# Wellbutrin XL ### (bupropion hydrochloride) **[Wellbutrin XL](https://wiki.joshnp.com/books/drug-library/page/wellbutrin-xl)** (bupropion hydrochloride); not controlled
[**Full Prescribing Information**](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a435da9d-f6e8-4ddc-897d-8cd2bf777b21&type=display)[**DailyMed Drug Information**](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a435da9d-f6e8-4ddc-897d-8cd2bf777b21)
--- ### **Summary** Wellbutrin XL is an aminoketone antidepressant supplied as a once-daily extended-release tablet, approved for major depressive disorder and for prevention of seasonal affective disorder in adults. It has no pediatric indication at any age, so every use in a child or adolescent is off-label. Among antidepressants it is distinctive for no serotonergic action and no sexual dysfunction or weight gain, at the cost of a dose-related seizure risk. Not controlled; brand and generic. --- ### **Forms & Strengths** - **Extended-release (XL) tablets:** 150 mg, 300 mg, the only two XL strengths - **Sustained-release (SR) tablets:** 100 mg, 150 mg, 200 mg, dosed twice daily - **Immediate-release tablets:** 75 mg, 100 mg, dosed three times daily - **Separate NDAs:** Forfivo XL 450 mg; Aplenzin (hydrobromide) 174 mg, 348 mg, 522 mg - **Combination products:** dextromethorphan-bupropion (Auvelity); naltrexone-bupropion (Contrave) --- ### **Dosing** - **Age:** adults only. No pediatric indication at any age and no pediatric ADHD indication at any age; any use in a young person is off-label. - **Onset:** 1 to 2 weeks for early effect; 4 to 6 weeks for full response - **Duration:** continuous with once-daily dosing; bupropion half-life 21 hours, hydroxybupropion about 20 hours - **Release Profile:** once-daily matrix tablet, bioequivalent over 24 hours to immediate-release 100 mg three times daily - **Initial Dose:** 150 mg once daily, for both approved indications - **Titration:** - Major depressive disorder: may increase to 300 mg once daily after 4 days - Seasonal affective disorder: may increase to 300 mg once daily after 1 week - Increase gradually; abrupt escalation raises the seizure risk - **Max Dose:** 300 mg/day. The 450 mg ceiling belongs to Forfivo XL, a different product - **Considerations:** Moderate to severe hepatic impairment caps the dose at 150 mg every other day; mild impairment or GFR under 90 mL/min needs a reduced dose or frequency. --- ### **Pharmacology** - **Mechanism:** norepinephrine-dopamine reuptake inhibitor; no serotonin reuptake or monoamine oxidase inhibition - **Metabolism:** CYP2B6 to hydroxybupropion, the principal active metabolite. Renal excretion of metabolites means impairment causes accumulation - **Class Positioning:** chosen for the absent serotonergic action: no sexual dysfunction, appetite suppression rather than weight gain. Approved non-stimulant alternatives are [Strattera](https://wiki.joshnp.com/link/4) and [Qelbree](https://wiki.joshnp.com/link/36) --- ### **Indications** - **Major Depressive Disorder** (ICD-10: F32.x, F33.x): adults only - **Seasonal Affective Disorder, prevention** (ICD-10: F33.x seasonal pattern): adults only. Start in autumn, continue through winter - **No pediatric indication at any age,** and specifically no pediatric ADHD indication --- ### **Off-Label Uses** - **ADHD in children and adolescents** (ICD-10: F90.x): limited data. Second-line where a stimulant is not tolerated and depression coexists. - The label carries no ADHD indication and no ADHD trial. - AHRQ found medication improves ADHD symptoms overall but graded no bupropion-specific pediatric evidence. (AHRQ 2024) - Weigh the seizure risk against the two approved non-stimulants first. - **Pediatric major depressive disorder** (ICD-10: F32.x, F33.x): insufficient; the adult indication does not extend downward. - **Adolescent smoking or vaping cessation** (ICD-10: F17.2x): insufficient. The label's neuropsychiatric warning applies at any age. - **Any use in a patient with an eating disorder** (ICD-10: F50.x): contraindicated, not merely unsupported. --- ### **Contraindications & Warnings** - **Boxed Warning:** SUICIDAL THOUGHTS AND BEHAVIORS. Antidepressants increased suicidal thinking and behaviour in children, adolescents and young adults. Monitor for worsening and emergent suicidality, including in off-label pediatric use. - **Contraindicated:** - Seizure disorder. - Current or prior bulimia or anorexia nervosa; absolute, and easily missed in an adolescent. - Abrupt discontinuation of alcohol, benzodiazepines, barbiturates or antiepileptics; withdrawal lowers the seizure threshold. - Concomitant MAOI, or use within 14 days of stopping one; initiation on linezolid or intravenous methylene blue. - Known hypersensitivity to bupropion or any other ingredient. - **Use with caution:** - Conditions lowering the seizure threshold: severe head injury, arteriovenous malformation, CNS tumour or infection, stroke, hypoglycemia, hyponatremia, hypoxia. - Never co-prescribe two bupropion products, and see Drug Interactions for other threshold-lowering drugs. - Insulin- or oral-hypoglycemic-treated diabetes, and anorectic drugs; both predispose to seizure. - Pre-existing hypertension, because bupropion raises blood pressure. - Bipolar disorder or risk factors: activation of mania or hypomania. - Untreated anatomically narrow angles: angle-closure glaucoma. - Renal impairment below GFR 90 mL/min; active metabolites accumulate. - **Screen before starting:** - Seizure and head injury history, and any eating disorder. Ask the adolescent alone; bulimia is rarely volunteered. - Current alcohol, benzodiazepine or antiepileptic use, and any plan to stop. - Personal and family history of bipolar disorder or mania. - Blood pressure, measured before initiation. - Medication list for MAOIs, other bupropion products, seizure-threshold drugs. - Hepatic and renal function where impairment is plausible; both change the dose. --- ### **Drug Interactions** - **MAOIs** (phenelzine, tranylcypromine, linezolid, intravenous methylene blue): hypertensive reactions. Contraindicated; allow 14 days in either direction. - **CYP2D6 substrates** (venlafaxine, nortriptyline, paroxetine, fluoxetine, risperidone, metoprolol, flecainide, atomoxetine): bupropion raises exposure. Reduce the substrate dose. - **CYP2B6 inducers** (ritonavir, efavirenz, carbamazepine, phenytoin): exposure falls. An increase may be needed, never above 300 mg/day. - **CYP2B6 inhibitors** (ticlopidine, clopidogrel): bupropion exposure rises 38% to 85%. Adjust on clinical response. - **Seizure-threshold drugs** (other bupropion products, antipsychotics, tricyclics, theophylline, corticosteroids, tramadol): additive risk. Avoid, or hold at 150 mg/day. - **Levodopa and amantadine:** CNS toxicity. Use lower doses. - **Urine drug screens:** false-positive for amphetamines. Confirm before treating a positive as diversion of a prescribed amphetamine ([Adderall](https://wiki.joshnp.com/link/8)). --- ### **Administration** - Give once daily in the morning to limit early insomnia. - Swallow whole; breaking the matrix converts a daily dose into an immediate-release bolus. - An intact tablet shell in the stool is expected, not a missed dose. - Never escalate faster than the label allows: 4 days to 300 mg for depression, 1 week for SAD. - Switching from immediate-release or SR: same total daily dose as one XL dose; confirm the product. - For seasonal affective disorder, start in autumn, continue through winter, taper in early spring. - Do not stop abruptly from 300 mg. See Discontinuation & Taper. --- ### **Side Effects** - **Common** (at least 5% and twice placebo): dry mouth, nausea, insomnia, dizziness, abdominal pain, agitation, anxiety, tremor, palpitation, sweating, anorexia, rash - **Serious:** - Suicidal thoughts and behaviour: the boxed warning. - Seizure, dose-related: about 0.1% up to 300 mg/day sustained-release, about 0.4% at 300 to 450 mg/day immediate-release. Discontinue permanently. - Serious neuropsychiatric events during smoking cessation: depression, mania, psychosis, hallucinations, aggression, agitation, panic. - Hypertension. - Activation of mania or hypomania: stop and reassess the diagnosis. - Angle-closure glaucoma: sudden eye pain, redness or visual change needs same-day ophthalmology. - Hypersensitivity, including serum-sickness-like reactions. --- ### **Monitoring & Labs** - **Suicidality:** weekly for 4 weeks, every visit through 3 months, every dose change, then each routine visit. - **Blood pressure:** baseline, 4 weeks, every dose change, then every 3 months. - **Seizure risk review:** at every dose increase and at least every 6 months. Re-ask about threshold-lowering drugs, alcohol or benzodiazepine use, and disordered eating. - **Weight and appetite:** baseline and every 3 months. Unexplained loss prompts a direct question about disordered eating. - **Psychiatric:** ask about mania, agitation, anxiety and insomnia each visit during titration, then every 3 months. - **Renal and hepatic function:** no routine schedule; recheck when circumstances change. - **Urine drug screens:** confirm any positive amphetamine result rather than acting on the immunoassay. --- ### **Discontinuation & Taper** - Taper before stopping: from 300 mg once daily, decrease to 150 mg once daily before discontinuation. - Discontinue permanently and never restart if a seizure occurs. - Stop and seek review for serious neuropsychiatric symptoms. - Drug holidays are not appropriate; the effect depends on continuous exposure. - For seasonal affective disorder, taper in early spring rather than continuing year-round. --- ### **Pregnancy & Lactation** - **Pregnancy:** first-trimester studies show no increased risk of congenital malformations overall. - Registry cardiovascular malformation rate 1.3% against a roughly 1% background; cardiac findings are inconsistent. - Background risk is 2 to 4% for birth defects, 15 to 20% for miscarriage; weigh continuation against relapse. - **Lactation:** maternal doses up to 300 mg daily give low milk levels. Case reports describe possible seizure in partially breastfed 6-month-olds; prefer another agent for a newborn. (LactMed 2026) - **Exposure Registry:** National Pregnancy Registry for Antidepressants, 1-844-405-6185, [womensmentalhealth.org](https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/) --- ### **Counseling Points** - **Counsel the family on:** - This being an adult medication used off-label, with no pediatric dose ladder. - Never taking two bupropion products; the drug is sold under several brands. - Swallowing the tablet whole; an empty shell in the stool is normal. - Insomnia and jitteriness in the first weeks, fixed by morning dosing. - Telling any clinician ordering a urine drug test, because it reads as amphetamine. - Stepping the dose down before stopping rather than stopping outright. - **Advise them to call for:** - Any seizure, including a staring spell or single whole-body jerk; stop and call the same day. - New or worsening talk of self-harm, or a sudden mood change. - A burst of high energy, reduced need for sleep, or racing speech. - Hearing or seeing things that are not there, or new suspiciousness. - Sudden eye pain, redness or blurred vision. - Rash, hives, facial or tongue swelling, or joint pains with fever. - Any plan to stop alcohol, a benzodiazepine, or a seizure medicine abruptly. --- ### **References** 1. DailyMed. Wellbutrin XL (bupropion hydrochloride extended-release tablets) prescribing information. 2025. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a435da9d-f6e8-4ddc-897d-8cd2bf777b21 2. LactMed. Bupropion. Drugs and Lactation Database, National Institute of Child Health and Human Development. 2026. https://www.ncbi.nlm.nih.gov/books/NBK501184/ 3. AHRQ. ADHD diagnosis and treatment in children and adolescents. Comparative Effectiveness Review No. 267. 2024. https://www.ncbi.nlm.nih.gov/books/NBK603001/ 4. FDA. National Drug Code Directory, openFDA. Queried by generic name bupropion. 2026. https://api.fda.gov/drug/ndc.json?search=generic\_name:%22bupropion%22&limit=1000