Major Depression

Around 1 in 10 primary-care patients has depression. Lifetime risk is ~15%; 12-month prevalence 4.1% (1 in 25); twice as common in women. Mean age at diagnosis is 27, with 40% presenting by age 20; 80% of patients experience two or more episodes. At 6 months, 54% have recovered; at 1 year, 70%; 12–15% fail to recover. Lifetime suicide risk is around 6% — effective treatment roughly halves this.

Diagnosis

Duration >2 weeks, with 5 of the following 9 criteria (at least one of the first two must be present):

• Depressed mood*
• Loss of interest or enjoyment*
• Weight change (≥5% in a month) or appetite change
• Sleep change (increased or decreased)
• Psychomotor agitation or retardation
• Loss of energy/fatigue
• Feelings of worthlessness or guilt
• Poor concentration/attention
• Suicidal ideation

Mood typically varies little day to day, with little response to circumstances. Melancholic depression is a specifier for a more severe presentation — psychomotor retardation/agitation, marked weight loss, loss of interest in almost all activities, and lack of mood reactivity even to positive events; see below for full criteria.

Elderly patients are commonly under-diagnosed — depression may present atypically (agitation, histrionic behaviour, delusions, disordered thinking), and a change in sleep pattern is a useful clue. Management is the same, but elderly patients are more susceptible to medication side effects.

Children and adolescents are often difficult to diagnose — depression presents as hopelessness, worthlessness, and despair, but children are more likely to have somatic complaints and irritability than overt sadness, alongside sleep difficulty, poor appetite, poor concentration, and low self-esteem.

Investigations

Screen for organic mimics/contributors: FBC (anaemia); ferritin (iron deficiency); monospot/EBV serology (infectious mononucleosis, especially in adolescents); TSH (thyroid dysfunction); cortisol/UEC/glucose (hyponatraemia, hyperkalaemia, hypoglycaemia, or low cortisol suggesting Addison’s disease); consider OSA on history/examination; consider HIV testing in high-risk patients (IVDU, MSM).

Management

Severity guides the initial approach:

• Minor depression — psychotherapy.
• Moderate depression — psychotherapy and/or pharmacotherapy.
• Severe depression — pharmacotherapy first, with psychotherapy once the patient is well enough to engage; consider ECT, augmenting agents, and psychiatry review.

Psychotherapy

All patients: lifestyle changes, problem-solving, guided self-help, structured supervised exercise, supportive counselling.

Select patients: CBT, ACT, or interpersonal therapy.

Pharmacotherapy

First-line for moderate-severe depression: SSRI or mirtazapine; SNRIs (desvenlafaxine, duloxetine, venlafaxine) and agomelatine/vortioxetine are second-line. About 60% of patients respond to the first antidepressant tried, though only 40% achieve full symptom resolution; if there’s no response, try another agent.

• Assess response at 2–4 weeks.
• Good response → continue at the effective dose.
• No initial response → increase the dose.
• Still no response at 2–4 weeks on the higher dose → switch drug.
• Partial response → increase the dose and reassess again at 2–4 weeks; if there’s no further improvement, switch drug.
• SSRIs have a relatively flat dose-response curve, so increasing the dose has limited extra benefit — there’s more evidence supporting dose increases for venlafaxine specifically.

Typical dosing:

Drug	Usual initial dose	Maximum dose
Citalopram	20 mg (10 mg if >65)	40 mg (20 mg if >65)
Escitalopram	10 mg	20 mg
Fluoxetine	20 mg	60 mg
Fluvoxamine	50 mg at night	300 mg
Paroxetine	20 mg	50 mg
Sertraline	50 mg	200 mg
Desvenlafaxine (CR)	50 mg	200 mg
Duloxetine	60 mg	120 mg
Venlafaxine (CR)	75 mg	375 mg
Mirtazapine	15–30 mg at night	60 mg

If no response to two first-line agents: consider TCAs, mianserin, or MAOIs — ideally with psychiatry referral before prescribing any of these. TCAs are more likely to be effective for severe or melancholic depression (75–150 mg daily, maximum 200–300 mg), but carry anticholinergic effects, orthostatic hypotension, sexual dysfunction, weight gain, and sedation.

If still no response to adequate trials of antidepressant therapy, refer to a psychiatrist and consider:

• ECT — 50–80% response rate.
• Lithium augmentation of an SSRI or TCA.
• Second-generation antipsychotic augmentation — aripiprazole, brexpiprazole, cariprazine, olanzapine, and quetiapine have the most evidence, though only quetiapine is TGA-approved for this indication.
• Liothyronine (T3) augmentation.

ECT is safe and effective, though it carries a risk of transient — and sometimes longer-term — memory impairment. Indications: psychotic depression; melancholic depression unresponsive to antidepressants; severe postnatal depression with psychosis; severe psychomotor retardation (e.g. catatonic refusal to eat/drink).

Melancholic depression (DSM-5 specifier)

Applied to a major depressive episode when, at its most severe, there is:

• Loss of pleasure in almost all activities, or lack of reactivity to usually pleasurable stimuli,

plus 3 or more of: a distinct quality of mood (extreme despondency/despair/ moroseness, or an “empty” mood); mood worse in the morning; early-morning waking; marked psychomotor agitation/retardation; significant anorexia/weight loss; excessive or inappropriate guilt.

Related/adjacent diagnoses

• Persistent depressive disorder (dysthymia) — the current DSM-5 term for dysthymia: ≥2 years of enduring, fluctuating low mood, with insufficient symptoms to meet full major-depression criteria. Antidepressants are generally not helpful.
• Adjustment disorder with depressed and/or anxious mood — distress and emotional disturbance, usually interfering with social functioning, following a significant stressor, where duration/severity don’t meet criteria for another depressive or anxiety disorder. Antidepressants are generally not helpful.
• Seasonal affective disorder — more common in cold, dark-winter climates. Sleeping difficulty, sadness, lethargy, irritability, anxiety, and sometimes somnolence with increased appetite. Treatment: SSRIs, psychotherapy, and phototherapy.

Perinatal depression

~10% of pregnant patients experience depression — it’s the biggest risk factor for postnatal depression, and untreated depression carries its own obstetric/neonatal risk (suicide is a leading cause of perinatal death), so don’t withhold effective treatment purely over fetal drug-exposure concerns, especially with a history of severe/recurrent depression. Screen with the Edinburgh Postnatal Depression Scale (EPDS) — a score of ≥13 indicates possible depression needing further assessment; a ≥4-point change is a meaningful treatment-response signal. For mild-moderate depression, psychological therapy is first-line; drug-therapy principles otherwise mirror major depression in the general population, adjusted for pregnancy-specific psychotropic safety considerations.