Antidepressant drug use in glioblastoma patients: an epidemiological view

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Antidepressant drugs have shown antitumor activity in preclinical glioblastoma studies. Antidepressant drug use, as well as its association with survival, in glioblastoma patients has not been well characterized on a population level.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Patient characteristics, including the frequency of antidepressant drug use, were assessed in a glioblastoma cohort diagnosed in a 10-year time frame between 2005 and 2014 in the Canton of Zurich, Switzerland. Cox proportional hazards regression models were applied for multivariate analysis. Kaplan-Meier survival curves were used to estimate overall survival (OS) data and the log-rank test was performed for comparisons.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>A total of 404 patients with isocitrate dehydrogenase wild-type glioblastoma were included in this study. Sixty-five patients (16.1%) took antidepressant drugs at some point during the disease course. Patients were most commonly prescribed selective serotonin reuptake inhibitors at any time (N = 46, 70.8%). Nineteen patients (29.2%) were on antidepressant drugs at the time of their tumor diagnosis. No differences were observed in OS between those patients who had taken antidepressants at some point in their disease course and those who had not (P = .356). These data were confirmed in a multivariate analysis including age, Karnofsky Performance Scale (KPS), sex, extent of resection, O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and first-line treatment as cofounders (P = .315). Also, there was no association of use of drugs modulating voltage-dependent potassium channels (citalopram; escitalopram) with survival (P = .639).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>This signal-seeking study does not support the hypothesis that antidepressants have antitumor efficacy in glioblastoma on a population level.</jats:p> </jats:sec>

Association of antidepressant drug use with outcome of patients with glioblastoma

“…Smaller studies also found no statistically significant association between use of antidepressants and survival 4,6 . However, depression was associated with shorter survival in several studies and meta‐analyses on glioma patients 1,42 .…”

“…Patients with glioma may receive antidepressants less frequently than the general population according to a study from Norway, 2 but it is unclear, if this may be translated to other countries as well. Challenges in the pharmacological treatment of depression in glioma patients may be difficulties to diagnose depression because of tumor symptoms, an uncertainty whether antidepressants are active in these patients, whether their use has adverse effects on seizure frequency, fatigue and cognition, or whether they interact with antiepileptic drugs or chemotherapy 3‐6 . Conversely, there is also an assumption that these drugs may positively affect outcome 7‐9 …”

“…Challenges in the pharmacological treatment of depression in glioma patients may be difficulties to diagnose depression because of tumor symptoms, an uncertainty whether antidepressants are active in these patients, whether their use has adverse effects on seizure frequency, fatigue and cognition, or whether they interact with antiepileptic drugs or chemotherapy. [3][4][5][6] Conversely, there is also an assumption that these drugs may positively affect outcome. [7][8][9] Glioblastomas are WHO grade 4 gliomas with poor prognosis.…”

Fabrication and Assessment of Diosgenin Encapsulated Stearic Acid Solid Lipid Nanoparticles for Its Anticancer and Antidepressant Effects Using in vitro and in vivo Models

“…The development of a therapeutic agent against brain pathologies has always been a challenge due to the complexity of the disorder and the disability of the therapeutic agent to reach the brain. However, pathologies like cancer and MDD have been even more challenging to treat due to the fact that both support each other in the pathogenesis of the disease ( Gramatzki et al, 2020 ). Due to this reason, many therapeutic drugs have shown less efficacy against such pathologies.…”

A systematic review of pharmacologic treatment efficacy for depression in older patients with cancer

“…( Rooney and Grant, 2013 ; Hill et al., 2015 ) Some in vitro data suggests that SSRIs may have anti-brain tumor effects ( Liu et al., 2015 ; Jeon et al., 2011 ; Ma et al., 2016 ; Chen et al., 2018 ). However, retrospective analyses have yet to report any significance ( Gramatzki et al., 2020 ; Otto-Meyer et al., 2020 ; Caudill et al., 2011 ). The use of antidepressant therapy among brain tumor patients may improve mood and function within a population that undergoes treatment with radiation, chemotherapy, and progressive neurosurgical insults to the brain.…”