Definition & Key Features

What is Depression in adults? Depression is a mental health condition characterised by a persistent low mood and/or a loss of interest and enjoyment in everyday activities (anhedonia). This is accompanied by a range of associated emotional, cognitive, physical, and behavioural symptoms that cause significant distress or impairment in social, occupational, or other important areas of functioning. The NICE guideline categorises new episodes of depression based on severity:

• Less Severe Depression: Encompasses subthreshold and mild depression. Corresponds to a Patient Health Questionnaire-9 (PHQ-9) score of less than 16.
• More Severe Depression: Encompasses moderate and severe depression. Corresponds to a PHQ-9 score of 16 or more.

Hallmark Features & Typical Signs/Symptoms Based on ICD-11/DSM-5 criteria, a diagnosis requires the presence of core symptoms for at least 2 weeks, nearly every day:

• Core Symptoms:
  • Depressed mood.
  • Loss of interest or pleasure (anhedonia).
• Associated Symptoms:
  • Reduced concentration, attention, or marked indecisiveness.
  • Beliefs of low self-worth or excessive/inappropriate guilt.
  • Hopelessness about the future.
  • Recurrent thoughts of death, suicidal ideation, or suicide attempts.
  • Disrupted sleep (insomnia or hypersomnia).
  • Significant change in appetite or weight.
  • Psychomotor agitation or retardation.
  • Reduced energy, fatigue, or decreased efficiency.

Important Complications if Untreated

• Significant impairment in personal and social functioning.
• Increased risk of self-harm and suicide.
• Development of chronic depressive symptoms.
• Loss of employment and social withdrawal.
• Worsening of co-existing chronic physical health problems.

Epidemiology & Risk Factors

Who is most affected? Depression can affect anyone, but certain factors increase risk and likelihood of relapse.

• Prevalence: While specific numbers are not given, depression is noted as common, particularly in those with chronic physical health problems. Anxiety symptoms frequently co-exist with depression, especially in older adults.
• Age/Gender Patterns:
  • Young Adults (18-25): At higher risk of suicidal ideation in the initial stages of antidepressant treatment.
  • Older Adults: At increased risk of falls, fractures, and hyponatraemia when taking antidepressants.
  • Men: Identified as a group that may have difficulty accessing mental health services.
• Non-Modifiable Risk Factors:
  • Past personal history of depression.
  • Family history is implied but not explicitly stated as a risk factor.
• Modifiable and Other Risk Factors:
  • Chronic physical health problems (e.g., diabetes, heart disease).
  • Co-existing mental health disorders (e.g., anxiety).
  • Past or recent stressful/traumatic life events (e.g., bereavement, divorce, redundancy).
  • Ongoing interpersonal relationship difficulties.
  • Loneliness and social isolation.
  • Difficult living conditions, debt, and unemployment.
  • Lifestyle factors: poor diet, lack of physical activity, poor sleep.
  • Drug (illicit or prescribed) and alcohol use.

Clinical Presentation & Diagnosis

Typical Symptoms & Initial Identification

• Be alert to possible depression, especially in high-risk individuals.
• Initial Screening Questions:
  1. “During the last month, have you often been bothered by feeling down, depressed or hopeless?”
  2. “During the last month, have you often been bothered by having little interest or pleasure in doing things?”
• A ‘yes’ to either question warrants a comprehensive mental health assessment.

Red Flags (Indications for Urgent Referral or Action)

• Urgent Referral to Specialist Mental Health Services (including Crisis Team):
  • If a person presents a considerable immediate risk to themselves or others.
  • Presence of psychotic symptoms (hallucinations, delusions).
  • Severe self-neglect (e.g., patient is not eating or drinking), which makes the depression life-threatening.

Diagnostic Criteria

• Diagnosis relies on a comprehensive clinical assessment, not just a symptom count. This includes assessing symptom severity, duration, functional impairment, and previous history.
• Severity Definition:
  • Less Severe: PHQ-9 score < 16.
  • More Severe: PHQ-9 score ≥ 16.
• Use a validated measure (e.g., PHQ-9) to inform assessment and monitor treatment response.

Differential Diagnoses

• Bipolar Disorder: Always assess for any history of mood elevation (hypomania/mania) to exclude bipolar disorder.
• Anxiety Disorders: If an anxiety disorder is the primary problem with comorbid depressive symptoms, treat the anxiety disorder first. If depression is primary, treat that first.
• Physical Health Conditions: Consider underlying physical causes for symptoms.
• Acquired Cognitive Impairments: Be aware of these as they can mimic or coexist with depression.

Investigations

• No routine diagnostic blood tests or imaging are recommended for depression itself.
• Pre-treatment investigations are required for specific medications:
  • Lithium: Assess weight, renal function (U&Es), thyroid function (TFTs), and calcium levels before starting. Consider an ECG in those with cardiovascular risk.
  • Antipsychotics: Check baseline pulse, blood pressure, weight, fasting blood glucose/HbA1c, and fasting lipids before starting.

Initial Management

Treatment choice should be a shared decision, respecting the patient’s preferences. The least intrusive, most resource-efficient option appropriate for the clinical need should be offered first.

Initial Management: New Episode of LESS SEVERE Depression (PHQ-9 < 16)

• First-line Approach: Antidepressant medication is NOT a routine first-line treatment, unless it is the patient’s preference. The recommended first step is a low-intensity psychological intervention.
• Treatment Options (in order of preference):
  • Guided Self-Help: Based on CBT, BA, or problem-solving principles. Delivered via printed/digital materials with support from a practitioner over 6-8 sessions.
  • Group Cognitive Behavioural Therapy (CBT): Typically 8 regular sessions.
  • Group Behavioural Activation (BA): Typically 8 regular sessions.
  • Individual CBT or Individual BA: Typically 8 regular sessions.
  • Group Exercise: A structured physical activity programme designed for depression, typically >1 session per week for 10 weeks.
  • Group Mindfulness and Meditation: Typically 8 regular sessions.
  • Interpersonal Psychotherapy (IPT): Typically 8-16 regular sessions.
  • Selective Serotonin Reuptake Inhibitors (SSRIs): An option if preferred by the patient.
  • Counselling for Depression: Typically 8 regular sessions.
  • Short-Term Psychodynamic Psychotherapy (STPP): Typically 8-16 regular sessions.

Initial Management: New Episode of MORE SEVERE Depression (PHQ-9 ≥ 16)

• First-line Approach: Patients should be offered a choice from the following evidence-based treatments.
• Treatment Options (in order of preference):
  • Combination Therapy: Individual CBT (typically 16 sessions) and an antidepressant. This is the top recommendation.
  • Individual CBT: Typically 16 sessions.
  • Individual Behavioural Activation (BA): Typically 12-16 sessions.
  • Antidepressant Medication: An SSRI, SNRI, or other antidepressant based on history and preference.
  • Other Psychological Therapies: Individual Problem-Solving Therapy, Counselling, STPP, IPT.
  • Lower-intensity options (Guided Self-Help, Group Exercise) are less preferred for more severe depression but remain an option.

Pharmacological Measures (When an Antidepressant is Chosen)

• Drug Choice:
  • First-line: A Selective Serotonin Reuptake Inhibitor (SSRI) is generally the first choice due to good tolerability and safety.
  • Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs) are also an option.
  • Tricyclic Antidepressants (TCAs) are generally not used first-line (except lofepramine) due to toxicity in overdose.
• Dosage & Formulation: Start at a standard therapeutic dose as per the British National Formulary (BNF). Liquid preparations may be considered for slow tapering when stopping.
• Duration: Continue for at least 6 months after remission of symptoms to prevent relapse.
• Route & Frequency: Oral, once daily for most SSRIs/SNRIs.
• Major Side Effects: Discuss common side effects (e.g., gastrointestinal upset, effects on sexual function, sedation, weight gain) and withdrawal effects.
• Contraindications & Cautions:
  • Suicide Risk: Be aware of a potential increased risk of suicidal thoughts and self-harm in the early stages, especially in adults aged 18-25. Do not prescribe TCAs (except lofepramine) to patients at high risk of suicide.
  • St. John’s Wort: Do not prescribe or advise its use due to variable potency and serious drug interactions (e.g., with hormonal contraceptives, anticoagulants).
  • Older Adults: Increased risk of falls, fractures, and hyponatraemia (especially with diuretics).

Non-Pharmacological Measures & Patient Education

• Patient Education: Provide verbal and written information about depression, treatment options (benefits and harms), side effects, and withdrawal symptoms. Discuss the expected time to see an effect (usually within 4 weeks for antidepressants).
• Active Monitoring: For patients with less severe depression who decline initial treatment, arrange a follow-up assessment within 2-4 weeks.
• Lifestyle Advice: Advise on the benefits of regular physical activity (especially outdoors), a healthy diet, good sleep hygiene, and avoiding excessive alcohol.

Initial Monitoring Parameters

• All Treatments: Review progress between 2 and 4 weeks after starting.
• Antidepressants:
  • Review within 2 weeks of starting.
  • Urgent Review (within 1 week): For patients aged 18-25 or those at increased risk of suicide.
• Monitoring should assess:
  • Symptom improvement (using a validated scale like PHQ-9).
  • Side effects and harms.
  • Treatment concordance.
  • Suicidal ideation (ask directly at each review).

Further Management & Escalation

If First-Line Treatment Fails (or is Contraindicated) Review the diagnosis, adherence, and any unresolved psychosocial factors.

• If Psychological Therapy Fails:
  • Switch to an alternative psychological treatment (e.g., from CBT to IPT).
  • Add an SSRI to the current psychological therapy.
  • Switch to an SSRI alone.
• If Antidepressant Fails (after 4 weeks at a therapeutic dose):
  • Increase the dose of the current antidepressant (if well-tolerated).
  • Switch to another antidepressant in the same class (e.g., another SSRI).
  • Switch to an antidepressant in a different class (e.g., from an SSRI to an SNRI or mirtazapine). Switching to or from a Monoamine Oxidase Inhibitor (MAOI) requires specialist advice.
  • Add a psychological therapy (e.g., CBT, IPT).
• If Combination Therapy Fails:
  • Switch to another psychological therapy.
  • Change the antidepressant (increase dose or switch).
  • Consider adding another medication (augmentation).

Second-Line & Specialist Interventions These options often require referral to, or advice from, specialist mental health services.

• Second-Line Medications:
  • Vortioxetine: An option after failure of at least two other antidepressants.
  • Augmentation: Adding a second drug to an antidepressant:
    • Another antidepressant (e.g., mirtazapine or trazodone added to an SSRI).
    • A second-generation antipsychotic (e.g., aripiprazole, olanzapine, quetiapine, risperidone).
    • Lithium.
• Specialist Referral for:
  • More severe or chronic depression with significant functional impairment and complicating problems (e.g., co-existing conditions, unemployment, housing issues).
  • Psychotic depression.
  • Depression with a co-existing personality disorder.
  • Consideration of complex medication regimens (e.g., MAOIs, augmentation).
• Electroconvulsive Therapy (ECT): Consider for severe depression when:
  • A rapid response is needed (e.g., life-threatening self-neglect).
  • Other treatments have failed.
  • It is the patient’s preference based on past positive experience.
• Psychotic Depression: Refer to specialist mental health services. Treatment is typically a combination of an antidepressant and an antipsychotic.

Surgical Options

• Implanted Vagus Nerve Stimulation: May be considered for treatment-resistant depression under specialist guidance.

Follow-up & Safety Netting

Frequency of Follow-up Visits

• Starting any treatment: Review within 2-4 weeks.
• Starting antidepressants: Review within 2 weeks (1 week for under-25s or high suicide risk).
• Continuing antidepressants for relapse prevention: Review at least every 6 months.
• Lithium: Monitor levels weekly after starting/dose change until stable, then every 3 months for the first year, then every 6 months (or 3-monthly for high-risk groups).
• Antipsychotics: Monitor weight weekly for the first 6 weeks, then at 12 weeks and annually. Monitor blood glucose and lipids at 12 weeks and annually.

Monitoring Requirements

• General: Use a validated scale (e.g., PHQ-9) to track symptoms. Monitor for side effects and suicidal ideation.
• Lithium: Monitor renal function, thyroid function, calcium, and serum lithium levels (target 0.4-1.0 mmol/L, consider 0.4-0.6 mmol/L for older adults).
• Antipsychotics: Monitor weight, blood pressure, fasting glucose/HbA1c, lipids, and for extrapyramidal side effects.

Patient Advice on Self-Management & Health Promotion

• Stopping Antidepressants:
  • Advise patients never to stop abruptly.
  • The dose must be tapered slowly in stages over weeks or months, guided by the patient’s withdrawal symptoms.
  • Explain withdrawal symptoms (e.g., dizziness, “electric shock” sensations, anxiety, sleep problems) and reassure them this is not a relapse. Paroxetine and venlafaxine are associated with more withdrawal symptoms.
• Relapse Prevention: Discuss continuing treatment (medication or psychological therapy) for at least 6 months post-remission, especially for those at high risk of relapse. Provide relapse prevention skills (e.g., identifying triggers and warning signs).
• Lifestyle: Encourage ongoing physical activity, a healthy diet, and good sleep hygiene.

Warning Signs Prompting Urgent Reassessment

• Advise the patient and their family/carers to seek help promptly if they notice:
  • Marked or prolonged agitation or anxiety.
  • Worsening mood, negativity, or hopelessness.
  • The emergence or worsening of suicidal ideation.
• These are particularly important during high-risk periods like starting or changing treatment.

Key Points to Remember

• Categorise Severity: Use the PHQ-9 to distinguish between less severe (<16) and more severe (≥16) depression to guide initial treatment choice.
• Matched Care is Key: Treatment must be a shared decision. For less severe depression, the first-line choice is a low-intensity psychological intervention (e.g., guided self-help); antidepressants are a second-line option unless preferred by the patient.
• More Severe Depression: The top recommendation is combination therapy (Individual CBT + antidepressant). Antidepressants or high-intensity psychological therapy alone are also first-line options.
• Antidepressant Choice & Duration: SSRIs are the first-line drug class. Continue treatment for at least 6 months after remission.
• Assess Suicide Risk: Always ask directly about suicide. Risk is increased in the first weeks of antidepressant treatment, especially in those aged 18-25, who require a follow-up review within 1 week.
• Stopping Antidepressants: Always taper the dose slowly over weeks or months to minimise withdrawal symptoms. Never stop abruptly.
• Red Flags for Urgent Referral: Immediate risk to self/others, psychotic symptoms, or severe self-neglect (not eating/drinking).
• Monitor Specific Drugs: Lithium and antipsychotics require specific baseline and ongoing physical health monitoring (bloods, weight, BP, etc.).
• TCAs are Toxic: Avoid Tricyclic Antidepressants (except lofepramine) in patients at risk of suicide due to high toxicity in overdose.
• Educate the Patient: Provide clear information on the condition, treatment options, side effects, and the importance of a withdrawal plan for medication.

This MedDigest summary is intended for educational purposes only and should not be used for clinical purposes. It is an independent resource, prepared by MedDigest, to offer an accessible overview of information drawn from the NICE guidelines. While MedDigest strives for accuracy in its educational summaries, this content has not been reviewed or produced by NICE. For comprehensive and definitive recommendations, please always refer to the complete NICE guidelines.

References

NICE (2022) Depression in adults: treatment and management. https://www.nice.org.uk/guidance/ng222