efficacy, and Tolerability.
J Clin Psychopharmacol. 2006. Department of Psychiatry, University of Pittsburgh Medical Center, Western Psychiatric Institute, Pittsburgh, PA; Department of Psychiatric Medicine, University of Virginia, Charlottesville, VA; and double dagger GlaxoSmithKline, Research Triangle Park, NC and section signInnovaa Research, Chapel Hill, NC.
In this double-blind, multicenter study, bupropion XL, a norepinephrine - dopamine reuptake inhibitor, and venlafaxine XR, a serotonin -norepinephrine reuptake inhibitor, were compared with regard to sexual functioning, efficacy, and tolerability. A total of 348 sexually active adult outpatients with depression were randomized to receive bupropion XL (titrated to a target dose of 300-450 mg/d) or venlafaxine XR (titrated to a target dose of 150-225 mg/d) for 12 weeks. Total scores on the primary dependent variable, the Changes in Sexual Functioning Questionnaire (self-report), increased for subjects receiving bupropion XL and decreased for those treated with venlafaxine XR; the mean change scores differed significantly between groups from week 2 onward. Among subjects with normal pretreatment sexual functioning, Changes in Sexual Functioning Questionnaire total scores remained essentially unchanged for the bupropion XL group but were decreased significantly for the venlafaxine XR group; mean change scores also differed between groups from week 2 onward. Although the therapies resulted in similar change on the 17-item Hamilton Depression Rating Scale, remission rates were significantly higher among those treated with bupropion XL (46%) versus venlafaxine XR (33%). Aside from adverse effects of venlafaxine XR on sexual function, both treatments were reasonably well tolerated. In conclusion, in this patient population (ie, relatively young, sexually active outpatients), bupropion XL was at least as effective as venlafaxine XR and had a significantly more favorable sexual side effect profile.

 

Dr. Mohammad Reza Safarinejad of Shahid Beheshti University in Tehran found that bupropion sustained-release (Wellbutrin SR) generally boosted sex drive among 116 women with hypoactive sexual desire disorder HSDD who took the drug for 12 weeks. HSDD refers to low sex drive that is not better accounted for by depression or other mental health disorders, and not caused by a medical condition or drug side effect. In Europe, a testosterone patch called Intrinsa is approved for treating HSDD in postmenopausal women. Dr. Mohammad Reza Safarinejad says that studies have shown bupropion SR to improve sexual function in women who are having sexual side effects from using other antidepressants known as selective serotonin reuptake inhibitors (SSRIs). BJU International, online February 11, 2010.

 

Bupropion and Smoking

Over the past decade, bupropion has become a major pharmacotherapy for smoking cessation in the Western world. Unlike other smoking cessation pharmacotherapies, bupropion is a non-nicotine treatment. Compared with a placebo control, bupropion approximately doubles smoking quit rates. Most smoking cessation pharmacotherapies are thought to work, in part, by reducing nicotine withdrawal and craving. Human laboratory studies have demonstrated that bupropion can alleviate some nicotine withdrawal symptoms, including depressed mood, irritability, difficulty concentrating and increased appetite. Moreover, bupropion has shown some efficacy in alleviating craving to smoke. Clinical trials of bupropion have offered mixed support of its ability to reduce nicotine withdrawal, weight gain during treatment and craving.

 

Bupropion and weight loss
A few studies have shown that bupropion hcl may be helpful in weight loss, but additional ones are needed to determine the long term safety and bupropion side effects when used for obesity.

 

Rodent Studies

Bupropion: pharmacology and therapeutic applications. Expert Rev Neurother. 2006. University of Vermont, Department of Medical Laboratory and Radiation Sciences Burlington, VT
A total of 17 years after its introduction, bupropion has become a commonly used antidepressant, suitable for first-line use. Bupropion undergoes metabolic transformation to an active metabolite, 4-hydroxybupropion, through hepatic cytochrome P450-2B6 (CYP2B6) and has inhibitory effects on cytochrome P450-2D6, thus raising concern for clinically-relevant drug interactions. The mechanism of action of bupropion is still uncertain but may be related to inhibition of presynaptic dopamine and norepinephrine reuptake transporters. The activity of vesicular monoamine transporter-2, the transporter pumping dopamine, norepinephrine and serotonin from the cytosol into presynaptic vesicles, is increased by bupropion and may be a component of its mechanism of action. Bupropion is approved for use in major depression and seasonal affective disorder and has demonstrated comparable efficacy to other antidepressants in clinical trials. Bupropion is also useful in augmenting a partial response to selective serotonin reuptake inhibitor antidepressants, although bupropion should not be combined with monoamine oxidase inhibitors. It may be less likely to provoke mania than antidepressants with prominent serotonergic effects. Bupropion is effective in helping people quit tobacco smoking. Anecdotal reports indicate bupropion may lower inflammatory mediators such as tumor necrosis factor-alpha, may lower fatigue in cancer and may help reduce concentration problems.

 

In rats undergoing nicotine withdrawal, bupropion can dose-dependently lower changes in brain-reward threshold and somatic signs of nicotine withdrawal.

 

Availability, how it is sold, generic
Buproprion SR - sustained-release tablets - Generic bupropion SR sustained-release tablets for Wellbutrin SR are available.

    Bupropion is presumed to be a dopamine-norepinephrine reuptake inhibitor and is an antidepressant. It is available as three oral formulations: (i) bupropion immediate release (IR) Wellbutrin administered three times daily; (ii) bupropion sustained release (SR) Wellbutrin SR administered twice daily; and (iii) bupropion extended/modified release (XR) Wellbutrin XL / Wellbutrin XR administered once daily.

 

Generic version of Wellbutrin - In 2006, the U. S. Food and Drug Administration approved the first generic version of Wellbutrin XL Extended-Release Tablets, which are indicated for the treatment of major depressive disorder. The approval is an important step in the agency's effort to increase the availability of lower-cost generic medications. In 2005, Wellbutrin XL was the 21st highest-selling brand-name drug in the United States, with sales totaling $1,326,000,000 as reported in the online magazine Drug Topics. Bupropion hydrochloride is a widely used antidepressant, and its generic version can bring significant savings to the millions of Americans with depression. FDA received a citizen petition (a formal request for FDA action) that asked FDA to consider several issues for bupropion hydrochloride extended-release tablets, including how similarly the drug is absorbed into the bloodstream. After reviewing the issues raised in the petition, FDA determined that its standards for approval of the generic drug application for bupropion are appropriate. Bupropion Hydrochloride Extended-Release Tablets, 150 mg and 300 mg are manufactured by Anchen Pharmaceuticals Inc, of Irvine, CA.

 

A common misspelling is bupriprion