SSRIs and SNRIs in Hematology – A Systematic Review and Qualitative Analysis
Jan Puchowski, Karol Grabowski, Agnieszka PiekarskaBackground
Depression and neurotoxic complications are frequently observed in patients with hematologic malignancies (HM). Serotonergic antidepressants, mainly selective serotonin reuptake inhibitors (SSRIs) and serotonine-norepinephrine reuptake inhibitors (SNRIs) are commonly prescribed as the first line-treatment of depression because they are safer and have fewer side effects than other medications antid. Among SNRIs, duloxetine has shown promise, with multiple experimental studies demonstrating its ability to prevent or alleviate chemotherapy-induced peripheral neuropathy (CIPN). However, SSRI/SNRIs use raise several biological and pharmacological considerations due to clinically relevant drug–drug interactions. Despite the widespread use of antidepressants in this population, robust clinical evidence supporting their efficacy and safety specifically in HM patients remains limited.
Objective
The aim of this review is to evaluate the effects of SSRIs/SNRIs in HM, their impact on CIPN, drug interactions relevant to HM therapy, and clinical outcomes of antidepressant use in this population.
Methods
Following PRISMA guidelines, a systematic search of several databases (PubMed, Scopus and Web Of Science) covering the period from January 1, 2000, to January 31, 2025, was conducted.
Results
A total of 251 articles were initially identified. Ultimately, 24 articles were eligible for analysis. The data relies solely from in vitro studies indicate that SSRIs and SNRIs may enhance the effectiveness of chemotherapy. Only one clinical study evaluated antidepressant efficacy in HM patients, showing improvement in depressive symptoms with paroxetine. Moreover, duloxetine has an established clinical role in the treatment of painful CIPN. However, the evidence supporting its use for CIPN prevention remains limited to preclinical models and lacks definitive clinical validation. The safety issues include serotonin toxicity, a risk of bleeding related to SSRIs and SNRIs impact on platelet functions and other potential drug-drug interactions.
Conclusions
Based on available data, it is not possible to clearly recommend SSRIs and SNRIs for HM patients beyond the registered indications. Clinical studies are needed to confirm anticancer and chemosensitizing effects of SSRIs and SNRIs demonstrated in experimental models of leukemia and lymphoma. Nevertheless, the potential broader therapeutic benefits of duloxetine and related serotonergic agents in CIPN warrant further investigation. Due to the high prevalence of depression in HM patients, more data on safety in this population is warranted.