Diagnosis and Management of Depression

Introduction

Depression is a common disorder and 1 in 5 individuals may experience it during their lifetime. It is twice as prevalent in women as in men. It most commonly presents between the ages of 20 and 50 years, but children and older persons also present with mild to severe symptoms. The suicide rate in depression is up to 4 times higher than in any other mental health disorder, and 20–30 times higher than the suicide rate in the general population.

Recognition of severe depression is relatively straightforward, but mild depression can be difficult to identify. It is also challenging to differentiate between a normal emotional reaction to life events — such as social or financial difficulties — and a true depressive illness requiring medical attention.

A thorough initial work-up, as outlined in the Psychiatric History Taking series on this site, will help clinicians to recognise and diagnose almost all cases of depression. If insufficient time is available during the first consultation, arranging a follow-up appointment within a few days ensures that the patient can be assessed and managed carefully rather than rushed.

It is worth remembering that the time invested in the first consultation correlates positively with better outcomes, greater patient compliance with treatment, and higher overall satisfaction.

A brief physical examination and essential haematological and biochemistry investigations not only establish the patient's baseline physical health but also exclude common physical disorders that may present with symptoms of depression. In older patients, always exclude malignancy, diabetes, thyroid disease, and liver and renal dysfunction. A routine PSA in all men aged 50 years or over is good clinical practice.

Sometimes initial symptoms of lethargy, tiredness, inability to cope with daily stressors, lowered mood, disturbed sleep, and changes in appetite or weight may be due to underlying occult physical pathology such as lung or pancreatic malignancy. If a patient does not respond to standard treatment for depression, a thorough re-evaluation of their physical state is strongly advisable.

Diagnosis of Depression

Most psychiatric disorders present with psychological, physical (biological), and behavioural (social) signs and symptoms. Recognising them in these distinct categories helps in understanding the probable aetiological factors and guides management.

Psychological Symptoms

• Low mood lasting at least 14 days, representing a change from previous functioning
• Reduced or absent interest and pleasure in almost all activities (anhedonia)
• Feelings of worthlessness, self-blame, inappropriate guilt, feeling a burden on others, tearfulness, and low self-esteem and confidence
• Difficulty making decisions
• Feeling anxious or worried
• Reduced attention, concentration, and memory
• Suicidal thoughts, such as feeling that life is not worth living or holds no future

Physical (Biological) Symptoms

• Change in appetite and weight (reduced or increased)
• Disturbed sleep pattern (early, middle, or late insomnia; or hypersomnia)
• Reduced energy level and decreased physical activity
• Increased tiredness and fatigue
• Decreased libido
• Agitation and restlessness (psychomotor agitation)
• Psychomotor retardation (slowed movement and speech)
• Increased irritability and anger
• Change in menstrual cycle
• Constipation

Behavioural Symptoms

• Self-neglect
• Social withdrawal and isolation
• Inability to manage household chores and related responsibilities
• Poor performance at work — poor time-keeping and increased absences
• Dropping out from social activities, hobbies, and interests

In clinical practice, mild to moderate depression is characterised by a significant number of psychological symptoms, while severe depression involves many more physical symptoms together with depressive delusions — such as delusions of sin, poverty, malignancy, or infection — and other irrational fears (overvalued ideation).

ICD-10 Diagnostic Criteria

According to ICD-10 (WHO, 1992), the following criteria are applied to differentiate between mild, moderate, and severe depression. All symptoms must be present for a minimum of two weeks and must represent a change from previous functioning.

List A — Core Symptoms (minimum duration: 2 weeks)

• Depressed mood
• Loss of interest and enjoyment (anhedonia)
• Reduced energy level and decreased physical activity (fatigue)

List B — Additional Symptoms

• Reduced concentration and attention
• Reduced self-esteem and confidence
• Ideas of guilt and unworthiness
• Pessimistic thoughts about the future
• Ideas of self-harm or suicide
• Disturbed sleep pattern
• Change in appetite and weight

Mild Depression

• At least 2 symptoms from List A, plus
• At least 2 symptoms from List B

Moderate Depression

• At least 2 symptoms from List A, plus
• At least 3 symptoms from List B

Severe Depression

• All 3 symptoms from List A, plus
• At least 4 symptoms from List B

Important clinical note: In clinical practice, the change in the level of functioning at social, professional, and family levels should remain the guiding principle of severity assessment in addition to the above symptom count. Severe depression may also present with psychotic features (depressive delusions and hallucinations), which requires specialist management.

Validated Rating Scales

Rating scales are valuable for both the patient and the treating clinician, as they help to monitor progress and give insight into the range of symptoms associated with depressive illness. Commonly used scales include:

1. PHQ-9 (Patient Health Questionnaire-9) — widely used in UK primary care; scores 0–27; guides treatment decisions (score ≥10 indicates moderate depression)
2. Hospital Anxiety and Depression Scale (HADS) — Zigmond and Snaith, 1983
3. Beck Depression Inventory (BDI) — Aaron T. Beck, 1961
4. 17-item Hamilton Depression Rating Scale (HAM-D) — M. Hamilton, 1967
5. Pierce Suicide Intent Scale — for use only after a suicide attempt (1977)

Treatment Options

Once the diagnosis of depression has been established, the next step is to decide whether the patient can be treated as an outpatient by a GP or whether referral to specialist services is required. This decision is based on the severity of symptoms, risk assessment, and the views of the patient and their main caregiver.

Patients with severe depression and psychotic features, or where there is risk to themselves or others, should be referred to local mental health services. Such patients typically require inpatient treatment and may occasionally need admission under the Mental Health Act 1983.

Patients with mild to moderate depression are normally managed as outpatients by GPs and/or the community mental health team.

There are four key steps in managing depression in the community:

• Step 1: Diagnosis and investigations
• Step 2: Briefing and involvement of key family members or the patient's partner
• Step 3: Non-pharmacological treatment
• Step 4: Pharmacological treatment

Step 1 — Diagnosis and Investigations

The first consultation should include:

• An explanation to the patient of why you believe they may be suffering from depression
• Discussion of likely aetiological factors — genetic, biological, social, and psychological
• Explanation of the investigations to be carried out and why. In keeping with the patient's age and clinical symptoms, consider: full blood count, urea and electrolytes, liver function tests, thyroid function tests, blood glucose, PSA (in men aged 50 or over), chest X-ray, ECG, and CT brain scan where indicated

The first consultation should end with the patient feeling reassured and better informed. The patient should also be encouraged to bring their key caregiver or partner to the next consultation.

Step 2 — Involving Family and Completing Assessment

The second consultation should include:

• Gathering additional information from key family members or the patient's partner
• Informing the patient of the results of their investigations
• Carrying out a brief physical examination if not already done
• Completing depression questionnaires such as the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS)
• Asking the key caregiver or partner to complete the questionnaires about the patient's condition — this can improve the family member's understanding and empathy, and forms the natural beginning of Interpersonal Psychotherapy (IPT)

The theory of IPT is based on the principle that the symptoms of depression result from relationship difficulties, and that resolving these difficulties — as well as improving the patient's attitudes towards themselves and others — will improve most symptoms of mild to moderate severity.

By this stage, the clinical diagnosis and its severity should be established, physical pathology excluded, and a therapeutic alliance built with the patient and their caregiver.

Step 3 — Non-Pharmacological Treatment

Non-pharmacological treatment options should be actively offered and include:

• Physical activity (30 minutes of brisk walking daily — sufficient to cause mild perspiration, which stimulates endorphin release)
• Balanced nutrition and healthy lifestyle
• Sleep hygiene advice and improving sleep patterns
• Reducing and modifying stressors
• De-stressing activities — relaxation, yoga, meditation, breathing exercises, swimming
• Supportive, cognitive, interpersonal, and marital psychotherapy
• Advice and support in managing young children
• Advice and support with household and financial matters
• Cognitive Behavioural Therapy (CBT) — NICE first-line recommendation for mild to moderate depression
• Interpersonal Therapy (IPT) — particularly effective for depression arising from relationship difficulties

Step 4 — Pharmacological Treatment

Before prescribing any medication, inform the patient of:

• Which antidepressant is being prescribed, and why
• How long it will take for symptoms to improve (typically 2–4 weeks for initial effects; full effect may take 4–6 weeks)
• What side effects may occur and what to do if they arise
• That antidepressants are not addictive, but should not be stopped abruptly

The British National Formulary lists antidepressants under four broad categories:

Tricyclic Antidepressants (TCAs)

These are one of the oldest classes. Although effective, their use has declined because of their side-effect profile and significant toxicity in overdose. They are not recommended as first-line treatment. Examples include: amitriptyline, clomipramine, dosulepin (dothiepin), doxepin, imipramine, lofepramine, nortriptyline, trimipramine. Related antidepressants: mianserin, trazodone.

Monoamine Oxidase Inhibitors (MAOIs)

Rarely used as first-line agents due to dietary restrictions (tyramine-free diet required) and drug interactions. Examples: phenelzine, isocarboxazid, tranylcypromine. Reversible MAOI: moclobemide.

Selective Serotonin Reuptake Inhibitors (SSRIs) — First-Line Treatment

SSRIs are the recommended first-line antidepressants in NICE CG90 for all severities of depression in adults. They are safer in overdose, have a more tolerable side-effect profile, and are effective across a range of presentations. Examples include: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.

NICE recommends sertraline or fluoxetine as preferred first-line SSRIs, based on their efficacy, tolerability, and cost-effectiveness data (Cipriani et al., 2018).

Other Antidepressants (SNRIs, NaSSAs, and Others)

• Duloxetine (SNRI) — 5 times more potent at inhibiting serotonin reuptake than noradrenaline reuptake; does not carry the cardiac side effects of venlafaxine; useful in depression with significant lethargy, low energy, and low motivation; dose 30–60 mg daily
• Venlafaxine (SNRI) — effective but requires monitoring of blood pressure and ECG; useful in treatment-resistant cases
• Mirtazapine (NaSSA) — noradrenergic and specific serotonergic antidepressant; particularly useful when poor sleep is a dominant symptom; dose 15–45 mg nocte; watch for weight gain, excessive sedation, and rarely agranulocytosis
• Reboxetine — selective noradrenaline reuptake inhibitor
• Flupenthixol (low dose) — occasionally used in mild depression with anxiety

Prescribing Decision Framework

Before writing a prescription, ask the following questions:

1. Can the patient be managed with non-pharmacological methods alone? (Consider for mild depression)
2. Is the patient safe to be treated as an outpatient? (Mild to moderate depression without active suicidal intent and with good social support)
3. Does the patient require referral to community mental health or inpatient services? (Severe depression with active suicidal intent, psychotic symptoms, bipolar disorder, co-existing substance misuse or schizophrenia, or poor social support)

The choice of antidepressant should be guided by:

• Previous response to a particular antidepressant
• Family history of response to a particular antidepressant
• Patient preference
• Safety in overdose
• Interaction with other prescribed medications
• Most troublesome current symptoms (e.g. sleep problems favour mirtazapine; anxiety and panic attacks favour SSRIs or escitalopram)

Suggested Management for Mild Depression

• Physical activity — 30 minutes daily, e.g. brisk walking to the point of mild perspiration (stimulates endorphin release)
• Balanced nutrition — reduce alcohol and smoking; eat plenty of fruit, vegetables, fish, and lean protein; consider referral to a nutritionist
• Organise practical help with children at home; minimise stressors such as housing and financial issues
• Supportive and marital psychotherapy, via a practice-based counsellor or NHS psychology services
• Relaxation techniques — yoga, meditation, breathing exercises, acupuncture, swimming
• Signpost to Department of Housing and Social Services for accommodation and financial support
• Consider whether return to work is beneficial (social contact often helps)
• Review weekly — within 3–4 weeks most patients show signs of improvement
• If sleep is a significant problem, consider a short course of zopiclone 3.75 mg or temazepam 10 mg nocte
• If no improvement after 4–6 weeks, consider starting a low-dose SSRI (e.g. sertraline 50 mg or citalopram 10 mg daily, increasing to 20 mg after 3–4 days)
• Continue the antidepressant for a minimum of 6 months after achieving full remission in a first episode (NICE CG90)

Suggested Management for Moderate Depression

• Start an antidepressant as first-line treatment alongside non-pharmacological interventions
• Sertraline 50 mg daily (first-line per NICE) or citalopram 10 mg daily increasing to 20 mg after 3–4 days
• Add night sedation if required (zopiclone 3.75 mg or temazepam 10 mg nocte)
• If restlessness or agitation is prominent, consider a low-dose antipsychotic such as quetiapine 25 mg nocte or risperidone 0.5–1.0 mg nocte
• Improvement is typically first noticed in sleep, anxiety, and energy levels within 2–3 weeks; mood, motivation, and confidence improve thereafter
• Continue the antidepressant for 6–12 months after full recovery; withdraw gradually over 3–6 months thereafter

If there is no response after 6 weeks:

• Review the diagnosis
• Check compliance with medication
• Exclude concurrent physical or psychiatric disorders
• If there is partial response, increase the dose (e.g. citalopram from 20 mg to 30 mg, then 40 mg)
• Re-evaluate environmental stressors and ensure relationship issues are being addressed
• If still no response after a further 3 weeks, consider switching to a different antidepressant

Switching Antidepressants

Fluoxetine

Consider if the patient also has symptoms of bulimia or obsessive compulsive disorder. Dose: 20 mg daily, increasing to 40–60 mg daily over 4–6 weeks.

Escitalopram

Consider if generalised anxiety disorder or social phobia with or without panic attacks is a prominent feature. Dose: 5–20 mg daily.

Mirtazapine

Consider if poor sleep pattern is the dominant symptom. Dose: 15 mg nocte, increasing gradually to a maximum of 45 mg nocte. Watch for: weight gain, excessive daytime sedation, oedema; rarely — headaches, dizziness, arthralgia, akathisia, rash, and reversible agranulocytosis.

Duloxetine

Consider if lethargy, low energy, lack of motivation, and social withdrawal are prominent. Classified as a serotonin and noradrenaline reuptake inhibitor (SNRI), similar to venlafaxine but without serious cardiac side effects. Does not cause sexual dysfunction to the same degree as SSRIs. Dose: 30 mg nocte, increasing to 60 mg nocte. Watch for: nausea, vomiting, dyspepsia, diarrhoea, insomnia, headaches, and dizziness.

A combination of citalopram 10–20 mg in the morning and mirtazapine 15–30 mg at night may be considered if the patient has initially responded to citalopram but is troubled by major sleep disorders. If there is no response to at least two different antidepressants, the patient should be referred to local mental health services.

Treatment of severe depression with active suicidal intent and psychotic features must be managed by a specialist team, typically as an inpatient.