Updated management of major depressive disorder in adults

1. Initial assessment and safety

• Confirm a major depressive episode and assess severity and functional impairment, preferably with a validated scale such as PHQ-9.
• Assess suicide risk: ideation, intent, plan, access to means, prior attempts, substance use, protective factors, and ability to maintain safety.
• Screen for a present or past manic or hypomanic episode before prescribing antidepressants, because antidepressant-associated persistent mania suggests bipolar disorder.
• Evaluate psychotic symptoms, anxiety, substance use, medical conditions, medications, pregnancy status, and psychosocial stressors.
• Establish previous treatment response, adverse effects, family response, adherence barriers, and patient preferences.

2. First-line treatment

Less severe depression

• Guided self-help and structured psychoeducation
• Exercise and behavioural activation
• Cognitive behavioural therapy (CBT)
• Interpersonal psychotherapy (IPT)
• Mindfulness-based approaches
• Counselling or short-term psychodynamic psychotherapy

Moderate to severe depression

1. Evidence-based psychotherapy, or
2. Antidepressant pharmacotherapy, or
3. Combined psychotherapy plus medication if depression is severe, recurrent, chronic/persistent, or there is an incomplete response to monotherapy.

3. Antidepressant selection

• Explain delayed benefit. Some improvement may occur in 2 to 4 weeks, but a full response often takes longer.
• Discuss early adverse effects, sexual effects, activation, interaction risks, alcohol/substance use, and discontinuation symptoms.
• Warn younger people and carers to seek help promptly if agitation, worsening mood, or suicidal thinking emerges.

4. Follow-up and measurement-based care

• Review within 2 to 4 weeks after starting or changing treatment, sooner if suicide risk is elevated or the patient is young.
• Assess symptoms, functioning, adverse effects, adherence, suicidality, and emerging mania.
• Use the same symptom scale to quantify change.
• Ensure the dose is therapeutic and adherence is adequate before declaring treatment failure.

• Early improvement: continue and optimize.
• Partial response after an adequate trial: optimize dose if tolerated, add psychotherapy, or consider augmentation/switching.
• No response: recheck diagnosis, adherence, substance use, psychosocial drivers, bipolarity, medical causes, and treatment adequacy before switching.

5. Inadequate response and treatment-resistant depression

After one inadequate treatment

• Switch to another antidepressant.
• Switch between medication and psychotherapy.
• Add evidence-based psychotherapy.
• For partial medication response, augment with a second-generation antipsychotic in selected patients, balancing benefit against akathisia, weight gain, metabolic effects, and sedation.
• Consider lithium augmentation in appropriate patients under monitoring.

After two or more adequate medication trials

• Repetitive transcranial magnetic stimulation (rTMS)
• Ketamine or intranasal esketamine as specialist-supervised augmentation in selected treatment-resistant MDD
• Electroconvulsive therapy (ECT)
• Selected use of TCAs or MAOIs, with specialist expertise and safety precautions
• Lithium or antipsychotic augmentation
• Review for psychiatric and medical comorbidity, especially bipolar spectrum disorder, substance use, personality disorder, trauma, sleep disorders, and endocrine disease.

6. When ECT is preferred

• Severe suicidal depression requiring rapid relief
• Psychotic depression
• Catatonia
• Severe nutritional compromise or inability to care for self
• Previous excellent response to ECT
• Failure or intolerance of multiple treatments

7. Continuation and relapse prevention

• Continue the antidepressant at the effective dose for at least 6 months after symptom resolution for a first episode.
• Continue longer, often 2 years or more, for recurrent episodes, persistent symptoms, severe past episodes, high relapse risk, or residual symptoms.
• Offer relapse-prevention psychotherapy, including CBT or mindfulness-based cognitive therapy where appropriate.
• Do not stop antidepressants abruptly. Taper gradually and individualize the pace, particularly with agents associated with more discontinuation symptoms.

8. Key updates in current practice

1. Psychotherapy is not merely adjunctive. It is a first-line option for many people, particularly in less severe depression and when preferred.
2. Combination treatment is targeted, especially for severe, chronic, or recurrent MDD, rather than automatically used for every patient.
3. Measurement-based follow-up improves recognition of nonresponse and supports timely treatment adjustment.
4. rTMS, ketamine/esketamine, and ECT are established advanced-care options, but selection and monitoring should be specialist-led.
5. Safety and bipolar screening must precede and accompany antidepressant treatment.
6. Maintenance treatment and slow tapering are central to preventing relapse and avoiding discontinuation symptoms.

Recent-evidence note