From the FDA Drug Label
Combined use of haloperidol and lithium. An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leucocytosis, elevated serum enzymes, BUN and FBS) followed by irreversible brain damage has occurred in a few patients treated with lithium plus haloperidol A causal relationship between these events and the concomitant administration of lithium and haloperidol has not been established; however, patients receiving such combined therapy should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear
The connection between lithium and encephalopathy is that an encephalopathic syndrome has occurred in a few patients treated with lithium plus haloperidol, characterized by symptoms such as weakness, lethargy, and confusion. Although a causal relationship between lithium and encephalopathy has not been established, patients receiving lithium and haloperidol concomitantly should be closely monitored for signs of neurological toxicity 1.
From the Research
Lithium therapy is associated with a significant risk of developing encephalopathy, particularly when lithium levels in the blood become elevated, and this risk can be mitigated with careful monitoring and management. The relationship between lithium carbonate therapy and the risk of developing encephalopathy is well-established, with a narrow therapeutic window (typically 0.6-1.2 mEq/L) and levels exceeding 1.5 mEq/L leading to neurotoxicity and encephalopathy 2. This risk is increased by factors such as dehydration, sodium depletion, renal impairment, and concurrent use of certain medications like NSAIDs, ACE inhibitors, and diuretics that can raise lithium levels. Symptoms of lithium-induced encephalopathy include confusion, disorientation, slurred speech, tremors, ataxia, and in severe cases, seizures or coma.
The risk of encephalopathy is higher in elderly patients and those with pre-existing neurological conditions, and regular monitoring of lithium levels is essential, particularly after dose adjustments or when starting medications that might interact with lithium 3. Patients should maintain adequate hydration, consistent salt intake, and report early signs of toxicity. If encephalopathy is suspected, lithium should be temporarily discontinued and medical attention sought immediately. Most cases resolve with proper management and lithium level normalization, though severe cases may require hemodialysis 4.
It is also important to note that lithium intoxication can occur even at normal serum levels, especially in patients with advanced age, co-morbidity with pre-existing neurological or other general diseases, and in combination with the use of antipsychotics, antidepressants, or mood stabilizers 3. Therefore, clinical signs of intoxication should be carefully monitored, and discontinuation of lithium medication should be considered on the basis of these signs, rather than relying solely on serum lithium levels.
In terms of management, hemodialysis may be necessary in severe cases of lithium poisoning, although the evidence for its effectiveness is limited, and it should be considered on a case-by-case basis 4. Overall, careful monitoring and management of lithium therapy are crucial to minimizing the risk of encephalopathy and ensuring the safe and effective use of this medication.