Pharmacological Augmentation in Unipolar Depression: A Guide to the Guidelines.

BACKGROUND: Pharmacological augmentation is a recommended strategy for patients with treatment-resistant depression. A range of guidelines provide advice on treatment selection, prescription, monitoring and discontinuation, but variation in the content and quality of guidelines may limit the provision of objective, evidence-based care. This is of importance given the side effect burden and poorer long-term outcomes associated with polypharmacy and treatment-resistant depression. This review provides a definitive overview of pharmacological augmentation recommendations by assessing the quality of guidelines for depression and comparing the recommendations made. METHODS: A systematic literature search identified current treatment guidelines for depression published in English. Guidelines were quality assessed using the Appraisal of Guidelines for Research and Evaluation II tool. Data relating to the prescription of pharmacological augmenters were extracted from those developed with sufficient rigor, and the included recommendations compared. RESULTS: Total of 1696 records were identified, 19 guidelines were assessed for quality, and 10 were included. Guidelines differed in their quality, the stage at which augmentation was recommended, the agents included, and the evidence base cited. Lithium and atypical antipsychotics were recommended by all 10, though the specific advice was not consistent. Of the 15 augmenters identified, no others were universally recommended. CONCLUSIONS: This review provides a comprehensive overview of current pharmacological augmentation recommendations for major depression and will support clinicians in selecting appropriate treatment guidance. Although some variation can be accounted for by date of guideline publication, and limited evidence from clinical trials, there is a clear need for greater consistency across guidelines to ensure patients receive consistent evidence-based care.

Patient perspectives of lithium and quetiapine augmentation treatment in treatment-resistant depression: A qualitative assessment.

BACKGROUND: Treatment-resistant depression (TRD) has a profound cost to patients and healthcare services worldwide. Pharmacological augmentation is one therapeutic option for TRD, with lithium and quetiapine currently recommended as first-line agents. Patient opinions about pharmacological augmentation may affect treatment outcomes, yet these have not been systematically explored. AIMS: This study aimed to qualitatively assess patient experiences of lithium and quetiapine augmentation. METHODS: Semi-structured interviews were conducted with 32 patients from the ongoing lithium versus quetiapine open-label trial comparing these augmentation agents in patients with TRD. Interviews were audio recorded, transcribed and a thematic analysis was used to assess patient opinions of each agent. RESULTS: Four main themes were generated from the thematic analysis: 'Initial concerns', 'Experience of side effects', 'Perception of treatment efficacy' and 'Positive perception of treatment monitoring'. Patient accounts indicated a predominantly positive experience of lithium and quetiapine augmentation. Greater apprehension about side effects was reported for lithium prior to treatment initiation, but greater experience of negative side effects was reported for quetiapine. Clinical monitoring was perceived positively. CONCLUSION: Patient accounts suggested treatment augmentation with lithium or quetiapine was acceptable and helpful for most patients. However, anticipation and experiences of adverse side effects may prevent some patients from benefitting from these treatments.

The Maudsley 3-item Visual Analogue Scale (M3VAS): Validation of a scale measuring core symptoms of depression.

AIMS: Low mood and anhedonia are the core symptoms of major depressive disorder (MDD). However, there is no established visual analogue scale that measures pervasiveness of both symptoms. We aimed to validate the Maudsley 3-item Visual Analogue Scale (M3VAS) as a measure of core depressive symptoms and suicidality. METHODS: This is a cross-sectional secondary analysis combining data from two randomised controlled trials covering a broad range of depression severity from euthymia to severe depression. We validated the M3VAS by testing: 1) latent construct domains using factor analysis; 2) internal consistency using Cronbach's alpha; and 3) convergent validity by correlating M3VAS scores against scores on the Quick Inventory of Depressive Symptomatology-16 item (QIDS-SR-16), which is validated for use in clinical trials. RESULTS: Of 180 patients in the combined cohort, 177 (98.3%) provided complete data on the M3VAS and QIDS-SR-16. The mean (SD) age was 41.6 (13.0) years and 59.3% were female. Using factor analysis, one eigenvalue above 1 was produced (2.39) that explained 79.6% of the variance, indicating a one-factor model. Cronbach's alpha was 0.87, demonstrating good internal consistency. Total M3VAS scores correlated strongly (r = 0.72, p<0.001) with QIDS-SR-16 scores, indicating good convergent validity. LIMITATIONS: This was a cross-sectional study and was not validated against a clinician-rated assessment for depression. CONCLUSION: The M3VAS is a simple, valid instrument for the assessment of core depressive symptoms and suicidality across the depression spectrum. Future studies should test the longitudinal validity of the M3VAS in detecting changes in core depressive symptoms and suicidality over time.