What additional labs should be checked for a patient with a complex psychiatric condition on Abilify (aripiprazole) and Seroquel (quetiapine) with a decreasing but still elevated creatine kinase MM (CK MM) level?

Laboratory Workup for Elevated CK-MM on Dual Antipsychotic Therapy

For a patient on aripiprazole and quetiapine with persistently elevated CK-MM (282 IU/L), you should immediately check: troponin, AST/ALT, aldolase, LDH, myoglobin, urinalysis for myoglobinuria, renal function (BUN/creatinine), electrolytes, and inflammatory markers (ESR/CRP). 1 This workup distinguishes between benign asymptomatic CK elevation versus early neuroleptic malignant syndrome (NMS), serotonin syndrome, or rhabdomyolysis—all potentially life-threatening complications of antipsychotic therapy.

Essential Laboratory Panel

Cardiac and Muscle Injury Markers

• Troponin to evaluate myocardial involvement, as cardiac complications can occur with antipsychotic-induced muscle injury 1
• CK-MB by mass assay to differentiate cardiac from skeletal muscle origin 1
• AST, ALT, and LDH as these transaminases are elevated in muscle inflammation and can help assess severity 1
• Aldolase provides additional confirmation of muscle inflammation 1

Renal Function and Rhabdomyolysis Assessment

• BUN and creatinine to detect renal compromise, as rhabdomyolysis can cause acute kidney injury even with moderately elevated CK 1, 2
• Urinalysis with myoglobin to identify gross muscle damage; myoglobinuria indicates clinically significant rhabdomyolysis requiring aggressive intervention 3
• Electrolytes including calcium, as electrolyte disturbances accompany muscle breakdown 1

Inflammatory and Systemic Markers

• ESR and CRP to assess inflammatory activity and help differentiate between drug-induced myositis versus other inflammatory conditions 1

Critical Diagnostic Considerations

Distinguishing Between Clinical Syndromes

Massive Asymptomatic CK Elevation (MACKE) is the most likely diagnosis given the patient is asymptomatic with decreasing CK. This condition occurs in approximately 10% of patients on antipsychotics, with CK levels ranging from 1,206 to 177,363 IU/L (median 9,600 IU/L), and typically resolves spontaneously within 4-28 days. 3, 4 Your patient's CK of 282 IU/L is relatively modest and trending downward, suggesting benign MACKE rather than a dangerous syndrome.

Neuroleptic Malignant Syndrome must be ruled out, though it typically presents with CK levels of 500-3,000 IU/L accompanied by fever (>100.4°F), rigidity, mental status changes, and autonomic instability. 1, 5 The absence of these clinical features makes NMS unlikely, but the laboratory workup above is essential to confirm this.

Serotonin Syndrome is a consideration given the dual antipsychotic regimen, particularly with quetiapine's serotonergic properties. This syndrome presents with the clinical triad of mental status changes, autonomic hyperactivity (tachycardia, hypertension, diaphoresis), and neuromuscular abnormalities (hyperreflexia, clonus, tremor). 1, 6 CK elevation with rhabdomyolysis occurs in severe cases with hyperthermia >41.1°C and muscle rigidity. 6

Clinical Monitoring Strategy

Physical Examination Focus

• Vital signs including temperature, blood pressure (checking for fluctuations ≥20 mm Hg diastolic or ≥25 mm Hg systolic), heart rate, and respiratory rate 1
• Neurological examination specifically assessing for muscle rigidity (lead-pipe rigidity suggests NMS), hyperreflexia, clonus (inducible or spontaneous), and tremor 1, 6
• Mental status evaluation for confusion, agitation, or altered consciousness 1, 6
• Muscle strength testing as weakness is more typical of myositis than pain 1

Ongoing Laboratory Monitoring

• Weekly CK monitoring is recommended only if there are clinical concerns for toxicity or harm, not routinely for asymptomatic patients 2, 4
• Repeat CK in 3-7 days to confirm the downward trend; if CK continues to decrease without symptoms, this supports benign MACKE 3, 4

Management Algorithm Based on Findings

If Laboratory Results Show:

Normal troponin, normal renal function, no myoglobinuria, CK continuing to decrease:

• Continue current antipsychotic regimen with clinical monitoring 4
• No medication changes needed as this represents benign MACKE 3, 4
• Educate patient to report muscle pain, weakness, dark urine, or flu-like symptoms immediately 2

Elevated troponin or myoglobinuria:

• Immediately discontinue both antipsychotics 1
• Initiate aggressive IV hydration (4+ liters) to prevent renal failure 5
• Consider ICU admission for continuous cardiac monitoring 6

Signs of NMS (fever, rigidity, altered mental status):

• Hold both antipsychotics immediately 1
• Initiate supportive care with benzodiazepines for agitation 1
• Consider dantrolene or bromocriptine for severe cases 1

Signs of serotonin syndrome (hyperreflexia, clonus, autonomic instability):

• Discontinue all serotonergic agents 6
• Administer cyproheptadine 12 mg initially, then 2 mg every 2 hours until symptom improvement 6
• Provide benzodiazepines and external cooling measures 6

Common Pitfalls to Avoid

• Do not assume elevated CK always requires antipsychotic discontinuation. MACKE is often self-limiting and resolves despite continuing treatment in up to 20% of cases. 3, 4
• Do not routinely monitor CK in asymptomatic patients. This leads to unnecessary medication changes and diagnostic confusion. 2, 3
• Do not rechallenge with the same antipsychotic if rhabdomyolysis occurred. Two-thirds of patients redeveloped massive CK elevation within one week of rechallenge. 3
• Do not switch to another antipsychotic assuming it is "safer." MACKE has been reported with clozapine, olanzapine, risperidone, quetiapine, aripiprazole, haloperidol, and amisulpiride—there is no consistently safe alternative. 3, 4, 7

Special Considerations for This Patient

Given your patient is on both aripiprazole and quetiapine, the combination may increase risk through different mechanisms: aripiprazole as a D2 partial agonist and quetiapine with significant serotonergic activity. 1 However, the 2025 INTEGRATE guidelines support aripiprazole augmentation strategies in schizophrenia, suggesting this combination can be clinically appropriate when monitored properly. 1

The decreasing CK trend (currently 282 IU/L) without symptoms strongly suggests benign MACKE rather than a progressive dangerous syndrome. Complete the laboratory workup above to definitively rule out cardiac involvement, renal compromise, and rhabdomyolysis, then continue clinical monitoring without medication changes if results are reassuring. 2, 4