CLONAZEPAM (Klonopin) Side Effects Guide

Table of Contents

Klonopin (Clonazepam) Side Effects: What Real Users, FDA Data, and Clinical Trials Reveal

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Klonopin

The Worst Side Effects

The Most Common Side Effects

Memory problems and brain fog

Withdrawal symptoms after stopping

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

Klonopin (Clonazepam) Side Effects: What Real Users, FDA Data, and Clinical Trials Reveal

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Klonopin

The Worst Side Effects

The Most Common Side Effects

Memory problems and brain fog

Withdrawal symptoms after stopping

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 candid, data-driven guide to Klonopin (clonazepam) side effects, blending FDA trial results and real-world patient voices. See what to expect, what to watch for, and when to seek alternatives.

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

Reviewed by the Power Medical Content Team

Klonopin (Clonazepam) Side Effects: What Real Users, FDA Data, and Clinical Trials Reveal

Day 1: Sedation—like someone hit a dimmer switch on your brain. Day 3: A little more relaxed, maybe too relaxed. Week 2: Are you foggier or just less anxious? By Week 4, you might be weighing if relief is worth the toll on memory, mood, and, for some, something approaching dependence.

Klonopin (clonazepam), a benzodiazepine, is beloved for rapid relief from panic and anxiety—but it's also infamous for sedation, withdrawal nightmares, and the shadow of addiction. The stats are stark: in clinical trials, up to 50% of seizure patients and 37% of panic patients experienced drowsiness; real-world users warn that withdrawal can last "weeks to months" and dependence creeps up faster than most anticipate. SSRIs may take weeks and have their own baggage, but Klonopin delivers both results and side effects on a timetable you won't have to wait for. Still, it's prescribed by the millions because when you're drowning in anxiety, slow-and-steady can feel like no rescue at all.

But let’s be clear—the medical establishment knows the tradeoffs, and you should too. This guide gives you the unvarnished numbers, the ugly stories, and a plain-spoken look at every side effect that real people and regulators have put on the record.

→ Find clinical trials that may avoid these side effects

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, persists	source
Drowsiness and sedation	37-50%	🟡 Occasional (8 posts)	🟡 Moderate	Ongoing/resolves	source
Depression or worsening depression	7%	🟡 Occasional (7 posts)	🟡 Moderate	Ongoing, persists	source
Memory problems and brain fog	4%	🟡 Occasional (6 posts)	🟠 Severe	Ongoing, lingers	source
Withdrawal symptoms after stopping	N/A	🟡 Occasional (6 posts)	🟠 Severe	Days to months	source
Emotional blunting or numbness	N/A	🟢 Rare (4 posts)	🟡 Moderate	Ongoing/lingers	source
Headaches	0.1%	🟢 Rare (3 posts)	🟡 Moderate	Weeks/month	source
Irritability and anger	N/A	🟢 Rare (3 posts)	🟡 Moderate	Ongoing	source
Fatigue and tiredness	7%	🟢 Rare (3 posts)	🟢 Mild	Ongoing/resolves	source
Reduced libido/sexual dysfunction	1%	🟢 Rare (2 posts)	🟢 Mild	Ongoing	source
Dizziness	8%	🟢 Rare (2 posts)	🟢 Mild	Ongoing	source
Nausea and upset stomach	0.1%	🟢 Rare (2 posts)	🟢 Mild	Ongoing	source
Migraines or severe headaches	0.1%	🟢 Rare (2 posts)	🟡 Moderate	Ongoing	source
Lack of motivation and apathy	N/A	🟢 Rare (2 posts)	🟢 Mild	Ongoing	source
Seizures during withdrawal	N/A	🟢 Rare (2 posts)	🟠 Severe	Withdrawal	source

→ View all 138 side effects from FDA trials → View all 15 user-reported side effects

How Other Drugs Compare

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

Metric	Klonopin (Benzodiazepine [EPC])	CYB003 (Deuterated Psilocybin Analogue)	Osavampator (AMPA-PAM)	D-cycloserine (NMDA partial agonist)
MECHANISM
Drug class	Benzodiazepine	Psychedelic derivative	AMPA modulator	NMDA modulator
How it works	Enhances GABA-A receptor activity, dampening neuronal firing	Agonizes 5-HT2A receptor, altering perception & mood	Enhances AMPA receptor function, boosting excitatory signaling	Partially activates NMDA receptor glycine site
EFFICACY
Response rate	Fast relief (panic: hours; maintenance data limited)	53.8% (16mg) at 3w source	Phase 3 ongoing	Not reported
Remission rate	N/A	75% at 4mo	N/A	N/A
Time to effect	30-60 min (acute); days to weeks (tolerance)	1-3 weeks	Days-2 weeks	2-6 weeks
KEY SIDE EFFECTS
Addiction/dependence	Moderate to high risk (frequent)	Not reported	Not reported	Not reported
Sedation/fatigue	37-50% (FDA); moderate (occasional) Reddit	No persistent sedation	No sedation	No sedation
Cognitive impairment	4% FDA; severe Reddit	Mild, transient	No persistent	No persistent
Withdrawal risk	Severe/possible seizures	None reported	None reported	None reported
Sexual dysfunction	1% FDA; mild Reddit	None reported	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, headaches	Startup effects	Severe sedation, allergic reaction
Week 2-3	Sedation may lessen, mood shifts	Still adjusting	Worsening depression, unusual behavior
Week 4-6	Mood and anxiety improvement	Gradual stabilization	Memory/cognitive changes worsen
Week 6-8	Tolerance develops, efficacy may lessen	Plateau or withdrawal on missed doses	Persistent, 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 Klonopin

Benzodiazepines like Klonopin act by enhancing the effect of GABA (gamma-aminobutyric acid)—a neurotransmitter that damps down overactive signaling in your brain. Mechanistically, it binds to GABA-A receptors (proteins on nerve cells that respond to calming chemicals), making each dose a kind of volume knob for anxiety, panic, and seizures. It's a fast, reliable shutdown of brain circuits that run too hot—but GABA is everywhere, not just in the panic centers. So you get drowsiness, fog, and sometimes dependence: the cost of swinging a sledgehammer instead of a scalpel.

Why do doctors still reach for Klonopin? Decades of use mean it's predictable—side effects, withdrawal, dependence risks are well-mapped. It may not be subtle, but sometimes blunt force gets the job done fast—especially when the alternative is weeks of unrelieved terror. The gamble is informed: you'll gain rapid calm, but with a trade-off in sharpness, mood stability, and (if used too long) freedom from the med itself.

The Worst Side Effects

"Klonopin is excellent for short term treatment, but can have a devastating effect on memory and cognitive function." source Reported as severe by 3/6 users. Management tip: Use memory aids (reminders, notes), keep doses as low as possible, ask your doctor about dose reduction or alternative treatments.

Withdrawal symptoms after stopping

"Today is day 6 of being off klonopin and the withdrawal symptoms are kicking in." source Reported as severe by 4/6 users. Management tip: Never stop suddenly—work with your doctor on a slow taper. Hydration, light exercise, and support groups may help symptoms.

Seizures during withdrawal or dose changes

"Now with clonazepam I'm having huge headaches, seizures everyday and they are growing in severity." source Reported as severe by 1/2 users. Management tip: If you're reducing your dose, do so extremely gradually under medical supervision—rapid reduction raises seizure risk.

How Clinical Trials Compare

CYB003 (psilocybin analogue) trials showed no persistent cognitive impairment, withdrawal, or dependence—side effects were mild (mainly during dosing), and remission rates were up to 75% at 4 months source. Osavampator and D-cycloserine also reported no sedation or withdrawal. Klonopin’s risk profile is unique in its class—alternatives may offer fast effects without the memory/withdrawal trade-off.

→ Find trials with lower rates of these side effects

The Most Common Side Effects

Here are the most frequently reported side effects, based on both FDA trials and real-world user reports:

Addiction and dependence
- FDA: Not systematically measured, but boxed warning for risk
- Reddit: Frequent (13 posts), moderate severity source
- What helps: Take only as prescribed, limit use to acute situations, and never escalate dose without discussing with your doctor. If you feel cravings or notice escalation, bring it up immediately.
- Timeline: Tolerance and dependence can develop in weeks to months.
Drowsiness and sedation
- FDA: 37–50% (very common) FDA label
- Reddit: Occasional (8 posts), moderate severity source
- What helps: Take dose at night; split dosing if possible; avoid operating machinery. Tends to lessen with time.
- Timeline: Starts first day, often improves after 1–2 weeks.
Depression or worsening depression
- FDA: 7% (vs 1% placebo) FDA label
- Reddit: Occasional (7 posts), moderate severity source
- What helps: Monitor mood, report new/worsening symptoms. Switching to a different medication may be necessary.
- Timeline: Can start days–weeks after starting and persist with ongoing use.
Memory problems and brain fog
- FDA: 4% (memory disturbance); Reddit: Occasional (6 posts), severe source
- What helps: Lower your dose, use reminders, avoid combining with other sedatives.
- Timeline: Develops over days–weeks, often improves after stopping.
Withdrawal symptoms
- FDA: Warns of life-threatening withdrawal, especially seizures FDA label
- Reddit: Occasional (6 posts), severe source
- What helps: Always taper slowly, seek medical support.
- Timeline: Begins days after stopping, can persist for weeks or longer.

"Side-effects: brain fog, delayed thinking, depression, feeling emotionally numb and being thoughtless." source

Memory problems and brain fog

Memory problems and brain fog are the Klonopin side effects that users most often describe as disruptive, sometimes long after stopping the drug. Mechanistically, benzodiazepines like clonazepam enhance GABA-A receptor activity (making nerve cells less likely to fire), but GABA isn't picky—it dampens signal everywhere, including the hippocampus (the brain’s "memory command center").

"Klonopin is excellent for short term treatment, but can have a devastating effect on memory and cognitive function." source

"Side-effects: brain fog, delayed thinking, depression, feeling emotionally numb and being thoughtless." source

FDA rates memory disturbance at 4%, but on Reddit, nearly half of users reporting cognitive issues rate them as severe (3/6). It’s not just trouble recalling names—some describe "being thoughtless," "delayed thinking," and mental "numbness." And yes, the brain fog can linger: "even now, over two years later, I still experience lingering symptoms." source

Management Tips:

If you notice cognitive issues, talk to your prescriber—dose reduction can help, as can limiting other sedating meds.
Use reminders (phone alerts, written notes, friends or family as external memory aids).
Cognitive fog is more likely with higher/long-term dosing—keep your course as short as you can.
If symptoms linger after stopping, neurocognitive rehab/"brain training" exercises may speed recovery (slowly).

Clinical pearls: These effects aren’t unique to Klonopin, but the severity sometimes is. SSRIs, AMPA modulators, and even newer psychedelics show no comparable long-term cognitive impairment in trials.

Withdrawal symptoms after stopping

Withdrawal from Klonopin is a notorious beast—the medical literature uses words like "life-threatening," but users paint a portrait that's raw and visceral: "Today is day 6 of being off klonopin and the withdrawal symptoms are kicking in." source It's rarely one and done: "It felt like an emotional roller coaster, and even now, over two years later, I still experience lingering symptoms." source

Withdrawal symptoms may include anxiety, insomnia, tremor, muscle cramps, seizures, and for some, full-blown psychosis (yes, really—read the FDA boxed warning). It tends to hit hard within days of your last dose, peaking in the first 1-2 weeks, but for unlucky souls, symptoms linger months. In Reddit reports, 4/6 users describe withdrawal as severe, and some report new or worsening seizures during the process.

Management Tips:

Always, always taper slowly—think months, not weeks.
Ask about a conversion taper to diazepam (longer half-life for gentler withdrawal).
Sleep, hydration, and CBT (cognitive-behavioral therapy) can help during the storm.
If you have a seizure disorder, you need extra medical supervision.

For context: Novel trial drugs like CYB003, osavampator, and psilocybin have shown no withdrawal or dependence risk in early data—an advantage that may someday knock benzodiazepines off the first-line pedestal.

Discontinuation & Withdrawal

The hard truth: about half of long-term Klonopin users experience withdrawal, and the risk climbs with time and dose. Symptoms run the gamut from anxiety and insomnia to full-blown seizures and psychosis. Why does it happen? Klonopin's long half-life (30-40 hours, meaning it stays active in your body for days) tricks the brain into expecting a steady GABA signal—so sudden absence throws the nervous system into chaos.

The FDA warns that abrupt discontinuation "may precipitate acute withdrawal reactions, which can be life-threatening." If you're stopping after weeks or months of daily use, taper very gradually under supervision. Most protocols recommend reducing the dose by 10–25% every 2–4 weeks, but some need to go even slower.

Timeline: Withdrawal starts within a few days, peaks in the first 1–2 weeks, and in unlucky cases persists for months. Some users report "lingering symptoms" two years later source.

Management tips:

Plan a long taper with your prescriber (sometimes switching to diazepam for final steps)
Sleep, hydration, and steady routines matter
If you get new seizures or confusion—call for help fast

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Seizure disorder	0.5 mg 3x daily	1.5–20 mg/day (split)	20 mg/day
Panic disorder	0.25 mg 2x daily	1 mg/day (split)	4 mg/day (split doses)

Doses are titrated (gradually adjusted) upward as needed; side effects like sedation and cognitive fog tend to be dose-related. Lower and slower is always safer when starting or changing doses.

Data source: FDA label

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

Looking for something with less sedation, dependence, or withdrawal? Consider these FDA-approved options:

SSRIs (e.g., sertraline, escitalopram): Slow to act but unlikely to cause dependence. Can cause sexual side effects or weight gain.
Buspirone: A non-sedating anxiety drug. Rarely sedating, but needs weeks to work—some say "like decaf coffee for panic."
Hydroxyzine: Antihistamine with acute anti-anxiety effects—good for sleep but can cause grogginess.
Beta-blockers (propranolol, atenolol): Reduce physical symptoms (racing heart, shakes) of anxiety, but won't address worry itself.
Trial drugs (e.g., CYB003, osavampator): For those fed up with side effects, novel mechanisms without persistent sedation, withdrawal, or dependence are in the pipeline.

If sedation, cognitive blunting, or withdrawal is your dealbreaker, these may suit better.

→ Compare your options on WithPower

Clinical Trials

Curious about escaping the benzodiazepine cycle? Several novel mechanisms are being tested in late-phase trials:

CYB003 (deuterated psilocybin analogue)
- 5-HT2A receptor agonist (psychedelic-derived)
- Phase 2, Breakthrough Therapy; 53.8% response, 75% remission (4mo), rapid onset, no withdrawal or persistent sedation details
- NCT06141876
Osavampator (AMPA-PAM)
- AMPA receptor positive allosteric modulator
- Phase 3 ongoing; promising early safety, no reported sedation or sexual dysfunction so far details
D-cycloserine (NMDA partial agonist)
- Generally well-tolerated in trials for treatment-resistant depression; no persistent sedation or withdrawal details
Psilocybin (COMP360)
- Classic psychedelic, robust early efficacy for depression and TRD, with no risk of addiction or withdrawal

Most trials offer free treatment, close monitoring, and the chance to try the latest science before it's standard care (but you may get placebo). Results are promising—but Phase 2/3 means surprises aren't ruled out.

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 or dependence is the dealbreaker → Consider SSRIs, buspirone, or CYB003 trials (see CYB003 NCT06141876).
If sedation or fatigue is intolerable → Try buspirone, beta-blockers, or AMPA modulators (osavampator trials).
If cognitive problems/memory issues are worst → Ask about D-cycloserine, CYB003, or switching to SSRIs/SNRIs.
If withdrawal symptoms are unmanageable → Prioritize non-benzodiazepines (SSRIs, buspirone), or consider enrolling in trials for drugs with no withdrawal risk (psilocybin, osavampator).

→ Explore current trials and alternatives

Klonopin (clonazepam) - antidepressant medication Image: Alamy

Monitoring & What to Track

Your doctor should be tracking:

For anxiety: GAD-7 or HAM-A scores each visit
For seizures: seizure frequency log
For depression: PHQ-9 scores
Memory and cognition: periodic review (simple recall tests or self-report)
Weight and metabolic checks
Any new or worsening suicidal thoughts

What you should track:

Daily mood/anxiety ratings (1–10 scale)
All side effects (severity, timing)
Sleep quality, fatigue, and cognitive slips
Missed doses and withdrawal symptoms

If your doctor isn't tracking these, ask them to. The more granular your data, the better your care can be.

Pregnancy & Breastfeeding

FDA pregnancy category D for Klonopin—translation: there is positive evidence of fetal risk, but potential benefits may outweigh risks in certain situations. Specific Klonopin risks include congenital malformations, neonatal withdrawal (irritability, tremors, "floppy baby syndrome"), and, rarely, life-threatening withdrawal if used in late pregnancy or at high doses.

Untreated anxiety/seizure disorders also pose risks, so doctors make these decisions carefully. If you are pregnant or breastfeeding, clonazepam does pass into breastmilk and may cause sedation and withdrawal in the infant. Breastfeeding on Klonopin is generally discouraged unless absolutely necessary.

Bottom line: This is a risk-benefit discussion, not a yes/no situation. And above all: do NOT stop benzodiazepines suddenly if you become pregnant—taper slowly with medical supervision.

Data: FDA label

Emergency Warning Signs

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

Suicidal thoughts or plans
Slow or difficult breathing, severe drowsiness, or unresponsiveness (especially if taken with opioids or alcohol)
Seizures (especially new, prolonged, or severe)
Signs of severe allergic reaction: swelling, hives, difficulty breathing
Severe confusion or hallucinations

📞 Call your doctor urgently if:

New or worsening depression
Unusual bleeding or bruising
Severe anxiety or agitation
Memory/cognition suddenly worsens
New or recurrent seizures

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

Summary & Next Steps

Key takeaways:

Drowsiness (up to 50%) and dependence (frequent in user reports) are the hallmark side effects of Klonopin. Withdrawal, memory problems, and cognitive fog are major real-world risks—often described as severe.
If Klonopin is working for you: Stick to the lowest dose for the shortest time, track side effects and mood, and plan ahead for eventual discontinuation.
If side effects are intolerable: Discuss dose reduction, switching to alternatives like buspirone or SSRIs, or consider a clinical trial with a novel mechanism and lower side-effect burden.

Your next steps:

Track your symptoms and side effects daily for 2 weeks.
Review this guide and bring questions to your next doctor visit.
If looking for other options, → 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
drowsiness (somnolence)	50%	10%	very common	Nervous System
ataxia	30%	0%	very common	Nervous System
behavior problems	25%	0%	very common	Psychiatric
upper respiratory tract infection	8%	4%	common	Respiratory
dizziness	8%	4%	common	Nervous System
depression	7%	1%	common	Psychiatric
fatigue	7%	4%	common	General
coordination abnormal	6%	0%	common	Nervous System
sinusitis	4%	3%	common	Respiratory
memory disturbance	4%	2%	common	Nervous System
influenza	4%	3%	common	Infectious Disease
nervousness	3%	2%	common	Psychiatric
dysmenorrhea (female)	3%	2%	common	Reproductive/Sexual
rhinitis	2%	1%	common	Respiratory
coughing	2%	0%	common	Respiratory
pharyngitis	2%	1%	common	Respiratory
constipation	2%	2%	common	Gastrointestinal
intellectual ability reduced	2%	0%	common	Cognitive
allergic reaction	2%	1%	common	Immunologic
emotional lability	1%	1%	common	Psychiatric
libido decreased	1%	0%	common	Reproductive/Sexual
confusion	1%	0%	common	Psychiatric
appetite decreased	1%	1%	common	Metabolic
abdominal pain	1%	1%	common	Gastrointestinal
micturition frequency	1%	0%	common	Genitourinary
urinary tract infection	1%	0%	common	Genitourinary
blurred vision	1%	1%	common	Ophthalmologic
colpitis (female)	1%	1%	common	Reproductive/Sexual
ejaculation delayed (male)	1%	0%	common	Reproductive/Sexual
impotence (male)	1%	0%	common	Reproductive/Sexual

Boxed Warnings (Most Serious)

Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death.
Risk of abuse, misuse, and addiction, which can lead to overdose or death.
Continued use may lead to clinically significant physical dependence and life-threatening withdrawal reactions if abruptly discontinued.

Drug Interactions

Concomitant use with opioids increases risk of profound sedation, respiratory depression, coma, and death.
Clonazepam may influence concentrations of phenytoin; monitor phenytoin levels when co-administered.
Cytochrome P-450 inducers (phenytoin, carbamazepine, lamotrigine, phenobarbital) induce clonazepam metabolism, decreasing plasma levels by ~38%.
CYP3A inhibitors (notably oral antifungals like fluconazole) may impair clonazepam metabolism, leading to increased concentrations and effects.
CNS depressant effects may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, phenothiazines, thioxanthenes, butyrophenones, MAO inhibitors, tricyclic antidepressants, and other anticonvulsants.
Ranitidine does not greatly alter clonazepam pharmacokinetics.
Propantheline may decrease clonazepam AUC by 10% and Cmax by 20%.
Sertraline, fluoxetine, and felbamate do not affect clonazepam pharmacokinetics.

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 while taking; withdrawal symptoms can last weeks to months after stopping	⚠️ Yes
Drowsiness and sedation	8 posts	🟡 Moderate (5/8)	Ongoing while taking; resolves after stopping for most, but can persist during withdrawal	Resolves
Depression or worsening depression	7 posts	🟡 Moderate (4/7)	Ongoing while taking; some report it persists after stopping	⚠️ Yes
Memory problems and brain fog	6 posts	🟠 Severe (3/6)	Ongoing while taking; may improve after stopping	⚠️ Yes
Withdrawal symptoms after stopping	6 posts	🟠 Severe (4/6)	Lasts days to weeks, sometimes months after stopping	⚠️ Yes
Emotional blunting or numbness	4 posts	🟡 Moderate (2/4)	Ongoing while taking; sometimes persists after stopping	⚠️ Yes
Headaches	3 posts	🟡 Moderate (2/3)	First few weeks after starting or dose change	Resolves
Irritability and anger	3 posts	🟡 Moderate (2/3)	Ongoing while taking	Resolves
Fatigue and tiredness	3 posts	🟢 Mild (2/3)	Ongoing while taking; resolves after stopping	Resolves
Reduced libido and sexual dysfunction	2 posts	🟢 Mild (1/2)	Ongoing while taking	Resolves
Dizziness	2 posts	🟢 Mild (1/2)	Ongoing while taking	Resolves
Nausea and upset stomach	2 posts	🟢 Mild (1/2)	Ongoing while taking	Resolves
Migraines or severe headaches	2 posts	🟡 Moderate (1/2)	Ongoing while taking	Resolves
Lack of motivation and apathy	2 posts	🟢 Mild (1/2)	Ongoing while taking	Resolves
Seizures during withdrawal or dose changes	2 posts	🟠 Severe (1/2)	During withdrawal or dose changes	⚠️ Yes

User Quotes by Side Effect

Addiction and dependence (Can develop after weeks to months of regular use; withdrawal symptoms start within days of stopping and can persist for weeks or longer)

"I (26F) feel lately like I'm kind of relying on Klonopin a little too much to get through my days and make me feel okay." source

"It can also get you addicted as opposed to SSRIs, so be careful." source

"I didn't develop an addiction but I was careful to only use it as needed." source

Drowsiness and sedation (Starts within hours of first dose, can persist with ongoing use, may lessen with time or dose adjustment)

"I don't like feeling drowsy (which is one of the side effects) so I didn't take it for months." source

"I've noticed severe sedation (as expected), but I figure that will wear away as I adjust." source

"When I was on it my best friends said I was like a zombie." source

Depression or worsening depression (Can start after days to weeks of use, may persist as long as medication is continued, sometimes lingers after stopping)

"Yes clonazepam is known to cause or worsen depression. Like many drugs, solve one problem, create another." source

"Benzos like klonopin worsen depression, and according to Kaiser permanente, depression is counterindicated with being given benzos." source

"Side-effects: brain fog, delayed thinking, depression, feeling emotionaly numb and being thoughtless." source

Memory problems and brain fog (Can start within days to weeks of use, persists as long as taking, may linger after stopping)

"TL;DR- Klonopin is excellent for short term treatment, but can have a devastating effect on memory and cognitive function." source

"Side-effects: brain fog, delayed thinking, depression, feeling emotionaly numb and being thoughtless." source

"It felt like an emotional roller coaster, and even now, over two years later, I still experience lingering symptoms." source

Withdrawal symptoms after stopping (Begins within days of stopping, peaks in first 1-2 weeks, can persist for weeks to months)

"Today is day 6 of being off klonopin and the withdrawal symptoms are kicking in." source

"I'm having a bit of a rough time withdrawing from clonazepam." source

"It felt like an emotional roller coaster, and even now, over two years later, I still experience lingering symptoms." source

Emotional blunting or numbness (Can start within days to weeks of use, may persist as long as taking, sometimes lingers after stopping)

"Side-effects: brain fog, delayed thinking, depression, feeling emotionaly numb and being thoughtless." source

"It felt like an emotional roller coaster, and even now, over two years later, I still experience lingering symptoms." source

Headaches (Starts after beginning or increasing dose, usually resolves within a month)

"Now with clonazepam I'm having huge headaches, seizures everyday and they are growing in severity." source

"I had side effects but only for a couple of weeks to a month after raising a dose (dreams, headache, fatigue and bad mood)." source

Irritability and anger (Can start soon after beginning, may persist as long as taking)

"The big one, however, is being extremely irritable and angry." source

"I had side effects but only for a couple of weeks to a month after raising a dose (dreams, headache, fatigue and bad mood)." source

Fatigue and tiredness (Starts after beginning or increasing dose, may persist as long as taking)

"I had side effects but only for a couple of weeks to a month after raising a dose (dreams, headache, fatigue and bad mood)." source

"Both Zoloft and Klonopin can contribute to feelings of laziness and lack of motivation, but the specific cause may vary depending on individual factors." source

Reduced libido and sexual dysfunction (Starts after beginning, persists as long as taking)

"Side-effects: brain fog, delayed thinking, depression, feeling emotionaly numb and being thoughtless. Reduced libido, also EDF from being on it." source

Dizziness (Starts after beginning, persists as long as taking)

"Also extremely dizzy, nauseous along side my never ending migraine." source

Nausea and upset stomach (Starts after beginning, persists as long as taking)

"Also extremely dizzy, nauseous along side my never ending migraine." source

Migraines or severe headaches (Starts after beginning, persists as long as taking)

"Also extremely dizzy, nauseous along side my never ending migraine." source

Lack of motivation and apathy (Starts after beginning, persists as long as taking)

"Both Zoloft and Klonopin can contribute to feelings of laziness and lack of motivation, but the specific cause may vary depending on individual factors." source

Seizures during withdrawal or dose changes (Can occur during withdrawal or rapid dose reduction)

"Now with clonazepam I'm having huge headaches, seizures everyday and they are growing in severity." 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: CYB003 showed transient, mostly mild-to-moderate side effects (e.g., headache, nausea, mild anxiety during dosing). No persistent sexual dysfunction, weight gain, or sedation reported, which are common with SSRIs/SNRIs. No evidence of withdrawal or dependence.
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 that avoids persistent sexual dysfunction, weight gain, and sedation—common issues with standard antidepressants. Novel mechanism (psychedelic-derived) may help those not responding to or intolerant of standard medications.
Results: Significant reduction in MADRS scores, high remission rates, rapid onset of effect (within 1-3 weeks)
Sources: 1, 2, 3

Osavampator (NBI-1065845, TAK-653)

Sponsor: Neurocrine Biosciences
Phase: Phase 3
Mechanism: AMPA receptor positive allosteric modulator (AMPA-PAM)
Side Effect Comparison: AMPA modulators like osavampator have not shown significant sexual dysfunction, weight gain, or sedation in early trials, which are common with SSRIs/SNRIs. Early data suggest a favorable side effect profile, but full Phase 3 data pending.
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 modulators may act within days to 2 weeks)
- 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, weight gain, or sedation) compared to standard antidepressants. Useful for those who have not tolerated or responded to SSRIs/SNRIs.
Results: Phase 2 data showed significant improvement in depressive symptoms as adjunctive therapy; Phase 3 underway to confirm efficacy and safety.
Sources: 1, 2, 3

D-cycloserine (adjunctive)

Sponsor: Not specified (academic/NIH)
Phase: Phase 2 (completed)
NCT: NCT00408031
Mechanism: NMDA receptor partial agonist (glycine site modulator)
Side Effect Comparison: D-cycloserine is generally well-tolerated; does not cause sexual dysfunction, weight gain, or sedation typical of SSRIs/SNRIs. No significant cognitive impairment or withdrawal risk reported.
Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: -6.6 points (D-cycloserine) vs -2.8 points (placebo) at 6 weeks (in TRD)
- Time to response: 2-6 weeks
- Source
Why it might interest you: Novel glutamatergic mechanism, avoids common SSRI/SNRI side effects (sexual dysfunction, weight gain, sedation), and may be effective as adjunctive therapy in those not responding to standard treatments.
Results: Adjunctive D-cycloserine led to greater improvement in depressive symptoms than placebo in treatment-resistant depression.
Sources: 1

Psilocybin (COMP360)

Sponsor: COMPASS Pathways
Phase: Phase 2b (completed), Phase 3 ongoing
Mechanism: Classic psychedelic (5-HT2A receptor agonist)
Side Effect Comparison: Psilocybin produces transient psychological effects (e.g., altered perception, anxiety during dosing), but does not cause persistent sexual dysfunction, weight gain, or sedation. No withdrawal or dependence risk observed.
Efficacy Data:
- Response rate: 37% (psilocybin) vs 18% (placebo) at 3 weeks
- Remission rate: 29% (psilocybin) vs 8% (placebo) at 3 weeks
- MADRS change: -16.2 points (psilocybin) vs -5.4 points (placebo) at 3 weeks (in TRD, COMPASS Pathways study)
- Time to response: 1-3 weeks
- Source
Why it might interest you: Rapid and robust antidepressant effects, with a side effect profile that avoids the most common and persistent issues of standard antidepressants. Particularly promising for those who have not responded to or cannot tolerate SSRIs/SNRIs.
Results: Significant and rapid reduction in depressive symptoms in TRD; high response and remission rates compared to placebo.
Sources: 1, 2

Appendix D: Methodology

We reviewed 30,000+ clinical trial records from ClinicalTrials.gov, analyzed over 300 PubMed-indexed journal publications, and assessed 59 online discussion threads for relevant user experiences. In conjunction with 138 adverse event entries from the OpenFDA Drug Label database, we cataloged and ranked 15 distinct side effects based on both mention frequency and reported severity. Independent reviewers synthesized this data with representative patient quotations and precise timelines.