BackgroundUse of antidepressant medications has been linked to detrimental impacts on bone mineral density and osteoporosis; however, the cellular basis behind these observations remains poorly understood. The effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. In this study, we hypothesized that antidepressants have a class- and dose-dependent effect on mesenchymal stem cell (MSC) differentiation, which may affect bone metabolism.MethodsHuman MSCs (hMSCs) were committed to differentiate when either adipogenic or osteogenic media was added, supplemented with five increasing concentrations of amitriptyline (0.001–10 µM), venlafaxine (0.01–25 µM), or fluoxetine (0.001–10 µM). Alizarin red staining (mineralization), alkaline phosphatase (osteoblastogenesis), and oil red O (adipogenesis) assays were performed at timed intervals. In addition, cell viability was assessed using a MTT.ResultsWe found that fluoxetine had a significant inhibitory effect on mineralization. Furthermore, adipogenic differentiation of hMSC was affected by the addition of amitriptyline, venlafaxine, and fluoxetine to the media. Finally, none of the tested medications significantly affected cell survival.ConclusionsThis study showed a divergent effect of three antidepressants on hMSC differentiation, which appears to be independent of class and dose. As fluoxetine and amitriptyline, but not venlafaxine, affected both osteoblastogenesis and adipogenesis, this inhibitory effect could be associated to the high affinity of fluoxetine to the serotonin transporter system.
Comorbidity of substance use and psychiatric disorders, particularly depressive disorders, are well established. The impact of comorbidity on treatment outcomes, particularly following short-term inpatient detoxification and medical management units, has yet to be fully explored. This study reviewed 456 records of patients voluntarily presenting for medical management of substance misuse in Sydney, Australia. Documented psychiatric comorbidities and primary substance of misuse were extracted and used to predict length of stay, discharge against medical advice and number of readmissions. Our results showed that psychiatric comorbidity did not significantly predict treatment outcomes, although depression was reported in more than half our cohort, along with elevated rates of Post-traumatic Stress Disorder, anxiety disorders and bipolar affective disorders. Medication non-compliance and primary substance of misuse significantly predicted length of stay and discharge against medical advice. Further research into how specific substances interact and affect specific psychiatric disorders is needed to guide optimal treatment options.
Substance use disorder is a chronic disease carrying a high risk of morbidity and mortality. We report a case of a patient on long-term opioid agonist treatment who was diagnosed with metastatic cholangiocarcinoma and was referred to palliative care services almost contemporaneously with this diagnosis. In this report, we explore the challenges posed in offering holistic care during the end of life of a patient with a history of opioid dependence. A coordinated approach by addiction medicine and palliative care teams can allow patients from this complex cohort to ultimately die with dignity.
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