Wellbutrin Side Effects: What to Expect and When to Worry

Three days on Wellbutrin. Can't sleep. Heart pounding. More anxious than before you started.

You're Googling "Wellbutrin side effects" at 2 AM, convinced something is wrong.

Here's what the research shows: most of what you're experiencing is predictable, temporary, and doesn't mean the medication won't work for you (Fava et al., 2005). But some symptoms require immediate attention---and knowing the difference matters.

This guide covers everything you need to know about Wellbutrin (bupropion) side effects: what's typical in week one, what usually resolves, what's serious, and what might signal underlying medical issues worth investigating.

What Is Wellbutrin?

Wellbutrin (bupropion) is an atypical antidepressant that works differently from SSRIs like Lexapro or Zoloft. While SSRIs increase serotonin, Wellbutrin is an NDRI (norepinephrine-dopamine reuptake inhibitor)---it increases dopamine and norepinephrine in the brain.

This mechanism explains both its benefits and its side effects:

Benefits of the NDRI mechanism:

• More energy and motivation (vs SSRI fatigue)
• No sexual dysfunction (vs 40-70% with SSRIs) (Clayton et al., 2006)
• No weight gain (often weight loss)
• Helpful for concentration and focus

Side effects from the NDRI mechanism:

• Activation, restlessness, jitteriness
• Insomnia
• Anxiety worsening (in some patients)
• Increased heart rate
• Appetite suppression

Common Side Effects: What to Expect

Here are the most common side effects from clinical trials, with the percentages of patients who experienced them (Fava et al., 2005; Dunner et al., 1998):

Central Nervous System Effects

• Headache: 25-34% — Yes, week 2-3
• Insomnia: 11-20% — Often, or manageable
• Dizziness: 7-11% — Yes, week 1-2
• Tremor: 3-6% — Sometimes
• Agitation: 2-9% — Varies

Gastrointestinal Effects

• Dry mouth: 17-26% — Often persists (mild)
• Nausea: 9-18% — Yes, week 1-2
• Constipation: 5-10% — Varies
• Appetite decrease: 5-11% — Often persists

Cardiovascular Effects

• Elevated heart rate: 2-11% — Sometimes
• Elevated blood pressure: 1-2% — Monitor long-term

Other Effects

• Sweating: 5-22% — Sometimes
• Weight loss: 14-28%* — Often persists
• Rash: 5% — Usually transient

*Weight loss is often a desired effect, not a side effect

Week 1: The "Activation Period"

The first week on Wellbutrin is often the hardest. Here's what commonly happens:

Days 1-3: The "Honeymoon Effect"

Many patients experience an initial boost in energy and mood within the first few days. This is NOT the medication working yet (that takes 4-6 weeks)---it's an early dopamine/norepinephrine effect. Don't be alarmed if this initial boost fades by week two. That's expected.

Days 3-7: The Jitters

By mid-week one, many patients report:

• Feeling "wired but tired" - energized but unable to relax
• Insomnia - difficulty falling asleep, waking at 3 AM
• Increased heart rate - palpitations, awareness of heartbeat
• Anxiety - feeling keyed up, restless, on edge
• Appetite suppression - food seems less appealing

This is the "activation period" and it's why many people quit Wellbutrin before it has a chance to work. The mistake is assuming these early symptoms mean the medication isn't right for you.

What to Do During Week 1

1. Take your dose in the morning - Taking Wellbutrin after noon significantly increases insomnia risk

2. Reduce caffeine - You may need 50% less caffeine than before

3. Don't judge the medication yet - Give it 4-6 weeks before deciding

4. Track symptoms - Note which effects are improving day by day

5. Stay hydrated - Helps with dry mouth and headaches

6. Contact your provider if symptoms are intolerable (dose adjustment may help)

A 34-Year-Old's Wellbutrin Journey: From Activation to Improvement

A 34-year-old software engineer started Wellbutrin XL 150mg for depression characterized by fatigue, low motivation, and difficulty concentrating. She'd previously tried sertraline but discontinued due to weight gain and emotional blunting.

Week 1: Significant jitteriness, insomnia (sleeping only 4-5 hours), and increased anxiety. She messaged asking whether to stop.

Intervention: Recommended cutting caffeine by 75%, taking melatonin 0.5mg for sleep, and continuing---these symptoms typically resolve.

Week 2: Jitteriness decreased substantially. Sleep improved to 6 hours. Energy noticeably better.

Week 4: Minimal remaining activation. Energy and motivation significantly improved. Concentration better at work. No weight gain, no emotional blunting.

Week 6: Depression symptoms 70% improved by PHQ-9 score. Side effects negligible except mild dry mouth (easily managed with more water).

The key insight: Had she stopped in week 1, she would have missed a medication that eventually worked very well for her. The activation period was uncomfortable but temporary.

Weeks 2-4: The Adjustment Period

Most common side effects start improving by week 2-3:

Usually improves:

• Headache
• Nausea
• Initial anxiety surge
• Dizziness
• The "wired" feeling

May persist but become tolerable:

• Dry mouth (often mild)
• Some insomnia (manageable with sleep hygiene)
• Appetite suppression (often welcomed)

Therapeutic effects begin:

• Energy improvement
• Motivation returning
• Mood stabilization beginning

Weeks 4-6+: Full Effect

By week 4-6, you should have a clear picture of whether Wellbutrin is working:

Signs it's working:

• More consistent energy throughout the day
• Improved motivation and follow-through
• Mood feels more stable
• Anhedonia (lack of pleasure) improving
• Easier to get out of bed

Signs it may not be the right fit:

• Persistent severe anxiety (not mild activation)
• Insomnia that isn't responding to interventions
• Agitation that affects relationships or work
• No improvement in target symptoms despite adequate dose

Serious Side Effects: When to Stop and Call

Some side effects require immediate attention. Contact your provider right away if you experience:

Seizures (Risk: ~0.1% at 300mg; ~0.4% at 400mg)

Wellbutrin lowers the seizure threshold (Dunner et al., 1998). Risk factors:

• History of seizures or head trauma
• Eating disorders (current or history)
• Alcohol withdrawal
• Concurrent medications that lower seizure threshold
• Doses above 450mg/day
• Taking immediate-release more than 150mg per dose

If you have a seizure: Stop medication, seek emergency care, do not restart without medical guidance.

Severe Allergic Reactions

Stop Wellbutrin and seek care if you experience:

• Difficulty breathing or swelling of face/throat
• Severe rash, hives, or blistering
• Fever with rash
• Joint pain with skin symptoms

Neuropsychiatric Emergencies

Contact your provider urgently for:

• Suicidal thoughts (especially new or worsening)
• Manic symptoms - decreased need for sleep, grandiosity, racing thoughts, impulsive behavior
• Psychotic symptoms - paranoia, hallucinations, severe confusion

Black Box Warning Context: All antidepressants carry a warning about increased suicidal thinking in young adults (18-24) in the first weeks of treatment. This doesn't mean the medication causes suicidality---it means close monitoring is essential during the initiation period.

Cardiovascular Concerns

Seek evaluation if you experience:

• Chest pain
• Irregular heartbeat (not just fast, but irregular rhythm)
• Severe blood pressure elevation
• Fainting or near-fainting

Formulation Differences: SR vs XL vs IR

Wellbutrin comes in three formulations with different side effect profiles:

Immediate Release (IR)

• Dosing: 3 times daily
• Peak: Sharp peaks, then drops
• Side effects: More pronounced peaks of activation, higher seizure risk per dose
• Rarely used for depression (higher seizure risk)

Sustained Release (SR)

• Dosing: Twice daily
• Peak: Smoother than IR
• Side effects: Moderate; some patients do better splitting the activating effect

Extended Release (XL)

• Dosing: Once daily (morning)
• Peak: Smoothest release
• Side effects: Often best tolerated; lower peak levels
• Most commonly prescribed

If you're having side effects on one formulation: Ask your provider about switching. XL is generally best tolerated. Some patients do better on SR if XL causes late-afternoon energy drops.

The Anxiety Paradox: Why Wellbutrin Makes Some People More Anxious

One of the most confusing aspects of Wellbutrin: it can either worsen or improve anxiety, depending on the patient.

Who gets more anxious on Wellbutrin:

• Patients with primary anxiety disorders (anxiety is the main problem)
• People who are already "keyed up" or hyperaroused
• Those with panic disorder (activating medications can trigger panic)
• Patients sensitive to stimulating effects

Who often feels less anxious on Wellbutrin:

• Patients with "sluggish" depression - low energy, low motivation, fatigue
• People whose anxiety comes from not being able to function (secondary anxiety)
• ADHD patients whose anxiety is driven by overwhelm and disorganization
• Those who were more anxious on SSRIs due to emotional blunting or sexual dysfunction

Distinguishing "Activation" from "Anxiety"

Activation (usually resolves):

• Physical restlessness
• Difficulty sitting still
• Feeling "energized but uncomfortable"
• Generally occurs early, improves over weeks

Anxiety worsening (may not resolve):

• Racing thoughts, worry spirals
• Dread, panic, doom feeling
• Avoidance behaviors increasing
• Doesn't improve or worsens over 4+ weeks

If you have significant anxiety worsening: Consider whether a different medication (SSRI, buspirone) might be more appropriate, or whether the anxiety has a medical cause worth investigating.

Side Effects That Rarely Get Discussed

Beyond the clinical trial data, patients often report effects that are less commonly discussed:

Hair Thinning

Some patients report hair shedding, usually temporary:

• Occurs in ~5% of patients (may be underreported)
• Usually begins 2-3 months after starting
• Often reversible after stopping or with time
• May be related to stress on hair follicles during the adjustment period

Tinnitus (Ringing in Ears)

• Reported in clinical trials at 1-6%
• Usually mild
• Can be persistent in some patients
• Worth discussing with provider if bothersome

Increased Sweating

• More common than many realize (5-22%)
• Can be embarrassing (especially night sweats)
• Sometimes manageable with aluminum chloride antiperspirant

Emotional Changes

Some patients report:

• Feeling "flat" - less emotional range (less common than with SSRIs)
• Feeling "sharper" - more focused, less foggy
• Irritability - especially in first weeks
• Emotional clarity - some patients feel emotions are cleaner/clearer

Changes in Taste

• Metallic taste (uncommon but reported)
• Decreased interest in sweets
• Changed food preferences

Weight Effects: What to Really Expect

Weight loss is common with Wellbutrin---and often desired. Here's what the research shows (Thase et al., 2005):

Average weight loss: 2-10 lbs over 6-12 months (varies widely)

Mechanism:

• Dopamine effects on reward pathways decrease food cravings
• Appetite suppression
• Increased energy leading to more activity
• Decreased emotional eating (if depression was driving overeating)

Who loses weight:

• Those who were overeating due to depression
• Patients switching from SSRIs that caused weight gain
• People whose main symptom was fatigue/inactivity

Who might not lose weight (or might gain):

• Those already at low weight
• Patients who weren't overeating
• Rare cases of paradoxical increased appetite

Red flag: Significant, rapid weight loss (more than 5% body weight in a month) without trying should be reported---this could indicate medication effect, but also underlying medical issues.

Drug Interactions That Worsen Side Effects

Some medications interact with Wellbutrin and can increase side effect risk:

CYP2D6 Inhibitors (Increase Wellbutrin Levels)

These medications can increase Wellbutrin levels, intensifying side effects:

• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Quinidine
• Ritonavir

If you're taking these together, your provider may need to lower your Wellbutrin dose.

Medications That Lower Seizure Threshold

Combining with Wellbutrin increases seizure risk:

• Tramadol
• Theophylline
• Systemic steroids
• Other antidepressants in high doses
• Stimulants
• Antipsychotics

MAOIs (Absolutely Contraindicated)

Never combine Wellbutrin with MAO inhibitors:

• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Selegiline (EMSAM patch)

Wait at least 14 days between stopping an MAOI and starting Wellbutrin.

Alcohol

Wellbutrin + alcohol = increased seizure risk. Additionally:

• Alcohol metabolism may be altered
• More severe hangovers reported
• Don't abruptly stop heavy alcohol use while starting Wellbutrin (withdrawal + Wellbutrin = seizure risk)

When Side Effects Signal Underlying Medical Issues

Sometimes what looks like a medication side effect is actually revealing an underlying medical problem.

Severe Anxiety on Wellbutrin: What to Investigate

If Wellbutrin dramatically worsens your anxiety, consider whether these were already present:

Thyroid dysfunction:

• Hyperthyroidism causes symptoms identical to Wellbutrin activation
• Wellbutrin may "unmask" subclinical hyperthyroidism
• Check: TSH, Free T4, Free T3

Blood sugar issues:

• Reactive hypoglycemia causes anxiety, palpitations, tremor
• Wellbutrin's appetite suppression may worsen this
• Check: Fasting glucose, consider CGM monitoring

Cardiac Symptoms: What's Medication vs Medical

Wellbutrin-related heart symptoms are usually:

• Mild heart rate increase (10-15 bpm)
• Palpitations (awareness of normal heartbeat)
• Occurs early, may stabilize

Seek evaluation if:

• Resting heart rate consistently >100
• Irregular rhythm (not just fast)
• Chest pain or pressure
• Significant blood pressure elevation

Some patients discover underlying cardiac conditions when Wellbutrin brings attention to their cardiovascular system. That's actually useful information, even if it's not a medication "side effect."

Fatigue Despite "Activating" Medication

If you're taking Wellbutrin---an activating medication---and you're still exhausted, don't just blame the medication. Consider:

Check labs:

• Ferritin (not just hemoglobin---iron stores matter)
• Vitamin D
• B12
• Thyroid panel
• Fasting glucose/HbA1c

Consider:

• Sleep apnea (common, underdiagnosed)
• Underlying anemia
• Metabolic dysfunction

Wellbutrin should provide more energy, not less. Persistent fatigue on Wellbutrin is a clue that something else is going on.

Managing Common Side Effects

Insomnia

Strategies:

1. Take dose early (7-9 AM, never after noon)

2. Reduce or eliminate afternoon caffeine

3. Practice sleep hygiene: cool room, dark, consistent bedtime

4. Consider melatonin 0.5-1mg for sleep onset

5. If persistent, consider switching to SR (twice daily) with lower evening dose

6. Discuss with provider: low-dose trazodone or hydroxyzine if needed

Dry Mouth

Strategies:

1. Increase water intake

2. Sugar-free gum or lozenges

3. Biotene products (designed for dry mouth)

4. Avoid mouthwash with alcohol

5. Usually becomes tolerable even if doesn't fully resolve

Headache

Strategies:

1. Stay hydrated

2. OTC pain relief (acetaminophen, ibuprofen) short-term

3. Usually resolves by week 2-3

4. If severe or persistent, may need dose adjustment

Nausea

Strategies:

1. Take with food

2. Ginger tea or ginger supplements

3. Eat smaller, more frequent meals

4. Usually resolves within 1-2 weeks

Jitteriness/Restlessness

Strategies:

1. Reduce caffeine significantly

2. Physical exercise (helps burn off excess activation)

3. Deep breathing exercises

4. Usually improves over 2-4 weeks

5. Consider dose reduction if severe

What About Cost?

Wellbutrin is available as generic bupropion, which significantly reduces cost:

Generic bupropion prices (approximate):

• Bupropion XL 150mg: $10-30/month with insurance, $15-60/month without (GoodRx)
• Bupropion XL 300mg: $10-40/month with insurance, $20-80/month without (GoodRx)
• Bupropion SR 150mg: $10-25/month with insurance, $15-45/month without (GoodRx)

Brand-name Wellbutrin:

• Significantly more expensive ($300-600/month without insurance)
• Rarely necessary---generics are equivalent
• Some patients prefer brand if they've had issues with generic inconsistency

Cost-saving options:

• Use GoodRx or similar discount cards (often cheaper than insurance copay)
• 90-day supplies typically offer better per-pill pricing
• Manufacturer coupons occasionally available
• Patient assistance programs for those who qualify

Insurance coverage: Bupropion is on most formularies as a Tier 1 or Tier 2 medication, meaning lower copays than newer antidepressants.

When to Consider Stopping

Not everyone is the right fit for Wellbutrin. Consider stopping (with your provider's guidance) if:

Clear reasons to stop:

• Seizure occurs
• Severe allergic reaction
• Manic episode triggered
• Suicidal thoughts emerging or worsening
• Intolerable side effects not improving after 6+ weeks
• No therapeutic benefit after adequate trial (8+ weeks, therapeutic dose)

Ambiguous situations (discuss with provider):

• Side effects are bothersome but manageable---worth tolerating for benefits?
• Some improvement but not complete remission---add augmentation or switch?
• Partial response at current dose---try increasing or switch?

Discontinuation: What to Expect

Unlike SSRIs, Wellbutrin has minimal discontinuation syndrome. Most patients can stop without significant withdrawal symptoms.

What some patients notice:

• Temporary fatigue for a few days
• Mood dip (original symptoms may return, not "withdrawal")
• Occasional headache

Tapering recommendation:

• Though not strictly necessary for physical reasons, gradual tapering (reducing by 150mg every 3-7 days) allows you to monitor whether symptoms return
• Helps distinguish "withdrawal" from "original symptoms returning"

The Bottom Line: Side Effects in Context

Wellbutrin side effects are real, but they're also predictable and usually temporary. The first 2-3 weeks are the hardest. If you can push through the activation period, most patients find a medication that:

• Doesn't cause sexual dysfunction
• Doesn't cause weight gain
• Provides energy and motivation
• Has minimal withdrawal symptoms if you ever stop

The key insight: Side effects are information. They tell you how your body is responding to increased dopamine and norepinephrine. Severe or persistent side effects sometimes reveal underlying medical issues worth investigating---not just "medication intolerance."

Thorough investigation of what's causing side effects---whether it's the medication, an underlying medical condition, or both---often leads to better outcomes than simply switching medications repeatedly.

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Ready for a Thorough Evaluation?

If you're starting Wellbutrin, experiencing concerning side effects, or wondering whether it's the right medication for you, a comprehensive assessment can help determine what's happening and what to do about it.

What to expect:

• 75-90 minute comprehensive assessment
• Full review of medical history and current medications
• Lab workup to rule out underlying medical contributions
• Careful medication selection based on YOUR presentation
• Close monitoring during medication initiation

Locations: Medication management in Rancho Palos Verdes, Medication management in Phoenix, Medication management in Chandler, and telehealth throughout California and Arizona

Book Your Consultation →

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Disclaimer: This article is for educational purposes only and does not constitute medical advice. Side effects and medication responses vary by individual. All medication decisions should be made in consultation with your prescriber. If you're experiencing severe side effects, contact your healthcare provider immediately. If you're having thoughts of suicide or self-harm, call 988 (Suicide & Crisis Lifeline) or go to your nearest emergency room.

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References

• Clayton AH, Croft HA, Horrigan JP, et al. (2006). Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies. Journal of Clinical Psychiatry, 67(5), 736-746. PMID: 16841624
• Dunner DL, Zisook S, Billow AA, et al. (1998). A prospective safety surveillance study for bupropion sustained-release in the treatment of depression. Journal of Clinical Psychiatry, 59(7), 366-373. PMID: 9714265
• Fava M, Rush AJ, Thase ME, et al. (2005). 15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL. Primary Care Companion to the Journal of Clinical Psychiatry, 7(3), 106-113. PMID: 16027765
• Thase ME, Haight BR, Richard N, et al. (2005). Remission rates following antidepressant therapy with bupropion or selective serotonin reuptake inhibitors: a meta-analysis of original data from 7 randomized controlled trials. Journal of Clinical Psychiatry, 66(8), 974-981. PMID: 16086611
• Wellbutrin XL Prescribing Information. GlaxoSmithKline.