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Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis

  • Rebecca Strawbridge (a1), Ben Carter (a2), Lindsey Marwood (a3), Borwin Bandelow (a4), Dimosthenis Tsapekos (a5), Viktoriya L. Nikolova (a6), Rachael Taylor (a5), Tim Mantingh (a7), Valeria de Angel (a8), Fiona Patrick (a5), Anthony J. Cleare (a9) and Allan H. Young (a10)...
  • Please note a correction has been issued for this article.

Abstract

Background

Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.

Aims

We conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD.

Method

Participants with TRD (defined as insufficient response to at least two antidepressants) were randomised to at least one augmentation treatment in the trial. Pre-post analysis assessed treatment effectiveness, providing an effect size (ES) independent of comparator interventions.

Results

Of 28 trials, 3 investigated psychological treatments and 25 examined pharmacological interventions. Pre-post analyses demonstrated N-methyl-d-aspartate-targeting drugs to have the highest ES (ES = 1.48, 95% CI 1.25–1.71). Other than aripiprazole (four studies, ES = 1.33, 95% CI 1.23–1.44) and lithium (three studies, ES = 1.00, 95% CI 0.81–1.20), treatments were each investigated in less than three studies. Overall, pharmacological (ES = 1.19, 95% CI 1.08–1.30) and psychological (ES = 1.43, 95% CI 0.50–2.36) therapies yielded higher ESs than pill placebo (ES = 0.78, 95% CI 0.66–0.91) and psychological control (ES = 0.94, 95% CI 0.36–1.52).

Conclusions

Despite being used widely in clinical practice, the evidence for augmentation treatments in TRD is sparse. Although pre-post meta-analyses are limited by the absence of direct comparison, this work finds promising evidence across treatment modalities.

Declaration of interest

In the past 3 years, A.H.Y. received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion and Janssen; and research grant support from Janssen. In the past 3 years, A.J.C. received honoraria for speaking from AstraZeneca and Lundbeck; honoraria for consulting with Allergan, Janssen, Livanova, Lundbeck and Sandoz; support for conference attendance from Janssen; and research grant support from Lundbeck. B.B. has recently been (soon to be) on the speakers/advisory board for Hexal, Lilly, Lundbeck, Mundipharma, Pfizer, and Servier. No other conflicts of interest.

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Copyright

Corresponding author

Correspondence: Rebecca Strawbridge, Centre for Affective Disorders, PO74 Institute of Psychiatry, Psychology and Neuroscience, King's College London, 103 Denmark Hill, London SE5 8AZ, UK. Email: becci.strawbridge@kcl.ac.uk

Footnotes

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The original version of this article was published with incorrect results in the abstract. A notice detailing this has been published and the errors rectified in the online PDF and HTML versions, and also in the printed issue.

Footnotes

References

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Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis

  • Rebecca Strawbridge (a1), Ben Carter (a2), Lindsey Marwood (a3), Borwin Bandelow (a4), Dimosthenis Tsapekos (a5), Viktoriya L. Nikolova (a6), Rachael Taylor (a5), Tim Mantingh (a7), Valeria de Angel (a8), Fiona Patrick (a5), Anthony J. Cleare (a9) and Allan H. Young (a10)...
  • Please note a correction has been issued for this article.

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Augmentation therapies for treatment-resistant depression: systematic review and meta-analysis

  • Rebecca Strawbridge (a1), Ben Carter (a2), Lindsey Marwood (a3), Borwin Bandelow (a4), Dimosthenis Tsapekos (a5), Viktoriya L. Nikolova (a6), Rachael Taylor (a5), Tim Mantingh (a7), Valeria de Angel (a8), Fiona Patrick (a5), Anthony J. Cleare (a9) and Allan H. Young (a10)...
  • Please note a correction has been issued for this article.
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