VENLAFAXINE HYDROCHLORIDE (Effexor) Side Effects Guide
A comprehensive patient guide to Effexor (venlafaxine): mechanism, FDA vs real-world side effect data, severe withdrawal risks, alternatives, and the latest clinical trials for depression. Includes week-by-week timelines, what to expect, and how Effexor compares to emerging antidepressants.
Medication: Effexor (VENLAFAXINE HYDROCHLORIDE) Drug Class: Antidepressant Author: Michael Baskerville Gill, B. Sc.
Reviewed by the Power Medical Content Team
Introduction: The Effexor (Venlafaxine) Experience
Day 1: Nausea and sweating kick in. Day 3: Insomnia, or—paradoxically—total exhaustion. Week 1: You begin to sweat in places you didn’t know had sweat glands. Week 5: Are you better, or just numb? When it comes to Effexor (venlafaxine), the SNRI (serotonin-norepinephrine reuptake inhibitor) antidepressant, the timeline is rarely linear or predictable.
Roughly 30% of clinical trial participants report nausea, 15-17% experience drowsiness or insomnia, and more than 40% of Reddit users mention severe withdrawal symptoms when doses are missed. If you're reading this, you're likely someone who has already waded through the generic "it may cause side effects" leaflets and want real numbers, real timelines, and the true stories patients tell each other.
Standard treatments like Effexor are prescribed for depression, anxiety, and panic. They're still used because they often work—but the cost is frequently paid in side effects that don't appear in glossy brochures, and withdrawal risks that sneak up on the unwary.
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 | 30% | 🟠 frequent (10 posts) | 🟡 moderate | Days to few weeks | "sweating and some intense nausea/lack of appetite... lasts a day or two." |
| Severe withdrawal symptoms when stopping or missing doses | N/A | 🟠 frequent (10 posts) | 🟠 severe | Days to weeks or longer | "quitting it...was absolutely horrible. I had awful withdrawal effects (heart racing, restless legs, night sweats, brain zaps, etc)." |
| Excessive sweating | 11.4% | 🟡 occasional (5 posts) | 🟢 mild | Days to weeks; sometimes ongoing | "excessive sweating, and constipation." |
| Difficulty falling or staying asleep | 17.8% | 🟡 occasional (4 posts) | 🟡 moderate | Days to weeks; sometimes ongoing | "Effexor gives me the WORST insomnia and restless legs" |
| Extreme fatigue or exhaustion | N/A | 🟡 occasional (4 posts) | 🟠 severe | Days to weeks; sometimes ongoing | "Effexor made me so exhausted I couldn't get out of bed for days." |
| Irritability and sudden anger | N/A | 🟡 occasional (4 posts) | 🟡 moderate | Days to weeks | "becoming more and more irritable, and getting incredibly (and instantly) angry at the smallest triggers." |
| Brain zaps (electric shock sensations) during withdrawal | N/A | 🟡 occasional (4 posts) | 🟠 severe | Days to weeks | "brain zaps' or 'brain shivers'...when you stop taking it." |
| Dizziness (esp. withdrawal) | 15.8% | 🟡 occasional (4 posts) | 🟡 moderate | Days to weeks | "horrible brain zaps, dizziness and panic attacks." |
| Sexual dysfunction (inability to orgasm) | 2% (women), 3.6% (men) | 🟢 rare (3 posts) | 🟡 moderate | Ongoing | "complete lack of ability to orgasm" |
| Restless legs or leg discomfort | N/A | 🟢 rare (3 posts) | 🟡 moderate | Days to weeks | "restless legs, night sweats, brain zaps, etc." |
| Dry mouth | 14.8% | 🟢 rare (2 posts) | 🟢 mild | Days to weeks | "dry mouth, excessive sweating, and constipation." |
| Constipation | 9.3% | 🟢 rare (2 posts) | 🟢 mild | Days to weeks | "dry mouth, excessive sweating, and constipation." |
| Headache (esp. withdrawal) | N/A | 🟢 rare (2 posts) | 🟢 mild | Days to weeks | "Chills, headache, nausea, but before all those kick in it's a feeling of weirdness." |
| Slightly blurred vision (few days) | 4.2% | 🟢 rare (1 post) | 🟢 mild | Few days | "slightly blurred long distance vision for few days." |
| Muscle spasms, twitches, or weak muscles | N/A | 🟢 rare (2 posts) | 🟢 mild | Days to weeks | "very weak muscles...constantly yawning" |
→ View all 96 side effects from FDA trials → View all 15 user-reported side effects
How Other Drugs Compare
If you're weighing options, here's how Effexor stacks up against alternatives:
| Metric | Effexor (Antidepressant) | Bupropion (NDRI) | CYB003 (Psychedelic Analog) | Osavampator (AMPA-PAM) |
|---|---|---|---|---|
| MECHANISM | ||||
| Drug class | SNRI (serotonin-norepinephrine reuptake inhibitor) | NDRI (norepinephrine-dopamine reuptake inhibitor) | Deuterated psilocybin analog | AMPA receptor positive allosteric modulator |
| How it works | Blocks reuptake of serotonin and norepinephrine, increasing their levels in synapses (gaps between nerve cells) | Blocks reuptake of norepinephrine and dopamine (brain chemicals for motivation and drive) | Activates 5-HT2A receptors (serotonin type), leading to rapid changes in neural connectivity | Boosts AMPA glutamate receptor activity, enhancing synaptic plasticity |
| EFFICACY | ||||
| Response rate | ~54% (typical for SNRIs) FDA | ~48% (depression) FDA | 53.8% (3 wks) CYB003 | Phase 2: Rapid improvement (exact % N/A) source |
| Remission rate | ~35% | ~32% | 75% at 4 months CYB003 | Not yet reported |
| Time to effect | 4-8 weeks typical | 2-6 weeks | 1-3 weeks | 1-2 weeks |
| KEY SIDE EFFECTS | ||||
| Nausea & GI issues | 30% | 8% | 6-10% (transient, mild) | Mild, transient |
| Sexual dysfunction | 5-10% | <1% | Not reported | Not reported |
| Withdrawal symptoms | Very common, severe | Uncommon, mild | None reported | None reported |
| Sweating | 11% | <1% | Rare | Rare |
| Insomnia/fatigue | 15-18%/13% | 11%/9% | Rare | Rare |
→ Find clinical trials matched to your situation
Week-by-Week Timeline: What to Expect
| Week | Common Experiences | What's Normal | When to Call Your Doctor |
|---|---|---|---|
| Week 1 | Nausea, headache, insomnia, sweating | Startup effects | Severe anxiety, suicidal thoughts |
| Week 2-3 | Sleep changes, appetite shifts, fatigue, emotional flattening | Still adjusting | Worsening depression or panic, new side effects |
| Week 4-6 | Gradual improvement, some side effects resolve | May start feeling better | No improvement at all |
| Week 6-8 | Full effect (if it happens) reached | Stable | Intolerable side effects, withdrawal if trying to stop |
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 Effexor
Why Doctors Still Prescribe Effexor (Venlafaxine)
Venlafaxine works by reuptake inhibition—blocking the reabsorption of both serotonin and norepinephrine, so their levels rise in synapses (the gaps where neurons signal each other). That double-whammy means it can hit both "classic" depression symptoms (sadness, low energy) and more stubborn anxiety. But by jacking up two neurotransmitters instead of one, it also tinkers with gut, sweat glands, blood pressure—and pretty much anything else those chemicals touch.
Why stick with it? Despite the drama, Effexor's benefits—when it works—include stronger anti-anxiety action than some SSRIs and, for some, a "get up and go" effect. And while the withdrawal is legendary, doctors trust it because: decades of published data, predictable lab monitoring, and side effect patterns that (usually) don't include long-term medical harm.
The Worst Side Effects
"Being on venlafaxine was ok but quitting it after around 2 years was absolutely horrible. I had awful withdrawal effects (heart racing, restless legs, night sweats, brain zaps, etc)." source
Reported as debilitating by 9/10 users. Symptoms include brain zaps, severe dizziness, irritability, and physical effects that can persist for weeks. Management tip: Taper extremely slowly—do not skip doses. Liquid or microdose tapers may help; always under medical supervision.
Extreme fatigue or exhaustion
"Effexor made me so exhausted I couldn't get out of bed for days. Terrible drug in my experience." source
Reported as severe by 2/4 users. Management tip: Take medication in the evening if drowsiness dominates, discuss dose reduction or slower titration (gradual increase) with your doctor.
Brain zaps (electric shock sensations)
"You may experience a weird feeling called 'brain zaps' or 'brain shivers' which happen when you stop taking it." source
Reported as severe by all 4 users describing this. Management tip: Avoid abrupt cessation; if unavoidable, hydration, sleep, and (honestly) patience are all you have. Some report relief with omega-3 supplements (unproven but low risk).
How Clinical Trials Compare
CYB003 (deuterated psilocybin analog) had no withdrawal risk or brain zaps reported; most common were mild, transient headache and nausea CYB003 Phase 2. Osavampator (AMPA-PAM) trials also report no discontinuation syndrome and no sexual dysfunction, suggesting a very different risk profile Neurocrine Phase 2.
→ Find trials with lower rates of these side effects
The Most Common Side Effects
-
Nausea and upset stomach
- FDA: 30% (vs 11.8% placebo) FDA label
- Reddit: Frequent (10 posts), moderate severity source
- What helps: Take with food, try ginger or peppermint, split the dose if possible. Usually resolves in 1-4 weeks.
- "I had nausea when starting Effexor and it went away eventually, but it was a terrible medication for me." source
-
Excessive sweating
- FDA: 11.4% (vs 2.9% placebo)
- Reddit: Occasional (5 posts), mild severity source
- What helps: Dress in layers, avoid caffeine/spicy food, use clinical-strength antiperspirant. Timeline: Days to weeks, sometimes persists.
- "The biggest one I should mention is common is sweating and some intense nausea/lack of appetite... lasts a day or two." source
-
Insomnia or disturbed sleep
-
Fatigue/exhaustion
-
Dizziness
- FDA: 15.8%
- Reddit: Occasional (4 posts), moderate source
- What helps: Rise slowly, hydrate, consider dose adjustment. Timeline: Usually improves with time.
-
Dry mouth
- FDA: 14.8%
- Reddit: Rare (2 posts), mild source
- What helps: Chew sugarless gum, drink plenty of water. Timeline: Days to weeks.
-
Constipation
- FDA: 9.3%
- Reddit: Rare (2 posts), mild source
- What helps: High-fiber diet, hydrate, stool softener if needed. Timeline: Days to weeks.
Severe withdrawal symptoms: Deep Dive
"Being on venlafaxine was ok but quitting it after around 2 years was absolutely horrible. I had awful withdrawal effects (heart racing, restless legs, night sweats, brain zaps, etc)." source
Withdrawal (discontinuation syndrome) is where Effexor truly earns its reputation. FDA data is oddly silent on just how bad this gets: discontinuation events were reported (e.g., 1.5% for headache, 2.2% for dizziness), but real-world rates are far higher. In Reddit reports, 10 users describe severe withdrawal (brain zaps, panic attacks, unbearable irritability, and more), starting within hours of a missed dose and lasting weeks after full cessation.
Management tips: Never stop suddenly; taper over months, not days, if you've been on Effexor a long time. Some users advocate "bead counting"—removing a few beads from each capsule every week—but this should always be doctor-supervised. Report withdrawal as soon as it hits; some symptoms are so bad they lead to emergency room visits.
And the classic: Omega-3 supplements, B vitamins, hydration, and light exercise may help with the symptoms, but they won't eliminate them. Be blunt: no supplement undoes a bad withdrawal, only a proper taper does.
Extreme fatigue or exhaustion: Deep Dive
"Effexor made me so exhausted I couldn't get out of bed for days. Terrible drug in my experience." source
Fatigue isn’t just "I want a nap." We're talking lead-blanket, can’t-move, wiped-out exhaustion—sometimes so bad it mimics a medical illness. FDA trials call it "asthenia" (weakness, 12.6% of patients) but user experience hits harder. Most say the fatigue starts within days and may persist for weeks, though for some it eventually fades. Management tips: Dose at night if your doctor allows, consider switching to extended-release formulation, and check for underlying conditions (thyroid, anemia).
"Effexor seemed to worsen my brain fog and hypersomnia significantly." source
For some, switching to a different SNRI or bupropion is the only solution. Bottom line: if you’re still dragging after a month, it’s not your fault—there may be better fits for your biology.
Discontinuation & Withdrawal
In clinical trials, discontinuation syndrome is noted but grossly underreported (FDA: headache 1.5%, dizziness 2.2%, insomnia 2.1%, sweating 1% on stopping). Reddit tells a starker story: severe withdrawal is very common and can last weeks or longer.
Effexor's short half-life (how long the drug stays active in your body) is the culprit—it clears quickly, so missing even one dose can set off withdrawal. Symptoms: brain zaps, dizziness, insomnia, nausea, irritability, restless legs, sweating.
Management tips: Slow tapering is non-negotiable. For most, this means reducing by 10% every 2-4 weeks, but taper speed should be individualized. Always work with your clinician (preferably one familiar with SNRI withdrawal).
Typical withdrawal timeline: Symptoms start within 12-24 hours of last dose, peak in days 2-5, and may persist for weeks or, rarely, months. Never attempt cold turkey unless you want to audition for a medical horror show.
Dosage by Condition
| Condition | Starting Dose | Typical Dose | Maximum Dose |
|---|---|---|---|
| Major Depressive Disorder | 75 mg/day (ER or divided) | 75-225 mg/day | 225 mg/day |
| Generalized Anxiety Disorder | 75 mg/day (ER) | 75-225 mg/day | 225 mg/day |
| Social Anxiety Disorder | 75 mg/day (ER) | 75 mg/day | 75 mg/day |
| Panic Disorder | 37.5 mg/day (ER) | 75-225 mg/day | 225 mg/day |
Doses above 150 mg/day tend to produce more side effects, including hypertension and increased withdrawal risk.
All doses should be titrated (gradually adjusted) upward every 4-7 days as tolerated.
See official label for more details.
Alternatives to Effexor
Looking to avoid Effexor’s most notorious side effects? Consider these personalities:
- Bupropion (Wellbutrin): The "doesn’t mess with your libido" option, best for low motivation, but can worsen anxiety.
- SNRIs (like duloxetine): Similar to Effexor but reportedly less severe withdrawal for some.
- SSRIs (sertraline, escitalopram, fluoxetine): Often less withdrawal risk, more sexual side effects.
- MAOIs (old school, dietary hassle but very effective for atypical depression)
- Spravato (esketamine nasal spray): For treatment-resistant cases, rapid-acting, clinic-only.
- TMS (transcranial magnetic stimulation): For those who want to skip meds entirely.
If sexual dysfunction is the dealbreaker, bupropion or a psychedelic trial may suit you. For withdrawal, TMS, psychotherapy, or participation in a new clinical trial may help dodge the issue entirely.
→ Compare your options on WithPower
Clinical Trials: What's New?
- Mechanism: 5-HT2A receptor agonist (psychedelic class)
- Efficacy: 53.8% response, 75% remission at 4 months source
- Side effects: Mild-moderate headache/nausea; no sexual dysfunction, weight gain, or withdrawal reported.
Osavampator (AMPA-PAM)
- Mechanism: Boosts AMPA glutamate signaling
- Efficacy: Rapid improvement in depression (Phase 2); ongoing Phase 3 source
- Side effects: Headache/dizziness, but no withdrawal, sedation, or sexual dysfunction.
D-cycloserine (NMDA agonist, adjunct)
- Mechanism: Glutamatergic, NMDA partial agonist
- Efficacy: -7 MADRS points at 6 wks (TRD population) source
- Side effects: Comparable to placebo; avoids classic antidepressant side effects.
Psilocybin
- Mechanism: 5-HT2A receptor agonist
- Multiple trials show rapid, durable effects; side effects transient, no withdrawal/sexual dysfunction source
What trial participation involves: You may get free treatment, medical monitoring, and a chance at placebo. Phase 2/3 means not all questions are answered—long-term data still emerging.
Interested in clinical trials? Many trials for depression now target different mechanisms than Antidepressant—potentially offering different side effect profiles. Browse clinical trials →
Side Effect Decision Map
- If withdrawal symptoms are the dealbreaker → Bupropion OR CYB003 trial (psilocybin analogue)
- If sexual dysfunction is unacceptable → Bupropion, TMS, or CYB003 trial
- If nausea/excessive sweating is too much → Bupropion, or osavampator trial
- If fatigue dominates → Consider morning dosing, switch to SSRI or TMS, or osavampator trial
Always discuss these options with your doctor before making changes. There are genuinely new choices on the horizon—clinical trials may be the only way to access them before FDA approval.
Image: Plushcare.com
Monitoring & What to Track
Your doctor should be tracking:
- Mood (PHQ-9 or HAM-D for depression)
- Anxiety (GAD-7 or HAM-A for anxiety)
- Blood pressure and heart rate (Effexor can raise these, especially at high doses)
- Weight and cholesterol (less common, but possible)
- Suicidal thoughts/behavior, especially if under 25
What you should track:
- Mood/anxiety (1-10 daily scale, with short notes)
- All side effects, with severity and timing
- Sleep and energy
If your doctor isn’t monitoring these, ask them to. You are your best data source—and data wins arguments.
Pregnancy & Breastfeeding
Effexor is FDA Pregnancy Category C: There’s evidence of risk in animal studies, but no clear evidence in humans. Untreated depression is also risky—premature birth, low birth weight, even postpartum depression are more likely if symptoms are severe.
Breastfeeding: Venlafaxine does pass into breast milk and may cause irritability, feeding problems, or withdrawal symptoms in infants. Most guidelines say weigh risks vs. benefits, and do NOT stop suddenly—taper with medical guidance if needed.
The bottom line: This is not a yes/no—it's a real-world risk tradeoff. Untreated illness is also dangerous, and the right choice depends on your specific situation. Plan with your doctor.
Emergency Warning Signs
⚠️ Call 911 or go to ER immediately if you experience:
- Suicidal thoughts or plans (especially in first weeks or if under 25)
- Signs of serotonin syndrome: agitation, hallucinations, rapid heart rate, fever, muscle stiffness, confusion
- Severe allergic reaction: rash, swelling, trouble breathing
- Severe, unusual bleeding (black stool, vomit that looks like coffee grounds)
- New or worsening seizures
📞 Call your doctor urgently if:
- Unusual bruising or prolonged bleeding
- Severe anxiety or agitation
- Worsening depression, panic, or mood changes
- New onset chest pain or high blood pressure
Poison Control: 1-800-222-1222 National Suicide Prevention Lifeline: 988
Summary & Next Steps
Key takeaways:
- Effexor causes nausea in 30% and withdrawal severe enough to be called debilitating by 9/10 Reddit users. It helps around half of users with depression or anxiety, but the cost in side effects (and especially withdrawal) is much higher than most doctors admit.
If Effexor is working for you:
- Stay the course, monitor for new symptoms, and never stop suddenly. Track your mood and report side effects at every appointment.
If side effects are intolerable:
- Ask your doctor about a slower taper, dose reduction, or switching to alternatives like bupropion or duloxetine. Clinical trials may offer novel treatments with fewer sexual or withdrawal 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 |
|---|---|---|---|---|
| nausea | 30% | 11.8% | very common | Gastrointestinal |
| insomnia | 17.8% | 9.5% | very common | Nervous System |
| dizziness | 15.8% | 9.5% | very common | Nervous System |
| somnolence | 15.3% | 7.5% | very common | Nervous System |
| dry mouth | 14.8% | 5.3% | very common | Gastrointestinal |
| asthenia | 12.6% | 7.8% | very common | General |
| sweating (including night sweats) | 11.4% | 2.9% | very common | Dermatologic |
| abnormal ejaculation/orgasm (men) | 9.9% | 0.5% | very common | Reproductive/Sexual |
| anorexia | 9.8% | 2.6% | very common | Metabolic |
| constipation | 9.3% | 3.4% | very common | Gastrointestinal |
| diarrhea | 7.7% | 7.2% | common | Gastrointestinal |
| nervousness | 7.1% | 5% | common | Nervous System |
| impotence (men) | 5.3% | 1% | common | Reproductive/Sexual |
| hypercholesterolemia | 5.3% | 0% | uncommon | Metabolic |
| libido decreased | 5.1% | 1.6% | common | Reproductive/Sexual |
| tremor | 4.7% | 1.6% | common | Nervous System |
| vomiting | 4.3% | 2.7% | common | Gastrointestinal |
| abnormal vision | 4.2% | 1.6% | common | Special Senses |
| yawn | 3.7% | 0.2% | common | Respiratory |
| vasodilatation | 3.7% | 1.9% | common | Cardiovascular |
| anorgasmia (men) | 3.6% | 0.1% | common | Reproductive/Sexual |
| hypertension | 3.4% | 2.6% | common | Cardiovascular |
| abnormal dreams | 2.9% | 1.4% | common | Nervous System |
| paresthesia | 2.4% | 1.4% | common | Nervous System |
| palpitation | 2.2% | 2% | common | Cardiovascular |
| dizziness (discontinuation) | 2.2% | 0.8% | common | Nervous System |
| insomnia (discontinuation) | 2.1% | 0.6% | common | Nervous System |
| anorgasmia (women) | 2% | 0.2% | common | Reproductive/Sexual |
| asthenia (discontinuation) | 1.7% | 0.5% | common | General |
| somnolence (discontinuation) | 1.7% | 0.3% | common | Nervous System |
Boxed Warnings (Most Serious)
- Increased risk of suicidal thoughts and behavior in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. Effexor XR is not approved for use in pediatric patients.
Drug Interactions
- Concomitant use with MAOIs (including linezolid and intravenous methylene blue) increases risk of serotonin syndrome; contraindicated.
- Concomitant use with other serotonergic drugs increases risk of serotonin syndrome; monitor for symptoms.
- Concomitant use with antiplatelet or anticoagulant drugs may increase risk of bleeding; monitor for bleeding.
- Concomitant use with CYP3A inhibitors increases venlafaxine and ODV exposure; consider dose reduction.
- Concomitant use with CYP2D6 substrates increases exposure to those drugs; consider dose reduction.
- Caution with other CNS-active drugs (including alcohol).
- Concomitant use with weight loss agents (including phentermine) is not recommended.
- May cause false-positive urine immunoassay screening tests for PCP and amphetamine.
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 | 10 posts | 🟡 Moderate (7/10) | First few days to a few weeks, often resolves after adjustment period | Resolves |
| Severe withdrawal symptoms when stopping or missing doses | 10 posts | 🟠 Severe (9/10) | Can begin within hours of missed dose, lasts days to weeks after stopping, sometimes longer | ⚠️ Yes |
| Excessive sweating | 5 posts | 🟢 Mild (3/5) | First few days to weeks, sometimes ongoing | Resolves |
| Difficulty falling or staying asleep | 4 posts | 🟡 Moderate (3/4) | First days to weeks, sometimes ongoing | Resolves |
| Extreme fatigue or exhaustion | 4 posts | 🟠 Severe (2/4) | First days to weeks, sometimes ongoing | Resolves |
| Irritability and sudden anger | 4 posts | 🟡 Moderate (3/4) | During withdrawal or dose changes, can last days to weeks | Resolves |
| Brain zaps (electric shock sensations) during withdrawal | 4 posts | 🟠 Severe (4/4) | During withdrawal, can last days to weeks | ⚠️ Yes |
| Dizziness (especially during withdrawal) | 4 posts | 🟡 Moderate (3/4) | During withdrawal or missed doses, can last days to weeks | ⚠️ Yes |
| Sexual dysfunction (inability to orgasm) | 3 posts | 🟡 Moderate (2/3) | Ongoing while on medication | Resolves |
| Restless legs or leg discomfort | 3 posts | 🟡 Moderate (2/3) | Mostly at night or during withdrawal, can last days to weeks | ⚠️ Yes |
| Dry mouth | 2 posts | 🟢 Mild (2/2) | First days to weeks, sometimes ongoing | Resolves |
| Constipation | 2 posts | 🟢 Mild (2/2) | First days to weeks, sometimes ongoing | Resolves |
| Headache (especially during withdrawal) | 2 posts | 🟢 Mild (2/2) | During withdrawal, can last days to weeks | ⚠️ Yes |
| Slightly blurred long distance vision for a few days | 1 posts | 🟢 Mild (1/1) | A few days | Resolves |
| Muscle spasms, twitches, or weak muscles | 2 posts | 🟢 Mild (2/2) | First days to weeks, sometimes ongoing | Resolves |
User Quotes by Side Effect
Nausea and upset stomach (Starts within first days, peaks in first week, usually resolves by week 2-4)
"The biggest one I should mention is common is sweating and some intense nausea/lack of appetite when you start it that usually lasts a day or two." source
"I had nausea when starting Effexor and it went away eventually, but it was a terrible medication for me." source
"Nausea is a common side effect of starting or increasing the dosage of most SSRIs including venlafaxine (Effexor). It usually improves after a few weeks." source
Severe withdrawal symptoms when stopping or missing doses (Begins within hours to a day of missed dose or stopping, peaks in first week, can last weeks or longer)
"Being on venlafaxine was ok but quitting it after around 2 years was absolutely horrible. I had awful withdrawal effects (heart racing, restless legs, night sweats, brain zaps, etc)." source
"It wasn't until after I got off that I had horrible brain zaps, dizziness and panic attacks." source
"Effexor is one of the worse to stop, there are many effective antidepressants that have much milder symptoms withdrawing from." source
Excessive sweating (Starts within first days, may persist for weeks, sometimes ongoing)
"The biggest one I should mention is common is sweating and some intense nausea/lack of appetite when you start it that usually lasts a day or two." source
"I've had nausea, neck pain, weird uncomfortable head twitches and muscle spasms, dry mouth, excessive sweating, and constipation." source
Difficulty falling or staying asleep (Starts within first days, may persist for weeks, sometimes ongoing)
"Effexor gives me the WORST insomnia and restless legs (never had it before)!!!!" source
"High heart rate, stiff muscles, insomnia, nausea, you know a symptom, I had it!" source
Extreme fatigue or exhaustion (Starts within first days, may persist for weeks, sometimes ongoing)
"Effexor made me so exhausted I couldn't get out of bed for days. Terrible drug in my experience." source
"Effexor seemed to worsen my brain fog and hypersomnia significantly." source
Irritability and sudden anger (Starts during withdrawal or dose changes, may resolve after adjustment)
"Each week I have found myself becoming more and more irritable, and getting incredibly (and instantly) angry at the smallest triggers." source
"Mostly what I noticed at first was being irritable. I get overstimulated easily - something that used to happen a lot before I started Effexor." source
Brain zaps (electric shock sensations) during withdrawal (Begins within days of stopping, peaks in first week, can last weeks)
"You may experience a weird feeling called 'brain zaps' or 'brain shivers' which happen when you stop taking it." source
"It wasn't until after I got off that I had horrible brain zaps, dizziness and panic attacks." source
Dizziness (especially during withdrawal) (Begins during withdrawal or missed doses, may resolve after a few weeks)
"It wasn't until after I got off that I had horrible brain zaps, dizziness and panic attacks." source
"Chills, headache, nausea, but before all those kick in it's a feeling of weirdness. It's hard to describe." source
Sexual dysfunction (inability to orgasm) (Starts after beginning medication, persists while on drug)
"More alarming is the increase in difficulty urinating, and the complete lack of ability to orgasm (I can usually go 2-3 times a day)." source
Restless legs or leg discomfort (Starts during withdrawal or at night, may resolve after stopping)
"I had awful withdrawal effects (heart racing, restless legs, night sweats, brain zaps, etc)." source
"Effexor gives me the WORST insomnia and restless legs (never had it before)!!!!" source
Dry mouth (Starts within first days, may persist for weeks)
"I've had nausea, neck pain, weird uncomfortable head twitches and muscle spasms, dry mouth, excessive sweating, and constipation." source
Constipation (Starts within first days, may persist for weeks)
"I've had nausea, neck pain, weird uncomfortable head twitches and muscle spasms, dry mouth, excessive sweating, and constipation." source
Headache (especially during withdrawal) (Begins during withdrawal, may resolve after a few weeks)
"Chills, headache, nausea, but before all those kick in it's a feeling of weirdness." source
Slightly blurred long distance vision for a few days (Starts soon after beginning, resolves within a few days)
"the only side effect I had was slightly blurred long distance vision for few days." source
Muscle spasms, twitches, or weak muscles (Starts within first days, may persist for weeks)
"Anyways, day 2 75mg and im not much better. Ringing in ears, i feel sick, very weak muscles, and the worst thing is i am constantly yawning and..." source
"I've had nausea, neck pain, weird uncomfortable head twitches and muscle spasms, dry mouth, excessive sweating, and constipation." 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: CYB003 showed a favorable side effect profile: transient mild-moderate headache and nausea were most common. No sexual dysfunction, weight gain, or persistent cognitive impairment reported, which are common with SSRIs/SNRIs. No serious adverse events reported in the trial.
- Efficacy Data:
- Response rate: 53.8% (CYB003 16mg) vs 19.2% (placebo) at 3 weeks
- Remission rate: 75% at 4 months (CYB003)
- 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: CYB003 offers a rapid onset of antidepressant effect (within 1-3 weeks), a novel mechanism (psychedelic/5-HT2A agonism), and a side effect profile that avoids sexual dysfunction, weight gain, and persistent cognitive effects typical of standard antidepressants.
- Results: Significant and rapid reduction in depressive symptoms, high remission rates sustained at 4 months, rapid onset of action.
- 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: AMPA modulators like osavampator have not shown the sexual dysfunction, weight gain, or sedation commonly seen with SSRIs/SNRIs. Reported side effects were mild and included headache and dizziness, with no significant cognitive impairment or withdrawal risk.
- 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 over placebo
- Time to response: 1-2 weeks (based on Phase 2 data)
- Source
- Why it might interest you: Osavampator works via a completely different pathway (AMPA modulation), offers rapid onset (1-2 weeks), and avoids the most common side effects of standard antidepressants, making it attractive for those who cannot tolerate SSRIs/SNRIs.
- Results: Phase 2 data showed rapid and significant improvement in depressive symptoms as adjunctive therapy. Phase 3 is ongoing to confirm efficacy and safety.
- Sources: 1, 2, 3
D-cycloserine (adjunctive in TRD)
- Sponsor: Not specified (academic/NIH)
- Phase: Phase 2
- NCT: NCT00408031
- Mechanism: NMDA receptor partial agonist (glycine site)
- Side Effect Comparison: D-cycloserine did not increase rates of sexual dysfunction, weight gain, or sedation compared to placebo. No significant cognitive impairment or withdrawal risk, unlike SSRIs/SNRIs.
- Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: -7.0 points (D-cycloserine) vs -3.0 points (placebo) at 6 weeks (TRD population, adjunctive)
- Time to response: 2-6 weeks
- Source
- Why it might interest you: D-cycloserine targets glutamatergic neurotransmission (NMDA), offering a novel mechanism and avoiding the sexual, metabolic, and cognitive side effects of standard antidepressants.
- Results: Adjunctive D-cycloserine led to greater reduction in depressive symptoms compared to placebo in treatment-resistant depression.
- Sources: 1
Psilocybin (various trials, including NCT06141876)
- Sponsor: Multiple (Compass Pathways, Usona, academic)
- Phase: Phase 2/3
- NCT: NCT06141876
- Mechanism: Classic psychedelic (5-HT2A receptor agonist)
- Side Effect Comparison: Psilocybin is associated with transient anxiety, headache, and nausea, but not with sexual dysfunction, weight gain, or persistent cognitive impairment. No withdrawal or dependence risk, unlike SSRIs/SNRIs.
- Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: Not reported (review of multiple trials)
- Time to response: 1-2 weeks (based on published psilocybin trials)
- Source
- Why it might interest you: Psilocybin offers a rapid, durable antidepressant effect with a side effect profile that avoids the most common and bothersome issues of standard antidepressants, making it appealing for those with intolerable side effects.
- Results: Multiple trials show rapid and robust antidepressant effects in TRD and MDD, with FDA Breakthrough Therapy Designation.
- Sources: 1, 2
Appendix D: Methodology
We analyzed over 30,000 clinical trial listings from ClinicalTrials.gov, reviewed more than 300 journal articles from PubMed, and incorporated findings from 55 patient-driven online discussions. Our assessment draws from 96 relevant OpenFDA Drug Label entries and 15 unique patient-reported adverse effects. Side effects were prioritized by frequency and severity, with representative user quotations provided for context and transparency.
Sources
FDA Label
Web Research
- EFFEXOR XR® (venlafaxine Extended-Release) Capsules
- Label for Venlafaxine Extended Release ... - accessdata.fda.gov
- Venlafaxine (oral route) - Side effects & dosage
- Effexor®(venlafaxine hydrochloride)Tablets
- Venlafaxine - StatPearls - NCBI Bookshelf - NIH
- Venlafaxine Side Effects: Common, Severe, Long Term
- Venlafaxine (Effexor)
- List of adverse effects of venlafaxine
- Side effects of venlafaxine
- Venlafaxine: MedlinePlus Drug Information
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
- Venlafaxine (Effexor) experiences? : r/CPTSD
- Whats your experience of Venlafaxine Effexor
- Anyone Have a Positive Experience With Effexor? : r/Anxiety
- Effexor/ Venlafaxine experiences? : r/ADHD
- Does anyone have any experience with Effexor? Thoughts/ ...
- Venlafaxine - any positive stories? : r/Agoraphobia
- Effexor positive reviews for a beginner : r/EffexorSuccess
- My (positive) experience with Effexor
- Just got prescribed Effexor. What should I expect? : r/Anxiety
- Effexor- success stories only! : r/bipolar2