Which anticancer drug can cause psychosis?

Anticancer Drugs That Cause Psychosis

Ifosfamide is the most notorious anticancer drug for causing psychosis and delirium, along with other chemotherapy agents including methotrexate, cisplatin, vincristine, procarbazine, asparaginase, cytarabine, 5-fluorouracil, high-dose etoposide, nitrosourea compounds, and high-dose or intra-arterial alkylating agents. 1

Primary Chemotherapy Agents Associated with Psychosis

The European Society for Medical Oncology (ESMO) guidelines specifically identify the following chemotherapy agents as direct causes of cognitive impairment and psychotic symptoms 1:

• Ifosfamide - Most commonly associated with acute encephalopathy and psychotic features 1
• Methotrexate - Can cause acute or delayed neurotoxicity 1
• Cisplatin - Associated with cognitive disturbances 1
• Vincristine - Known for neuropsychiatric complications 1
• Procarbazine - Causes CNS toxicity 1
• Asparaginase - Can induce encephalopathy 1
• Cytarabine (cytosine arabinoside) - Particularly at high doses 1
• 5-Fluorouracil - Associated with acute confusional states 1
• High-dose etoposide - Dose-dependent neurotoxicity 1
• Nitrosourea compounds - CNS penetration leads to toxicity 1
• High-dose or intra-arterial alkylating agents - Route and dose-dependent effects 1
• Tamoxifen - Rarely causes psychotic symptoms 1

Interferon-Alpha: A Special Consideration

While not traditional chemotherapy, interferon-alpha used in cancer treatment (particularly melanoma) can cause severe psychotic symptoms including paranoid delusions and auditory hallucinations 2, 3, 4:

• Psychotic symptoms typically appear between 1-3 months of treatment 2
• Approximately 10 cases per large retrospective study showed frank psychotic disorders 2
• Symptoms can persist for weeks to months after discontinuation (up to 28 weeks reported) 3
• The mechanism involves effects on neuroendocrine, cytokine, and neurotransmitter systems 4, 5

Clinical Context and Mechanisms

These drugs cause psychosis through direct neurotoxicity rather than as part of delirium alone, though the distinction can be blurred 1:

• The ESMO guidelines note that 69% of confused cancer patients have multiple contributing factors, with chemotherapy being a direct precipitant in many cases 1
• Perceptual disturbances include hallucinations (usually visual or tactile), illusions, and transient delusions 1
• Psychotic features may present as hyperactive delirium with agitation or as isolated psychotic symptoms 1

Critical Management Points

Immediate discontinuation or dose reduction of the offending agent is the primary intervention 3, 6:

• For interferon-induced psychosis, quetiapine has shown marked efficacy when other antipsychotics failed 3
• Standard antipsychotic management follows ESMO guidelines: olanzapine 2.5-5 mg or quetiapine 25 mg as first-line 7
• Haloperidol 0.5-1 mg is second-line for acute management 7

Common Pitfall to Avoid

Do not assume all psychiatric symptoms in cancer patients are due to brain metastases or metabolic derangements—direct chemotherapy neurotoxicity is a frequent and often reversible cause that requires recognition and drug modification 1.