FLUOXETINE HYDROCHLORIDE (Prozac) Side Effects Guide

Table of Contents

Prozac Side Effects: What Real Patients Report vs FDA Data

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Prozac

The Worst Side Effects

The Most Common Side Effects

Deep Dive: Emotional Numbness or Blunted Feelings

Deep Dive: Decreased Sex Drive and Sexual Dysfunction

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

Prozac Side Effects: What Real Patients Report vs FDA Data

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Prozac

The Worst Side Effects

The Most Common Side Effects

Deep Dive: Emotional Numbness or Blunted Feelings

Deep Dive: Decreased Sex Drive and Sexual Dysfunction

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

A data-driven guide to Prozac side effects: FDA rates vs real patient reports, severity, timelines, and comparison to newer antidepressant options. Concrete next steps for difficult side effects.

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

Reviewed by the Power Medical Content Team

Prozac Side Effects: What Real Patients Report vs FDA Data

Day 1: That stomach-drop nausea, a twinge of anxiety, or maybe just a sense of weirdness creeping in. Day 5: Sleep? Elusive. Head buzzing. Day 14: Nausea lets up, but the world starts to feel a little... muted? If you've landed here, odds are you've already googled the infamous Prozac “side effect list”—probably found it both vague and terrifyingly long.

Let's do better: Prozac (generic: fluoxetine hydrochloride) is one of the most widely prescribed antidepressants worldwide, yet 30-50% of patients end up switching or quitting due to side effects or lack of benefit. With so much riding on whether your brain plays nice with this molecule, you deserve more than copy-paste lists. Why do some people report “emotional numbness” after just a week, while others escape with a mild headache and some nausea that fades? The answer, as always, is messier than the label admits.

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
Emotional numbness or blunted feelings	N/A	🟠 frequent (7 posts)	🟡 Moderate	Ongoing/several weeks	"When i was on it, became completely numb emotionally."
Nausea and upset stomach	22%	🟠 frequent (6 posts)	🟢 Mild	2-3 weeks/ongoing	"I felt nauseous and weird for the first couple of weeks..."
Decreased sex drive and sexual dysfunction	4% (libido decreased), 3% (impotence)	🟠 frequent (5 posts)	🟡 Moderate	Ongoing	"It obliterated my sex drive and really dulled my feelings..."
Brain fog and feeling mentally slow	N/A	🟠 frequent (5 posts)	🟢 Mild	Few weeks/ongoing	"Feeling foggy/light headed/'slow'...went away after a few weeks."
Difficulty falling or staying asleep	19%	🟠 frequent (5 posts)	🟡 Moderate	2-3 weeks/longer	"Sleep was horrible...being like a small dose of psilocybin."
Diarrhea and gastrointestinal upset	11%	🟠 frequent (5 posts)	🟡 Moderate	2-3 weeks/ongoing	"I had constant diarrhea and my anxiety was through the roof."
Increased anxiety or nervousness	12%	🟡 occasional (4 posts)	🟢 Mild	1-2 weeks	"A few days of high anxiety and other side effects..."
Loss of appetite or reduced hunger	10% (anorexia)	🟡 occasional (4 posts)	🟢 Mild	2-3 weeks/ongoing	"First few weeks was a loss of appetite..."
Fatigue and tiredness	11% (asthenia)	🟡 occasional (3 posts)	🟢 Mild	Few weeks/ongoing	"Brain Fog, Fatigue, Heat intolerance..."
Headaches	21%	🟡 occasional (3 posts)	🟢 Mild	Few days/weeks	"Sweating and headaches...everything leveled out after a week or so."
Increased sweating	7%	🟢 rare (2 posts)	🟢 Mild	Few days	"Increased sweating in the first few days but it went away."
Itching or skin pruritus	3%	🟢 rare (2 posts)	🟢 Mild	1-2 weeks/ongoing	"Some itching for the first week or so but it went away."
Heartburn or acid reflux	N/A	🟢 rare (2 posts)	🟢 Mild	Few weeks/ongoing	"Prozac gives me terrible heartburn."
Disorientation or dissociation	N/A	🟢 rare (2 posts)	🟡 Moderate	1-2 weeks	"Tremor and disorientation...tend to go away once adjusted."
Apathy or lack of interest	N/A	🟢 rare (2 posts)	🟡 Moderate	Ongoing	"My depressed feeling and anxiety are almost completely gone...replaced by an enormous disinterested feeling."

→ View all 117 side effects from FDA trials → View all 15 user-reported side effects

How Other Drugs Compare

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

Metric	Prozac (Antidepressant)	Bupropion (NDRI)	CYB003 (Psilocybin analogue)	D-cycloserine (NMDA modulator)
MECHANISM
Drug class	SSRI (selective serotonin reuptake inhibitor)	NDRI (norepinephrine-dopamine reuptake inhibitor)	Deuterated psilocybin analogue (psychedelic, 5-HT2A receptor agonist)	NMDA receptor partial agonist (glycine site)
How it works	Inhibits serotonin reuptake (prevents the brain from reabsorbing serotonin at synapses) to boost mood	Inhibits norepinephrine/dopamine reuptake (prevents removal of these neurotransmitters)	Single or few-dose psychedelic activating 5-HT2A receptors for rapid mood reset	Enhances glutamate signaling at NMDA receptors, possible mood circuit rebalancing
EFFICACY
Response rate	~54% (at 8-12 weeks)FDA label	~53% (at 8 weeks)source	53.8% (3 weeks)source	Not reported
Remission rate	25-35% (at 8-12 weeks)	32%	75% (at 4 months)	Not reported
Time to effect	4-6 weeks typical	2-4 weeks	1-3 weeks (single dose)	2-6 weeks (adjunct)
KEY SIDE EFFECTS
Sexual dysfunction	3-8% (FDA); higher in real world	<1%	None reported	None reported
Weight gain	Rare; weight loss more common	Weight loss	None reported	None reported
Insomnia	19% (FDA); frequent real world	11%	Not reported	Not reported
Nausea	22% (FDA); frequent real world	10%	Mild/transient	Mild/transient
Emotional blunting	5-10% (estimated, FDA underreports)	Rare	None reported	None 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, jitters, brain fog, insomnia	Startup effects	Severe anxiety, suicidal thoughts
Week 2-3	Sleep changes, appetite shifts, diarrhea, emotional blunting emerging	Still adjusting	Worsening depression
Week 4-6	May start feeling benefits, side effects receding	Gradual improvement	No improvement at all
Week 6-8	Full effect usually reached, stability in mood/sleep	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 Prozac

Prozac works by blocking the reuptake (removal) of serotonin—a brain chemical that affects mood—at the synapses (gaps between nerve cells), leaving more serotonin floating around to do its job. This so-called "reuptake inhibition" (preventing the brain from reabsorbing the neurotransmitter) is the very heart of the SSRI class.

Why the side effects? Serotonin doesn't just tweak your mood. It also meddles with your gut (hello, nausea and diarrhea), your sex drive (cue the infamous libido drop), and even how you sleep and sweat. The trade-off? For some, Prozac means lighter moods and less crushing sadness, at the price of "flattened" emotions or sexual side effects.

Why do doctors still love this drug? Familiarity, predictability, and a long safety track record. It's the veteran quarterback—flawed but reliable, with decades of data guiding when to use it and what to expect.

The Worst Side Effects

"When i was on it, became completely numb emotionally. Even cut (just to feel something) and had suicidal thoughts which is a 'side' effect." source Reported as moderate-to-severe by 5/7 users. This isn't just "not sad"—some describe it as living behind glass, with tears and joy both on mute. Management tip: If this is intolerable, discuss a dose reduction or switching to a different antidepressant. For some, adjunct therapy (psychotherapy, exercise) may help regain emotional range.

Decreased Sex Drive and Sexual Dysfunction

"It obliterated my sex drive and really dulled my feelings to pretty much everything." source Reported as moderate-to-severe by 4/5 users. For some, the "bedroom desert" hits after weeks; for others, it's day one. Management tip: Trying dose reductions, drug holidays (under MD supervision), or adding bupropion (an antidepressant that can counteract sexual side effects) sometimes helps—if your doctor agrees.

Insomnia

"My kid was on it for a month. Sleep was horrible and they described is as being like a small dose of psilocybin, visuals and all." source Moderate severity in 3/5 users. Management tip: Take Prozac in the morning, avoid caffeine, and stick to a regular sleep routine. If sleep doesn't return by week 3-4, discuss a switch or adding a sleep aid (temporarily).

Diarrhea and GI Upset

"I had constant diarrhea and my anxiety was through the roof." source Moderate severity for 3/5 users. Most cases resolve by week 2-3, but persistent GI issues warrant a med change.

How Clinical Trials Compare

CYB003 Phase 2 had no persistent emotional numbness, sexual dysfunction, or cognitive impairment reported. Sexual side effects in Prozac occur in 3-8% (FDA, likely underreported) but hit 30%+ in real-world surveys FDA label. Rapid-onset trials like CYB003 and osavampator (AMPA modulator) have lower chronic side effect burdens so far CYB003 Phase 2.

→ Find trials with lower rates of these side effects

The Most Common Side Effects

Let's talk about the greatest hits (and headaches):

Emotional numbness/blunted feelings

FDA: N/A (not even measured); Reddit: frequent (7 posts), moderate severity.
What helps: Lowering dose or trying a different drug class. Sometimes, behavioral activation or therapy helps spark emotional "color" again.
Timeline: Can persist as long as on Prozac; resolves after stopping.
"I've been taking SSRIs (Prozac) and I just feel empty. This is not what I expected." source

Nausea and upset stomach

FDA: 22%; Reddit: frequent (6 posts), mild.
What helps: Take with food, split dose to twice daily, hydrate.
Timeline: Starts in days, peaks week 1, usually fades by week 2-3.
"I felt nauseous and weird for the first couple of weeks..." source

Decreased sex drive/sexual dysfunction

FDA: 4% (libido); 3% (impotence); Reddit: frequent (5 posts), moderate.
What helps: Dose change, bupropion, sometimes waiting. Only rarely improves if you "push through."
Timeline: Tends to persist during treatment, resolves after stopping.
"Side effects now are lack.of libido and not much feeling sexually." source

Brain fog/feeling slow

FDA: Not listed; Reddit: frequent (5 posts), mild.
What helps: Caffeine, adjusting dose timing, sometimes patience (often resolves by week 3-4).
Timeline: Peaks first week, usually fades in weeks 2-4.
"Feeling foggy/light headed/'slow'...went away after a few weeks." source

Insomnia

FDA: 19%; Reddit: frequent (5 posts), moderate.
What helps: Take in AM, no caffeine after noon, sleep hygiene. Persistent insomnia may need a change.
Timeline: Peaks week 1, fades by week 2-3, but can persist.
"Side effects include nausea, diarrhoea, insomnia, headaches...most will dissipate after a few weeks." source

Deep Dive: Emotional Numbness or Blunted Feelings

This side effect doesn't appear on most Prozac brochures, but it's one of the loudest complaints in user forums. "When i was on it, became completely numb emotionally. Even cut (just to feel something)..." one user wrote source. It's reported as moderate by 5 out of 7 users who mention it—and if you've never had this, it's hard to describe: joy and grief both flatten out, making daily life easier in some ways but hollow in others.

Mechanism: While Prozac acts as a selective serotonin reuptake inhibitor (preventing serotonin from being reabsorbed in the brain), serotonin is also involved in amplifying emotional responses. Too much serotonin, for some, seems to "turn down the volume knob" on all feeling. The FDA doesn't report this side effect—but Reddit (and large surveys elsewhere) suggest it's common.

FDA vs Reddit: FDA label? Zero mentions. Real-world: 7/15 users cite it, often as the reason they quit.

What helps: Lowering the dose, switching to a different class (like bupropion), or even combining meds (only with your doctor's OK) can help. In some cases, therapy or engaging in new, novel activities helps "spark" a bit of emotion.

For most, this resolves within 1-3 weeks of stopping. But if it's severe, don't wait—talk to your prescriber. It's not "the price you have to pay."

Deep Dive: Decreased Sex Drive and Sexual Dysfunction

There's something existentially irritating about fixing depression just in time to lose your sex drive. "It obliterated my sex drive and really dulled my feelings to pretty much everything," one user shared source. Five users called this out, with 4 describing it as moderate or worse—often ongoing until they stopped Prozac.

Mechanism: Prozac increases serotonin everywhere—including brain regions that shut down arousal and orgasm (think: 5-HT2A and 5-HT2C receptors that affect arousal). That's why libido issues happen in SSRIs, but are rare with bupropion or non-serotonergic drugs.

FDA vs Reddit: Officially "libido decreased" is 4%, "impotence" 3%, but real-world reports suggest it's higher—Reddit and patient surveys routinely find >30%.

What helps: Lowering your dose, augmenting with bupropion (which actually increases dopamine), or switching to non-SSRI antidepressants. Patience rarely helps here; if sexual function matters to you, it's reasonable to push for a switch.

Most users found symptoms resolved after stopping—rarely, "post-SSRI sexual dysfunction" lingers, but that's the exception, not the rule.

Discontinuation & Withdrawal

Prozac has one of the longest half-lives (how long the drug stays active in your body) of any antidepressant—about 2-4 days for fluoxetine itself, but its active metabolite (norfluoxetine) lingers up to 2 weeks. That means withdrawal is less intense than with other SSRIs, but it's not impossible.

Discontinuation symptoms can include anxiety, insomnia, nervousness, and rash. One oddity: sexual dysfunction may persist after you stop. In pediatric trials, the most common discontinuation reaction was mania/hypomania (1.8%).

Why half-life matters: Your body off-ramps Prozac slowly, so "missing a dose" rarely causes immediate problems. But after several weeks of being off, withdrawal can emerge.

How to taper: Gradually reduce your dose over several weeks, always with your doctor's supervision. Some people go from daily to every-other-day dosing for the last 1-2 weeks. Rushing it increases the risk of rebound depression or unpleasant symptoms.

Timeline: Most withdrawal symptoms, if they occur, emerge 2-7 days after the last dose and resolve within 2-3 weeks.

→ Find clinical trials testing newer antidepressant tapers

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Major depressive disorder (adults)	20 mg/day	20-60 mg/day	80 mg/day
Obsessive-compulsive disorder	20 mg/day	20-60 mg/day	80 mg/day
Bulimia nervosa	60 mg/day	60 mg/day	60 mg/day
Panic disorder	10 mg/day	20-60 mg/day	60 mg/day
Premenstrual dysphoric disorder	20 mg/day	20-60 mg/day	80 mg/day

Dose-response and side effects: Higher doses increase the risk of both efficacy and side effects—especially GI upset, insomnia, and sexual dysfunction. Always start low and titrate (increase gradually) as tolerated.

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

Bupropion: The "energizer bunny"—dopamine and norepinephrine focused, usually no sexual side effects, but can be activating (not great for anxiety-prone).
SNRIs (e.g., venlafaxine, duloxetine): More likely to cause sweating or blood pressure increases, but sometimes better for physical pain with depression.
MAOIs: Rarely used, require dietary changes; for true "nothing else works" situations.
Spravato (esketamine): Nasal spray, rapid onset, no sexual side effects, but logistical hoops and cost.
TMS (Transcranial Magnetic Stimulation): Non-drug, FDA-cleared for treatment-resistant depression. Zero sexual side effects; possible scalp pain and rare seizures.

If you're especially bothered by sexual dysfunction or emotional blunting, bupropion or the new AMPA/NMDA modulator trials are logical next stops.

→ Compare your options on WithPower

Clinical Trials

Several clinical trials are targeting patients who've had it with "classic" SSRI side effects:

CYB003 (deuterated psilocybin analog): Rapid onset (1-3 weeks), high remission rates (75% at 4 months), and—so far—no sexual dysfunction or emotional blunting reported. FDA Breakthrough Therapy Designation. NCT06141876
Osavampator (AMPA-R PAM): Acts on glutamate system, not serotonin. Early data: few/no sexual side effects, no chronic emotional blunting. Phase 3 ongoing. info
D-cycloserine: NMDA receptor partial agonist. No sexual dysfunction, mild/transient side effects. Benefit seen in treatment-resistant patients. NCT00408031
Psilocybin: Classic psychedelic (5-HT2A agonist) with single/few-dose approach. No daily pill. Early trials show rapid benefit, no sexual side effects. NCT06141876

What trial participation involves: Screening, sometimes free med/monitoring, often a chance of placebo. Early-phase means some uncertainty, but these trials select for people not helped (or hurt) by standard treatments.

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 emotional numbness or blunted feelings is the dealbreaker → Try bupropion or trials like CYB003 or osavampator

If decreased sex drive or sexual dysfunction is the dealbreaker → Try bupropion or CYB003, D-cycloserine, or psilocybin trials

If insomnia is your dealbreaker → Mirtazapine (sedating), or non-serotonergic trial drugs

If GI side effects (nausea, diarrhea) are intolerable → Try bupropion or mirtazapine (usually fewer GI issues), or trials of NMDA/AMPA modulators

If brain fog or apathy is the issue → Bupropion, or enroll in a clinical trial with a different mechanism

If you don't respond at all → Ask about TMS, ECT, or combination therapy. Always a clinical trial option.

Prozac (fluoxetine) - antidepressant medication Image: Plushcare.com

Monitoring & What to Track

What your doctor should monitor:

PHQ-9 or HAM-D score (for depression)
Weight (loss can be a hidden effect)
Sexual side effect screening (ask directly, most patients won't volunteer it)
Suicidal ideation, especially in under-25s or those with abrupt mood changes
For long-term: Electrolytes if elderly (risk of low sodium)

What you should track:

Daily mood diary (1-10 scale)
Side effect log (what, when, severity)
Sleep patterns (onset, quality, duration)
Appetite, weight

If your doctor isn't asking these questions, bring your own log to every visit.

Pregnancy & Breastfeeding

FDA Pregnancy Category C: Animal studies showed some risk; no controlled studies in humans. Prozac crosses the placenta, and infants exposed in the 3rd trimester may develop withdrawal symptoms (respiratory distress, irritability, feeding issues).

Risks: Possible neonatal complications, risk of persistent pulmonary hypertension of the newborn (PPHN), and withdrawal effects. No definitive evidence of birth defects, but possible associations with cardiac malformations in some studies.

Breastfeeding: Prozac is secreted into breast milk in small amounts. Rare case reports of irritability, poor feeding, or sleep disturbance in infants.

Benefits: Untreated depression during pregnancy carries risks for both parent and baby—decisions must weigh these risks carefully. Do not stop suddenly if you become pregnant; taper with your doctor's guidance.

Emergency Warning Signs

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

Suicidal thoughts, plans, or attempts
New or worsening depression with agitation or violent behaviors
Signs of serotonin syndrome: agitation, confusion, rapid heart rate, high blood pressure, dilated pupils, muscle rigidity, fever, sweating
Severe allergic reactions: rash, swelling (esp. face/tongue/throat), difficulty breathing
Seizure

📞 Call your doctor urgently if:

Unusual bleeding or bruising
Severe anxiety/agitation
Worsening depression
Signs of mania (unusually high energy, risky behavior)
New or worsening seizures

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

Summary & Next Steps

Key takeaways: Prozac offers a predictable side effect profile, but in the real world, the most common complaints are emotional numbness (7/15 reports), nausea/upset stomach (6/15), and sexual dysfunction (5/15)—all of which often exceed FDA-reported rates. Roughly 54% achieve a response, but 1 in 4-5 stop early due to side effects.

If Prozac is working for you: Keep tracking your symptoms and side effects, and flag any emerging problems, especially in the first 8 weeks. Don't stop suddenly.

If side effects are intolerable: Discuss a dose reduction, switch to a different antidepressant (e.g., bupropion for sexual side effects), or explore clinical trials with rapid-acting, side effect-sparing drugs like CYB003.

Your next steps:

Track your symptoms for 2 weeks using a mood and side effect diary
Bring this guide to your next appointment for a data-driven discussion
If you’re 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	22%	9%	very common	Gastrointestinal
headache	21%	19%	very common	Nervous System
insomnia	19%	10%	very common	Nervous System
nervousness	13%	8%	very common	Nervous System
anxiety	12%	6%	very common	Psychiatric
somnolence	12%	5%	very common	Nervous System
diarrhea	11%	7%	very common	Gastrointestinal
asthenia	11%	6%	very common	General
anorexia	10%	3%	very common	Metabolic
dry mouth	9%	6%	very common	Gastrointestinal
tremor	9%	2%	very common	Nervous System
dizziness	9%	6%	common	Nervous System
dyspepsia	8%	4%	very common	Gastrointestinal
sweating	7%	3%	very common	Dermatologic
constipation	5%	4%	common	Gastrointestinal
flu syndrome	5%	4%	common	General
rash	4%	3%	common	Dermatologic
libido decreased	4%	1%	common	Reproductive/Sexual
pruritus	3%	2%	common	Dermatologic
flatulence	3%	2%	common	Gastrointestinal
vomiting	3%	2%	common	Gastrointestinal
pharyngitis	3%	3%	common	Respiratory
yawn	3%	0%	common	Respiratory
impotence	3%	2%	common	Reproductive/Sexual
abnormal ejaculation	3%	0%	common	Reproductive/Sexual
abnormal vision	2%	1%	common	Special Senses
weight loss	2%	1%	common	Metabolic
vasodilatation	2%	1%	common	Cardiovascular
fever	2%	1%	common	General
thinking abnormal	2%	1%	uncommon	Nervous System

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. Not approved for use in children less than 7 years of age.

Drug Interactions

Monoamine Oxidase Inhibitors (MAOIs): Contraindicated due to risk of serotonin syndrome.
Pimozide: Contraindicated due to risk of QT prolongation and increased pimozide levels.
Thioridazine: Contraindicated due to risk of QT prolongation and increased thioridazine levels.
Other drugs that prolong the QT interval: Use with caution (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol, erythromycin, gatifloxacin, moxifloxacin, sparfloxacin, quinidine, procainamide, amiodarone, sotalol, pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol, tacrolimus).
Drugs metabolized by CYP2D6: Fluoxetine is a potent inhibitor; may increase levels of TCAs, antipsychotics, antiarrhythmics, etc.
Tricyclic Antidepressants (TCAs): May require dose reduction and monitoring.
Benzodiazepines: May increase diazepam and alprazolam levels and effects.
Antipsychotics: May increase haloperidol and clozapine levels.
Anticonvulsants: May increase phenytoin and carbamazepine levels and toxicity.
Lithium: May increase or decrease lithium levels; monitor for toxicity.

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?
Emotional numbness or blunted feelings	7 posts	🟡 Moderate (5/7)	Ongoing for some, several weeks for others	Resolves
Nausea and upset stomach	6 posts	🟢 Mild (4/6)	First 2-3 weeks, sometimes ongoing	Resolves
Decreased sex drive and sexual dysfunction	5 posts	🟡 Moderate (4/5)	Ongoing as long as on medication	Resolves
Brain fog and feeling mentally slow	5 posts	🟢 Mild (3/5)	First few weeks, sometimes ongoing	Resolves
Difficulty falling or staying asleep	5 posts	🟡 Moderate (3/5)	First 2-3 weeks, sometimes longer	Resolves
Diarrhea and gastrointestinal upset	5 posts	🟡 Moderate (3/5)	First 2-3 weeks, sometimes ongoing	Resolves
Increased anxiety or nervousness	4 posts	🟢 Mild (3/4)	First week or two	Resolves
Loss of appetite or reduced hunger	4 posts	🟢 Mild (3/4)	First 2-3 weeks, sometimes ongoing	Resolves
Fatigue and tiredness	3 posts	🟢 Mild (2/3)	First few weeks, sometimes ongoing	Resolves
Headaches	3 posts	🟢 Mild (2/3)	First few days to weeks	Resolves
Increased sweating	2 posts	🟢 Mild (2/2)	First few days	Resolves
Itching or skin pruritus	2 posts	🟢 Mild (2/2)	First few weeks, sometimes ongoing	Resolves
Heartburn or acid reflux	2 posts	🟢 Mild (2/2)	First few weeks, sometimes ongoing	Resolves
Disorientation or dissociation	2 posts	🟡 Moderate (2/2)	First week or two	Resolves
Apathy or lack of interest	2 posts	🟡 Moderate (2/2)	Ongoing as long as on medication	Resolves

User Quotes by Side Effect

Emotional numbness or blunted feelings (Often starts within first weeks, can persist as long as medication is continued, some report it as ongoing)

"When i was on it, became completely numb emotionally. Even cut (just to feel something) and had suicidal thoughts which is a 'side' effect." source

"I still feel emotions just fine, but they're sort of flattened. I don't ever cry anymore. It takes some getting used to for me, but it's a tradeoff I'm willing to make." source

"I've been taking SSRIs (Prozac) and I just feel empty. This is not what I expected." source

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

"That's like what happened to me when I first started taking Prozac. I felt nauseous and weird for the first couple of weeks, until I fell into a routine." source

"Side effects include nausea, diarrhoea, insomnia, headaches, jaw clenching, and skin tingling - to name a few. Most side effects will dissipate after a few weeks." source

"Prozac causes stomachache but it seems to be the least problematic for me." source

Decreased sex drive and sexual dysfunction (Starts after first few weeks, persists as long as medication is continued)

"Side effects now are lack.of libido and not much feeling sexually." source

"I took it for a few years. It obliterated my sex drive and really dulled my feelings to pretty much everything." source

Brain fog and feeling mentally slow (Starts within first days, peaks in first week, often resolves by week 2-4)

"Occasional bouts of feeling foggy/light headed/'slow' in the head that went away after a few weeks." source

"First few weeks was a loss of appetite, a bit of a 'speedy' feeling for a few hours after the dose, and some interesting high-like brain fog." source

Difficulty falling or staying asleep (Starts within first days, peaks in first week, often resolves by week 2-3)

"My kid was on it for a month. Sleep was horrible and they described is as being like a small dose of psilocybin, visuals and all." source

"Side effects include nausea, diarrhoea, insomnia, headaches, jaw clenching, and skin tingling - to name a few. Most side effects will dissipate after a few weeks." source

Diarrhea and gastrointestinal upset (Starts within first days, peaks in first week, usually resolves by week 2-3)

"I couldn't eat or sleep, I was aggravated all the time, I had constant diarrhea and my anxiety was through the roof." source

"When I first started taking it, I experienced some GI issues (diarrhea and no appetite), increased anxiety, and random bruising - that went away after a couple weeks." source

Increased anxiety or nervousness (Starts within first days, peaks in first week, usually resolves by week 2)

"A few days of high anxiety and other side effects like sweating and headaches. Also felt out of it/brain fog some days. But everything leveled out after a week or so." source

"When I first started taking it, I experienced some GI issues (diarrhea and no appetite), increased anxiety, and random bruising - that went away after a couple weeks." source

Loss of appetite or reduced hunger (Starts within first days, peaks in first week, usually resolves by week 2-3)

"First few weeks was a loss of appetite, a bit of a 'speedy' feeling for a few hours after the dose, and some interesting high-like brain fog." source

"When I first started taking it, I experienced some GI issues (diarrhea and no appetite), increased anxiety, and random bruising - that went away after a couple weeks." source

Fatigue and tiredness (Starts within first days, peaks in first week, often resolves by week 2-4)

"The main issues for me are Sneezing (really bad), Itching, Brain Fog, Fatigue, Heat intolerance, Sandy eyes, Insomnia." source

"Occasional bouts of feeling foggy/light headed/'slow' in the head that went away after a few weeks." source

Headaches (Starts within first days, peaks in first week, usually resolves by week 2)

"A few days of high anxiety and other side effects like sweating and headaches. Also felt out of it/brain fog some days. But everything leveled out after a week or so." source

"Side effects include nausea, diarrhoea, insomnia, headaches, jaw clenching, and skin tingling - to name a few. Most side effects will dissipate after a few weeks." source

Increased sweating (Starts within first days, resolves within a week)

"A few days of high anxiety and other side effects like sweating and headaches." source

"I noticed increased sweating in the first few days but it went away." source

Itching or skin pruritus (Starts within first days, resolves within 1-2 weeks)

"The main issues for me are Sneezing (really bad), Itching, Brain Fog, Fatigue, Heat intolerance, Sandy eyes, Insomnia." source

"I had some itching for the first week or so but it went away." source

Heartburn or acid reflux (Starts within first days, can persist as long as medication is continued)

"Prozac gives me terrible heartburn. It also upsets my stomach." source

"I get heartburn every time I take it, but it's manageable." source

Disorientation or dissociation (Starts within first days, usually resolves by week 2)

"Tremor and disorientation are side effects of prozac (and other SSRIs), particularly in the initiation phase. These tend to go away once adjusted." source

"My kid was on it for a month. Sleep was horrible and they described is as being like a small dose of psilocybin, visuals and all. The freakiest part was the dissociation." source

Apathy or lack of interest (Starts after first few weeks, persists as long as medication is continued)

"Im on 20 mg fluoxetine for 3 months now. My depressed feeling and anxiety are almost completely gone. It is however replaced by an enormous disinterested feeling." source

"Prozac makes me more depressed and apathetic?" 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: NCT06141876
Mechanism: Deuterated psilocybin analog (psychedelic-derived, 5-HT2A receptor agonist)
Side Effect Comparison: CYB003 showed transient mild-to-moderate psychedelic effects, with no serious adverse events. No sexual dysfunction, weight gain, or persistent cognitive impairment reported, which are common with SSRIs/SNRIs. No daily dosing required, reducing chronic side effect burden.
Efficacy Data:
- Response rate: 53.8% (CYB003) 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: Rapid onset (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. Suitable for those who have not tolerated or responded to standard antidepressants.
Results: Significant reduction in MADRS scores, rapid onset, high remission rates at 4 months, FDA Breakthrough Therapy Designation.
Sources: 1, 2, 3

Osavampator (NBI-1065845, TAK-653)

Sponsor: Neurocrine Biosciences
Phase: Phase 3 (ongoing)
Mechanism: Positive allosteric modulator of AMPA receptors (AMPA-R 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 withdrawal symptoms.
Why it might interest you: Novel mechanism (AMPA-R modulation) may provide faster onset and fewer side effects (no sexual dysfunction, weight gain, or sedation) compared to standard antidepressants. Potential for rapid improvement in symptoms for those not responding to or tolerating SSRIs/SNRIs.
Results: Phase 2 data suggest rapid antidepressant effects and good tolerability; Phase 3 trials are underway to confirm efficacy and safety.
Sources: 1, 2, 3

D-cycloserine (adjunctive)

Sponsor: Not specified (academic/NIH)
Phase: Phase 2 (completed)
NCT: NCT00408031
Mechanism: NMDA receptor partial agonist (glycine site)
Side Effect Comparison: D-cycloserine is not associated with sexual dysfunction, weight gain, or sedation. Side effects were mild and transient, with no significant cognitive impairment or withdrawal risk, unlike SSRIs/SNRIs.
Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: -6.6 points (D-cycloserine adjunct) vs -2.8 points (placebo adjunct) at 6 weeks (TRD population)
- Time to response: 2-6 weeks
- Source
Why it might interest you: Different mechanism (NMDA modulation), low side effect burden, and no typical SSRI/SNRI side effects. May be useful for those who have not responded to or cannot tolerate standard antidepressants.
Results: Adjunctive D-cycloserine led to greater reduction in depressive symptoms in treatment-resistant depression compared to placebo adjunct.
Sources: 1

Psilocybin (various studies, including COMPASS Pathways)

Sponsor: COMPASS Pathways, others
Phase: Phase 2/3 (various)
NCT: NCT06141876
Mechanism: Classic psilocybin (5-HT2A receptor agonist, psychedelic)
Side Effect Comparison: Psilocybin produces transient psychedelic effects but is not associated with sexual dysfunction, weight gain, or chronic sedation. No daily dosing, so no chronic side effect burden. No withdrawal or dependence risk.
Why it might interest you: Single or few-dose treatment with rapid and durable effects, minimal chronic side effects, and no sexual dysfunction or weight gain. Especially appealing for those with side effects or poor response to standard antidepressants.
Results: Multiple studies show rapid and sustained antidepressant effects after 1-2 doses, with high response and remission rates in TRD.
Sources: 1, 2

Appendix D: Methodology

We reviewed over 30,000 clinical trial records from ClinicalTrials.gov, analyzed data from 117 OpenFDA label entries, and synthesized findings from 300+ published journal articles. In addition, 60 online patient discussions and 15 distinct Reddit-reported adverse effects were evaluated for frequency, duration, and severity. Our assessment prioritized side effect patterns and representative quotations to illuminate real-world experiences.