Depression and Pluvicto (Lutetium-177 PSMA) for Prostate Cancer
Depression is not a documented side effect of Pluvicto (Lutetium-177 PSMA) therapy itself based on available evidence. However, depression is highly prevalent in prostate cancer patients generally, affecting up to 30% with clinically relevant distress and nearly 10% with major depressive disorder, regardless of the specific treatment modality 1.
Understanding Depression in Prostate Cancer Context
The provided evidence does not contain specific data linking Pluvicto to depression. The one study mentioning Lu-PSMA-617 actually describes a case where the therapy improved bone marrow function rather than causing psychiatric side effects 2. This absence of evidence regarding depression as a Pluvicto side effect is notable.
Depression Risk Factors in Prostate Cancer Patients
Patients receiving Pluvicto should still be screened for depression because they typically have advanced, metastatic castrate-resistant prostate cancer and often receive concurrent androgen deprivation therapy (ADT), which carries significant depression risk 1.
Key risk factors for depression in prostate cancer patients include:
- Advanced disease stage - which characterizes Pluvicto candidates 1
- Concurrent ADT use - associated with 41% increased depression risk 3, 4
- History of prior depression - men with depression history on ADT are more likely to develop major depressive disorder 1
- Being single/unmarried 1
- Low educational level 1
- Medical comorbidities 1
- Younger age 1
Clinical Management Algorithm
Screening Approach
All prostate cancer patients, including those on Pluvicto, should be routinely screened for distress using a simple tool like the Distress Thermometer 1. This screening should occur:
- At treatment initiation
- During active treatment
- At follow-up visits across all stages of survivorship 1
Important Caveat
Some survivors underreport distress, so consider partner and family reports of survivor distress 1. This is particularly important as partners are often distressed themselves and their reports can provide crucial information 5.
Intervention Pathway
Positive screens warrant referral for further evaluation and/or treatment if office-based counseling is insufficient 1. The evidence shows that routine distress screening with resource referral is effective in relieving distress over time 1.
ADT-Related Depression Considerations
Since Pluvicto patients often receive concurrent ADT, understanding ADT's psychiatric effects is critical:
- ADT increases depression risk by 41% and dementia risk by 47% 3
- Low testosterone from ADT can cause depressed mood and irritability 1
- Depression rates increase from 28% at ADT initiation to 39% at 6-month follow-up 6
However, one study found no significant worsening of depressive symptoms over 12 months of ADT in initially non-depressed patients 7, highlighting some conflicting evidence. The meta-analysis showing 41% increased risk represents the strongest and most comprehensive evidence 4.
Clinical Bottom Line
Depression in Pluvicto patients is attributable to the cancer burden, disease stage, and concurrent treatments (especially ADT) rather than Pluvicto itself. Nonetheless, these patients require vigilant depression screening and early intervention given their advanced disease status and frequent ADT co-administration 1, 3, 4.