Wellbutrin XL

Bupropion (Wellbutrin XL, Wellbutrin SR)

  • Generic name: Bupropion hydrochloride
  • Brand names: Wellbutrin, Wellbutrin SR, Wellbutrin XL, Zyban
  • Dosages:
    150 mg, 300 mg extended release tablets
    150 mg, 200 mg sustained release tablets
  • Pharmacologic category: Aminoketone antidepressant, Norepinephrine and Dopamine Reuptake Inhibitor
  • FDA approved: August 29, 2003
  • Manufacturer: GlaxoSmithKline
  • Habit forming? No
  • Pregnancy risk factor: C

Medical uses

Bupropion hcl (Wellbutrin) is an antidepressant indicated for the treatment of major depressive disorder and nicotine addiction. Bupropion is also used to prevent episodes of seasonal affective disorder (form of depression occurring mainly during the autumn and winter months). This antidepressant useful for depression depression characterized by reduced energy and interest, concentration problems, excessive sedation.

Bupropion hcl is often prescribed for depression when selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) cannot be used or are not effective.

Difference between Wellbutrin XL and SR

Wellbutrin XL contains the same active ingredient as Wellbutrin SR -- Bupropion -- but XL is formulated in an extended-release once-daily tablet, whereas SR is formulated in an sustained-release twice-daily tablet. This means that with Wellbutrin XL you can take one tablet in the morning, continue with your daily activities, and not worry about remembering to take a second dose.

Both formulations are bioequivalent in terms of systemic exposure to bupropion, but differ in their pharmacokinetics and dosing.

Wellbutrin XL (extended-release) versus SR (sustained-release) comparison:

  • Effectiveness - Both Wellbutrin XL and Wellbutrin SR are preparations of the same antidepressant medication bupropion and are equally effective.
  • Absorption - Absorption of the XL formulation is prolonged compared with the SR formulations - T (max) is approximately 5 hours vs approximately approximately 3 hours.
  • Compliance - Convenient once-daily dosage regimen of Wellbutrin XL ensures better patient adherence 6
  • Cost - XL formulation is significantly more expensive.

Wellbutrin + SSRI combination

Although not an approved indication, the combination of Wellbutrin and either an SSRI or an SNRI is generally well tolerated and can boost antidepressant response. Combining two antidepressants has become a common strategy in the treatment of resistant depression. The results of clinical study have shown that when the patient fails to respond to an SSRI or venlafaxine, an addition of Wellbutrin SR can increase the chances of response 9.

Wellbutrin appears to significantly affect dopaminergic neurotransmission and may help with fatigue and sexual dysfunction induced by SSRIs of SNRIs. A study by Papakostas and associates examined the impact of bupropion vs SSRIs on sleepiness and fatigue in patients with depression. The investigators pooled data from 6 double-blind, randomized clinical trials and found greater improvements in fatigue scores among both bupropion-treated and SSRI-treated groups than placebo-treated patients, and greater improvements in fatigue scores among bupropion-treated than SSRI-treated patients 7.

Wellbutrin may reverse SSRI-induced sexual dysfunction due to its dopaminergic effect. In addition to the SSRI produces an increase in desire to engage in sexual activity and frequency of engaging in sexual activity 8.

Pharmacological characteristics

  • Metabolism: Extensively metabolized by hydroxylation or oxidation in the liver. CYP2B6 is involved in formation of hydroxybupropion (50% as potent as bupropion). The other 2 main metabolites are threohydrobupropion and erythrohydrobupropion, which are 20% as potent as bupropion.
  • Elimination half-life: about 21 hr, about 20 hr (hydroxybupropion), about 37 hr (threohydrobupropion), and about 33 hr (erythrohydrobupropion).
  • Excretion: 87% excreted in urine, 10% in feces, and 0.5% as unchanged drug.


  • Once a day dosage regimen.
  • Low risk of sexual dysfunction [2]: does not lower libido, produce impotence or impair orgasms. In fact, bupropion may improve sexual functioning in both men and women5.
  • Low risk of weight gain -- bupropion is beneficial for people who afraid to gain weight.
  • Decreased appetite and weight loss (however, may be a harmful effect for anorectic persons).
  • Low potential for triggering mania in the bipolar disorder.


  • Frequently cause agitation, anxiety, and insomnia (addition of a sedative agent or discontinuation of therapy may be required; gradual escalation of dose helps minimize symptoms)
  • Risk of seizures, particularly at doses > 450 mg/day
  • Risk of hypertension
  • Potential for interactions. Bupropion can interact with other drugs that are metabolized by CYP2B6. Also bupropion inhibits CYP2D6 and may reduce clearance of drugs metabolized by this enzyme.

Unlabeled uses

  • Attention-deficit/hyperactivity disorder (ADHD)
  • Depression associated with bipolar disorder (in combination with mood stabilizers)
  • Enhancement of weight loss
  • Combination of naltrexone plus bupropion is an experimental promising therapeutic option for treatment of obesity [3]
  • Augmenting a partial response to SSRIs

Mechanism of action

The mechanism of activity is not fully understood. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine, and does not inhibit monoamine oxidase or the reuptake of serotonin. Hydroxybupropion metabolite inhibits the reuptake of norepinephrine. The primary mechanism of action is thought to be dopaminergic and/or noradrenergic.


  • 1. U.S. FDA. Wellbutrin XL Prescribing Information PDF
  • 2. Labbate LA, Brodrick PS, Nelson RP, Lydiard RB, Arana GW. Effects of bupropion sustained-release on sexual functioning and nocturnal erections in healthy men. J Clin Psychopharmacol. 2001 Feb;21(1):99-103. PubMed
  • 3. Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010 Aug 21;376(9741):595-605. PubMed
  • 4. Bupropion Hydrochloride Extended-Release 300 mg Bioequivalence Studies FDA
  • 5. Sayuk GS, Gott BM, Nix BD, Lustman PJ. Improvement in sexual functioning in patients with type 2 diabetes and depression treated with bupropion. Diabetes Care. 2011 Feb;34(2):332-4. PubMed
  • 6. Stang P1, Suppapanaya N, Hogue SL, Park D, Rigney U. Persistence with once-daily versus twice-daily bupropion for the treatment of depression in a large managed-care population. Am J Ther. 2007 May-Jun;14(3):241-6.
  • 7. Papakostas GI1, Nutt DJ, Hallett LA, Tucker VL, Krishen A, Fava M. Resolution of sleepiness and fatigue in major depressive disorder: A comparison of bupropion and the selective serotonin reuptake inhibitors. Biol Psychiatry. 2006 Dec 15;60(12)
  • 8. Safarinejad MR. The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study. BJU Int. 2010 Sep;106(6):840-7. PubMed
  • 9. Gulrez G, Badyal DK, Deswal RS, Sharma A. Bupropion as an augmenting agent in patients of depression with partial response.

By HealthyStock Research Group, October 2009
Medical resources reviewed: August 2018

Interesting facts

Wellbutrin XL

  • According to the FDA Budeprion XL 300 mg (manufactured by Impax Laboratories) is NOT therapeutically equivalent to Wellbutrin XL 300 mg4.
  • Bupropion was first synthesized by Burroughs Research in 1966, and patented by Burroughs-Wellcome (later Glaxo-Wellcome) in 1974. It was approved by the FDA in 1989 and marketed under the name Wellbutrin as an antidepressant.
  • Wellbutrin XL is the first and only once-daily norepinephrine and dopamine reuptake inhibitor (NDRI) for the treatment of depression in adults.

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