Abstract
About two thirds of the patients with major depressive disorder (MDD) do not sufficiently respond to monotherapy with antidepressants (ADs) which makes them reliant on further treatment approaches. Hereby, combination of different ADs and augmentation with second-generation antipsychotics (SGAs) are widely used and recommended psychopharmacotherapeutic strategies.The present secondary analyses are based on an international, naturalistic, cross-sectional multicenter study conducted by the European Group for the Study of Resistant Depression. Comparing socio-demographic and clinical characteristics of 436 adult MDD patients receiving either SGAs (N = 191, 43.8%) or ADs (N = 245, 56.2%), that were additionally administered to their first-line AD psychopharmacotherapy, we aimed to identify possible trajectories of decision-making for clinicians regarding which treatment option to prefer in individual patients.Our most robust findings represent an association of SGA augmentation with the presence of psychotic symptoms, longer mean duration of lifetime psychiatric hospitalizations, employment of further augmentation strategies with mood-stabilizers and benzodiazepines, and a trend towards higher mean daily dosages of their first-line ADs and current suicidal risk. Treatment outcome was not significantly different between patients receiving either SGA augmentation or AD combination.Being aware of limitations inherent to the cross-sectional study design and the lack of randomization, more severe and rather chronic conditions in MDD seemed to encourage clinicians to choose SGA augmentation over AD combination. The fact that mood-stabilizers and/or benzodiazepines were more frequently co-administered with SGAs may represent a requirement of an overall refined psychopharmacotherapy including additional fast-acting agents with potent AD, tranquilizing and anti-suicidal effects in MDD patients experiencing challenging clinical manifestations. New glutamatergic substances seem to be promising in this regard.
Highlights
Major depressive disorder (MDD) ranks among the most frequent and most debilitating adult disorders on a global scale (Vos et al, 2016)
Patients who received second-generation antipsychotics (SGAs) augmentation experienced a longer overall duration of psychiatric hospitalizations during their lifetime given in weeks (13.3 ± 41.2 vs. 6.7 ± 14.7, p = 0.008) and exhibited psychotic features (18.8% vs. 8.2%, p < 0.001) more often as compared to MDD patients receiving AD combination treatment
The larger proportion of our MDD patients who received AD com bination compared to SGA augmentation might reflect the current approval situation in Europe, where a plethora of ADs are approved for the treatment of MDD, while only one SGA - quetiapine XR - is officially licensed by the European Medicines Agency for augmentation in MDD (EMA; http://www.ema.europa.eu) (Bauer, Severus et al, 2017; Dold and Kasper, 2017)
Summary
Major depressive disorder (MDD) ranks among the most frequent and most debilitating adult disorders on a global scale (Vos et al, 2016). Frequently applied psychopharmacotherapeutic approaches following insufficient response to the first-line AD agent include its combination with an additional AD or its augmentation with second-generation antipsychotics (SGAs) (Ng et al, 2006; Thase, 2016; Bauer, Severus et al, 2017; Dold and Kasper, 2017; Kraus et al, 2019). The latter strategy has received approval by regulatory authorities in some countries (quetiapine extended release (XR) in Europe and aripi prazole, quetiapine XR, olanzapine plus fluoxetine combination and brexpiprazole in the United States (U.S.)) (Wang et al, 2016)
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