What You Should Know About Rexulti Side Effects

Every medication comes with potential side effects, and Rexulti (Brexpiprazole) is no exception. Whether you're just starting Rexulti or considering it as a treatment option, understanding what side effects to expect — and which ones need immediate medical attention — can help you feel more prepared and in control.

This guide covers the most common side effects from FDA clinical trial data, serious risks to watch for, and practical tips for managing them.

What Is Rexulti?

Rexulti is an atypical antipsychotic made by Otsuka Pharmaceutical and Lundbeck. It's FDA-approved for three conditions:

• Major depressive disorder (MDD) — as an add-on to antidepressants
• Schizophrenia
• Agitation associated with Alzheimer's dementia

For a deeper look at what Rexulti is and how it's used, see our full guide: What Is Rexulti? Uses, Dosage, and What You Need to Know.

Common Side Effects of Rexulti

In clinical trials, the following side effects were reported most frequently. They vary somewhat depending on which condition Rexulti is treating.

For Depression (Adjunct to Antidepressants)

• Akathisia (restlessness, inability to sit still) — reported in about 6.6% of patients
• Weight gain — about 6.3% of patients
• Drowsiness/sedation
• Upper respiratory tract infection — about 6.9%
• Nasopharyngitis (common cold symptoms) — about 5%

For Schizophrenia

• Extrapyramidal symptoms (involuntary movements, tremor, stiffness)
• Weight gain
• Akathisia
• Drowsiness

For Alzheimer's-Related Agitation

• Headache
• Dizziness
• Urinary tract infection
• Nasopharyngitis
• Sleep disturbances (insomnia or excessive sleepiness)

Other Common Side Effects (All Indications)

• Tremor
• Insomnia
• Headache
• Tiredness or fatigue
• Constipation
• Increased appetite

Most common side effects are mild and may improve after the first few weeks as your body adjusts to the medication.

Serious Side Effects of Rexulti

Rexulti carries two FDA boxed warnings — the most serious type of safety alert. Beyond those, there are several other serious side effects to be aware of.

Boxed Warning #1: Increased Risk of Death in Elderly Patients with Dementia-Related Psychosis

Antipsychotic medications, including Rexulti, are associated with an increased risk of death in elderly patients with dementia-related psychosis. Rexulti is not approved for treating dementia-related psychosis except for agitation specifically associated with Alzheimer's disease.

Boxed Warning #2: Suicidal Thoughts and Behaviors in Young People

Rexulti and antidepressant medications may increase suicidal thoughts and actions in children, adolescents, and young adults (under 25), especially in the first few months of treatment or when doses change. Patients and caregivers should closely monitor for worsening depression or unusual behavior changes.

Other Serious Side Effects

• Neuroleptic malignant syndrome (NMS) — A rare but life-threatening reaction. Symptoms include high fever, rigid muscles, confusion, rapid heartbeat, and changes in blood pressure. This is a medical emergency — call 911 immediately.
• Tardive dyskinesia — Uncontrollable movements of the face, tongue, or other body parts. This may not go away even after stopping Rexulti.
• Metabolic changes — Including high blood sugar (hyperglycemia), increased cholesterol and triglycerides, and significant weight gain. Your doctor should monitor blood sugar and lipid levels regularly.
• Orthostatic hypotension — A drop in blood pressure when standing up, causing dizziness or fainting.
• Seizures
• Low white blood cell count — Increases the risk of infections.
• Compulsive behaviors — Some patients have reported uncontrollable urges to gamble, shop, eat, or engage in sexual activity.
• Stroke — In elderly patients with dementia, cerebrovascular events including stroke have been reported.
• Difficulty regulating body temperature — Be cautious during exercise or in hot weather.

Side Effects in Specific Populations

Elderly Patients

Older adults, especially those with dementia, face higher risks including stroke, falls, and death. Rexulti is approved for Alzheimer's-related agitation but not for other forms of dementia-related psychosis.

Pregnant or Breastfeeding Women

Rexulti is classified as Pregnancy Category C in Australia. It is not known whether Brexpiprazole passes into breast milk. If you are pregnant, planning to become pregnant, or breastfeeding, talk to your doctor before starting or continuing Rexulti.

CYP2D6 Poor Metabolizers

Some people metabolize Rexulti more slowly due to genetic differences in the CYP2D6 enzyme. These individuals may have higher drug levels in their blood and may need a lower dose. Your doctor can order genetic testing if needed. Learn more about how Rexulti is processed in your body in our article on how Rexulti works.

How to Manage Rexulti Side Effects

Here are practical tips for dealing with the most common side effects:

For Akathisia (Restlessness)

• Talk to your doctor — they may adjust your dose or add a medication like Propranolol to help
• Gentle exercise like walking can help relieve the feeling
• Avoid caffeine, which can make restlessness worse

For Weight Gain

• Monitor your weight regularly
• Focus on a balanced diet and regular physical activity
• Your doctor may suggest dietary counseling or medication adjustments if weight gain is significant

For Drowsiness

• Take Rexulti at bedtime if your doctor approves
• Avoid alcohol and other sedating medications
• Don't drive or operate heavy machinery until you know how Rexulti affects you

For Dizziness (Orthostatic Hypotension)

• Stand up slowly from sitting or lying positions
• Stay hydrated
• Let your doctor know if dizziness is frequent or severe

When to Call Your Doctor

Contact your healthcare provider right away if you experience:

• High fever, rigid muscles, or confusion (possible NMS)
• Uncontrollable facial or body movements
• Signs of high blood sugar (extreme thirst, frequent urination, weakness)
• Suicidal thoughts or sudden mood changes
• Severe dizziness or fainting
• Seizures
• New compulsive behaviors (gambling, binge eating, etc.)

If symptoms seem life-threatening, call 911 immediately.

Final Thoughts

Rexulti is an effective medication for many people with depression, schizophrenia, and Alzheimer's-related agitation. Like all medications, it comes with potential side effects — most of which are manageable with your doctor's guidance.

The key is to stay informed and communicate openly with your healthcare provider. Report any new or worsening symptoms promptly, attend your follow-up appointments, and don't stop taking Rexulti without talking to your doctor first.

If you're ready to fill your Rexulti prescription, use Medfinder to find a pharmacy with Rexulti in stock near you. And if cost is a concern, check out our guide to saving money on Rexulti.