AMITRIPTYLINE HYDROCHLORIDE (Elavil) Side Effects Guide

Table of Contents

Intro

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Elavil

The Worst Side Effects

The Most Common Side Effects

Daytime drowsiness and sedation

Weight gain

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 Elavil

The Worst Side Effects

The Most Common Side Effects

Daytime drowsiness and sedation

Weight gain

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

Comprehensive guide to Elavil (amitriptyline): side effects, user reports, timelines, dosing, withdrawal, and trial alternatives. Integrates FDA data and real patient experiences for adults seeking deeper insights.

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

Reviewed by the Power Medical Content Team

Intro

Day 1: "I know one of the most common side effects is drowsiness and boy do I have that!!" Day 7: That classic dry mouth creeps in. By Week 3: Some are dealing with morning grogginess; others, a scale-busting appetite. Month 2: For a few, the sedation lessens; for others, the weight gain is unshakeable.

Amitriptyline (Elavil) is one of those medications whose story is written in both dusty FDA archives and on the migraine subreddits. Officially: zero percent for most side effects in trials. Reality: "It made me dangerously drowsy and constantly starving" source.

Tricyclic antidepressants like Elavil can mean transformative relief—when they work. But for many, it's a trade: sedation for sleep, at the cost of a scale that creeps up and a mouth dry as parchment. If the standard SSRIs felt like a dud (or a roulette wheel of sexual side effects), Elavil's appeal is its reliability. Or its tyranny, depending on whether the morning grogginess ever lets up.

We break down the most common—and worst—side effects as real people report them, how long they last, and where novel trials might offer relief.

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
Daytime drowsiness and sedation	0%	🔴 very_frequent (18 posts)	🟡 Moderate	Ongoing (may improve after 2-4 weeks for some)	source
Dry mouth and dry eyes	0%	🟠 frequent (12 posts)	🟢 Mild	Ongoing (may resolve in weeks to months)	source
Significant weight gain	0%	🟠 frequent (8 posts)	🟡 Moderate	Months to ongoing	source
Constipation and difficulty with bowel movements	0%	🟡 occasional (7 posts)	🟢 Mild	Ongoing or may resolve after a few weeks	source
Increased appetite and constant hunger	0%	🟡 occasional (5 posts)	🟢 Mild	Ongoing while on medication	source
Vivid and excessive dreams	0%	🟡 occasional (5 posts)	🟢 Mild	Ongoing for some, fades after few weeks for others	source
Morning grogginess and feeling zombified	0%	🟡 occasional (4 posts)	🟡 Moderate	Ongoing for some, may improve	source
Difficulty falling or staying asleep	0%	🟡 occasional (4 posts)	🟢 Mild	Ongoing for some, may resolve	source
Nausea and upset stomach	0%	🟢 rare (2 posts)	🟢 Mild	First days to weeks	source
Visual disturbances during dose changes	0%	🟢 rare (2 posts)	🟢 Mild	Resolves after dose stabilized	source
Feeling blue or apathetic mood	0%	🟢 rare (2 posts)	🟢 Mild	Ongoing	source
Acid reflux and heartburn	0%	🟢 rare (1 post)	🟢 Mild	Ongoing	source
Irritability and mood swings	0%	🟢 rare (1 post)	🟡 Moderate	Ongoing	source
Sore throat	0%	🟢 rare (1 post)	🟢 Mild	First days to weeks	source
Urinary retention and difficulty urinating	0%	🟢 rare (1 post)	🟡 Moderate	Ongoing/persistent	source

→ View all 89 side effects from FDA trials → View all 15 user-reported side effects

How Other Drugs Compare

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

Metric	Elavil (Antidepressant)	Bupropion (NDRI)	CYB003 (Psilocybin analogue)	Osavampator (AMPA-PAM)
MECHANISM
Drug class	Tricyclic Antidepressant	Norepinephrine-Dopamine Reuptake Inhibitor	Deuterated Psilocybin Analogue	AMPA Receptor Positive Allosteric Modulator
How it works	Blocks reuptake of serotonin and norepinephrine (prevents neurotransmitter reabsorption), strong anticholinergic effects	Inhibits norepinephrine and dopamine reuptake	5-HT2A receptor agonist (psychedelic mechanism)	Enhances AMPA receptor activity (boosts glutamatergic signaling)
EFFICACY
Response rate	~60% (MDD) source	~56% (MDD) source	53% (3 wks, MDD) source	Phase 3 ongoing; phase 2: significant improvement vs placebo source
Remission rate	~30% (MDD) source	~31% (MDD) source	75% at 4 months (open label, MDD) source	Not yet reported
Time to effect	2-6 weeks	2-4 weeks	1-3 weeks	Expected faster than SSRIs
KEY SIDE EFFECTS
Daytime drowsiness/sedation	0% FDA; 🔴 very_frequent Reddit	Rare	None reported	None reported
Weight gain	0% FDA; 🟠 frequent Reddit	None/slight loss	None	None
Sexual dysfunction	Rare	None/minimal	None	None
Anticholinergic effects (dry mouth, constipation)	High	Very rare	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, dry mouth, constipation, increased appetite	Startup effects	Severe grogginess, confusion, suicidal thoughts
Week 2-3	Weight gain, vivid dreams, morning grogginess	Still adjusting	Severe mood swings, urinary retention
Week 4-6	Benefits for pain/sleep/depression may begin	Gradual improvement	No change in mood, intolerable sedation
Week 6-8	Maximum effect likely reached	Stable	If side effects persist or worsen

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 Elavil

Elavil works by blocking the reuptake of serotonin and norepinephrine (preventing your brain from absorbing these neurotransmitters), which boosts their levels in synapses (the gaps between nerve cells). It's also a classic tricyclic—meaning it slams hard on the brakes for a whole menagerie of other brain and body signals, thanks to its antagonism (blocking) of histamine, acetylcholine, and adrenergic receptors (the proteins on cells that respond to specific chemicals).

That kitchen-sink effect is why the side effects are so, well, "retro": dry mouth, constipation, blurred vision, morning hangover, a scale that suddenly starts climbing. Why do docs still go for it? It works, especially for pain and sleep issues when newer antidepressants don't. It's old, it's cheap, and after fifty years, the risks are predictable—if you're prepared for them.

The Worst Side Effects

1. Daytime drowsiness and sedation

"It made me dangerously drowsy and constantly starving." source

Reported as moderate to severe by 12/18 users
Management tip: Take Elavil at bedtime; consider lowering dose; discuss switching to a less sedating alternative if daytime function remains impaired.

2. Significant weight gain

"Gained migraines, a dry-ass mouth, and 15+ kilos of unshakeable body weight that I can't lose." source

Reported as moderate by 6/8 users
Management tip: Log food intake, consider dietary consult, monitor weight weekly; alternatives like bupropion or clinical trials may avoid this effect.

3. Morning grogginess

"I feel like a zombie during the day. My energy is nonexistent." source

Moderate in 3/4 users
Management tip: Hydration, caffeine, shifting dose earlier in the evening can help (if doctor agrees); some users see improvement after a few weeks.

4. Urinary retention and difficulty urinating

"If you've been on it for months with consistent retention then it sounds like it is not going away. Some people are more sensitive to retention than others." source

Moderate/severe in 1/1 user
Management tip: Cut dose or switch to alternative; immediate physician attention for new, severe, or persistent symptoms. Never ignore retention.

How Clinical Trials Compare

CYB003 (psilocybin analogue) reported no chronic sedation, weight gain, or urinary retention, with most side effects (headache, nausea) being mild and transient source. Osavampator phase 2 showed similar safety: no significant increase in sedation or weight gain compared to placebo source. → Find trials with lower rates of these side effects

The Most Common Side Effects

1. Daytime drowsiness and sedation

FDA rate: 0%. Reddit: very frequent (18 posts), moderate severity source
What helps: Take at night, don't drive until you know your reaction, some find drowsiness fades after 2-4 weeks.
"I feel like a zombie during the day. My energy is nonexistent."

2. Dry mouth and dry eyes

FDA rate: 0%. Reddit: frequent (12 posts), mild source
What helps: Water, sugarless gum, xylitol lozenges. Tends to improve in some after weeks.
"My side effects are just that it dries me out—dry eyes, dry mouth."

3. Weight gain

FDA rate: 0%. Reddit: frequent (8 posts), moderate source
What helps: Calorie tracking, avoid late-night snacks, talk to doctor about switching if rapid or high gain. Rarely resolves unless stopped.
"It made me gain a ton of weight."

4. Constipation

FDA rate: 0%. Reddit: occasional (7 posts), mild source
What helps: Fiber, hydration, occasional stool softeners if cleared by your doctor. Some adapt after a few weeks.

5. Morning grogginess

FDA rate: 0%. Reddit: occasional (4 posts), moderate source
What helps: Water, caffeine, don't drive or operate machinery until you know your response. Sometimes eases after 2-4 weeks.

→ Find clinical trials that may avoid this side effect

Daytime drowsiness and sedation

You'd think sleepiness is just part of the antidepressant package, but with Elavil, it's almost the main course. "I know one of the most common side effects is drowsiness and boy do I have that!!" source.

Reddit users put it bluntly: "It made me dangerously drowsy and constantly starving." source. Of the 18 users reporting sedation, a whopping 12 call it moderate—and for a few, it's more than just nap-tempting; it's dangerous. Compare that to the FDA's clinical trial data, which reports a 0% sedation rate. So either the trials screened out anyone who couldn’t power through, or real-world life is just messier.

Most people see sedation start in the first few days, often peaking in week 1-2. Some report improvement after 2-4 weeks, others feel like "a zombie" for the duration source.

Management tips:

Always dose at night (unless specifically told otherwise)
Start low, go slow; if you're sensitive, even 5-10mg can be enough
Do not mix with alcohol, benzos, or other sedating meds
If you must drive, wait until you know how sedated you get (seriously—traffic doesn't care about your sleep hygiene)
Discuss dose reduction or switching drugs if morning grogginess doesn't fade by week 4

If you ever nod off at work, at the wheel, or at dinner, don't tough it out—talk to your doctor. Newer clinical trial drugs (psilocybin analogues, AMPA modulators) show little to no sedation in the data—watch these closely if you're stuck in a pharmaceutical fog.

Weight gain

Weight gain isn't subtle on Elavil: "Gained migraines, a dry-ass mouth, and 15+ kilos of unshakeable body weight that I can't lose." source. Officially, FDA trials clock it in at 0%, but Reddit's not fooled—8 real-world users, most rating it moderate, describe persistent weight gain starting after a few weeks and not letting up.

Why does this happen? Amitriptyline's antagonism of histamine and serotonin receptors (the cell gatekeepers for things like hunger and satiety) ramps up appetite and slows down metabolism. For many, the battle isn't just with hunger but with a body that seems to cling to every extra calorie.

"It made me gain a ton of weight," one user shared, a refrain common enough to show up in nearly every major side effect thread. Attempts to diet, exercise, or shift mealtimes often yield little effect until the medication is stopped.

Management tips:

Track weight and appetite weekly from day one
Keep healthy snacks handy, as cravings for carbs and sweets are common
If weight climbs fast or above 5% of baseline in a month, push your doctor for a review
Bupropion and clinical trial drugs (e.g., CYB003) have very low weight gain risk—options to discuss if this becomes a dealbreaker

While FDA clinical trials might not "see" weight gain, for real users it’s as obvious as the tightness in their jeans. The decision: control mood or pain at the cost of your waistline, or seek out something newer and leaner?

Discontinuation & Withdrawal

Tricyclics like Elavil can make goodbyes awkward. About 20-30% of patients experience some withdrawal symptoms after stopping suddenly (based on TCA data). While not physically "addictive," you can expect symptoms: irritability, restlessness, vivid dreams, insomnia, nausea, headache, and malaise. The official line: "May occur within two weeks of gradual dosage reduction."

Why? Amitriptyline's long half-life (how long it stays active in your body) gives you a slightly softer landing than an SSRI like paroxetine, but not as gentle as, say, fluoxetine.

What helps:

Taper slowly, dropping by 10-25% every 1-2 weeks, guided by your doctor
Watch for mood swings or sleep disruption—classic "discontinuation syndrome" for TCAs
For severe withdrawal, consider slower taper or bridging with another agent

Timeline: Most symptoms begin within days of dose reduction or stopping, peak at 3-7 days, and fade over 1-3 weeks. Mania or hypomania has been reported rarely in the first week after stopping. If symptoms are severe or long-lasting, call your doctor ASAP.

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Depression	25-50 mg bedtime or in divided doses	100-200 mg/day	300 mg/day
Chronic pain, migraine, fibromyalgia (off-label)	10-25 mg bedtime	25-75 mg/day	150 mg/day

Most patients start low (10-25 mg) to minimize side effects
Dose-response: Side effects often increase at higher doses
Always titrate (increase) slowly per doctor
Data from FDA label: source

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

Bupropion: Energizing, minimal weight gain, can worsen anxiety for some. Might be your holy grail if Elavil's sedation or hunger is intolerable.
SNRIs (venlafaxine, duloxetine): Less sedation than Elavil, risk of hypertension.
SSRIs (sertraline, fluoxetine, escitalopram): Fewer anticholinergic effects (less constipation/dry mouth), but sexual dysfunction more likely.
MAOIs: Strict diet needed, rarely used except for hard-to-treat depression.
Spravato (esketamine): Rapid effect, must be given in a clinic.
TMS (transcranial magnetic stimulation): Device-based, minimal side effects.

For pain: Gabapentin/pregabalin, topiramate, or newer clinical trials.

If sedation, weight gain, or constipation are dealbreakers, bupropion and modern trials (psilocybin, AMPA modulators) may spare you those.

→ Compare your options on WithPower

Clinical Trials

CYB003 (deuterated psilocybin analogue) (NCT05385783): Acts at 5-HT2A receptors; no chronic sedation, weight gain, or urinary retention reported. Rapid effect: 53% response, 75% remission at 4 months. Read more
Osavampator (AMPA modulator): Enhances glutamate signaling; phase 2 showed no increased sedation/weight gain. Trial info
D-cycloserine (NCT00408031): NMDA receptor partial agonist, minimal cognitive/weight/sedation effects. Trial paper
Psilocybin (COMPASS Pathways, NCT06141876): Robust antidepressant effects, side effects: transient headache, nausea, no sedation/weight gain. Study

Trial participation usually means free care, extra safety monitoring, and a 1 in 2 or 1 in 3 chance of placebo. Phase 2 and 3 trials aren't guarantees: they might wow or disappoint. If the current side effects are intolerable or the benefits never arrive, this is how new possibilities happen.

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 sedation/drowsiness is the dealbreaker → Try bupropion OR CYB003 trials (no sedation reported)
If weight gain is your breaking point → Consider bupropion OR Osavampator/CYB003 trials
If constipation/dry mouth make life miserable → Try SSRIs or SNRIs (less anticholinergic effect) OR CYB003/D-cycloserine trials
If urinary retention occurs → Avoid all strong anticholinergics; bupropion or AMPA modulator trials

For every tough side effect, there's at least one plausible alternative—FDA-approved or still in the works. Clinical trials might finally skip the trade-offs.

Elavil (Amitriptyline) - antidepressant medication Image: Plushcare.com

Monitoring & What to Track

What your doctor should monitor:

PHQ-9 for depression, pain questionnaires for neuropathic conditions
Weight (especially if initial BMI >25)
Blood pressure, heart rate (TCAs can affect both)
Suicidal ideation, particularly in under 25s (increased risk)
Liver function if on high dose/long term

What you should track:

Daily mood/energy log (1-10)
All side effects—timing, severity, duration
Sleep quality and pattern
Appetite and weight changes
Any trouble with urination or constipation

If your doctor isn't tracking these, ask them to. Many side effects creep up—and if you don't write them down, they're easy to miss until they're impossible to ignore.

Pregnancy & Breastfeeding

FDA pregnancy category: Not assigned (older drugs like amitriptyline pre-date current categorization). Animal studies show possible risk; human studies are inadequate. Birth defect risk appears low but not zero.

Risks:

Untreated depression and pain disorders carry their own risks (preterm birth, poor maternal care, suicide risk)
Potential for neonatal withdrawal (jitteriness, drowsiness) if used late in pregnancy
Possible anticholinergic toxicity in newborns (rare)

Breastfeeding:

Amitriptyline is excreted in breast milk, but at low levels. Most data suggest it's relatively safe, but sedation in infants is possible. Monitor baby for feeding or alertness changes.

This is always a risk-benefit discussion, not a simple yes/no. Never stop suddenly if you become pregnant—always taper under supervision.

Emergency Warning Signs

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

Suicidal thoughts, plans, or attempt
Chest pain, severe palpitations, or sudden weakness/numbness (possible stroke/MI)
Severe confusion, fever, muscle rigidity, sweating (possible serotonin syndrome or NMS)
Allergic reaction: swelling, rash, difficulty breathing

📞 Call your doctor urgently if:

Unusual bleeding or bruising
Severe mood swings, agitation, or new/worsening anxiety
Persistent or worsening urinary retention or constipation
Severe or unresolving grogginess/sedation
Yellowing of skin/eyes (possible liver injury)

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

Summary & Next Steps

Key takeaways: Elavil (amitriptyline) stands out for its high rates of sedation (18 user reports, moderate severity), dry mouth, and weight gain (8 reports, often persistent)—not just in theory, but in the wild. While many find relief, side effects drive others to bail or seek new science. Most symptoms fade within the first month, but weight gain and morning grogginess can stick around.

If Elavil is working for you: Keep tracking side effects and mood; review weight, sedation, and sleep with your doctor every few months.

If side effects are intolerable: Don’t tough it out—ask about dose reduction, bupropion, SNRIs, or join a clinical trial (like CYB003) that ditches classic TCA baggage.

Your next steps:

Track your symptoms for 2 weeks using a mood and side effect 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
suicidal thinking and behavior (suicidality) ⚠️	0%	0%	unknown	Psychiatric
myocardial infarction ⚠️	0%	0%	unknown	Cardiovascular
stroke ⚠️	0%	0%	unknown	Cardiovascular
nonspecific ECG changes and changes in AV conduction ⚠️	0%	0%	unknown	Cardiovascular
heart block ⚠️	0%	0%	unknown	Cardiovascular
arrhythmias ⚠️	0%	0%	unknown	Cardiovascular
hypotension, particularly orthostatic hypotension ⚠️	0%	0%	unknown	Cardiovascular
syncope ⚠️	0%	0%	unknown	Cardiovascular
hypertension ⚠️	0%	0%	unknown	Cardiovascular
tachycardia	0%	0%	unknown	Cardiovascular
palpitation	0%	0%	unknown	Cardiovascular
coma ⚠️	0%	0%	unknown	Nervous System
seizures ⚠️	0%	0%	unknown	Nervous System
hallucinations ⚠️	0%	0%	unknown	Psychiatric
delusions ⚠️	0%	0%	unknown	Psychiatric
confusional states ⚠️	0%	0%	unknown	Nervous System
disorientation ⚠️	0%	0%	unknown	Nervous System
incoordination	0%	0%	unknown	Nervous System
ataxia	0%	0%	unknown	Nervous System
tremors	0%	0%	unknown	Nervous System
peripheral neuropathy	0%	0%	unknown	Nervous System
numbness, tingling and paresthesias of the extremities	0%	0%	unknown	Nervous System
extrapyramidal symptoms including abnormal involuntary movements and tardive dyskinesia ⚠️	0%	0%	unknown	Nervous System
dysarthria	0%	0%	unknown	Nervous System
disturbed concentration	0%	0%	unknown	Nervous System
excitement	0%	0%	unknown	Psychiatric
anxiety	0%	0%	unknown	Psychiatric
insomnia	0%	0%	unknown	Psychiatric
restlessness	0%	0%	unknown	Psychiatric
nightmares	0%	0%	unknown	Psychiatric

Boxed Warnings (Most Serious)

Increased risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies. Monitor all patients for clinical worsening, suicidality, or unusual changes in behavior.

Drug Interactions

Topiramate: may increase amitriptyline concentration; adjust dose based on clinical response.
Drugs metabolized by P450 2D6: Poor metabolizers or those taking inhibitors (e.g., quinidine, cimetidine, SSRIs, phenothiazines, propafenone, flecainide) may have increased TCA levels and toxicity; monitor and adjust dose as needed.
SSRIs (e.g., fluoxetine, sertraline, paroxetine): May inhibit P450 2D6 and increase TCA levels; allow at least 5 weeks after fluoxetine before starting amitriptyline.
Monoamine oxidase inhibitors (MAOIs): Contraindicated due to risk of hyperpyretic crises, severe convulsions, and death.
Guanethidine or similarly acting compounds: See warnings.
Thyroid medication: See warnings.
Alcohol, barbiturates, and other CNS depressants: See warnings.
Disulfiram: See warnings.
Anticholinergic agents or sympathomimetic drugs (including epinephrine with local anesthetics): May require close supervision and dose adjustment.
Neuroleptic drugs: Hyperpyrexia risk, especially during hot weather.

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?
Daytime drowsiness and sedation	18 posts	🟡 Moderate (12/18)	Ongoing for many; some report improvement after 2-4 weeks	Resolves
Dry mouth and dry eyes	12 posts	🟢 Mild (8/12)	Ongoing for many; some report improvement after a few weeks	Resolves
Significant weight gain	8 posts	🟡 Moderate (6/8)	Several months to ongoing; some report persistent weight gain	Resolves
Constipation and difficulty with bowel movements	7 posts	🟢 Mild (5/7)	Ongoing for some; improves for others after a few weeks	Resolves
Increased appetite and constant hunger	5 posts	🟢 Mild (4/5)	Ongoing while on medication	Resolves
Vivid and excessive dreams	5 posts	🟢 Mild (4/5)	Ongoing for some; others report it fades after a few weeks	Resolves
Morning grogginess and feeling zombified	4 posts	🟡 Moderate (3/4)	Ongoing for some; may improve after a few weeks	Resolves
Difficulty falling or staying asleep	4 posts	🟢 Mild (3/4)	Ongoing for some; may develop after initial sedation	Resolves
Nausea and upset stomach	2 posts	🟢 Mild (2/2)	First few days to weeks, usually resolves	Resolves
Visual disturbances during dose changes	2 posts	🟢 Mild (2/2)	During dose titration, resolves after stabilizing dose	Resolves
Feeling blue or apathetic mood	2 posts	🟢 Mild (2/2)	Ongoing while on medication	Resolves
Acid reflux and heartburn	1 posts	🟢 Mild (1/1)	Ongoing while on medication	Resolves
Irritability and mood swings	1 posts	🟡 Moderate (1/1)	Ongoing while on medication	Resolves
Sore throat	1 posts	🟢 Mild (1/1)	First few days to weeks	Resolves
Urinary retention and difficulty urinating	1 posts	🟡 Moderate (1/1)	Ongoing for some, especially with higher doses or long-term use	⚠️ Yes

User Quotes by Side Effect

Daytime drowsiness and sedation (Starts within first days, peaks in first 1-2 weeks, may improve after 2-4 weeks for some, persists for others)

"I know one of the most common side effects is drowsiness and boy do I have that!! I'm just wondering if that goes away after a period of time or improves at all." source

"It made me dangerously drowsy and constantly starving." source

"I feel like a zombie during the day. My energy is nonexistent." source

Dry mouth and dry eyes (Starts within first days, may persist for weeks to months, sometimes resolves)

"My side effects are just that it dries me out- dry eyes, dry mouth." source

"I experienced dry mouth for the first few months, but it went away." source

"There is some weight gain & dry mouth. Maybe some constipation." source

Significant weight gain (Usually starts after a few weeks, persists as long as medication is continued)

"It did nothing to help my migraines or my depression and it made me gain a ton of weight." source

"Gained migraines, a dry-ass mouth, and 15+ kilos of unshakeable body weight that I can't lose." source

"I took 20mg for 4 months, originally for insomnia, and the side effects I had were weight gain, acid reflux and constipation." source

Constipation and difficulty with bowel movements (Starts within first week, may persist or improve after a few weeks)

"I had really bad side effects with amitriptyline, nausea, constipation, drowsiness and insomnia. They gradually went away however whenever I'd stop and restart, they'd come back." source

"I do have some side effects, like sleepiness, constipation, and increased appetite." source

"There is some weight gain & dry mouth. Maybe some constipation." source

Increased appetite and constant hunger (Starts within first week, persists as long as medication is continued)

"It made me dangerously drowsy and constantly starving." source

"Very sleepy, very hungry. I decided to take a quarter of it instead to start and feel normal appetite now." source

"I do have some side effects, like sleepiness, constipation, and increased appetite." source

Vivid and excessive dreams (Starts within first week, may persist or fade after a few weeks)

"excessive dreams most of them oddly realistic and mundane to the point i am not sure if they ARE dreams." source

"It gave me vivid dreams and I would wake up feeling like I hadn't slept at all." source

"If I don't take it, I get stressful dreams and poor sleep quality." source

Morning grogginess and feeling zombified (Starts immediately, peaks in first week, may improve after a few weeks)

"I feel like a zombie during the day. My energy is nonexistent." source

"I deal with the morning grogginess by drinking a lot of water and coffee." source

"I took it at bedtime, and it made me super groggy in the morning." source

Difficulty falling or staying asleep (May develop after initial sedation, can persist or resolve after a few weeks)

"I had really bad side effects with amitriptyline, nausea, constipation, drowsiness and insomnia. They gradually went away however whenever I'd stop and restart, they'd come back." source

"Although it's supposed to make you sleepy, after a few weeks on 10mg, it actually started causing insomnia for me (4am wake ups, tested 2-3 times)." source

"She takes 10mg every night and I take 20mg. It really helps me sleep, and it helps her too, although her insomnia has always been much worse than mine." source

Nausea and upset stomach (Starts within first days, usually resolves within 1-2 weeks)

"I had really bad side effects with amitriptyline, nausea, constipation, drowsiness and insomnia. They gradually went away however whenever I'd stop and restart, they'd come back." source

"I had some nausea when I first started, but it went away after a week or so." source

Visual disturbances during dose changes (During dose increases, resolves within 1-2 weeks)

"I had some dry mouth and visual disturbances when I was titrating up to 30mg. But they weren't too bad." source

"I noticed some visual disturbances when increasing my dose, but they faded after a week." source

Feeling blue or apathetic mood (Starts within first month, persists as long as medication is continued)

"I was switched to amitriptyline (10mg) about a month ago, and I've been feeling blue, very apathetic." source

"Granted, I still felt zombified by my existence, but I did notice a bit of improvement." source

Acid reflux and heartburn (Starts after a few weeks, persists as long as medication is continued)

"I took 20mg for 4 months, originally for insomnia, and the side effects I had were weight gain, acid reflux and constipation." source

Irritability and mood swings (Starts within first week, persists as long as medication is continued)

"Dry mouth, irritability is through the roof, excessive dreams most of them oddly realistic and mundane to the point i am not sure if they ARE dreams." source

Sore throat (Starts within first days, usually resolves within a week or two)

"I started with 10mg every night, got a sore throat." source

Urinary retention and difficulty urinating (Starts after a few weeks, persists as long as medication is continued, may not resolve after stopping for some)

"If you've been on it for months with consistent retention then it sounds like it is not going away. Some people are more sensitive to retention than others." 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 2/3
NCT: NCT05385783
Mechanism: Deuterated psilocybin analog (psychedelic-derived, 5-HT2A receptor agonist)
Side Effect Comparison: Transient mild-to-moderate headache and nausea most common; no sexual dysfunction, weight gain, or sedation reported (unlike SSRIs/SNRIs); no evidence of dependence or withdrawal.
Efficacy Data:
- Response rate: 53% (CYB003 16mg) vs 18% (placebo) at 3 weeks
- Remission rate: 75% at 4 months (phase 2, open-label extension)
- MADRS change: -14.08 points (CYB003 16mg) vs -8.24 points (placebo) at 3 weeks
- Time to response: 1-3 weeks
- Source
Why it might interest you: Rapid onset (1-3 weeks), high remission rates, and a side effect profile lacking common SSRI/SNRI issues (sexual dysfunction, weight gain, sedation). Single or few doses may reduce need for daily medication.
Results: Significant and rapid reduction in depressive symptoms; high remission rates at 4 months; well-tolerated in phase 2 trial.
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: No significant increase in weight gain, sexual dysfunction, or sedation compared to placebo; side effect profile appears favorable vs SSRIs/SNRIs.
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 vs placebo
- Time to response: Expected to be faster than SSRIs (based on AMPA mechanism)
- Source
Why it might interest you: Novel AMPA modulation may offer faster onset and fewer side effects (less sexual dysfunction, weight gain, sedation) than standard antidepressants. Useful for those who do not tolerate or respond 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
NCT: NCT00408031
Mechanism: NMDA receptor partial agonist (glycine site)
Side Effect Comparison: Generally well-tolerated; no increase in sedation, weight gain, or sexual dysfunction compared to standard antidepressants; cognitive side effects rare.
Efficacy Data:
- Response rate: Not specified
- Remission rate: Not specified
- MADRS change: Not specified; significant improvement in depressive symptoms in phase 2 trial (NCT00408031)
- Time to response: Within 2 weeks (reported in some studies)
- Source
Why it might interest you: Different mechanism (NMDA modulation), rapid onset, and minimal side effects compared to SSRIs/SNRIs. May be especially useful for those with side effects or inadequate response to standard medications.
Results: Adjunctive D-cycloserine improved depressive symptoms in treatment-resistant depression and bipolar depression.
Sources: 1

Psilocybin (various studies, e.g., COMPASS Pathways, NCT06141876)

Sponsor: Multiple (COMPASS Pathways, Usona, academic)
Phase: Phase 2/3
NCT: NCT06141876
Mechanism: Classic psychedelic (5-HT2A receptor agonist)
Side Effect Comparison: Transient anxiety, headache, and nausea most common; no sexual dysfunction, weight gain, or chronic sedation; no evidence of dependence or withdrawal.
Efficacy Data:
- Response rate: Up to 54% at 3 weeks in TRD
- Remission rate: Varies by study; up to 29% at 3 weeks in TRD
- MADRS change: Not specified; psilocybin has shown large effect sizes in prior TRD studies (e.g., -17.8 vs -5.4 placebo at 3 weeks)
- Time to response: 1-3 weeks
- Source
Why it might interest you: Single or few doses, rapid onset, and side effect profile lacking common SSRI/SNRI issues. May be appealing for those seeking alternatives to daily medication with fewer chronic side effects.
Results: Rapid and robust antidepressant effects in TRD; FDA Breakthrough Therapy Designation; durable response in some patients.
Sources: 1, 2

Appendix D: Methodology

To prepare this guide, we reviewed over 30,000 clinical trial entries from ClinicalTrials.gov, screened more than 300 peer-reviewed articles via PubMed, and analyzed 54 user discussions alongside 89 OpenFDA Drug Label entries. We identified 15 unique adverse effects, ranked by frequency and severity. Real-world duration, resolution patterns, and user quotations with source links were then synthesized into the final resource.