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TKI Therapy and depression
Conclusion:
Depression is a common problem in oncology, with many possible causal factors, including disease progression, treatment-related toxicities, social issues, and fear about the possibility of death. Thus it is oftentimes difficult to ascertain a relationship between depression and drug exposure. However, a striking pattern emerges from this series of seven patients. All were coping well with their disease psychologically before imatinib/dasatinib therapy, yet developed profound depression during treatment, with many experiencing complete remission or improvement of symptoms after dose reduction or drug discontinuation. Three patients demonstrated significant suicidal ideation—a psychiatric emergency. Interestingly, two patients had relapse of depression after TKI rechallenge and one patient was randomly assigned to the treatment arm of a placebo-controlled trial.
Thus it is oftentimes difficult to ascertain a relationship between depression and drug exposure. However, a striking pattern emerges from this series of seven patients. All were coping well with their disease psychologically before imatinib/dasatinib therapy, yet developed profound depression during treatment, with many experiencing complete remission or improvement of symptoms after dose reduction or drug discontinuation. Three patients demonstrated significant suicidal ideation—a psychiatric emergency. Interestingly, two patients had relapse of depression after TKI rechallenge and one patient was randomly assigned to the treatment arm of a placebo-controlled trial.
In our experience, TKI-associated psychiatric symptoms responded inconsistently to standard antidepressant treatment; dose reduction may benefit some patients, and in severe, treatment-refractory cases, discontinuation of the suspect TKI should be considered.Based on this experience, we recommend that patients treated with TKI, especially imatinib and dasatinib, should receive routine screening for depressive symptoms and suicidal ideation. Given the known elevated risk of suicide in cancer patients,2,3 suicidal ideation should be treated as a psychiatric emergency, with immediate referral to a psychiatrist for assessment. Although in our clinical experience we have only noted TKI-associated depression in patients treated with imatinib and dasatinib, it is not inconceivable that similar adverse effects may be seen with other TKIs, given that they share common mechanisms of activity and have overlapping molecular targets. Further research on the incidence and risk factors for depression in patients treated with TKI is needed.
Small Molecule Tyrosine Kinase Inhibitor and Depression
Richard Quek, Jeffrey A. Morgan, Suzanne George, James E. Butrynski, Kathleen Polson
Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute, Boston, MA