What can cause elevated Creatine Kinase (CK) levels, specifically CK Total of 152 U/L and CK Muscle Fraction (CK MF) of 9.9, in a psychiatric patient?

Elevated CK in Psychiatric Patients: Causes and Clinical Approach

Direct Answer

In a psychiatric patient with CK Total of 152 U/L and CK-MM of 9.9, the most likely causes are antipsychotic medication effects, recent physical activity or agitation, muscle trauma from restraints or falls, or underlying subclinical myopathy—with antipsychotic-induced CK elevation being particularly common in this population. 1

Understanding the CK Elevation

Context of These Values

• CK Total of 152 U/L represents a mild elevation (typically 1-2 times the upper limit of normal, depending on laboratory reference ranges), which is commonly seen in psychiatric patients and does not indicate severe muscle damage 2, 1
• The CK-MM fraction of 9.9 confirms skeletal muscle origin rather than cardiac involvement, as CK-MM is the predominant isoform in skeletal muscle 3, 4
• This level of elevation does not suggest rhabdomyolysis or neuroleptic malignant syndrome, which typically show CK values of 500-3,000 IU/L or much higher 1

Primary Causes in Psychiatric Patients

1. Antipsychotic Medication Effects

• Antipsychotic drugs can cause marked elevations in CK activity of the skeletal muscle (MM) form, with increases ranging from 1,206 to 177,363 IU/L in some cases, though most are asymptomatic 1
• This occurs in approximately 10% of patients treated with antipsychotics including clozapine, olanzapine, risperidone, haloperidol, and loxapine 1
• The onset can occur anywhere from 5 days to 2 years after initiating treatment, and elevations typically last 4-28 days (median 8 days) 1
• Most patients with antipsychotic-induced CK elevation are asymptomatic, and the increases are often self-limiting even with continued treatment 1
• The mechanism may involve increased cell membrane permeability in skeletal muscle, possibly related to serotonergic effects of these medications 1

2. Physical Activity and Agitation

• Acute psychotic agitation and excessive physical activity commonly cause CK elevation in psychiatric patients 1
• Strenuous or unaccustomed exercise, including eccentric muscle contractions, results in sarcomeric damage and increased serum CK that peaks at 24 hours and gradually returns to baseline with rest 2
• In psychiatric settings, this includes struggling against restraints, pacing, or other repetitive movements during acute episodes 1

3. Muscle Trauma

• Physical trauma from falls, restraints, or intramuscular injections can elevate CK levels 4
• Skeletal muscle trauma can produce CK-MB elevation (up to 8.6% of trauma victims show CK-MB >5.0 EU/L) as part of increased total CK, even without cardiac injury 4
• This is particularly relevant in psychiatric patients who may have falls or require physical intervention during acute episodes 1

4. Underlying Myopathy

• Persistently increased CK levels may indicate early or subclinical muscle disease, which can be asymptomatic in pre-clinical stages 2
• Approximately 9.9% of myasthenia gravis patients show CK elevation, and some have concomitant myositis or other neuromuscular diseases 5
• Early myopathy may become manifest only after exercise or stress, making diagnosis challenging in resting patients 2

Essential Clinical Workup

Immediate Assessment

• Obtain a detailed medication history, specifically documenting all antipsychotic medications, doses, duration of treatment, and any recent changes 1
• Assess for muscle symptoms: Ask specifically about muscle soreness, tenderness, pain, weakness (particularly proximal muscles), or stiffness 3, 6
• Evaluate recent physical activity: Document any recent agitation, restraint use, falls, intramuscular injections, or unusual physical exertion 2, 1
• Screen for signs of neuroleptic malignant syndrome: Check for fever, rigidity, altered mental status, and autonomic instability—though CK of 152 U/L makes this unlikely 1

Laboratory Evaluation

• Obtain cardiac troponin to exclude myocardial involvement, as biomarkers reflect myocardial damage regardless of mechanism 3
• Check thyroid-stimulating hormone (TSH), as hypothyroidism predisposes to myopathy and can exacerbate muscle injury 3, 6, 7
• Measure transaminases (AST, ALT) and LDH, which may be elevated reflecting enzymes released from muscle rather than liver injury 3
• Consider vitamin D (25-OH) level, as deficiency is common (67.3% in one study) and may contribute to muscle symptoms 5
• Evaluate for myositis-specific and myositis-associated antibodies (MSA/MAA) if clinical suspicion for inflammatory myopathy exists, though these are found in only 18.8% of patients with neuromuscular symptoms 5

Additional Testing When Indicated

• Urinalysis for myoglobinuria to assess for rhabdomyolysis, though this is unlikely at CK 152 U/L 3, 1
• Electromyography (EMG) and muscle MRI if weakness is present or underlying myopathy is suspected 3
• Muscle biopsy should be reserved for cases where diagnosis remains uncertain after non-invasive testing 3

Management Approach

For Antipsychotic-Related Elevation

• Continue current antipsychotic therapy if the patient is asymptomatic and CK is <10 times upper limit of normal, as these elevations are often self-limiting 6, 1
• Monitor CK levels weekly if elevation persists or symptoms develop 3, 6
• Consider dose reduction or switching to an alternative antipsychotic if CK continues to rise or symptoms emerge 6, 7
• Do not routinely discontinue effective antipsychotic therapy for mild asymptomatic CK elevation, as this may destabilize psychiatric condition 1

For Exercise or Trauma-Related Elevation

• Allow adequate rest and recovery time, as CK typically normalizes within 4-7 days after cessation of the inciting activity 2, 1
• Repeat CK measurement after 1 week of rest to confirm downward trend 2
• Implement fall prevention strategies and minimize use of physical restraints when possible 1

For Suspected Myopathy

• Refer to neurology if CK remains persistently elevated after rest and medication adjustment, or if muscle weakness is present 3, 2
• Counsel patients with suspected myopathy to continue physical activity at lower intensity to prevent muscle damage from high-intensity exercise while allowing adequate recovery 2
• Consider that strength training may be safe even in patients with myopathy, though evidence for routine exercise prescription remains insufficient 2

Critical Pitfalls to Avoid

• Do not assume all CK elevation in psychiatric patients represents neuroleptic malignant syndrome—mild elevations are common and usually benign 1
• Do not overlook hypothyroidism as a contributing factor, as it significantly increases myopathy risk and is easily treatable 3, 6, 7
• Do not dismiss normal or minimally elevated CK in symptomatic patients—some myopathies present with symptoms before significant CK elevation 6, 7
• Do not routinely monitor CK in asymptomatic patients on antipsychotics, as this provides little clinical value and may lead to unnecessary medication changes 6, 1
• Do not confuse CK-MB elevation from skeletal muscle trauma with myocardial injury—always correlate with troponin, ECG, and clinical context 4, 3
• Do not immediately discontinue effective psychiatric medications for mild CK elevation without considering the risk-benefit ratio for the patient's mental health 1