How to manage muscle aches and tremor side effects of Rexulti (brexpiprazole)?

Managing Muscle Aches and Tremor with Rexulti (Brexpiprazole)

If you are experiencing muscle aches and tremor on Rexulti, first rule out serious neuromuscular complications (neuroleptic malignant syndrome or tardive dyskinesia), then consider dose reduction or symptomatic management, as these side effects are generally less common with brexpiprazole compared to other antipsychotics but can still occur. 1

Immediate Assessment Required

Evaluate for serious complications that require immediate intervention:

• Check for neuroleptic malignant syndrome (NMS) - Look specifically for high fever, muscle rigidity (stiffness), changes in pulse/blood pressure/heart rate, increased sweating, and confusion. This is a medical emergency requiring immediate discontinuation of Rexulti and emergency care 1

• Assess for tardive dyskinesia - Examine for uncontrolled movements in face, tongue, or other body parts. While tremor alone is not tardive dyskinesia, new-onset involuntary movements warrant stopping the medication as this condition may not resolve even after discontinuation 1

• Evaluate for serotonin syndrome if on other serotonergic medications - Look for mental status changes (confusion, agitation), neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity), and autonomic symptoms (hypertension, tachycardia, diaphoresis). This typically occurs within 24-48 hours of combining serotonergic drugs 2

If Serious Complications Are Ruled Out

For isolated muscle aches and tremor without concerning features:

Dose-Related Considerations

• Consider dose reduction - Brexpiprazole demonstrates relatively low incidence of extrapyramidal symptoms compared to other antipsychotics, and these effects may be dose-dependent 3, 4

• Review current dose - The therapeutic range is 2-4 mg/day for schizophrenia; if on higher end of dosing, reduction may alleviate symptoms while maintaining efficacy 4

Symptomatic Management Options

For muscle aches:

• Acetaminophen is first-line for pain management without contraindications 2

• NSAIDs can be used if no contraindications (avoid if on anticoagulants, history of bleeding, renal impairment, or cardiovascular disease) 2

• Monitor for drug interactions - NSAIDs combined with SSRIs or anticoagulants increase bleeding risk 2

For tremor:

• Assess medication list for other tremor-inducing drugs - SSRIs, stimulants, and other medications can contribute to tremor 2

• Check for metabolic causes - Obtain thyroid function tests, electrolytes (particularly potassium and magnesium), and glucose levels as brexpiprazole can affect metabolism 1

• Consider beta-blockers for symptomatic tremor management if no contraindications (avoid in bradycardia, heart block, severe asthma) - though this requires coordination with prescribing psychiatrist

Monitoring Parameters

Track the following to guide management:

• Creatine kinase (CK) levels - Elevated CK with muscle symptoms suggests myositis or rhabdomyolysis requiring immediate intervention 2

• Blood pressure including orthostatic measurements - Brexpiprazole can cause orthostatic hypotension which may manifest as dizziness and contribute to falls 1

• Weight and metabolic parameters - Check blood sugar and lipid levels as metabolic changes can occur 1

Important Clinical Pitfalls

Avoid these common errors:

• Do not abruptly discontinue brexpiprazole - If switching medications is necessary, taper gradually to avoid withdrawal symptoms and symptom recurrence 2

• Do not dismiss tremor as benign - New-onset tremor requires evaluation for NMS, serotonin syndrome, or metabolic abnormalities before attributing to medication side effect 2, 1

• Do not combine multiple serotonergic agents without close monitoring - If patient is on antidepressants, stimulants, or other serotonergic drugs with brexpiprazole, monitor closely for 24-48 hours after any dose changes 2

• Avoid dehydration and overheating - Brexpiprazole impairs temperature regulation; ensure adequate hydration, avoid excessive exercise, stay in cool environments, and limit sun exposure 1

When to Contact Prescribing Psychiatrist

Immediate contact required for:

• Fever with muscle rigidity
• Uncontrolled movements
• Severe muscle weakness
• Confusion or altered mental status
• Dark urine (suggesting rhabdomyolysis)

Routine contact for:

• Persistent tremor or muscle aches affecting function
• Need for dose adjustment
• Consideration of alternative antipsychotic medication