CARIPRAZINE (Vraylar) Side Effects Guide

Table of Contents

Intro

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Vraylar

The Worst Side Effects

The Most Common Side Effects

Weight Gain (Weight gain)

Drowsiness and Sedation

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 Vraylar

The Worst Side Effects

The Most Common Side Effects

Weight Gain (Weight gain)

Drowsiness and Sedation

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 a detailed side effects guide to Vraylar (cariprazine), blending FDA data with real user experiences. Find honest severity ratings, timelines, and alternative options for informed decisions.

Medication: Vraylar (CARIPRAZINE) Drug Class: Atypical Antipsychotic [EPC] Author: Michael Baskerville Gill, B. Sc.

Reviewed by the Power Medical Content Team

Intro

Day 1: A weird fizz of energy—maybe nerves, maybe something else. Day 7: Restlessness creeping in. Month 2: "Nothing much changed... until the scale did."

Vraylar (cariprazine) is an atypical antipsychotic—one of the newer kids on the psychiatric block—used for bipolar disorder, schizophrenia, and as an adjunct in major depressive disorder (MDD). The pitch: fewer old-school antipsychotic side effects, more mood stability, sometimes even a brighter outlook for depression.

But the story rarely unfolds as neatly as a commercial might promise. In FDA trials, up to 20% had movement-related symptoms (the dreaded EPS), and 14% got akathisia (that crawling-out-of-your-skin feeling). Real-world users? They'll tell you about everything from unstoppable drowsiness to inexplicable weight gain that creeps up after months. Standard treatments have never been perfect for these illnesses—and Vraylar is no exception. For some, it’s a lifeline; for others, another stop on the psychiatric merry-go-round. The truth is, we still don’t know why certain people get hammered by side effects and others don’t.

If you’re searching for answers beyond the package insert, you’re in the right place.

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

Side Effects Overview Table

Side Effect	FDA Rate	Reddit Reports	Severity	Duration	Example
Weight gain	3%	🟡 Occasional (4 posts)	🟠 Severe	Ongoing (months)	"I've gained about 50lbs. I think it's due to Vraylar..."
Restlessness and inability to sit still (akathisia)	14%	🟡 Occasional (4 posts)	🟡 Moderate	Weeks to months	"I've been incredibly restless and unable to sit still..."
Nausea and upset stomach	13%	🟡 Occasional (4 posts)	🟡 Moderate	Days to ongoing	"I took my first dose Tuesday night and all day yesterday I was so sick..."
Difficulty falling or staying asleep (insomnia)	13%	🟢 Rare (3 posts)	🟠 Severe	1 week to ongoing	"Insomnia - I wake between 3-4am every. single. day..."
Drowsiness and feeling very sleepy	11% (somnolence)	🟢 Rare (3 posts)	🟠 Severe	Days to weeks	"It made me so drowsy I could barely move..."
Dry mouth	5%	🟢 Rare (3 posts)	🟢 Mild	Days to weeks	"Dry Mouth."
Increased anxiety or agitation	6%	🟢 Rare (3 posts)	🟡 Moderate	Weeks to ongoing	"The good feelings simmered... then it was just anxiety + agitation."
Worsening or persistent depression	N/A	🟢 Rare (3 posts)	🟡 Moderate	Ongoing	"Ever since I started Vraylar, I have been feeling more depressed..."
Tremors and muscle spasms	N/A	🟢 Rare (2 posts)	🟡 Moderate	Days to weeks	"Twitching/Muscle Spasms"
Fatigue and muscle weakness	10%	🟢 Rare (2 posts)	🟡 Moderate	Days to weeks	"It knocked me out, made me grumpy and angry, lethargic."
Decreased sexual desire (libido)	N/A	🟢 Rare (2 posts)	🟡 Moderate	Ongoing	"...but completely killed my libido."
Excessive sweating	2%	🟢 Rare (1 post)	🟢 Mild	Days to weeks	"...Akathisia, sweating, nausea, insomnia..."
Headaches	18%	🟢 Rare (1 post)	🟢 Mild	Days to weeks	"Headaches, sleepiness, dry mouth, upset tummy."
Irritability and anger	N/A	🟢 Rare (1 post)	🟡 Moderate	Days to weeks	"It knocked me out, made me grumpy and angry, lethargic."
Dizziness and lightheadedness	7%	🟢 Rare (1 post)	🟢 Mild	Days to weeks	"...slight nausea and being lightheaded."

→ View all 48 side effects from FDA trials → View all 15 user-reported side effects

How Other Drugs Compare

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

Metric	Vraylar (Atypical Antipsychotic [EPC])	CYB003 (Deuterated Psilocybin)	Osavampator (AMPA-R PAM)	D-cycloserine (NMDA partial agonist)
MECHANISM
Drug class	Atypical antipsychotic	Psychedelic analog	Glutamatergic modulator	NMDA receptor modulator
How it works	D2/D3 dopamine receptor partial agonist, modulates dopamine/serotonin	Activates 5-HT2A receptors, promotes neuroplasticity	Positive allosteric modulator of AMPA receptors (increases glutamatergic signaling)	Glycine-site partial agonist at NMDA receptor
EFFICACY
Response rate	44-60% (bipolar, MDD adjunct)FDA	79% (Phase 2, 3 weeks)1	Not yet reported	Not reported
Remission rate	~22-40% (MDD adjunct, bipolar)FDA	75% (Phase 2, 4 months)1	Not yet reported	Not reported
Time to effect	1-4 weeks	1-3 weeks	Expected rapid	2-6 weeks
KEY SIDE EFFECTS
Weight gain	3% (up to 50 lbs real-world, severe)[see above]	None chronic (transient nausea/headache only)[1]	None chronic reported	None chronic reported
Akathisia/restlessness	14% (occasional, moderate-severe)[see above]	Rare, acute anxiety only[1]	Not reported	Not reported
Sexual dysfunction	Rare	None[1]	None reported	None reported
Sedation/drowsiness	11% (severe for some)	None chronic[1]	None reported	None reported

→ Find clinical trials matched to your situation

Week-by-Week Timeline

Week	Common Experiences	What's Normal	When to Call Your Doctor
Week 1	Nausea, headache, restlessness, insomnia	Startup effects	Severe agitation, suicidal thoughts
Week 2-3	Sleep/appetite shifts, drowsiness, possible anxiety	Still adjusting	Worsening depression
Week 4-6	May start noticing benefit, side effects may ease	Gradual improvement	No improvement or severe side effects
Week 6-8	Full effect often reached	Stable	Intolerable or new 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 Vraylar

Let’s get into the weirdness under the hood: Vraylar is a dopamine D2/D3 receptor partial agonist (which means it gently activates these receptors—proteins on your neurons that respond to dopamine, the brain’s motivation/alertness chemical—instead of slamming the pedal to the metal). It also pokes at serotonin receptors (brain chemicals for mood and calm), but in a less direct way than SSRIs.

Why do side effects like restlessness or movement disorders crop up? Because when you nudge dopamine transmission in the motor system (think: the parts of the brain that make your hands, arms, and face move), things can get twitchy. Akathisia—restlessness, like you want to run a marathon while stuck in an MRI—is a classic result.

What’s the trade-off? For some, real relief from mania, mood swings, or depression. For others: side effects that crowd out any benefit. Doctors still prescribe Vraylar because, for a subset of patients, it works when nothing else does, the risks are predictable, and (unlike older antipsychotics) it doesn’t tank white blood cells or unleash permanent movement disorders—at least not often.

The Worst Side Effects

Weight gain

"I've gained about 50lbs. I think it's due to Vraylar and he finally let me get off of it." source Reported as severe by 2/4 users. Weight gain can creep in months after starting and is often a "tipping point" for quitting. Management tip: Track your weight monthly. If gain exceeds 5% of baseline or you’re distressed, ask about alternatives like aripiprazole, ziprasidone, or medications known for weight neutrality.

Drowsiness and sedation

"It made me so drowsy I could barely move, I felt like a zombie for weeks." source Rated severe by 2/3 users. Can lead to missed work, accidents, or quitting the drug. Management tip: Try moving your dose to the evening. Some adjust slowly and the drowsiness fades, but for others, it’s persistent.

Insomnia

"Insomnia - I wake between 3-4am every. single. day and cannot go back to sleep." source Severe for 2/3 users mentioning it. For some, sleep never normalizes. Management tip: Strict sleep hygiene, early-in-the-day dosing, or adjunct low-dose trazodone. If nothing helps, consider switching.

Akathisia (restlessness)

"I've been incredibly restless and unable to sit still, a condition known as akathisia." source Rated moderate (and extremely unpleasant) by 3/4 users. Sometimes persists, sometimes fades after several weeks. Management tip: Beta blockers, dose reduction, or switching medications may help; always report severe restlessness immediately.

How Clinical Trials Compare

CYB003 (deuterated psilocybin) had no chronic weight gain or sedation, and only brief nausea/anxiety during dosing session (source). In contrast, Vraylar real-world users report severe, persistent weight gain and sedation in a subset. Osavampator and D-cycloserine also show minimal chronic side effects so far (source). → Find trials with lower rates of these side effects

The Most Common Side Effects

1. Extrapyramidal symptoms (movement issues)

FDA: 20% (up to 29% in mania)
Reddit: Multiple users, moderate to severe
What helps: Report symptoms promptly; dose reduction, switching, or adjunct medications (benztropine) can help. Some see gradual improvement.
Timeline: Usually starts within weeks. May persist if not addressed.

"Vraylar has more EPS than some other antipsychotics and... does often cause some weight gain." source

2. Akathisia (restlessness/inability to sit still)

FDA: 14% (up to 23% in MDD adjunctive)
Reddit: 4 posts, moderate
What helps: Beta blockers, moving dose to AM, reducing dose. Severe? Talk to your prescriber.
Timeline: Starts week 1. Persists weeks to months, may resolve for some.

"I've been incredibly restless and unable to sit still..." source

3. Nausea and upset stomach

FDA: 13% (up to 13% mania/MDD)
Reddit: 4 posts, moderate
What helps: Take with food, split dose, ginger chews. Sometimes anti-nausea medication if severe.
Timeline: Days to weeks, sometimes never resolves.

"the nausea side effect my pdoc hoped would go away never did." source

4. Weight gain

FDA: 3% (but see real-world rates)
Reddit: 4 posts, severe
What helps: Track weight, minimize carb/snack intake, regular exercise. If >5% weight gain or distress, discuss alternative meds.
Timeline: Can start months in; rarely reverses unless drug stopped.

"I've gained about 50lbs... finally let me get off of it." source

5. Insomnia

FDA: 13%
Reddit: 3 posts, severe
What helps: Strict sleep schedule, AM dosing. If persists, low-dose sleep adjuncts.
Timeline: Starts week 1, may persist; some acclimate, others don't.

"Insomnia - I wake between 3-4am every. single. day and cannot go back to sleep" source

Weight Gain (Weight gain)

For a drug advertised as "weight neutral," Vraylar’s relationship with the bathroom scale is complicated. FDA trials reported a 3% rate for weight gain—so why do real people keep showing up on Reddit describing major gains?

"I was fine for the first 5 months on it but then the weight gain started..." source

"I've gained about 50lbs. I think it's due to Vraylar and he finally let me get off of it." source

The real-world data (severe, ongoing in 2/4 Reddit users) suggest a subset experience substantial, persistent weight gain—sometimes after months of smooth sailing. This may be partly explained by Vraylar’s partial effect at serotonin 5-HT2C receptors (proteins that, when blocked, tend to increase appetite and weight).

What can you do?

Track your weight monthly—don’t assume it’s “just life.”
Switch antipsychotics if gain is rapid, distressing, or exceeds 5-7% of baseline body weight.
Some users find benefit from upping exercise or tightening diet, but the effect is often modest until the drug is stopped.

For many, the weight begins to drop only after discontinuing Vraylar. Always discuss options before stopping, as withdrawal or relapse is possible. Remember, if this is a dealbreaker, some clinical trial agents (like CYB003 or osavampator) report no chronic weight gain so far.

Drowsiness and Sedation

Antipsychotics are infamous for flattening your get-up-and-go, but Vraylar is supposed to be less zombifying than the older crowd. The FDA says 11% got "somnolence" or sedation. In the wild? It’s still a real problem for some.

"I couldn't handle Vraylar at all. It made me so drowsy I could barely move..." source

But the effect isn’t universal.

"I have been on 1.5 mg Vraylar for 3 years. It has worked really well for me — no side effects so far, and it does not make me drowsy." source

Why does it happen? Vraylar modulates dopamine and serotonin. Both are crucial for staying awake and alert. For some, this means lights out at noon. The drowsiness can be dose-dependent: more drug, more "gravity."

Management tips:

Switch to nighttime dosing if approved by your prescriber
Lower the dose (if possible)
Wait it out; some acclimate after a couple weeks

But if you’re the unlucky sort where drowsiness just doesn’t let go, switching to a trial agent or a different antipsychotic might be the best ticket out.

Discontinuation & Withdrawal

The FDA label is pretty blunt: Vraylar doesn’t trigger a classic withdrawal syndrome. But abrupt stopping—especially after months—can make old symptoms roar back (mood swings, psychosis, agitation) or spark withdrawal-like effects: anxiety, insomnia, or even "brain zaps" (yes, that’s what patients actually call them).

Vraylar has a long half-life (stays active in your body for 1-3 weeks, counting active metabolites), so withdrawal symptoms, if they happen, often creep in slowly and persist longer than, say, an SSRI.

Akathisia is the main reason for discontinuation at ≥2% rate (vs placebo) in bipolar mania and MDD.
Sudden discontinuation? Not recommended.

Management tips:

Always taper—gradually reduce your dose over weeks under supervision
Monitor for return of old symptoms or new side effects
Consider bridging with a longer-acting antipsychotic if sensitivity is high

Timeline: Withdrawal (if any) may develop over 1-3 weeks after stopping.

If you're in trouble, don't wait—call your doctor.

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Schizophrenia	1.5 mg daily	1.5–6 mg daily	6 mg daily
Bipolar I (manic/mixed)	1.5 mg daily	3–6 mg daily	6 mg daily
Bipolar I (depressive)	1.5 mg daily	1.5–3 mg daily	3 mg daily
Adjunctive MDD	1.5 mg daily	1.5–3 mg daily	3 mg daily

Dose-response: Many side effects, including sedation and movement problems, worsen at higher doses. Some users report more tolerability at 1.5–3mg than 4.5–6mg. Changes should always be made under medical guidance.

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

You’ve tried Vraylar—maybe it’s the drowsiness, maybe it’s the extra pounds, maybe you just want something different. Here’s what’s on the menu:

Aripiprazole (Abilify): A partial dopamine agonist like Vraylar, but often with less weight gain. Can cause restlessness (akathisia), but some find it more "activating."
Ziprasidone (Geodon): Less likely to cause weight gain. Needs to be taken with food. Some tolerate it better on the metabolic front.
Bupropion (Wellbutrin): Not an antipsychotic, but sometimes used adjunctively. Stimulating, minimal sexual side effects, may even cause weight loss—but beware of anxiety or insomnia.
SNRIs/SSRIs: Classic antidepressants for MDD, but carry their own risks (sexual dysfunction, weight changes).
Spravato (esketamine): Nasal spray, rapid acting, low risk for chronic weight/sexual side effects, but restricted to in-clinic use.

Some clinical trial options—like CYB003 or osavampator—may offer efficacy without chronic weight gain or sedation.

→ Compare your options on WithPower

Clinical Trials

CYB003 (deuterated psilocybin analog, NCT05385783): 5-HT2A receptor agonist (psychedelic). Phase 2 data: rapid onset, up to 75% remission by 4 months, no chronic sedation/weight gain.

Osavampator (NBI-1065845, TAK-653): AMPA receptor modulator, Phase 3 ongoing. Early data: few chronic side effects, potentially rapid antidepressant effect.

D-cycloserine (NCT00408031): NMDA receptor partial agonist; well tolerated as adjunct, no chronic sedation or metabolic impact seen.

Psilocybin (NCT06141876): Classic psychedelic. Durable benefit after single/few doses, side effects limited to dosing session (headache, anxiety, transient nausea).

Participation usually means free treatment, careful monitoring, and possible placebo assignment. These are promising—but not miracles yet: early-phase results don’t always translate to broad success. If you've hit a wall with standard medications, it might be worth a conversation.

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

Decision Map

If weight gain is the dealbreaker → try ziprasidone (weight neutral) OR trials of CYB003, osavampator, or psilocybin
If drowsiness/sedation is the dealbreaker → try aripiprazole or bupropion OR osavampator trial
If akathisia/restlessness is the dealbreaker → try quetiapine (lower akathisia rate, but more sedation/weight gain risk) OR d-cycloserine trial
If sexual dysfunction is the dealbreaker → try bupropion OR psilocybin/CYB003 trials
If insomnia is the dealbreaker → try olanzapine (caution: weight gain) OR osavampator trial

Vraylar (cariprazine) - antidepressant medication Image: Plushcare.com

Monitoring & What to Track

What your doctor should monitor:

For depression: PHQ-9 or HAM-D scores (standardized mood checklists)
For anxiety: GAD-7 or HAM-A scores
Weight (at baseline, monthly for 3-6 months, then quarterly)
Movement exams (AIMS scale for abnormal involuntary movements)
Blood pressure, blood sugar, and cholesterol (antipsychotics can raise all three)
Suicidal ideation, especially in first weeks or under age 25

What you should track:

Daily mood/anxiety levels (1–10 scale)
Side effect diary (note when, how severe, and how long)
Sleep patterns (bedtime, wake, quality)
Weight, at least monthly

If your doctor isn’t tracking these, ask for it—data beats guesswork.

Pregnancy & Breastfeeding

Vraylar is not recommended during pregnancy (Category: Not assigned; animal studies show risk, and human data is lacking). Like all atypical antipsychotics, Vraylar may increase the risk of abnormal muscle movements or withdrawal symptoms in newborns if taken late in pregnancy. Risks include extrapyramidal symptoms (unusual muscle movements) and withdrawal in the infant (agitation, feeding issues).

Breastfeeding: Not recommended. Cariprazine and its active metabolites are expected to be present in breast milk and may harm the baby (effects on neurologic development, withdrawal symptoms, etc.).

But untreated bipolar disorder, psychosis, or depression also carry risk for mother and child. It’s a real tradeoff.

Key message: Never stop Vraylar suddenly if you become pregnant. Discuss a tailored taper with your doctor for risk mitigation. This is a nuanced risk/benefit call, not a simple yes/no.

Emergency Warning Signs

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

Suicidal thoughts or plans
Severe allergic reaction: rash, swelling of face/tongue/throat, trouble breathing
Seizures or loss of consciousness
New muscle stiffness, high fever, confusion, or irregular pulse (could be neuroleptic malignant syndrome)
Sudden weakness, speech or vision changes (possible stroke)

📞 Call your doctor urgently if:

Unusual bleeding or easy bruising
Severe anxiety, agitation, or restlessness
Worsening depression or new behavioral changes
Signs of liver injury: yellow skin/eyes, dark urine, upper belly pain
New or worsening involuntary movements (especially face, mouth, tongue)

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

Summary & Next Steps

Key takeaways:

In real-world reports, weight gain (up to 50 lbs, severe in 2/4 users) and sedation/insomnia are the biggest dealbreakers for many, even though FDA rates for weight gain are just 3%. Akathisia/restlessness occurs in up to 14% (FDA) and is rated moderate to severe by users. Most side effects start in the first few weeks, but some (weight gain) can sneak up months later and last until the drug is stopped.

If Vraylar is working for you: Keep tracking mood and side effects. See your provider regularly. Watch for late-emerging side effects and don’t ignore weight or movement changes.

If side effects are intolerable:

Ask about dose adjustments or switching drugs
Explore alternatives with fewer metabolic or sedation risks (aripiprazole, ziprasidone, or bupropion for some)
Consider clinical trials with novel mechanisms and different side effect profiles

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
extrapyramidal symptoms	20%	8%	very common	Nervous System
headache	18%	13%	common	Nervous System
akathisia	14%	4%	very common	Nervous System
insomnia	13%	7%	very common	Psychiatric
nausea	13%	3%	very common	Gastrointestinal
somnolence	11%	4%	common	Nervous System
constipation	11%	1%	common	Gastrointestinal
fatigue	10%	4%	common	General
vomiting	10%	3%	common	Gastrointestinal
dyspepsia	9%	4%	common	Gastrointestinal
restlessness	8%	3%	common	Psychiatric
abdominal pain	8%	5%	common	Gastrointestinal
dizziness	7%	2%	common	Nervous System
anxiety	6%	4%	common	Psychiatric
hypertension	6%	1%	common	Cardiovascular
diarrhea	6%	3%	common	Gastrointestinal
toothache	6%	2%	common	Gastrointestinal
blood creatine phosphokinase increased	6%	4%	common	Investigations
dry mouth	5%	2%	common	Gastrointestinal
increased appetite	5%	2%	common	Metabolic
agitation	5%	4%	common	Psychiatric
pain in extremity	4%	2%	common	Musculoskeletal
nasopharyngitis	4%	2%	common	Infections
vision blurred	4%	1%	common	Eye
pyrexia	4%	2%	uncommon	General
weight increased	3%	1%	common	Metabolic
tachycardia	3%	1%	common	Cardiovascular
back pain	3%	1%	common	Musculoskeletal
hepatic enzyme increased	3%	1%	common	Investigations
palpitations	2%	1%	common	Cardiovascular

Boxed Warnings (Most Serious)

Increased mortality in elderly patients with dementia-related psychosis: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. VRAYLAR is not approved for the treatment of patients with dementia-related psychosis.
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 the emergence of suicidal thoughts and behaviors.

Drug Interactions

Strong or moderate CYP3A4 inhibitors: Increase cariprazine and DDCAR exposure. Reduce VRAYLAR dosage when used concomitantly.
CYP3A4 inducers: Effect on cariprazine exposure is unclear. Concomitant use is not recommended.

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?
Weight gain	4 posts	🟠 Severe (2/4)	Ongoing for months; started after 5 months for some, persisted until stopping for others	Resolves
Restlessness and inability to sit still (akathisia)	4 posts	🟡 Moderate (3/4)	Several weeks to months; sometimes resolves, sometimes persists	Resolves
Nausea and upset stomach	4 posts	🟡 Moderate (3/4)	First few days to ongoing; sometimes never goes away	Resolves
Difficulty falling or staying asleep (insomnia)	3 posts	🟠 Severe (2/3)	First week to ongoing; sometimes resolves, sometimes persists	Resolves
Drowsiness and feeling very sleepy	3 posts	🟠 Severe (2/3)	First days to weeks; sometimes ongoing	Resolves
Dry mouth	3 posts	🟢 Mild (2/3)	First days to weeks; sometimes ongoing	Resolves
Increased anxiety or agitation	3 posts	🟡 Moderate (2/3)	First weeks to ongoing; sometimes improves, sometimes worsens	Resolves
Worsening or persistent depression	3 posts	🟡 Moderate (3/3)	Ongoing; sometimes persists despite treatment	Resolves
Tremors and muscle spasms	2 posts	🟡 Moderate (2/2)	First days to weeks; sometimes ongoing	Resolves
Fatigue and muscle weakness	2 posts	🟡 Moderate (2/2)	First days to weeks; sometimes ongoing	Resolves
Decreased sexual desire (libido)	2 posts	🟡 Moderate (1/2)	Ongoing while on medication	Resolves
Excessive sweating	1 posts	🟢 Mild (1/1)	First days to weeks	Resolves
Headaches	1 posts	🟢 Mild (1/1)	First days to weeks	Resolves
Irritability and anger	1 posts	🟡 Moderate (1/1)	First days to weeks	Resolves
Dizziness and lightheadedness	1 posts	🟢 Mild (1/1)	First days to weeks	Resolves

User Quotes by Side Effect

Weight gain (Can start after several months (e.g., after 5 months), persists as long as medication is continued, may resolve after stopping)

"I was fine for the first 5 months on it but then the weight gain started. I have been thin my whole life but starting these type of medicines..." source

"I've gained about 50lbs. I think it's due to Vraylar and he finally let me get off of it." source

"Vraylar has more EPS than some other antipsychotics and, although it is marketed as weight neutral, it does often cause some weight gain." source

Restlessness and inability to sit still (akathisia) (Starts within first week, can persist for weeks to months, sometimes resolves after 1-2 months)

"I've been on Vraylar (aka Cariprazine) for a week now. And I've been incredibly restless and unable to sit still, a condition known as akathisia." source

"Vraylar can cause restlessness and agitation. People talk about antipsychotics being emotionally blunting, but I've never heard of them causing..." source

"When I first started taking it I felt very restless. Now that..." source

Nausea and upset stomach (Starts within first few days, may persist for weeks or longer, sometimes never resolves)

"I just started Vraylar 3 days ago. I have the classic side effects that's should go away. Headaches, sleepiness, dry mouth, upset tummy." source

"I took my first dose Tuesday night and all day yesterday I was so sick (dizziness, nausea, tremors, muscle weakness, fatigue). I threw up twice." source

"the nausea side effect my pdoc hoped would go away never did." source

Difficulty falling or staying asleep (insomnia) (Starts within first week, can persist as long as medication is continued, sometimes resolves after stopping)

"Insomnia - I wake between 3-4am every. single. day and cannot go back to sleep" source

"insomnia (didn't sleep for the week I was on it)" source

Drowsiness and feeling very sleepy (Starts within first few days, may persist or resolve with dose adjustment)

"I couldn't handle Vraylar at all. It made me so drowsy I could barely move..." source

"I have been on 1.5 mg Vraylar for 3 years. It has worked really well for me — no side effects so far, and it does not make me drowsy." source

"my depression is persisting. I'm currently taking 1.5mg of Vraylar after finding that higher doses made me very sleepy." source

Dry mouth (Starts within first few days, often resolves after a few weeks)

"Dry Mouth." source

"I just started Vraylar 3 days ago. I have the classic side effects that's should go away. Headaches, sleepiness, dry mouth, upset tummy." source

Increased anxiety or agitation (Can start after a few days to weeks, may persist or improve with time)

"increased anxiety, Akathisia, sweating, nausea, insomnia (didn't sleep for the week I was on it) and increased anxiety." source

"The good feelings simmered after about 3 weeks and then it was just anxiety + agitation." source

"Vraylar is the best medication for me. It got rid of my anxiety and really helps with the depression." source

Worsening or persistent depression (Can start soon after beginning medication, may persist as long as medication is continued)

"Ever since I started Vraylar, I have been feeling more depressed then usual." source

"I feel like vraylar (1.5) isn't helping my depression, it's only stabilizing my mood as far as mania goes." source

"my depression is persisting. I'm currently taking 1.5mg of Vraylar after finding that higher doses made me very sleepy." source

Tremors and muscle spasms (Starts within first few days, may persist or resolve)

"Twitching/Muscle Spasms" source

"I took my first dose Tuesday night and all day yesterday I was so sick (dizziness, nausea, tremors, muscle weakness, fatigue)." source

Fatigue and muscle weakness (Starts within first few days, may persist or resolve)

"It knocked me out, made me grumpy and angry, lethargic." source

"I took my first dose Tuesday night and all day yesterday I was so sick (dizziness, nausea, tremors, muscle weakness, fatigue)." source

Decreased sexual desire (libido) (Starts after beginning medication, persists as long as medication is continued)

"It worked wonders for my depression and irritability but completely killed my libido." source

Excessive sweating (Starts within first few days, may resolve)

"Increased appetite, Akathisia, sweating, nausea, insomnia (didn't sleep for the week I was on it) and increased anxiety." source

Headaches (Starts within first few days, often resolves after a few weeks)

"I just started Vraylar 3 days ago. I have the classic side effects that's should go away. Headaches, sleepiness, dry mouth, upset tummy." source

Irritability and anger (Starts within first few days, may persist or resolve)

"It knocked me out, made me grumpy and angry, lethargic." source

Dizziness and lightheadedness (Starts within first few days, often resolves after a few weeks)

"At first the only thing I noticed was slight nausea and being lightheaded." source

Appendix C: Clinical Trials with Different Mechanisms

These trials target mechanisms different from Atypical Antipsychotic [EPC]. Phase 2 results do not guarantee Phase 3 success.

CYB003 (deuterated psilocybin analog)

Sponsor: Cybin Inc.
Phase: Phase 2 (Breakthrough Therapy Designation, Phase 3 planned)
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 sexual dysfunction, weight gain, or chronic sedation reported. Side effects are acute and resolve within hours, unlike persistent side effects with SSRIs/SNRIs.
Efficacy Data:
- Response rate: 79% at 3 weeks (CYB003 16mg)
- Remission rate: 75% at 4 months (Phase 2, CYB003)
- MADRS change: -14.08 points (CYB003 16mg) vs -8.24 (placebo) at 3 weeks
- Time to response: 1-3 weeks
- Source
Why it might interest you: Very rapid onset (1-3 weeks), durable remission, and side effects limited to dosing session (no chronic weight gain, sexual dysfunction, or sedation). Novel mechanism for those not responding or intolerant to standard antidepressants.
Results: Rapid and robust reduction in depressive symptoms, high remission and response rates, durable effect at 4 months post-dose.
Sources: 1, 2, 3

Osavampator (NBI-1065845, TAK-653)

Sponsor: Neurocrine Biosciences
Phase: Phase 3 (recruiting)
Mechanism: Positive allosteric modulator of AMPA receptors (AMPA-R PAM)
Side Effect Comparison: Phase 2 data suggest lower rates of sexual dysfunction, weight gain, and sedation compared to SSRIs/SNRIs. No significant cognitive impairment or withdrawal symptoms reported.
Efficacy Data:
- Response rate: Not yet reported
- Remission rate: Not yet reported
- MADRS change: Not yet reported (Phase 3 ongoing)
- Time to response: Expected to be faster than SSRIs/SNRIs (based on AMPA modulation)
- Source
Why it might interest you: AMPA modulation is a novel, non-monoaminergic mechanism. Potential for faster onset and fewer chronic side effects (sexual dysfunction, weight gain, sedation) than standard antidepressants.
Results: Phase 2 showed rapid antidepressant effects and good tolerability; 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: Generally well-tolerated; no significant increase in sedation, weight gain, or sexual dysfunction compared to placebo. Side effect profile appears milder than SSRIs/SNRIs.
Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: -6.6 points vs placebo at 6 weeks (D-cycloserine adjunctive, TRD)
- Time to response: 2-6 weeks
- Source
Why it might interest you: Novel glutamatergic mechanism, may benefit those not responding to standard drugs. Side effects are mild and do not include common SSRI/SNRI issues.
Results: Significant improvement in depressive symptoms as adjunctive therapy in treatment-resistant depression.
Sources: 1

Psilocybin (various sponsors)

Sponsor: Multiple (Compass Pathways, Usona, academic)
Phase: Phase 2/3 (multiple ongoing)
NCT: NCT06141876
Mechanism: Classic psychedelic (5-HT2A receptor agonist)
Side Effect Comparison: Transient anxiety, headache, and nausea during dosing. No chronic weight gain, sexual dysfunction, or sedation. Side effects are acute and resolve within hours.
Efficacy Data:
- Response rate: 37% (psilocybin) vs 18% (placebo) at 3 weeks
- Remission rate: 29% (psilocybin) vs 8% (placebo) at 3 weeks
- MADRS change: -16.2 points (psilocybin) vs -5.4 (placebo) at 3 weeks (from prior phase 2 studies)
- Time to response: 1-3 weeks
- Source
Why it might interest you: Rapid onset, durable effect, and side effects limited to dosing session. No chronic side effects typical of SSRIs/SNRIs.
Results: Rapid and robust antidepressant effects in TRD and MDD, with durable response after single or few doses.
Sources: 1, 2

Appendix D: Methodology

To create this guide, we examined over 30,000 clinical trial records from ClinicalTrials.gov, more than 300 journal articles via PubMed, and analyzed 46 online patient discussions. We systematically reviewed 48 entries from the OpenFDA Drug Label dataset and identified 15 distinct user-reported side effects, assessing them for frequency and severity. Representative patient quotes with source links and duration patterns were selected to reflect true patient experience.