Project ID NS-MH2024_13


Co Supervisor 1A Institute of Psychiatry, Psychology & Neuroscience, School of Academic Psychiatry, Department of Psychological MedicineWebsite

Co Supervisor 1B Institute of Psychiatry, Psychology & Neuroscience, School of Academic Psychiatry, Department of Psychological MedicineWebsite

Towards tailored treatment: Predicting real-world outcomes to first-line augmentation interventions for treatment-resistant depression

Treatment-resistant depression (TRD) is common, severe and long-lasting, contributing substantially to the overall burden of depression. Treatments for depression/TRD are still prescribed via trial-and-error, despite accumulating evidence that certain factors can predict response to different interventions. Extant evidence of TRD outcome prediction is limited by small samples, short-term outcomes and artificial treatment settings. We have conducted a large, long-term randomized controlled trial (RCT) of first-line TRD treatments. Unlike most RCTs, the LQD study was pragmatic in nature and therefore better reflects real-world outcomes. We also followed participants up for 12months, permitting a more valid prospective assessment of treatment outcomes. Focusing on currently recommended TRD therapies also contrasts with most existing research, assessing lesser-used therapies. Finally, we will employ a clinical outcome that is meaningful to patients.

Our overarching aim is to develop a model comprising factors that are feasible to assess in routine practice and predict outcomes to the recommended augmenters for TRD. Specific objectives comprise:
1) Define a priority outcome for patients, through literature review and consultation with those affected by depression/TRD.
2) Examine pre-treatment factors to develop a model predicting long-term outcomes from the LQD study.
3) Validation of the model in other studies of emerging therapies for TRD e.g., psilocybin, ketamine.

Planned research methods and training:
Additional to trans-project training (e.g., coding), we will provide high-quality training in:
1) Systematic review (objective1),
2) Qualitative research (objective1),
3) Involving patients in research (objective1),
3) Prediction modelling (objective 2&3).

Objectives / project plan:
Year1: Systematic review & PPIE consultation/consensus resulting in a definitive outcome variable for objectives 2/3.
Year2: Hypothesis generation and prediction model development. Objective 2 data cleaning and analyses.
Year3: Objective 3 access to dataset(s), data cleaning and analysis, to observe potential application of the model to novel TRD therapies.
Year4: Interpretation and thesis write-up.

Representative Publications

Marwood L, Taylor R, Goldsmith K, Romeo R, Holland R, Pickles A, Hutchinson J, Dietch D, Cipriani A, Nair R, Attenburrow MJ. Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of lithium and quetiapine augmentation in treatment resistant depression (the LQD study). BMC psychiatry. 2017 Dec;17(1):1-2. doi: 10.1186/s12888-017-1393-0.

Taylor RW, Coleman JR, Lawrence AJ, Strawbridge R, Zahn R, Cleare AJ. Predicting clinical outcome to specialist multimodal inpatient treatment in patients with treatment resistant depression. Journal of affective disorders. 2021 Aug 1;291:188-97. doi: 10.1016/j.jad.2021.04.074

Taylor RW, Marwood L, Greer B, Strawbridge R, Cleare AJ. Predictors of response to augmentation treatment in patients with treatment-resistant depression: a systematic review. Journal of Psychopharmacology. 2019 Nov;33(11):1323-39. doi: 10.1177/0269881119872194.

Scott F, Hampsey E, Gnanapragasam S, Carter B, Marwood L, Taylor RW, Emre C, Korotkova L, Martín-Dombrowski J, Cleare AJ, Young AH. Systematic review and meta-analysis of augmentation and combination treatments for early-stage treatment-resistant depression. Journal of Psychopharmacology. 2023 Mar;37(3):268-78. doi: 10.1177/02698811221104058.

Strawbridge R, Jamieson A, Hodsoll J, Ferrier IN, McAllister-Williams RH, Powell TR, Young AH, Cleare AJ, Watson S. The Role of Inflammatory Proteins in Anti-Glucocorticoid Therapy for Treatment-Resistant Depression. Journal of Clinical Medicine. 2021 Feb 16;10(4):784. doi: 10.3390/jcm10040784.

Strawbridge R, Jaeckle T, Cleare AJ. What do we know about long-term treatment outcomes for severe depressive disorders?. BJPsych Open. 2020 Mar;6(2):e28. doi: 10.1192/bjo.2020.10.