What are the signs of medication-related extrapyramidal effects from Rexulti (brexpiprazole)?

Signs of Medication-Related Extrapyramidal Effects from Rexulti

Monitor patients on Rexulti (brexpiprazole) for four main categories of extrapyramidal symptoms: akathisia (restlessness), dystonia (muscle spasms), parkinsonism (tremor, rigidity, bradykinesia), and tardive dyskinesia (involuntary movements), with akathisia being the most common adverse effect reported in clinical trials.

Acute Extrapyramidal Symptoms

Akathisia

• Subjective feeling of severe restlessness that manifests as pacing or physical agitation 1, 2
• Most common extrapyramidal symptom with Rexulti, occurring in 4-9% of patients depending on dose and indication 3
• In pediatric patients (13-17 years), akathisia occurred in 3-4% of cases 3
• Often misinterpreted as psychotic agitation or anxiety, leading to inappropriate dose increases rather than recognition as a medication side effect 1
• Typically occurs within the first few days of antipsychotic therapy 2

Dystonia

• Sudden spastic contraction of distinct muscle groups, most commonly affecting:
  • Neck muscles (torticollis)
  • Eyes (oculogyric crisis - forced upward deviation of eyes)
  • Torso (opisthotonus)
  • Limbs 1, 2
• Laryngeal dystonia presents as choking sensation, difficulty breathing, or stridor and is potentially life-threatening 2
• Risk factors include young age, male gender, and use of high-potency agents 1
• Usually occurs after the first few doses or after dose increases 2

Drug-Induced Parkinsonism

• Bradykinesia (slowness of movement)
• Tremors (shaking, particularly at rest)
• Muscle rigidity (stiffness)
• Muscle stiffness and hypokinesia (reduced movement) 1, 3
• In pediatric schizophrenia trials, difficulty moving or slow movement was a common adverse effect 3
• Can be difficult to differentiate from negative symptoms of schizophrenia or, in severe cases, catatonia 1

Additional Acute Movement Disorders

In pediatric patients specifically, watch for:

• Abnormal eye movements
• Blepharospasm (involuntary eyelid closure)
• Extrapyramidal disorder (general movement abnormalities)
• Psychomotor hyperactivity 3

Tardive Dyskinesia (Late-Onset)

• Involuntary movement disorder consisting of athetoid (writhing) or choreic (dance-like) movements 1
• Most commonly affects the orofacial region: rapid involuntary facial movements including blinking, grimacing, chewing, or tongue movements 2
• Can affect any part of the body, including extremities and trunk 1, 2
• May persist even after discontinuing the medication, unlike withdrawal dyskinesias which typically resolve 1
• Associated with long-term use of antipsychotics 1
• Respiratory dyskinesia is often undiagnosed and includes orofacial dyskinesia, dysphonia, dyspnea, and can lead to recurrent aspiration pneumonia 2

Clinical Context and Monitoring

Incidence with Rexulti

The FDA label indicates that Rexulti has a relatively favorable extrapyramidal symptom profile compared to traditional antipsychotics 3. In adult schizophrenia trials:

• Akathisia: 6% (vs 5% placebo)
• Other EPS-related reactions: 5% (vs 4% placebo)
• Tremor: 2-3% 3

In pediatric patients (13-17 years), the incidence of extrapyramidal symptoms was higher at 36% compared to adults 3.

Important Clinical Pitfalls

Akathisia is frequently misdiagnosed as worsening psychosis or anxiety, leading to inappropriate medication increases rather than dose reduction or treatment of the akathisia itself 1. This is a common reason for medication noncompliance and increases relapse risk 1.

Children and adolescents may be at higher risk for extrapyramidal side effects than adults and may have greater difficulty communicating their concerns due to developmental issues 1.

Monitoring Recommendations

• Baseline assessment of abnormal movements should be recorded before starting Rexulti 1
• Use standardized scales:
  • Simpson-Angus Scale (SAS) for general EPS
  • Barnes Akathisia Rating Scale (BARS) for akathisia
  • Abnormal Involuntary Movement Scale (AIMS) for dyskinesia 3
• Assessment for dyskinesias should occur at least every 3 to 6 months once therapy has started 1
• In clinical trials, 4% of patients shifted from normal to abnormal on the BARS and SAS scales with Rexulti treatment 3

Neuroleptic Malignant Syndrome

While not strictly an extrapyramidal symptom, neuroleptic malignant syndrome (NMS) is a serious dopamine-related adverse effect that requires immediate recognition:

• High fever
• Severe muscle rigidity/hypertonicity
• Mental status changes
• Autonomic dysfunction (changes in pulse, blood pressure, heart rate, breathing, sweating) 3, 2
• This is a potentially lethal syndrome requiring immediate medical attention 3

The evidence consistently demonstrates that while Rexulti has a more favorable extrapyramidal symptom profile than traditional high-potency antipsychotics 4, 5, vigilant monitoring remains essential, particularly for akathisia which represents the most common movement-related adverse effect 6, 7.