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Olanzapine enabled rechallenge after lorlatinib-induced psychosis: A case report

Akiyoshi Yokode1, Masaki Fujiwara1, Yuko Nakamura1

  • 1Department of Neuropsychiatry Okayama University Hospital Okayama Japan.

PCN Reports : Psychiatry and Clinical Neurosciences
|April 28, 2025
PubMed
Abstract

Insights

Lorlatinib-induced psychosis in anaplastic lymphoma kinase-positive non-small cell lung cancer patients can be managed with olanzapine. This case demonstrates successful lorlatinib rechallenge after psychosis resolution, maintaining cancer control.

Area of Science:

  • Oncology
  • Pharmacology
  • Neuroscience

Background:

  • Lorlatinib is a third-generation tyrosine kinase inhibitor for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).
  • While effective against intracranial lesions, lorlatinib can cause central nervous system complications, including psychosis.
  • Managing these adverse events is crucial for maintaining cancer treatment efficacy.

Purpose of the Study:

  • To present a case of lorlatinib-induced psychosis in a patient with ALK-positive NSCLC and brain metastases.
  • To illustrate the successful management of lorlatinib-induced psychosis with olanzapine.
  • To demonstrate the feasibility of lorlatinib rechallenge after psychosis resolution.

Main Methods:

  • A 32-year-old woman with ALK-positive NSCLC and brain metastases was treated with lorlatinib.
  • The patient developed hallucinations and delusions, initially treated with risperidone without full resolution.
  • Psychosis resolved upon lorlatinib discontinuation; olanzapine was substituted for risperidone prior to lorlatinib rechallenge.

Main Results:

  • Lorlatinib rechallenge with olanzapine was successful, with no recurrence of psychiatric symptoms.
  • Continued lorlatinib treatment was enabled, with no observed progression of lung cancer.
  • This approach allowed for sustained management of brain metastases.

Conclusions:

  • Lorlatinib is vital for controlling brain metastases in ALK-positive NSCLC.
  • Psychotic symptoms are a potential adverse effect of lorlatinib that requires careful management.
  • Multidisciplinary collaboration between oncologists and psychiatrists is essential for managing cancer treatment-related adverse effects.
Keywords:
lorlatiniblung cancermedication‐induced psychosispsycho‐oncology

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