DULOXETINE HYDROCHLORIDE (Cymbalta) Side Effects Guide
A brutally honest look at Cymbalta’s (duloxetine) side effects: what you’ll likely feel, how bad it gets, and how long it lasts—straight from patients and clinical trials.
Medication: Cymbalta (DULOXETINE HYDROCHLORIDE) Drug Class: Antidepressant Author: Michael Baskerville Gill, B. Sc.
Reviewed by the Power Medical Content Team
Intro
Day 1: Light nausea, some jitters, and a headache. Day 4: The stomach revolt reaches its peak, sleep is a mess, but by the end of Week 2—things just might calm down. Sound familiar? That’s the typical first month with Cymbalta (duloxetine), an SNRI (serotonin-norepinephrine reuptake inhibitor—meaning it keeps more of these mood-regulating brain chemicals floating around your synapses, those tiny gaps between nerve cells). It’s prescribed for depression, anxiety, fibromyalgia, and nerve pain. About 60-65% of patients in trials see measurable improvement, but the trade-off is clear: up to 23% face nausea, and 9% quit due to side effects. Add to that the Reddit crowd, who bring receipts—vivid stories of brain zaps, sexual dysfunction, and withdrawal that lingers for months. The hard truth: Cymbalta works well for some, but for many, the early days are a white-knuckle ride, and the long-term side effect baggage is real. The status quo leaves plenty of room for skepticism—and new options.
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 |
|---|---|---|---|---|---|
| Nausea and upset stomach | 23% | 🟠 frequent (13 posts) | 🟡 moderate | 1-4 weeks, sometimes ongoing | source |
| Headaches and migraines | 14% | 🟡 occasional (7 posts) | 🟡 moderate | 1-4 weeks, may recur | source |
| Fatigue and tiredness | 9% | 🟡 occasional (7 posts) | 🟡 moderate | 1-4 weeks, sometimes ongoing | source |
| Excessive sweating and night sweats | 6% | 🟡 occasional (6 posts) | 🟢 mild | Ongoing, may improve | source |
| Decreased libido and sexual side effects | 3-4%* | 🟡 occasional (5 posts) | 🟢 mild | Ongoing, may lessen | source |
| Dizziness and lightheadedness | 9% | 🟡 occasional (5 posts) | 🟢 mild | 1-4 weeks, with dose changes | source |
| Difficulty falling or staying asleep | 9% | 🟡 occasional (5 posts) | 🟡 moderate | 1-4 weeks, sometimes ongoing | source |
| Loss of appetite or reduced hunger | 7% | 🟢 rare (4 posts) | 🟢 mild | 1-4 weeks, may persist | source |
| Brain zaps when stopping or missing doses | N/A | 🟢 rare (4 posts) | 🟠 severe | Days-weeks after stopping | source |
| Nightmares or vivid bad dreams | N/A | 🟢 rare (4 posts) | 🟢 mild | 1-4 weeks, may persist | source |
| Dilated pupils or changes in vision | 3% (blurred vision) | 🟢 rare (3 posts) | 🟢 mild | First 2-3 weeks | source |
| Restlessness or agitation | 4% | 🟢 rare (3 posts) | 🟡 moderate | 1-4 weeks, sometimes ongoing | source |
| Heart palpitations or racing heart | 2% | 🟢 rare (3 posts) | 🟡 moderate | Ongoing, may resolve | source |
| Brain fog or difficulty thinking | N/A | 🟢 rare (3 posts) | 🟡 moderate | Ongoing, may improve | source |
| Withdrawal symptoms after stopping | N/A | 🟢 rare (3 posts) | 🟠 severe | Days-months after stopping | source |
*Sexual dysfunction is almost certainly underreported; clinical estimates may be low.
→ View all 129 side effects from FDA trials → View all 15 user-reported side effects
How Other Drugs Compare
If you're weighing options, here's how Cymbalta stacks up against alternatives:
| Metric | Cymbalta (SNRI Antidepressant) | Bupropion (NDRI) | CYB003 (Psilocybin analogue) | Osavampator (AMPA-PAM) |
|---|---|---|---|---|
| MECHANISM | ||||
| Drug class | SNRI (serotonin-norepinephrine reuptake inhibitor) | NDRI (norepinephrine-dopamine reuptake inhibitor) | Psychedelic-derived (5-HT2A receptor agonist) | Glutamatergic (AMPA receptor modulator) |
| How it works | Blocks reuptake (prevents reabsorption) of serotonin & norepinephrine at synapses | Inhibits reuptake of norepinephrine & dopamine | Activates serotonin 5-HT2A receptors | Modulates AMPA receptors (boosts glutamate signaling) |
| EFFICACY | ||||
| Response rate | ~60% FDA label | 56% source | 79% at 6 wks CYB003 | Not yet reported |
| Remission rate | ~40% FDA label | 35% source | 75% at 4 mo CYB003 | Not yet reported |
| Time to effect | 2-4 weeks | 2-4 weeks | 1-2 weeks | ~2 weeks* |
| KEY SIDE EFFECTS | ||||
| Nausea | 23% | 6% | 13% | No significant increase |
| Sexual dysfunction | 4% (likely underreported) | 1-2% | Not reported | No significant increase |
| Weight gain | Low | 0-1% | 0% | 0% |
*Based on class; not confirmed in Phase 3 yet
→ Find clinical trials matched to your situation
Week-by-Week Timeline
| Week | Common Experiences | What's Normal | When to Call Your Doctor |
|---|---|---|---|
| Week 1 | Nausea, headache, jittery, fatigue | Startup effects | Severe anxiety, suicidal thoughts |
| Week 2-3 | Sleep trouble, appetite drop, sweating, dizziness | Still adjusting | Worsening depression |
| Week 4-6 | Early benefit possible, fewer side effects | Gradual improvement | No improvement at all |
| Week 6-8 | Full effect (if any) reached | 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 Cymbalta (Duloxetine)
Here’s the mechanistic elevator pitch: Cymbalta blocks the reuptake (prevents the brain from reabsorbing) both serotonin and norepinephrine. That double-whammy means more mood-regulating brain chemicals stick around your synapses (the gaps between nerve cells), which for some people, boosts both mood and pain relief.
But there’s a catch: those same brain chemicals don’t just control mood. Norepinephrine plays traffic cop for blood pressure, sweat glands, even your gut. Serotonin’s everywhere, so side effects happen when those chemicals aren’t exactly where you want them. Nausea? That’s serotonin flooding your gut nerves. Sweating, insomnia, and sexual side effects? Blame the system-wide reach.
So why does Cymbalta keep its slot in the first-line antidepressant roster? Simple: decades of trial data, predictability (you mostly know what you’re going to get), and a broad FDA label from depression to fibromyalgia. Side effects may be common, but at least they’re not mysterious, and for a sizable minority, it’s the only thing that moves the needle.
The Worst Side Effects
Brain Zaps When Stopping
"The worst side effects are the brain zaps you get from cold turkey stopping and pee constipation because it also works for urinary ..." source
Reported as severe by 3/4 users (Reddit).
Management tip: Taper SLOWLY under your doctor's guidance. Never stop Cymbalta abruptly; dose reductions of 10-20% every 1-2 weeks are typical.
Withdrawal Symptoms After Stopping
"The largest downfall—withdrawals. If I don't take it, even for a day, the side effects are unreal. Don't take it if you have issues refilling ..." source
Reported as severe by 2/3 users.
Management tip: Always have a backup prescription. Symptoms can last days to months. Flu-like symptoms, brain zaps, and mood swings are textbook—hydrate, rest, and push for a professional taper protocol.
Nausea and Upset Stomach
"Both times I couldn't get past a week of horrible side effects like nausea..." source
Moderate-severe (8/13 users). Usually resolves in 2-4 weeks. Ginger tea, bland food, and taking with a small meal may help.
How Clinical Trials Compare
CYB003 (psilocybin analog) and Osavampator showed no evidence of withdrawal syndrome or brain zaps (so far) in Phase 2 studies, whereas Cymbalta’s withdrawal rate approaches 50% in abrupt discontinuation cases FDA label. Novel mechanisms may skip the worst of withdrawal.
→ Find trials with lower rates of these side effects
The Most Common Side Effects
Nausea and Upset Stomach
- FDA: 23%
- Reddit: 13 reports (🟠 frequent); moderate severity
- What helps: Take with food or at bedtime, bland diet, consider a ginger supplement
- Timeline: Peaks week 1, resolves for most by week 2-4
"I started 30mg duloxetine a few days ago, and the side effects are certainly affecting me, especially the nausea and stomach issues." source
Headaches and Migraines
- FDA: 14%
- Reddit: 7 reports (🟡 occasional); moderate severity
- What helps: Stay hydrated, OTC pain relievers, regular sleep
- Timeline: First week, often gone by week 2-4
"On top of this I'm also experiencing intense migraines and headaches." source
Fatigue and Tiredness
- FDA: 9%
- Reddit: 7 reports (🟡 occasional); moderate
- What helps: Gentle activity, morning dosing, watch for sleep cycle changes
- Timeline: Week 1-4, sometimes ongoing
"It affects me mainly with fatigue, brain fog, shooting/stabbing pains, and general hypersensitivity." source
Sweating & Night Sweats
- FDA: 6%
- Reddit: 6 reports (🟡 occasional); mild
- What helps: Dress in layers, cooling pillow, gentle exercise
- Timeline: Ongoing, may decrease after first month
"I did have initial side effects of dry mouth, sweating, sexual side effects but all these become less over time..." source
Difficulty Sleeping
- FDA: 9%
- Reddit: 5 reports (🟡 occasional); moderate
- What helps: Avoid caffeine late, regular bedtime, evening dosing
- Timeline: Week 1-4, sometimes longer
"Both times I couldn't get past a week of horrible side effects like nausea, appetite loss, nightmares, insomnia, headaches, and fatigue." source
Deep Dive: Nausea and upset stomach
If you’ve ever found yourself Googling “will Cymbalta nausea go away?” at 2am, you’re not alone. The clinical data says 23% (that’s nearly 1 in 4) get it—most in the first week. On Reddit, it’s the most talked-about issue: “Day 1 - light nausea, muscle weakness, heart palpitations, headache, sleepiness...” source and “Both times I couldn’t get past a week of horrible side effects like nausea, appetite loss...” source. Most describe it as moderate, peaking in the first week and gradually fading by week 2-4—but for some, it lingers if doses are pushed too fast.
The culprit? Serotonin’s not just a brain chemical; about 90% of it actually lives in your gut. Amp up serotonin and the digestive tract reacts. Practical tricks: Take Cymbalta with a small meal, skip spicy foods, and use ginger (tea, capsule, or even just the raw stuff). For the unlucky few, dose-splitting or a slower titration (gradual dose increase) can blunt the gut punch. If it’s still disabling after a month, your doctor may recommend a switch.
Deep Dive: Brain zaps when stopping or missing doses
It’s the stuff of legends (and night terrors): those brief, electrical, "zzzt" sensations zapping across your skull when you miss a dose or stop Cymbalta. No, you’re not making it up. Three out of four users who mention it on Reddit call it severe, and it can linger for weeks—sometimes months—after discontinuation. Official clinical trials didn’t bother to name this side effect, but the FDA label does warn of discontinuation syndrome: dizziness, headache, nausea, paraesthesia (tingling), irritability, insomnia, and yes, “electric shock-like sensations.”
Quotes paint the picture: “The worst side effects are the brain zaps you get from cold turkey stopping…” source and "You'll very likely be fine and not feel much. Besides brain zaps other discontinuation symptoms for me are oversleeping/having issues getting out of bed..." source.
Why does it happen? Cymbalta’s half-life (how long it stays active in your body) is only about 12 hours—miss a dose and blood levels plummet. Management: absolute best bet is a slow, methodical taper (dose decrease), preferably using bead-counting (opening capsules to reduce by 1-2mg per day). Cold turkey is not just unpleasant, it’s dangerous. If you’re prone to these shocks, set a pillbox alarm and stock emergency doses.
Discontinuation & Withdrawal
Discontinuation syndrome (the fancy phrase for withdrawal after stopping or missing doses) is the reason "brain zaps" and flu-like misery end up as memes on depression boards. Around 44-50% of patients report withdrawal symptoms after stopping SNRIs like Cymbalta—even after a slow taper.
FDA label lists: dizziness, headache, nausea, diarrhea, tingling, irritability, vomiting, insomnia, anxiety, sweating, and fatigue. Unique to Cymbalta: a half-life of just 12 hours (meaning it clears the body fast), which increases the risk of withdrawal if you miss or delay a dose.
Management tips:
- Taper slowly—1-2 weeks per drop is safer than "as fast as you can stand."
- Dose splitting with bead-counting or liquid if possible
- Always under medical supervision—don't DIY your taper
Typical timeline: symptoms begin 1-2 days after last dose, can last for weeks (occasionally months, especially with abrupt discontinuation).
"It sucks brain zaps, worsening anxiety and depression, heart palpitations, mood swings. My withdrawal lasted about 6 months." source
If withdrawal is severe or you have seizures, seek medical help immediately.
Dosage by Condition
| Condition | Starting Dose | Typical Dose | Maximum Dose |
|---|---|---|---|
| Major depressive disorder | 30-60 mg once daily | 60 mg/day | 120 mg/day |
| Generalized anxiety disorder | 30 mg once daily | 60 mg/day | 120 mg/day |
| Diabetic peripheral neuropathy | 30 mg once daily | 60 mg/day | 60 mg/day |
| Fibromyalgia | 30 mg once daily | 60 mg/day | 60 mg/day |
| Chronic musculoskeletal pain | 30 mg once daily | 60 mg/day | 90 mg/day |
Dose increases should occur no sooner than every 1-2 weeks (titration—gradual adjustment). Higher doses may raise the risk of side effects. Start low and go slow if you’re sensitive.
Alternatives
If Cymbalta feels like too much chaos, you have options. Here’s the landscape:
- Bupropion (Wellbutrin, an NDRI) – The “caffeine of antidepressants.” Often energizing, and almost never causes sexual side effects or weight gain.
- SNRIs (venlafaxine, desvenlafaxine) – Cousins to Cymbalta; similar effectiveness, but venlafaxine is notorious for tough withdrawal too.
- SSRIs (sertraline, escitalopram) – Gentle for some, but sexual side effects often trade off with fewer gut issues.
- MAOIs – Old school, rarely used, major food/drug restrictions, but still workhorses in tough cases.
- Esketamine (Spravato) – Intranasal, rapid-acting (works in hours to days), may dodge sexual and gut side effects, but insurance hurdles are real.
- TMS (transcranial magnetic stimulation) – Zaps your head (literally), not your gut or libido. No systemic side effects.
If sexual side effects are a dealbreaker, bupropion is the go-to alternative. For withdrawal phobia, consider SSRIs with a longer half-life, or clinical trials for novel mechanisms.
→ Compare your options on WithPower
Clinical Trials
CYB003 (deuterated psilocybin analog) [NCT05385783]
- Mechanism: 5-HT2A receptor agonist (psychedelic-derived, not a reuptake inhibitor)
- Why it matters: Rapid onset (within 1-2 weeks), durable benefits after only 1-2 doses, and no reported sexual dysfunction or withdrawal syndrome
- Results: 79% response, 75% remission at 4 months source
Osavampator (AMPA receptor modulator) [Phase 3 ongoing]
- Mechanism: Boosts glutamate transmission (completely outside serotonin/dopamine playbook)
- Why it matters: Side effect profile looks mild; little to no sexual dysfunction or sedation source
D-cycloserine (NMDA partial agonist adjunctive) [NCT00408031]
- Mechanism: Modulates NMDA/glutamate pathway
- Why it matters: Well tolerated, no cognitive blunting or sexual side effects in trials
Psilocybin (COMP360) [NCT03775200]
- Mechanism: Classic psychedelic (5-HT2A receptor agonist)
- Results: 37% response, 29% remission vs placebo, rapid effects within days source
Trial participation usually means no cost for treatment, but you might get placebo. Phase 2 is promising, not a guarantee. Keep your expectations grounded.
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
- Brain zaps or withdrawal → Consider bupropion, or CYB003/COMP360 trials
- Sexual side effects → Try bupropion, or osavampator trials
- Severe nausea → Consider mirtazapine (appetite booster), or D-cycloserine trials
- Night sweats/excessive sweating → Try SSRIs like sertraline or escitalopram, or bupropion
- Fatigue or brain fog → Consider switching to bupropion, or glutamatergic trials like osavampator
Every side effect is a dealbreaker for someone; the alternatives can be tailored.
Monitoring & What to Track
Your doctor should be keeping tabs on:
- Depression scores (PHQ-9, HAM-D) at regular intervals
- Weight changes (especially if on for >3 months)
- Blood pressure and heart rate (Cymbalta can raise both)
- Liver function tests (especially with risk factors)
- Suicidal ideation (first few weeks, under 25 years old)
What YOU should track:
- Mood/anxiety rating (0-10 daily)
- All side effects (what, when, how bad)
- Sleep quality, energy, appetite
If your doctor isn’t tracking these, bring it up. This is basic safety.
Pregnancy & Breastfeeding
Cymbalta is pregnancy category C—meaning, animal studies show risk, but there are no well-controlled human studies. FDA label warns of potential neonatal withdrawal syndrome (jitteriness, feeding trouble, irritability, abnormal crying, respiratory distress, seizures), especially if used late in pregnancy.
Risks:
- Potential for preterm birth, low birthweight, and withdrawal symptoms in newborn
- Breastmilk excretion is low to moderate; infant exposure occurs, but long-term effects aren’t known
Benefits:
- Untreated depression is risky for both mom and baby (poor self-care, worse outcomes)
Bottom line: This is a true risk-benefit call. Never stop Cymbalta suddenly if you become pregnant—taper under medical guidance.
For breastfeeding, discuss with your doctor; benefits may outweigh risks in some cases. Data are limited but suggest risk of side effects in exposed infants is low to moderate.
Emergency Warning Signs
⚠️ Call 911 or go to ER immediately if you experience:
- Suicidal thoughts or plans
- Severe allergic reaction (rash, swelling, trouble breathing)
- Seizure or new onset of confusion
- Signs of serotonin syndrome: fever, agitation, hallucinations, muscle stiffness, rapid heart rate
- Severe, sudden abdominal pain (possible liver or pancreas issue)
- Uncontrollable bleeding or black stool
📞 Call your doctor urgently if:
- New or worsening anxiety/agitation
- Severe insomnia or nightmares
- Abnormal bruising
- New-onset chest pain, racing heart, or unexplained fainting
- Visual changes (eye pain, halos)
- Symptoms of hyponatremia: headache, weakness, confusion
Poison Control: 1-800-222-1222 National Suicide Prevention Lifeline: 988
Summary & Next Steps
Key takeaways:
- 23% of patients report nausea and up to 14% get headaches—but most side effects improve within a month. The withdrawal risks (“brain zaps,” mood crashes) are real and often severe if you stop too fast.
If Cymbalta is working for you: Keep track of side effects and mood for the first 6-8 weeks. Don’t stop suddenly. Be alert for signs of serotonin syndrome or suicidal thinking—especially in the first month.
If side effects are intolerable: Talk to your doctor about a slower titration, dose adjustment, or trying bupropion or a clinical trial for a drug with a different mechanism. Don’t tough out severe withdrawal or disabling symptoms on your own.
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 |
|---|---|---|---|---|
| nausea | 23% | 8% | very common | Gastrointestinal |
| headache (pediatric) | 18% | 13% | common | Nervous System |
| headache | 14% | 12% | very common | Nervous System |
| decreased weight (pediatric) | 14% | 6% | common | Metabolic |
| dry mouth | 13% | 5% | very common | Gastrointestinal |
| somnolence (pediatric) | 11% | 6% | common | Nervous System |
| somnolence | 10% | 3% | very common | Nervous System |
| decreased appetite (pediatric) | 10% | 5% | common | Metabolic |
| fatigue | 9% | 5% | common | General |
| insomnia | 9% | 5% | common | Psychiatric |
| constipation | 9% | 4% | common | Gastrointestinal |
| dizziness | 9% | 5% | common | Nervous System |
| diarrhea | 9% | 6% | common | Gastrointestinal |
| nasopharyngitis (pediatric) | 9% | 2% | common | Infectious |
| dizziness (pediatric) | 8% | 4% | common | Nervous System |
| decreased appetite | 7% | 2% | common | Metabolic |
| fatigue (pediatric) | 7% | 5% | common | General |
| insomnia (pediatric) | 7% | 4% | common | Psychiatric |
| upper respiratory tract infection (pediatric) | 7% | 2% | common | Infectious |
| hyperhidrosis | 6% | 1% | common | Dermatologic |
| abdominal pain | 5% | 4% | common | Gastrointestinal |
| viral gastroenteritis (pediatric) | 5% | 0% | common | Infectious |
| vomiting | 4% | 2% | common | Gastrointestinal |
| agitation | 4% | 2% | common | Psychiatric |
| erectile dysfunction | 4% | 1% | common | Reproductive/Sexual |
| oropharyngeal pain (pediatric) | 4% | 2% | common | Respiratory |
| vision blurred | 3% | 1% | common | Ophthalmologic |
| anxiety | 3% | 2% | common | Psychiatric |
| libido decreased | 3% | 1% | common | Reproductive/Sexual |
| musculoskeletal pain | 3% | 3% | common | Musculoskeletal |
Boxed Warnings (Most Serious)
- Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults taking antidepressants. Monitor for worsening and emergence of suicidal thoughts and behaviors.
Drug Interactions
- Potent CYP1A2 inhibitors (e.g., fluvoxamine, cimetidine, ciprofloxacin, enoxacin) can greatly increase duloxetine levels and should be avoided.
- Potent CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, quinidine) may increase duloxetine concentrations.
- Duloxetine is a moderate inhibitor of CYP2D6 and may increase levels of drugs metabolized by CYP2D6 (e.g., tricyclic antidepressants, phenothiazines, antiarrhythmics).
- Concomitant use with MAOIs is contraindicated due to risk of serotonin syndrome.
- Increased risk of bleeding with NSAIDs, antiplatelets, anticoagulants.
- Serotonergic drugs (SSRIs, SNRIs, triptans, tramadol, tryptophan, St. John's Wort) increase risk of serotonin syndrome.
- Alcohol increases risk of liver injury.
- Drugs that increase blood pressure or heart rate may have additive effects.
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? |
|---|---|---|---|---|
| Nausea and upset stomach | 13 posts | 🟡 Moderate (8/13) | First week to first month, sometimes ongoing if dose is increased | Resolves |
| Headaches and migraines | 7 posts | 🟡 Moderate (5/7) | First week to first month, sometimes recurring with dose changes | Resolves |
| Fatigue and tiredness | 7 posts | 🟡 Moderate (4/7) | First week to first month, sometimes ongoing | Resolves |
| Excessive sweating and night sweats | 6 posts | 🟢 Mild (3/6) | Ongoing while on medication, sometimes improves over time | Resolves |
| Decreased libido and sexual side effects | 5 posts | 🟢 Mild (2/5) | Ongoing while on medication, sometimes improves with time or dose adjustment | Resolves |
| Dizziness and lightheadedness | 5 posts | 🟢 Mild (2/5) | First week to first month, sometimes with dose changes | Resolves |
| Difficulty falling or staying asleep | 5 posts | 🟡 Moderate (2/5) | First week to first month, sometimes ongoing | Resolves |
| Loss of appetite or reduced hunger | 4 posts | 🟢 Mild (2/4) | First week to first month, sometimes ongoing | Resolves |
| Brain zaps when stopping or missing doses | 4 posts | 🟠 Severe (3/4) | During withdrawal or missed doses, can last days to weeks | ⚠️ Yes |
| Nightmares or vivid bad dreams | 4 posts | 🟢 Mild (2/4) | First week to first month, sometimes ongoing | Resolves |
| Dilated pupils or changes in vision | 3 posts | 🟢 Mild (1/3) | First 2-3 weeks, usually resolves | Resolves |
| Restlessness or agitation | 3 posts | 🟡 Moderate (1/3) | First week to first month, sometimes ongoing | Resolves |
| Heart palpitations or racing heart | 3 posts | 🟡 Moderate (2/3) | Ongoing while on medication, sometimes resolves after stopping | Resolves |
| Brain fog or difficulty thinking clearly | 3 posts | 🟡 Moderate (2/3) | Ongoing while on medication, sometimes improves over time | Resolves |
| Withdrawal symptoms after stopping | 3 posts | 🟠 Severe (2/3) | Days to months after stopping, can be prolonged | ⚠️ Yes |
User Quotes by Side Effect
Nausea and upset stomach (Starts within first 1-3 days, peaks in first week, often resolves by week 2-4 or after dose stabilization)
"I started 30mg duloxetine a few days ago, and the side effects are certainly affecting me, especially the nausea and stomach issues." source
"Both times I couldn't get past a week of horrible side effects like nausea, appetite loss, nightmares, insomnia, headaches, and fatigue." source
"Day 1 - light nausea, muscle weakness, heart palpitations, headache, sleepiness. I felt that I wasn't thinking clearly. Day 2 - nausea..." source
Headaches and migraines (Starts within first few days, peaks in first week, often resolves by week 2-4 or after dose stabilization)
"On top of this I'm also experiencing intense migraines and headaches." source
"Both times I couldn't get past a week of horrible side effects like nausea, appetite loss, nightmares, insomnia, headaches, and fatigue." source
"I'd only been on it five days and suddenly yesterday had severe muscle spasms, headaches, a fever, nausea, no appetite, severely restless, couldn't sleep..." source
Fatigue and tiredness (Starts within first few days, peaks in first week, may resolve by week 2-4 or persist)
"It affects me mainly with fatigue, brain fog, shooting/stabbing pains, and general hypersensitivity." source
"Both times I couldn't get past a week of horrible side effects like nausea, appetite loss, nightmares, insomnia, headaches, and fatigue." source
"1st night on it and granted, im not insanely fatigued anymore. But i have a really bad frontal headache, chest pains are worse, i'm dizzy and ..." source
Excessive sweating and night sweats (Starts within first week, may persist but often lessens over time)
"I did have initial side effects of dry mouth, sweating, sexual side effects but all these become less over time and you ..." source
"My psychiatrist prescribed Cymbalta. I've been reading up ... -Negative sexual side effects -Night sweats -Bad dreams/nightmares -always feeling hot -dizziness and nausea - ..." source
"Sweating, shaking, nausea, and irritability were the main complaints. It took 2 months after coming off to feel somewhat 'normal' again." source
Decreased libido and sexual side effects (Starts within first week, may persist but often lessens over time)
"I did have initial side effects of dry mouth, sweating, sexual side effects but all these become less over time and you ..." source
"I really need to hear about others' experiences. -Negative sexual side effects -Night sweats -Bad dreams/nightmares -always feeling hot -dizziness and nausea - ..." source
Dizziness and lightheadedness (Starts within first few days, peaks in first week, often resolves by week 2-4)
"I feel somewhat dizzy, and super fatigued." source
"My psychiatrist prescribed Cymbalta. I've been reading up ... -Negative sexual side effects -Night sweats -Bad dreams/nightmares -always feeling hot -dizziness and nausea - ..." source
Difficulty falling or staying asleep (Starts within first week, may resolve by week 2-4 or persist)
"Both times I couldn't get past a week of horrible side effects like nausea, appetite loss, nightmares, insomnia, headaches, and fatigue." source
"That being said, the first few weeks were difficult for me, as I experienced nausea, loss of appetite, insomnia, 'brain jolts', delayed ..." source
Loss of appetite or reduced hunger (Starts within first week, may resolve by week 2-4 or persist)
"Both times I couldn't get past a week of horrible side effects like nausea, appetite loss, nightmares, insomnia, headaches, and fatigue." source
"I'd only been on it five days and suddenly yesterday had severe muscle spasms, headaches, a fever, nausea, no appetite, severely restless, couldn't sleep, ..." source
Brain zaps when stopping or missing doses (Occurs during withdrawal or missed doses, can last days to weeks)
"The worst side effects are the brain zaps you get from cold turkey stopping and pee constipation because it also works for urinary ..." source
"You'll very likely be fine and not feel much. Besides brain zaps other discontinuation symptoms for me are oversleeping/ having issues getting ..." source
Nightmares or vivid bad dreams (Starts within first week, may resolve by week 2-4 or persist)
"Both times I couldn't get past a week of horrible side effects like nausea, appetite loss, nightmares, insomnia, headaches, and fatigue." source
"My psychiatrist prescribed Cymbalta. I've been reading up ... -Negative sexual side effects -Night sweats -Bad dreams/nightmares -always feeling hot -dizziness and nausea - ..." source
Dilated pupils or changes in vision (Starts within first week, usually resolves by week 2-3)
"I had the dilated pupils and psychedelic feeling for the first couple weeks. I've been on it 3 weeks now and most of that has subsided." source
Restlessness or agitation (Starts within first week, may resolve by week 2-4 or persist)
"I'd only been on it five days and suddenly yesterday had severe muscle spasms, headaches, a fever, nausea, no appetite, severely restless, couldn't sleep, ..." source
Heart palpitations or racing heart (Can start within first week, may persist or resolve after dose adjustment or stopping)
"So after two months on Cymbalta my depression seems to be improving. But now I feel like my heart is racing most days and I feel like I'm ..." source
"Day 1 - light nausea, muscle weakness, heart palpitations, headache, sleepiness. I felt that I wasn't thinking clearly." source
Brain fog or difficulty thinking clearly (Starts within first week, may persist or improve over time)
"It affects me mainly with fatigue, brain fog, shooting/stabbing pains, and general hypersensitivity." source
"I've noticed brain fog, difficulty ..." source
Withdrawal symptoms after stopping (Begins after stopping, can last days to months, especially if stopped abruptly)
"The largest downfall- withdrawals. If I don't take it, even for a day, the side effects are unreal. Don't take it if you have issues refilling ..." source
"It sucks brain zaps, worsening anxiety and depression, heart palpitations, mood swings. My withdrawal lasted about 6 months. I stayed off for a ..." 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
- NCT: NCT05385783
- Mechanism: Deuterated psilocybin analog (psychedelic-derived, 5-HT2A receptor agonist)
- Side Effect Comparison: Transient mild-moderate headache and nausea most common; no sexual dysfunction, weight gain, or sedation reported (unlike SSRIs/SNRIs). No evidence of dependence or withdrawal.
- Efficacy Data:
- Response rate: 79% at 6 weeks (CYB003)
- Remission rate: 75% at 4 months (CYB003)
- MADRS change: -14.08 points (CYB003 16mg) vs -8.24 (placebo) at 6 weeks
- Time to response: 1-2 weeks
- Source
- Why it might interest you: Rapid onset (within 1-2 weeks), durable effects after only 1-2 doses, and a side effect profile lacking common SSRI/SNRI issues (sexual dysfunction, weight gain, sedation). Novel mechanism may help those not responding to or intolerant of standard antidepressants.
- Results: Significant and rapid reduction in depressive symptoms; high remission and response rates sustained for months after dosing.
- Sources: 1, 2, 3
Osavampator (NBI-1065845, TAK-653)
- Sponsor: Neurocrine Biosciences
- Phase: Phase 3
- Mechanism: AMPA receptor positive allosteric modulator (AMPA-PAM)
- Side Effect Comparison: Phase 2: No significant increase in weight gain, sexual dysfunction, or sedation compared to placebo. Side effect profile appears favorable vs SSRIs/SNRIs.
- Efficacy Data:
- Response rate: Not yet reported (Phase 3 ongoing)
- Remission rate: Not yet reported (Phase 3 ongoing)
- MADRS change: Not yet reported (Phase 3 ongoing); Phase 2 showed significant improvement vs placebo
- 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 faster onset and fewer side effects (notably less sexual dysfunction, weight gain, or sedation) than standard antidepressants.
- Results: Phase 2 data showed significant improvement in depressive symptoms as adjunctive therapy; Phase 3 underway to confirm efficacy and safety.
- Sources: 1, 2, 3
D-cycloserine (adjunctive)
- Sponsor: Not specified (academic/NIH)
- Phase: Phase 2
- 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. Generally well tolerated; no cognitive impairment reported (unlike some standard antidepressants).
- Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: -7.6 points (D-cycloserine) vs -3.1 (placebo) at 6 weeks (TRD population)
- Time to response: 2-4 weeks
- Source
- Why it might interest you: Novel glutamatergic mechanism, potential for fewer side effects (especially cognitive, sexual, and metabolic) than SSRIs/SNRIs, and may benefit those not responding to standard treatments.
- Results: Adjunctive D-cycloserine led to greater reduction in depressive symptoms vs placebo in treatment-resistant depression.
- Sources: 1
Psilocybin (COMP360)
- Sponsor: COMPASS Pathways
- Phase: Phase 2b
- NCT: NCT03775200
- Mechanism: Classic psychedelic (5-HT2A receptor agonist)
- Side Effect Comparison: Transient headache, nausea, and mild anxiety most common; no sexual dysfunction, weight gain, or chronic sedation (unlike SSRIs/SNRIs). No evidence of dependence or withdrawal.
- Efficacy Data:
- Response rate: 37% (psilocybin) vs 18% (placebo) at 3 weeks
- Remission rate: 29% (psilocybin) vs 8% (placebo) at 3 weeks
- MADRS change: -16.2 points (psilocybin) vs -5.4 (placebo) at 3 weeks (TRD population)
- Time to response: 1-2 days after dosing
- Source
- Why it might interest you: Very rapid onset (within days), durable effects after a single dose, and a side effect profile that avoids common SSRI/SNRI issues (sexual dysfunction, weight gain, sedation). Suitable for those who have not responded to or cannot tolerate standard antidepressants.
- Results: Single dose produced rapid and significant reduction in depressive symptoms in TRD; effects seen within days and sustained for weeks.
- Sources: 1, 2
Appendix D: Methodology
Our reviewers examined over 30,000 clinical trial records from ClinicalTrials.gov, 300+ peer-reviewed PubMed articles, and 63 patient forum threads, cross-referencing these with 129 OpenFDA Drug Label entries. This effort identified and ranked 15 specific adverse effects by how often they appeared and their reported severity. Representative patient quotations and duration patterns were included to reflect real-world experience.
Sources
FDA Label
Web Research
- Cymbalta (duloxetine hydrochloride) capsules
- Label for CYMBALTA (Duloxetine Delayed-Release Capsules)
- Duloxetine (oral route) - Side effects & dosage
- CYMBALTA (duloxetine - accessdata.fda.gov
- Cymbalta: Side effects, dosage, generic, uses, and more
- Side effects of duloxetine
- Duloxetine Side Effects: Common, Severe, Long Term
- The 13 Cymbalta (Duloxetine) Side Effects You Should ...
- Duloxetine (Cymbalta)
- The 13 Cymbalta (Duloxetine) Side Effects You Should ...
Clinical Trial Research
- Depression clinical trials worldwide: a systematic analysis ...
- Depressive disorders: systematic review of approved ...
- Emerging Medications for Treatment-Resistant Depression
- Current drug targets for the treatment of depression
- Trends in research on novel antidepressant treatments
- Neurocrine Biosciences Announces Initiation of Phase 3 ...
- Osavampator (NBI-1065845, TAK-653) as adjunctive ...
- All roads lead to glutamate: NMDA and AMPA receptors as ...
Reddit Discussions
- Cymbalta - GOOD experiences : r/Fibromyalgia
- Experience with cymbalta (duloxetine)? : r/AutisticWithADHD
- My psychiatrist prescribed Cymbalta. I've been reading up ...
- Hi! Anyone on cymbalta (duloxetine)? I've tried a few ...
- Experiences with cymbalta for pain? : r/ehlersdanlos
- Positive and honest experience on Cymbalta so far
- r/cymbalta
- Any good reviews on Cymbalta?
- One of the ACTUALLY positive experiences with Cymbalta
- Adding a positive experience story : r/cymbalta