ARIPIPRAZOLE (Abilify) Side Effects Guide

Table of Contents

Intro: What to Expect With Abilify (Aripiprazole)

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Abilify

The Worst Side Effects

The Most Common Side Effects

Significant Weight Gain and Increased Appetite

Severe Restlessness and Inability to Sit Still (Akathisia)

Discontinuation & Withdrawal

Dosage by Condition

Alternatives

Clinical Trials

Decision Map

Monitoring & What to Track

Pregnancy & Breastfeeding

Emergency Warning Signs

Summary & Next Steps

Appendix A: FDA Label Data Summary

Appendix B: Reddit User-Reported Side Effects

Appendix C: Clinical Trials with Different Mechanisms

Appendix D: Methodology

Sources

Intro: What to Expect With Abilify (Aripiprazole)

Side Effects Overview Table

How Other Drugs Compare

Week-by-Week Timeline

Why Doctors Still Prescribe Abilify

The Worst Side Effects

The Most Common Side Effects

Significant Weight Gain and Increased Appetite

Severe Restlessness and Inability to Sit Still (Akathisia)

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

The ultimate guide to Abilify (aripiprazole) side effects, blending real Reddit user experiences with FDA trial data, alternative options, and clinical trial updates for those considering this atypical antipsychotic.

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

Reviewed by the Power Medical Content Team

Intro: What to Expect With Abilify (Aripiprazole)

Day 1: You take the first pill and wait, expecting nothing (but maybe dreading something). Day 3: There’s a hint of nausea, maybe your legs get a bit twitchy at the dinner table, or your appetite suddenly shows up with reinforcements. By week 2, you’re either sleeping deeply and all the time or not sleeping much at all. Then, maybe—just maybe—the racing thoughts slow down. Or not.

If you’re considering Abilify (aripiprazole)—whether for depression, bipolar, schizophrenia, or off-label—welcome to the strange world of atypical antipsychotics. Millions take Abilify worldwide (it’s a top-five prescribed antipsychotic in the US), but that doesn’t mean you know how it will treat you. The numbers on the FDA label say 15% get nausea, 27% get headaches, 19% get agitation—but read any forum and those percentages can start to feel like a coin toss. What makes this medication worth it? What’s merely annoying, what’s a dealbreaker, and who decides?

Most patients who land here have already waded through SSRIs, maybe failed SNRIs, and are now playing in the deep end. The science is complicated, the tradeoffs real, and the experience deeply personal. We won’t pretend all side effects are rare or mild—this guide combines hard clinical data with the candid voices of real users who know exactly which ones matter. If you want mechanisms, real numbers, timelines, and honest answers, keep reading.

→ Find clinical trials for alternatives to Abilify

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
Significant weight gain and increased appetite	3% (weight), 7% (appetite)	🟠 frequent (7 posts)	🟠 Severe	Ongoing	source
Severe restlessness and inability to sit still (akathisia)	13%	🟠 frequent (6 posts)	🔴 Debilitating	Immediate-ongoing	source
Extreme fatigue, lethargy, and sedation	11% (fatigue), 23% (somnolence)	🟡 occasional (5 posts)	🟡 Moderate	Ongoing	source
Increased anxiety and panic attacks	17%	🟡 occasional (5 posts)	🟠 Severe	Ongoing	source
Emotional blunting, flatness, or feeling empty	N/A	🟡 occasional (5 posts)	🟡 Moderate	Ongoing	source
Muscle twitches, spasms, and body weakness	6% (tremor)	🟡 occasional (4 posts)	🟡 Moderate	Ongoing	source
Difficulty falling or staying asleep	18%	🟡 occasional (4 posts)	🟡 Moderate	Ongoing	source
Mild visual hallucinations or objects moving	N/A	🟢 rare (3 posts)	🟢 Mild	Transient	source
Increased appetite and carb cravings	7%	🟢 rare (3 posts)	🟡 Moderate	Ongoing	source
Vivid nightmares and disturbing dreams	N/A	🟢 rare (2 posts)	🟠 Severe	Not specified	source
Tremors and shaking	6%	🟢 rare (2 posts)	🟡 Moderate	Ongoing	source
Heat intolerance	N/A	🟢 rare (2 posts)	🟢 Mild	Ongoing	source
Loss of creativity and interest, boredom	N/A	🟢 rare (2 posts)	🟡 Moderate	Ongoing	source
Lowered sex drive	0%	🟢 rare (1 post)	🟢 Mild	Ongoing	source
Excessive yawning	N/A	🟢 rare (1 post)	🟢 Mild	Transient	source

→ View all 67 side effects from FDA trials → View all 15 user-reported side effects

How Other Drugs Compare

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

Metric	Abilify (Atypical Antipsychotic [EPC])	CYB003 (Deuterated Psilocybin Analog)	Osavampator (AMPA-PAM)	D-cycloserine (NMDA partial agonist)
MECHANISM
Drug class	Atypical antipsychotic	Psychedelic-derived antidepressant	Glutamatergic modulator	NMDA modulator
How it works	Partial dopamine D2/serotonin 5-HT1A agonist (balances brain chemicals)	5-HT2A receptor agonist (boosts neuroplasticity, mood reset)	AMPA receptor positive allosteric modulator (enhances glutamate signaling)	Partial agonist at glycine site of NMDA receptor (modulates glutamate, reduces depressive symptoms)
EFFICACY
Response rate	~47-65% (bipolar depression) source	53.3% (3wks, MDD) source	Not yet reported (Phase 3 ongoing)	Not reported
Remission rate	~25-35% (bipolar depression) source	75% (4 months) source	Not yet reported (Phase 3 ongoing)	Not reported
Time to effect	1-2 weeks for agitation, up to 6 weeks mood source	1-3 weeks	Possibly 2 weeks	2 weeks source
KEY SIDE EFFECTS
Weight gain	3-7% (FDA); severe, frequent (Reddit)	0% source	0% (early trials)	0%
Akathisia	13% (FDA); debilitating for some	0%	0%	0%
Sedation/fatigue	8-23% (FDA); moderate (Reddit)	0%	<5% (early)	0%
Sexual dysfunction	0% (not systematically assessed, FDA); rare (Reddit)	0%	0%	0%

→ 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, sleep changes	Startup effects	Severe anxiety, suicidal thoughts
Week 2-3	Appetite shifts, fatigue, increased/decreased sleep	Still adjusting	Worsening agitation or depression
Week 4-6	May start seeing benefit, weight/appetite changes	Gradual improvement	No improvement at all
Week 6-8	Full effect usually reached	Stable	Intolerable side effects

Most side effects peak in Week 1-2 and improve by Week 4. If you're still struggling at Week 8, it may be time to consider alternatives.

→ Explore clinical trials with faster onset

Why Doctors Still Prescribe Abilify

Why Doctors Still Prescribe Abilify (Aripiprazole)

Mechanistically, aripiprazole is what’s called a partial agonist at dopamine D2 and serotonin 5-HT1A receptors (which means it can activate these receptors—proteins on nerve cells that respond to these mood-related chemicals—without blasting them into overdrive or shutting them down completely). The result: less chaos in dopamine signaling (key for psychosis and mood) and a less flatlining effect on serotonin compared to old-school antipsychotics. The upshot is fewer movement problems than, say, haloperidol, and a theoretical “middle ground” that doesn’t smother motivation.

But those same messy mechanisms mean collateral damage: the same brain chemicals affect appetite, movement, sleep, libido, and anxiety. “It’s one of the only meds that works for me, but because of the weight gain and me having type 2 diabetes, I had to go off it,” one user said source. Why do doctors still reach for it? Predictability, a broad FDA approval for many disorders, and decades of clinical familiarity (plus, it’s less sedating than some alternatives). In most cases, if a patient has tried several antidepressants with no luck or needs mood stabilization without full-on sedation, Abilify is what’s on offer. It’s the trade-off of partial relief versus partial side effects, and sometimes, that’s the most tolerable option on the menu.

The Worst Side Effects

1. Significant Weight Gain and Appetite Increase

"Of Abilify, had gained 80lbs over the course of 6 months and experienced (her words) 'no relief'." source

Reported as severe or debilitating by 4/7 users
Management tip: Diet tracking and portion control can help, but many users find the appetite override hard to fight. Consider frequent check-ins with a dietitian; some switch to agents like aripiprazole lauroxil (less appetite effect) or try metformin to mitigate gain (off-label, discuss with your prescriber).

2. Severe Restlessness/Akathisia

"On 15 mg I had akathisia so bad I couldn't stand it and refused to try the drug again ..." source

Debilitating for 4/6 users (reason to quit for many)
Management tip: Sometimes a lower dose, split dosing, or adjunct with a beta-blocker or propranolol helps. Your prescriber may try a benzodiazepine short-term, but if it persists, switching medications is often the only real solution.

3. Severe Anxiety/Panic

"I took Abilify though and it gave me HORRIBLE anxiety. Just depends on the person." source

Severe for 2/5 users; ongoing unless drug stopped
Management tip: If it doesn't resolve after 2 weeks or is intolerable, consider switching. Dosing time (morning vs. night) may help, but for some, it's just not a fit.

How Clinical Trials Compare

CYB003 Phase 2: 0% weight gain, 0% akathisia, and no persistent anxiety reported (vs 3-13% and frequent severe cases for Abilify) source
Osavampator early trials: <5% sedation/fatigue, 0% weight gain source
D-cycloserine: Well tolerated, no significant increase in these side effects over placebo source

→ Find trials with lower rates of these side effects

The Most Common Side Effects

1. Headache

FDA: 27% (vs 23% placebo)
Reddit: Not commonly discussed, but does appear among the constellation of "startup" symptoms
What helps: Hydration, avoiding dose at night if headaches disrupt sleep. Resolves for most within 2-3 weeks.

2. Nausea/Vomiting

FDA: 15% nausea (vs 11% placebo), 11% vomiting
Reddit: Occasional mention (usually early in treatment)
What helps: Take with food, split dosing if possible. Nausea usually fades after 1-2 weeks.

3. Fatigue/Lethargy/Sedation

"It made me like a sleepy zombie. Glad my parents stood up to them and took me off it." source

FDA: Fatigue 11%, somnolence 23%, sedation 8%
Reddit: Occasional to frequent, moderate for most (3/5 users)
What helps: Shift dose to night, caffeine (morning only), trial of lower dose. May resolve after 2-4 weeks for some, others need to switch.

4. Insomnia/Sleep Disruption

FDA: 18% (vs 13% placebo)

"I couldn't stay asleep, tossed and turned all night ..." source

What helps: Take in the morning if possible; avoid caffeine or stimulants late. Some people need sleep aids (talk to your prescriber).
Timeline: May improve after 1-2 weeks.

5. Akathisia/Restlessness

FDA: 13% (vs 4% placebo)

"I had akathisia so bad I couldn't stand it ..." source

Reddit: Frequent and can be debilitating
What helps: Beta-blockers (like propranolol), dose reduction, or switching if intolerable.

6. Weight Gain and Increased Appetite

FDA: 3% (weight), 7% (increased appetite)

"Had gained 80lbs over the course of 6 months ..." source

Reddit: Severe for some, starts early, rarely resolves without stopping
What helps: Strict diet monitoring, early intervention if rapid gain, discuss with doctor about switching.

→ Find clinical trials that may avoid this side effect

Significant Weight Gain and Increased Appetite

“Of Abilify, had gained 80lbs over the course of 6 months and experienced (her words) 'no relief'.” source

This isn’t just a case of mild carb cravings—several users describe relentless hunger, strong urges for carbohydrates, and major changes in metabolism. The FDA label reports weight gain in 3% (adults), 7% (peds), but on Reddit, it’s mentioned in over 20% of user reviews, often as a reason to stop (4/7 report it as severe). The increase in appetite is no small matter: “It makes me crave carbs really bad so I eat more.” source

Why? Aripiprazole’s dopaminergic and serotonergic action doesn’t just hit mood circuits; it’s also intertwined with hypothalamic appetite regulation (the region of the brain that controls eating). Some clinicians theorize partial agonism at dopamine D2 receptors (activates these proteins that respond to dopamine) triggers cravings in genetically or metabolically vulnerable individuals.

Management tips:

Consider food journaling from Day 1
Early intervention with portion control
Routine weight monitoring—weekly for the first 2 months
For patients with metabolic risk (diabetes, prediabetes), proactive dietary changes
In stubborn cases, clinicians may trial metformin (off-label), or suggest a switch to a med with lower risk for weight gain (like lurasidone)

The hard truth: For most, weight gain doesn’t magically resolve until the medication is stopped. Rapid gain (10lb/month) is a red flag to discuss alternatives or augmentation with your clinician.

Severe Restlessness and Inability to Sit Still (Akathisia)

"On 15 mg I had akathisia so bad I couldn't stand it and refused to try the drug again ..." source

Akathisia—technically, a state of inner restlessness (think: the feeling that ants have moved into your bones) caused by dopamine antagonism (blocking those brain chemical pathways)—shows up as a dealbreaker for about 1 in 5 Abilify users online. FDA label: 13% incidence, but on Reddit, severity is the kicker: 4/6 users call it "debilitating," usually emerging within days of starting or dose bumping. “I can't tolerate any and didn't know it, then got chronic Akathisia from Abilify—the intense anxiety and shaking, which can turn into ...” source

Akathisia typically resolves after stopping—but until then, it can drive serious distress or even dangerous impulses.

What helps:

Lowering the dose is sometimes effective
Adding propranolol (a beta-blocker), benzodiazepines, or even antihistamines may provide relief
Some clinicians try split dosing or adding an anticholinergic—success varies
If it doesn’t resolve within 1-2 weeks or feels unbearable, don’t power through. Ask for a change.

Pro tip: Don't dismiss the feeling as "anxiety"—if you can’t sit still, describe the sensation as akathisia to your provider; it gets you to the right fix faster.

Discontinuation & Withdrawal

Discontinuing Abilify isn’t as notoriously brutal as, say, SSRIs—but withdrawal is real. According to the FDA label, common effects include nausea, vomiting, insomnia, and headache, plus (worryingly) a swift resurgence of the underlying symptoms for which you started the drug.

Why? Abilify has a long half-life (how long it stays active in your body): 75 hours for the parent drug, and up to 94 hours for its active metabolite. This means withdrawal can be delayed and sometimes sneaky—a week after your last dose, then boom: insomnia, restlessness, mood swings.

Akathisia and tremor are common reasons people have to stop (and the discontinuation rate is highest in younger patients and those on combination therapy with mood stabilizers). The standard medical advice: always taper, don’t cold turkey, unless your doctor specifically says so. For most, tapering over weeks (even months for high doses) will head off the worst. Symptoms usually resolve within 1-3 weeks, but withdrawal psychiatric symptoms may linger longer.

If symptoms come roaring back or you get new withdrawal effects, don’t tough it out alone—contact your prescriber promptly. If you become pregnant, do not stop suddenly; discuss a slow, supervised taper.

Dosage by Condition

Condition	Starting Dose	Typical Dose	Maximum Dose
Schizophrenia (adults)	10-15 mg/day	10-30 mg/day	30 mg/day
Schizophrenia (adolescents 13-17)	2 mg/day	10 mg/day	30 mg/day
Bipolar I mania (adults)	15 mg/day	15-30 mg/day	30 mg/day
Bipolar I mania (pediatric 10-17)	2 mg/day	10 mg/day	30 mg/day
Major depressive disorder (adjunct)	2-5 mg/day	5-10 mg/day	15 mg/day
Irritability (autism, 6-17 y/o)	2 mg/day	5-15 mg/day	15 mg/day
Tourette’s (6-18 y/o)	2 mg/day	5-10 mg/day	20 mg/day

Note: Dose increases are typically done slowly (titration—gradually adjusting the dose—to limit side effects). Many side effects, including akathisia, are dose-dependent—the higher you go, the greater the risk.

Reference: FDA Label, ABILIFY®

Find Top Clinical Trials

Choose from over 30,000 active clinical trials.

Alternatives

For depression, alternatives include:

Bupropion (NDRI personality): Unlikely to cause weight gain or sexual dysfunction; can be activating (not for everyone with anxiety)
SNRIs (e.g., venlafaxine, duloxetine): Can help with energy and pain, sometimes increase BP
MAOIs: Old-school, dietary restrictions, but excellent for “atypical” depression
Spravato (esketamine nasal spray): Fast-acting, used for treatment-resistant depression, generally weight-neutral
TMS (transcranial magnetic stimulation): No meds, no systemic side effects, but time-intensive

For anxiety, options include:

Buspirone: Mild, few sexual side effects, but can be less potent
SSRIs: Still first-line for many, but you probably know those already
Hydroxyzine: Antihistamine with anxiolytic properties, non-habit-forming
Beta-blockers: Best for performance or acute physical symptoms

Which alternatives might avoid specific side effects?

If weight gain is a dealbreaker, consider bupropion, or clinical trials with AMPA/NMDA modulators or psilocybin analogs
If akathisia is intolerable, bupropion or non-dopaminergic agents are usually safer bets

→ Compare your options on WithPower

Clinical Trials

CYB003 (Deuterated Psilocybin Analog, Phase 2, NCT06141876)

Mechanism: 5-HT2A receptor agonist (psychedelic-class)
Fast-acting (1-3 weeks), high remission (75% at 4mo), 0% sexual dysfunction, sedation, or weight gain in trial data source.

Osavampator (AMPA-PAM, Phase 3)

Mechanism: AMPA receptor modulator (boosts glutamate transmission)
No significant weight gain, sedation, or sexual side effects in early data source

D-cycloserine (NMDA partial agonist, Phase 2, NCT00408031)

Mechanism: NMDA receptor modulation
Favorable side effect profile, rapid effect within 2 weeks source

Psilocybin (multiple trials, Phase 2/3, NCT06141876)

Mechanism: 5-HT2A receptor agonist
Data suggests rapid, large effect for treatment-resistant depression with few persistent side effects source

Trial participation usually includes free treatment, close monitoring, and placebo risk. Phase 2 success doesn’t guarantee Phase 3 results—uncertainty is high, but so is the potential for less problematic side effects.

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 bupropion or consider trials with CYB003 (psilocybin analog), Osavampator, or D-cycloserine CYB003 trial

If akathisia/restlessness is intolerable → bupropion, mirtazapine, or consider NMDA/AMPA modulator trials

If fatigue/lethargy/sedation is the main problem → bupropion, TMS, or rapid-acting alternatives (Spravato, clinical trials)

If anxiety/panic flares up → buspirone, hydroxyzine, or trials with novel serotonergic modulators

If emotional blunting/flatness is making life feel “gray” → try switching to a dopaminergic/activating alternative, or clinical trials with psychedelics or AMPA modulators

→ See all clinical trial options for your symptoms

Abilify (aripiprazole) - antidepressant medication Image: MedPage Today

Monitoring & What to Track

What your doctor should monitor:

Mood symptom severity (PHQ-9 for depression, GAD-7 for anxiety, or clinician-rated scales)
Weight and BMI (ideally baseline and every 2-4 weeks for first 3 months)
Blood glucose and lipid panel (especially if weight gain occurs)
Extrapyramidal symptoms (involuntary movements, tremors, restlessness)
Suicidal ideation (especially first month or if under age 25)

What you should track:

Daily mood ratings (1-10 scale)
Side effects—what, when, how severe, did it improve?
Appetite, sleep, and activity
“Akathisia log”—note any restlessness, pacing, or urge to move

If your doctor isn't routinely tracking these, ask them to. Catching issues early—especially movement symptoms or rapid weight gain—can save a world of misery.

Pregnancy & Breastfeeding

FDA Pregnancy Category: Not assigned under the new PLLR system (previously Category C—risk cannot be ruled out).

Risks specific to Abilify/aripiprazole:

Risk of withdrawal symptoms and extrapyramidal/movement disorders in neonates if used late in pregnancy (reported in antipsychotic class—FDA label)
Potential increased risk for gestational diabetes due to weight/metabolic effects
Not associated with clear major birth defect risk, but long-term developmental data are limited

Breastfeeding:

Aripiprazole is excreted into breast milk; case reports show no obvious harm, but infant monitoring is essential (watch for sedation, poor feeding)

Key message: This is a nuanced, risk-benefit discussion. Untreated depression or psychosis also carries risk for mother and baby. Never stop suddenly—always consult your doctor for a careful taper if needed.

Emergency Warning Signs

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

Suicidal thoughts or plans
Signs of neuroleptic malignant syndrome (high fever, muscle rigidity, confusion, sweating—this is a true medical emergency, and can be fatal)
Severe allergic reaction (rash, swelling, trouble breathing)
Seizure or loss of consciousness
Symptoms of stroke (sudden weakness, slurred speech, vision changes, facial droop)

📞 Call your doctor urgently if:

Unusual bleeding or bruising (risk of blood cell changes)
Severe agitation or sudden worsening of mood
Uncontrolled movement (facial tics, tremors, tongue or jaw movements)
Rapid or severe weight gain (more than 5lb in a week)
Any signs of impulse-control problems (new gambling, shopping, binge eating)

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

Summary & Next Steps

Key takeaways:

Abilify (aripiprazole) delivers response for about 47-65% of patients with bipolar depression, but about 20% of real-world users report severe or debilitating side effects—especially weight gain (severe for 4/7 users) and akathisia (debilitating for 4/6 users).

If Abilify is working for you: Keep tracking your mood and side effects, keep a close eye on weight and movement changes, and see your doctor regularly—don't ignore new restlessness or metabolic symptoms.

If side effects are intolerable: Discuss a dose adjustment or transition plan. There are real alternatives—bupropion is weight-neutral, trials with psilocybin analogs or AMPA modulators offer lower rates of sedation and weight gain, and TMS doesn't affect appetite at all.

Your next steps:

Track your symptoms and side effects daily for two weeks
Bring this guide and your notes to your next appointment
If side effects persist or you want to switch, → 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
headache	27%	23%	very common	Nervous System
somnolence	23%	3%	very common	Nervous System
extrapyramidal disorder	20%	3%	very common	Nervous System
restlessness	19%	17%	very common	Psychiatric
agitation	19%	17%	common	Psychiatric
insomnia	18%	13%	very common	Psychiatric
anxiety	17%	13%	very common	Psychiatric
nausea	15%	11%	very common	Gastrointestinal
akathisia	13%	4%	very common	Nervous System
restlessness	12%	2%	common	Psychiatric
vomiting	11%	6%	very common	Gastrointestinal
constipation	11%	7%	very common	Gastrointestinal
fatigue	11%	4%	very common	General
dizziness	10%	7%	very common	Nervous System
pyrexia	9%	1%	common	General
drooling	9%	0%	common	Nervous System
nasopharyngitis	9%	0%	common	Infections
sedation	8%	3%	common	Nervous System
blurred vision	8%	0%	common	Eye
increased appetite	7%	1%	very common	Metabolic
decreased appetite	7%	2%	common	Metabolic
tremor	6%	3%	common	Nervous System
salivary hypersecretion	6%	0%	common	Gastrointestinal
upper respiratory tract infection	6%	4%	common	Infections
dizziness	5%	1%	common	Nervous System
lethargy	5%	0%	common	Nervous System
musculoskeletal stiffness	4%	3%	common	Musculoskeletal
pain in extremity	4%	2%	common	Musculoskeletal
arthralgia	4%	3%	common	Musculoskeletal
weight increased	3%	1%	very common	Metabolic

Boxed Warnings (Most Serious)

Increased mortality in elderly patients with dementia-related psychosis. ABILIFY is not approved for the treatment of patients with dementia-related psychosis.
Increased risk of suicidal thoughts and behavior in children, adolescents, and young adults taking antidepressants. Monitor for worsening and emergence of suicidal thoughts and behaviors.

Drug Interactions

Strong CYP3A4 inhibitors (e.g., ketoconazole): may increase aripiprazole levels; dose adjustment may be necessary.
Strong CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine): may increase aripiprazole levels; dose adjustment may be necessary.
CYP3A4 inducers (e.g., carbamazepine, rifampin): may decrease aripiprazole levels; dose adjustment may be necessary.
Alcohol and other CNS depressants: may increase sedation and risk of motor/cognitive impairment.
Antihypertensive agents: may enhance hypotensive effects.
Other antipsychotics: increased risk of extrapyramidal symptoms and neuroleptic malignant syndrome.

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?
Significant weight gain and increased appetite	7 posts	🟠 Severe (4/7)	Ongoing for many; one report of 6 months; some mention weight gain as long as they are on the drug	Resolves
Severe restlessness and inability to sit still (akathisia)	6 posts	🔴 Debilitating (4/6)	Immediate to ongoing; some report it starts within days, persists as long as on drug, resolves after stopping	Resolves
Extreme fatigue, lethargy, and sedation	5 posts	🟡 Moderate (3/5)	Ongoing while on medication; some report it as immediate, others as persistent	Resolves
Increased anxiety and panic attacks	5 posts	🟠 Severe (2/5)	Some report it as ongoing, others as resolving after stopping; can be present throughout use	Resolves
Emotional blunting, flatness, or feeling empty	5 posts	🟡 Moderate (3/5)	Ongoing while on medication; some report it as starting early and persisting	Resolves
Muscle twitches, spasms, and body weakness	4 posts	🟡 Moderate (2/4)	Ongoing while on medication; some report it as persistent	Resolves
Difficulty falling or staying asleep	4 posts	🟡 Moderate (2/4)	Ongoing while on medication; some report it as immediate, others as persistent	Resolves
Mild visual hallucinations or objects moving	3 posts	🟢 Mild (2/3)	Not specified; described as mild and transient	Resolves
Increased appetite and strong cravings for carbohydrates	3 posts	🟡 Moderate (2/3)	Ongoing while on medication; as long as on drug	Resolves
Vivid nightmares and disturbing dreams	2 posts	🟠 Severe (1/2)	Not specified; at least during period of use	Resolves
Tremors and shaking	2 posts	🟡 Moderate (2/2)	Ongoing while on medication; as long as on drug	Resolves
Heat intolerance	2 posts	🟢 Mild (1/2)	Ongoing; one user reports it persisted after stopping	⚠️ Yes
Loss of creativity and interest, feeling bored	2 posts	🟡 Moderate (2/2)	Ongoing while on medication	Resolves
Lowered sex drive	1 posts	🟢 Mild (1/1)	Ongoing while on medication	Resolves
Excessive yawning	1 posts	🟢 Mild (1/1)	Transient; resolved after a while	Resolves

User Quotes by Side Effect

Significant weight gain and increased appetite (Often starts within first few weeks, continues as long as medication is taken, no reports of resolving while on drug)

"Of Abilify, had gained 80lbs over the course of 6 months and experienced (her words) 'no relief'." source

"It's one of the only meds that works for me, but because of the weight gain and me having type 2 diabetes, I had to go off it." source

"There's a chance it will increase your appetite/change your metabolism a bit, but it's ..." source

Severe restlessness and inability to sit still (akathisia) (Can start within days of starting or dose increase; persists as long as on drug; resolves after stopping)

"On 15 mg I had akathisia so bad I couldn't stand it and refused to try the drug again ..." source

"I can't tolerate any and didn't know it, then got chronic Akathisia from Abilify—the intense anxiety and shaking, which can turn into ..." source

"It made me restless and when I was weaned off it, I couldn't keep still, my legs would continually shake and I had to keep walking to tire ..." source

Extreme fatigue, lethargy, and sedation (Can start immediately or within first week; persists as long as on drug; resolves after stopping)

"It made me like a sleepy zombie. Glad my parents stood up to them and took me off it." source

"Took a month or so to really make a difference, but it diid. Side effects were blurred vision, restlessness, and fatigue/lethargy." source

"I take abilify 2mg at night because otherwise I get tired during the day if taken early." source

Increased anxiety and panic attacks (Often starts at initiation or dose increase; may resolve after a few weeks or after stopping)

"I took Abilify though and it gave me HORRIBLE anxiety. Just depends on the person." source

"When I started and with dose increases, I'd have increased anxiety and agitation. That resolved after a couple of weeks." source

"However, now that I've been off of abilify for about a month now I feel completely back to normal. No more debilitating anxiety and I am ..." source

Emotional blunting, flatness, or feeling empty (Can start early in treatment; persists as long as on drug; resolves after stopping)

"I felt a weird emptiness and lack of personality so ..." source

"Another side effect of Abilify is reduced intensity of emotions." source

"I felt an overall sense of Meh at the beginning." source

Muscle twitches, spasms, and body weakness (Can start early; persists as long as on drug; resolves after stopping)

"For me, it caused muscle twitches, excessive yawning, and heat intolerance." source

"My whole body would fall weak, especially my muscles. It caused dyskinesia, which is uncontrollable muscle spasm and ..." source

"Shaking/tremors in left arm. Inability to type fluently. Loss of creativity and or ability to make art." source

Difficulty falling or staying asleep (Can start immediately; persists as long as on drug; resolves after stopping)

"I started out taking it in the evening, but I couldn't stay asleep, tossed and turned all night, and was grinding my teeth like crazy all night." source

"I only take 5 -10mg and it keeps me awake for an extra hour. I'm ready to sleep around 2am-3am and, ideally would get to sleep between 10am and ..." source

Mild visual hallucinations or objects moving (Not specified; likely early in treatment)

"And I think I'm having mild hallucinations. The objects around the room are slightly moving, it's like everything around me is alive, but it ..." source

"It's knocked out my irritability/anger and hallucinations and has boosted my ..." source

Increased appetite and strong cravings for carbohydrates (Starts early; persists as long as on drug)

"I'm on Abilify & so far it has worked great for my bipolar depression. The bad thing is that it makes me crave carbs really bad so I eat more." source

"There's a chance it will increase your appetite/change your metabolism a bit, but it's ..." source

Vivid nightmares and disturbing dreams (Not specified; likely early in treatment)

"It gave me vivid nightmares that I was on fire to where I would wake up screaming at the top of my lungs and couldn't get any sleep." source

Tremors and shaking (Can start early; persists as long as on drug)

"Shaking/tremors in left arm. Inability to type fluently." source

"I can't tolerate any and didn't know it, then got chronic Akathisia from Abilify—the intense anxiety and shaking, which can turn into ..." source

Heat intolerance (Starts during use; may persist after stopping)

"For me, it caused muscle twitches, excessive yawning, and heat intolerance. The yawning thing went away after a while, but the heat intolerance ..." source

Loss of creativity and interest, feeling bored (Can start after a few weeks; persists as long as on drug)

"Loss of creativity and or ability to make art." source

"I started abilify a couple months ago and lately I've been feeling so bored. Nothing interests me I thought it was depression at first but I don't really feel ..." source

Lowered sex drive (Not specified; likely ongoing while on drug)

"Side effects are benign such as increased thirst, little bit lower libido (though that could be lack of mania) and better sleep." source

Excessive yawning (Starts early; resolves after a while even if continuing medication)

"For me, it caused muscle twitches, excessive yawning, and heat intolerance. The yawning thing went away after a while, but the heat intolerance ..." 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)
NCT: NCT06141876
Mechanism: Deuterated psilocybin analog (psychedelic-derived, 5-HT2A receptor agonist)
Side Effect Comparison: Transient mild-moderate headache and nausea most common; no sexual dysfunction, weight gain, or sedation reported (unlike SSRIs/SNRIs). No evidence of dependence or withdrawal. 0% sexual dysfunction vs ~30% for SSRIs/SNRIs.
Efficacy Data:
- Response rate: 53.3% (CYB003) vs 20% (placebo) at 3 weeks
- Remission rate: 75% at 4 months (CYB003)
- MADRS change: -14.08 points (CYB003 16mg) vs -8.24 points (placebo) at 3 weeks
- Time to response: 1-3 weeks
- Source
Why it might interest you: Rapid onset (1-3 weeks), high remission rates, and a side effect profile lacking sexual dysfunction, weight gain, or sedation make this attractive for those experiencing side effects from standard antidepressants.
Results: Significant reduction in MADRS scores, rapid onset, high remission rates at 4 months, well-tolerated in trial population.
Sources: 1, 2, 3

Osavampator (NBI-1065845, TAK-653)

Sponsor: Neurocrine Biosciences
Phase: Phase 3
Mechanism: AMPA receptor positive allosteric modulator (AMPA-PAM)
Side Effect Comparison: No significant weight gain, sexual dysfunction, or sedation reported in early trials. Side effect profile appears favorable compared to SSRIs/SNRIs, with lower rates of common adverse effects (e.g., <5% headache, dizziness).
Efficacy Data:
- Response rate: Not yet reported (Phase 3 ongoing)
- Remission rate: Not yet reported (Phase 3 ongoing)
- MADRS change: Not yet reported (Phase 3 ongoing); Phase 2 showed significant improvement over placebo
- Time to response: Potentially within 2 weeks (based on AMPA modulator class)
- Source
Why it might interest you: Novel mechanism (AMPA modulation) offers potential for rapid onset and fewer side effects (notably less sexual dysfunction, weight gain, or sedation) compared to standard antidepressants.
Results: Phase 2 data suggest 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 more favorable than SSRIs/SNRIs.
Efficacy Data:
- Response rate: Not reported
- Remission rate: Not reported
- MADRS change: Not specified for D-cycloserine in MDD; in TRD, significant improvement over placebo in phase 2 trial (NCT00408031)
- Time to response: Within 2 weeks (based on trial data)
- Source
Why it might interest you: Different mechanism (NMDA modulation), rapid onset, and minimal side effects make this an attractive adjunct for those who cannot tolerate standard antidepressants.
Results: Adjunctive D-cycloserine improved depressive symptoms in treatment-resistant depression with rapid onset.
Sources: 1

Psilocybin (various formulations)

Sponsor: Multiple (Compass Pathways, Usona, academic)
Phase: Phase 2/3
NCT: NCT06141876
Mechanism: Classic psychedelic (5-HT2A receptor agonist)
Side Effect Comparison: Transient headache, nausea, and mild anxiety during dosing session; no chronic sexual dysfunction, weight gain, or sedation. No withdrawal or dependence risk. 0% sexual dysfunction vs ~30% for SSRIs/SNRIs.
Efficacy Data:
- Response rate: Not specified in this trial; other psilocybin studies report 54-71% response at 4-6 weeks
- Remission rate: Not specified in this trial; other psilocybin studies report 29-54% remission at 4-6 weeks
- MADRS change: Not specified (psilocybin studies show large effect sizes, e.g., -17.6 vs -5.4 for placebo in other trials)
- Time to response: 1-2 weeks
- Source
Why it might interest you: Very rapid onset, high response/remission rates, and a side effect profile lacking the most common SSRI/SNRI issues (sexual dysfunction, weight gain, sedation) make this a compelling alternative for those with side effects from standard medications.
Results: Multiple studies show rapid, robust antidepressant effects with a single or few doses; FDA Breakthrough Therapy Designation for TRD.
Sources: 1, 2

Appendix D: Methodology

We examined 30,000+ clinical trial listings from ClinicalTrials.gov, reviewed more than 300 journal articles on PubMed, and analyzed 62 patient discussions in online forums. Our review included 67 adverse event listings from the OpenFDA Drug Label database. We identified 15 user-reported side effects, assessed by frequency and severity, supported by direct patient quotes and clinical context.