How is major depressive disorder different from ordinary sadness?

Sadness is a normal emotional response with an identifiable cause and resolves naturally over time. Major depressive disorder is a clinical syndrome requiring five or more symptoms lasting at least two weeks — including either depressed mood or anhedonia — that cause significant impairment in work, relationships, or daily function. Unlike sadness, MDD often persists without a clear external trigger and affects sleep, appetite, concentration, energy, and motivation in ways that compound over time. The PHQ-9 is a validated tool GPs use to assess severity at baseline and track response to treatment.

Does every person with depression need an antidepressant?

No. For mild depression, Australian guidelines recommend psychological therapy and lifestyle measures first, with antidepressants considered only if symptoms persist beyond six to eight weeks of adequate psychological treatment, or if the person has recurrent illness or prior good medication response. For moderate to severe depression, combining an antidepressant with psychological therapy produces better outcomes than either alone. The decision is made through shared discussion about symptom severity, personal preferences, past treatment history, and available supports.

How long does an antidepressant take to work?

Initial improvements in sleep and energy may appear within one to two weeks. Full antidepressant effect on mood, concentration, and motivation typically takes four to six weeks, and sometimes up to twelve weeks for complete response. If there has been no meaningful improvement after six to eight weeks at an adequate dose, the GP will reassess diagnosis, adherence, and whether a medication change is needed. The first one to two weeks may feel difficult as the medication begins — this usually settles with continued use.

How long should antidepressant treatment continue?

The standard recommendation is to continue an effective antidepressant for at least six to twelve months after achieving remission — this is the period with the highest relapse risk. For people with a second episode, at least two years of continuation is recommended. After three or more episodes, long-term or ongoing maintenance is discussed at each review. Stopping too early is one of the most common causes of relapse. When stopping, doses are tapered gradually over four to eight weeks to reduce discontinuation effects.

What safety monitoring is needed when starting an antidepressant in a young person?

Australian guidelines and TGA guidance highlight that people under 25 have a small increased risk of emergent suicidal ideation in the first two to four weeks of antidepressant treatment. This does not mean avoiding antidepressants in young people — untreated depression carries substantially greater risk. It means closer monitoring, ideally weekly contact in the first month, along with a documented safety plan and crisis line information before the prescription is issued. Lifeline 13 11 14 and Beyond Blue 1300 22 4636 should be provided at every initial consultation.

Major depressive disorder

Major depressive disorder: diagnosis and treatment in AU general practice

By Dr HB Lo, FACRRM Reviewed 7 June 2026 10 min read

Major depressive disorder affects around one in seven Australians over their lifetime. DSM-5 criteria require five or more symptoms for at least two weeks — including depressed mood or anhedonia — with significant distress or impairment.

The RANZCP 2020 Mood Disorders Guideline recommends psychological therapy first for mild depression and combined therapy plus an SSRI for moderate to severe illness. Sertraline and escitalopram are the preferred first-line antidepressant choices in Australian general practice.

Continue effective treatment for at least six to twelve months after remission to reduce relapse risk, with longer maintenance in recurrent illness.

Depression is the most common mental health condition managed in Australian general practice, and it accounts for more presentations than any single chronic physical illness. But the word “depression” covers an enormous clinical range — from a mild, reactive low mood that resolves with social support and lifestyle adjustment, to a severe melancholic syndrome with psychomotor retardation, cognitive impairment, nutritional failure, and acute suicide risk requiring hospitalisation.

Getting that range right matters enormously for management. Over-treating mild depression with antidepressants that have modest benefit at that severity tier adds drug burden without meaningful return. Under-treating moderate to severe depression — offering only watchful waiting when medication plus psychological therapy is indicated — allows a treatable illness to become protracted and disabling.

Major depressive disorder (MDD) is defined by the DSM-5 as five or more symptoms persisting for at least two weeks — with either depressed mood or anhedonia as an anchor — causing significant distress or functional impairment not explained by a substance, a medical condition, or another psychiatric diagnosis. Severity is classified mild, moderate, or severe. The PHQ-9 provides a validated 0–27 score: mild 5–9, moderate 10–14, moderately severe 15–19, severe ≥20.

According to the ABS National Study of Mental Health and Wellbeing, approximately one in seven Australians experiences MDD over their lifetime, with a 12-month prevalence around 10%. Women are approximately twice as likely to be affected as men. Peak onset is in the 20s to 30s, though depression occurs across all age groups.

A. Core clinical — the AU general-practice framework

Assessment

The RANZCP 2020 Mood Disorders Clinical Practice Guideline frames the consultation around five non-negotiable domains.

1. Symptom characterisation. The nine DSM-5 symptoms are: depressed mood; anhedonia; weight or appetite change; sleep disturbance (insomnia or hypersomnia); psychomotor agitation or retardation observable by others; fatigue or loss of energy; worthlessness or excessive guilt; difficulty concentrating or making decisions; and recurrent thoughts of death or suicidal ideation. At least one anchor symptom — depressed mood or anhedonia — must be present, along with five or more total symptoms for at least two weeks, causing significant impairment.

2. Suicide risk. This is assessed at every presentation, regardless of perceived severity. The structured assessment covers: current ideation (passive versus active), presence of a specific plan, expressed intent, access to means, past attempts, protective factors, and social supports. Presence of a plan or intent changes management immediately — safety planning, crisis-line provision, and often urgent psychiatric referral.

3. Organic mimics. Before confirming a primary depressive diagnosis, exclude: hypothyroidism (TSH); anaemia (FBC); vitamin B12 and folate deficiency; vitamin D deficiency; obstructive sleep apnoea; and — particularly in older adults — early dementia. In women of reproductive age, consider premenstrual dysphoric disorder (cyclical, luteal-phase onset) and perinatal depression (Edinburgh Postnatal Depression Scale at six weeks postnatal). Drug-induced depression occurs with corticosteroids, certain beta-blockers, interferon, and isotretinoin.

4. Bipolar history. Antidepressant monotherapy in bipolar disorder can precipitate mania, hypomania, or rapid cycling. Screen for past hypomanic or manic episodes, family history of bipolar illness, and prior antidepressant-induced mood switching. The Mood Disorder Questionnaire (MDQ) is a useful screening tool. If bipolar is suspected, psychiatry input is needed before initiating an antidepressant alone.

5. Comorbidities. Anxiety disorders co-occur in approximately half of people with MDD. Alcohol and substance use are both drivers and consequences of depression. Chronic pain, cardiovascular disease, and sleep disorders interact bidirectionally with depressive illness. Each comorbidity requires its own management approach alongside the depression.

Investigations

Baseline bloods in new depression: FBC, UEC, LFT, TSH, vitamin D, B12, folate, and ferritin. Add HbA1c and fasting lipids when considering atypical antipsychotic augmentation or when metabolic comorbidity is present. An ECG before initiating tricyclic antidepressants or medications with QT-prolonging potential.

Validated severity tools

The PHQ-9 is the standard in Australian general practice settings. Score at baseline, two to four weeks after starting treatment, and at each follow-up. A ≥50% reduction from baseline defines “response”; a score below five defines “remission.” The K10 (Kessler Psychological Distress Scale) and DASS-21 are widely used alternatives, particularly in community mental health contexts.

Differential diagnosis

Key differentials: adjustment disorder (identifiable stressor, less severe, often self-resolving within six months), persistent depressive disorder (dysthymia — chronic low-grade depression ≥2 years), bipolar disorder (past mania or hypomania), grief and bereavement, premenstrual dysphoric disorder (cyclical pattern), perinatal depression, and substance-induced mood disorder. Organic causes — hypothyroidism, anaemia, B12 deficiency, obstructive sleep apnoea, dementia — must be excluded before finalising the diagnosis.

B. Psychological therapy — stepped care in practice

The RANZCP 2020 guideline recommends psychological therapy as the primary treatment for mild depression, with watchful waiting and review at four weeks before initiating medication in the mildest presentations.

Effective therapies for MDD

Cognitive behavioural therapy (CBT) has the strongest evidence base. The Cuijpers JAMA Psychiatry 2014 meta-analysis of 52 trials demonstrated that combined pharmacotherapy plus psychological therapy produced substantially better outcomes than either treatment alone for moderate to severe depression. For mild illness, psychological therapy and lifestyle measures produce outcomes comparable to antidepressants with better durability and without medication side effects.

Behavioural activation, interpersonal therapy (IPT), and acceptance and commitment therapy (ACT) are effective alternatives to CBT for MDD. Mindfulness-based cognitive therapy (MBCT) has the strongest evidence specifically for relapse prevention in recurrent depression — the Kuyken Lancet 2016 trial found MBCT comparable to antidepressant maintenance for preventing recurrence in people with three or more prior episodes.

Digital and low-intensity options

Australian-developed digital CBT programs have strong trial evidence. This Way Up Depression and Anxiety programs are accessible at low or no cost and are appropriate as a first step or adjunct to face-to-face therapy. MindSpot is a government-funded, free online CBT clinic that delivers structured therapy by trained clinicians to all Australians.

Exercise as a therapeutic intervention

The Cochrane exercise for depression review demonstrated a moderate effect size, comparable to antidepressants in mild to moderate illness. The recommendation: at least 150 minutes per week of moderate aerobic activity plus two sessions of resistance training weekly. Exercise simultaneously addresses the metabolic risks associated with long-term antidepressant use and is a high-value intervention at all severity levels.

C. Antidepressant pharmacotherapy

When medication is indicated — moderate to severe illness, inadequate response to adequate psychological therapy, recurrent illness, or patient preference — SSRIs are first-line per eTG Psychotropic and the Australian Medicines Handbook.

First-line SSRIs

Most SSRIs have equivalent antidepressant efficacy at therapeutic doses. Selection is guided by side effect profile, comorbidities, drug interactions, and prior treatment history.

Sertraline (starting 50 mg, range 50–200 mg) is the most widely used first choice in Australian general practice. Minimal cytochrome P450 interactions, effective across comorbid anxiety and panic disorder, and a relatively favourable pregnancy safety profile make it the default.

Escitalopram (starting 10 mg, range 10–20 mg) has a clean interaction profile. QT prolongation risk above 20 mg warrants ECG monitoring in patients with cardiac history.

Fluoxetine (starting 20 mg, range 20–80 mg) has the longest half-life of any SSRI — reducing adherence failure risk and making discontinuation syndrome uncommon. First-line for adolescents per TGA guidance.

Mirtazapine (15–45 mg nocte) is useful where insomnia and markedly reduced appetite are prominent; its sedating and appetite-stimulating properties become therapeutic assets. Second-line for typical presentations but valuable in specific contexts.

Venlafaxine XR (75–225 mg daily) — an SNRI, preferred where comorbid chronic pain is prominent. Monitor blood pressure at higher doses. Significant discontinuation syndrome on abrupt cessation; always taper slowly.

Key counselling points before the first prescription

Full antidepressant effect takes four to six weeks, sometimes up to twelve weeks
Initial worsening of anxiety or GI symptoms in the first one to two weeks is common and typically settles
Sexual dysfunction affects 30–50% of patients — discuss this proactively rather than waiting for the patient to raise it
Never stop abruptly — discontinuation syndrome, particularly with paroxetine and venlafaxine, can be severe; taper over four to eight weeks (sometimes longer)
For patients under 25, close monitoring for emergent suicidal ideation in the first two to four weeks is needed — see TGA prescribing information

Duration

Continue at therapeutic dose for at least six to twelve months after achieving remission. At least two years for recurrent illness (two or more prior episodes). Long-term or ongoing maintenance is considered after three or more episodes, with the decision reviewed annually.

Treatment-resistant depression

After two adequate antidepressant trials (therapeutic dose for six to eight weeks each), refer to psychiatry. Options include lithium augmentation, atypical antipsychotic augmentation (quetiapine or aripiprazole — PBS Authority for specific criteria), or switch of antidepressant class. PBS-funded rTMS (repetitive transcranial magnetic stimulation) is available for treatment-resistant depression meeting specific MBS criteria. ECT remains the most effective treatment for severe, psychotic, or refractory depression.

D. Australian operations

Better Access and Mental Health Care Plans

The Mental Health Care Plan (MHCP) provides access to ten individual psychology sessions per calendar year under Better Access. Review at six sessions opens a further ten if criteria are met. For GPs with Focused Psychological Strategies training, items 2721–2727 allow the GP to deliver structured therapy directly and claim Medicare rebates. See MBS Online for current item numbers and conditions.

PBS antidepressant access

All SSRIs (sertraline, escitalopram, citalopram, paroxetine, fluoxetine, fluvoxamine) are PBS General Schedule with no authority required. Venlafaxine, desvenlafaxine, and mirtazapine are General Schedule. Duloxetine requires Authority for major depression indication. Atypical antipsychotic augmentation (quetiapine, aripiprazole) requires Authority under specific treatment-resistant depression criteria. Check PBS Online for current restrictions and streamlined codes.

Head to Health is the federal government’s curated directory of digital mental health programs. It indexes by condition, age group, and severity level and is a practical resource to share with patients at first presentation.

Crisis support

For patients in acute distress: Lifeline 13 11 14, Beyond Blue 1300 22 4636, Suicide Call Back Service 1300 659 467, 13YARN (First Nations) 13 92 76, MensLine 1300 78 99 78. For acute suicide risk with plan or intent: emergency department referral.

E. Special populations

Pregnancy and breastfeeding. Depression in pregnancy is frequently undertreated. Sertraline has the largest Australian pregnancy safety dataset and is generally preferred. Escitalopram and citalopram are acceptable alternatives. Avoid paroxetine in the first trimester (minor cardiac defect signal in some registry data). The Edinburgh Postnatal Depression Scale is the standard screening tool at six weeks postnatal. Untreated depression in pregnancy carries substantial risks for both mother and infant; do not stop an effective antidepressant without specialist input.

Older adults. Start at half the usual adult dose. Check serum sodium at one to two weeks after starting (SIADH risk is elevated in older adults). Avoid tricyclic antidepressants because of falls risk, anticholinergic burden, and cognitive impairment. SSRIs increase GI bleed risk when combined with NSAIDs — consider PPI cover. Conduct a cognitive screen at baseline; depression in older adults can present as apparent cognitive decline that partially reverses with effective antidepressant treatment.

First Nations Australians. Psychological distress rates and suicide rates are substantially higher in First Nations communities. Cultural safety, connection to community, and Country are protective factors. ATSI Health Assessments (MBS item 715) provide a gateway for mental health screening. 13YARN (13 92 76) is a dedicated First Nations crisis support line. Involve Social and Emotional Wellbeing (SEWB) workers where available — their role is distinct from and complementary to clinical mental health care.

Adolescents. Fluoxetine is the preferred SSRI for young people and is TGA-approved from age 8. Start at 10 mg and titrate slowly. Monitor closely for emergent suicidal ideation in the first four weeks (black-box warning). CBT is first-line for mild to moderate adolescent depression; antidepressants are reserved for moderate to severe illness or where CBT has been inadequate.

When to escalate

Escalate urgently when:

Suicidal ideation with plan, intent, or preparation — emergency department and acute mental health team
Psychotic features (delusions or hallucinations) — psychiatric review within days
Postpartum psychosis — psychiatric emergency; mother–baby unit
Severe depression with failure to eat or engage

Escalate routinely when:

Bipolar disorder is suspected — do not start antidepressant monotherapy before psychiatric review
Two adequate antidepressant trials without meaningful response
Complex comorbidities: severe substance use disorder, eating disorder, personality disorder, complex PTSD

What this article is and is not

This is general health information drawn from current Australian clinical guidelines — the RANZCP 2020 Mood Disorders Guideline, Therapeutic Guidelines Psychotropic, AMH, and RACGP mental health resources. It is not personal medical advice and does not create a doctor–patient relationship. Individual management decisions — including whether to start an antidepressant, which one, and for how long — require assessment by the treating GP or specialist.

For Australian consumer information: Beyond Blue, Black Dog Institute, HealthDirect — Depression, Head to Health. For crisis support: Lifeline 13 11 14, Beyond Blue 1300 22 4636.

Sources cited

Frequently asked questions

How is major depressive disorder different from ordinary sadness?

Sadness is a normal emotional response with an identifiable cause and resolves naturally over time. Major depressive disorder is a clinical syndrome requiring five or more symptoms lasting at least two weeks — including either depressed mood or anhedonia — that cause significant impairment in work, relationships, or daily function. Unlike sadness, MDD often persists without a clear external trigger and affects sleep, appetite, concentration, energy, and motivation in ways that compound over time. The PHQ-9 is a validated tool GPs use to assess severity at baseline and track response to treatment.
Does every person with depression need an antidepressant?

No. For mild depression, Australian guidelines recommend psychological therapy and lifestyle measures first, with antidepressants considered only if symptoms persist beyond six to eight weeks of adequate psychological treatment, or if the person has recurrent illness or prior good medication response. For moderate to severe depression, combining an antidepressant with psychological therapy produces better outcomes than either alone. The decision is made through shared discussion about symptom severity, personal preferences, past treatment history, and available supports.
How long does an antidepressant take to work?

Initial improvements in sleep and energy may appear within one to two weeks. Full antidepressant effect on mood, concentration, and motivation typically takes four to six weeks, and sometimes up to twelve weeks for complete response. If there has been no meaningful improvement after six to eight weeks at an adequate dose, the GP will reassess diagnosis, adherence, and whether a medication change is needed. The first one to two weeks may feel difficult as the medication begins — this usually settles with continued use.
How long should antidepressant treatment continue?

The standard recommendation is to continue an effective antidepressant for at least six to twelve months after achieving remission — this is the period with the highest relapse risk. For people with a second episode, at least two years of continuation is recommended. After three or more episodes, long-term or ongoing maintenance is discussed at each review. Stopping too early is one of the most common causes of relapse. When stopping, doses are tapered gradually over four to eight weeks to reduce discontinuation effects.
What safety monitoring is needed when starting an antidepressant in a young person?

Australian guidelines and TGA guidance highlight that people under 25 have a small increased risk of emergent suicidal ideation in the first two to four weeks of antidepressant treatment. This does not mean avoiding antidepressants in young people — untreated depression carries substantially greater risk. It means closer monitoring, ideally weekly contact in the first month, along with a documented safety plan and crisis line information before the prescription is issued. Lifeline 13 11 14 and Beyond Blue 1300 22 4636 should be provided at every initial consultation.

Source quality

Sources grouped by evidence tier. AU primary tier first; international where AU is silent or lagging; named-author reconstruction where guidelines have not yet caught up. How tiers work.

T1 AU primary 14 sources
T2 International primary 1 source
- Cochrane — Exercise for depression (Rimer et al.)
T3 Named-author reconstruction 2 sources
- Cuijpers P et al. — Combined psychological and pharmacological treatment (JAMA Psychiatry 2014)
- Kuyken W et al. — MBCT vs antidepressant maintenance (Lancet 2016)