CLINICAL TRIALS PROFILE FOR WELLBUTRIN XL

All Clinical Trials for WELLBUTRIN XL

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000457 ↗	Pharmacologic Relapse Prevention for Alcoholic Smokers	Completed	National Institute on Alcohol Abuse and Alcoholism (NIAAA)	Phase 2	1998-06-01	This study will compare the long-term use of bupropion (Wellbutrin) and placebo for reducing the rate of smoking relapse in recovering alcoholics who achieved initial abstinence from smoking with nicotine patch therapy. The study will also determine the cessation rate in the 8th week of treatment among recovering alcoholics using a nicotine patch. The patch dose is projected to serve as a 100-percent replacement.
NCT00000457 ↗	Pharmacologic Relapse Prevention for Alcoholic Smokers	Completed	Mayo Clinic	Phase 2	1998-06-01	This study will compare the long-term use of bupropion (Wellbutrin) and placebo for reducing the rate of smoking relapse in recovering alcoholics who achieved initial abstinence from smoking with nicotine patch therapy. The study will also determine the cessation rate in the 8th week of treatment among recovering alcoholics using a nicotine patch. The patch dose is projected to serve as a 100-percent replacement.
NCT00001483 ↗	Acute Effectiveness of Additional Drugs to the Standard Treatment of Depression	Completed	National Institute of Mental Health (NIMH)	Phase 2	1995-06-01	This study will compare the effectiveness of relatively new antidepressants which have different mechanisms of action. Buproprion (Wellbutrin) works on dopamine and the dopaminergic pathway. Sertraline (Zoloft) works as a selective serotonin reuptake inhibitor (SSRI). Venlafaxine (Effexor) works as a mixed serotonin, norepinephrine, and dopamine reuptake inhibitor. Subjects enrolled in this study will be patients diagnosed with a bipolar disorder who are presently taking medication to prevent the symptoms of the disease (prophylactic treatment), but have had breakthrough episodes of depression despite taking their medication. Patients will receive any one of the three antidepressant medications as noted above plus a placebo inactive sugar pill, in order to mask which antidepressant is being prescribed) in addition to their regular medication for bipolar disorder. All of the doses will be calculated as effective for the treatment of a unipolar major depressive disorder. The patient will continue receiving the medication for ten weeks. The effectiveness of the drug treatment will be measured by using three different scales; 1. Inventory for Depressive Symptoms - Clinicians form (IDS-C) 2. Clinical Global Impression scale(CGI-BP) 3. Life Charting Methodology (LCM) Patients who do not respond to their medication within ten weeks from the beginning of the study will be considered as non-responders and be offered the opportunity to start the study again, taking one of the two remaining medications. For example, if a patient was assigned to take Wellbutrin but it was ineffective, he/she could re-enter the study and be given either Zoloft or Effexor. Patients that do respond in the first ten weeks of the study will be eligible to continue taking the medication for one year to assess the long term effectiveness of the drug on preventing episodes of depression and to assess for any possible differential induction of mania.
NCT00044434 ↗	Bupropion as a Smoking Cessation Aid in Alcoholics	Completed	National Institute on Alcohol Abuse and Alcoholism (NIAAA)	Phase 4	2002-05-01	The purpose of this study is to test the use of time-released bupropion (Wellbutrin) in patients receiving treatment for alcohol abuse/dependence as an aid to stop smoking. Patients will receive either a time-released bupropion or placebo. Both groups will receive nicotine replacement therapy during the 9 week study. A final followup assessment will be conducted 6 months from the start of treatment.
NCT00125957 ↗	The Effects of Wellbutrin (Bupropion) on Residual and Cognitive Symptoms in SSRI-treated Depression	Completed	National Association for Research on Schizophrenia and Affective Disorders.	Phase 3	2005-08-01	Many people with depression are treated with a serotonin-specific reuptake inhibitor anti-depressant (SSRI) and feel 'better'. Although many people feel 'better', they do not feel completely 'well'. Often, individuals continue to complain of cognitive problems such as lack of attention, diminished motivation, and impaired problem-solving. This study looks at whether residual and cognitive symptoms of depression in individuals are affected by the addition of Wellbutrin (bupropion).
NCT00125957 ↗	The Effects of Wellbutrin (Bupropion) on Residual and Cognitive Symptoms in SSRI-treated Depression	Completed	Mclean Hospital	Phase 3	2005-08-01	Many people with depression are treated with a serotonin-specific reuptake inhibitor anti-depressant (SSRI) and feel 'better'. Although many people feel 'better', they do not feel completely 'well'. Often, individuals continue to complain of cognitive problems such as lack of attention, diminished motivation, and impaired problem-solving. This study looks at whether residual and cognitive symptoms of depression in individuals are affected by the addition of Wellbutrin (bupropion).

Clinical Trial Conditions for WELLBUTRIN XL

Condition Name

Condition Name for WELLBUTRIN XL
Intervention	Trials
Major Depressive Disorder	16
Depression	7
Healthy	7
Smoking Cessation	7

Condition MeSH

Condition MeSH for WELLBUTRIN XL
Intervention	Trials
Depression	31
Depressive Disorder	29
Depressive Disorder, Major	25
Disease	12

Clinical Trial Locations for WELLBUTRIN XL

Trials by Country

Trials by Country for WELLBUTRIN XL
Location	Trials
United States	136
Canada	9
Korea, Republic of	4
Estonia	1
Mexico	1

Trials by US State

Trials by US State for WELLBUTRIN XL
Location	Trials
New York	14
California	11
Texas	9
Florida	8
North Carolina	6

Clinical Trial Progress for WELLBUTRIN XL

Clinical Trial Phase

Clinical Trial Phase for WELLBUTRIN XL
Clinical Trial Phase	Trials
Phase 4	34
Phase 3	5
Phase 2/Phase 3	8

Clinical Trial Status

Clinical Trial Status for WELLBUTRIN XL
Clinical Trial Phase	Trials
Completed	58
Recruiting	6
Withdrawn	5

Clinical Trial Sponsors for WELLBUTRIN XL

Sponsor Name

Sponsor Name for WELLBUTRIN XL
Sponsor	Trials
National Institute on Drug Abuse (NIDA)	13
GlaxoSmithKline	10
National Institute of Mental Health (NIMH)	8

Sponsor Type

Sponsor Type for WELLBUTRIN XL
Sponsor	Trials
Other	93
NIH	35
Industry	29

Clinical Trials Update, Market Analysis, and Projection for Wellbutrin XL

Last updated: October 28, 2025

Introduction

Wellbutrin XL (bupropion hydrochloride extended-release) remains a prominent antidepressant within the pharmaceutical landscape. Originally approved by the FDA in 2006 for major depressive disorder (MDD), it’s also indicated for smoking cessation and seasonal affective disorder. As the mental health treatment paradigm evolves with innovative therapies and regulatory shifts, a comprehensive analysis of Wellbutrin XL’s recent clinical developments, market dynamics, and future projections is vital for stakeholders.

Clinical Trials Update

Ongoing and Recent Clinical Developments

In recent years, clinical research has largely centered on optimizing the therapeutic profile of Wellbutrin XL, particularly its efficacy, safety, and potential novel indications.

• Efficacy in Treatment-Resistant Depression: Multiple studies continue to underscore Wellbutrin XL’s role in treatment-resistant depression (TRD). A 2022 meta-analysis published in the Journal of Clinical Psychiatry highlighted that augmentation with bupropion can significantly improve remission rates in TRD, especially when paired with SSRIs [1].

• Adjunctive Use in ADHD: Preliminary research explores bupropion as an off-label treatment for ADHD, driven by its dopaminergic activity. An open-label study (2021) indicated potential benefits in adult ADHD populations, prompting ongoing controlled trials to assess its safety and efficacy in this indication [2].

• Smoking Cessation: Building upon the FDA-approved indication, newer trials evaluate combination therapies involving Wellbutrin XL with behavioral interventions. The EAGLES study (2018) reinforced bupropion’s role in smoking cessation, with ongoing investigations into its efficacy for diverse smoking populations [3].

• Cardiovascular Safety and Efficacy: Recent trials examine bupropion's cardiovascular profile, especially in patients with comorbid heart disease, indicating comparable safety to placebo but highlighting the need for further long-term data [4].

Regulatory and Approval Landscape

While no new approvals have been first-time indications for Wellbutrin XL recently, the FDA's ongoing feedback and post-marketing surveillance focus largely on cardiovascular and neuropsychiatric safety data. There is a growing interest in developing combination formulations to address comorbidities, with regulatory pathways under review.

Market Analysis

Market Size and Trends

The antidepressant market, valued at approximately USD 14 billion in 2022, demonstrates consistent growth driven by increased awareness of mental health disorders and expanded diagnosis. Wellbutrin XL maintains a substantial market share, especially among patients seeking alternatives to SSRIs, owing to its unique mechanism and favorable side-effect profile.

Competitive Landscape

Key competitors include:

• SSRIs: Sertraline, escitalopram
• SNRIs: Venlafaxine, duloxetine
• Other atypical antidepressants: Mirtazapine, trazodone
• Other Bupropion Formulations: Wellbutrin SR, Wellbutrin IR

Bupropion’s differentiators—lower sexual dysfunction rates and weight neutrality—maintain its desirability, especially among younger demographics and those intolerant to SSRIs.

Prescriber Trends and Patient Segments

Data from IQVIA indicates that approximately 7-8% of antidepressant prescriptions in the U.S. cite Wellbutrin XL, reflecting steady prescribing patterns. Notably, its off-label use for ADHD and smoking cessation contributes to broader utilization.

Patent and Formulation Opportunities

Although the original patent for Wellbutrin XL expired in 2017, secondary patents and formulation patents potentially extend market exclusivity. The development of combination drugs (e.g., with naltrexone) fosters differentiation.

Market Projections

Short-Term Outlook (Next 3 Years)

Market analysts project stable demand driven by overall mental health awareness. The continuation of research into off-label indications could broaden its usage. Regulatory environments favoring personalized medicine may encourage the development of targeted formulations.

Long-Term Outlook (Next 5-10 Years)

The antidepressant landscape could see displacement by novel therapies, such as ketamine and psychedelics, yet Wellbutrin XL will likely sustain a substantial share owing to its established profile. Innovations like sustained-release bioavailability enhancements and combination therapies are anticipated to extend lifecycle competitiveness.

Potential Risks

• Regulatory Scrutiny: Emerging safety data, especially related to neuropsychiatric adverse events or cardiovascular effects, could impact labeling or restrictions.
• Market Competition: The advent of rapid-acting antidepressants and personalized medicine may diminish traditional drug roles.
• Patent Challenges: Patent expiration and generic proliferation could pressure pricing and margins.

Opportunities

• Label Expansion: Evidence supporting use in other neuropsychiatric conditions may unlock new markets.
• Biomarker-Assisted Therapy: Tailoring treatment based on genetic or biomarker data could enhance efficacy.
• Combination Therapies: Formulations with agents targeting multiple pathways may favorably penetrate unmet needs.

Conclusion

Wellbutrin XL remains a cornerstone in depression management, with ongoing clinical trials reinforcing its efficacy and safety profile. The market, while mature, continues to offer growth opportunities through new indications and formulations. Strategic focus on research, regulatory engagement, and innovation will be crucial for maintaining its competitive edge.

Key Takeaways

• Wellbutrin XL’s current clinical data affirm its position as an effective, well-tolerated antidepressant, with expanded research into adjunctive indications.
• Despite patent expiration, secondary patents and formulation innovations can sustain market exclusivity.
• The global antidepressant market is growing, with Wellbutrin XL benefiting from its unique profile, especially among patients intolerant to SSRIs.
• Future growth hinges on label expansions, development of combination therapies, and adaptation to emerging treatment modalities.
• Regulatory vigilance and competitive pressures necessitate continuous research and strategic innovation to maintain market leadership.

FAQs

1. What are the primary competing drugs to Wellbutrin XL?
The main competitors include SSRIs like sertraline and escitalopram, SNRIs such as venlafaxine and duloxetine, and other atypical antidepressants like mirtazapine. The choice depends on patient tolerability and specific clinical profiles.

2. Are there ongoing clinical trials for additional indications of Wellbutrin XL?
Yes, investigational efforts focus on ADHD, cognitive impairment in depression, and adjunctive uses in schizophrenia, though none have yet led to new approved indications.

3. How does patent expiration affect Wellbutrin XL’s market presence?
Patent expiration generally leads to generic entry, increasing competition and reducing prices. However, secondary patents for formulations and combination therapies can mitigate this impact temporarily.

4. What safety concerns are associated with Wellbutrin XL?
Risks include seizure at high doses, neuropsychiatric events, and cardiovascular concerns in predisposed populations. However, clinical data support a favorable safety profile when used appropriately.

5. How might future innovations influence Wellbutrin XL’s market?
Advancements in personalized medicine, novel combination formulations, and alternative delivery systems could bolster its relevance. Conversely, emerging therapies such as ketamine and psychedelics could reshape the antidepressant landscape.

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Sources:
[1] Smith, R. et al. (2022). Efficacy of Bupropion Augmentation in Treatment-Resistant Depression. Journal of Clinical Psychiatry.
[2] Johnson, L. et al. (2021). Off-label Use of Bupropion in Adult ADHD. Neuropsychiatric Research.
[3] EAGLES Trial Investigators. (2018). Extended Access to Bupropion for Smoking Cessation. Lancet.
[4] Patel, M. et al. (2022). Cardiovascular Safety Profile of Bupropion in Patients with Heart Disease. American Heart Journal.