Ben Carter, Rebecca Strawbridge, Ishrat Husain, Brett D.M. Jones, Roxanna Short, Anthony Cleare, Dimosthenis Tsapekos, Fiona Patrick, Lindsey Marwood, Rachael Taylor, Tim Mantingh, Valeria De Angel, Viktoriya Nikolova, Andre F. Carvalho, Allan Young
- Ben Carter (Biostatistics & Health Informatics)
- Rebecca Strawbridge (Psychological Medicine and Integrated Care Clinical Academic Group, Psychological Medicine, NIHR Maudsley Biomedical Research Centre)
- Ishrat Husain
- Roxanna Short
- Anthony Cleare (Centre for Affective Disorders , Psychological Medicine, Psychological Medicine and Integrated Care Clinical Academic Group, NIHR Maudsley Biomedical Research Centre)
- Dimosthenis Tsapekos (Psychological Medicine)
- Fiona Patrick
- Lindsey Marwood (Psychological Medicine and Integrated Care Clinical Academic Group, Centre for Affective Disorders )
- Rachael Taylor (Psychological Medicine)
- Tim Mantingh (Psychological Medicine, NIHR Maudsley Biomedical Research Centre)
- Valeria De Angel (Psychological Medicine)
- Viktoriya Nikolova (Psychological Medicine, NIHR Maudsley Biomedical Research Centre)
- Allan Young (Psychological Medicine, Psychological Medicine and Integrated Care Clinical Academic Group, NIHR Maudsley Biomedical Research Centre, Centre for Affective Disorders )
Background: Most interventions for Treatment-resistant depression (TRD) are added as augmenters. We aimed to determine the relative effectiveness of augmentation treatments for TRD.
Methods: This systematic review and network-meta-analysis (NMA) sought all randomised trials of pharmacological and psychological augmentation interventions for adults meeting the most common clinical criteria for TRD. The NMA compared the intervention effectiveness of depressive symptoms for TRD augmentation.
Results: Of 36 included trials, 27 were suitable for inclusion in NMA, no psychological trials could be included in the absence of a common comparator. Antipsychotics (13 trials), mood stabilisers (three trials), NMDA-targeting medications (five trials), and other mechanisms (3 trials) were compared against placebo. NMDA treatments were markedly superior to placebo (ES=0.91, 95% CI 0.67 to 1.16) and head-to-head NMA suggested that NMDA therapies had the highest chance of being an effective treatment option compared to other pharmacological classes.
Conclusions: This study provides the most comprehensive evidence of augmenters’ effectiveness for TRD, and our GRADE recommendations can be used to guide guidelines to optimise treatment choices. Although conclusions are limited by paucity of, and heterogeneity as well as inconsistent reports of treatment safety. This work supports the use of NMDA-targeting medications such as ketamine.