Background Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores. The purpose of this analysis is to establish the relation of baseline severity and antidepressant efficacy using a relevant dataset of published and unpublished clinical trials. Methods and Findings We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess linear and quadratic effects of initial severity on improvement scores for drug and placebo groups and on drug–placebo difference scores. Drug–placebo differences increased as a function of initial severity, rising from virtually no difference at moderate levels of initial depression to a relatively small difference for patients with very severe depression, reaching conventional criteria for clinical significance only for patients at the upper end of the very severely depressed category. Meta-regression analyses indicated that the relation of baseline severity and improvement was curvilinear in drug groups and showed a strong, negative linear component in placebo groups.

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Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration.

This is the latest updated volume in a well-established series bringing together information from a variety of sources to estimate national unit costs for a wide range of health and social care services. This report consists of tables for more than 130 types of service which, as well as providing the most detailed and comprehensive information possible, also quotes sources and assumptions so users can adapt the information for their own purposes. This year we have included a guest editorial on ‘Big Data’: increasing productivity while reducing costs in health and social care and three short articles on The cost of integrated care; Shared lives – improving understanding of the costs of family-based support and the costs of providing a group intervention to people with dementia and their family carers:SHIELD: RYCT & CSP intervention costs (Remembering Yesterday Caring Today and Carer Support Programme). There are also several new schema providing the costs of: advocacy for people with learning disabilities; a hospice rapid response service; the early years classroom management programme; residential parenting assessments; independent review officers; time banks; dentists and care home costs for people with dementia. The 2014 edition is also available in full, free of charge, at the PSSRU website www.pssru.ac.uk/unit-costs/2014/ as an Acrobat file.

Unit Costs of Health and Social Care 2014

Context Antidepressant medications represent the best established treatment for major depressive disorder, but there is little evidence that they have a specific pharmacological effect relative to pill placebo for patients with less severe depression. Objective To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression. Data Sources PubMed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews. Study Selection Randomized placebo-controlled trials of antidepressants approved by the Food and Drug Administration in the treatment of major or minor depressive disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, they included a medication vs placebo comparison for at least 6 weeks, they did not exclude patients on the basis of a placebo washout period, and they used the Hamilton Depression Rating Scale (HDRS). Data from 6 studies (718 patients) were included. Data Extraction Individual patient-level data were obtained from study authors. Results Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with HDRS scores below 23, Cohen d effect sizes for the difference between medication and placebo were estimated to be less than 0.20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline depression severity and crossed the threshold defined by the National Institute for Clinical Excellence for a clinically significant difference at a baseline HDRS score of 25. Conclusions The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.

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Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)60046-5.pdf

Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis

A 4-item measure of depression and anxiety: Validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population.

The National Institute for Clinical Excellence and the National Collaborating Centre for Mental Health have published a guideline for the NHS in England and Wales on the management of depression in primary and secondary care.

Nice

Papers

Depression: management of depression in primary and secondary care