El credo del chorreo

This trial is registered as ISRCTN37558856.

Funding

Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.

Chapter 1

Introduction

Background

Prevalence of depression

Depression is one of the main mental health disorders presenting in primary care.1_{The prevalence of major}

depression in the general population ranges from 3% to 10% with more than 150 million people at a time suffering from depression across the world.2_{In the UK prevalence of depression in 2009–10 was}

11% in England, 11.5% in Northern Ireland, 8.6% in Scotland, and 7.9% in Wales.3_{Unipolar depression}

leads to 12.15% of years lived with disability, and is ranked as the third leading contributor to the global burden of diseases.2_{Indeed depression is currently the second cause of disability worldwide for males and}

females between the ages of 15 and 44 years and is predicted to reach second place for all ages by 2020.4

Depression has become the leading cause of disability in Europe, leading to a loss of one in every 10 healthy years of life, and the leading cause of early retirement.5_{Depression and stress are now the}

commonest reported causes for sickness absence from work in the UK6_{with over 100 million working days}

lost across Europe at a cost of 1% Gross Domestic Product (GDP).7_{A higher prevalence of depression is}

observed in women than men across the 18- to 64-year age range with women up to 2.5 times more likely to develop depression.8

Characteristics of depression

The core symptoms of depression are low mood and loss of interest or enjoyment in usually pleasurable activities. Associated symptoms include disturbances to sleep and appetite, reduced energy and

concentration, negative thoughts of guilt or worthlessness and suicidal ideation. TheInternational Statistical Classification of Diseases & Related Health Problems(ICD-10) states that for a diagnosis of depression at leastfive symptoms need to be present, including at least one of the core symptoms, at an intensity that causes functional impairment and for a minimum duration of 2 weeks. Depression is classified as mild, moderate or severe according to the number of symptoms present and degree of functional impairment, and the grading of severity is of direct relevance to the treatment approaches recommended.9_{Depression is}

associated with increased mortality linked to suicide, alcohol and drug misuse, and increased rates of cardiovascular disease.10_{Depression thus burdens individuals, families, the NHS, and the national}

economy.11_{One UK study estimated the total cost of depression to the UK in 2000 at £9 billion; at that}

time, before the introduction of Improving Access to Psychological Therapies (also known as IAPT) in NHS England, the direct cost of treatment, mainly antidepressant medication (ADM), was £370 million; and indirect costs of 110 million working days lost to depression accounted for the vast majority of the total cost.12_{The sub-optimal treatment of depressive disorders is therefore of great public health concern.}

Treatments for depression

In accordance with the joint report of the World Health Organization (WHO) and World Organization of National Colleges & Associations of Family Doctors (WONCA)1_{and the National Institute for Health and}

Care Excellence (NICE) guidance9_{the majority of people with depression are identified, treated and}

managed within primary care. Treatment aims to relieve symptoms, restore functioning and, in the long term, prevent relapse. The goal of treatment is complete remission which is associated with better functioning and reduced risk of relapse.13_{While there is some evidence that people with depressive}

symptoms improve over time without treatment,14,15_{a significant proportion follow a chronic course with}

significant levels of depressive symptoms and functional continuing for several years.16,17

Antidepressants are recommended as a treatment option for moderate to severe depression either in combination with psychotherapy9_{or as monotherapy.}18_{Owing to their greater tolerability selective}

serotonin reuptake inhibitors (SSRIs) are recommended asfirst-line treatment in primary care.9_Patients

tricyclic antidepressants (TCAs).19_{In clinical trials of antidepressants typically 50% of patients with}

depression respond to active treatment, while one-third respond to placebo20_{with the placebo response}

appearing to increase over time in clinical trials.21_{Withfirst-line treatments about one-third of patients}

achieve remission from depression, increasing to two-thirds with refinement of treatment.22_{A study of}

mental disorders in 14 centres worldwide found that 50% of patients continued to have a diagnosis of depression after 1 year23_{with at least 10% having persistent or chronic depression.}24_{Furthermore, at least}

50% of people will go on to have at least one further episode of depression following theirfirst episode of major depression.25_{The risk of further recurrences after second and third episodes rises to 70% and 90%}

respectively.25_{Cumulative rates of recurrence remain linear over long periods of follow-up (30–40 years),}

indicating a constant risk of recurrence over the lifespan.26_{Therefore recurrence rates increase with length}

of follow-up, and for the majority of patients depression is a recurrent condition.

Depression is a prevalent global health problem resulting in high levels of disability. While effective treatments are available outcomes remain sub-optimal with a significant proportion of patients failing to achieve remission and experiencing chronic illness, early relapse and multiple recurrences across the lifespan. There remains a pressing need for research to optimise outcomes from antidepressant treatment.