Major depressive disorder

• Major depressive disorder (MDD) is a recurrent, episodic illness in which a person has at least two weeks of depressed mood or loss of interest or pleasure, together with other cognitive, somatic and behavioural symptoms, plus clear impairment of functioning. ^[3][6]
• It is common: an estimated 5.2% of adults worldwide were living with depression in 2023, and about 322 million people overall. Depression is roughly 1.5 times more common in women than in men. ^[1]
• No blood test or scan diagnoses it. The diagnosis rests on a careful clinical assessment, and the main task is to separate it from grief, bipolar disorder, substance use, and medical causes. ^[3]
• Treatment is stepwise and individualised: psychological approaches first for less severe illness, antidepressant medication (usually a selective serotonin reuptake inhibitor) added or used alone for more severe illness, with augmentation and specialist care when response is inadequate. ^[2][4]
• Most first episodes resolve, but episodes tend to recur; continuing treatment for months after remission and staying engaged with follow-up are what prevent the next episode. ^[2]

By the end of this page you should be able to:

1. State the definition of a major depressive episode and the five-of-nine symptom rule, using the SIG E CAPS mnemonic. ^[6]
2. Recognise the main specifiers of depression and explain when each changes management. ^[3]
3. Plan screening and assessment of a person with low mood, including which tests are justified and which are not. ^[3]
4. Match first-line psychological and pharmacological treatment to severity, and name typical doses and monitoring. ^[2][4]
5. Outline the stepwise approach to treatment-resistant depression, including where esketamine fits. ^[5]
6. Distinguish depression from grief and from bipolar, anxious and medical mimics. ^[1][3]

Depression is a syndrome rather than a single disease. The older umbrella "depression" covers a family of conditions that differ by duration, severity and cause. MDD sits at the episodic, more severe end of this family; persistent depressive disorder (dysthymia) is the chronic, lower-grade cousin; and bipolar disorder includes depressive episodes that alternate with mania or hypomania. ^[3]

A major depressive episode is therefore the building block. Five or more of the nine groups below are required, present most of the day, nearly every day, for at least two weeks, with at least one of the first two (depressed mood; loss of interest or pleasure). ^[1][6]

The mnemonic is SIG E CAPS:

• S = Sleep disturbance (insomnia or hypersomnia)
• I = loss of Interest or pleasure
• G = excessive Guilt or worthlessness
• E = loss of Energy
• C = poor Concentration or indecisiveness
• A = change in Appetite or weight
• P = Psychomotor agitation or retardation
• S = Suicidal thoughts or acts, or thoughts of death.

Add the depressed mood itself and the total reaches nine. ^[6]

Subthreshold symptoms that do not reach five items, or a single two-week episode, are common in primary care and still matter: they predict progression to a full episode and are an indication for prevention. ^[3]

Classification that is useful in practice includes:

• Episode number. A single episode is the first and only episode. Recurrent depressive disorder means two or more episodes, and recurrence risk rises with each episode.
• Severity. Mild, moderate or severe, based on the number and intensity of symptoms and on functional impairment. WHO describes the same three levels. ^[1]
• Duration. An episode is acute while it is present; remission is the return to near-baseline for a sustained period; recovery is the maintained well state after an episode.
• Course. Chronic when symptoms persist beyond two years. CANMAT notes that roughly 20 to 30% of people with a major depressive episode have a chronic course longer than two years, and these cases do less well with standard treatments. ^[3]

Depression is one of the leading causes of disability worldwide. ^[1][3]

• Population burden. An estimated 4% of the world's population had depression in 2023, including 5.2% of adults (4.1% of men and 6.2% of women) and 5.4% of adults aged 70 or over. About 322 million people live with depression. ^[1]
• Sex. Depression is roughly 1.5 times more common in women than in men, especially in adolescence and midlife; there is little sex difference in late life. CANMAT also lists female sex as a risk factor, except where female risk equals male risk in older age. ^[1][3]
• Babies. More than 10% of pregnant women and women who have recently given birth experience depression. ^[1]
• Care gap. In high-income countries only about one third of people with depression receive mental health treatment, and under-detection is even worse in low- and middle-income settings. Up to 60% of cases are missed or mis-identified in primary care. ^[1][3]
• Suicide. Depression can lead to suicide; in 2021 an estimated 727,000 people died by suicide, and suicide is the third leading cause of death in 15 to 29 year olds. This is the single most important reason to assess and treat depression seriously. ^[1]
• Canada (illustrative). About 12% of Canadians aged 12 or older report a lifetime episode of MDD, and 4.7% have had a major depressive episode within the past year. ^[3]
• Recurrence. A first episode often returns. Each episode increases the risk of the next, which is why continuation and maintenance treatment exists. ^[2]

No single cause has been found. Depression is best understood as the result of a biological vulnerability interacting with psychological and social stress. ^[1][3]

Static, largely non-modifiable factors include female sex, a family history of mood disorders, childhood maltreatment or adversity (particularly emotional abuse, bullying and parental loss), and bereavement of a spouse. ^[3]

Dynamic, potentially modifiable factors include:

• chronic physical illness (chronic pain, cardiovascular disease, diabetes, cancer, inflammatory bowel disease, sleep disorders, obesity), which has a bidirectional relationship with depression; ^[3]
• other psychiatric conditions, especially anxiety disorders, alcohol and substance use disorders; ^[3]
• hormonal transitions (puberty, perinatal, perimenopausal periods); ^[3]
• stressful life events and circumstances (unemployment, divorce, trauma, immigration, job strain, income inequality, poor housing, loneliness and social isolation); ^[1][3]
• sleep disturbance, night shift work, sedentary lifestyle and excessive screen time; ^[3]
• adolescence-specific risks such as peer victimisation and high-potency cannabis use. ^[3]

Bereavement deserves a special mention. Grief after a loss is a normal process and many of its features overlap with depression. Severe or prolonged grief can, however, trigger a major depressive episode, and depression can coexist with grief. The distinction is discussed in the differential diagnosis section. ^[1][3]

Depression is not simply a "serotonin deficiency". A useful way to organise what is known is to link the vulnerability factors above to changes in brain and body. ^[3]

• Monoamine systems. Serotonin, noradrenaline and dopamine transmission are disturbed, which is why drugs that modulate these systems are effective. ^[4]
• Stress systems. Chronic stress and trauma activate the hypothalamic-pituitary-adrenal axis; cortisol dysregulation and altered feedback are characteristic of melancholic depression. ^[3]
• Neuroplasticity. Reduced synaptic plasticity, lower neurotrophic signalling (including brain-derived neurotrophic factor) and, in severe or recurrent illness, grey-matter changes are implicated, supporting the idea that depression is also a disorder of brain adaptation. ^[3]
• Circadian and sleep systems. Sleep-wake and circadian gene disturbance help explain the diurnal mood variation, early morning waking and seasonal pattern. ^[3]
• Inflammation and medical illness. Depression and chronic inflammatory or endocrine illness (thyroid, Cushing, diabetes, cardiovascular disease) influence each other in both directions; cytokine signalling is one candidate mechanism. ^[3]
• Cognitive models. Negative schemas about the self, world and future, and behavioural withdrawal that confirms those beliefs, explain maintenance and relapse. This is the basis of cognitive behavioural therapy. ^[4]

These mechanisms are not mutually exclusive; they converge on impaired regulation of mood, reward, sleep and energy, which is what produces the syndrome.

Patients rarely say "I am depressed". They say "I feel empty", "everything is an effort", "I cannot enjoy anything any more". Open questions and patience matter more than any tool. ^[3]

Core mood symptoms

• Depressed mood: sad, empty, hopeless, irritable or "flat"; present most of the day, nearly every day. ^[1]
• Anhedonia: loss of interest or pleasure in food, hobbies, sex, people. ^[1]

Neurovegetative symptoms (the rest of SIG E CAPS)

• Sleep change: early morning waking is classic for melancholic depression; hypersomnia can occur in atypical depression. ^[6]
• Appetite and weight change in either direction. ^[6]
• Fatigue and loss of energy. ^[1]
• Psychomotor slowing or restless agitation. ^[6]
• Poor concentration and memory complaints ("brain fog"), often prominent and sometimes misdiagnosed as dementia. ^[3]
• Guilt, shame, hopelessness and feelings of worthlessness, sometimes delusional. ^[6]
• Thoughts of death, dying, or suicide, and sometimes suicide attempts. ^[6]

Associated features

• Anxiety is very common, in older people especially; treat the depression first unless a separate anxiety disorder dominates. ^[2]
• Somatic complaints (headache, chest pain, abdominal pain, fatigue) are a common presentation, particularly in some cultures and in younger or older patients. ^[3]
• Irritability, anger or "burnout" can dominate in men and in adolescents. ^[1]
• Cognitive "executive" difficulties explain much of the work and social disability. ^[3]

Specifiers and what they look like

• Melancholic features: loss of pleasure and reactivity to good news, distinct (qualitatively different) mood, early morning waking, worse in the morning, significant weight loss, excessive guilt, psychomotor change. ^[6]
• Atypical features: mood brightens to positive events, plus hypersomnia, hyperphagia with weight gain, leaden paralysis and long-standing rejection sensitivity. ^[3]
• Psychotic features: delusions or hallucinations consistent with depressive themes (guilt, poverty, illness, nihilism) or not; this changes treatment (antidepressant plus antipsychotic, or ECT). ^[3]
• Catatonic features: stupor, mutism, negativism, posturing or waxy flexibility, or extreme agitation; can occur in severe depression. ^[3]
• Anxious distress: restless, tense, fearful of losing control, difficulty concentrating. ^[3]
• Mixed features: some manic or hypomanic symptoms present. ^[3]
• Seasonal pattern: recurrent winter (or sometimes summer) depressions; CANMAT singles this specifier out as one with clear treatment implications. ^[3]
• Peripartum onset: onset in pregnancy or the first weeks after delivery. ^[3]
• Chronic course: full criteria for more than two years, with lower response rates. ^[3]

There is no pathognomonic physical sign. The examination aims to confirm the syndrome, exclude organic causes, and assess risk.

Mental state examination. Record appearance and self-care, psychomotor state, mood and affect, thought form and content (guilt, hopelessness, suicidal and homicidal ideas, psychotic symptoms), perception (hallucinations), cognition and insight. A useful opening is "tell me what a typical day is like for you now". ^[3]

Risk assessment. This is mandatory and repeated at every contact. Ask directly about suicidal thoughts, plans, means, intent, protective factors and previous attempts. Assess also non-suicidal self-harm, harm to others, self-neglect, exploitation and, in the postpartum period, risk to the baby. ^[2][3]

Physical examination. Weight, height and body mass index, pulse and blood pressure, thyroid palpation, neurological signs, and signs of self-neglect or alcohol use. Look for causes such as tremor, rigidity and bradykinesia in Parkinson disease. ^[3]

Suicide risk in context. Antidepressants can transiently increase agitation and suicidal ideation in the first weeks, especially in those aged 18 to 25. Starting treatment therefore includes safety planning and close early review, not the withholding of treatment. ^[2]

Two questions arise: is this really depression, and if so, which other conditions must be considered alongside it?

There is no diagnostic test for depression. Investigations exist to exclude organic causes, to check safety before treatment, and to monitor for adverse effects. ^[3]

NICE adds pregnancy-specific and comorbidity-specific considerations, and advocates routine outcome monitoring (for example with the PHQ-9) once treatment has started. ^[2]

Paraphrasing DSM-5-TR: a major depressive episode (and therefore MDD, once the episode and course criteria are met) requires five or more of nine symptoms during the same two-week period, representing a change from previous functioning, with at least one symptom being depressed mood or loss of interest or pleasure, plus clinically significant distress or impairment, and not attributable to a substance, a medical condition, or another psychiatric disorder such as schizophrenia or mania. ^[6]

Screening and outcome tools

• PHQ-2 is the two-item screen (depressed mood and anhedonia). A score of at least 2 is considered positive. ^[3]
• PHQ-9 is then used to confirm and monitor. A positive PHQ-2 followed by a positive PHQ-9 (score of at least 10) has similar sensitivity but better specificity than the PHQ-9 alone. Screening questionnaires are not diagnostic; a positive screen must be followed by a full diagnostic assessment. ^[3]
• Severity cut-offs used in guidelines. NICE defined a PHQ-9 score under 16 as less severe depression and a score of 16 or more as more severe depression, and built this into its treatment recommendations. ^[2]
• CANMAT defines mild, moderate or severe by the number and intensity of symptoms together with the degree of functional impairment, measured with a validated scale. ^[3]

Severity mapping used in this page

• Less severe (subthreshold/mild). Fewer symptoms, modest functional impairment.
• More severe (moderate/severe). More symptoms, or suicidal ideation, psychotic features, severe functional impairment, severe physical symptoms, or need for hospital care. ^[2][1]

CANMAT explicitly notes that most specifiers have limited value for choosing treatment, with two exceptions: psychotic features and seasonal pattern. ^[3]

This section follows the three guidelines named here: NICE NG222 (published 29 June 2022, last reviewed 30 January 2026), the APA Clinical Practice Guideline across three age cohorts (adopted February 2019), and the CANMAT 2023 update (published May 2024). ^[2][3][4]

• Base treatment on a shared decision, and respect the person's preference, past experience and goals. ^[2][3]
• Use the least intrusive, least resource-intensive effective treatment first, and escalate only when needed. ^[2]
• Treat depression and physical health together; chronic physical illness and depression worsen each other. ^[3]
• Review all treatment 2 to 4 weeks after starting, and more often for younger adults, older adults where needed, and anyone at suicide risk. ^[2]
• After remission, continue treatment for at least 6 months before any reduction. ^[2][4]
• Watch for side effects, adherence problems, suicide risk (especially early), and withdrawal if doses are changed. ^[2]

CANMAT retains a two-phase model. ^[3]

• Acute phase (roughly 8 to 16 weeks) aims at remission: safety first, then a therapeutic alliance, psychoeducation, choice and delivery of evidence-based treatment, and monitoring. ^[3]
• Maintenance phase (roughly 6 to 24 months, or longer if indicated) aims at sustained remission, restoring functioning and quality of life, treating comorbidities and preventing recurrence. ^[3]

NICE defines less severe depression as subthreshold and mild depression and is explicit: do not routinely offer antidepressant medication as first-line treatment; offer it only if that is the person's informed preference. ^[2] WHO agrees that antidepressant medicines are not needed for mild depression. ^[1]

First-line options, roughly in order of how NICE ranks them by clinical and cost effectiveness, are: ^[2]

1. Guided self-help (six to eight structured regular sessions; CBT, behavioural activation, problem solving or psychoeducation, delivered in person, by telephone or digitally).
2. Group cognitive behavioural therapy (CBT) (about eight regular sessions).
3. Group behavioural activation (about eight regular sessions).
4. Individual CBT (about eight sessions, more if comorbidities).
5. Individual behavioural activation (about eight sessions, more if comorbidities).

If there is no preference or no access, active monitoring (review in 2 to 4 weeks; education and support) is appropriate for someone who is improving or who does not want treatment. ^[2]

For more severe depression, NICE supports a wider range: individual CBT, behavioural activation, other psychotherapies and an antidepressant, alone or in combination. WHO recommends that psychological treatments can be combined with antidepressant medication in moderate and severe depression. ^[1][2] Practical points:

• An antidepressant is usually appropriate, alongside or instead of psychotherapy, depending on preference. ^[2]
• Combination (antidepressant plus CBT or interpersonal psychotherapy) tends to outperform either alone and is particularly useful where symptoms are severe or chronic. ^[4]
• Offer choice of which psychological therapy and how it is delivered. ^[2]
• If the person does not want the first option offered, respect that and try another. ^[2]

For a single severe episode, or when psychotic features are present, combine an antidepressant with an antipsychotic, or consider electroconvulsive therapy (ECT). ^[3]

APA's 2019 guideline recommends a second-generation antidepressant (selective serotonin reuptake inhibitor (SSRI), serotonin-noradrenaline reuptake inhibitor (SNRI) or noradrenaline-dopamine reuptake inhibitor (NDRI)) for adults with depression, but found the evidence insufficient to recommend any specific drug over another. ^[4]

Typical adult dose ranges (from the APA guideline page; always check the product label and local formulary): ^[4]

How to use a first antidepressant

• Start at a low dose and titrate towards the usual effective range within the first 2 to 4 weeks, adjusting for side effects and comorbidity. ^[2][4]
• Explain that benefit, if it comes, usually appears within 4 weeks, with continued improvement thereafter. ^[2]
• Review at 2 to 4 weeks after starting, and earlier (about 1 week) for patients aged 18 to 25 and for anyone with suicide risk. ^[2]
• Monitor mood, functioning, side effects and suicidal ideation at each contact; regular sessional measures such as the PHQ-9 are encouraged. ^[2][3]
• Continue at the effective dose for at least 6 months after remission (often longer after repeated episodes). ^[2][4]
• Tailor drug choice to side-effect and cautions profile: for example, mirtazapine helps when insomnia and weight loss are prominent; bupropion is less sedating and has less sexual side effect; avoid paroxetine and venlafaxine where possible in pregnancy; and in a person at high suicide risk avoid routine TCAs because of overdose lethality (except lofepramine). ^[2][4]
• Stop gradually (taper) when discontinuing, taking into account half-life; paroxetine and venlafaxine are more prone to discontinuation symptoms, and fluoxetine can sometimes be tapered by alternate-day dosing. ^[2]
• Warn about early activation, nausea, sexual dysfunction and sleep changes, and about the risk of antidepressant-induced mania (which flags bipolar disorder). ^[2][4]

Augmentation for partial or non-response

• Lithium. NICE supports lithium as an adjunct. Aim for plasma lithium at or above 0.4 mmol/L (therapeutic augmentation usually 0.4 to 0.6 mmol/L; use the lower end in people aged 65 or over), and do not exceed 1.0 mmol/L. Check renal and thyroid function, calcium and weight before starting and at least every 6 months, measure levels weekly during titration and then at defined intervals, and taper over 1 to 3 months when stopping. ^[2]
• Antipsychotic. NICE supports augmentation with an oral antipsychotic under shared care, with baseline pulse, blood pressure, weight, fasting glucose or HbA1c and lipids, and ongoing monitoring of cardiometabolic and extrapyramidal effects. ECG at baseline and at final dose for those with cardiovascular risk or concomitant QT-prolonging drugs such as citalopram or escitalopram. ^[2]
• Psychological. Adding or intensifying CBT or behavioural activation while medication is continued remains an evidence-based step. ^[4]

APA recommends seven psychotherapies for adult depression, with seven typical session ranges: ^[4]

Difficult-to-treat depression is depression that has not remitted after adequate treatment. The practical stepwise approach is:

1. Reassess the diagnosis (bipolar, substance, medical), comorbidity, adherence, dose and duration, and psychosocial stressors. ^[3]
2. Optimise or switch the current antidepressant (a different SSRI, an SNRI, or bupropion or mirtazapine). ^[3][4]
3. Combine antidepressants of different classes with care, or add psychotherapy if not already given. ^[4]
4. Augment with lithium or an antipsychotic as above. ^[2]
5. Consider neuromodulation: ECT for severe, persistent, psychotic, catatonic, or treatment-resistant depression, for postpartum depression, or where risk is high; repetitive transcranial magnetic stimulation (rTMS) as a non-invasive option. ^[2][3]
6. Additional options in specialist care include intravenous ketamine protocols and other experimental or augmentation strategies; discuss openly and avoid overstating the evidence. ^[3]

NICE lists ECT, TMS and a specific treatment-resistant depression section in NG222, and its ECT advice is to use ECT for severe depression that has not responded to other treatments, or where rapid response is necessary, or in the particular circumstances listed in the guideline. ^[2]

Esketamine nasal spray is indicated for treatment-resistant depression in adults, as monotherapy or together with an oral antidepressant, and for depressive symptoms in MDD with acute suicidal ideation or behaviour alongside an oral antidepressant. ^[5] It is administered only under direct supervision in certified settings. ^[5]

• Dose for TRD: 56 mg or 84 mg intranasally, twice a week in weeks 1 to 4, once a week in weeks 5 to 8, then every 2 weeks or once a week as the least frequent dosing that maintains remission or response. ^[5]
• Device: each nasal device delivers 28 mg; use 2 devices for 56 mg or 3 for 84 mg, with a 5-minute rest between devices. ^[5]
• Dose for MDD with acute suicidal ideation or behaviour: 84 mg twice weekly for 4 weeks, reduced to 56 mg twice weekly if not tolerated. Benefit beyond 4 weeks has not been systematically evaluated. ^[5]
• Monitoring: at least 2 hours of post-dose observation (sedation, dissociation, blood pressure, breathing), and patients must not drive or operate machinery until the next day after restful sleep. ^[5]
• Safety: pregnancy planning (embryo-fetal toxicity), blood-pressure checks, and REMS-controlled dispensing; avoid with uncontrolled hypertension or relevant vascular disease. ^[5]

Evidence of benefit should be reviewed at the end of the induction phase to decide whether to continue. ^[5]

• Light therapy. NICE's advice is clear that evidence of benefit is uncertain for winter-pattern depression; it should be used only in informed preference. ^[2]
• Physical activity and lifestyle. Advice about regular activity, healthy diet, alcohol limits and sleep hygiene is part of care, and should be emphasised rather than left as an afterthought. ^[1][2]
• St. John's Wort. NICE advises against prescribing or recommending it because of uncertain dosing, variable preparations and serious drug interactions. ^[2]
• Complementary and digital options (for example guided self-help apps) can extend access where services are limited. ^[3]

• After remission, continue treatment at the full effective dose for at least 6 months (NICE), reviewing regularly, and longer after recurrent illness (CANMAT 6 to 24 months). ^[2][3][4]
• Taper antidepressants slowly when stopping, usually over several weeks or longer for long-half-life or short-half-life drugs, with monitoring. ^[2]
• Withdrawal is common with short-half-life drugs such as paroxetine and venlafaxine. Fluoxetine can sometimes be given on alternate days. Reassure that withdrawal is not relapse. ^[2]
• Write a relapse prevention plan: early warning signs (insomnia, anxiety, low mood, withdrawal, suspiciousness), triggers, who to contact, and how to reach crisis services. ^[2]
• Address ongoing stress, relationships, work and sleep; MBCT and maintenance CBT reduce recurrence in recurrent depression. ^[4]

• Emergency or same-day referral for acute suicidal intent or plan, psychosis, catatonia, severe self-neglect or inability to care for children. ^[2][3]
• Specialist assessment for a first episode in a young person; for severe, psychotic or bipolar features; for treatment resistance (failure of two adequate trials); and for pregnancy and breastfeeding decisions. ^[2][3]
• Primary care can lead treatment of less severe first episodes, with easy access back to specialist care. ^[2][3]

• Suicide and suicidal behaviour. The most serious complication; ask directly about ideation and intent, make a safety plan, and treat vigorously. ^[1][2]
• Chronic course. Around 20 to 30% of people with a major depressive episode have a chronic course longer than two years, with lower response and remission. ^[3]
• Treatment resistance. Many (up to 60%) are never recognised in primary care, let alone treated to response. ^[3]
• Functional decline. Work loss, social withdrawal, strained relationships and loss of education or employment. ^[1]
• Medical and substance comorbidity. Depression and physical disease are bidirectional; alcohol and other substance use worsen outcomes. ^[3]
• Antidepressant-induced mania. Unmasks bipolar disorder; pause and reassess if a person on an antidepressant develops elevated mood, decreased sleep need or disinhibition. ^[2][3]
• Medication adverse effects. Sexual dysfunction, gastrointestinal upset, insomnia or sedation, weight gain, and (with SNRIs and others) discontinuation syndromes. TCAs and MAOIs are not first line. ^[2][4]
• Antipsychotic and lithium adverse effects when used for augmentation, including metabolic, renal, thyroid and cardiac effects. ^[2]
• ECT and esketamine carry their own risks (cognitive effects, dissociation and blood-pressure rise) and require appropriate monitoring and consent. ^[2][5]

With treatment, prognosis is good but not guaranteed. WHO notes that there are effective treatments for mild, moderate and severe depression. ^[1]

Factors associated with better outcome include shorter episode duration before treatment, fewer previous episodes, milder symptoms, good physical health, strong social support, and engagement with treatment. Poorer outcomes are associated with early onset, insidious onset, chronic pain or medical comorbidity, substance use, residual symptoms after remission, and adversity. ^[3] Prognosis is variable: a substantial proportion achieve remission, many relapse without continued treatment, and a minority (those with chronic depression, comorbidity or adversity) has more persistent difficulties. ^[1][3]

Each recurrence changes the odds: after a second episode, maintenance treatment for a longer period (CANMAT suggests 6 to 24 months, longer if clinically indicated) is strongly recommended. ^[3]

WHO and CANMAT agree that prevention is possible and that screening should be targeted and resourced rather than universal and automatic. ^[1][3]

• Community prevention (school-based coping skills programmes, parent-training for children's behavioural problems, exercise programmes for older adults, and suicide prevention) reduces depression and is cost effective. ^[1]
• Recognise risk factors early and intervene with psychoeducation and problem-solving. ^[1]
• Screening in primary and secondary care should use validated tools (CANMAT recommends the PHQ-2 followed, if positive, by the PHQ-9) for people with risk factors, where there are resources for assessment and treatment; a positive screen is not a diagnosis and must be followed by a full assessment. ^[3]
• Routine universal screening of average-risk adults is recommended by some task forces (CANMAT cites the USPSTF's finding of moderate net benefit) and opposed by others (the Canadian Task Force recommended against it, albeit weakly). NICE recommends being alert to possible depression and asking the two standard identification questions. ^[2][3]
• Primary-care identification questions: "During the last month, have you often been bothered by feeling down, depressed or hopeless?" and "During the last month, have you often been bothered by having little interest or pleasure in doing things?" ^[2]
• Physical health is the largest modifiable contributor to premature mortality; monitor and treat cardiovascular and metabolic risk from the start, especially once an antidepressant or antipsychotic is prescribed. ^[2][3]

Pregnancy and the postpartum period. Depression in this group affects more than 10% of pregnant and recently delivered women worldwide. ^[1] Base decisions on weighing the risks of untreated depression against those of medication, with obstetric and mental-health teams. Use the lowest effective dose; psychological therapies (including IPT and CBT) are particularly suitable. Drugs with longer safety records are generally preferred, but the choice is individual; escitalopram or fluoxetine are often used in practice when medication is needed, and avoid paroxetine and venlafaxine where possible. Do not stop antidepressants abruptly in pregnancy. Esketamine is not recommended in pregnancy (it should be avoided) because of the risk of embryo-fetal toxicity, though it is not listed as an absolute contraindication; decision-making rests on balancing the risks of untreated depression against potential fetal harm. NICE's perinatal guideline applies. ^[2][5]

Children and adolescents. Antidepressants are not used for depression in children and are not first-line in adolescents, in whom they must be used with extra caution and close monitoring. Psychological therapies (CBT, behavioural activation, interpersonal therapy) are the foundation, with family and school involvement. ^[1][4]

Older adults. Depression is under-recognised and often presents with somatic or cognitive symptoms. NICE advises taking physical health, comorbidities and drug interactions into account; monitoring side effects closely; being alert to falls, fractures and hyponatraemia; using lower starting doses and slower titration; and preferring agents with lower anticholinergic burden. ^[2]

People with equity-deserving barriers. CANMAT notes higher prevalence and lower access among racialised, Indigenous, gender-minority and other marginalised groups; culturally competent, trauma-informed, collaborative care and validated translations of screening tools (the PHQ is available in many languages) reduce this gap. ^[3]

• Non-specialists can recognise and manage depression with structured guidelines like WHO's mhGAP: identify cases, assess safety, and offer basic psychosocial and pharmacological care, referring when possible. ^[1][3]
• A single, low-cost SSRI (or another affordable antidepressant) plus structured behavioural activation, problem-solving therapy or interpersonal therapy delivered in brief sessions is a realistic minimum. ^[1][3]
• Internet- or phone-based guided self-help, community health workers and trained lay counsellors (Problem Management Plus) extend reach where specialists are scarce. ^[1][3]
• CBC and TSH are low-cost tests to exclude anaemia and thyroid dysfunction; ECG, neuroimaging and specialist biochemistry can be reserved for clear indications. ^[3]
• Where ECT is unavailable, maximise antidepressants, augmentation and psychotherapy, and transfer urgent or resistant cases to a centre that can provide it. ^[2]
• Reducing stigma and improving social protection (housing, income, safety from violence) are part of treatment in practice. ^[1]

• MDD is an episodic syndrome: at least two weeks of depressed mood or loss of interest, five of the nine SIG E CAPS symptom groups, and impaired functioning, with exclusion of substances, medical causes and bipolar disorder. ^[6]
• It is common (estimated 4% of the world population, 5.2% of adults in 2023) and under-treated (only about one third of affected people receive care in high-income settings). ^[1]
• Women are affected more often than men (roughly 1.5:1), and more than 10% of pregnant or postpartum women experience depression. ^[1]
• Diagnosis is clinical: no blood test or scan confirms it; a full assessment with collateral history matters more than any test; CBC and TSH are low-cost, useful screens. ^[3]
• NICE: PHQ-9 under 16 is less severe depression and 16 or more is more severe; antidepressants are not routine first line for less severe depression. ^[2]
• First-line care matches severity: psychological therapies for less severe illness; antidepressant (SSRI by default) plus or instead of therapy for more severe; augmentation and ECT or esketamine where indicated. ^[1][2][4]
• Use typical adult dose ranges from the APA guideline as a starting point, and titrate and monitor (2 to 4 weeks, earlier in 18-25 year olds) rather than prescribing blindly. ^[2][4]
• Treat psychotic depression with an antidepressant plus antipsychotic, or with ECT; CANMAT singles out psychotic and seasonal specifiers as treatment-relevant. ^[3]
• After remission, continue treatment for at least 6 months (often 6-24) before any taper; avoid abrupt stopping; monitor withdrawal, especially with short-half-life drugs. ^[2][3][4]
• Esketamine (56-84 mg intranasally) has a strict induction-maintenance schedule and 2-hour post-dose monitoring under a REMS; it can be used for treatment-resistant depression, as monotherapy or with an oral antidepressant. ^[5]
• Grief usually preserves self-esteem and comes in waves; severe or prolonged grief can become or coexist with MDD. Always ask about mood elevation to exclude bipolar disorder before prescribing an antidepressant alone. ^[3]
• Suicide risk is the overriding consideration: assess at every contact, safety-plan, and treat vigorously rather than withholding treatment. ^[1][2]

• Schizophrenia and other psychotic disorders
• Bipolar disorder
• Anxiety disorders
• Persistent depressive disorder
• Post-traumatic stress disorder
• Obsessive compulsive disorder
• Substance use disorders
• Electroconvulsive therapy
• Suicide prevention
• Postnatal depression
• Older adult depression
• Chronic pain