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“Comorbid Substance Use Disorder Raises Risk of Treatment-Resistant Depression”

Current or recent substance use disorder may be a risk factor for treatment resistance among patients with depression. This discovery is according to the results of a Swedish nested case-control study published in Addiction. Philip Brenner, MD, Ph.D., and his colleagues of the Karolinska Institute in Stockholm, Sweden, used “Swedish governmental healthcare registers and data on prescription drugs and diagnoses from specialized healthcare to establish a cohort of subjects initiating antidepressants for depression from 2006 to 2014.”


The findings

The researchers found that “substance use disorder before the start of, or during, treatment increases the risk for subsequent treatment-resistant depression. Findings were similar for alcohol, opioid, cannabinoid, sedative, and combined drug substance use disorder. Conversely, the risk for treatment-resistant depression was lowered among patients with a history of alcohol substance use disorder further back than 180 days before treatment started.”


Complex and multidimensional

The authors of the study are cautious of the relationships between substance use disorder and treatment-resistant depression. They note that these relationships are likely “complex and multidimensional.” These disorders may not be directly associated with one another but may share underlying sociodemographic and biological risk factors. They also note that “substance use disorder may cause structural and biochemical changes in the brain, particularly in the dopamine system, which may result in depression and affect antidepressant mechanism substrates at the same time.”



The definition of treatment-resistant depression that was tested has “not yet been verified through clinical data.” It’s also important to note that there is an “inability to assess depression severity level, side effects, the clinical effectiveness of treatment, reasons for treatment discontinuation, and patient adherence to antidepressant regimens” beyond what the patients are willing to report. Future research must be done to “identify effective interventions for patients with treatment-resistant depression and present or recent comorbid substance use disorders.”


Villa Tranquil Recovery is committed to furthering our commitment to treatment. If you are struggling with substance use and a co-occurring mental illness, we want to help. Call us today at 214-799-3080. We can’t wait to help you today.