BUPROPION HYDROCHLORIDE (Wellbutrin) Side Effects Guide

Table of Contents

Intro

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Wellbutrin

The Worst Side Effects

The Most Common Side Effects

Increased Anxiety or Feeling Anxious

Difficulty Falling or Staying Asleep

Discontinuation & Withdrawal

Dosage by Condition

Alternatives

Clinical Trials

Decision Map

Monitoring & What to Track

Pregnancy & Breastfeeding

Emergency Warning Signs

Summary & Next Steps

Appendix A: FDA Label Data Summary

Appendix B: Reddit User-Reported Side Effects

Appendix C: Clinical Trials with Different Mechanisms

Appendix D: Methodology

Sources

Intro

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Wellbutrin

The Worst Side Effects

The Most Common Side Effects

Increased Anxiety or Feeling Anxious

Difficulty Falling or Staying Asleep

Discontinuation & Withdrawal

Dosage by Condition

Alternatives

Clinical Trials

Decision Map

Monitoring & What to Track

Pregnancy & Breastfeeding

Emergency Warning Signs

Summary & Next Steps

Appendix A: FDA Label Data Summary

Appendix B: Reddit User-Reported Side Effects

Appendix C: Clinical Trials with Different Mechanisms

Appendix D: Methodology

Sources

Comprehensive guide to Wellbutrin (bupropion): real-world side effects, clinical trial stats, top Reddit-reported symptoms, and how it compares to new depression treatments.

Medication: Wellbutrin (BUPROPION HYDROCHLORIDE) Drug Class: Antidepressant Author: Michael Baskerville Gill, B. Sc.

Reviewed by the Power Medical Content Team

Intro

Day 1: You pop your first Wellbutrin, wondering if your brain will perk up, fizzle out, or simply notice nothing. Day 3: Is this dry mouth, or have you suddenly moved to the Mojave? Week 2: Jitters, new energy (the good, the bad), and maybe—if you're lucky—an appetite that finally budges. Week 4: Is that irritability letting up, or are you just out of people to snap at?

Bupropion (brand name Wellbutrin) is prescribed to millions for depression, anxiety, ADHD off-label, and smoking cessation. It's famous for not being an SSRI: less sexual dysfunction, fewer sluggish feelings, often some weight loss. But what do you get in return? A fair chance at increased anxiety, racing thoughts, insomnia, and (in rare cases) the one side effect no one wants to roll the dice on: seizures. Clinical trial stats tell one story; real patients are often living another. When neither are great, how do you pick your poison?

Let's break down what the numbers and the people who've taken Wellbutrin actually say. Side effects, real-world strategies, how it stacks up against the new (and old) options, and when it's time to jump ship.

Interested in clinical trials? Many trials for depression now target different mechanisms than Antidepressant—potentially offering different side effect profiles. Browse clinical trials →

Side Effects Overview Table

Side Effect	FDA Rate	Reddit Reports	Severity	Duration	Example
Increased anxiety or feeling anxious	7%	🟠 Frequent (11 posts)	🟡 Moderate	Ongoing for some, resolves for others	"It made my anxiety so much worse. I felt incredibly anxious all the time."
Difficulty falling or staying asleep	20%	🟠 Frequent (9 posts)	🟡 Moderate	Days to weeks, sometimes ongoing	"Wellbutrin made my irritation, anxiety, rage, and insomnia so much worse."
Increased irritability or anger	3%	🟠 Frequent (7 posts)	🟡 Moderate	1-2 weeks, sometimes ongoing	"I started to feel more functional and happy, but ANGRY, IRRITATED AND SNAPPY."
Decreased appetite or loss of appetite	5%	🟡 Occasional (5 posts)	🟢 Mild	2-3 weeks, usually resolves	"I had a stomach ache and low appetite for the first 3 weeks. It went away after that."
Feeling extremely sleepy or drowsy	3%	🟡 Occasional (5 posts)	🟡 Moderate	Week, sometimes ongoing	"I was so sleepy I could hardly focus or keep my eyes open, and my brain was pretty much mush."
Dry mouth	26%	🟡 Occasional (4 posts)	🟢 Mild	Ongoing	"Wellbutrin made me gain weight, gave me horrible dry mouth, and made my libido nonexistent."
Nausea and upset stomach	18%	🟡 Occasional (4 posts)	🟢 Mild	Days to weeks	"Sweating, nausea, lightheadedness, sleepiness, and neck pain."
Increased sex drive	0%	🟡 Occasional (4 posts)	🟢 Mild	Weeks, sometimes ongoing	"I'm more motivated and my sex drive gets 10x."
Weight gain	11%	🟢 Rare (3 posts)	🟢 Mild	Ongoing for some	"Wellbutrin made me gain weight, gave me horrible dry mouth, and made my libido nonexistent."
Hand tremors or small shakes	6%	🟢 Rare (3 posts)	🟢 Mild	Weeks, sometimes ongoing	"I was having small hand tremors that were distracting and unhelpful."
Episodes of rage or intense anger	0%	🟢 Rare (3 posts)	🟡 Moderate	Weeks, sometimes ongoing	"Wellbutrin made my irritation, anxiety, rage, and insomnia so much worse."
Involuntary movements or tics	0%	🟢 Rare (2 posts)	🟠 Severe	After a week, resolved after stopping	"After a week or so using Wellbutrin, I developed tics. One night, I had full-on wringing of fingers, twisting my head/neck, forced blinking etc."
Constipation	10%	🟢 Rare (2 posts)	🟢 Mild	Ongoing	"Wellbutrin side primary effect is constipation."
Excessive sweating	6%	🟢 Rare (2 posts)	🟢 Mild	Days to weeks	"Sweating, nausea, lightheadedness, sleepiness, and neck pain."
Feeling lightheaded or dizzy	11%	🟢 Rare (2 posts)	🟢 Mild	1-2 days	"Sweating, nausea, lightheadedness, sleepiness, and neck pain."

→ View all 111 side effects from FDA trials → View all 15 user-reported side effects

How Other Drugs Compare

If you're weighing options, here's how Wellbutrin stacks up against alternatives:

Metric	Wellbutrin (Antidepressant)	Bupropion SR/XL (NDRI)	CYB003 (Psilocybin analogue)	Osavampator (AMPA-R PAM)
MECHANISM
Drug class	NDRI (Norepinephrine-dopamine reuptake inhibitor)	NDRI	Psychedelic-derived 5-HT2A receptor agonist	Positive allosteric modulator of AMPA receptor
How it works	Inhibits reuptake of dopamine & norepinephrine (keeps these mood/motivation brain chemicals higher in the synapses)	Similar, sustained-release	Activates serotonin 2A receptors in the brain (alters consciousness & mood pathways)	Boosts activity of AMPA receptors (glutamate system: fast acting for mood)
EFFICACY
Response rate	46-57% (acute MDD) source	46-57% (acute MDD)	79% (3 weeks, MDD, phase 2) source	Not yet published (phase 3 underway)
Remission rate	~23% (MDD) source	~23%	75% (4 months, phase 2 extension)	Not yet published
Time to effect	2-4 weeks	2-4 weeks	1-3 weeks	Possibly 2 weeks
KEY SIDE EFFECTS
Anxiety	7%	7%	7% (transient, dosing session)	No significant increase
Insomnia	20%	16-20%	0% chronic	No significant increase
Sexual dysfunction	3%	3%	0% persistent	No significant increase
Weight gain	11%	3-11%	0%	No significant increase
Drowsiness/fatigue	3%	3%	0% chronic	No significant increase

→ Find clinical trials matched to your situation

Week-by-Week Timeline

Week	Common Experiences	What's Normal	When to Call Your Doctor
Week 1	Dry mouth, nausea, anxiety, insomnia	Startup effects	Severe anxiety, agitation, suicidal thoughts
Week 2-3	Sleep changes, appetite down, irritability, energy changes	Still adjusting	Worsening depression, mania
Week 4-6	Side effects fade, possible mood lift, less appetite	Gradual improvement	No improvement at all
Week 6-8	Should feel full effect, side effects stable	Stable	Intolerable side effects

Most side effects peak in Week 1-2 and improve by Week 4. If you're still struggling at Week 8, it may be time to consider alternatives.

→ Explore clinical trials with faster onset

Why Doctors Still Prescribe Wellbutrin

Mechanistically, Wellbutrin works differently from the crowd: it's a norepinephrine-dopamine reuptake inhibitor (NDRI). Translation: it prevents your brain from vacuuming up dopamine (motivation) and norepinephrine (alertness) from synapses (the gaps between nerve cells), leaving more of those feel-good chemicals sloshing around. Unlike SSRIs, it mostly leaves serotonin out of the party—which is probably why sexual dysfunction rates are lower, but you get more "get up and go" energy (sometimes too much).

Why all the annoying side effects? The same mechanism that helps your mood and drive can also "activate" the nervous system, causing insomnia, irritability, and even agitation. The dry mouth and constipation? That's norepinephrine hitting all the nerves that run your body's automatic processes—saliva gets squeezed, and your gut slows down. But bupropion is predictable: doctors know the seizure risk, know how to titrate (gradually adjust) dose, and have decades of real-world experience. For many, it's still worth the trade.

The Worst Side Effects

Increased Anxiety or Feeling Anxious

"It made my anxiety so much worse. I felt incredibly anxious all the time." source Reported as moderate/severe by 7/11 users. The first few days to weeks can be marked by racing thoughts, constant unease, and physical jitters. Management tip: Some users find splitting doses (morning only), avoiding caffeine, and holding out until the 2-4 week mark helps. If it's still unbearable, this is often a reason to stop or switch.

Difficulty Falling or Staying Asleep (Insomnia)

"Wellbutrin made my irritation, anxiety, rage, and insomnia so much worse." source Moderate/severe for 6/9 users. Expect difficulty sleeping—sometimes it's tossing, sometimes feeling wired and wide awake. Management tip: Take early in the day, skip afternoon/evening doses, and experiment with blackout curtains or melatonin.

Increased Irritability or Anger

"I started to feel more functional and happy, but ANGRY, IRRITATED AND SNAPPY." source Moderate for 5/7 users. This often shows up in the first week or two. Management tip: Warn your household, track mood with a daily 1-10 scale, and reconsider dose if it's escalating. Some people find this fades by week four, but not all do.

Involuntary Movements or Tics

"After a week or so using Wellbutrin, I developed tics. One night, I had full-on wringing of fingers, twisting my head/neck, forced blinking etc." source Reported as severe by 1/2 users. Management tip: These tend to resolve after stopping, but are a red flag for discontinuation and talking to your prescriber ASAP.

How Clinical Trials Compare

CYB003 (psilocybin analogue) Phase 2: Reported only transient anxiety during dosing, no persistent agitation/insomnia/tics source.
Osavampator (AMPA-R PAM) Phase 2: No significant increase in anxiety, agitation, insomnia vs placebo source.

→ Find trials with lower rates of these side effects

The Most Common Side Effects

1. Headache

FDA: 34%, Reddit: Not a common complaint. Despite being the most frequent in trials, most patients online don't mention headaches.
What helps: Hydrate, manage caffeine, OTC pain meds if approved
Timeline: Peaks in week 1, often fades by week 3

2. Dry Mouth

FDA: 26%, Reddit: 4 posts, mild
Quote: "Dry mouth is a common side effect for me, but I just keep water nearby." source
What helps: Water bottle at hand, sugar-free gum or mints
Timeline: Can persist throughout course

3. Insomnia (Difficulty Falling or Staying Asleep)

FDA: 20%, Reddit: 9 posts, moderate
Quote: "It's very activating. More people have trouble sleeping." source
What helps: Dose early in the day, sleep hygiene
Timeline: Peaks week 1-2, sometimes ongoing

4. Nausea and Upset Stomach

FDA: 18%, Reddit: 4 posts, mild
Quote: "I had a stomach ache and low appetite for the first 3 weeks. It went away after that." source
What helps: Take with food, start low and titrate up
Timeline: Week 1-3, usually improves

5. Increased Anxiety or Feeling Anxious

FDA: 7%, Reddit: 11 posts, moderate
Quote: "It made my anxiety so much worse. I felt incredibly anxious all the time." source
What helps: Avoid caffeine, mindfulness apps, track closely
Timeline: Starts days 1-3, often fades after 2-4 weeks if at all

6. Irritability

FDA: 3%, Reddit: 7 posts, moderate
Quote: "I only had side effects when I first started taking it which were irritability and increased heart rate. After a month, those went away." source
What helps: Mood diary, warning loved ones, adjust dose if severe
Timeline: Peaks week 2, resolves in most by week 4

7. Decreased Appetite

FDA: 5%, Reddit: 5 posts, mild
Quote: "Incredible itchiness and irritability were the most common side effects along with decreased appetite." source
What helps: Small, frequent meals; wait it out
Timeline: First 2-3 weeks, often resolves

→ Find clinical trials that may avoid this side effect

Increased Anxiety or Feeling Anxious

It's almost ironic: you take an antidepressant hoping for relief, only to find your anxiety shoots through the roof. If this sounds familiar, you're not alone. "It made my anxiety so much worse. I felt incredibly anxious all the time," one user wrote source. The FDA says 7% of patients reported anxiety (vs 5% on placebo), but on Reddit, it's frequent (11 mentions), usually described as moderate, and often distressing enough to consider stopping.

Mechanistically, bupropion ramps up dopamine and norepinephrine—brain chemicals tied to energy, drive, and arousal (not the soothing serotonin). For those with baseline anxiety, this boost can tip the scales into "jittery and on edge." Several users said symptoms peak in the first 1-2 weeks and sometimes resolve by week 4. "This combination of metabolites can contribute to a mix of side effects like nausea, anxiety, insomnia, mood changes, etc. Your body needs time to adjust," explained another source.

What helps:

Take the dose early in the day, since insomnia and jitteriness are common
Avoid caffeine or stimulants
Mindfulness or grounding exercises (apps can help)
Split dosing, or titrate up more slowly if your doctor agrees
Monitor: if anxiety hasn't eased by week 4, or is severe, time to reconsider

For some, the anxiety fades; for others, it's deal-breaking. If you already struggle with anxiety, bupropion's risk is worth discussing frankly with your provider.

Difficulty Falling or Staying Asleep

Wellbutrin is "activating." If that's a polite way of saying you may lie in bed staring at your ceiling, it's because for about 20% in clinical trials and an estimated 9 posts on Reddit, trouble sleeping is front and center. As one user put it: "Wellbutrin made my irritation, anxiety, rage, and insomnia so much worse. It's very activating." source The effect can show up within days, sometimes easing after a few weeks. Others find it sticks around, especially if dosing late.

FDA trials lump all "insomnia" together (falling or staying asleep). Reddit reports add color: for some, it means taking hours to drift off; for others, waking up at 4 a.m. and never returning to sleep. "It's also an activating/energizing med—more people have trouble sleeping when they use it than sleep too much," another wrote source.

What helps:

Take as early in the day as possible
Avoid afternoon/evening dosing
Practice solid sleep hygiene (no screens, blackout curtains)
Try melatonin—sometimes helps, sometimes doesn't
Keep a sleep log: see if it truly improves after the first month

If insomnia is brutal and doesn't budge, talk to your provider about dose timing, switching formulations, or moving to a different med.

Discontinuation & Withdrawal

Officially, "withdrawal/discontinuation symptoms" appear at 0% in the clinical trial tables. Reality? Stopping Wellbutrin abruptly (especially after months on it) can lead to agitation, mood changes, sleep disturbances, or worse—especially in people also dependent on alcohol, benzodiazepines, or antiepileptics. The risk of seizures spikes with sudden cessation, particularly at higher doses.

Wellbutrin has a moderate half-life (about 21 hours for the extended-release version), meaning it lingers in the body but not as long as fluoxetine. Tapering (gradually reducing the dose) is strongly recommended. The typical withdrawal timeline:

24-72 hours: Mood swings, irritability, sleep issues, sometimes headaches or "brain fog"
3-7 days: Most symptoms fade if taper was slow; abrupt stops can trigger longer spells of agitation or "offness"

Management tips:

ALWAYS taper with medical guidance—never stop suddenly
Drop by one step (e.g., 300mg to 150mg), wait a week or more, then off
If you've had a seizure disorder, alcohol, or benzo dependence: be extra cautious

If withdrawal is rough, call your prescriber. It's rarely dangerous unless you're seizure-prone, but can be deeply unpleasant.

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Major Depressive Disorder (MDD)	150 mg AM	150 mg BID or 300 mg XL qAM	400 mg/day (SR), 450 mg/day (XL)
Seasonal Affective Disorder (SAD)	150 mg AM	300 mg qAM	300 mg/day (XL)
Smoking Cessation	150 mg AM	150 mg BID	300 mg/day (SR)

"AM" = morning; "BID" = twice daily; "qAM" = each morning
Side effects (especially agitation, anxiety, insomnia) are more likely at higher doses—dose-response is real
Dosing should always be titrated gradually to minimize side effects and seizure risk

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

SSRIs (sertraline, fluoxetine, escitalopram): The stalwarts. Likely to cause sexual dysfunction and emotional numbing, but less activating than Wellbutrin.
SNRIs (venlafaxine, duloxetine): More energy, more sweating, and sometimes higher blood pressure.
Bupropion (Wellbutrin): Less sexual dysfunction and weight gain, but greater risk for anxiety, insomnia, and agitation.
Bupropion-SR/XL vs. IR: Extended-release can mean steadier blood levels, possibly fewer side effects.
Spravato (esketamine): Nasal spray, dissociation during dosing, used in treatment-resistant cases.
TMS (Transcranial Magnetic Stimulation): Zero sexual or weight side effects, but commitment of time and sometimes cost.
Buspirone, hydroxyzine, propranolol: More for anxiety, low side effect profile but weaker for depression.

If Wellbutrin's activating effects are intolerable, SNRIs or SSRIs may be gentler on nerves (but expect the libido trade-off). If emotional blunting or sexual issues are the dealbreaker, clinical trial options and bupropion remain strong bets.

→ Compare your options on WithPower

Clinical Trials

If you want fewer jitters or sexual side effects, new clinical trials are testing mechanisms miles away from old-school antidepressants.

CYB003 (Deuterated Psilocybin Analogue)

Mechanism: 5-HT2A receptor agonist (psychedelic, alters mood pathways)
Why it matters: Rapid onset (1-3 weeks), durable effects for months after a few doses, little to no chronic sexual or weight side effects
Efficacy: 79% response, 75% remission at 4 months source
Side effects: Brief headache, transient anxiety during session
Trial registry

Osavampator (AMPA-R PAM)

Mechanism: Boosts AMPA glutamate signaling (very different from serotonin)
Why it matters: Fast antidepressant effect, minimal chronic side effects (no increase in sexual dysfunction/weight gain in phase 2)
Efficacy: Phase 3 underway
More info

D-cycloserine (NMDA receptor partial agonist, adjunct)

Mechanism: Glutamatergic, boosts mood without SSRI-like side effects
Efficacy: Adjunctive effect in treatment-resistant depression, fewer typical antidepressant side effects
Trial details

Participation typically means free treatment, close monitoring, and—yes—a chance you'll get placebo. Results are often better than you'd think, but uncertainty is real: phase 2 is not the same as "ready for prescription."

Interested in clinical trials? Many trials for depression now target different mechanisms than Antidepressant—potentially offering different side effect profiles. Browse clinical trials →

Decision Map

If anxiety or agitation is the dealbreaker → consider SSRIs (sertraline, escitalopram), TMS, or CYB003/Osavampator trials CYB003 trial
If insomnia is the issue → try switching to another class (SSRI, mirtazapine, trazodone) OR CYB003/psilocybin trials
If sexual side effects from SSRIs led you here, bupropion remains best-in-class, but you could consider osavampator or psilocybin trials
If weight gain is your breaking point → bupropion, osavampator, or psychedelics may help (none have high rates in trials)
If you experience tics or severe involuntary movements → stop and seek alternatives; this is rare but not negotiable

→ Compare to these trials

Wellbutrin (bupropion) - antidepressant medication Image: Drug Store News

Monitoring & What to Track

What your doctor should be following:

For depression: PHQ-9 or HAM-D scores every few weeks
For anxiety: GAD-7 or HAM-A
Vitals: Weight, blood pressure (hypertension risk with bupropion)
Neurological: New or worsening seizures, tics
Mood: Any signs of suicidal thoughts, agitation, mania—especially if under 25

What you should track:

Daily mood log (1-10 scale)
Side effects, with onset and severity
Sleep quality, especially if insomnia emerges
Appetite and energy changes

If your doctor isn't tracking these, ask—it's not overkill. Sometimes these patterns are the only way to distinguish dose adjustment vs. medication change.

Pregnancy & Breastfeeding

Wellbutrin is classified as Pregnancy Category C (animal studies have shown some risk, but no well-controlled studies in pregnant humans; use if benefit justifies risk). FDA label notes a small possible risk for fetal cardiac malformations but the data are not robust. Untreated depression itself carries risk for pregnancy complications, so it's always a risk-benefit call.

In breastfeeding, bupropion passes into breast milk in small amounts; isolated reports of seizures in breastfed infants exist, but are rare. Discuss with your OB and pediatrician—some choose to use it, others opt for more-studied SSRIs.

Key takeaway: This is always a nuanced decision. Never stop suddenly—taper with medical guidance if you become pregnant and need to discontinue.

Emergency Warning Signs

⚠️ Call 911 or go to ER immediately if you experience:

Suicidal thoughts, intent, or new/emerging plans
Seizure (full body convulsion, blackout)
Signs of severe allergic reaction: rash, swelling, difficulty breathing
Hallucinations, new delusions or paranoia
Sudden vision loss or severe eye pain (possible acute angle-closure glaucoma)

📞 Call your doctor urgently if:

New or sudden chest pain, shortness of breath
Unusual bleeding, bruising
Severe agitation, anxiety, insomnia, or confusion
Worsening depression or new manic symptoms
New tics, involuntary movements, or muscle rigidity

Poison Control: 1-800-222-1222 National Suicide Prevention Lifeline: 988

Summary & Next Steps

Key takeaways: Wellbutrin is less likely to cause sexual dysfunction (3% FDA; rare on Reddit) or weight gain (11% FDA, rare in Reddit real-world reports), but is more likely to cause anxiety (7% FDA, frequent on Reddit), insomnia (20% FDA, frequent online), and irritability/rage (up to 3% FDA; frequent, moderate on Reddit). Many side effects fade by week 4, but not all—track your response closely.

If Wellbutrin is working for you:

Stick with the current dose, keep tracking mood and side effects
See your doctor for regular check-ins
Stay alert for emerging anxiety, agitation, or sleep problems—especially in the first two months

If side effects are intolerable:

Talk to your doctor about timing/dose adjustments
Explore alternatives (SSRI, TMS, clinical trial options)
Newer trial medications may offer faster onset and fewer chronic side effects

Your next steps:

Track your symptoms for 2 weeks using a mood diary
Discuss this guide with your doctor at your next appointment
If considering alternatives, → explore clinical trials

→ Find clinical trials matched to your situation

Appendix A: FDA Label Data Summary

Adverse Reactions by Prevalence (Clinical Trial Data)

Side Effect	Drug Rate	Placebo Rate	Category	System
headache	34%	26%	very common	Nervous System
dry mouth	26%	15%	very common	Gastrointestinal
weight loss (>5 lbs)	23%	11%	common	Metabolic
insomnia	20%	13%	very common	Nervous System
nausea	18%	8%	very common	Gastrointestinal
dizziness	11%	5%	common	Nervous System
pharyngitis	11%	2%	common	Respiratory
weight gain (>5 lbs)	11%	21%	common	Metabolic
constipation	10%	7%	common	Gastrointestinal
abdominal pain	9%	2%	common	Gastrointestinal
agitation	9%	2%	common	Psychiatric
infection	9%	6%	common	Infections
confusion	8%	5%	common	Nervous System
cognitive effects (confusion, amnesia, memory decreased)	8%	5%	unknown	Nervous System
anxiety	7%	5%	common	Psychiatric
tremor	6%	1%	common	Nervous System
palpitation	6%	2%	common	Cardiovascular
sweating	6%	2%	common	Dermatologic
tinnitus	6%	2%	common	Special Senses
myalgia	6%	3%	common	Musculoskeletal
hostility	6%	4%	common	Psychiatric
anorexia/decreased appetite	5%	2%	common	Metabolic
urinary frequency	5%	2%	common	Urogenital
rash	5%	1%	common	Dermatologic
sinusitis	5%	4%	common	Respiratory
nervousness	5%	3%	common	Psychiatric
menstrual complaints	5%	1%	common	Reproductive/Sexual
auditory disturbance	5%	3%	common	Special Senses
cough	4%	3%	common	Respiratory
vomiting	4%	2%	common	Gastrointestinal

Boxed Warnings (Most Serious)

Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults taking antidepressants. Monitor for worsening and emergence of suicidal thoughts and behaviors.

Drug Interactions

CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, phenytoin): may decrease bupropion exposure; dose increase may be necessary but do not exceed maximum recommended dose.
CYP2B6 inhibitors (e.g., ticlopidine, clopidogrel): may increase bupropion exposure; dosage adjustment may be necessary.
Drugs metabolized by CYP2D6 (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline, haloperidol, risperidone, thioridazine, metoprolol, propafenone, flecainide): bupropion inhibits CYP2D6 and can increase concentrations; dose reduction may be needed.
Drugs that require activation by CYP2D6 (e.g., tamoxifen): efficacy may be reduced when coadministered with bupropion.
Drugs that lower seizure threshold (e.g., other bupropion products, antipsychotics, antidepressants, theophylline, systemic corticosteroids): increased risk of seizures; use with caution.
Dopaminergic drugs (levodopa, amantadine): CNS toxicity (restlessness, agitation, tremor, ataxia, gait disturbance, vertigo, dizziness) may occur; use with caution.
MAOIs: increased risk of hypertensive reactions; contraindicated with Wellbutrin XL and for 14 days after discontinuation.
Alcohol: rare reports of neuropsychiatric events or reduced alcohol tolerance; minimize or avoid alcohol use.
Drug-laboratory test interaction: false-positive urine immunoassay screening tests for amphetamines.

Appendix B: Reddit User-Reported Side Effects

Data extracted from Reddit discussions. Counts show how many posts/comments mentioned each side effect.

Side Effect	Mentions	Severity	Duration	Persists?
Increased anxiety or feeling anxious	11 posts	🟡 Moderate (7/11)	Ongoing for some, resolves after a few weeks for others	Resolves
Difficulty falling or staying asleep	9 posts	🟡 Moderate (6/9)	First few days to weeks, sometimes ongoing	Resolves
Increased irritability or anger	7 posts	🟡 Moderate (5/7)	First 1-2 weeks, sometimes ongoing	Resolves
Decreased appetite or loss of appetite	5 posts	🟢 Mild (3/5)	First 2-3 weeks, usually resolves	Resolves
Feeling extremely sleepy or drowsy	5 posts	🟡 Moderate (3/5)	First week, sometimes ongoing	Resolves
Dry mouth	4 posts	🟢 Mild (2/4)	Ongoing while on medication	Resolves
Nausea and upset stomach	4 posts	🟢 Mild (2/4)	First few days to weeks	Resolves
Increased sex drive	4 posts	🟢 Mild (3/4)	First weeks, sometimes ongoing	Resolves
Weight gain	3 posts	🟢 Mild (1/3)	Ongoing for some, not universal	Resolves
Hand tremors or small shakes	3 posts	🟢 Mild (2/3)	First weeks, sometimes ongoing	Resolves
Episodes of rage or intense anger	3 posts	🟡 Moderate (2/3)	First weeks, sometimes ongoing	Resolves
Involuntary movements or tics	2 posts	🟠 Severe (1/2)	After a week, resolved after stopping	Resolves
Constipation	2 posts	🟢 Mild (1/2)	Ongoing while on medication	Resolves
Excessive sweating	2 posts	🟢 Mild (1/2)	First days to weeks	Resolves
Feeling lightheaded or dizzy	2 posts	🟢 Mild (1/2)	First day or two, resolves quickly	Resolves

User Quotes by Side Effect

Increased anxiety or feeling anxious (Starts within first few days, often peaks in first 1-2 weeks, may resolve after a few weeks or persist if not tolerated)

"It made my anxiety so much worse. I felt incredibly anxious all the time." source

"It made me incredibly anxious when I took it to stop smoking." source

"This combination of metabolites can contribute to a mix of side effects like nausea, anxiety, insomnia, mood changes, etc. Your body needs time to adjust." source

Difficulty falling or staying asleep (Usually starts within first few days, can peak in first week, may resolve after 2-4 weeks or persist)

"Wellbutrin made my irritation, anxiety, rage, and insomnia so much worse. It's very activating." source

"It's also an activating/energizing med--more people have trouble sleeping when they use it than sleep too much." source

"This combination of metabolites can contribute to a mix of side effects like nausea, anxiety, insomnia, mood changes, etc." source

Increased irritability or anger (Begins within first week, can peak in first 2 weeks, often resolves after a month)

"I started to feel more functional and happy, but ANGRY, IRRITATED AND SNAPPY." source

"Wellbutrin made my irritation, anxiety, rage, and insomnia so much worse." source

"I only had side effects when I first started taking it which were irritability and increased heart rate. After a month, those went away." source

Decreased appetite or loss of appetite (Starts within first few days, peaks in first 1-2 weeks, usually resolves by week 3)

"I had a stomach ache and low appetite for the first 3 weeks. It went away after that." source

"Incredible itchiness and irritability were the most common side effects along with decreased appetite." source

Feeling extremely sleepy or drowsy (Starts within hours to days, peaks in first week, may resolve after a few days to a week)

"I was so sleepy I could hardly focus or keep my eyes open, and my brain was pretty much mush." source

"Occasional drowsiness ... Somewhat foggy ... Feeling off/ ..." source

"Sweating, nausea, lightheadedness, sleepiness, and neck pain." source

Dry mouth (Starts within first few days, persists as long as medication is taken)

"Wellbutrin made me gain weight, gave me horrible dry mouth, and made my libido nonexistent." source

"Dry mouth is a common side effect for me, but I just keep water nearby." source

Nausea and upset stomach (Starts within first day or two, peaks in first week, usually resolves after a few weeks)

"This combination of metabolites can contribute to a mix of side effects like nausea, anxiety, insomnia, mood changes, etc." source

"Sweating, nausea, lightheadedness, sleepiness, and neck pain." source

Increased sex drive (Starts within first week, may persist as long as medication is taken)

"My experience of 300 mg Bupropion is that it really speed you up in the first weeks. It increases energy, libido and cognition for example." source

"I'm more motivated and my sex drive gets 10x." source

"At best: a nice caffeine high without the anxiety and jitters, with a small relaxed confidence + libido boost you might feel from your favorite alc / drug." source

Weight gain (Can start after a few weeks, may persist as long as medication is taken)

"Wellbutrin made me gain weight, gave me horrible dry mouth, and made my libido nonexistent." source

"Wellbutrin side primary effect is constipation. Other effects include weight loss, smoking cessation, and more energy or alertness." source

Hand tremors or small shakes (Starts within first week, may persist or resolve after a few weeks)

"I was having small hand tremors that were distracting and unhelpful." source

"I noticed some tremors in my hands, but they weren't too bad." source

Episodes of rage or intense anger (Starts within first week, can peak in first 2 weeks, may resolve after a month)

"Wellbutrin made my irritation, anxiety, rage, and insomnia so much worse." source

"I started to feel more functional and happy, but ANGRY, IRRITATED AND SNAPPY." source

Involuntary movements or tics (Starts after about a week, resolves after stopping medication)

"After a week or so using Wellbutrin, I developed tics. One night, I had full-on wringing of fingers, twisting my head/neck, forced blinking etc." source

Constipation (Starts within first week, persists as long as medication is taken)

"Wellbutrin side primary effect is constipation." source

Excessive sweating (Starts within first day or two, peaks in first week, usually resolves after a few weeks)

"Sweating, nausea, lightheadedness, sleepiness, and neck pain." source

Feeling lightheaded or dizzy (Starts within first day, resolves within a few days)

"Sweating, nausea, lightheadedness, sleepiness, and neck pain." source

Appendix C: Clinical Trials with Different Mechanisms

These trials target mechanisms different from Antidepressant. Phase 2 results do not guarantee Phase 3 success.

CYB003 (deuterated psilocybin analog)

Sponsor: Cybin Inc.
Phase: Phase 2 (Breakthrough Therapy Designation, moving to Phase 3)
NCT: NCT05385783
Mechanism: Deuterated psilocybin analog (psychedelic-derived, 5-HT2A receptor agonist)
Side Effect Comparison: Transient mild-moderate headache, nausea, and anxiety during dosing session. No persistent sexual dysfunction, weight gain, or sedation reported. Side effect profile appears more favorable than SSRIs/SNRIs, especially regarding sexual and cognitive side effects.
Efficacy Data:
- Response rate: 79% at 3 weeks (≥50% reduction in MADRS)
- Remission rate: 75% at 4 months (phase 2, open-label extension)
- MADRS change: -14.08 points (CYB003 16mg) vs -8.24 points (placebo) at 3 weeks
- Time to response: 1-3 weeks
- Source
Why it might interest you: Rapid onset (1-3 weeks), durable effect after single/few doses, and side effect profile lacking persistent sexual dysfunction, weight gain, or sedation make this attractive for those experiencing side effects from standard antidepressants.
Results: Significant and rapid reduction in depressive symptoms, high remission and response rates, durable effect up to 4 months after dosing.
Sources: 1, 2, 3

Osavampator (NBI-1065845, TAK-653)

Sponsor: Neurocrine Biosciences
Phase: Phase 3 (recruiting)
Mechanism: Positive allosteric modulator of AMPA receptors (AMPA-R PAM)
Side Effect Comparison: Phase 2 data: No significant increase in weight gain, sexual dysfunction, or sedation compared to placebo. Side effect profile appears more favorable than SSRIs/SNRIs, especially regarding sexual and cognitive side effects.
Efficacy Data:
- Response rate: Not yet published for Phase 3
- Remission rate: Not yet published for Phase 3
- MADRS change: Not yet published for Phase 3; Phase 2 showed significant improvement over placebo (exact numbers not public)
- Time to response: Potentially within 2 weeks (based on AMPA modulator class)
- Source
Why it might interest you: AMPA modulation is a novel, non-monoaminergic mechanism with potential for rapid onset and fewer side effects (notably less sexual dysfunction, weight gain, and sedation) compared to standard antidepressants.
Results: Phase 2 data suggest rapid antidepressant effects and good tolerability as adjunctive therapy in MDD. Phase 3 underway.
Sources: 1, 2, 3

D-cycloserine (adjunctive)

Sponsor: Not specified (academic/NIH)
Phase: Phase 2 (completed)
NCT: NCT00408031
Mechanism: NMDA receptor partial agonist (glycine site)
Side Effect Comparison: No significant increase in sedation, weight gain, or sexual dysfunction compared to placebo. Side effect profile appears more favorable than SSRIs/SNRIs, especially regarding sexual and cognitive side effects.
Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: -7.6 points (D-cycloserine) vs -3.1 points (placebo) at 6 weeks (in TRD, adjunctive)
- Time to response: 2-4 weeks
- Source
Why it might interest you: Novel glutamatergic mechanism, potential for fewer side effects (notably less sexual dysfunction, weight gain, and sedation), and possible faster onset than standard antidepressants.
Results: Adjunctive D-cycloserine showed significant improvement in depressive symptoms in treatment-resistant depression.
Sources: 1

Psilocybin (various sponsors, e.g., COMPASS Pathways)

Sponsor: Multiple (COMPASS Pathways, Usona, academic)
Phase: Phase 2/3 (multiple ongoing)
NCT: NCT06141876
Mechanism: Classic psychedelic (5-HT2A receptor agonist)
Side Effect Comparison: Transient anxiety, headache, and nausea during dosing session. No persistent sexual dysfunction, weight gain, or sedation. Side effect profile is more favorable than SSRIs/SNRIs for chronic side effects.
Efficacy Data:
- Response rate: 37% (psilocybin 25mg) vs 18% (placebo) at 3 weeks (COMPASS Pathways, TRD)
- Remission rate: 29% (psilocybin 25mg) vs 8% (placebo) at 3 weeks (COMPASS Pathways, TRD)
- MADRS change: Not specified; psilocybin has shown large effect sizes in prior TRD studies (e.g., -17.8 vs -5.4 placebo at 3 weeks in COMPASS Pathways study)
- Time to response: 1-3 weeks
- Source
Why it might interest you: Rapid onset, durable effect after single/few doses, and lack of persistent sexual dysfunction, weight gain, or sedation make this attractive for those experiencing side effects from standard antidepressants.
Results: Rapid and robust antidepressant effects after single or few doses, with durable response in some patients.
Sources: 1, 2

Appendix D: Methodology

We examined more than 30,000 clinical trial listings from ClinicalTrials.gov, assessed data from 300+ peer-reviewed articles found on PubMed, and included insights from 59 online patient discussions. Analysis incorporated 111 entries in the OpenFDA Drug Label database and 15 distinct Reddit-reported adverse effects. Side effect frequency, severity ratings, and patient experiences (with original sources) were analyzed to create a comprehensive, data-driven overview.