LORAZEPAM (Ativan) Side Effects Guide

Table of Contents

Intro

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Ativan (Lorazepam)

The Worst Side Effects

The Most Common Side Effects

Addiction and dependence

Rebound anxiety or increased anxiety after the effect wears off

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 Ativan (Lorazepam)

The Worst Side Effects

The Most Common Side Effects

Addiction and dependence

Rebound anxiety or increased anxiety after the effect wears off

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

In-depth Ativan (lorazepam) side effects guide: real-world risks, FDA data, severe withdrawal, timeline, top alternatives, and clinical trial options.

Medication: Ativan (LORAZEPAM) Drug Class: Benzodiazepine [EPC] Author: Michael Baskerville Gill, B. Sc.

Reviewed by the Power Medical Content Team

Intro

Day 1: That warm, drifting calm. Day 7: Sleep comes easier, maybe a little too often. Day 14: For some, the anxious undercurrent actually comes back, stronger. If you’re using Ativan (lorazepam)—whether it’s for panic, insomnia, or “just to take the edge off”—the timeline of side effects isn’t a straight line.

Here’s the double-edged sword: Ativan’s popularity is built on rapid, reliable relief. Nearly 20 million prescriptions in the U.S. each year, across ERs, psych clinics, and hospital wards. But for every tale of instant calm, there’s a quieter chorus about drowsiness, cravings, and a “hangover” that can spiral into rebound anxiety or full-on dependence. The clinical trial stats say one thing; the lived reality can look very different. The good, the bad, and the foggy—we’ll get under the hood, numbers and all.

Interested in clinical trials? Many trials for depression now target different mechanisms than Benzodiazepine [EPC]—potentially offering different side effect profiles. Browse clinical trials →

Side Effects Overview Table

Side Effect	FDA Rate	Reddit Reports	Severity	Duration	Example
Addiction and dependence	N/A	🟠 Frequent (13 posts)	🟡 Moderate	Ongoing/after stopping	"It worked like magic and I found that I could potentially get addicted to it because it literally made me feel high."
Drowsiness and sedation	3.5-6%	🟡 Occasional (7 posts)	🟡 Moderate	Hours to days	"Ativan always knocks me out for what feels like DAYS."
Rebound anxiety/increased anxiety after effect wears off	N/A	🟡 Occasional (6 posts)	🟡 Moderate	Hours to days after stopping	"For 2 or 3 days I really felt it, increased panic and anxiety, increased heart rate, probably blood pressure too."
Dizziness or feeling lightheaded	0.1%	🟢 Rare (3 posts)	🟡 Moderate	Hours to 1 day	"Dizziness is a pretty common side effect as is mood crash after it wears off."
Depression or worsening depression	N/A	🟢 Rare (3 posts)	🟡 Moderate	Ongoing/with use	"I think it might be making my depression worse, too."
Irritability	0.1%	🟢 Rare (2 posts)	🟢 Mild	Few hours–1 day	"Maybe some mild irritability ..."
Disconnection from reality/derealization	N/A	🟢 Rare (2 posts)	🟡 Moderate	Hours	"I feel disconnected from reality ..."
Loss of appetite	N/A	🟢 Rare (1 post)	🟢 Mild	Hours	"Loss in appetite."
Memory loss/amnesia	0.05%	🟢 Rare (1 post)	🟡 Moderate	Ongoing/with use	"What is your experience with memory loss?"
Exhaustion and fatigue	N/A	🟢 Rare (1 post)	🟡 Moderate	Days	"That alone could leave a person pretty exhausted for a few days."
Feeling foggy or tipsy	N/A	🟢 Rare (1 post)	🟢 Mild	Hours	"Very foggy and almost like I was tipsy."
→ View all 80 side effects from FDA trials
→ View all 11 user-reported side effects

How Other Drugs Compare

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

Metric	Ativan (Benzodiazepine [EPC])	CYB003 (Deuterated Psilocybin Analog)	Osavampator (AMPA-PAM)	D-cycloserine (NMDA partial agonist)
MECHANISM
Drug class	Benzodiazepine	Psychedelic analogue	Glutamate modulator	NMDA modulator
How it works	Enhances GABA activity to suppress brain activity rapidly	5-HT2A receptor agonist; psychedelic effect, rewiring mood circuits	Increases AMPA receptor activity, boosting synaptic strength	Partially stimulates NMDA receptors for neuroplasticity
EFFICACY
Response rate	N/A (for depression); ~70% for acute anxiety	53.3% (3 weeks MDD)	Phase 3 ongoing	Phase 2: significant TRD improvement
Remission rate	N/A (not for chronic depression)	75% at 4 months	Not yet reported	Not reported
Time to effect	30–60 min (anxiety relief)	1-3 weeks	Under 2 weeks?	Weeks (adjunctive)
KEY SIDE EFFECTS
Addiction/dependence	Frequent	None observed	None reported	None reported
Sedation/fatigue	3.5–6%	Transient, session-bound	None reported	None reported
Cognitive issues (amnesia, fog)	Up to 0.05–0.8%	None persistent	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	Drowsiness, fatigue, foggy feeling	Startup effects	Trouble breathing, severe confusion
Week 2–3	Sleep changes, dependency signals, rebound anxiety	Mild withdrawal	Heightened or new anxiety after missed dose
Week 4–6	Dependency risk rises, some report depression	May stabilize if used sparingly	Tolerance, craving doses earlier
Week 6–8	Memory/focus issues if used daily, possible withdrawal	Should be managed on as-needed basis	Any uncontrolled symptoms

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 Ativan (Lorazepam)

How does a pill that sometimes makes people feel drunk, sleepy, and stuck in bed still end up on so many prescription pads?

Ativan works by boosting the activity of GABA—a brain chemical that dampens neuron firing and calms the nervous system. By enhancing GABA signaling at its receptor (a protein on brain cells that responds to this inhibitory chemical), Ativan can shut down anxiety, panic, and agitation within minutes to hours. Think of it as slamming the brakes on an overactive brain.

But those brakes affect more than just panic: the same mechanism that dials down anxiety also blunts alertness, slows reaction time, and clouds short-term memory. This is why you get the drowsy/foggy feeling, and why addiction is a risk if you use it regularly. And yet, Ativan keeps its place in the toolkit because when you truly need fast relief—acute panic, catatonia, seizures, or pre-procedure nerves—there’s little else that works as reliably, or as fast, with such a well-mapped side effect landscape.

The Worst Side Effects

Addiction and dependence (moderate; 8/13 users):

"It's super addictive, I was taking it at about 5pm everyday and after about a week (might have been 2) by 4.45pm I was very anxious, irritable ..." source

Reported as moderate or worse by 8 of 13 users.
Management tip: Limit use to the shortest possible period; if craving or using earlier than scheduled, talk to your doctor immediately about a taper. Never stop abruptly.

Rebound anxiety/increased anxiety after effect wears off (moderate; 4/6 users):

"For 2 or 3 days I really felt it, increased panic and anxiety, increased heart rate, probably blood pressure too. Maybe some mild irritability ..." source

4 of 6 users reported this as moderate.
Management tip: Use only as-needed, not daily if possible. Consider switching to a medication with a longer half-life or a non-benzodiazepine if rebound symptoms are severe.

Memory loss or amnesia (moderate; 1/1 users):

"Benzodiazepines (Ativan, Xanax, etc) is a big trigger if you take those. Ask your ..." source

Moderate, can persist after stopping—particularly with long-term use.
Management tip: If you notice repeated forgetfulness or "lost time," review your dose and frequency with your doctor. Memory returns gradually after stopping, but recovery may take weeks to months after heavy use.

How Clinical Trials Compare

CYB003 Phase 2: No reports of addiction/dependence, sedation, or cognitive dulling—in contrast, up to 3.5–6% of Ativan users report significant drowsiness/sedation in trials and up to 10% report cognitive side effects in some studies. CYB003 results

→ Find trials with lower rates of these side effects

The Most Common Side Effects

Addiction and dependence

FDA: N/A | Reddit: 13 reports (moderate, ongoing)
What helps: Strictly limit use, avoid daily dosing, plan regular check-ins for review. Risk rises fast after a few doses.
Timeline: Can begin in 1–2 weeks; persistent after stopping for some.
Quote: "I got off it quick and got ..." source

Drowsiness and sedation

FDA: 3.5–6% | Reddit: 7 reports (moderate)
What helps: Dose at night if possible, avoid driving or heavy machinery after dosing, discuss dose adjustment.
Timeline: Immediate (30–60 minutes), can linger several hours to a day.
Quote: "Ativan always knocks me out for what feels like DAYS."

Rebound anxiety/increased anxiety after effect wears off

FDA: N/A | Reddit: 6 reports (moderate)
What helps: Avoid daily use, set alarms for consistent scheduling, watch for signs of emerging anxiety after a dose fades.
Timeline: Appears as drug wears off, may last 1–2 days after stopping.
Quote: "I was very anxious, irritable ... by 4.45pm ..." source

Dizziness or feeling lightheaded

FDA: 0.1% | Reddit: 3 reports (moderate)
What helps: Rise slowly from sitting, hydrate, split doses if feasible.
Timeline: Starts 30–60 minutes after dosing, resolves in hours.
Quote: "Dizziness is a pretty common side effect ..."

Depression or worsening depression

FDA: N/A | Reddit: 3 reports (moderate)
What helps: Log mood daily, screen for underlying depression before starting, alert your provider if mood worsens.
Timeline: Can start within days, typically persists while using.
Quote: "I think it might be making my depression worse, too."

Irritability

FDA: 0.1% | Reddit: 2 reports (mild)
What helps: Track timing of irritability; if persistent, review other medications and consider alternative anxiety treatments.
Timeline: Occurs as medication wears off, resolves in a day or two.
Quote: "Maybe some mild irritability ..."

Disconnection from reality/derealization

FDA: N/A | Reddit: 2 reports (moderate)
What helps: Reduce dose, switch dosing time, or trial alternative med if this is persistent or distressing.
Timeline: Starts soon after dosing, fades as drug leaves system.
Quote: "I feel disconnected from reality ..."

→ Find clinical trials that may avoid this side effect

Addiction and dependence

Let’s not mince words: "It worked like magic and I found that I could potentially get addicted to it because it literally made me feel high" source. Ativan’s ability to melt anxiety comes at a cost—use it daily and the risk of dependence rises at a brisk jog, not a lazy amble.

Cravings? "After the 3rd dose, I started craving it." source. For most, dependence can start in as little as 1–2 weeks of regular use. The FDA boxed warning doesn’t sugarcoat it: misuse and addiction can lead to overdose or death, and withdrawal can be life-threatening.

The mechanism’s simple: Benzodiazepines (like lorazepam) flood GABA-A receptors (proteins that calm the brain), teaching your brain that peace comes from a pill. When you try to stop suddenly, your nervous system is left high and dry—hence the notorious withdrawal.

What helps?

Never use daily unless absolutely necessary
Set a strict time/duration plan with your doctor
If you find yourself "clock-watching" for the next dose, flag this early—don’t try to "white-knuckle" through cravings

FDA rate vs Reddit:

FDA label gives no clinical trial percentage, but labels addiction risk as boxed warning. Reddit shows 13 reports, moderate severity, usually ongoing until tapered off.

Bottom line: Ativan can be a life raft in a storm. Just make sure you’re not building your house on it.

Rebound anxiety or increased anxiety after the effect wears off

One of the great ironies: The very med prescribed to silence your anxiety can sometimes spin the dial back up the second it leaves your system.

"It's super addictive, I was taking it at about 5pm everyday and after about a week (might have been 2) by 4.45pm I was very anxious, irritable ..." source

"You probably went 4 days without anxiety, and then when you stopped, your ..." source

Mechanistically, your brain adapts fast. Ativan cranks up GABA-A activity (inhibitory signals), but when that support gets yanked, you’re left with a GABA deficit and a nervous system in overdrive. It’s especially common in short half-life (how long the drug stays active in your body) benzos like lorazepam.

What helps?

Avoid daily dosing; use "as-needed" when possible
Consider a benzo with a longer half-life if rebound is unavoidable (clonazepam, diazepam)
Track rebound symptoms—are they actually new anxiety, or withdrawal?
Discuss alternatives with your provider if this cycle is persistent

FDA vs Reddit:

No FDA label percentage, but the mechanism is well-established.
Reddit: 6 reports, moderate severity, often appears after just a week or two of regular dosing.

Discontinuation & Withdrawal

Here’s the not-so-fun plot twist: stopping Ativan suddenly can trigger not just anxiety, but full-body withdrawal—seizures, confusion, even death in rare cases. Clinical trials barely scratch the surface, but patient stories spell it out.

Roughly 50% of patients on long-term benzodiazepines report some kind of withdrawal symptom. Symptoms can start within 8–24 hours of the last dose and peak in the first week. Lorazepam’s half-life (how long the drug stays active in your body) is about 10–20 hours: short enough that withdrawal comes on fast.

Typical withdrawal effects include:

Rebound anxiety
Insomnia
Irritability
Tremors
(In severe cases) Seizures, psychosis

Management tips:

Taper slowly: reduce dose by 10–25% every 1–2 weeks (customize to your experience)
Always taper under a doctor’s supervision
Avoid alcohol and other CNS depressants during withdrawal

Timeline:

Symptoms may start in 8–24 hours, peak at 2–7 days, resolve within weeks for most, but persistent psychological symptoms can linger longer.

And don’t just stop because you find out you’re pregnant, feel better, or run out of pills—always, always taper with guidance.

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Anxiety	2–3 mg per day in divided doses	2–6 mg per day (divided)	10 mg per day
Insomnia	2–4 mg at bedtime	2–4 mg at bedtime	10 mg per day
Pre-anesthesia	0.05 mg/kg IM, 2 hours before	2–4 mg IM	4 mg IM
Status epilepticus (IV)	4 mg initially	May repeat once	N/A

Doses should be tailored for the frail/elderly and those with hepatic impairment. Side effects (especially sedation and amnesia) are dose-related: higher doses = higher risk.

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

Buspirone – A gentle nudge at serotonin receptors (proteins that respond to serotonin, a brain chemical for mood). Not habit-forming, but can take weeks to work. No sedation.
SSRIs/SNRIs (e.g., sertraline, venlafaxine) – Build up slowly, low addiction risk, but bring their own baggage (sexual dysfunction, sometimes insomnia or weight gain).
Hydroxyzine – Old-school antihistamine, sedating but not addictive; no withdrawal, but may cause drowsiness.
Beta-blockers (e.g., propranolol) – Blunt physical symptoms (heart racing), especially handy for public speaking.
Non-habit forming sleep aids – Melatonin, CBT-I (cognitive behavioral therapy for insomnia), trazodone.

Which avoids your worst side effect? If addiction/dependence is the issue, buspirone or SSRIs/SNRIs are better bets. If drowsiness is the problem, buspirone or beta-blockers tend to win.

→ Compare your options on WithPower

Clinical Trials

CYB003 (deuterated psilocybin analog) [NCT06141876] — A one-off dosing session, not a daily pill; lacks chronic sedation, sexual dysfunction, or cognitive fog. High remission (75% at 4 months), rapid effect (within 1-3 weeks) source.
Osavampator (AMPA-PAM) — Non-sedating, no addiction/dependence signals, may work faster than SSRIs, currently in Phase 3 source.
D-cycloserine — Adds neuroplasticity, avoids sedation and withdrawal issues; for treatment-resistant cases source.
Psilocybin (classic, COMPASS Pathways) — Transient anxiety/headache only, zero reports of sedation/dependence source.

Why try a trial?

Access to experimental medications with unique mechanisms (not just another benzo or SSRI)
Typically includes close monitoring, free medication, and medical supervision
Phase 2 ≠ proven: rapid effect and clean side-effect profiles still need confirmation

You might skip months of trial-and-error, or you might find a next-gen treatment actually feels "cleaner."

Interested in clinical trials? Many trials for depression now target different mechanisms than Benzodiazepine [EPC]—potentially offering different side effect profiles. Browse clinical trials →

Decision Map

If addiction/dependence is the dealbreaker → Try buspirone or SSRIs (sertraline, escitalopram), OR CYB003/Osavampator trials
If drowsiness/fatigue is the dealbreaker → Buspirone, beta-blockers, or Osavampator, D-cycloserine trials
If rebound anxiety is the dealbreaker → Hydroxyzine, beta-blockers, or Psilocybin trials
If memory loss/cognitive fog is the dealbreaker → Buspirone, SSRIs, or CYB003, Osavampator, D-cycloserine trials

Nobody gets out of the side effect casino scot-free, but the odds really do shift between classes.

Ativan (lorazepam) - antidepressant medication Image: 123RF

Monitoring & What to Track

Your doctor should track:

Severity of your anxiety (GAD-7) or insomnia scale
Signs of dependence: dose escalation, craving, withdrawal symptoms
Suicidal ideation, especially first few weeks or if depression worsens
Memory, coordination, and drowsiness levels
Liver function (rarely, if on high doses or multiple CNS depressants)

What YOU should track:

Daily mood/anxiety log (rate 1–10)
Exact time and dose of each pill
Any craving or clock-watching
Side effects (timing, severity)
Sleep hours and sleep quality

If your doctor isn't tracking these, ask them to—especially dependence and memory changes.

Pregnancy & Breastfeeding

Ativan is FDA Pregnancy Category D: there is positive evidence of human fetal risk, but potential benefits may warrant use in pregnant women in serious situations. Risks specific to benzodiazepines include floppy infant syndrome, withdrawal in newborns (irritability, feeding difficulties, respiratory depression), and potential birth defects. If you’re breastfeeding, Ativan passes into breast milk and can sedate the infant—apnea and poor feeding have been reported.

Still, severe untreated anxiety, panic, or seizures also pose real risk to mother and fetus. This is a genuine risk-benefit discussion—not a simple yes/no. If you become pregnant, do NOT stop suddenly; your doctor will help taper or select a safer alternative if possible.

Emergency Warning Signs

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

Suicidal thoughts or plans
Severe breathing trouble, slow or absent breathing
Coma or unresponsiveness
Seizures (if tapering or after rapid discontinuation)
Profound sedation: cannot be awakened
Severe allergic reaction: rash, swelling, difficulty breathing
Signs of heart issues: chest pain, fainting, irregular heartbeat

📞 Call your doctor urgently if:

New or severe confusion
Worsening depression or agitation
Unusual bleeding or bruising
Memory loss or unsteady gait
Any sign of withdrawal (tremor, hallucinations, agitation)

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

Summary & Next Steps

Key takeaways: Ativan delivers rapid relief, but the real-world risk of addiction (13 reports, frequent, moderate severity) and rebound anxiety (6 reports, moderate) is substantial—often beginning within weeks. Drowsiness affects 3.5–6% in trials, with Reddit users echoing "persistently drunk" or "knocked out" experiences. Withdrawal can be severe: never stop abruptly.

If Ativan is working for you: Stick to the lowest dose, as-needed only, and monitor closely for increasing use or cravings. Watch for memory issues and drowsiness, especially if driving or making big decisions.

If side effects are intolerable:

Talk to your doctor about dose adjustment or a gradual taper
Explore alternatives: buspirone, SSRIs, hydroxyzine for anxiety; beta-blockers for performance anxiety
Consider clinical trials for next-gen treatments with lower risks (psilocybin analogs, AMPA modulators)

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
pain and burning at injection site (IM)	17%	0%	very common	Dermatologic
somnolence	3.5%	0%	common	Nervous System
redness at injection site (IV)	2.5%	0%	common	Dermatologic
hypotension	2.4%	0%	common	Cardiovascular
respiratory failure ⚠️	2.4%	0%	common	Respiratory
redness at injection site (IM)	2%	0%	common	Dermatologic
pain at injection site (IV)	1.6%	0%	common	Dermatologic
restlessness	1.3%	0%	uncommon	Psychiatric
crying/sobbing/delirium	1.3%	0%	uncommon	Psychiatric
headache	1.2%	0%	common	Nervous System
apnea	1.2%	0%	common	Respiratory
coma ⚠️	1.2%	0%	common	Nervous System
hypoventilation	1.2%	0%	common	Respiratory
stupor	1.2%	0%	common	Nervous System
respiratory disorder	1.2%	0%	common	Respiratory
airway obstruction ⚠️	1.1%	0%	uncommon	Respiratory
hallucinations	1%	0%	uncommon	Psychiatric
infection	0.8%	0%	uncommon	Infection
abnormal liver function tests	0.8%	0%	uncommon	Metabolic
nausea	0.8%	0%	uncommon	Gastrointestinal
vomiting	0.8%	0%	uncommon	Gastrointestinal
acidosis	0.8%	0%	uncommon	Metabolic
brain edema	0.8%	0%	uncommon	Nervous System
convulsion	0.8%	0%	uncommon	Nervous System
thinking abnormal	0.8%	0%	uncommon	Nervous System
hyperventilation	0.8%	0%	uncommon	Respiratory
injection site reaction	0.8%	0%	uncommon	Dermatologic
cystitis	0.8%	0%	uncommon	Urogenital
agitation	0.8%	0%	uncommon	Psychiatric
confusion	0.8%	0%	uncommon	Nervous System

Boxed Warnings (Most Serious)

Profound sedation, respiratory depression, coma, and death may result from concomitant use of benzodiazepines and opioids.
Risk of abuse, misuse, and addiction, which can lead to overdose or death.
Clinically significant physical dependence and life-threatening withdrawal reactions may occur, especially with prolonged use or abrupt discontinuation.

Drug Interactions

Opioids: Increased risk of profound sedation, respiratory depression, coma, and death.
Other CNS depressants (ethyl alcohol, phenothiazines, barbiturates, MAO inhibitors, antidepressants): Additive CNS depression.
Scopolamine: Increased incidence of sedation, hallucinations, and irrational behavior.
Loxapine: Rare reports of significant respiratory depression, stupor, and/or hypotension.
Clozapine: Marked sedation, excessive salivation, ataxia, and rarely, death.
Haloperidol: Apnea, coma, bradycardia, arrhythmia, heart arrest, and death.
Valproate: Decreases lorazepam clearance by 40%; reduce lorazepam dose by 50%.
Oral contraceptive steroids: Increases lorazepam clearance; may require increased lorazepam dose.
Probenecid: Prolongs lorazepam half-life by 130%, decreases clearance by 45%; reduce lorazepam dose by 50%.
No significant interaction with metoprolol, cimetidine, ranitidine, disulfiram, propranolol, metronidazole, or propoxyphene.

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?
Addiction and dependence	13 posts	🟡 Moderate (8/13)	Ongoing with repeated use; cravings can start after a few doses or within 1-2 weeks	⚠️ Yes
Drowsiness and sedation	7 posts	🟡 Moderate (4/7)	Several hours to days; can feel persistent if used regularly	Resolves
Rebound anxiety or increased anxiety after the effect wears off	6 posts	🟡 Moderate (4/6)	Several hours to days after dose wears off or during withdrawal	⚠️ Yes
Dizziness or feeling lightheaded	3 posts	🟡 Moderate (2/3)	Several hours to a day after taking	Resolves
Depression or worsening depression	3 posts	🟡 Moderate (2/3)	Ongoing or worsens with use; may persist as long as taking medication	Resolves
Irritability, especially during withdrawal or rebound	2 posts	🟢 Mild (2/2)	A few hours to a day, especially during withdrawal or after effect wears off	Resolves
Disconnection from reality or derealization	2 posts	🟡 Moderate (1/2)	Several hours after taking; resolves as drug wears off	Resolves
Loss of appetite	1 posts	🟢 Mild (1/1)	Several hours after taking	Resolves
Memory loss or amnesia	1 posts	🟡 Moderate (1/1)	Ongoing with use; can persist after stopping if used long-term	⚠️ Yes
Exhaustion and fatigue	1 posts	🟡 Moderate (1/1)	Several days after use	Resolves
Feeling foggy or tipsy	1 posts	🟢 Mild (1/1)	Several hours after taking	Resolves

User Quotes by Side Effect

Addiction and dependence (Cravings and dependence can start after a few doses, often within 1-2 weeks of regular use; persists as long as medication is used and can continue after stopping)

"It worked like magic and I found that I could potentially get addicted to it because it literally made me feel high. I got off it quick and got ..." source

"At first it worked really well. I took one fourth of a pill to make it last longer, and had no issues. After the 3rd dose, I started craving it." source

"It's super addictive, I was taking it at about 5pm everyday and after about a week (might have been 2) by 4.45pm I was very anxious, irritable ..." source

Drowsiness and sedation (Begins within 30-60 minutes of dose, peaks in first few hours, can last into the next day especially with repeated use)

"Ativan always knocks me out for what feels like DAYS. I felt like I was persistently drunk with no sight of a hangover or morning after in sight ..." source

"At most, that dose made me feel a bit tired. It's been such a helpful and positive tool for me, I ..." source

"I've taken it twice and it helps me feel somewhat calmer but I slept way too much and I don't feel rested." source

Rebound anxiety or increased anxiety after the effect wears off (Starts as the medication wears off (several hours after dose), peaks within 1-2 days, can persist for days after stopping)

"For 2 or 3 days I really felt it, increased panic and anxiety, increased heart rate, probably blood pressure too. Maybe some mild irritability ..." source

"It's super addictive, I was taking it at about 5pm everyday and after about a week (might have been 2) by 4.45pm I was very anxious, irritable ..." source

"You probably went 4 days without anxiety, and then when you stopped, your ..." source

Dizziness or feeling lightheaded (Begins within 30-60 minutes of taking, peaks in first few hours, usually resolves within a day)

"Dizziness is a pretty common side effect as is mood crash after it wears off." source

"The effects are so strong: I get incredibly dizzy, I feel disconnected from reality and I've noticed a pretty serious loss in appetite." source

Depression or worsening depression (Can start after first few doses, may persist as long as medication is used)

"I've taken it twice and it helps me feel somewhat calmer but I slept way too much and I don't feel rested. I think it might be making my depression worse, too." source

"I am currently on 2mg for sleep but they don't seem to help. Are there other medication others have tried with success?" source

Irritability, especially during withdrawal or rebound (Occurs as medication wears off or during withdrawal, resolves within a day or two)

"For 2 or 3 days I really felt it, increased panic and anxiety, increased heart rate, probably blood pressure too. Maybe some mild irritability ..." source

"It's super addictive, I was taking it at about 5pm everyday and after about a week (might have been 2) by 4.45pm I was very anxious, irritable ..." source

Disconnection from reality or derealization (Begins within 30-60 minutes of taking, peaks in first few hours, resolves as drug wears off)

"The effects are so strong: I get incredibly dizzy, I feel disconnected from reality and I've noticed a pretty serious loss in appetite." source

Loss of appetite (Begins within 30-60 minutes of taking, resolves as drug wears off)

"The effects are so strong: I get incredibly dizzy, I feel disconnected from reality and I've noticed a pretty serious loss in appetite." source

Memory loss or amnesia (Can develop with ongoing use, may persist after stopping especially with long-term use)

"Benzodiazepines (Ativan, Xanax, etc) is a big trigger if you take those. Ask your ..." source

Exhaustion and fatigue (Begins after stopping or after heavy use, can last several days)

"If he was completely taken off medication suddenly and then had 4 seizures, that alone could leave a person pretty exhausted for a few days." source

Feeling foggy or tipsy (Begins within 30-60 minutes of taking, resolves as drug wears off)

"Even at a low dose I just wasn't a fan of how it made me feel - very foggy and almost like I was tipsy." source

Appendix C: Clinical Trials with Different Mechanisms

These trials target mechanisms different from Benzodiazepine [EPC]. 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: Transient mild-to-moderate headache, nausea, and anxiety during dosing session; no persistent sexual dysfunction, weight gain, or sedation as seen with SSRIs/SNRIs. No daily dosing required, reducing chronic side effect burden.
Efficacy Data:
- Response rate: 53.3% (CYB003) vs 19.4% (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. Novel mechanism may help those not responding to standard drugs.
Results: Significant reduction in MADRS scores, rapid onset, high remission rates at 4 months, well-tolerated in trial population.
Sources: 1, 2, 3

Osavampator (NBI-1065845, TAK-653)

Sponsor: Neurocrine Biosciences
Phase: Phase 3
Mechanism: AMPA receptor positive allosteric modulator (AMPA-PAM)
Side Effect Comparison: Phase 2 data suggest lower rates of sexual dysfunction, weight gain, and sedation compared to SSRIs/SNRIs. No significant cognitive impairment or withdrawal risk reported.
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: Potentially faster than SSRIs (AMPA modulation)
- Source
Why it might interest you: AMPA modulation is a novel, non-monoaminergic mechanism with potential for faster onset and fewer side effects (notably less sexual dysfunction and weight gain) than standard antidepressants.
Results: Phase 2 data showed significant improvement in depressive symptoms as adjunctive therapy; Phase 3 underway to confirm efficacy and safety.
Sources: 1, 2, 3

D-cycloserine (adjunctive in TRD)

Sponsor: Not specified (academic/NIH)
Phase: Phase 2 (completed)
NCT: NCT00408031
Mechanism: NMDA receptor partial agonist (glycine site)
Side Effect Comparison: Generally well-tolerated; lacks sexual dysfunction, weight gain, and sedation typical of SSRIs/SNRIs. No significant cognitive impairment or withdrawal risk reported in trial.
Efficacy Data:
- Response rate: Not specified
- Remission rate: Not specified
- MADRS change: Not specified for D-cycloserine in MDD; in TRD, significant improvement over placebo in phase 2 trial (NCT00408031)
- Time to response: Within weeks (adjunctive use)
- Source
Why it might interest you: Novel glutamatergic mechanism, potential for rapid improvement, and a side effect profile that avoids the most common SSRI/SNRI issues.
Results: Adjunctive D-cycloserine improved depressive symptoms in treatment-resistant depression.
Sources: 1

Psilocybin (various sponsors, e.g., COMPASS Pathways)

Sponsor: Multiple (COMPASS Pathways, academic centers)
Phase: Phase 2/3
NCT: NCT06141876
Mechanism: Classic psilocybin (5-HT2A receptor agonist, psychedelic)
Side Effect Comparison: Transient anxiety, headache, and nausea during dosing; no persistent sexual dysfunction, weight gain, or sedation. No daily dosing required, reducing chronic side effect burden.
Why it might interest you: Single or few doses can produce rapid, durable antidepressant effects with minimal ongoing side effects, avoiding the chronic issues of standard antidepressants.
Results: Multiple studies show rapid and sustained antidepressant effects after 1-2 dosing sessions; FDA Breakthrough Therapy Designation for TRD.
Sources: 1, 2

Appendix D: Methodology

We analyzed over 30,000 clinical trial listings from ClinicalTrials.gov, 300+ peer-reviewed articles via PubMed, and scrutinized 53 online patient discussions in addition to 80 relevant OpenFDA Drug Label data entries. From these sources, 11 user-reported adverse effects were catalogued and prioritized based on mention frequency and severity. The evaluation included detailed duration patterns, comparative severity ratings, and curated patient quotations with direct source links for transparency.