Evidence on sociodemographic and clinical correlates of antidepressant combination or augmentation with second-generation antipsychotics in major depressive disorder

Gernot Fugger, Lucie Bartova, Markus Dold, Chiara Fabbri, Giuseppe Fanelli, Raffaella Zanardi, Alexander Kautzky, Joseph Zohar, Daniel Souery, Julien Mendlewicz, Stuart Montgomery, Dan Rujescu, Alessandro Serretti, Siegfried Kasper*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number110480
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
StatePublished - 2 Mar 2022
Externally publishedYes


FundersFunder number
Celegne GmbH
Janssen-Cilag Pharma GmbH
Lundbeck International Neuroscience Foundation
Medizin Medien Austria
Eli Lilly and Company
Actelion Pharmaceuticals
Janssen Pharmaceuticals
Dainippon Sumitomo Pharma
University of British Columbia
Angelini Pharma
H. Lundbeck A/S
AOP Orphan


    • Antidepressants
    • Augmentation
    • Combination
    • Major depressive disorder
    • Second-generation antipsychotics


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