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Long-Term Effects of Wellbutrin

Alternative to Meds Editorial Team Medically Reviewed by Dr John Motl MD Table of Contents: Video:  Drugs & the Synapse What is Wellbutrin©? What is Wellbutrin Prescribed For? What are the

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Alternative to Meds Editorial Team
Medically Reviewed by Dr John Motl MD

Wellbutrin is in some ways considered unique in the crowded world of antidepressants today. But like most other antidepressants, the long-term effects of Wellbutrin are not commonly discussed at the time of prescribing.

In the rush to treatment, there are very real time constraints. There is usually a pressing need for relief. But one should be apprised of these consequences, especially if the drug is used for significant periods of time.
Does Depression Treatment Always Require Antidepressants?



wellbutrin long-term effects

Our published evidence, collected by independent researchers, shows the dramatic, positive results that our clients have achieved at the center. We have been operating for close to 20 years now delivering medically supervised recovery programs for a diverse set of clientele. Many of our clients had lost hope altogether and had even been told there was no chance of recovery. Many of our professional staff experienced similar crises and frustrations in the past, but have now recovered in similar ways. We have been there. This is what makes us the compassionate and dedicated team that we are.

What is Wellbutrin?

what is wellbutrinThe antidepressant Wellbutrin (first approved in 1986) is classed as an NDRI. NDRI is is an acronym for the 2 main neurochemicals that it targets, and the reuptake-inhibiting mechanism that the drug imposes on the transmission of these natural chemicals throughout the nervous system.1,4

Wellbutrin affects the transmission of norepinephrine and dopamine, but despite suggestive advertising, it does not function as a vitamin supplement. Antidepressants do not add or create more of these vital neurochemicals. The drug binds to or blocks receptors of these natural chemicals. One might compare this to a roadblock along a highway. This blockage in transmission creates a build-up of neurochemicals. Both norepinephrine (a form of adrenaline) and dopamine (the “reward” chemical) are activating or excitatory neurochemicals. The concentration of naturally produced neurochemicals is proffered as a way to positively influence depressed mood and many other mental and physical factors. But drug regulators and drugmakers clearly note that the exact mechanisms of action are unknown. Drugs like Wellbutrin can have varying effects on different people, and over time, can have unpredictable and changing outcomes and negative long-term effects.

Want medical support while you taper? Learn how our residential medication tapering program in Sedona works, or call (888) 907-7075.

What is Wellbutrin Prescribed For?

The FDA approved Wellbutrin for MDD (major depressive disorders), seasonal affective disorder, and the generic version bupropion, under a different brand name, for smoking cessation. (Zyban©). For all uses, the drug carries a black-box warning cautioning against risks of suicide, and unspecified “neuropsychiatric” symptoms. Shortly after the drug was first brought to market, it had to be withdrawn due to a reported increase in the onset of seizures. After expanding the black-box warning to include the risk of seizures (AKA neuropsychiatric symptoms), the drug was re-launched in 1989.1,3

Off-label uses are diverse and include alleviating drug-induced sexual dysfunction, as well as ADHD, obesity, depressive episodes of BiPolar, anxiety, Dysthymic disorder, (see FAQs for more information),  PTSD, social phobias, neuropathic pain, and many others.2,4
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What Are the Long-Term Effects of Wellbutrin? Latest Research Here

Before approval, the drug was only tested in very short drug trials. This is not uncommon in the fast-paced world of drug manufacturing. Later independent studies and case history reports have provided more information over time. While no information yet appears on the drug label concerning the long-term effects of Wellbutrin, a mammoth review of the FAERS database has shown a clear picture of the long-term effects of Wellbutrin.18

Some previously unreported long-term effects of Wellbutrin according to this 2024 review include abnormal stool, increased suicidal risk in adults, and absent oculocephalogyric reflex, which means that there is absence of the involuntary (normal response) of how the eye responds when the head is turned, as in turning toward the source of outside auditory or sight signals. This is sometimes used as a test in comatose patients, that can show whether the brain stem is intact, or has been potentially compromised. Authors of the study urge much more stringent monitoring of patients who are prescribed Wellbutrin for long periods of time to avoid these and other negative outcomes referenced in the study.

Short-term effects are explained quite clearly on the label. Many short trials on bupropion and a wide body of research have established that adverse reactions can linger and become long-term effects of Wellbutrin or Zyban, or any other antidepressant drug. Now that the FAERS data has been collected and analysed, this is an area that is receiving the attention it deserves.1,5,6,18

The long-term effects of Wellbutrin may include:
  • possible long term effects of wellbutrinSuicidality
  • Risk of seizures
  • Agitation, hostility, aggressiveness, unusual behavioral changes
  • Anxiety
  • Depressed mood
  • Psychosis
  • Hallucination
  • Confusion
  • Akathisia (extreme psychomotor restlessness)
  • Addiction, cravings
  • Mania, hypomania
  • Panic attacks
  • Insomnia
  • Delusions
  • Inability to concentrate
  • Dry mouth
  • Nausea
  • Absent oculocephalogyric reflux
  • Abnormal stool

Does Taking Wellbutrin Long-Term Change the Brain?

We could find no published long-term or extensive studies on the effects of Wellbutrin on the human brain. A case report of one female given bupropion for 6 weeks showed an increased volume of grey matter, white matter, and overall brain volume compared to pre-treatment. In a study published in the German Journal of Psychopharmacology, monkeys were given amphetamines over a period of time, and then their brains were scanned. Their brain images showed similar increases in grey matter volume in one specified area of the brain. Other studies on humans who were recovering from dopaminergic drug use showed that brain volume is altered both during drug use and after a period of abstinence. Dopaminergic drugs such as heroin and amphetamines, but not Wellbutrin, were studied. The results were inconclusive beyond demonstrating that drug use was associated with increased volume in some areas of the brain, and decreased volume in other areas of brain tissue, and that drug abstinence was also associated with similar alterations of brain volume. As Wellbutrin is also a dopaminergic drug, these results are of some interest here, but researchers will have to test further to determine any information that would be helpful to drug regulators, prescribers, and consumers.7-9

Does Wellbutrin Taken Long-Term Become Habit-forming?

In drug terminology, habit-forming means having addictive characteristics. Stimulants, including coffee, all have a tendency to become habit-forming. Drug tolerance is a factor in the architecture of addiction. Drug tolerance means reduced or diminished effect, therefore as a result of prolonged exposure, one is led to take a higher dose to get similar effects, and to avoid discontinuation syndrome. At the cellular and biological level, a complex set of changes occurs, referred to as plasticity, that results from the chronic effects of daily ingestion of the substance on the internal organs and tissues, including the brain. Over time, these changes become chronic, and addiction or dependence develops.15

Studies have reported on crushing and snorting bupropion, and intravenous use for recreational users as a substitute drug for cocaine or crack. Wellbutrin has been nicknamed “poor man’s cocaine” in news stories, and its addictive potential has been reported in research published in the Journal of Addictions Nursing and the Journal of Addictive Medicine.10,11 Bupropion has become extensively used in the prison population as it is legal and easy to procure. Users who inject are particularly vulnerable to abscesses that form at the injection site due to the caustic nature of the drug which can cause deep tissue injuries that extend right down to the bone and also can cause spinal injury. Users who snort the crushed powder have been shown particularly vulnerable to seizures, due to the high doses that are involved. Bupropion has seen a significant rise in the number of people between the ages of 13 and 29 who abuse the drug and may end up at the emergency department suffering from seizures, hallucinations, tremors, tachycardia, agitation, and many other unmanageable reactions, including death. It is worth noting that the length or chronicity or method of use did not significantly determine the frequency of patients presenting with seizures.12,13,16

However, most users of Wellbutrin are not recreational users but are taking it as prescribed. Nonetheless, any dopaminergic or stimulant drug can become habit-forming, especially after it has been used for a long time and tolerance or dependence has developed. Never abruptly stop taking Wellbutrin, but seek medical assistance for a well-supervised, gradual reduction to avoid severe discontinuation symptoms.1

What About Treatment-Resistant Depression?

Statistics on persons who don’t respond adequately to one, two, or multiple antidepressants are not widely published. But estimates suggest that perhaps a million people worldwide, a significant percentage, who start antidepressants do not respond favorably, and it is quite common to be switched to another drug, in trial-and-error fashion.19

Patients who do not respond to antidepressants are referred to as “treatment-resistant.” Treatment-resistive depression has the ominous sound of being another type of disorder and may leave a person feeling confused and desperate for help. This scenario can become quite complex as a person may be switched from one drug to another, and then prescribed additional drugs to counteract emerging adverse reactions. It is not uncommon that a person will stop drug therapy altogether, due to not liking the adverse effects. Sometimes, the adverse effects disappear when the medication is stopped. This is not always the case and a person may continue to suffer even long after the drug has been stopped.1 These reactions tend to persist over time, becoming long-term effects of Wellbutrin, and one may feel trapped in a set of continuing symptoms that can be overwhelming. Perhaps in desperation, some allopathic physicians advise their patients to turn to more exotic treatments including psychedelics, electroconvulsive therapy, and even one or multiple antipsychotic medications. Yet many of these cases were never presented with gentler, holistic and workable options, as some leaders in the research field are now calling for.20

Are There Drug-free Options to Avoid Long-Term effects of Wellbutrin?

In the best of all worlds, holistic remedies for depression would be considered first-line treatments. But we live in an imperfect world, and many become tangled up in prescription drug treatments that have the potential to worsen rather than improve conditions.

In contrast, nutrition is a highly effective, though largely overlooked, therapy for preventing and reversing mental health sub-optimum conditions. Nutritional neuroscience has demonstrated how factors such as emotions, behavior, and cognition are reliant on nutrition.23

Whether one has not yet begun drug treatment or is in a recovery phase that likely includes cessation, holistic therapies exist that can help eliminate the original symptoms that led to a prescribed drug regimen.

Alternative to Meds Center uses an extensive palette of drug-free treatments for recovery after Wellbutrin or other drugs failed to achieve the desired results. You can view these in great detail on our services overview pages.

Because of complications that can arise from abrupt dopaminergic drug cessation, medical oversight and a gradual discontinuation approach are strongly advised.

Is Wellbutrin Safe for Pregnancy?

Safety studies have shown that bupropion is excreted into breast milk. Wellbutrin is classed as a C drug for pregnancy, which indicates the drug should be avoided unless there is strong medical justification to take the drug.2

A long-term study conducted on 136 pregnant women discovered that there were significantly more spontaneous abortions (miscarriages) in the women who were taking bupropion in the first trimester — 20 in total, from a group of 136 women.17

These are safety concerns that should be discussed with caregivers so that healthy decisions can be made well before any negative consequences may arise for the mother or child.

Recovery from Long-Term Effects of Wellbutrin at Alternative to Meds Center

Orthomolecular medicine provides a foundation for a successful transition to becoming drug-free and achieving improvements in mental well-being. There are many aspects to recovery that include testing for nutritional deficiencies, neurotoxin removal, correction of diet, as well as an enormous number of therapies that can bring about positive changes that can be sustained for the rest of one’s life without relying on prescription drugs for relief.

Please contact us for more information on our holistic, medically supervised recovery programs and any other information that may be useful such as insurance coverage, length of programs, and other questions you may have. Alternative to Meds Center has been focused for nearly 2 decades on helping people recover from diverse conditions including successful recovery from the long-term effects of Wellbutrin and other mental health concerns.

for Help with Wellbutrin Long-Term Effects

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Wellbutrin Long-Term Effects FAQs

Here are some of the questions we are commonly asked, but if your question isn’t covered below please reach out to us directly for the answers you need. 

Is Wellbutrin an SSRI?

No.  Wellbutrin is classed as an NDRI,  The implied mechanism is that the drug inhibits reuptake of norepinephrine and dopamine. 

What is Dysthymic Disorder?

Dysthymic Disorder is also called PDD or persistent depressive disorder. According to the DSM, the symptoms are described as mild, and persisting for very long duration of time. 22  The term comes from the Greek “dys” meaning “bad”,  and “thymos”, meaning mind or spirit. 

What is the Role of Nutrition in Mental Health?

Through the work of many exceptional medical researchers, it has been found that nutrition plays extensive, vital, and intricate functions in attaining and maintaining both mental and physical wellness. 23 

Why do Allopathic Physicians Tend to Overlook Holistic Treatment?

Allopathic, or Western medicine, trains doctors to use drugs and surgery as remedies.  They are well-trained in these genres of treatment. But their training background does not cover holistic and drug-free practices, such as those found in Orthomolecular and Naturopathic Medicine. 

What Role do Neurotoxins Play in Mental Health?

Neurotoxins are poisons that affect the human nervous system. Reactions to neurotoxins are known to mimic mental health symptoms, often leading to misdiagnosis. Examples of consequences of exposure to neurotoxins include nerve damage, disruption of communication between cells, cognitive impairment, mood dysfunction, endocrine disruption, and many others. Examples of neurotoxins include heavy metals such as lead, cadmium and mercury, as well as chemicals found in cleaning products, foods, agriculture, polluted air and water, everyday plastics, and many more. 21

Can a Person Safely Stop Taking an Antidepressant?

The safest way to stop taking antidepressant medication is to gradually reduce the dosage over an adequate period of time. The CNS needs time to readjust to the absence of the drug. Never stop taking an antidepressant too quickly, or all at once.  Find out more about safe withdrawal from Wellbutrin and share with your prescriber. 24 

Sources:

1. FDA label Wellbutrin (bupropion hydrochlordie) tablets approval 1985 [cited 2026 July 28]

2. Huecker MR, Smiley A, Saadabadi A. Bupropion. [Updated 2022 Oct 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470212/ [cited 2026 July 28]

3. Pink Sheet Pharma Intelligence, Burroughs Wellcome to Relaunch Antidepressant Wellbutrin in Mid-July After Aborted Launch in 1986: FDA-approved labelling Includes Data on Seizure Risk [published online July 03, 1989 [cited 2026 July 28]

4. Berigan TR. The Many Uses of Bupropion and Bupropion Sustained Release (SR) in Adults. Prim Care Companion J Clin Psychiatry. 2002 Feb;4(1):30-32. doi: 10.4088/pcc.v04n0110a. PMID: 15014734; PMCID: PMC314381. [cited 2026 July 28]

5. Akil H, Gordon J, Hen R, Javitch J, Mayberg H, McEwen B, Meaney MJ, Nestler EJ. Treatment resistant depression: A multi-scale, systems biology approach. Neurosci Biobehav Rev. 2018 Jan;84:272-288. doi: 10.1016/j.neubiorev.2017.08.019. Epub 2017 Aug 30. PMID: 28859997; PMCID: PMC5729118. [cited 2026 July 28]

6. Bet PM, Hugtenburg JG, Penninx BW, Hoogendijk WJ. Side effects of antidepressants during long-term use in a naturalistic setting. Eur Neuropsychopharmacol. 2013 Nov;23(11):1443-51. doi: 10.1016/j.euroneuro.2013.05.001. Epub 2013 May 30. PMID: 23726508.  [cited 2026 July 28]

7. Zhang et al., Alternation in Brain Stucture With Long-term Abstinance of Methamphetamine by Voxel-based Morphometry published in Frontiers in Psychiatry Journal, 20 December, 2018 [cited 2026 July 28]

8. Groman SM, Morales AM, Lee B, London ED, Jentsch JD. Methamphetamine-induced increases in putamen gray matter associate with inhibitory control. Psychopharmacology (Berl). 2013 Oct;229(3):527-38. doi: 10.1007/s00213-013-3159-9. Epub 2013 Jun 10. PMID: 23748383; PMCID: PMC3770792. [cited 2026 July 28]

9. Hou YC, Lai CH. The Accompanying Changes in Brain Structure of a Remitted Depression Patient with the Bupropion Treatment. Clin Psychopharmacol Neurosci. 2015 Dec 31;13(3):319-20. doi: 10.9758/cpn.2015.13.3.319. PMID: 26598593; PMCID: PMC4662168. [cited 2026 July 28]

10. Phillips D. Wellbutrin®: misuse and abuse by incarcerated individuals. J Addict Nurs. 2012 Feb;23(1):65-9. doi: 10.3109/10884602.2011.647838. PMID: 22468662. [cited 2026 July 28]

11. Alnıak İ, Ulusoy S. Bupropion Use Disorder by Chewing. J Addict Med. 2022 Jul-Aug 01;16(4):492-494. doi: 10.1097/ADM.0000000000000941. Epub 2021 Dec 3. PMID: 34864787. [cited 2026 July 28]

12. Baribeau D, Araki KF. Intravenous bupropion: a previously undocumented method of abuse of a commonly prescribed antidepressant agent. J Addict Med. 2013 May-Jun;7(3):216-7. doi: 10.1097/ADM.0b013e3182824863. PMID: 23519045. [cited 2026 July 28]

13. Oppek K, Koller G, Zwergal A, Pogarell O. Intravenous administration and abuse of bupropion: a case report and a review of the literature. J Addict Med. 2014 Jul-Aug;8(4):290-3. doi: 10.1097/ADM.0000000000000044. PMID: 24950138. [cited 2026 July 28]

14. Rao TS, Asha MR, Ramesh BN, Rao KS. Understanding nutrition, depression and mental illnesses. Indian J Psychiatry. 2008 Apr;50(2):77-82. doi: 10.4103/0019-5545.42391. PMID: 19742217; PMCID: PMC2738337. [cited 2026 July 28]

15. Pietrzykowski AZ, Treistman SN. The molecular basis of tolerance. Alcohol Res Health. 2008;31(4):298-309. PMID: 23584007; PMCID: PMC3860466. [cited 2026 July 28]

16. Stassinos GL, Klein-Schwartz W. Bupropion “Abuse” Reported to US Poison Centers. J Addict Med. 2016 Sep-Oct;10(5):357-62. doi: 10.1097/ADM.0000000000000249. PMID: 27504927. [cited 2026 July 28]

17. Chun-Fai-Chan B, Koren G, Fayez I, Kalra S, Voyer-Lavigne S, Boshier A, Shakir S, Einarson A. Pregnancy outcome of women exposed to bupropion during pregnancy: a prospective comparative study. Am J Obstet Gynecol. 2005 Mar;192(3):932-6. doi: 10.1016/j.ajog.2004.09.027. PMID: 15746694. [cited 2026 July 28]

18. Rongrong Lu, Ying Jiang, Zhiqiang Du, Qin Zhou, Yuan Shen, Haohao Zhu,
Multidimensional assessment of adverse events of bupropion: A large-scale data analysis from the FAERS database, Journal of Affective Disorders, Volume 354, 2024,
Pages 649-655, ISSN 0165-0327 [cited 2026 July 28]

19.  McIntyre RS, Alsuwaidan M, Baune BT, Berk M, Demyttenaere K, Goldberg JF, Gorwood P, Ho R, Kasper S, Kennedy SH, Ly-Uson J, Mansur RB, McAllister-Williams RH, Murrough JW, Nemeroff CB, Nierenberg AA, Rosenblat JD, Sanacora G, Schatzberg AF, Shelton R, Stahl SM, Trivedi MH, Vieta E, Vinberg M, Williams N, Young AH, Maj M. Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions. World Psychiatry. 2023 Oct;22(3):394-412. doi: 10.1002/wps.21120. PMID: 37713549; PMCID: PMC10503923. [cited 2026 July 28]

20.  Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry. 2023 Aug;28(8):3243-3256. doi: 10.1038/s41380-022-01661-0. Epub 2022 Jul 20. PMID: 35854107; PMCID: PMC10618090. [cited 2026 July 28]

21.  Garay-Canales CA, Rodríguez-Santiago Y, Ruiz-Antonio DL, Nava-Castro KE, Ríos-Avila MDS, Zavala-López CA, Chavez-Ramos YD, Sánchez-García L, Jiménez-Hernández LE, Pavón L, Morales-Montor J. Deciphering the neurotoxic effects of emerging pollutants: Bisphenols and phthalates as disruptors of brain function and mental health. iScience. 2026 May 26;29(6):115882. doi: 10.1016/j.isci.2026.115882. PMID: 42256292; PMCID: PMC13233803. [cited 2026 July 28]

22.  APA DSM V  Criteria for Dysthymia published 2013 [cited 2026 July 28]

23.  Wu J, Barbey AK. Nutrition and Mental Health: Advances in Nutritional Cognitive Neuroscience. Annu Rev Food Sci Technol. 2026 Apr;17(1):1-24. doi: 10.1146/annurev-food-052824-043906. Epub 2026 Jan 12. PMID: 41525155. [cited 2026 July 28]

24.  Horowitz MA, Framer A, Hengartner MP, Sørensen A, Taylor D. Estimating Risk of Antidepressant Withdrawal from a Review of Published Data. CNS Drugs. 2023 Feb;37(2):143-157. doi: 10.1007/s40263-022-00960-y. Epub 2022 Dec 14. PMID: 36513909; PMCID: PMC9911477. [cited 2026 July 28]

Originally Published November 29, 2022 by Diane Ridaeus


This content has been reviewed and approved by a licensed physician.

Dr. John Motl, M.D.

Dr. Motl is currently certified by the American Board of Psychiatry and Neurology in Psychiatry, and Board eligible in Neurology and licensed in the state of Arizona.  He holds a Bachelor of Science degree with a major in biology and minors in chemistry and philosophy. He graduated from Creighton University School of Medicine with a Doctor of Medicine.  Dr. Motl has studied Medical Acupuncture at the Colorado School of Traditional Chinese Medicine and at U.C.L.A.

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Medical disclaimer

This article is for educational purposes only and does not provide medical advice, diagnosis, or treatment. Never start, stop, or change a prescription medication without consulting a qualified healthcare professional who understands your medical history. If you are experiencing an immediate medical or safety emergency, call 911.