Is quetiapine (Qutan SR) appropriate for a patient with a space‑occupying lesion in the splenium of the corpus callosum, and what initial dose and monitoring are recommended?

Quetiapine (Qutan SR) for Space-Occupying Lesion in Splenium of Corpus Callosum

Quetiapine is not appropriate for a patient with a space-occupying lesion in the splenium of the corpus callosum, as this drug has been directly implicated in causing reversible splenial lesions and may worsen the underlying pathology. 1

Critical Safety Concern: Quetiapine-Induced Splenial Lesions

• A documented case report demonstrates that quetiapine (500 mg/day) combined with lithium caused a reversible lesion in the splenium of the corpus callosum (SCC) that completely resolved within two weeks after discontinuing both medications. 1
• The patient in this case presented with neuropsychiatric symptoms including generalized tremors, rigidity, dysarthria, high fever, hypertension, tachycardia, and tachypnea—symptoms that fulfilled diagnostic criteria for neuroleptic malignant syndrome. 1
• Cerebral MRI demonstrated a reversible lesion with transiently reduced diffusion in the SCC, a finding that resolved completely after drug discontinuation. 1

Pathophysiology of Splenial Lesions

• Reversible splenial lesion syndrome (RESLES) is characterized by transient lesions in the splenium of the corpus callosum with various etiologies including antiepileptic drug withdrawal, metabolic abnormalities, and drug toxicity. 1
• Splenial lesions in epilepsy patients have been associated with antiepileptic drug intoxication, edema after generalized seizures, or rapid changes in antiepileptic drug levels, though no single etiologic factor has been definitively identified. 2
• Carbamazepine has been documented to cause transient splenial lesions both during treatment and after sudden withdrawal, with complete resolution occurring within two months. 3

Clinical Implications for This Patient

• Administering quetiapine to a patient who already has a space-occupying lesion in the splenium carries the risk of exacerbating the existing pathology or creating additional drug-induced splenial injury. 1
• The mechanism by which quetiapine causes splenial lesions is not fully elucidated, but the documented case suggests a direct neurotoxic effect that manifests as cytotoxic edema visible on diffusion-weighted MRI. 1
• RESLES is often detected incidentally and easily neglected; clinicians should maintain high suspicion in patients exhibiting neuropsychiatric symptoms, particularly those taking medications irregularly or at high doses. 1

Alternative Management Strategies

If Antipsychotic Therapy Is Absolutely Required

• Haloperidol is the preferred first-line antipsychotic in patients with neurologic compromise, starting at 0.5–1 mg orally or subcutaneously once or twice daily, with titration by 0.5 mg increments every 2–3 days as needed (maximum 5 mg/day). 4
• ECG monitoring for QTc prolongation is mandatory with haloperidol, as it can cause dysrhythmias and sudden death, especially in patients with neurologic disease who may have electrolyte abnormalities. 4
• Daily in-person examination is required to reassess the need for antipsychotic therapy and detect extrapyramidal symptoms (tremor, rigidity, bradykinesia) amid fluctuating neurologic status. 4

Contraindicated Alternatives

• Olanzapine should be avoided due to significant drowsiness, fatigue, and sleep disturbances that occur in the majority of patients, which would be particularly problematic in a patient with an existing CNS lesion. 4
• Benzodiazepines must not be used for agitation in patients with CNS lesions (except for alcohol or benzodiazepine withdrawal) because they increase delirium incidence, prolong its duration, and can precipitate neurologic deterioration. 4

Monitoring Requirements If Antipsychotic Use Is Unavoidable

• Serial MRI imaging should be performed to monitor the splenial lesion for progression or development of additional drug-induced changes. 1
• Neuropsychiatric symptoms including tremors, rigidity, dysarthria, altered consciousness, and focal neurological signs must be monitored daily, as these may indicate drug-induced neurotoxicity. 1
• Vital signs including temperature, blood pressure, and heart rate require close monitoring, as neuroleptic malignant syndrome can develop in patients with underlying CNS pathology. 1

Underlying Etiology Investigation

• Before initiating any psychotropic medication, systematically investigate and treat reversible causes of neuropsychiatric symptoms including infections, metabolic disturbances, electrolyte imbalances, seizures, and increased intracranial pressure. 4, 5
• Intracranial hypertension has been documented as a cause of splenial lesions that resolve quickly following treatment of elevated intracranial pressure, making lumbar puncture with opening pressure measurement essential in the diagnostic workup. 5
• Pain assessment and appropriate analgesia are critical, as untreated pain is a major driver of behavioral disturbances in patients with CNS lesions who may be unable to verbalize discomfort. 4

Common Pitfalls to Avoid

• Do not assume that neuropsychiatric symptoms in a patient with a splenial lesion require antipsychotic treatment without first excluding treatable medical causes such as increased intracranial pressure, infection, or metabolic derangements. 5, 1
• Avoid polypharmacy with multiple psychotropic agents, as the combination of quetiapine with other medications (such as lithium or valproate) increases the risk of severe neurotoxicity including neuroleptic malignant syndrome. 1
• Do not initiate quetiapine at standard doses (150–750 mg/day) in patients with CNS pathology, as even therapeutic doses have been implicated in causing splenial lesions. 1, 6