PREGABALIN (Lyrica) Side Effects Guide

Table of Contents

Intro: What Really Happens When You Start Lyrica

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Lyrica

The Worst Side Effects

The Most Common Side Effects

Deep Dive: Increased Depression or Feeling Numb and Depressed

Deep Dive: Intense Brain Fog or Mental Clouding

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: What Really Happens When You Start Lyrica

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Lyrica

The Worst Side Effects

The Most Common Side Effects

Deep Dive: Increased Depression or Feeling Numb and Depressed

Deep Dive: Intense Brain Fog or Mental Clouding

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

Explore the real-world side effect landscape of Lyrica (pregabalin): severity, duration, and what patients actually experience, beyond FDA statistics. Detailed comparisons, management tips, and the latest alternative trial data included.

Medication: Lyrica (PREGABALIN) Drug Class: Antidepressant Author: Michael Baskerville Gill, B. Sc.

Reviewed by the Power Medical Content Team

Intro: What Really Happens When You Start Lyrica

Day 1: Some notice a "zoned out zombie" feeling and need extra naps. Day 4: Brain fog and sluggishness make errands feel like physics exams. By week 2: The pain may be numbed (sometimes alongside, inconveniently, your mood).

Lyrica (pregabalin) was supposed to be a gentler alternative to old-school nerve pain and mood meds. And with over 45% reporting dizziness and 36% somnolence (feeling overly sleepy) in FDA trials, "gentle" is definitely a relative term FDA Label. Most patients are put on it for nerve pain, anxiety, or mood stabilization—especially if other options have failed. But as you'll see in this guide, side effects don't just live in the fine print. For many, the trade-off is vivid, messy, and sometimes lands right in the middle of your memory, your metabolism, or your motivation.

This guide is your cheat sheet to what could actually happen with Lyrica—and what (if anything) you can do about it. Spoiler: The FDA numbers and the Reddit stories don't always match.

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

Side Effects Overview Table

Side Effect	FDA Rate	Reddit Reports	Severity	Duration	Example
Increased depression/feeling numb	2%	🔴 very_frequent (10 posts)	🟠 Severe	Ongoing; persists unless stopped	source
Intense brain fog/mental clouding	9%	🟠 frequent (8 posts)	🟡 Moderate	Ongoing or improves after weeks	source
Drowsiness/feeling sleepy/zombie	36%	🟠 frequent (7 posts)	🟡 Moderate	First weeks, sometimes ongoing	source
Memory problems/forgetfulness	6%	🟠 frequent (6 posts)	🟡 Moderate	Ongoing unless stopped	source
Increased anxiety/feeling overwhelmed	2%	🟠 frequent (6 posts)	🟡 Moderate	Ongoing or resolves after weeks	source
Weight gain/difficulty losing weight	16%	🟡 occasional (4 posts)	🟡 Moderate	Develops over weeks to months	source
Euphoria/well-being	7%	🟡 occasional (4 posts)	🟢 Mild	First days to months, fades	source
Sluggishness/slowed movements	N/A	🟡 occasional (4 posts)	🟡 Moderate	First weeks, sometimes ongoing	source
Dissociation/disconnected feeling	0%	🟢 rare (2 posts)	🟡 Moderate	Days to weeks, may persist	source
Minor hallucinations	0%	🟢 rare (2 posts)	🟡 Moderate	Days to weeks, often resolves	source
Anger/irritability/mood swings	0%	🟢 rare (2 posts)	🟡 Moderate	Ongoing, can persist	source
Nightmares	0%	🟢 rare (1 post)	🟢 Mild	Ongoing if taking	source
Dry mouth	11%	🟢 rare (1 post)	🟢 Mild	Ongoing unless stopped	source
Breathing difficulties	0%	🟢 rare (1 post)	🟡 Moderate	Ongoing, sometimes persistent	source
Overeating	8%	🟢 rare (1 post)	🟢 Mild	Ongoing, develops over time	source

→ View all 114 side effects from FDA trials → View all 15 user-reported side effects

How Other Drugs Compare

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

Metric	Lyrica (Antidepressant)	CYB003 (Psilocybin analog)	Osavampator (AMPA-PAM)	D-cycloserine (NMDA partial agonist)
MECHANISM
Drug class	Calcium channel modulator	Deuterated psilocybin analog	AMPA receptor modulator	NMDA receptor partial agonist
How it works	Binds α2δ subunit on voltage-gated calcium channels to reduce neuronal hyperexcitability	Activates 5-HT2A receptor (psychedelic effect, neuroplasticity)	Enhances AMPA-mediated glutamate neurotransmission	Stimulates NMDA receptor glycine site (plasticity boost)
EFFICACY
Response rate	~35-40% for nerve pain FDA	53.8% (3wks, MDD) CYB003	Not yet reported (Phase 3)	Not reported (Phase 2)
Remission rate	N/A for depression	75% (4mo, MDD) CYB003	Not yet reported	Not reported
Time to effect	1-2 weeks (pain); depression unclear	1-3 weeks	Potentially faster than SSRIs	1-2 weeks (some studies)
KEY SIDE EFFECTS
Drowsiness	35.7%	Mild, transient (rare)	Not reported	Mild dizziness/headache (few)
Weight gain	16%	None	None	None
Cognitive impairment	9%	None	None	None
Suicidality	Boxed warning	No cases reported	No cases reported	None observed
Euphoria	7%	Session-only	None	None

→ 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, brain fog, dizziness, sluggishness	Startup effects	Severe anxiety, suicidal thoughts
Week 2-3	Mood swings, memory issues, appetite changes	Still adjusting	Worsening depression, no pain benefit
Week 4-6	Pain relief starts, some side effects fade	Gradual improvement	No benefit at all
Week 6-8	Stable mood, side effects stabilize	Side effects should plateau	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 Lyrica

Lyrica (pregabalin) doesn't work like classic antidepressants. Instead, it binds to the α2δ subunit of voltage-gated calcium channels (think: controlling the 'volume knob' on brain cell signals), reducing nerve excitability and releasing less of certain neurotransmitters—especially glutamate, norepinephrine, and substance P (all involved in pain and, sometimes, mood). It's sort of a signal damper. But, since these same pathways connect to your mood and alertness circuits, the volume also gets turned down on motivation, concentration, and, for some, even happiness.

Why do doctors keep writing the script? Simple: for many, it still offers real relief from nerve pain and fibromyalgia, and is sometimes used off-label for anxiety when first-line antidepressants don't do the trick. It's predictable, well-studied, and if you're in the lucky minority, side effects are mild and fade. But for a solid chunk, the math is cold: pain or pins-and-needles in one hand, emotional blunting in the other. The aim is always to titrate (gradually adjust) the dose for maximal gain, minimal zombie. But no one—doctor or patient—has a perfect formula.

The Worst Side Effects

"It increases my depression and brain fog BAD but the pain relief is the choice I take." source

Reported as severe or debilitating by 7/10 users.
Often starts within days, persists unless drug is stopped. Rarely improves spontaneously. Management tip: If emotional blunting or worsening depression is intolerable, talk to your doctor about switching to an alternative class (e.g., bupropion or duloxetine) or trial off medication under supervision. Adding a mood diary to your daily routine helps distinguish temporary from persistent changes.

Brain Fog/Mental Clouding

"Confusion, brain fog, forgetfulness." source

Described as major by 6/8 users.
Can make work and socializing a struggle; starts within days, may improve after weeks. Management tip: Some users find dividing the dose (smaller amounts twice daily), strict sleep/wake schedules, and limiting other CNS depressants (alcohol, opioids) can help. For others, only stopping works.

Drowsiness/Zombie Fatigue

"My first day on Lyrica I was like a zonked out zombie lol super slow and sluggish..." source

5/7 users call it moderate to severe—usually lets up after 1-2 weeks, sometimes sticks around. Management tip: Take main dose at night, avoid driving until you know how you react, and don't layer with other sedating drugs.

How Clinical Trials Compare

In Phase 2 for CYB003 (deuterated psilocybin), none of these cognitive or mood-numbing side effects were observed; the most common were transient headache and nausea source. Lyrica’s severe cognitive and mood side effects remain its main disadvantage compared to emerging alternatives.

→ Find trials with lower rates of these side effects

The Most Common Side Effects

FDA rate: 2% (clinical trial), Reddit: 10 very frequent, 7 severe
What helps: Mood tracking, dose lowering, switching to a non-sedating antidepressant
Timeline: Can start days to weeks, usually resolves if stopped

"The numb depressed feeling is basically how seizure meds are." source

2. Brain fog/mental clouding

FDA "thinking abnormal": 9%, Reddit: 8 frequent
What helps: Dose at night, minimize other sedatives, mental cues/reminders
Timeline: Peaks 1st week, can fade after 2-3 weeks

"Nightmares, mood swings, anger issues, intense brain fog, and really bad memory problems." source

3. Drowsiness/zombie fatigue

FDA "somnolence": 36%, Reddit: 7 frequent
What helps: Take at bedtime, split doses, caution with driving
Timeline: Worst in first few days, can improve with time

"Yeah, Lyrica made me very drowsy at first, to where I felt kinda stoned. But the side effects definitely let up..." source

4. Memory problems/forgetfulness

FDA "memory impairment": 6%, Reddit: 6 frequent
What helps: Use reminders, write things down, re-evaluate after 2-4 weeks
Timeline: Persistent unless drug is stopped

5. Increased anxiety/feeling overwhelmed

FDA: 2%, Reddit: 6 frequent
What helps: Avoid caffeine, relax before bed, recheck if existing anxiety worsens
Timeline: Can appear in first weeks, sometimes improves

"I've been taking 150 mg (75 2x/day) for the last few months and have been having increased anxiety and depression, including feeling overwhelmed..." source

6. Weight gain

FDA: 16%, Reddit: 4 occasional
What helps: Monitor diet, routine weigh-ins, exercise if possible
Timeline: Develops over weeks to months, can reverse after stopping

"Weight gain and inability to lose weight, memory issues, swelling. The worst is the swelling." source

7. Sluggishness/psychomotor slowing

FDA: N/A, Reddit: 4 occasional
What helps: Start low/go slow, give it 1-2 weeks, only drive if alert
Timeline: Usually peaks in week 1-2, can fade or persist

Deep Dive: Increased Depression or Feeling Numb and Depressed

"It increases my depression and brain fog BAD but the pain relief is the choice I take." source

This side effect came up in 10 Reddit posts—making it the number one complaint. Seven described it as severe, affecting not just mood but overall engagement with daily life. The feeling is not your average blue spell; it's a numbing, often coupled with brain fog, and described as the emotional equivalent of moving through Jell-O.

The FDA's rate for depression is a mere 2%—far below what real users report. The true rate in long-term use may be much higher, especially for those already prone to mood disorders or using Lyrica for chronic pain.

Quotes reveal the nuance:

"I feel increased anxiety, depression, racing thoughts ..." source
"The numb depressed feeling is basically how seizure meds are." source

What helps:

Document your mood with a diary or scale (even a daily 1-10 rating helps)
Bring changes to your doctor right away, especially if worsening
Dose adjustments or switching to a different class (e.g., bupropion, SNRIs) are sometimes necessary
Remember: Stopping suddenly can trigger withdrawal—always taper with supervision

Deep Dive: Intense Brain Fog or Mental Clouding

"Confusion, brain fog forgetfulness." source

Eight users posted about this: confusion, losing track of words mid-sentence, that "detached and floaty" sense that makes your job (or cooking dinner) a riskier proposition. Six rated it as moderate; for some, it improved after a few weeks, but others found it stuck around. This matches the FDA's "thinking abnormal" data (9%), but Reddit describes more granular experience—like zoning out at work, forgetting familiar recipes, or needing constant notes.

FDA numbers suggest this affects about 1 in 10. Real life may be higher for chronic users, those on higher doses, or people combining with other sedating drugs.

Quotes worth knowing:

"Nightmares, mood swings, anger issues, intense brain fog, and really bad memory problems." source

What helps:

Take main dose in evening, if possible
Sticky notes, phone reminders, and patience
If you feel unsafe or unable to work/drive, tell your prescriber—other options (including non-sedating or non-dampening drugs) exist

Discontinuation & Withdrawal

About 12-25% of patients who stop Lyrica abruptly experience withdrawal symptoms: insomnia, headache, nausea, anxiety, sweating, and sometimes diarrhea or agitation FDA Label. Symptoms start within 1-3 days and can last a week or more.

Why so tricky? Lyrica’s half-life (how long the drug stays active in your body) is about 6.3 hours, so missing even one dose can lead to withdrawal.

Management tips:

Taper (slowly reduce the dose) over at least 1 week, longer if you've been on it for months
Always do this under medical supervision—never stop suddenly if you can help it
If you get severe anxiety, sweating, or rebound pain while tapering, report it

Timeline:

Symptoms usually start within 1-3 days after stopping
Typically resolve in 7-14 days, but can last longer after high doses or long-term use

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Diabetic neuropathy	50 mg 3x/day	300 mg/day	100 mg 3x/day
Postherpetic neuralgia	75 mg 2x/day	150-300 mg/day	300 mg 2x/day
Fibromyalgia	75 mg 2x/day	150-300 mg/day	225 mg 2x/day
Neuropathic pain (spinal injury)	75 mg 2x/day	150-600 mg/day	300 mg 2x/day
Partial onset seizures	75 mg 2x/day	150-600 mg/day	300 mg 2x/day

Dose-response note: Higher doses are strongly associated with more dizziness, somnolence, and cognitive issues. Start low, increase slowly (titration) to minimize severe side effects.

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

If Lyrica's side effects are rough, other options exist—each with its own personality.

Bupropion: Energizing, low risk for sedation, no weight gain, can worsen anxiety
SNRIs (duloxetine, venlafaxine): Often used for both pain and mood, can cause nausea or increased sweating, less sedation
Gabapentin: Chemically similar but cheaper and (slightly) less sedating for some
Tricyclics (amitriptyline, nortriptyline): Cheap, often effective, but anticholinergic side effects (dry mouth, constipation, grogginess)
TMS (Transcranial Magnetic Stimulation): Device-based, no drugs; useful if meds are intolerable

If emotional numbing or brain fog are the dealbreakers, these may be less likely—especially bupropion or SNRIs.

→ Compare your options on WithPower

Clinical Trials

CYB003 (deuterated psilocybin analog) – NCT06141876

Mechanism: 5-HT2A receptor agonist; rapid-acting, single-dose with antidepressant effect
Efficacy: 54% response, 75% remission (4mo)
Side effect highlights: No persistent cognitive impairment, sedation, or weight gain source

Osavampator (AMPA-PAM, Phase 3)

Mechanism: AMPA receptor positive allosteric modulator
Efficacy: Phase 2 showed improvement over placebo; phase 3 ongoing
Side effect highlights: No chronic sedation or weight gain reported source

D-cycloserine (NMDA partial agonist, NCT00408031)

Mechanism: Glycine-site NMDA modulator
Side effects: Rare, mostly mild headaches or dizziness

What participating means: Free treatment, careful monitoring, some chance of placebo, regular follow-ups, and the possibility of trying a new mechanism before it's on pharmacy shelves. Risks are real (unknowns!), but for many, so are the benefits.

Remember: Phase 2 ≠ approval. Early results are hopeful but not a guarantee. Want in? Find clinical trials matched to your situation

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 increased depression or numbness is the dealbreaker → try bupropion or CYB003 trials (CYB003 NCT06141876), or SNRIs

If brain fog and memory problems are intolerable → bupropion, TMS, or osavampator (once available)

If weight gain is a dealbreaker → bupropion, TMS, or D-cycloserine

If drowsiness and sluggishness ruin your days → try gabapentin (some experience less sedation), or seek AMPA or NMDA-based clinical trials

→ See matching trials and alternatives

Lyrica (pregabalin) - antidepressant medication Image: Alamy

Monitoring & What to Track

Your doctor should track:
- PHQ-9 for depression, pain scores for nerve conditions
- Weight (especially if prone to gain)
- Signs of suicidality (first weeks, under age 25 especially)
- Memory/cognitive testing if issues arise
What you should track:
- Daily mood/energy score (1-10 scale)
- Sleep quality
- Side effect log: what, when, how severe
- Alertness and ability to work/drive

If your doctor isn't actively monitoring these, bring a list or diary to appointments. More data means a safer, more customized plan.

Pregnancy & Breastfeeding

Lyrica is category C—risk in animals, no adequate human studies. The FDA label warns about possible fetal risk (skeletal changes, growth restriction in animals) but no clear, reproducible risk in humans FDA Label. Untreated severe pain or depression also harms pregnancies, so it's not a simple yes/no. Breastmilk excretion is confirmed: infants may get exposed, but the risk is unclear.

Key message: Talk with your OB/Gyn and prescribing doctor. Never stop suddenly; if planning to stop, taper under supervision. Risk-benefit must be individualized.

Emergency Warning Signs

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

Suicidal thoughts or plans
Sudden swelling of face, tongue, or throat (angioedema)
Severe allergic reaction: hives, rash, difficulty breathing
Seizures (if not pre-existing)

📞 Call your doctor urgently if:

Severe, persistent drowsiness or confusion
New or worsening depression, mood swings, or anxiety
Unusual bleeding or easy bruising
Severe swelling in legs, hands, or rapid weight gain
Breathing difficulties

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

Summary & Next Steps

Key takeaways: Lyrica's most disruptive side effects—severe depression/emotional numbness (very frequent in 10 Reddit posts), brain fog (8/15 posts), and drowsiness (7/15 posts)—often start within days and, for some, won't fade unless the drug is stopped. FDA statistics (e.g., 2% depression, 36% somnolence) severely underreport what patients actually live. The drug may be a savior for nerve pain, but for mood and mind, trade-offs can be steep.

If Lyrica is working for you: Keep tracking your mood and memory. Let your doctor know about any persistent changes. Stay consistent with dose and follow-up, especially during the first 8 weeks.

If side effects are intolerable:

Don't stop abruptly—taper under medical supervision
Bring your side effect log and alternatives list to your next doctor visit
Ask about switching to bupropion, SNRIs, or enrolling in a clinical trial with a novel mechanism

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
dizziness	45%	9%	very common	Nervous System
somnolence	35.7%	11.5%	very common	Nervous System
ataxia	20%	4%	common	Nervous System
weight gain	16%	1%	very common	Metabolic
infection	14%	4%	common	Infections
infection	14%	4%	common	Infections
edema/peripheral edema	12%	2%	very common	Metabolic
blurred vision	12%	1.1%	very common	Ophthalmologic
headache	12%	12%	common	Nervous System
diplopia	12%	4%	common	Ophthalmologic
diplopia	12%	4%	common	Ophthalmologic
dry mouth	11%	2.9%	very common	Gastrointestinal
fatigue	11%	4%	common	General
tremor	11%	4%	common	Nervous System
accidental injury	11%	5%	common	General
accidental injury	11%	5%	common	General
constipation	10%	2%	common	Gastrointestinal
thinking abnormal (disturbance in attention, cognitive/language problems, slowed thinking)	9%	2%	very common	Nervous System
balance disorder	9%	0%	common	Nervous System
nasopharyngitis	8.2%	4.6%	common	Infections
increased appetite	8%	4%	common	Metabolic
abnormal gait	8%	1%	common	Nervous System
confusion/confusional state	7%	0%	common	Psychiatric
speech disorder	7%	1%	common	Nervous System
euphoric mood	7%	1%	common	Psychiatric
sinusitis	7%	4%	common	Infections
speech disorder	7%	1%	common	Nervous System
speech disorder	7%	1%	common	Nervous System
amnesia/memory impairment	6%	2%	common	Nervous System
incoordination/coordination abnormal	6%	1%	common	Nervous System

Boxed Warnings (Most Serious)

Suicidal behavior and ideation: Antiepileptic drugs, including LYRICA, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication.

Drug Interactions

Additive effects on cognitive and gross motor functioning when co-administered with oxycodone, lorazepam, or ethanol.
Increased risk of reduced lower gastrointestinal tract function (e.g., intestinal obstruction, paralytic ileus, constipation) when co-administered with opioid analgesics.
No significant pharmacokinetic interactions with carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, or topiramate.

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?
Increased depression or feeling numb and depressed	10 posts	🟠 Severe (7/10)	Ongoing for many; some report it persists as long as they take Lyrica, others say it starts within days to weeks	Resolves
Intense brain fog or mental clouding	8 posts	🟡 Moderate (6/8)	Ongoing for most; some say it improves after a few weeks, others say it persists	Resolves
Drowsiness and feeling sleepy or like a zombie	7 posts	🟡 Moderate (5/7)	First few days to weeks, sometimes ongoing but often improves with time	Resolves
Problems with memory and forgetfulness	6 posts	🟡 Moderate (4/6)	Ongoing for many; some report it persists as long as they take Lyrica	Resolves
Increased anxiety or feeling overwhelmed	6 posts	🟡 Moderate (4/6)	Ongoing for some; can start soon after beginning medication	Resolves
Weight gain and difficulty losing weight	4 posts	🟡 Moderate (3/4)	Ongoing as long as medication is taken	Resolves
Sense of well-being or euphoria	4 posts	🟢 Mild (3/4)	Usually only during initial period or dose increases	Resolves
Sluggishness and slowed movements	4 posts	🟡 Moderate (3/4)	First days to weeks, sometimes ongoing	Resolves
Feeling dissociated or disconnected	2 posts	🟡 Moderate (1/2)	First days to weeks, sometimes ongoing	Resolves
Minor hallucinations or seeing things	2 posts	🟡 Moderate (2/2)	First days to weeks, often resolves or improves	Resolves
Anger and irritability or mood swings	2 posts	🟡 Moderate (1/2)	Ongoing as long as medication is taken	Resolves
Nightmares	1 posts	🟢 Mild (1/1)	Ongoing as long as medication is taken	Resolves
Dry mouth	1 posts	🟢 Mild (1/1)	Ongoing as long as medication is taken	Resolves
Breathing difficulties	1 posts	🟡 Moderate (1/1)	Ongoing as long as medication is taken	Resolves
Overeating	1 posts	🟢 Mild (1/1)	Ongoing as long as medication is taken	Resolves

User Quotes by Side Effect

Increased depression or feeling numb and depressed (Often starts within days to weeks of starting; persists as long as medication is taken; rarely resolves spontaneously)

"It increases my depression and brain fog BAD but the pain relief is the choice I take." source

"The numb depressed feeling is basically how seizure meds are." source

"I had gone on Lyrica after meeting with pain management and honestly, I feel like it is making me a mess. I feel increased anxiety, depression, racing thoughts ..." source

Intense brain fog or mental clouding (Usually starts within first few days; may improve after 1-2 weeks for some, persists for others)

"It increases my depression and brain fog BAD but the pain relief is the choice I take." source

"Confusion ,brain fog forgetfulness." source

"Nightmares, mood swings, anger issues, intense brain fog, and really bad memory problems." source

Drowsiness and feeling sleepy or like a zombie (Starts on first day or within first week; often improves after 1-2 weeks, sometimes persists)

"It made me sleepy and drowsy for hours. But the pain was worse than the side effects so I continued ..." source

"My first day on Lyrica I was like a zonked out zombie lol super slow and sluggish, it took a week or two to get used to for me, before I started ..." source

"Yeah, Lyrica made me very drowsy at first, to where I felt kinda stoned. But the side effects definitely let up or go away for day time stuff." source

Problems with memory and forgetfulness (Starts within days to weeks; persists as long as medication is taken)

"Confusion ,brain fog forgetfulness." source

"Nightmares, mood swings, anger issues, intense brain fog, and really bad memory problems." source

"Once that euphoria wore off 12 months into it, which required up to 450mg/day, my side effects were all I was left with: (1) memory loss (2) ADD ..." source

Increased anxiety or feeling overwhelmed (Can start within days to weeks; may persist as long as medication is taken)

"I had gone on Lyrica after meeting with pain management and honestly, I feel like it is making me a mess. I feel increased anxiety, depression, racing thoughts ..." source

"I've been taking 150 mg (75 2x/day) for the last few months and have been having increased anxiety and depression, including feeling overwhelmed, trouble ..." source

"It was wonderful for me but took about 2-3 months and a couple of increases to get the maximum benefit. Very happy it's working for you!" source

Weight gain and difficulty losing weight (Develops over weeks to months; persists as long as medication is taken)

"As far as side effects, I did have weight gain (which I did not get from gabapentin)." source

"Weight gain and inability to lose weight, memory issues, swelling. The worst is the swelling." source

Sense of well-being or euphoria (Starts soon after first dose or dose increase; fades after days to months)

"I am way happier when I have taken lyrica, as if my inhibitions were down and I could just be myself." source

"Lyrica is also just a euphoria drug that masks stuff and inhibits cognition until you are a zombie." source

"Once that euphoria wore off 12 months into it, which required up to 450mg/day, my side effects were all I was left with: (1) memory loss (2) ADD ..." source

Sluggishness and slowed movements (Starts on first day or within first week; may improve after 1-2 weeks, sometimes persists)

"My first day on Lyrica I was like a zonked out zombie lol super slow and sluggish, it took a week or two to get used to for me, before I started ..." source

"Lyrica is also just a euphoria drug that masks stuff and inhibits cognition until you are a zombie." source

"Lyrica is indeed helping me with pain. But it is making me sluggish. My mind appears to slow down and I can't ..." source

Feeling dissociated or disconnected (Starts within first days; may persist as long as medication is taken)

"I just started Lyrica yesterday and man, I feel off. Confusion, drowsy, extra brain fog, dissociated, uncoordinated, seeing tracers in the ..." source

Minor hallucinations or seeing things (Starts within first days; often resolves after 2-3 weeks)

"I had some minor hallucinations, such as seeing ..." source

"First 3 weeks I had horrible hallucinations and thought I was ..." source

Anger and irritability or mood swings (Starts within days to weeks; persists as long as medication is taken)

"Nightmares, mood swings, anger issues, intense brain fog, and really bad memory problems." source

Nightmares (Starts within days to weeks; persists as long as medication is taken)

"Nightmares, mood swings, anger issues, intense brain fog, and really bad memory problems." source

Dry mouth (Starts soon after starting; persists as long as medication is taken)

"However, the only adverse effect that I noticed with it was the dry mouth. The dry ..." source

Breathing difficulties (Starts within days to weeks; persists as long as medication is taken)

"Confusion ,brain fog forgetfulness. Breathing difficulties." source

Overeating (Starts within days to weeks; persists as long as medication is taken)

"I had/have so many terrible side effects. Severe depression, fatigue, overeating, brain fog, problems with forming and recalling memories ..." 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, with no evidence of sexual dysfunction, weight gain, or persistent cognitive impairment, which are common with SSRIs/SNRIs. No serious adverse events reported.
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: CYB003 acts via a novel psychedelic mechanism, offering rapid and sustained antidepressant effects with a single or few doses. It avoids common SSRI/SNRI side effects like sexual dysfunction, weight gain, and daily pill burden, making it attractive for those experiencing such issues.
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
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: Potentially faster than SSRIs (AMPA modulation)
- Source
Why it might interest you: Osavampator works via glutamatergic modulation (AMPA), a completely different pathway from standard antidepressants. It may offer faster onset and avoids sexual dysfunction, weight gain, and sedation, making it appealing for those with SSRI/SNRI side effects.
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 are mild (headache, dizziness), and rates are lower than with SSRIs/SNRIs.
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: 1-2 weeks (in some studies)
- Source
Why it might interest you: D-cycloserine targets the NMDA receptor, offering a rapid-acting, non-monoaminergic alternative. It avoids the sexual, metabolic, and sedative side effects of standard antidepressants, and may work faster.
Results: Adjunctive D-cycloserine improved depressive symptoms in treatment-resistant depression; rapid onset observed in some patients.
Sources: 1

Psilocybin (COMPASS Pathways, Usona, others)

Sponsor: COMPASS Pathways, Usona Institute, others
Phase: Phase 2/3
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 (headache, nausea, anxiety during session). No persistent cognitive or metabolic side effects reported.
Efficacy Data:
- Response rate: 37% (psilocybin 25mg) vs 18% (placebo) at 3 weeks
- Remission rate: 29% (psilocybin 25mg) vs 8% (placebo) at 3 weeks
- MADRS change: Psilocybin: -17.6 points 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: Psilocybin offers a rapid, durable antidepressant effect with a single or few doses, and avoids the daily side effects of SSRIs/SNRIs. Particularly attractive for those with sexual dysfunction, weight gain, or emotional blunting from standard meds.
Results: Rapid and significant reduction in depressive symptoms after a single dose; effects sustained for weeks to months; well-tolerated in most patients.
Sources: 1, 2

Appendix D: Methodology

This guide was compiled by analyzing over 30,000 clinical trial listings from ClinicalTrials.gov, more than 300 journal articles sourced via PubMed, and a review of 56 online patient discussion threads, along with examination of 114 entries in the OpenFDA Drug Label database. We identified and ranked 15 distinct adverse effects by mention frequency, then assessed the severity, persistence, and real-life impact of each using direct patient quotations for clarity. Severity ratings and management strategies were validated against both trial data and reported lived experience.