- Generic name: Bupropion hydrochloride
- Brand names: Wellbutrin®, Wellbutrin SR®, Wellbutrin XL®, Zyban®
- Therapeutic class: Antidepressant
- Pharmacologic class: Norepinephrine and Dopamine Reuptake Inhibitor (NDRI), Aminoketone
- FDA Approved:
December 30, 1985 - IR formulation
October 4, 1996 - SR formulation
August 29, 2003 - XL formulation
- Chemical Formula: C13H18ClNO·HCl
- Pregnancy Category: C
- Habit forming? No
- Originally discovered: 1966, United States
Based on "Essential Psychopharmacology"
written by Stephen M. Stahl, MD, PhD
Bupropion was synthesized in 1966 by Burroughs Research' group of scientists seeking "an agent that would be active in antidepressant screening models, but differ chemically and pharmacologically from the tricyclics, and not be sympathomimetic, cholinolytic, nor an inhibitor of monoamine oxidase" (Soroko et al. 1977). The bupropion research endeavour led to the discovery of a molecule with a novel mechanism of action and a favorable side-effect profile that minimized the anticholinergic, sympathomimetic, and cardiac effects of many of the antidepressants that were currently in use. Bupropion was patented by Burroughs-Wellcome (later Glaxo-Wellcome, and, as of 2000, GlaxoSmithKline) in 1974.
There is evidence that bupropion's development was inspired by the structure of amphetamine, which had been used, with limited success, as an antidepressant in the 1930s. Bupropion is similar in structure to the stimulant cathinone (a monoamine alkaloid found in the shrub Catha edulis - Khat), and to phenethylamines in general. It is a chemical derivative of diethylpropion, an amphetamine-like substance used as an anorectic.
The drug was originally approved by the FDA in 1985 and marketed under the name Wellbutrin (IR formulation) as an antidepressant. However, a significant incidence of seizures at the originally recommended dosage (400-600 mg) caused the removal of the drug from the market in 1986. It was subsequently discovered that reducing the dose by about half greatly reduced the risk of seizures. Bupropion was re-introduced to the market in 1989 with the maximum dose of 450 mg/day.
Glaxo then developed a sustained-release (SR) version which releases bupropion hydrochloride at a slower rate. It was approved by the FDA in 1996. In 1997, bupropion was approved as a smoking cessation aid under the brand name Zyban.
Extended release bupropion, Wellbutrin XL, is the most recent formulation (approved in 2003) and is taken orally once a day2. Because of this altered mechanism of delivery and reduced dosing, incidence of seizures is comparable to, and in some cases, lower than that of other antidepressants.
Bupropion was licensed as a pharmacotherapy for smoking cessation in the United Kingdom in 2000, and for the prevention of episodes of the seasonal affective disorder in the United States in 2006.
In some countries bupropion is approved only as a product for quitting smoking and not as a treatment of depression.
FDA approved indications
- Major depressive disorder
- Seasonal affective disorder (Extended-release formulation)
- Smoking cessation (Sustained-release formulation)
Off-label & Investigational uses
- weight loss 18, 19, 20
- attention-deficit hyperactivity disorder (ADHD) 2, 16
- bipolar depression 7
- chronic fatigue syndrome 24
- pathological gambling (PG) 27
- methamphetamine dependence 15
- improvement in sexual functioning in women 21, 23, including hypoactive sexual desire disorder 31
- augmentation of SSRIs and venlafaxine in partial and non-responders 8
- antidote for SSRI-induced sexual dysfunction 22
- dysthymic disorder (DD)
- neuropathic pain 17
- schizophrenia 25
- Internet gaming disorder - improves attention and impulsivity25
Switching to bupropion from SSRI
Switching to bupropion, for depressed patients not responding to SSRIs, is a popular strategy among clinicians. The study found that approximately 60% of patients with MDD resistant to fluoxetine experienced a full or partial response to bupropion. Bupropion is considered as a potential treatment for depression not responding to SSRIs 10.
Bupropion for weight loss
Bupropion efficacy and tolerability was studied in overweight and obese adult women. In the study18 were included 50 women all of which were prescribed a 1600 kcal/day balanced diet. 25 women received bupropion and 25 women were in placebo group.
|Results of study18||Bupropion||Placebo|
|Mean weight loss over the first 8 weeks||4.9% +/- 3.4%||1.3% +/- 2.4%|
|Weight loss over 5% of baseline body weight (% of participants)||67%
(12 of 18)
(2 of 13)
In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% +/- 5.6% with fat accounting for 73.5% +/- 3.7% of the weight lost and no change in bone mineral density. Bupropion was generally well-tolerated in this investigation 18.
Another clinical study evaluated bupropion sustained-release in reducing weight and depressive symptoms in obese adults. The bupropion SR group (193 participants) lost an average of 4.4 kg (4.6% of baseline weight), while those on placebo (191 participants) only 1.7 kg (1.8% of baseline weight). More patients on bupropion SR (40%) than on placebo (16%) lost at least 5% of baseline weight. The percentage of patients reporting 50% or more decrease in depressive symptoms did not differ between groups, but depressive symptoms improved more with bupropion SR than with placebo. In the sample as a whole, improvement in depressive symptoms was related to weight loss of > or =5% regardless of treatment 19.
The results of the 48-week double-blind, placebo- controlled trial have shown, that bupropion SR 300 and 400 mg/d are well-tolerated by obese adults and are associated with a 24-week weight loss of 7.2% and 10.1% and sustained weight losses at 48 weeks 20.
Bupropion for Attention-deficit hyperactivity disorder (ADHD)
Bupropion is used as an alternative nonstimulant treatment for ADHD/ADD. According to a 2011 meta-analysis, Bupropion is effective for ADHD in adults 2. Bupropion has dual dopamine-norepinephrine mechanism of action, and this pharmacologic activity is somewhat similar to the presumed action of stimulants3.
A double-blind, placebo-controlled, randomized, parallel, 6-week trial compared 21 patients receiving bupropion SR (up to 200 mg b.i.d.) to 19 patients receiving placebo. Bupropion treatment was associated with a significant 42% reduction of ADHD symptoms at the week-6 endpoint, which exceeded the effects of placebo (24% reduction). In analyses using a cutoff of 30% or better reduction to denote response, 76% of the patients receiving bupropion improved, compared to 37% of the patients receiving placebo. Similarly, in analyses using Clinical Global Impression scale scores, 52% of patients taking bupropion reported being "much improved" to "very improved," compared to 11% of patients taking placebo 16.
Bupropion "pros" and "cons"
- Low rates of sexual side effects 12
- Bupropion may increase sexual desire and pleasure, perhaps due to its dopaminergic properties
- Does not cause weight gain
- REM sleep enhancement (shortens REM latency and increases REM sleep) 4
- Least chance of triggering mania 5
- Lower risk of inducing switches to hypomania or mania in bipolar depression 7
- Does not affect psychomotor performance 9
- More beneficial with regard to cognitive function than other antidepressants. Bupropion may alleviate impaired cognitive performance during smoking cessation29.
- Very effective for depression with pronounced symptoms of low energy, lack of pleasure and interest32.
- Similar effectiveness to SSRIs 12, 13
- Less nausea, diarrhea, somnolence than with SSRIs 13
- May help with sleepiness and fatigue 28
- There is preliminary evidence that bupropion may reduce the risk of open-angle glaucoma 30
- Dose-related risk of seizures (with the dose 450 mg/day or less the risk is about 0.48%, and with 600 mg/day the risk is 2-3%) 6
- Potential for hepatotoxicity
- Not suitable for persons with anorexia or bulimia
- High rate of activating side effects
- High potential for drug interactions because of induction of CYP 2D6 hepatic microsomal enzymes.
Mechanism of action
Bupropion hydrochloride, an antidepressant of the aminoketone class, is chemically unrelated to tricyclic or tetracyclic agents. Its structure closely resembles that of diethylpropion; it is related to phenylethylamines. Bupropion is a selective catecholamine (norepinephrine and dopamine) reuptake inhibitor.
The mechanism of action of bupropion appears involve a unique, not well-understood, noradrenergic neurotransmission. Its metabolite hydroxybupropionplays an important role in bupropion's antidepressant activity, which appears to be predominantly associated with long-term noradrenergic effects. The mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms. There is some evidence that dopamine may contribute to bupropion's antidepressant properties. Its antidepressant effects are not serotonergically mediated 26.
Time for Bupropion to clear out the system
The mean elimination half-life of bupropion after chronic dosing is 21 (±9) hours, and steady-state plasma concentrations are reached within 8 days.
Bupropion has at least three active metabolites: hydroxybupropion, threohydrobupropion and erythrohydrobupropion. Hydroxybupropion's half-life is 20 hours, threohydrobupropion's half-life is 37 hours and erythrohydrobupropion's 33 hours.
So, it may take 5 to 8 days for bupropion to clear out the system.
Onset and duration of action
Full antidepressant effect may not be evident until several weeks of treatment.
The efficacy of bupropion SR in maintaining an antidepressant response for up to 44 weeks following 8 weeks of acute treatment was demonstrated in a placebo-controlled trial 1.
In animal studies and small studies with persons having experience with the use of amphetamines or cocaine, bupropion caused drug-seeking behaviour (animal experiments) and was recognized as an amphetamine-like drug by the humans. In a scale ranging from placebo on the lower side to benzedrine, it was given an intermediate score indicating moderate likelihood of abuse. In clinical practice, it has been shown that the dose required for significant abuse would cause seizures in most patients. Abuse has not become a significant problem in clinical usage, but the drug should be given with caution to patients with a history of drug or alcohol abuse or dependence.
- Bupropion vs Escitalopram
- Bupropion vs Venlafaxine
- Bupropion vs Duloxetine
- Bupropion vs Methylphenidate
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Published: March 31, 2008
Last updated: July 20, 2017
- Bupropion is the only antidepressant that ignores the serotonin system and acts selectively on the noradrenergic and dopaminergic systems.
- Sexual side effects normally accompanying SSRI's do not accompany bupropion. Interestingly, some people experience increased libido.
- In 2006 Bupropion was the fourth most prescribed antidepressant on the U.S. retail market.
- After unsuccessful treatment with an SSRI, approximately 25% of people have a remission of symptoms after switching to another SSRI, bupropion (Wellbutrin) or venlafaxine 11.
- The studies suggest that use of bupropion in the late pregnancy may run a risk of enhancing the offspring's susceptibility to stress and sensitivity to cocaine effects in adulthood 14.