Depressive Disorders

Depressive disorders are psychiatric conditions of persistent low mood or loss of interest and pleasure (anhedonia), with associated cognitive, physical and behavioural symptoms. They cause significant distress or functional impairment.

They are among the commonest mental health conditions in clinical practice. They carry substantial morbidity, functional impairment and, critically, mortality risk from suicide. They warrant careful, systematic assessment and evidence based treatment across the full range of severity.

The group includes:

• major depressive disorder
• persistent depressive disorder (dysthymia), with chronic, lower grade depressive symptoms persisting for at least two years
• depressive episodes in the context of other conditions, including bipolar disorder, and premenstrual dysphoric disorder

Classification and pathophysiology

• The pathophysiology is a complex interplay of genetic predisposition, neurobiological factors and psychosocial factors. The relative contribution of each varies substantially between individuals.
• Neurobiological factors include dysregulation of monoaminergic neurotransmitter systems, hypothalamic-pituitary-adrenal axis dysfunction and, increasingly recognised, neuroinflammatory processes and altered neuroplasticity.
• Psychosocial factors include early life adversity, ongoing life stressors, and interpersonal and social circumstances.
• Persistent depressive disorder (dysthymia) is chronic, low grade depressive symptoms of lower intensity than major depressive disorder, persisting for a minimum of two years.
• A substantial proportion of affected individuals have superimposed episodes of major depressive disorder level symptoms during the chronic course, a pattern sometimes termed double depression.
• Always consider and screen for secondary depression. It may occur with an underlying medical condition (including hypothyroidism, certain neurological conditions and various chronic medical illnesses) or as a medication adverse effect (including certain antihypertensive and other agents).
• Identifying and, where possible, addressing this cause alongside standard depression treatment is part of full assessment.

• The core, defining symptoms are persistent low mood and/or anhedonia (loss of interest or pleasure in previously enjoyed activities), present for most of the day, nearly every day, over a sustained period.
• Associated cognitive symptoms are poor concentration, indecisiveness, and feelings of worthlessness or excessive guilt.
• Associated physical symptoms are significant appetite or weight change, sleep disturbance (insomnia or, less commonly, hypersomnia), psychomotor agitation or retardation, and fatigue or loss of energy.
• Thoughts of death or suicide are important, given their particular clinical significance and the specific assessment approach required.
• Symptom pattern and severity vary considerably between individuals and across episodes in the same individual.
• Melancholic features are profound anhedonia, characteristic early morning waking, diurnal mood variation with symptoms worse in the morning, and significant psychomotor disturbance.
• Atypical features are increased appetite and weight gain, hypersomnia, and mood reactivity to positive events.
• Both are recognised clinical subtypes with some relevance to treatment selection in certain contexts.
• Functional impairment across occupational, social and personal domains, with the well established risk of self harm and suicide, warrants careful, systematic assessment in every patient with depressive symptoms (see suicide).
• Systematically explore the history: previous depressive episodes, relevant psychosocial stressors and family history of mood disorder.
• Specifically and carefully explore any history suggesting previous hypomanic or manic episodes. Underlying bipolar disorder rather than unipolar major depressive disorder has fundamentally different treatment implications (see bipolar disorder).

• Diagnosis is by full clinical psychiatric assessment. Explore the symptom pattern, duration and severity against established diagnostic criteria. Assess functional impairment and associated risk, particularly suicide risk.
• Validated screening and severity rating instruments (including the Patient Health Questionnaire-9 and other similar validated tools) support structured assessment, initial screening in appropriate clinical contexts, and monitoring of treatment response over time.
• Screen for an underlying medical cause or contributor. Include thyroid function testing, given the recognised association between hypothyroidism and depressive symptoms, and a medication review.
• Screen carefully for any history suggestive of previous hypomanic or manic episodes. Accurately distinguishing unipolar depression from bipolar disorder is critical (see bipolar disorder).
• Assess for coexisting psychiatric conditions, particularly anxiety disorders, which frequently coexist with depressive disorders, and for coexisting substance use. Both bear directly on treatment planning.

• Psychological therapy, including cognitive behavioural therapy and interpersonal therapy among other evidence based approaches, is an effective, well established treatment across the range of severity. There is strong evidence for it as standalone treatment for mild to moderate depression and as part of combined treatment, alongside pharmacotherapy, for more severe presentations.
• Selective serotonin reuptake inhibitors are generally first line pharmacological treatment, given their favourable tolerability and safety profile.
• Serotonin-noradrenaline reuptake inhibitors and other antidepressant classes are alternative or subsequent options according to individual response, tolerability and clinical considerations, including coexisting symptoms or conditions that might favour a particular agent.
• Assess response over a trial period of several weeks, given the characteristic delay in onset of therapeutic benefit.
• Combined treatment, with both psychological therapy and pharmacotherapy, is generally recommended for moderate to severe depression, given evidence of superior outcomes compared with either modality alone in this population.
• Monitor treatment response regularly and in a structured way. Reassess suicide risk systematically throughout treatment.
• Be particularly vigilant in the early weeks after starting or adjusting antidepressant therapy, and in younger patients, given recognised safety considerations in this population (see suicide).
• Treatment resistant depression is inadequate response to an adequate trial of at least two different antidepressant agents. It warrants specialist psychiatric reassessment.
• Options include augmentation (adding a second agent, including certain atypical antipsychotics or lithium, to the existing antidepressant) and a trial of a different antidepressant class. For severe, treatment resistant depression, options include electroconvulsive therapy or other interventional approaches.
• Manage holistically. Attend to psychosocial factors, sleep, physical activity and any coexisting medical or psychiatric conditions. Provide psychoeducation for the patient and, where relevant and with consent, involved family members.
• Arrange structured, ongoing longitudinal follow up, given the frequently chronic, relapsing and remitting natural history of depressive disorders.