Pharmacological treatments

The pharmacological treatments for depression include antidepressants and adjunctive agents. Most of the newer antidepressants (e.g. selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors (SNRIs), other agents) are first-line medications owing to improved safety and tolerability over first-generation medications (e.g. tricyclic antidepressants, monoamine oxidase inhibitors). Selection of an antidepressant must be personalized to an individual patient and must consider factors including efficacy, side-effect profile, safety, specific symptoms, comorbid conditions, concurrent medications, simplicity of use, and cost. Switching antidepressants must take into account factors such as side effects, discontinuation effects, potential drug interactions, and rapidity of switch. Maintenance treatment (6 months to 2 years or longer, depending on individual risk factors) is recommended for all patients treated with antidepressants.

Epidemiology and burden

Depression is a common condition with a lifetime prevalence of about 15%. People with depression experience significant impairment in psychosocial functioning, particularly in those with a recurrent or chronic course. Depression is now the leading cause of years lived with disability worldwide. Depression is also associated with increased risk of developing a medical illness and an increased risk of overall mortality, even when deaths from suicide are excluded. The economic costs of depression are staggering, largely owing to indirect costs associated with occupational impairment leading to work absence and reduced productivity. Depression remains undertreated, particularly in lower- and middle-income countries, but the World Health Organization has estimated that scaling up of depression treatment returns US$5 for every US$1 spent.

Introduction

Depression is a common psychiatric condition that is now recognized as the leading medical cause of functional disability. The high prevalence and its common comorbidity with other medical conditions mean that depression must be recognized and managed by all physicians and health professionals. There are many evidence-based treatments for depression, including psychotherapy, pharmacotherapy, and other somatic treatments. Unfortunately, however, many patients are not able to access treatments because of limitations in healthcare delivery systems. The principles of care for major depressive disorder include: thorough assessment and diagnosis, selection of appropriate and evidence-based treatments, and careful follow up using measurement-based care.

Special populations

The keys to optimal management of treatment-resistant depression (TRD) and depression in special populations include careful assessment, selection of evidence-based treatments tailored to the individual, and ongoing monitoring of response and outcome. For TRD, pharmacological strategies include switching antidepressants or adding an adjunctive agent. Adjunctive agents include second-generation (atypical) antipsychotics, other antidepressants, lithium, thyroid hormone, and psychostimulants. There is still a limited evidence base for pharmacotherapy and psychotherapy in special populations such as elderly patients, those with other medical illnesses, pregnant and breastfeeding women, and children and adolescents. For these patients, use and selection of antidepressants depends on an individual risk-benefit assessment.

Associated clinical features

In addition to the core depressive symptoms, patients with depression often have other non-specific clinical features including anxiety, irritability and anger, and pain. These features may be present as associated symptoms during a depressive episode or as specific comorbidities (e.g. generalized anxiety disorder). Other symptoms, including fatigue or low energy and cognitive dysfunction (problems with concentration, memory, decision-making), warrant special attention because they are major mediators of functional impairment and are common residual symptoms during treatment. The presence of these associated clinical features can affect the differential diagnosis and management of depression, e.g. in the selection and use of an antidepressant and/or a psychological treatment.

Pathogenesis

Depression is a heterogeneous condition, and its aetiology and pathophysiology likely involve multiple processes involving combinations of biological, psychological, and social factors. Neurobiological hypotheses include dysregulation in monoamine and other neurotransmitter systems, alterations in stress hormones and neuroimmune systems, disturbances in sleep and circadian rhythms, and neuropsychological and neurocircuitry dysfunction. Disturbed circadian rhythms, stressful life events, and stress reactivity can also modify genetic and biological processes (gene-by-environment interactions and epigenetics) to contribute to depression. Endophenotypes, or genetic expressions of neural systems involved in depression, are important in the study of the pathogenesis of depression and the development of biomarkers and novel treatments.

Psychological treatments

Evidenced-based psychological treatments for acute depression include problem solving therapy, behavioural activation, cognitive behavioural therapy, interpersonal psychotherapy, and, for chronic depression, cognitive behavioural-analysis system of psychotherapy. Mindfulness-based cognitive therapy, originally developed as a maintenance treatment, also has benefit in acute depressive episodes. Technologies that can deliver therapy via computer, internet or mobile devices, with or without therapist guidance, have increasing evidence to support their use as alternate forms of therapy. For mild to moderate severity of depression, evidence-based psychological treatments are first-line treatments and are as effective as pharmacotherapy. Combined treatment with psychotherapy and pharmacotherapy is more effective than either monotherapy and is clinically indicated for more severe, chronic or comorbid depressions.

Clinical management

Clinical management of depression includes targeted screening, comprehensive assessment, developing a therapeutic alliance, selecting treatment(s), monitoring outcomes, and regular follow up. The treatment of depression has two phases: the acute phase to achieve full remission of symptoms and restore functioning, and the maintenance phase to prevent relapse/recurrence and optimize functioning and quality of life. Measurement-based care using validated rating scales to guide clinical decisions can improve patient outcomes. Self-management by patients is an important component of disease management programmes for depression. Self-management can be enhanced by books and e-health resources, including internet information sites and health applications and emerging mobile apps for tablets and smartphones.

Clinical features and diagnosis

The core clinical features of depression include physical (sleep and appetite disturbances, psychomotor changes, fatigue, low energy), emotional (sadness, loss of interest, anhedonia), and cognitive (guilt, suicidal thoughts and behaviours, concentration and memory difficulties, indecisiveness) symptoms. DSM-5 classifies depressive disorders in adults as major depressive disorder (MDD), other depressive disorders, and persistent depressive disorder; the latter includes chronic MDD, unremitted MDD, and dysthymia (chronic, low-grade depressive symptoms). DSM-5 also includes specifiers, or sub-types, of MDD that have implications for prognosis and treatment choice and selection. The differential diagnosis of depression includes bereavement, bipolar disorder, and other medical or substance-induced conditions.

Somatic treatments

Somatic treatments for depression include non-invasive modalities such as wake therapy (sleep deprivation), exercise, and light therapy. The modern techniques now used for electroconvulsive therapy make it an effective, safe, and well-tolerated (but still underutilized) treatment for patients with severe, psychotic, or medication-resistant depression. Repetitive transcranial magnetic stimulation now has good evidence for acute efficacy, but its use is still limited by lack of data on maintenance and long-term management. Surgical and neuromodulation treatments, such as vagus nerve stimulation, deep brain stimulation, and limbic neurosurgery, may be clinically useful for some patients with difficult-to-treat and refractory depression.