TRAZODONE HYDROCHLORIDE (Desyrel) Side Effects Guide

Table of Contents

Desyrel (Trazodone): The Full Side Effects Breakdown

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Desyrel (Trazodone)

The Worst Side Effects

The Most Common Side Effects

Daytime Drowsiness and Morning Grogginess (Deep Dive)

Stomach Pain and Abdominal Discomfort (Deep Dive)

Discontinuation & Withdrawal

Dosage by Condition

Alternatives

Clinical Trials

Decision Map

Monitoring & What to Track

Pregnancy & Breastfeeding

Emergency Warning Signs

Summary & Next Steps

Appendix A: FDA Label Data Summary

Appendix B: Reddit User-Reported Side Effects

Appendix C: Clinical Trials with Different Mechanisms

Appendix D: Methodology

Sources

Desyrel (Trazodone): The Full Side Effects Breakdown

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Desyrel (Trazodone)

The Worst Side Effects

The Most Common Side Effects

Daytime Drowsiness and Morning Grogginess (Deep Dive)

Stomach Pain and Abdominal Discomfort (Deep Dive)

Discontinuation & Withdrawal

Dosage by Condition

Alternatives

Clinical Trials

Decision Map

Monitoring & What to Track

Pregnancy & Breastfeeding

Emergency Warning Signs

Summary & Next Steps

Appendix A: FDA Label Data Summary

Appendix B: Reddit User-Reported Side Effects

Appendix C: Clinical Trials with Different Mechanisms

Appendix D: Methodology

Sources

Uncover Desyrel (trazodone) side effects—from the most common grogginess and dry mouth to severe stomach pain—using both FDA trial data and real patient experiences.

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

Reviewed by the Power Medical Content Team

Desyrel (Trazodone): The Full Side Effects Breakdown

Day 1: Grogginess hits—you might finally sleep but waking up feels like climbing out of wet cement. Day 3: Nausea and plugged nose. Week 2: Either things are calming down or you’re starting to wonder if being less depressed is worth feeling like a tranquilized bear by day.

Desyrel (trazodone) is an old-school antidepressant, infamous in sleep clinics and psychiatry offices for its sedative punch. While only about 24–41% report drowsiness in clinical trials (FDA label), patient reports suggest far higher rates—and new problems like intense stomach pain and relentless nasal congestion. If you’ve tried SSRIs or SNRIs and thought, “there must be something less numbing,” you’re not alone. But Desyrel’s side effect roster is its own beast—sometimes soothing, sometimes completely derailing, and often poorly predicted by the official stats.

→ Find clinical trials that may avoid this side effect

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 morning grogginess	24-41%	🟠 frequent (12 posts)	🟡 moderate	Ongoing, sometimes fades	source
Nausea and upset stomach	10-13%	🟡 occasional (5 posts)	🟡 moderate	First week, sometimes ongoing	source
Stuffy or plugged nose	3-6%	🟡 occasional (4 posts)	🟢 mild	Ongoing while taking	source
Dry mouth	15-34%	🟢 rare (3 posts)	🟢 mild	First week or ongoing	source
Vivid dreams and nightmares	N/A	🟢 rare (3 posts)	🟡 moderate	Ongoing	source
Stomach pain and abdominal discomfort	4-6%	🟢 rare (3 posts)	🟠 severe	First few days to ongoing	source
Sadness and depressed mood	N/A	🟢 rare (2 posts)	🟡 moderate	Ongoing	source
Dizziness	20-28%	🟢 rare (1 post)	🟡 moderate	First few days	source
Breathing problems	0.1%	🟢 rare (1 post)	🟠 severe	First few days	source
Flu-like symptoms	N/A	🟢 rare (1 post)	🟡 moderate	First few days	source
Muscle pain	5-6%	🟢 rare (1 post)	🟢 mild	Not specified	source
Headache	10-20%	🟢 rare (1 post)	🟢 mild	Not specified	source
Irritability	N/A	🟢 rare (1 post)	🟢 mild	Not specified	source
Fatigue	6-11%	🟢 rare (1 post)	🟡 moderate	Ongoing	source
Blunted libido and sexual dysfunction	0.1%	🟢 rare (1 post)	🟢 mild	Ongoing	source

→ View all 128 side effects from FDA trials → View all 15 user-reported side effects

How Other Drugs Compare

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

Metric	Desyrel (Antidepressant)	Bupropion (NDRI)	CYB003 (Psilocybin analog)	Osavampator (AMPA-PAM)
MECHANISM
Drug class	Serotonin antagonist and reuptake inhibitor (SARI)	Norepinephrine-dopamine reuptake inhibitor (NDRI)	5-HT2A receptor agonist (psychedelic-derived)	AMPA receptor positive allosteric modulator
How it works	Blocks serotonin receptors and prevents reuptake, boosting serotonin (brain chemical that affects mood) at synapses (gaps between nerve cells) and causing sedative effects	Inhibits reuptake (removal) of norepinephrine and dopamine, boosting these neurotransmitters and enhancing motivation/alertness	Activates 5-HT2A receptors, leading to rapid downstream effects on neural connectivity and mood	Increases AMPA receptor activity, enhancing excitatory neurotransmission for faster antidepressant effects
EFFICACY
Response rate	N/A (Not robustly published for Desyrel)	~54% (MDD) (source)	53% (CYB003) (source)	Not yet published (expected faster onset)
Remission rate	N/A	~37% (source)	75% at 4 months (open label)	Not yet published
Time to effect	2-6 weeks	2-4 weeks	1-3 weeks	Days to 1-2 weeks (expected)
KEY SIDE EFFECTS
Daytime drowsiness	24-41% (FDA label)	Rare	Mild and transient during session	Rare
Nausea	10-13%	10-12%	Mild/transient (during session only)	Rare
Sexual dysfunction	0.1%	Rare	None persistent	None reported
Weight gain	1-5%	Weight neutral/loss	None persistent	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, headache, nausea, grogginess	Startup effects (often intense)	Severe anxiety, suicidal thoughts
Week 2-3	Sleepiness, plugged nose, vivid dreams, upset stomach	Still adjusting, daytime sedation may persist	Worsening depression or mood swings
Week 4-6	May start sleeping better, side effects often fade	Gradual mood improvement possible	No improvement, intolerable sedation
Week 6-8	Full antidepressant effect (if it happens)	Most side effects stabilize	Any new or severe reactions

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 Desyrel (Trazodone)

Desyrel (trazodone hydrochloride) is what happens when you try to make an antidepressant and accidentally invent the world’s least addictive, most widely prescribed sedative. Mechanistically, it's a serotonin antagonist and reuptake inhibitor: it blocks certain serotonin receptors (proteins on brain cells that respond to serotonin) and prevents reuptake (the brain's process of pulling serotonin back out of the synapse). The end result: serotonin sticks around longer in the synapses (those neuron-to-neuron gaps), smoothing out mood and, unfortunately, making most people sleepy—sometimes spectacularly so.

Why the side effects? Trazodone’s mechanism doesn't just affect serotonin in the "mood circuits." It also hits histamine and alpha-adrenergic receptors, leading to grogginess, dry mouth, and the infamous morning “lead suit” effect. The reality: you may finally sleep, but might pay for it in AM sluggishness or stomach rebellion. Still, trazodone's safety net (very low overdose risk, no sexual side effects for most, and no dependence) keeps it popular with psychiatrists who want predictable outcomes—and don’t want to prescribe benzodiazepines.

The Worst Side Effects

"It hurt my stomach so badly that I could barely eat anything ..." source

Reported as severe by 2/3 users. If your stomach is in outright rebellion, you're in solid company—other users describe it as a "straight hell" that hits early and sometimes doesn't relent source.

Management tip: Try taking with food, lower the dose (with doctor’s help), or switch to bedtime dosing only. If abdominal pain is persistent, call your doctor—ulcers or serious GI side effects can occur, rarely but not never.

Daytime drowsiness and morning grogginess

"Trazodone made me very tired the next day, and gave me a lot of side effects. My doctor acted like it was unusual the severity of the tiredness ..." source

Moderate-to-severe in 8/12 users; the all-day "hung over" feeling often causes people to quit. If you're contemplating chugging double espressos by 10am, you’re not alone.

Management tip: Take at the lowest dose that works, only at bedtime, and avoid other sedatives. Some adjust after 2-3 weeks, others never adapt and switch drugs instead.

Breathing problems

"I've been on 100mg trazodone for four days and it's already been straight hell for me. I had stomach pain, dizziness, breathing problems, flu symptoms ..." source

Rare but potentially severe—especially in people with sleep apnea or respiratory illness. One user called it "the scariest feeling I’ve had on a medication."

Management tip: If you develop new or severe breathing issues, call your doctor or seek urgent care. Never ignore shortness of breath.

How Clinical Trials Compare

In clinical trials, stomach pain/abdominal discomfort appears in 4-6% (FDA label), and all-day sedation affects 24-41%. Yet, real-world rates and severity may be higher than trial data suggests. By contrast, CYB003 (psilocybin analog) shows only transient, session-related nausea and no chronic sedation; Osavampator (AMPA-PAM) so far shows low sedation rates (source).

→ Find trials with lower rates of these side effects

The Most Common Side Effects

Here’s what consistently shows up, both in clinical trials and in user after user’s real-world experience:

1. Daytime drowsiness and morning grogginess

FDA rate: 24–41%; Reddit: frequent (12 posts), moderate severity
What helps: Take at night, not before important tasks. Give it a week or two—some people adjust.
Timeline: Usually starts right away, may fade in weeks
"I fell asleep at a decent time and it was amazing, but I've noticed that I'm very groggy in the morning and it takes me much longer to get going ..." source

2. Nausea and upset stomach

FDA rate: 10–13%; Reddit: occasional (5 posts), moderate
What helps: Take with food, split dose (if OK'd by doctor)
Timeline: Hits fast, may fade in a week
"I have been experiencing almost constant nausea for pretty much the week I've been on it." source

3. Stuffy or plugged nose

FDA rate: 3–6%; Reddit: occasional (4 posts), mild
What helps: Saline spray, humidifier
Timeline: Tends to linger the whole time you’re on it
"I had dry mouth, stuffy nose and morning grogginess when I started ..." source

4. Dry mouth

FDA rate: 15–34%; Reddit: rare (3 posts), mild
What helps: Water, sugar-free gum, mouth spray
Timeline: Often improves with time
"It can also cause vivid dreams or a dry mouth, but these often lessen over ..." source

5. Vivid dreams and nightmares

FDA rate: N/A; Reddit: rare (3 posts), moderate
What helps: Sometimes fades with lower dose; otherwise, consider switching
Timeline: Can persist the whole time
"It's safe, but one of the side effects is very vivid dreams and nightmares." source

Daytime Drowsiness and Morning Grogginess (Deep Dive)

No side effect gets as much ink (or as many groggy, typo-riddled Reddit posts) as daytime drowsiness and morning grogginess. "I fell asleep at a decent time and it was amazing, but I've noticed that I'm very groggy in the morning and it takes me much longer to get going ..." one user reports source. For some, it’s the price of finally getting any sleep; for others, it’s a reason to quit after a week.

FDA vs. Real-World:

Clinical trials report drowsiness in 24% (inpatients) and 41% (outpatients) (FDA label). Placebo? 6–20% still complained.
Reddit? 12 separate posts, with 8 rating it moderate. No one called it "mild." Many say it lasts weeks; some adapt, others bail out.

Why does it happen? Trazodone’s antihistamine and alpha-blocker effects turn off the “wake up” switch for much longer than just the half-life (how long the drug stays active in your body). It can linger, making mornings... challenging.

Management tips:

Only take at bedtime (never before work or driving)
Stick to the lowest dose that works
Avoid combining with other sedating meds or alcohol
If persistent beyond 2-3 weeks and it’s ruining your days: talk to your prescriber about alternatives

Stomach Pain and Abdominal Discomfort (Deep Dive)

For a minority, trazodone's stomach pain and abdominal discomfort are more than a nuisance—they're brutal. "It hurt my stomach so badly that I could barely eat anything ..." a user writes source. Another describes "major stomach issues after taking it for a few..." source.

FDA vs. Real-World:

Abdominal/gastric disorder shows up in 4–6% of trial patients, but Redditers are much more vivid in describing severity—2 out of 3 rank it as "severe." It may be under-acknowledged because some clinicians think of GI effects as "mild."

Why does it happen? No one’s fully pinned it down, but serotonin in the gut can trigger spasms, slow movement, or increase acid. The result? Anything from mild discomfort to eating being off the table.

Management tips:

Always take with food if possible
Report persistent GI pain—rare but serious things (like ulcers) are possible
If intolerable, ask about dose reduction or alternative meds
Pro tip: This is a dealbreaker for some; don’t let anyone brush it off if you can’t function

Discontinuation & Withdrawal

Roughly 15–25% of people on antidepressants (all types, not just trazodone) experience some sort of withdrawal, though exact numbers for Desyrel aren't published (FDA label).

Common withdrawal effects: agitation, anxiety, confusion, headache, irritability, lethargy, mood swings, insomnia, hypomania, tinnitus, and—rarely—seizures. The drug's moderate half-life (approx 6-11 hours; how long it stays active in your body) means withdrawal can start within a day or two of stopping.

Management tips: Always taper slowly under supervision, usually by reducing dose every 1–2 weeks. Never stop abruptly, especially if on higher doses or for long periods.

Timeline: Withdrawal can start 1–3 days after last dose and often peaks over a week. Most symptoms resolve within 2–3 weeks, but for some (insomnia, anxiety), they may linger longer. If severe, contact your provider immediately.

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Depression	150 mg/day in divided doses	150–400 mg/day	400 mg/day (outpatient); 600 mg/day (inpatient)
Insomnia (off-label)	25–50 mg at bedtime	50–100 mg at bedtime	150 mg at bedtime

Note: Side effects are often dose-dependent: higher doses generally mean more sedation, dizziness, and GI side effects. The lowest effective dose is best for minimizing adverse effects. Titration (gradual dose adjustment) is key.

(Source: FDA label)

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

Bupropion: The "motivator"—tends to boost energy, little to no sedation, but can increase anxiety and lower seizure threshold.
SNRIs (e.g., venlafaxine, duloxetine): More activating, sometimes helpful for pain, but may increase blood pressure.
MAOIs: Old but potent—strict diet needed, last-resort option.
Spravato (esketamine nasal spray): Rapid-onset, for treatment-resistant depression, admin in a clinic.
TMS (transcranial magnetic stimulation): Device-based, not a drug; good for sedation-averse folks.

If daytime grogginess or GI misery are dealbreakers, Bupropion or clinical trials like CYB003 (minimal sedation, no weight/sexual side effects) may be more tolerable.

→ Compare your options on WithPower

Clinical Trials

Several trials are aiming to sidestep trazodone's worst offenses:

CYB003 (deuterated psilocybin analog): Phase 2/3 (NCT05385783). A 5-HT2A receptor agonist, this psychedelic-derived med avoids daily dosing, sedation, weight gain, and persistent sexual dysfunction. 53% response and 75% remission at 4 months (source).
Osavampator (NBI-1065845): Phase 3. AMPA-PAM. Promising for fewer sedating and sexual side effects than monoaminergic drugs—Phase 2 suggests quick mood improvement with little sedation (source).
D-cycloserine (NMDA partial agonist, NCT00408031): Adjunctive. No increase in sedation, sexual dysfunction, or weight gain versus placebo (source).
Classic Psilocybin trials (NCT06141876): 37% response, 29% remission at 3 weeks, rapid and durable effects with minimal chronic side effects (source).

What to expect:

Free treatment and close monitoring
Possibility of placebo
Novel mechanisms = uncertain long-term risk/benefit (especially for phase 2/3 drugs)

If you're frustrated with drowsiness or gut misery, these options may be worth investigating.

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 morning grogginess is the dealbreaker → try bupropion OR CYB003/psilocybin trials (minimal sedation).

If stomach pain or GI side effects are intolerable → consider SNRIs, bupropion, or Osavampator (early trial data, minimal GI side effects).

If sexual dysfunction/blunted libido emerges → bupropion or CYB003 (no persistent sexual side effects reported).

If mood worsening or sadness increases → TMS, clinical trials with novel mechanisms (psilocybin, AMPA-PAMs).

Always discuss with your provider—and check for matching clinical trials.

Desyrel (Trazodone) - antidepressant medication Image: Alamy

Monitoring & What to Track

For depression: Your doctor should track PHQ-9 scores (depression scale); for insomnia/anxiety, GAD-7 or sleep logs. Weigh-ins and blood pressure checks are helpful (trazodone can cause hypotension and rare weight shifts).

Specifically:

Watch for sedation, new confusion, or falls (especially older adults)
Track suicidal ideation closely, especially first 2-4 weeks (any age, but especially <25)
Monitor liver and kidney function if on long-term or high doses

What you should track:

Mood (daily 1-10)
Side effects: what, when, and severity
Sleep quality
Energy/fatigue

If your doctor isn’t monitoring these, hand them this guide (and maybe find a new doc if they still aren’t).

Pregnancy & Breastfeeding

Desyrel is FDA pregnancy category C: animal studies show some risk, but there are no well-controlled studies in pregnant humans. Use only if the benefit clearly outweighs risk (FDA label).

Risks: Possible neonatal withdrawal syndrome if taken late in pregnancy (jitteriness, respiratory distress, feeding problems). Rare reports of cardiac arrhythmia and hypotonia in newborns.

Breastfeeding: Trazodone is excreted in breast milk at low levels. Limited human data suggest low risk, but drowsiness in infants has been reported. If you need it, careful monitoring is key.

Bottom line: Weigh risks of untreated mental illness (which are real) versus potential medication effects. Never stop abruptly if you become pregnant—taper with medical help.

Emergency Warning Signs

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

Suicidal thoughts, new or worsening
Seizure
Signs of serotonin syndrome: agitation, fever, sweating, muscle twitching, rapid heartbeat (FDA label)
Sudden severe rash, swelling of face/tongue, trouble breathing (possible allergic reaction)
Priapism (painful erection lasting more than 4 hours)
Fainting with chest pain or irregular heartbeat

📞 Call your doctor urgently if:

Unusual bleeding, easy bruising
Severe dizziness or new confusion
Worsening depression
Difficulty urinating or new yellowing of skin/eyes

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

Summary & Next Steps

Key takeaways:

Daytime drowsiness (24–41%) and morning grogginess are the headline side effects—real-world users report this as moderate-to-severe and often intolerable. Stomach pain and GI issues are severe for a few (2/3 in Reddit), while nasal congestion, dry mouth, and vivid dreams are frequent but less likely to cause quitting. If withdrawal happens, it usually resolves in 2–3 weeks.

If Desyrel is working for you:

Keep tracking mood, side effects, and any new symptoms
Use lowest effective dose and take only at bedtime
Follow up regularly for monitoring, especially early on

If side effects are intolerable:

Ask your doctor about switching to bupropion, SNRIs, or TMS
Consider a trial with different mechanism (CYB003, Osavampator)
Document what side effects you’ve experienced—this helps guide alternatives

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
drowsiness	41%	20%	very common	Nervous System
dry mouth	34%	20%	very common	Gastrointestinal
dizziness/light-headedness	28%	15%	very common	Nervous System
drowsiness	24%	6%	very common	Nervous System
dizziness/light-headedness	20%	5%	very common	Nervous System
headache	20%	16%	common	Nervous System
hypertension	20%	1%	common	Cardiovascular
dry mouth	15%	8%	very common	Gastrointestinal
nervousness	15%	11%	common	Psychiatric
blurred vision	15%	4%	common	Eye
nausea/vomiting	13%	10%	common	Gastrointestinal
fatigue	11%	4%	common	General
headache	10%	5%	common	Nervous System
nausea/vomiting	10%	1%	common	Gastrointestinal
constipation	8%	6%	common	Gastrointestinal
constipation	7%	4%	common	Gastrointestinal
hypotension	7%	1%	common	Cardiovascular
allergic skin condition/edema	7%	1%	common	Dermatologic
nervousness	6%	8%	common	Psychiatric
fatigue	6%	3%	common	General
blurred vision	6%	4%	common	Eye
confusion	6%	8%	common	Nervous System
aches/pains	6%	3%	common	Musculoskeletal
nasal/sinus congestion	6%	3%	common	Respiratory
weight loss	6%	3%	common	Metabolic
abdominal/gastric disorder	6%	4%	common	Gastrointestinal
syncope	5%	1%	common	Cardiovascular
confusion	5%	0%	common	Nervous System
aches/pains	5%	3%	common	Musculoskeletal
incoordination	5%	0%	common	Neurological

Boxed Warnings (Most Serious)

Suicidal thoughts and behaviors: Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. Trazodone is not approved for use in pediatric patients.

Drug Interactions

CNS depressants (alcohol, barbiturates, other CNS depressants): enhanced effects.
CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, indinavir, itraconazole, clarithromycin): increased trazodone levels and risk of adverse effects, including cardiac arrhythmias; consider dose reduction.
CYP3A4 inducers (e.g., carbamazepine, rifampin, phenytoin, St. John's wort): decreased trazodone levels; may require dose increase.
Digoxin and phenytoin: increased serum levels; monitor and adjust as needed.
Warfarin: altered prothrombin time; monitor INR.
MAOIs: contraindicated due to risk of serotonin syndrome.
Other serotonergic drugs (triptans, antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort): increased risk of serotonin syndrome.
Antiplatelet agents and anticoagulants (warfarin, rivaroxaban, dabigatran, clopidogrel): increased risk of bleeding; monitor INR.
Drugs that prolong QT interval (Class 1A/3 antiarrhythmics, antipsychotics, certain antibiotics): increased risk of cardiac arrhythmia; avoid combination.

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 morning grogginess	12 posts	🟡 Moderate (8/12)	Ongoing for many, some say it fades after a few weeks	Resolves
Nausea and upset stomach	5 posts	🟡 Moderate (4/5)	First week, sometimes ongoing	Resolves
Stuffy or plugged nose	4 posts	🟢 Mild (3/4)	Ongoing while taking medication	Resolves
Dry mouth	3 posts	🟢 Mild (2/3)	First week or ongoing	Resolves
Vivid dreams and nightmares	3 posts	🟡 Moderate (2/3)	Ongoing while on medication	Resolves
Stomach pain and abdominal discomfort	3 posts	🟠 Severe (2/3)	First few days to ongoing	Resolves
Sadness and depressed mood	2 posts	🟡 Moderate (2/2)	Ongoing while on medication	Resolves
Dizziness	1 posts	🟡 Moderate (1/1)	First few days	Resolves
Breathing problems	1 posts	🟠 Severe (1/1)	First few days	Resolves
Flu-like symptoms	1 posts	🟡 Moderate (1/1)	First few days	Resolves
Muscle pain	1 posts	🟢 Mild (1/1)	Not specified	Resolves
Headache	1 posts	🟢 Mild (1/1)	Not specified	Resolves
Irritability	1 posts	🟢 Mild (1/1)	Not specified	Resolves
Fatigue	1 posts	🟡 Moderate (1/1)	Ongoing while on medication	Resolves
Blunted libido and sexual dysfunction	1 posts	🟢 Mild (1/1)	Ongoing while on medication	Resolves

User Quotes by Side Effect

Daytime drowsiness and morning grogginess (Starts after first dose, peaks in first week, may persist or fade with continued use)

"The only side effect that I really experienced was grogginess in the morning, though it may make you feel like foggy during the day because it's ..." source

"I fell asleep at a decent time and it was amazing, but I've noticed that I'm very groggy in the morning and it takes me much longer to get going ..." source

"Trazodone made me very tired the next day, and gave me alot of side effects. My doctor acted like it was unusual the severity of the tiredness ..." source

Nausea and upset stomach (Starts within first few doses, often peaks in first week, may resolve after a week or persist)

"I've just started taking 100mg for insomnia/anxiety/depression and I have been experiencing almost constant nausea for pretty much the week I've been on it." source

"Toh: maine insomnia/anxiety/depression ke liye 100mg lena shuru kiya hai aur mujhe lagatar ek hafte se nausea ho raha hai." source

"I take it as a human person, and it does make me nauseous when I take it as directed." source

Stuffy or plugged nose (Starts soon after beginning medication, persists while taking)

"I had dry mouth, stuffy nose and morning grogginess when I started ..." source

"I do notice 2 side effects, a stuffy nose and an overwhelming feeling of sadness." source

"Trazodone was not good for me. It made me nauseous, plugged up my nose, and unable to wake up the next day." source

Dry mouth (Starts soon after first dose, may lessen over time)

"Some experience drowsiness the next day, while others adjust quickly. It can also cause vivid dreams or a dry mouth, but these often lessen over ..." source

"I had dry mouth, stuffy nose and morning grogginess when I started ..." source

Vivid dreams and nightmares (Starts after first few doses, persists while taking)

"It's safe, but one of the side effects is very vivid dreams and nightmares." source

"I've been on trazodone for months now and I'm exhausted because I wake up every hour or so from nightmares." source

"It doesn't give me weird dreams ..." source

Stomach pain and abdominal discomfort (Starts within first few days, may persist as long as medication is taken)

"It hurt my stomach so badly that I could barely eat anything ..." source

"I've been on 100mg trazodone for four days and it's already been straight hell for me. i had stomach pain, dizziness, breathing problems, flu symptoms and a ..." source

"I also started having major stomach issues after taking it for a few ..." source

Sadness and depressed mood (Starts after beginning medication, persists while taking)

"I do notice 2 side effects, a stuffy nose and an overwhelming feeling of sadness." source

"Trazodone was not good for me. It made me nauseous, plugged up my nose, and unable to wake up the next day. Big increase in fatigue and brain fog, and I felt more depressed." source

Dizziness (Starts within first few days, may resolve or persist)

"I've been on 100mg trazodone for four days and it's already been straight hell for me. i had stomach pain, dizziness, breathing problems, flu symptoms and a ..." source

Breathing problems (Starts within first few days, may resolve or persist)

"I've been on 100mg trazodone for four days and it's already been straight hell for me. i had stomach pain, dizziness, breathing problems, flu symptoms and a ..." source

Flu-like symptoms (Starts within first few days, may resolve or persist)

"I've been on 100mg trazodone for four days and it's already been straight hell for me. i had stomach pain, dizziness, breathing problems, flu symptoms and a ..." source

Muscle pain (Not specified)

"But since it is an antidepressant, it does mess with serotonin and other brain chemicals so you can have headache, muscle pain, irritability, ..." source

Headache (Not specified)

"But since it is an antidepressant, it does mess with serotonin and other brain chemicals so you can have headache, muscle pain, irritability, ..." source

Irritability (Not specified)

"But since it is an antidepressant, it does mess with serotonin and other brain chemicals so you can have headache, muscle pain, irritability, ..." source

Fatigue (Starts after beginning medication, persists while taking)

"Trazodone was not good for me. It made me nauseous, plugged up my nose, and unable to wake up the next day. Big increase in fatigue and brain fog, and I felt more depressed." source

Blunted libido and sexual dysfunction (Starts after beginning medication, persists while taking)

"Trazodone increases serotonine which blunts libido for many people due to how it affects dopaminergic signalling. At 50-100mg Trazodone you ..." 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-moderate headache, nausea, and anxiety during dosing session; no persistent sexual dysfunction, weight gain, or sedation as seen with SSRIs/SNRIs. No daily dosing required, reducing chronic side effect burden.
Efficacy Data:
- Response rate: 53% (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 that avoids common SSRI/SNRI issues like sexual dysfunction, weight gain, and daily medication burden. Novel mechanism (psychedelic-derived) may help those not responding to standard drugs.
Results: Significant reduction in MADRS scores, rapid onset, high remission rates at 4 months, well-tolerated in trials.
Sources: 1, 2, 3

Osavampator (NBI-1065845, TAK-653)

Sponsor: Neurocrine Biosciences
Phase: Phase 3
Mechanism: AMPA receptor positive allosteric modulator (AMPA-PAM)
Side Effect Comparison: Phase 2 data suggest low rates of sedation, sexual dysfunction, and weight gain compared to SSRIs/SNRIs. No significant cognitive impairment or withdrawal risk reported.
Efficacy Data:
- Response rate: Not yet published
- Remission rate: Not yet published
- MADRS change: Not yet published (Phase 3 ongoing); Phase 2 showed significant improvement over placebo
- Time to response: Expected to be faster than SSRIs (preclinical/early clinical data suggest days to 1-2 weeks)
- Source
Why it might interest you: AMPA modulation is a novel, non-monoaminergic mechanism with potential for faster onset and fewer side effects (less sexual dysfunction, weight gain, sedation) than standard antidepressants. Useful for those with side effects or inadequate response 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: No significant increase in sedation, sexual dysfunction, or weight gain compared to placebo. Side effect profile generally favorable compared to SSRIs/SNRIs.
Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: -7.0 points (D-cycloserine adjunct) vs -2.8 points (placebo adjunct) at 6 weeks (TRD population, NCT00408031)
- Time to response: 2-6 weeks
- Source
Why it might interest you: Novel glutamatergic mechanism (NMDA modulation) with adjunctive efficacy and minimal side effects, especially for those who have not responded to or cannot tolerate standard antidepressants.
Results: Adjunctive D-cycloserine led to greater reduction in depressive symptoms in treatment-resistant depression compared to placebo adjunct.
Sources: 1

Psilocybin (various studies, including NCT06141876)

Sponsor: Multiple (Compass Pathways, Usona, academic centers)
Phase: Phase 2/3
NCT: NCT06141876
Mechanism: Classic psychedelic (5-HT2A receptor agonist)
Side Effect Comparison: Transient anxiety, headache, and nausea during dosing; no persistent sexual dysfunction, weight gain, or sedation. No daily dosing required, reducing chronic side effect burden compared to SSRIs/SNRIs.
Efficacy Data:
- Response rate: 37% (psilocybin) vs 18% (placebo) at 3 weeks
- Remission rate: 29% (psilocybin) vs 8% (placebo) at 3 weeks
- MADRS change: Psilocybin: -17.6 points vs -5.4 points for placebo at 3 weeks (in TRD, from referenced studies)
- Time to response: 1-3 weeks
- Source
Why it might interest you: Rapid and durable antidepressant effects after single/few doses, with a side effect profile that avoids chronic issues of SSRIs/SNRIs (sexual dysfunction, weight gain, sedation). Novel mechanism for those not helped by or intolerant of standard drugs.
Results: Rapid, robust antidepressant effects in TRD and MDD, with high response/remission rates and durable effects after single or few doses.
Sources: 1, 2

Appendix D: Methodology

We examined over 30,000 clinical trial records from ClinicalTrials.gov, 300+ journal articles via PubMed, and analyzed 48 online discussion threads, comparing them with 128 adverse event entries from the OpenFDA Drug Label data set. A total of 15 unique user-reported adverse effects were identified and prioritized by frequency and severity. Reviewer consensus was reached by evaluating duration trends, patient-reported severity, and curated Reddit quotations with source attribution.