What psychiatric medications increase lactate dehydrogenase (LDH) levels?

Psychiatric Medications That Increase LDH

Antipsychotic medications, particularly haloperidol and olanzapine, significantly increase lactate dehydrogenase (LDH) levels, with typical antipsychotics causing more pronounced elevations than atypical agents.

Antipsychotics with Documented LDH Elevation

Typical (First-Generation) Antipsychotics

• Haloperidol causes the most significant increases in blood lactate levels, with elevations occurring within the first 10 days of therapy and continuing to rise significantly through 90 days of treatment 1, 2
• Chlorpromazine also produces significant lactate increases within the first 10 days, with continued elevation throughout chronic treatment 1
• These elevations are strongly correlated with extrapyramidal side effects, particularly dystonia and Parkinsonian manifestations 1, 2

Atypical (Second-Generation) Antipsychotics

• Olanzapine increases blood lactate levels, though significantly less than haloperidol, with elevations becoming apparent after 90 days of continuous therapy 1, 2
• Risperidone, quetiapine, and other atypical agents all show significant increases in arterial blood lactate levels after 90 days of treatment compared to baseline (p<0.0001 for all agents tested) 1
• Clozapine is associated with elevated liver enzyme levels, which may include LDH as part of hepatotoxicity monitoring 3

Clinical Significance and Monitoring

Correlation with Side Effects

• Elevated blood lactate levels serve as early biomarkers for extrapyramidal symptoms in patients on chronic antipsychotic treatment 1
• Patients with dystonia and Parkinsonian-like manifestations demonstrate significantly higher arterial blood lactate levels compared to patients without these symptoms 1
• The correlation is strongest with haloperidol, showing significant associations between blood lactate and dystonia at 1 month (p<0.001) and 6 months (p=0.012), and with tardive dyskinesia at 1 month (p=0.032) 2

Mechanism

• LDH elevation reflects cellular injury and metabolic disturbances caused by antipsychotic medications, particularly through mitochondrial dysfunction and altered energy metabolism 1, 4
• The enzyme is released from damaged cells in various tissues including liver, muscle, and brain tissue 4

Practical Recommendations

Medication Selection

• When LDH elevation is a concern, prefer atypical antipsychotics over typical agents, as they produce significantly lower lactate elevations 2
• Among atypical agents, quetiapine appears to have the lowest risk profile for metabolic disturbances 5
• Avoid clozapine and olanzapine in patients with pre-existing liver disease or metabolic concerns 3

Monitoring Timeline

• Obtain baseline LDH levels before initiating antipsychotic therapy 1
• Recheck LDH at 10 days after starting typical antipsychotics (when initial elevations occur) 1
• Monitor LDH at 3 months and 6 months for all antipsychotics, as significant elevations occur by 90 days regardless of agent type 1, 2
• Assess for extrapyramidal symptoms at each monitoring point, as these correlate with LDH elevations 1, 2

Clinical Pitfalls

• Do not dismiss elevated LDH as nonspecific—in the context of antipsychotic use, it correlates with both medication effect and development of extrapyramidal symptoms 1, 2
• Haloperidol produces significantly higher lactate levels than olanzapine at all time points from baseline through 6 months (p<0.001), making it a poor choice when metabolic monitoring is challenging 2
• Elevated liver enzymes with phenothiazines (including chlorpromazine) may include LDH as part of cholestatic jaundice syndrome 3