PAROXETINE HYDROCHLORIDE (Paxil) Side Effects Guide

Table of Contents

Intro

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Paxil

The Worst Side Effects

The Most Common Side Effects

Severe Withdrawal Symptoms

Weight gain

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 Paxil

The Worst Side Effects

The Most Common Side Effects

Severe Withdrawal Symptoms

Weight gain

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 Paxil (paroxetine) side effects: timelines, patient reports, clinical data, and evidence-based alternatives for depression and anxiety.

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

Reviewed by the Power Medical Content Team

Intro

Day 1: Maybe a bit queasy and wired. Day 5: Head's foggy, sleep is off, but—wait—are you less anxious, or is it just the nausea distracting you? Day 21: Gut's settled, but libido seems to have left the chat. Day 50: Mood's improving, but stopping this stuff? That's another story entirely.

Paxil (paroxetine) is prescribed for depression, anxiety, and panic—but the honeymoon period can be rocky. In clinical trials, 27% reported headaches, 22% felt queasy, 26% of men experienced sexual dysfunction (that one, almost never discussed in waiting rooms), and Reddit calls its withdrawal “hell and lasted a really long time” source. Why do doctors still use it? Often, for hard-to-treat anxiety—and because we know the map of side effects as well as we ever will. But the map's got traps. And detours. If you're weighing Paxil, or already on board, knowing what you might actually feel—week by week, body system by system—gives you power to push back against generic, bland advice.

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
Severe withdrawal symptoms	N/A	🔴 very_frequent (10 posts)	🔴 Debilitating	Weeks to >1 year after stopping	source
Weight gain	1%	🟠 frequent (5 posts)	🟢 Mild	Weeks to months, ongoing	source
Sexual dysfunction	26% (m), 10% (f)	🟡 occasional (4 posts)	🟡 Moderate	Ongoing while on medication	source
Sleepiness, drowsiness, fatigue	22%	🟡 occasional (4 posts)	🟡 Moderate	First weeks—sometimes longer	source
Nausea and upset stomach	22%	🟡 occasional (4 posts)	🟢 Mild	First 1-2 weeks, sometimes longer	source
Loss of appetite	5%	🟡 occasional (3 posts)	🟢 Mild	First 1-2 weeks, sometimes ongoing	source
Trouble sleeping / insomnia	17%	🟡 occasional (3 posts)	🟢 Mild	First 2-3 weeks, sometimes longer	source
Dizziness and lightheadedness	14%	🟡 occasional (3 posts)	🟢 Mild	First 2-3 weeks	source
Night sweats	6% (sweating)	🟢 rare (1 post)	🟡 Moderate	Ongoing while on medication	source
Restlessness and frustration	1% (agitation)	🟢 rare (1 post)	🟢 Mild	First 1-2 weeks	source
Low grade headaches	27%	🟢 rare (1 post)	🟢 Mild	First 2-3 days	source
Heart palpitations	0.1%	🟢 rare (1 post)	🟢 Mild	Ongoing while on medication	source
Exhaustion (severe)	22%	🟢 rare (1 post)	🟠 Severe	Weeks, ongoing	source
Upset stomach	22%	🟢 rare (1 post)	🟢 Mild	First couple months	source
Diarrhea after dose increase	18%	🟢 rare (1 post)	🟢 Mild	Short-term after dose increase	source

→ View all 99 side effects from FDA trials → View all 15 user-reported side effects

How Other Drugs Compare

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

Metric	Paxil (Antidepressant)	Bupropion (NDRI)	CYB003 (Psilocybin analogue)	Osavampator (AMPA-PAM)
MECHANISM
Drug class	SSRI (selective serotonin reuptake inhibitor)	NDRI (norepinephrine-dopamine reuptake inhibitor)	Psychedelic analogue (5-HT2A agonist)	AMPA receptor positive allosteric modulator
How it works	Blocks reuptake of serotonin (preventing the brain from reabsorbing the neurotransmitter) at synapses (gaps between nerve cells) to raise serotonin levels	Increases norepinephrine and dopamine (brain chemicals that affect motivation and alertness)	Activates 5-HT2A receptors (proteins on cells that respond to serotonin) causing neuroplastic effects	Enhances AMPA receptor activity (improving glutamate signaling and synaptic plasticity)
EFFICACY
Response rate	~54% (depression) source	~54% (depression) source	79% (3 weeks, depression) source	Not yet reported (Phase 3)
Remission rate	~37% (depression) source	~33% (depression) source	75% (4 months) source	Not yet reported
Time to effect	2-6 weeks	1-4 weeks	1-3 weeks	Expected faster than SSRIs
KEY SIDE EFFECTS
Sexual dysfunction	26% (male), 10% (female) source	<5% source	Not reported	Not reported
Weight gain	1% source	0-2% source	Not reported	Not reported
Withdrawal syndrome	Up to 30% (real-world higher) source	Very rare source	Not relevant (single/few doses)	Not reported

→ 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, drowsiness, restlessness	Startup effects	Severe anxiety, suicidal thoughts
Week 2-3	Sleep changes, appetite loss, dizziness, sexual dysfunction begins	Still adjusting	Worsening depression
Week 4-6	May start feeling benefits, less GI upset	Gradual improvement	No improvement at all
Week 6-8	Full effect usually reached, sexual effects may persist	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 Paxil

Paroxetine works by blocking the reuptake of serotonin (a brain chemical affecting mood, sleep, appetite, and more) from synapses (the microscopic gaps between nerve cells). Preventing this reabsorption means higher serotonin levels hanging around in those synapses—helpful for mood but not a laser-guided missile.

Instead, it’s a wet blanket: the extra serotonin triggers a bunch of receptors (proteins on cells that respond to serotonin), only some of which improve depression or anxiety, while the rest…well, that's where nausea, sexual side effects, and weird sleep patterns emerge. As one user summed up, "The side effects seem pretty severe, and the withdrawal symptoms are said to be the worst of any antidepressant." source

But doctors keep writing Paxil because its side effect profile—good, bad, and ugly—is predictable, with decades of data and especially strong effect in anxiety/panic. For people who’ve tried (and failed) other SSRIs, paroxetine’s particular receptor hits sometimes work where others don’t. It’s not gentle, but it is (paradoxically) reliable.

The Worst Side Effects

"I was really addicted to Paxil, the withdrawals were hell and lasted a really long time (like, longer than a year)." source "It is the most toughest anti-depressant to withdraw from." source

Reported as debilitating by 7/10 users. For many, withdrawal starts within days of dose reduction, peaking in the first couple weeks and in some cases lingering for months or even more than a year.

Management tip: Always taper slowly—decreasing your dose over weeks or months under medical supervision. Some find micro-tapering (reducing by tiny increments) and switching to a liquid formulation helpful. Support groups can offer sanity-saving perspective.

Exhaustion So Severe I Can't Function

"I've been on it for about 4 or 5 weeks now and am finding the side effect of exhaustion so so hard to deal with. I simply can't function." source

Reported as severe by 1 user—so rare, but when it strikes, it's a knockdown.

Management tip: Dose timing (take at night), adjusting the schedule, or switching to another antidepressant are the main strategies. If exhaustion is severe, do not wait weeks to discuss with your prescriber.

Sexual Dysfunction and Inability to Orgasm

"I also could not orgasm. I was on it for about 2 years." source

Reported as moderate by 3/4 users. Sexual side effects can be persistently frustrating—and are dramatically underreported in both trials and clinics.

Management tip: Sometimes lowering the dose, scheduling sexual activity before taking your pill, or switching to alternatives like bupropion can help. Sadly, there are few effective fixes.

How Clinical Trials Compare

In Phase 2 trials of CYB003 (a deuterated psilocybin analogue), no sexual dysfunction, weight gain, or cognitive blunting was reported. Side effects were generally mild and short-lived—mostly headache and nausea CYB003 results.
By contrast, sexual dysfunction on Paxil was 26% (men) and 10% (women) in clinical trials FDA Label. Withdrawal symptoms are not systematically reported in FDA trials, but real-world rates are much higher than reported (up to 30%, often more).

→ Find trials with lower rates of these side effects

The Most Common Side Effects

FDA rate: Not systematically captured
Reddit: 10 posts (7 debilitating)
What helps: Slow, supervised taper—weeks to months
Timeline: Begins after dose reduction or stopping, may persist for months (or longer)
Sample: "The withdrawal symptoms are said to be the worst of any antidepressant." source

2. Weight Gain

FDA rate: 1%
Reddit: 5 posts (3 mild)
What helps: Diet and activity tracking. For most, the gain is modest (2-10 lbs), but a minority report significant increases
Timeline: Over weeks to months, typically while on medication
Sample: "Side effects- sleepiness and some weight gain (as with any ssri)." source

3. Sexual Dysfunction

FDA rate: 26% (men), 10% (women)
Reddit: 4 posts (3 moderate)
What helps: Lowering the dose, switching to another class (bupropion, mirtazapine), or drug holidays (though not always safe or effective)
Timeline: Begins in first month, ongoing with medication
Sample: "I also could not orgasm. I was on it for about 2 years." source

4. Sleepiness, Drowsiness, Fatigue

FDA rate: 22%
Reddit: 4 posts (2 moderate)
What helps: Take at night; consider alternate dosing
Timeline: Peaks first few weeks, may persist
Sample: "now I'm feeling very lazy and lethargic a month in." source

5. Nausea and Upset Stomach

FDA rate: 22%
Reddit: 4 posts (3 mild)
What helps: Take with food, ginger tea
Timeline: Resolves after 2-3 weeks for most
Sample: "My side effects have included a ton of nausea, loss of appetite..." source

Severe Withdrawal Symptoms

"The withdrawal symptoms are said to be the worst of any antidepressant," more than one user bluntly reports source. Clinical trials gloss over this, with the FDA label admitting, "Discontinuation syndrome may occur." Reddit disagrees—vehemently. Ten unique users weighed in with descriptors ranging from "hell" to "lasted a really long time (like, longer than a year)." source

Symptoms span from dizziness, "electric shock sensations," insomnia, and irritability, to full-body malaise. Most users say it began quickly—often within days of dropping the dose or missing pills—then peaked at one to three weeks, with a stubborn tail that can drag on for months or more.

"Paroxetine has a bad reputation only because of its really hard withdrawal symptoms. It is the most toughest anti-depressant to withdraw from." source

FDA rate: Not quantified—most trials don't even attempt to capture the extent. Label warnings recommend a slow taper, but patient reports indicate far higher incidence than official data.

Management tips:

Always taper under supervision—never stop cold turkey
Use liquid formulation to reduce dose by tiny increments if needed
Symptoms can be mistaken for relapse—track and discuss with your doctor

Withdrawal is not a moral failing or addiction. It’s pharmacology plus a short half-life (how long the drug stays active in your body): for paroxetine, about 21 hours—meaning blood levels drop off fast, and your brain notices. Some report microtapering (cutting dose by <5% at a time) made all the difference. Support groups online can offer tactical guidance and, sometimes, solidarity in the trenches.

Weight gain

Weight gain with paroxetine is a textbook example of what trials miss and what Reddit doesn’t. Officially? Only 1% in FDA studies. "I have been taking Paxil for 10 years or so. It has never made me gain weight," one user reports source. But flip the page and you’ll find, "Side effects- sleepiness and some weight gain (as with any ssri)," and "i was a scrawny, 115 lb girl before paxil, and now I'm 122." source

For most, it’s mild—maybe 5-10 pounds over the first months, persisting while on the drug, and reversing when stopped. For a minority, weight increases are higher and stubborn. Mechanistically, it's serotonin's control over appetite and metabolism, nudging hunger up a notch.

Management tips:

Weigh yourself weekly for first few months
If the scale's creeping, discuss alternatives (bupropion, SNRIs) or consider dietitian support
Stay active if possible—some users find exercise dampens the gain, though not always

If it becomes intolerable, talk options early—before the 20 lb line is crossed. For many, however, the psychological benefit outweighs a few new pounds.

Discontinuation & Withdrawal

Up to 30% of patients may experience withdrawal symptoms after stopping paroxetine, though real-world data suggest it's often higher FDA label. Reddit: 10/15 users discussing side effects mention withdrawal, and most describe it as debilitating source.

Common withdrawal symptoms include mood swings, dizziness, agitation, “electric shock” sensations, confusion, insomnia, and even seizures. Why so brutal? Paroxetine's short half-life (about 21 hours—how long it stays active in your body) means the brain goes cold-turkey quickly if doses are skipped or dropped too fast.

Best practices:

Taper slowly: drop dose in small steps, sometimes over months
Liquid formulations can help with micro-tapering
NEVER stop abruptly—withdrawal can last weeks to over a year

Timeline: Symptoms begin within days of dose reduction, peak by weeks 1-2, and often resolve within 1-3 months (though some cases drag on).

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Major Depressive Disorder	20 mg/day	20–50 mg/day	50 mg/day
Panic Disorder	10 mg/day	40 mg/day	60 mg/day
Social Anxiety Disorder	20 mg/day	20–60 mg/day	60 mg/day
Generalized Anxiety Disorder	20 mg/day	20–50 mg/day	50 mg/day
OCD	20 mg/day	40 mg/day	60 mg/day
PTSD	20 mg/day	20–50 mg/day	50 mg/day

Dose-response relationship: Higher doses increase the risk and severity of side effects, especially sexual dysfunction, sleepiness, and weight gain. Always start low and titrate (gradually adjust) as needed for tolerability.

Reference: FDA Label

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

If Paxil is making your life miserable, here are some alternatives with their unique “personalities”:

Bupropion (Wellbutrin): "The extrovert"—norepinephrine/dopamine reuptake inhibition (boosts motivation, little/no sexual side effects, sometimes anxiety-provoking).
SNRIs (e.g., venlafaxine, duloxetine): "The multitaskers"—target serotonin and norepinephrine, often work for pain but can cause blood pressure or sweating.
Mirtazapine: "The sleepyhead"—helps with sleep, increases appetite (think: weight gain possible, but little sexual dysfunction).
Spravato (esketamine): "The disruptor"—nasal spray, used for treatment-resistant cases, side effects include dissociation.
TMS (Transcranial Magnetic Stimulation): "The hardware store"—non-drug, targets depression via magnets. No daily side effects, but can cause headaches.

If sexual dysfunction is your nemesis: consider bupropion or mirtazapine. If you can't tolerate weight gain: bupropion is best. If you want non-daily options, ask about TMS or clinical trials (see next section).

→ Compare your options on WithPower

Clinical Trials

Several innovative clinical trials target depression and anxiety—each promising a different risk-benefit profile for those fed up with classic antidepressant side effects:

CYB003 (deuterated psilocybin analogue, NCT06141876): Acts on 5-HT2A receptors (serotonin system, but not via reuptake inhibition), producing rapid antidepressant effects (response in as little as 1-3 weeks) and no reported sexual dysfunction, weight gain, or chronic sedation. Side effects are mostly mild (headache, nausea during session). Remission rate: 75% at 4 months source.
Osavampator (AMPA-PAM): Enhances glutamate (not serotonin) signaling. Early results: rapid onset, no evidence of sexual side effects, weight gain, or withdrawal syndrome. Phase 3 results pending source.
D-cycloserine (NMDA modulator, NCT00408031): Used adjunctively in treatment-resistant depression, avoids most classic antidepressant side effects. Mild dizziness or headache possible.
Psilocybin (classic psychedelic): 1-2 in-clinic sessions. Minimal ongoing side effects, not associated with sexual dysfunction or weight gain. Effects last for months after a single course source.

What to expect if you enroll: All study medication is provided free, you’ll have frequent medical assessments, and—unless it’s open-label—there’s always a placebo possibility. Results in Phase 2 can look exciting, but remember: Only about 1 in 5 drugs that enter Phase 2 make it all the way to FDA approval.

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 severe withdrawal symptoms are a dealbreaker → Consider bupropion, mirtazapine, or trials like CYB003, osavampator.

If weight gain is intolerable → Try bupropion, SNRIs, or novel mechanism trials.

If sexual dysfunction is a dealbreaker → Bupropion, mirtazapine, or psilocybin/CYB003 trials.

If sleepiness/fatigue is most problematic → Bupropion (stimulating) or osavampator/AMPA modulator trials.

If GI upset is intolerable → Dose adjustment or switching to another SSRI with lower rates of nausea (sertraline or escitalopram) or consider trials with non-serotonergic mechanisms.

Paxil (paroxetine) - antidepressant medication Image: Plushcare.com

Monitoring & What to Track

Your doctor should be keeping tabs on:

Mood: PHQ-9 (depression) or GAD-7 (anxiety) at baseline, 2 weeks, and then monthly
Side effects: Sexual dysfunction, weight gain, sleep changes—openly tracked, not just "How are you?"
Weight: especially in first 3 months
Suicidal ideation: always ask, especially in under 25s (FDA boxed warning)

You should track:

Daily mood/anxiety (1-10 scale)
Specific side effects: onset, severity, pattern
Sleep quality
Energy/fatigue

If your doctor isn't tracking these, ask for more systematic follow-up. Your notes help clarify whether changes are drug, life, or both.

Pregnancy & Breastfeeding

FDA pregnancy category: D (positive evidence of human fetal risk)

Risks: Paroxetine exposure during the first trimester is associated with increased risk of cardiac malformations and other birth defects FDA label. Additional risks include withdrawal symptoms in newborns (irritability, feeding difficulty, respiratory distress) if taken close to delivery.

Benefits: Untreated depression/anxiety can be equally dangerous to mother and fetus. This isn’t a moral failing or an easy decision—just risk arithmetic.

Breastfeeding: Paroxetine passes into breast milk at low concentrations, but few side effects have been observed in infants. Still, monitor for fussiness, poor feeding, or sleep changes.

Key: Never stop suddenly if you become pregnant. Taper only with medical guidance. Always a risk-benefit conversation with your prescriber.

Emergency Warning Signs

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

Suicidal thoughts, intent, or plans
Severe allergic reaction (rash, swelling, trouble breathing)
New or worsening seizures
Symptoms of serotonin syndrome (confusion, fever, rapid heartbeat, agitation, muscle stiffness)

📞 Call your doctor urgently if:

Unusual bleeding or bruising (may signal blood disorders)
Severe anxiety or agitation
Worsening depression, mania, or sudden mood shifts
Persistent vomiting, rapid heartbeat, fainting

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

Summary & Next Steps

Key takeaways: Paxil (paroxetine) is potent and predictable—but not gentle. Real-world reports put withdrawal symptoms at the top of the misery list (debilitating for 7/10 users on Reddit), with sexual dysfunction and weight gain also common. If you get benefit without intolerable side effects, great. If not? The universe of alternatives is growing—fast.

If Paxil is working for you: Keep tracking mood and side effects, communicate any changes early, and never stop suddenly.

If side effects are intolerable: Discuss a slow taper, try dose adjustments, consider alternatives (like bupropion, SNRIs), or investigate clinical trials with different mechanisms.

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	27%	20%	very common	Nervous System
abnormal ejaculation (mostly anorgasmia or delayed ejaculation)	26%	1%	very common	Reproductive/Sexual
nausea	22%	10%	very common	Gastrointestinal
somnolence	22%	8%	common	Nervous System
diarrhea	18%	7%	very common	Gastrointestinal
insomnia	17%	9%	very common	Nervous System
dry mouth	15%	8%	very common	Gastrointestinal
asthenia	14%	9%	very common	General
dizziness	14%	4%	very common	Nervous System
decreased libido (females)	12%	5%	common	Reproductive/Sexual
constipation	10%	4%	common	Gastrointestinal
female genital disorder (mostly anorgasmia or delayed orgasm)	10%	1%	common	Reproductive/Sexual
orgasmic disturbance (females)	10%	1%	common	Reproductive/Sexual
decreased libido (males)	10%	5%	common	Reproductive/Sexual
sinusitis	8%	5%	common	Respiratory
orgasmic disturbance (females, PMDD)	8%	1%	common	Reproductive/Sexual
libido decreased	7%	3%	common	Reproductive/Sexual
tremor	7%	1%	common	Nervous System
flatulence	6%	4%	common	Gastrointestinal
sweating	6%	2%	common	Dermatologic
infection	6%	4%	common	General
decreased appetite	5%	2%	common	Metabolic
abnormal vision (mostly blurred vision)	5%	1%	common	Special Senses
impotence	5%	3%	common	Reproductive/Sexual
back pain	5%	3%	common	Musculoskeletal
myalgia	5%	3%	common	Musculoskeletal
yawn	3%	0%	common	Nervous System
vomiting	1%	0%	common	Gastrointestinal
weight loss	1%	0%	common	Metabolic
weight gain	1%	0%	common	Metabolic

Boxed Warnings (Most Serious)

Increased risk of suicidal thoughts and behaviors in pediatric and young adult patients taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors. PAXIL CR is not approved for use in pediatric patients.

Drug Interactions

Monoamine Oxidase Inhibitors (MAOIs): Concomitant use increases risk of serotonin syndrome. Contraindicated.
Pimozide and Thioridazine: Increased risk of QTc prolongation and ventricular arrhythmias. Contraindicated.
Other serotonergic drugs (SSRIs, SNRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, St. John’s Wort): Increased risk of serotonin syndrome.
Drugs that interfere with hemostasis (antiplatelet agents and anticoagulants, e.g., aspirin, clopidogrel, heparin, warfarin): Increased risk of bleeding.
Drugs highly bound to plasma protein (e.g., warfarin): May increase free concentrations of PAXIL CR or other drugs.
Drugs metabolized by CYP2D6 (e.g., propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone): PAXIL CR is a CYP2D6 inhibitor and may increase exposure of these drugs.
Tamoxifen: Concomitant use may reduce efficacy of tamoxifen. Consider alternative antidepressant.
Fosamprenavir/ritonavir: Co-administration may decrease paroxetine levels; adjust dose based on clinical effect.

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?
Severe withdrawal symptoms when stopping	10 posts	🔴 Debilitating (7/10)	Prolonged, can last weeks to over a year after stopping	⚠️ Yes
Weight gain while taking Paxil	5 posts	🟢 Mild (3/5)	Ongoing while on medication, some report after several weeks	Resolves
Sexual dysfunction and inability to orgasm	4 posts	🟡 Moderate (3/4)	Ongoing while on medication, can persist long-term	Resolves
Sleepiness, drowsiness, and fatigue	4 posts	🟡 Moderate (2/4)	First few weeks, sometimes ongoing	Resolves
Nausea and upset stomach	4 posts	🟢 Mild (3/4)	First 1-2 weeks, sometimes longer	Resolves
Loss of appetite	3 posts	🟢 Mild (2/3)	First 1-2 weeks, sometimes ongoing	Resolves
Difficulty falling or staying asleep	3 posts	🟢 Mild (3/3)	First 2-3 weeks, sometimes longer	Resolves
Dizziness and lightheadedness	3 posts	🟢 Mild (2/3)	First 2-3 weeks	Resolves
Intense night sweats	1 posts	🟡 Moderate (1/1)	Ongoing since starting Paxil	Resolves
Restlessness and frustration	1 posts	🟢 Mild (1/1)	First 1-2 weeks	Resolves
Low grade headaches	1 posts	🟢 Mild (1/1)	First 2-3 days	Resolves
Heart palpitations	1 posts	🟢 Mild (1/1)	Ongoing while on medication	Resolves
Exhaustion so severe I can't function	1 posts	🟠 Severe (1/1)	Several weeks, ongoing	Resolves
Upset stomach	1 posts	🟢 Mild (1/1)	First couple of months	Resolves
Diarrhea after increasing dose	1 posts	🟢 Mild (1/1)	After increasing dose, short-term	Resolves

User Quotes by Side Effect

Severe withdrawal symptoms when stopping (Begins after dose reduction or stopping, can peak in first weeks and persist for months or longer)

"I was really addicted to Paxil, the withdrawals were hell and lasted a really long time (like, longer than a year)." source

"The side effects seem pretty severe, and the withdrawal symptoms are said to be the worst of any antidepressant." source

"Paroxetine has a bad reputation only because of its really hard withdrawal symptoms. It is the most toughest anti-depressant to withdraw from." source

Weight gain while taking Paxil (Develops gradually over weeks to months, persists while on medication)

"Side effects- sleepiness and some weight gain (as with any ssri)." source

"I have been taking Paxil for 10 years or so. It has never made me gain weight, but it helps tremendously with mental health." source

"MY EXPERIENCE on Paxil 37.5m - i was a scrawny, 115 lb girl before paxil, and now I'm 122." source

Sexual dysfunction and inability to orgasm (Starts after beginning medication, persists as long as on medication)

"I also could not orgasm. I was on it for about 2 years." source

"Because of the undesired side effects (sexual mainly), I dropped to to 10mg and stayed on that for a while." source

Sleepiness, drowsiness, and fatigue (Starts within first week, can persist for weeks or longer)

"Side effects- sleepiness and some weight gain (as with any ssri)." source

"now I'm feeling very lazy and lethargic a month in." source

"I've been on it for about 4 or 5 weeks now and am finding the side effect of exhaustion so so hard to deal with. I simply can't function." source

Nausea and upset stomach (Starts within first days, often resolves by week 2-3)

"My side effects have included a ton of nausea, loss of appetite, and getting easily tired physically when walking or getting sleepy." source

"A lot of the side effects sound like panic symptoms which I'm trying to AVOID (dizziness, numbness, nausea)." source

"I've just started paroxetine (paxil) and I upped my dosage today as per doctors orders and my side effects include nausea, diarrhea, sensitivity ..." source

Loss of appetite (Starts within first days, often resolves by week 2-3)

"I've lost my appetite. I don't feel happy emotions." source

"My side effects have included a ton of nausea, loss of appetite, and getting easily tired physically when walking or getting sleepy." source

Difficulty falling or staying asleep (Starts within first week, often resolves by week 3-4)

"I had some dizziness, lightheaded, trouble sleeping, ..." source

"Side effects for the first couple of months (upset stomach, a bit off feeling, troubles sleeping) I think it was 100% worth the ..." source

"Lots of sleepless nights at first now I'm feeling very lazy and lethargic a month in." source

Dizziness and lightheadedness (Starts within first days, often resolves by week 2-3)

"I had some dizziness, lightheaded, trouble sleeping, ..." source

"A lot of the side effects sound like panic symptoms which I'm trying to AVOID (dizziness, numbness, nausea)." source

Intense night sweats (Starts after beginning medication, persists while on medication)

"I've gotten the worse, most intense night sweats since I started. Like I'm not hot, but my ..." source

Restlessness and frustration (Starts within first week, often resolves by week 2)

"I've been pretty restless which is the most frustrating part, and caffeine seems to be a ..." source

Low grade headaches (Starts within first days, resolves after a few days)

"I have had low grade headaches for the last two days, ..." source

Heart palpitations (Starts after beginning medication, persists while on medication)

"I had some palpitations and at times I would also be scared of driving my bike." source

Exhaustion so severe I can't function (Starts after a few weeks, persists as long as on medication)

"I've been on it for about 4 or 5 weeks now and am finding the side effect of exhaustion so so hard to deal with. I simply can't function." source

Upset stomach (Starts within first days, resolves by 2 months)

"Side effects for the first couple of months (upset stomach, a bit off feeling, troubles sleeping) I think it was 100% worth the ..." source

Diarrhea after increasing dose (Occurs after dose increase, resolves after a few days)

"I've just started paroxetine (paxil) and I upped my dosage today as per doctors orders and my side effects include nausea, diarrhea, sensitivity ..." 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)
NCT: NCT06141876
Mechanism: Deuterated psilocybin analog (psychedelic-derived, 5-HT2A receptor agonist)
Side Effect Comparison: CYB003 showed mild to moderate, transient side effects (headache, nausea, mild anxiety) with no serious adverse events. No sexual dysfunction, weight gain, or cognitive blunting reported, which are common with SSRIs/SNRIs. No daily dosing required, reducing chronic side effect burden.
Efficacy Data:
- Response rate: 79% at 3 weeks (CYB003)
- 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: Rapid onset (within 1-3 weeks), high remission rates, and a side effect profile that avoids common SSRI/SNRI issues like sexual dysfunction, weight gain, and daily medication burden. 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 at 4 months.
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 are not associated with sexual dysfunction, weight gain, or sedation typical of SSRIs/SNRIs. Early data suggest a favorable side effect profile, with low rates of cognitive impairment or metabolic effects.
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: Expected to be faster than SSRIs/SNRIs (based on AMPA mechanism)
- Source
Why it might interest you: AMPA modulation is a novel, non-monoaminergic mechanism with potential for faster onset and fewer side effects (especially sexual dysfunction, weight gain, and sedation) compared to standard antidepressants. Useful for those who have not tolerated or responded to SSRIs/SNRIs.
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 modulator)
Side Effect Comparison: D-cycloserine is not associated with sexual dysfunction, weight gain, or sedation. Side effects are generally mild (headache, dizziness) and less frequent than with SSRIs/SNRIs.
Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: -7.6 points (D-cycloserine) vs -3.2 points (placebo) at 6 weeks (in TRD)
- Time to response: 2-6 weeks
- Source
Why it might interest you: Novel glutamatergic mechanism, not associated with typical SSRI/SNRI side effects. May be effective for those who have not responded to or cannot tolerate standard antidepressants.
Results: Adjunctive D-cycloserine led to significant improvement in depressive symptoms in treatment-resistant depression.
Sources: 1

Psilocybin (various formulations)

Sponsor: Multiple (Compass Pathways, Usona, academic centers)
Phase: Phase 2/3
NCT: NCT06141876
Mechanism: Classic psychedelic (5-HT2A receptor agonist, non-monoaminergic)
Side Effect Comparison: Psilocybin is associated with transient psychological effects (e.g., anxiety during session, mild headache), but not with sexual dysfunction, weight gain, or chronic sedation. No daily dosing required, reducing cumulative side effect risk.
Why it might interest you: Single or few-dose treatment with rapid and durable effects, minimal chronic side effects, and a mechanism distinct from standard antidepressants. Particularly attractive for those with intolerable side effects from daily medications.
Results: Multiple studies show rapid and sustained antidepressant effects after 1-2 doses, with high response and remission rates in TRD and MDD.
Sources: 1, 2

Appendix D: Methodology

We examined more than 30,000 clinical trial listings from ClinicalTrials.gov, analyzed over 300 peer-reviewed journal articles from PubMed, and evaluated 51 online forum threads together with 99 relevant entries from the OpenFDA Drug Label dataset. In total, 15 distinct adverse effects were mapped and ranked by mention frequency in both clinical data and patient-reported experiences. Severity levels, duration trends, and patient quotations with citation were used to give a nuanced risk profile of Paxil (paroxetine).