Antidepressant Combination/Augmentation Strategies Associated With Treatment-Resistant MDD

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Initiation of augmentation/combination treatment strategies was associated with treatment-resistant or difficult-to-treat MDD.

In patients with major depressive disorder (MDD), augmentation or combination treatment strategies are associated with treatment-resistant MDD and severe symptomatology, according to results published in Acta Psychiatrica Scandinavica.

The study included participants with MDD who were treated with monotherapy and augmentation/combination medication (n=1410). The researchers recorded sociodemographic, clinical, and treatment features for each participant.

Of all 1410 participants, 60.64% received augmentation and/or combination strategies, with a mean number of 2.18­±1.22 simultaneously-prescribed psychiatric medications.

After analysis, the researchers found that male gender, older age, white race, higher weight, low educational status, absence of occupation, psychotic symptoms, melancholic and atypical features, suicide risk, in-patient treatment, longer duration of hospitalization, some psychiatric comorbidities (panic disorder, agoraphobia, obsessive-compulsive disorder, and bulimia nervosa), comorbid somatic comorbidity in general and concurrent hypertension, thyroid dysfunction, diabetes, and heart disease in particular, higher current and retrospective Montgomery and Åsberg Depression Rating Scale total scores, treatment resistance, and higher antidepressant dosing were significantly associated with augmentation/combination treatment.

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“One major finding of our study represents the association between the administration of augmentation/combination medication and treatment resistance to previous medication. This observed prescription practice reflects clinical trial results and recommendation of treatment guidelines, whereupon augmentation and combination strategies should be preferentially applied in treatment-resistant and difficult-to-treat MDD conditions,” the researchers wrote.


Dold M, Bartova L, Mendlewicz J, et al. Clinical correlates of augmentation/combination treatment strategies in major depressive disorder. [published online February 28, 2018]  Acta Psychiatr Scand. doi:10.1111/acps.12870