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Depression

NICE guideline Depression in adults: treatment and management. Published: Jun 2022.

NICE CKS Depression. Last revised: Apr 2025.

Depression

General Psychiatry Article Disclaimer

  • DSM-5 criteria or ICD-11 diagnostic requirements are used to structure the Clinical Features and Diagnosis section. The classification system used is selected according to its clarity and suitability for non-specialist learning.
  • The criteria are summarised and simplified rather than reproduced in full, while preserving their original diagnostic meaning.
  • Where appropriate, a student-friendly pattern-recognition summary is provided to highlight the most clinically and exam-relevant features.

Exam tip (re-psychiatry questions)

  • Do not attempt to memorise every DSM-5 or ICD-11 criterion word-for-word. However, it is important to read through the criteria and become familiar with the key symptom clusters, duration thresholds, exclusions, and distinguishing features highlighted in this article.
  • Exam questions may not provide every feature required to meet the full diagnostic criteria. Familiarity with the criteria can help one recognise the most likely diagnosis, exclude important alternatives, and narrow the differential diagnosis.

Pathophysiology

Neurotransmitter abnormalities: [Ref]

  • Primarily, deficiency in monoamine neurotransmitters (e.g. serotonin, noradrenaline, dopamine)
  • Lower levels of GABA (inhibitory neurotransmitter) and glutamate / glycine (excitatory neurotransmitter) are also known to play a role

Other contributing mechanisms: [Ref]

  • Disturbances in more complex neuroregulatory systems and neural circuits
  • Structural and functional brain changes
    • Functional brain imaging often shows increased hyperintensities in subcortical regions and reduced anterior brain metabolism on the left side
  • Genetic susceptibility

Causes and Risk Factors

The underlying cause of depression is unknown, likely due to a complex interaction of genetic, environmental, biological, cultural, and psychological factors.

Risk factors for developing depression
  • Females
  • Older age
  • History of depression
  • Personal, social or environmental factors (e.g. relationship issues or breakdown, bereavement, stress, poverty, unemployment, homelessness, social isolation, history of child maltreatment)
  • Postpartum period (→ postpartum depression)
  • Family history of depression or suicide
  • History of other mental health conditions and/or substance misuse
  • Presence of chronic physical health conditions associated with functional impairment (e.g. diabetes, COPD, cardiovascular disease, chronic pain syndrome, epilepsy, stroke)
Risk factors for depression relapse
  • Older age of onset
  • Previous recurrent depression
  • Incomplete response to previous treatment
  • Unhelpful coping styles or behaviours (e.g. avoidance, rumination)
  • History of severe depression
  • Presence of other chronic or mental health conditions (esp. in the elderly)
  • Ongoing personal, social, or environmental factors

Important organic causes of depressive symptoms: [Ref]

  • Endocrine disorders
    • Hypothyroidism
    • Cushing’s syndrome
    • Addison’s disease
  • Haematological / nutritional
    • Anaemia
    • Vitamin B12 or folate deficiency
  • OSA
  • SLE
  • Infections (e.g. HIV, viral hepatitis)
  • Systemic causes (e.g. chronic pain, malignancy, liver disease)

Recognition and Assessment

NICE recommends asking the following 2 questions to screen for potential depression (depression identification questions – which screen for the 2 core symptoms of depression):

  • During the last month, have they often been bothered by feeling down, depressed or hopeless?
  • During the last month, have they often been bothered by having little interest or pleasure in doing things?

If the patient answers “yes” to EITHER of the above →

  • Perform a mental health assessment (mental state examination)
  • Assess for associated functional, interpersonal and social difficulties
  • Consider using a validated questionnaire (e.g. PHQ-9 – which is used to guide management)

Clinical Features and Diagnosis

High-yield pattern recognition for depression:

  • 2 core symptoms
    • Low mood
    • Anhedonia (loss of interest or pleasure in activities)
  • Other features (SEA CPG)
    • Sleep disturbances (insomnia or hypersomnia)
    • Energy level low (fatigue)
    • Appetite change / weight loss
    • Concentration impairment
    • Psychomotor agitation / retardation
    • Guilt and sense of worthlessness
  • Thoughts of death / suicidal ideation / suicide attempts

This is useful for learning the high-yield clinical features of depression and what to ask during an OSCE (or history taking for depression), as it maps onto the PHQ-9 domains.

To diagnose depression as per the DSM-5 criteria: ALL the following must be met: [Ref]

Diagnostic criteria Description
Presence of symptoms Overall, there must be at least 5 out of 9 of the following symptoms

  • At least 1 of the 2 core symptoms
    • Depressed mood
    • Anhedonia (markedly diminished interest or pleasure in activities)
  • Other symptoms
    • Weight or appetite changes
    • Insomnia or hypersomnia
    • Psychomotor agitation / retardation
    • Fatigue or loss of energy
    • Worthlessness or guilt
    • Impaired concentration
    • Recurrent thoughts of death
Symptom duration / timing Symptoms must occur during the same 2-week period
Functional impairment Symptoms must cause clinically significant distress or impairment (social, occupational or other important area of functioning)
Exclusion Symptoms not attributable to substance use or another medical condition

There has never been a manic or hypomanic episode (i.e. not bipolar disorder)

Complications

  • Impact on personal and social functioning (e.g. work, school, relationships, quality of life)
  • Potential increased risk of medical complications, functional impairment, and poorer prognosis of any coexisting physical and mental health conditions
  • Increased risk of associated alcohol and substance misuse
  • Increased risk of morbidity and mortality (due to self-harm, self-neglect, and suicide)

Depression Severity

NICE stratifies the management of a new depressive episode according to whether it is less severe or more severe depression, using a PHQ-9 score of 16 as the indicative cut-off:

  • PHQ-9 <16: less severe depression
  • PHQ-9 ≥16: more severe depression

The PHQ-9 assesses the frequency of nine core depressive symptoms over the preceding 2 weeks, with a total score from 0–27. Clinical judgement and the degree of functional impairment should also be considered; management should not be based on the score alone.

Key clinical determinants of a severe depressive episode: [Ref]

  • Symptoms are pronounced, persistent and difficult to relieve
  • Marked functional impairment (disruption of personal, social, educational or occupational functioning)
  • High-risk clinical features, particularly:
    • Suicidal thoughts, intent, plans or recent attempts
    • Severe hopelessness or guilt
    • Marked psychomotor retardation or agitation
    • Self-neglect (e.g. reducing eating or drinking)
    • Psychotic symptoms (e.g. mood-congruent delusions or hallucinations)

Management

Management disclaimer

NICE guidance on the management of depression is not intended as a rigid treatment algorithm. Recommendations are deliberately flexible, with treatment selected on a case-by-case basis according to depression severity, clinical needs, suicide risk, comorbidities, previous treatment response and patient preferences.

Key overriding concepts:

  • If the patient presents with immediate risk to themselves or othersrefer urgently to specialist mental health services
  • When depression is accompanied by symptoms of anxiety (which is particularly common in older people), the first priority should usually be to treat the depression

Less Severe Depression (PHQ-9 <16)

Management depends on the patient’s preference for treatment

Patient’s preference Recommended management
Patient does NOT wish to receive treatment Active monitoring, with the option to consider treatment at any time if needed
Patient wishes to receive treatment 1st line: guided self-help

If the patient prefers antidepressant therapy: offer antidepressants

  • 1st line: SSRIs

Other treatment options to consider (in descending order of appropriateness)

  • Group CBT
  • Group behavioural activation
  • Individual CBT
  • Individual behavioural activation
  • Group exercise
  • Group mindfulness and meditation
  • Interpersonal psychotherapy
  • SSRIs
  • Counselling
  • Short-term psychodynamic psychotherapy

In contrast to ‘more severe’ depression, antidepressants are NOT routinely given 1st line for ‘less severe’ depression.

More Severe Depression (PHQ-9 ≥16)

1st line:

  • CBT PLUS
  • Antidepressant (1st line: SSRI or SNRI)

Note that antidepressants usually take 4 weeks to start working

Follow-Up / Initial Review

All patients require initial review after 2-4 weeks (irrespective of management plan/depression severity)

An earlier initial review, after 1 week of starting antidepressant therapy should be arranged in:

  • All 18-25 y/o patients, OR
  • If there are particular concerns about risk of suicide

Antidepressants, particularly SSRIs, are associated with a small but significant increased risk of new-onset suicidal ideation and behaviour, particularly in the 18-25 y/o age group (thus warranting the earlier initial review).

Duration of Antidepressant Therapy 

Antidepressants are typically continued for at least 6 months after symptom resolution before gradual discontinuation is considered, to reduce the risk of relapse.

Further Treatment

Consider switching antidepressants to any of the following classes:

  • SSRI
  • SNRI
  • TCA (only in secondary care)
  • MAO-I (only in secondary care)

Consider combination treatment by adding:

  • Another antidepressant class – mirtazapine, or trazodone
  • 2nd generation antipsychotic (e.g. olanzapine, aripiprazole, quetiapine)
  • Lithium

Vortioxetine is recommended as an option if no or limited response to 2 antidepressants

Consider electroconvulsive therapy if:

  • Patient preference
  • Rapid response is needed (e.g. life-threatening depression due to refusal to eat or drink)
  • Other treatments have been unsuccessful

Switching antidepressants: [Ref]

Most antidepressants can be switched directly (with no cross-tapering or drug-free period needed):

  • SSRI (caution with fluoxetine – see below) → other SSRI OR SNRI
  • SNRI → SSRI OR other SNRI
  • TCA ↔ other TCA

Exceptions / Cautions (to prevent interactions & serotonin syndrome)

  • Fluoxetine → any SSRI/SNRI/TCA
    • Gradually taper down & discontinue fluoxetine → 4-7 days drug-free period → start new antidepressant (from low dose).
  • SSRI/SNRI ↔ TCA
    • Cross-taper: taper the initial antidepressant down whilst simultaneously starting a low dose of the new antidepressant (slowly uptitrated); works vice-versa
    • No need for a drug-free period
    • Further detail: fluvoxamine/paroxetine, clomipramine 
  • SSRI/SNRI/TCA ↔ irreversible MOA inhibitors
    • Gradually taper down & discontinue initial antidepressant → ≥ 2 weeks drug-free period (5 weeks after fluoxetine) → then start new antidepressant; works vice-versa

References


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