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PROPRANOLOL HYDROCHLORIDE (Inderal) Side Effects Guide

Intro

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Inderal (Propranolol)

The Worst Side Effects

The Most Common Side Effects

Depression and Mood Swings (Deep Dive)

Tiredness and Low Energy (Deep Dive)

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

Inderal (propranolol): Real-world side effects for depression and anxiety. Reddit user quotes, clinical trial data, and expert analysis—plus comparison to newer antidepressant options.

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

Reviewed by the Power Medical Content Team


Intro

Day 1: You swallow that first blue pill and, within hours, maybe you notice your hands feel a little lighter—or a little heavier, depending on luck. Day 3: Dizziness starts to creep in. Week 2: You’re tired, maybe more tired than seems reasonable, but also—just maybe—a hint less panicked. Or not. And so begins the often-circuitous journey with Inderal (propranolol) as an antidepressant.

Propranolol’s original claim to fame wasn’t mood, but rather blood pressure, stage fright, and shaking hands at the lectern. Yet it’s ventured into the world of mood—sometimes as a desperate attempt to dodge the infamous side effects of standard antidepressants. Of the estimated 30 million Americans who have tried an antidepressant, up to 40% quit in the first three months—side effects, inefficacy, or sheer exhaustion with the trial-and-error marathon (source).

But here’s the rub: traditional FDA trials for Inderal-as-antidepressant show zero percent rates for most side effects, while actual users on Reddit sing a very different, not always harmonious tune. This guide sifts through both the polished numbers and the messy reality to give you the clearest, most honest picture of what to expect.

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 EffectFDA RateReddit ReportsSeverityDurationExample
Dizziness and feeling lightheaded0%🟠 Frequent (7 posts)🟡 ModerateDays to weeks"The biggest side effect for me was dizziness. It got to the point that I didn't feel safe driving, which I have to do a lot of for work."
Tiredness and low energy0%🟠 Frequent (5 posts)🟡 ModerateOngoing, may improve"Propanalol gave me incredibly bad brain fog and fatigue. I felt like I was walking through water while simultaneously not living in my body."
Depression and mood swings0%🟠 Frequent (5 posts)🟠 SevereOngoing, resolves after stopping"I was on Propranolol and it made me have insane mood swings and gain a bunch of weight. I got off of it and lost weight and my mood is better ..."
Difficulty falling or staying asleep0%🟡 Occasional (4 posts)🟡 ModerateOngoing"Common side effects of Propranolol include insomnia and vivid dreams, which in my experience triggers PTSD, I suppose due to memory ..."
Headaches and head pressure0%🟡 Occasional (3 posts)🟢 MildShort-term, sometimes ongoing"The only side effect I've experienced are minor headaches and just generally feeling 'off' when I take it."
Shortness of breath and chest tightness0%🟡 Occasional (3 posts)🟡 ModerateHours to days"My chest felt tight, I experienced shortness of breath and dizziness and I had to go lie down."
Worsening anxiety or panic attacks0%🟡 Occasional (3 posts)🟡 ModerateImmediate or first week"On a side note, the first time I tried it at home I got the weirdest panic attack ever. I started to get paranoid that my heart would fail and ..."
Weight gain0%🟡 Occasional (3 posts)🟢 MildWeeks to months"I was on Propranolol and it made me have insane mood swings and gain a bunch of weight. I got off of it and lost weight and my mood is better ..."
Brain fog and feeling mentally slow0%🟢 Rare (2 posts)🟡 ModerateOngoing"Propanalol gave me incredibly bad brain fog and fatigue. I felt like I was walking through water while simultaneously not living in my body."
Nausea and upset stomach0%🟢 Rare (2 posts)🟢 MildShort-term"Dizzy/lightheaded, anxiety and panic bad as ever, extremely emotional, heaviness with breathing, nausea and zero appetite, constant headache, blurry vision."
Blurry vision and visual disturbances0%🟢 Rare (2 posts)🟢 MildOngoing"Dizzy/lightheaded, anxiety and panic bad as ever, extremely emotional, heaviness with breathing, nausea and zero appetite, constant headache, blurry vision."
Suicidal thoughts or ideation0%🟢 Rare (2 posts)🟠 SevereOngoing"I started propranolol about a month ago for inappropriate sinus tachycardia, for which it's been very helpful, but I've also noticed an increase in depression ..."
Digestive issues (diarrhea, constipation, cramps)0%🟢 Rare (1 post)🟡 ModerateFirst week"GI issues (alternating diarrhea/constipation/cramps), insomnia, fatigue during the day, ocular migraine. I lasted one week on it before giving up."
Ocular migraine0%🟢 Rare (1 post)🟡 ModerateFirst week"GI issues (alternating diarrhea/constipation/cramps), insomnia, fatigue during the day, ocular migraine. I lasted one week on it before giving up."
Heaviness with breathing0%🟢 Rare (1 post)🟡 ModerateOngoing"Dizzy/lightheaded, anxiety and panic bad as ever, extremely emotional, heaviness with breathing, nausea and zero appetite, constant headache, blurry vision."
View all 46 side effects from FDA trials
View all 15 user-reported side effects

How Other Drugs Compare

If you're weighing options, here's how Inderal (propranolol) stacks up against alternatives:

MetricInderal (Antidepressant)CYB003 (Psilocybin analog)Osavampator (AMPA-PAM)D-cycloserine (NMDA partial agonist)
MECHANISM
Drug classNonselective beta blockerDeuterated psilocybin analogAMPA receptor positive allosteric modulatorNMDA receptor partial agonist
How it worksBlocks beta-adrenergic receptors (reduces sympathetic overdrive)Activates serotonin 5-HT2A receptors (alters neural circuits)Increases AMPA activity (boosts synaptic plasticity)Modulates NMDA/glycine site (enhances learning/extinction)
EFFICACY
Response rateNot established for depression53.8% (3 wks) sourceNot yet reported (Phase 3)Not reported
Remission rateNot established75% (4 months)Not yet reportedNot reported
Time to effect1-2 days for anxiety, not established for depression1-3 weeksEstimated faster than SSRIs/SNRIs1-2 weeks
KEY SIDE EFFECTS
Dizziness/lightheadedFrequent (Reddit)Mild, transientMildMild
Fatigue/tirednessFrequentRareRareRare
Depression/moodSevere for someNot reportedNot reportedNot reported
GI effectsOccasionalNausea, mild-moderateMildMild
Sexual dysfunctionRareNone reportedNone reportedNone reported
Weight gainOccasionalNone reportedNone reportedNone reported
Find clinical trials matched to your situation

Week-by-Week Timeline

WeekCommon ExperiencesWhat's NormalWhen to Call Your Doctor
Week 1Dizziness, tiredness, maybe a strange mood shiftStartup effectsSevere chest pain, shortness of breath, or suicidal thoughts
Week 2-3Mood swings, trouble sleeping, maybe headachesStill adjustingWorsening depression, panic attacks
Week 4-6Fatigue may linger, some acclimateGradual adaptationNo improvement or intolerable side effects
Week 6-8Mood stabilizes (or not), side effects may persist or fadeStablePersistent severe depression or inability to function

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 Inderal (Propranolol)

Propranolol is a nonselective beta-adrenergic receptor antagonist—meaning it blocks the proteins on cells that respond to adrenaline and noradrenaline (the so-called 'fight or flight' brain chemicals). This makes it king of the hill for performance anxiety and certain heart issues, but it's also wandered into depression treatment territory when patients are desperate to dodge sexual dysfunction, weight gain, or the numbing fog of other antidepressants.

Side effects happen for the very same reason the drug sometimes works: blocking beta receptors affects everything from your heart rate to blood sugar, energy, and even parts of the brain that regulate mood. It's the sledgehammer approach—if you block adrenaline everywhere, not just in the sweaty palms or pounding heart, you get the full menu of effects (both wanted and less wanted).

Why prescribe anyway? Because after decades of use, doctors know what they're getting. There's predictability. It's well-studied, side effects are usually reversible, and—unlike some SSRIs—there's no sexual side effect in most. For those with treatment-resistant symptoms and specific contraindications to SSRIs, Inderal can sometimes fill a gap.


The Worst Side Effects

Depression and Mood Swings

"I was on Propranolol and it made me have insane mood swings and gain a bunch of weight. I got off of it and lost weight and my mood is better ..." source

Reported as severe by 3/5 users. For some, these depressive symptoms can be intense and disabling.

Management tip: If you notice mood worsening or suicidal thoughts, don't try to "wait it out"—report these changes promptly. Switching or discontinuing (with medical supervision) often resolves it.

Suicidal Thoughts

"Propranolol in particular is known for causing sudden shifts in depression levels, one day it'll help and the next it'll cause suicidal feelings ..." source

Reported as severe by 2/2 users. This is always an emergency—no "let's wait and see."

Management tip: If you experience suicidal thoughts, call your doctor or emergency services immediately.

Tiredness and Low Energy

"Propanalol gave me incredibly bad brain fog and fatigue. I felt like I was walking through water while simultaneously not living in my body." source

Moderate to severe for 3/5 users. Some push through, others find it unworkable.

Management tip: Consider adjusting the dose or timing, and discuss with your doctor if it's interfering with daily function.

How Clinical Trials Compare

In the CYB003 (psilocybin analog) Phase 2 study, no weight gain, sexual dysfunction, or cognitive blunting were reported—side effects that real-world Inderal users described as major reasons to quit (source). Trials of AMPA and NMDA modulators (osavampator, D-cycloserine) also show a more favorable cognitive side effect profile compared to Inderal, with most common adverse events being mild headache or transient nausea (source; source).

Find trials with lower rates of these side effects


The Most Common Side Effects

  1. Dizziness and feeling lightheaded

    • FDA rate: 0% | Reddit: Frequent (7 reports), moderate
    • What helps: Stand up slowly, hydrate, consider splitting doses. Usually improves after a few days.
    • Timeline: Days to weeks
    • "The biggest side effect for me was dizziness. It got to the point that I didn't feel safe driving, which I have to do a lot of for work." source

  2. Tiredness and low energy (fatigue)

    • FDA: 0% | Reddit: Frequent (5 reports), moderate
    • What helps: Take at bedtime if possible; reduce dose with your doctor if intolerable.
    • Timeline: Can persist, sometimes improves by Week 4
    • "It's been four days and so far I have been having pretty bad side effects, such as dizziness, fatigue, and a little anxiety." source

  3. Depression and mood swings

    • FDA: 0% | Reddit: Frequent (5), severe
    • What helps: Track mood, notify your provider at first sign of change.
    • Timeline: Can develop after a couple weeks
    • "Turns out, in a small percentage of users, it causes CNS side effects, including psychological ones like anxiety and depression." source

  4. Difficulty falling or staying asleep (insomnia)

    • FDA: 0% | Reddit: Occasional (4), moderate
    • What helps: Dose earlier in the day, avoid caffeine, consider non-drug sleep strategies.
    • Timeline: May persist as long as medication is continued
    • "Common side effects of Propranolol include insomnia and vivid dreams ..." source

  5. Shortness of breath and chest tightness

    • FDA: 0% | Reddit: Occasional (3), moderate
    • What helps: Stop and seek medical advice if persistent—can indicate an asthma-like reaction.
    • Timeline: Often occurs after first dose
    • "My chest felt tight, I experienced shortness of breath and dizziness and I had to go lie down." source


Depression and Mood Swings (Deep Dive)

If you’ve ever wondered if a heart medication could hijack your serotonin, you’re not alone. For some users, Inderal’s greatest liability is the subtle (or not so subtle) slide into depression. "Turns out, in a small percentage of users, it causes CNS side effects, including psychological ones like anxiety and depression," wrote one user, baffled by the lack of warning (source). Another was more blunt: "I was on Propranolol and it made me have insane mood swings and gain a bunch of weight. I got off of it and lost weight and my mood is better ..." (source).

FDA trial data are, frankly, useless here—zero percent reported. Real-world: 5/5 users called this out, with 3 describing it as severe. Most say it fades after stopping the medication, but some had to endure weeks before things "felt normal" again.

Why does this happen? The working theory: blocking beta receptors not only tames the heart, but also blunts neurotransmitter release and downstream effects on brain circuits involved in drive, mood, and pleasure. It's not classic serotonin reuptake inhibition (preventing the brain from reabsorbing the neurotransmitter), but it can cramp your neural style all the same.

What to do?

  • Track mood daily
  • Bring up any mood changes or sudden irritability at your next doctor visit
  • Discontinuing often resolves the symptoms, but only taper under guidance

There's a small—but vocal—contingent that finds this tradeoff unacceptable.


Tiredness and Low Energy (Deep Dive)

"Propanalol gave me incredibly bad brain fog and fatigue. I felt like I was walking through water while simultaneously not living in my body." source If there’s a single side effect that practically comes stapled to the prescription, it’s a sudden drop in your energy account. Fatigue is one of the first things people notice and, for some, the main reason they quit.

FDA data says: 0% (not even a whiff). Reddit: 5 users call it out as moderate, ongoing, sometimes improving by week 4, but occasionally so relentless that people give up. The mechanism? Blunt-force beta-blockade everywhere: less adrenaline, less "go," everywhere—from muscle to mind.

Management tips:

  • Consider taking Inderal in the evening to dodge the daytime slump
  • Hydrate, don’t over-caffeinate (can make things worse)
  • If fatigue is unmanageable after a few weeks, talk to your doctor about lowering the dose or switching drugs

Some trudge through, hoping their body acclimates. Many jump ship.


Discontinuation & Withdrawal

The FDA label is coy—no official withdrawal symptoms are described, apart from the advisory to be cautious if withdrawing from clonidine (another blood pressure drug). That doesn’t mean you’ll breeze through. Propranolol has a half-life (how long the drug stays active in your body) of around 3 to 6 hours for the immediate release, and up to 10-20 hours for the extended release. This short-to-moderate half-life means abrupt stopping can trigger a rebound in heart rate, blood pressure, and potentially mood—especially if you’re on a high dose or have been taking it for months.

Common withdrawal effects:

  • Palpitations
  • Tremor
  • Return of original symptoms (anxiety, sweating, etc.)
  • Rarely: worsening depression or "crash"

How to manage? Always taper—slowly and under supervision. For immediate-release, this can mean reducing by 10-20mg every 3-7 days, depending on your starting dose and tolerance. If switching to a different antidepressant, your doctor might overlap them, but not always.

Timeline: Withdrawal symptoms tend to appear within 2-5 days of stopping, resolving in a week or two. Long-term use or high-dose users may need slower tapers.

P.S. If you’re also on clonidine, consult your doctor closely: sudden withdrawal from one while on the other can be dangerous.


Dosage by Condition

ConditionStarting DoseTypical DoseMaximum Dose
Hypertension40 mg twice daily120-240 mg/day640 mg/day
Angina pectoris80-320 mg/day80-320 mg/day640 mg/day
Arrhythmias10-30 mg 3-4x/day30-160 mg/day640 mg/day
Migraine prophylaxis80 mg/day (divided)160-240 mg/day240 mg/day
Essential tremor40 mg twice daily120 mg/day320 mg/day
Anxiety (off-label)10-40 mg as needed10-40 mg as needed320 mg/day

Dose-dependent side effects: Fatigue and dizziness tend to be more pronounced at higher doses, especially when titration (gradually adjusting the dose) is rushed.

Always discuss with your provider before adjusting doses.


Alternatives

If Inderal isn’t your soulmate, several FDA-approved options target depression (and sometimes anxiety) via totally different mechanisms:

  • SSRIs (e.g., sertraline, fluoxetine): The vanilla ice cream of antidepressants. Common, familiar, but often plagued by sexual dysfunction and weight gain.
  • Bupropion (NDRI): The "no sexual side effects" renegade. Sometimes more activating (may worsen anxiety).
  • SNRIs (venlafaxine, duloxetine): Like SSRIs with a turbocharger—sometimes more energizing, but watch out for blood pressure bumps.
  • MAOIs: The eccentric grandparent—powerful but fussy, with a diet to match (tyramine warning).
  • Spravato (esketamine nasal spray): Fast-acting, expensive, used for tough cases. Less weight gain, but possible dissociation.
  • TMS (transcranial magnetic stimulation): Gadgetry for your brain. Fewer systemic side effects but requires multiple clinic visits.

Which might avoid your main side effects?

  • Fatigue: Consider bupropion
  • Depression from propranolol: Any alternative without beta-blockade
  • Weight gain: Bupropion or most new psychedelic trials

Compare your options on WithPower


Clinical Trials

  1. CYB003 (deuterated psilocybin analog, NCT06141876)

    • Rapid-acting, high remission rates (75% at 4 months)
    • Lacks most "classic" antidepressant side effects (no weight gain or sexual dysfunction)
    • Most common: transient headache, nausea
    • Details
  2. Osavampator (AMPA-PAM)

    • Novel mechanism—expected faster onset, lower risk for fatigue, cognitive slowing, or sexual dysfunction
    • Phase 3 details
  3. D-cycloserine (NMDA partial agonist, NCT00408031)

  4. Psilocybin (various formulations, NCT06141876)

    • Fast onset, transient (not chronic) side effects
    • No withdrawal, high user satisfaction in early studies
    • Overview

What do you get if you enroll? Free medication, expert monitoring, and the possibility (but not guarantee) of getting the investigational treatment over placebo. Phase 2/3 means "promising, but not yet definitive." Always expect more observation and follow-up than with standard care.

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 depression/mood swings are the dealbreaker → Consider bupropion, TMS, or psilocybin trials (CYB003, NCT06141876)

If fatigue/tiredness is your nemesis → Try bupropion or osavampator (AMPA-PAM), or enroll in rapid-acting trials

If weight gain is the major issue → Consider bupropion, CYB003, or traditional MAOIs (with dietary guidance), or novel trial options

If insomnia is driving you nuts → SSRIs or SNRIs may be no better, but non-drug sleep interventions or TMS might help

There is no perfect drug—but these choices let you play to your side effect priorities. If nothing on the market works, trial enrollment is a rational next step.


Inderal (propranolol) - antidepressant medication Image: Plushcare.com

Monitoring & What to Track

What your doctor should monitor:

  • For depression: PHQ-9 or HAM-D scores each visit
  • For anxiety: GAD-7 or HAM-A
  • Weight: at baseline, 4 weeks, and every few months
  • Blood pressure and heart rate (propranolol can hide warning signs)
  • Mood symptoms—especially early changes or any hints of suicidality

What you should track:

  • Daily mood (1-10 scale)
  • Side effects log (with date, time, and severity)
  • Sleep: quality and duration
  • Energy level and exercise tolerance

If your doctor isn’t tracking these, ask—these are standard for safe medication management.


Pregnancy & Breastfeeding

Inderal (propranolol) is FDA Pregnancy Category C: animal studies have shown adverse effects, but there's a lack of high-quality data in pregnant humans. It crosses the placenta and can lower fetal heart rate, cause hypoglycemia (low blood sugar), and—at high doses—restrict fetal growth. Untreated depression or anxiety in pregnancy, however, also carries risks: preterm birth, low birth weight, and postpartum complications.

Breastfeeding? Propranolol does enter breast milk, but in small amounts. Most guidelines say it's compatible with nursing at usual doses, but watch baby for signs of bradycardia (slow heartbeat) or poor feeding.

Key message: This is a genuine risk-benefit conversation with your doctor—not a knee-jerk yes or no. And never stop suddenly if you become pregnant: rapid withdrawal can be dangerous for both you and the fetus.

See FDA Label - Pregnancy Section


Emergency Warning Signs

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

  • Suicidal thoughts or plans
  • Severe allergic reaction: rash, swelling, difficulty breathing
  • Chest pain, palpitations, severe dizziness or fainting
  • Difficulty breathing not relieved by rest (possible bronchospasm)

📞 Call your doctor urgently if:

  • Unusual bleeding or bruising
  • Severe anxiety, agitation, or panic attacks
  • Worsening depression
  • New or worsening seizures

Poison Control: 1-800-222-1222

National Suicide Prevention Lifeline: 988


Summary & Next Steps

Key takeaways: Inderal (propranolol) brings a unique set of side effects as an antidepressant—dizziness (7/15 users), fatigue (5/15), and depression/mood swings (5/15) stood out as the most common and severe in real-world reports, even though FDA trials reported none of these. Suicidal thoughts, while rare, are always serious. Newer clinical trial drugs (like CYB003) show remission rates up to 75% with far fewer cognitive and weight effects.

If Inderal is working for you, track mood and side effects, keep your appointments, and don’t change the dose without talking to your doctor. If side effects are intolerable, your next steps are:

  • Ask about dose adjustment or changing the timing of your dose
  • Consider switching to bupropion or a trial of novel agents (like CYB003, osavampator)
  • Look into clinical trials targeting rapid, better-tolerated relief

Your next steps:

  1. Track your symptoms and side effects for the next 2 weeks (simple daily log works)
  2. Share this guide and your experiences with your doctor at your next appointment
  3. 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 EffectDrug RatePlacebo RateCategorySystem
Bradycardia ⚠️0%0%commonCardiovascular
Congestive heart failure ⚠️0%0%unknownCardiovascular
Intensification of AV block ⚠️0%0%unknownCardiovascular
Hypotension0%0%unknownCardiovascular
Paresthesia of hands0%0%unknownNervous System
Thrombocytopenic purpura ⚠️0%0%rareHematologic
Arterial insufficiency (Raynaud type)0%0%unknownCardiovascular
Light-headedness0%0%unknownNervous System
Mental depression (insomnia, lassitude, weakness, fatigue) ⚠️0%0%unknownPsychiatric
Catatonia ⚠️0%0%rarePsychiatric
Visual disturbances0%0%unknownNervous System
Hallucinations ⚠️0%0%rarePsychiatric
Vivid dreams0%0%unknownPsychiatric
Acute reversible syndrome (disorientation, memory loss, emotional lability, clouded sensorium, decreased performance) ⚠️0%0%unknownNervous System
Fatigue0%0%commonNervous System
Lethargy0%0%commonNervous System
Nausea0%0%commonGastrointestinal
Vomiting0%0%commonGastrointestinal
Epigastric distress0%0%commonGastrointestinal
Abdominal cramping0%0%commonGastrointestinal
Diarrhea0%0%commonGastrointestinal
Constipation0%0%commonGastrointestinal
Mesenteric arterial thrombosis ⚠️0%0%rareGastrointestinal
Ischemic colitis ⚠️0%0%rareGastrointestinal
Anaphylactic/anaphylactoid reactions ⚠️0%0%rareAllergic/Immunologic
Pharyngitis and agranulocytosis ⚠️0%0%rareAllergic/Immunologic
Erythematous rash ⚠️0%0%rareDermatologic
Fever with aching and sore throat ⚠️0%0%rareAllergic/Immunologic
Laryngospasm ⚠️0%0%rareRespiratory
Respiratory distress ⚠️0%0%rareRespiratory

Drug Interactions

  • Drugs affecting CYP2D6, 1A2, or 2C19 metabolic pathways may alter propranolol efficacy/toxicity
  • Alcohol increases plasma levels of propranolol
  • Propafenone (additive negative inotropic and beta-blocking effects)
  • Quinidine (increases propranolol concentration, greater beta-blockade, postural hypotension)
  • Amiodarone (additive negative chronotropic effects)
  • Lidocaine (reduced clearance, risk of toxicity)
  • Digitalis glycosides (increased risk of bradycardia)
  • Calcium channel blockers (verapamil, diltiazem: risk of bradycardia, heart failure, cardiovascular collapse)
  • ACE inhibitors (risk of hypotension, especially in acute MI)
  • Clonidine (antihypertensive effects antagonized; caution on withdrawal)

Appendix B: Reddit User-Reported Side Effects

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

Side EffectMentionsSeverityDurationPersists?
Dizziness and feeling lightheaded7 posts🟡 Moderate (4/7)Varies; some report it lasting a few days to weeks, others ongoing while on medicationResolves
Tiredness and low energy5 posts🟡 Moderate (3/5)Ongoing while on medication; some report it improves after a few weeksResolves
Depression and mood swings5 posts🟠 Severe (3/5)Ongoing while on medication; some report improvement after stoppingResolves
Difficulty falling or staying asleep4 posts🟡 Moderate (2/4)Ongoing while on medication; some report it persists for monthsResolves
Headaches and head pressure3 posts🟢 Mild (2/3)Usually short-term, sometimes ongoing with useResolves
Shortness of breath and chest tightness3 posts🟡 Moderate (2/3)Usually occurs soon after taking, can last hours to daysResolves
Worsening anxiety or panic attacks3 posts🟡 Moderate (2/3)Usually immediate or within first few doses; may persist if not discontinuedResolves
Weight gain3 posts🟢 Mild (2/3)Ongoing while on medication; some report reversal after stoppingResolves
Brain fog and feeling mentally slow2 posts🟡 Moderate (1/2)Ongoing while on medicationResolves
Nausea and upset stomach2 posts🟢 Mild (2/2)Short-term, usually within first few dosesResolves
Blurry vision and visual disturbances2 posts🟢 Mild (2/2)Ongoing while on medicationResolves
Suicidal thoughts or ideation2 posts🟠 Severe (2/2)Ongoing while on medication; resolves after stoppingResolves
Digestive issues (diarrhea, constipation, cramps)1 posts🟡 Moderate (1/1)Within first week of useResolves
Ocular migraine1 posts🟡 Moderate (1/1)Within first week of useResolves
Heaviness with breathing1 posts🟡 Moderate (1/1)Ongoing while on medicationResolves

User Quotes by Side Effect

Dizziness and feeling lightheaded (Often starts within first few doses, can persist for days to weeks, sometimes resolves with continued use)

"The biggest side effect for me was dizziness. It got to the point that I didn't feel safe driving, which I have to do a lot of for work." source

"My chest felt tight, I experienced shortness of breath and dizziness and I had to go lie down." source

"It's been four days and so far I have been having pretty bad side effects, such as dizziness, fatigue, and a little anxiety." source

Tiredness and low energy (Usually starts within first week, may persist or improve after a few weeks)

"It's been four days and so far I have been having pretty bad side effects, such as dizziness, fatigue, and a little anxiety." source

"Propanalol gave me incredibly bad brain fog and fatigue. I felt like I was walking through water while simultaneously not living in my body." source

"As long as you don't struggle with low blood pressure, I don't think the side effects are anything crazy other than maybe getting a little tired ..." source

Depression and mood swings (Can develop after a couple weeks of use, may resolve after stopping)

"I was on Propranolol and it made me have insane mood swings and gain a bunch of weight. I got off of it and lost weight and my mood is better ..." source

"Turns out, in a small percentage of users, it causes CNS side effects, including psychological ones like anxiety and depression." source

"There is a possibility of severe depression occurring after a couple weeks of use, so just be on ..." source

Difficulty falling or staying asleep (Can start soon after beginning medication, may persist as long as medication is continued)

"Common side effects of Propranolol include insomnia and vivid dreams , which in my experience triggers PTSD, I suppose due to memory ..." source

"Tried it for months and still was not sleeping. I ..." source

"GI issues (alternating diarrhea/constipation/cramps), insomnia, fatigue during the day, ocular migraine. I lasted one week on it before giving up." source

Headaches and head pressure (Often starts soon after taking, may resolve with continued use or dose adjustment)

"The only side effect I've experienced are minor headaches and just generally feeling “off” when I take it." source

"One downside for me is that it gives me weird head pressure/tension feeling in neck and head if I take too much and try to exercise." source

"Dizzy/lightheaded, anxiety and panic bad as ever, extremely emotional, heaviness with breathing, nausea and zero appetite, constant headache, blurry vision." source

Shortness of breath and chest tightness (Can start with first dose, may resolve with continued use or dose adjustment)

"My chest felt tight, I experienced shortness of breath and dizziness and I had to go lie down." source

"It doesn't magically make you play better, it simply lessens some of the physical symptoms of nerves, such as shaking, shortness of breath, etc." source

"They are good at preventing the physical effects that accompany that like shortness/unevenness of breath and shaking hands." source

Worsening anxiety or panic attacks (Can start with first dose, may resolve if medication is stopped or dose adjusted)

"It's been four days and so far I have been having pretty bad side effects, such as dizziness, fatigue, and a little anxiety." source

"Dizzy/lightheaded, anxiety and panic bad as ever, extremely emotional, heaviness with breathing, nausea and zero appetite, constant headache, blurry vision." source

"On a side note, the first time I tried it at home I got the weirdest panic attack ever. I started to get paranoid that my heart would fail and ..." source

Weight gain (Develops over weeks to months, may reverse after stopping)

"I was on Propranolol and it made me have insane mood swings and gain a bunch of weight. I got off of it and lost weight and my mood is better ..." source

"I've read that some medications, especially Inderal, can affect the metabolism or promote weight gain. Does anyone of you have experience with these two ..." source

Brain fog and feeling mentally slow (Starts after beginning medication, persists while on it)

"Propanalol gave me incredibly bad brain fog and fatigue. I felt like I was walking through water while simultaneously not living in my body." source

"Now jn a really good well paid job. Cons: · increased appetite · short term memory loss · slight reduction in libido." source

Nausea and upset stomach (Starts soon after taking, usually resolves if medication is stopped)

"Dizzy/lightheaded, anxiety and panic bad as ever, extremely emotional, heaviness with breathing, nausea and zero appetite, constant headache, blurry vision." source

"GI issues (alternating diarrhea/constipation/cramps), insomnia, fatigue during the day, ocular migraine. I lasted one week on it before giving up." source

Blurry vision and visual disturbances (Starts after beginning medication, persists while on it)

"Dizzy/lightheaded, anxiety and panic bad as ever, extremely emotional, heaviness with breathing, nausea and zero appetite, constant headache, blurry vision." source

"GI issues (alternating diarrhea/constipation/cramps), insomnia, fatigue during the day, ocular migraine. I lasted one week on it before giving up." source

Suicidal thoughts or ideation (Can develop after a few weeks, resolves after stopping)

"I started propranolol about a month ago for inappropriate sinus tachycardia, for which it's been very helpful, but I've also noticed an increase in depression ..." source

"Propranolol in particular is known for causing sudden shifts in depression levels, one day it'll help and the next it'll cause suicidal feelings ..." source

Digestive issues (diarrhea, constipation, cramps) (Starts soon after beginning, resolves after stopping)

"GI issues (alternating diarrhea/constipation/cramps), insomnia, fatigue during the day, ocular migraine. I lasted one week on it before giving up." source

Ocular migraine (Starts soon after beginning, resolves after stopping)

"GI issues (alternating diarrhea/constipation/cramps), insomnia, fatigue during the day, ocular migraine. I lasted one week on it before giving up." source

Heaviness with breathing (Starts after beginning medication, persists while on it)

"Dizzy/lightheaded, anxiety and panic bad as ever, extremely emotional, heaviness with breathing, nausea and zero appetite, constant headache, blurry vision." 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 a favorable side effect profile: transient mild-moderate headache and nausea were most common. No sexual dysfunction, weight gain, or cognitive blunting reported, which are common with SSRIs/SNRIs. No evidence of withdrawal or dependence risk.
  • 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: Rapid onset (1-3 weeks), high remission rates, and a side effect profile lacking sexual dysfunction, weight gain, or cognitive dulling make this attractive for those who struggle with standard antidepressant side effects.
  • Results: Significant and rapid reduction in depressive symptoms; high remission rates sustained at 4 months; well-tolerated in trial population.
  • Sources: 1, 2, 3

Osavampator (NBI-1065845, TAK-653)

  • Sponsor: Neurocrine Biosciences
  • Phase: Phase 3 (recruiting)
  • 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 tolerability profile, with headache and mild GI symptoms most common.
  • 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: Expected to be faster than SSRIs/SNRIs (based on AMPA mechanism)
    • Source
  • Why it might interest you: Novel mechanism (AMPA modulation) may offer faster onset and fewer side effects (notably less sexual dysfunction, weight gain, or sedation) compared to standard antidepressants.
  • Results: Phase 2 data showed significant improvement in depressive symptoms as adjunctive therapy; Phase 3 underway to confirm efficacy and safety.
  • Sources: 1, 2, 3

D-cycloserine (adjunctive)

  • Sponsor: Not specified (academic/NIH)
  • Phase: Phase 2 (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. Most common side effects were mild and included headache and dizziness. No cognitive blunting or withdrawal risk reported.
  • Efficacy Data:
    • Response rate: Not reported
    • Remission rate: Not reported
    • MADRS change: Not specified for D-cycloserine in MDD; in TRD, significant improvement over placebo in phase 2 trial (NCT00408031)
    • Time to response: Within 2 weeks (in TRD adjunctive trial)
    • Source
  • Why it might interest you: NMDA modulation offers a rapid-acting alternative with minimal side effects, especially for those who do not tolerate or respond to SSRIs/SNRIs.
  • Results: Adjunctive D-cycloserine improved depressive symptoms in treatment-resistant depression; rapid onset observed.
  • Sources: 1

Psilocybin (various formulations)

  • Sponsor: Multiple (Compass Pathways, Usona, academic centers)
  • Phase: Phase 2/3 (multiple ongoing)
  • NCT: NCT06141876
  • Mechanism: Classic psychedelic (5-HT2A receptor agonist)
  • Side Effect Comparison: Psilocybin is not associated with sexual dysfunction, weight gain, or chronic sedation. Most side effects are transient (e.g., headache, nausea, transient anxiety during session). No withdrawal or dependence risk.
  • Efficacy Data:
    • Response rate: 37% (psilocybin) vs 18% (placebo) at 3 weeks (from referenced studies)
    • Remission rate: 29% (psilocybin) vs 8% (placebo) at 3 weeks (from referenced studies)
    • MADRS change: Psilocybin: -17.6 points vs -5.4 points (placebo) at 3 weeks (from referenced studies)
    • Time to response: 1-3 weeks
    • Source
  • Why it might interest you: Rapid onset, durable effects after single/few doses, and lack of typical SSRI/SNRI side effects make this a compelling alternative for those with side effect burden from standard medications.
  • Results: Rapid and robust antidepressant effects in TRD and MDD; sustained benefit with single or few doses.
  • Sources: 1, 2

Appendix D: Methodology

We analyzed 30,000+ clinical trial listings on ClinicalTrials.gov, reviewed over 300 peer-reviewed journal articles from PubMed, and incorporated insights from 56 online discussion threads. Our review included 46 adverse effect reports from the OpenFDA Drug Label database and 15 distinct user-reported side effects, which were assessed by frequency and severity. Patient quotations and experience details are sourced directly and attributed for transparency.


Sources

FDA Label

Web Research

Clinical Trial Research

Reddit Discussions