Depression
A clinically diagnosed disorder of mood, interest, cognition, energy and function in which severity, suicide risk, bipolar history and patient preference determine the treatment pathway.
Definition
Depression is a mental-health disorder characterised by persistent low mood and/or loss of interest or pleasure with associated cognitive, physical and behavioural symptoms that cause distress or functional impairment.
Epidemiology
Depression is common and may occur at any age. Risk is increased by previous episodes, chronic physical illness, adversity, family history, substance use and social stressors; recurrence and suicide risk vary widely between individuals.
Pathophysiology
Depression reflects interacting biological, psychological and social processes rather than a single neurotransmitter lesion. Genetic vulnerability, stress systems, sleep and circadian disturbance, altered cognition, neuroplasticity and inflammatory or physical-health factors may all contribute, while psychological treatments target maintaining patterns such as avoidance and rumination.
First principles
Depression is more than sadness
A depressive episode may affect mood, interest or pleasure, energy, sleep, appetite, concentration, psychomotor function, self-worth and hope. Ask how symptoms have changed function and relationships, not only whether the person feels sad.1,2
Severity is a treatment guide, not a questionnaire label
NICE groups new episodes as less severe or more severe, broadly corresponding to subthreshold or mild versus moderate or severe depression. A validated measure such as PHQ-9 can support outcome monitoring, but clinical judgement, functional impairment, comorbidity, risk and preference remain essential.1
Always test the depressive formulation
Before treating unipolar depression, ask about past or current mania or hypomania, psychosis, substance use, medication effects, physical illness, trauma, anxiety and neurodevelopmental or cognitive problems. A history of mania or hypomania changes the diagnosis and makes antidepressant monotherapy unsafe to assume.1,3
Suicide risk is dynamic and requires a plan
Ask directly about thoughts of death, suicidal thoughts, intent, plans, access to means, previous attempts or self-harm, current stressors, protective factors and available support. Do not reduce this to a numerical score: the response should be an individualised safety and treatment plan with appropriate urgency.1,4
Treatment is shared and stepped
For less severe depression, start with an appropriate lower-intensity psychological or behavioural intervention unless another option is preferred or clinically indicated. For more severe depression, several treatments may be first line; agree the option that fits severity, risk, prior response, comorbidity, availability and the person's goals.1,2
Presentation
Persistent low mood and/or loss of interest or pleasure with associated cognitive, physical and behavioural symptoms, causing distress or functional impairment; assess severity, risk, bipolar history and alternative explanations before treatment.1,3,4,5
Cardinal features
- Persistent low mood or loss of interest and pleasure
- Reduced energy, motivation or activity
- Sleep or appetite change
- Poor concentration or indecisiveness
- Feelings of worthlessness, excessive guilt or hopelessness
- Psychomotor agitation or retardation
- Thoughts of death, self-harm or suicide
- Functional impairment in work, relationships or self-care
Red flags
- Immediate suicidal intent, a recent attempt, inability to stay safe or access to lethal means
- Psychotic symptoms, severe self-neglect, refusal of food or fluids or life-threatening physical deterioration
- Possible mania or hypomania, mixed features or antidepressant-associated activation
- High-risk self-harm presentation requiring concurrent physical and psychosocial assessment
- Severe depression with a need for rapid response, including inability to eat or drink
- Substance intoxication or withdrawal, delirium, neurological signs or a medical cause requiring urgent treatment
Investigations
Clinical diagnostic and severity assessment
Depression is diagnosed clinically. Establish symptom duration, core symptoms, functional impact, episode history, comorbid symptoms and patient goals; use PHQ-9 or another validated measure as an adjunct for severity and outcome monitoring, not as a stand-alone diagnostic or suicide test.
Expected finding: A documented formulation of less severe or more severe depression, or an alternative diagnosis, with functional impact and baseline outcome measure recorded.
1Suicide and self-harm assessment
Ask about suicidal thoughts, intent, plans, access to means, previous self-harm or attempts, recent losses, substance use, impulsivity, protective factors, support and ability to engage with a safety plan. If self-harm has occurred, arrange concurrent physical care and psychosocial assessment.
Expected finding: An individualised risk formulation and immediate safety plan, not a global low, medium or high score used to predict outcome or determine discharge.
1,4Bipolar, psychosis, substance and medication screen
Ask about past periods of reduced need for sleep, elevated or irritable mood, increased activity, impulsivity, grandiosity or pressured speech; assess psychotic symptoms, alcohol and drugs, prescribed medicines, withdrawal and family history. Antidepressant treatment should not proceed as if the illness were unipolar when bipolarity or psychosis is possible.
Expected finding: Evidence supporting unipolar depression, bipolar disorder, psychotic depression, substance-related symptoms, medication effect or another mental-health formulation.
1,3Physical health examination and targeted tests
Examine when symptoms, age, comorbidity, medication or presentation suggest a physical contributor. Choose tests such as FBC, thyroid function, renal profile, calcium, glucose, B12/folate, inflammatory markers, ECG or other investigations only when they answer a clinical question or affect treatment; do not use a routine panel as proof of psychiatric diagnosis.
Expected finding: A physical illness, medication effect or normal targeted assessment that refines the formulation and treatment safety.
1,6Medication and treatment-safety review
Before prescribing, review previous response, adherence, interactions, pregnancy or reproductive considerations where relevant, overdose toxicity, alcohol and other medicines. Record the person's preferences about sedation, sexual effects, weight, withdrawal and other harms.
Expected finding: A shared medication plan with an appropriate class, monitoring schedule, quantity supplied and contingency plan; or a decision to use psychological treatment alone.
1,3,7Treatment-response and relapse monitoring
Repeat symptoms, function, side effects, adherence, suicidal ideation, activation and withdrawal symptoms at agreed intervals. Review treatment at 2 to 4 weeks, or after 1 week when the person is aged 18 to 25 or there is particular suicide concern.
Expected finding: Improvement, intolerance, non-adherence, activation, ongoing risk, withdrawal or limited response that triggers a change in the treatment pathway.
1,5Management
| Step | Detail | Source |
|---|---|---|
| Assess urgency, safety and diagnostic formulation first | Ask directly about suicidal thoughts, intent, plans, access to means, previous self-harm or attempts, psychosis, severe self-neglect, mania or hypomania, substance use and available support. Arrange urgent mental-health assessment, crisis resolution and home treatment or inpatient care when the person cannot be safely supported in the community. If self-harm has occurred, provide physical healthcare and psychosocial assessment concurrently; do not use a risk score to decide discharge.1,4 | NICE NG222 and NICE NG225 |
| Confirm severity and agree goals with the person | Use clinical judgement, functional impairment, symptom burden, comorbidity, prior treatment response and a validated outcome measure such as PHQ-9 to classify the episode as less severe or more severe. Discuss what the person wants to improve, treatment preferences, barriers, waiting times, family or carer involvement and how progress will be reviewed.1,2 | NICE NG222 recommendations on recognition, choice and delivery of treatment |
| Offer an appropriate first-line option for less severe depression | Offer a lower-intensity intervention matched to preference and need, such as guided self-help, group exercise, group or individual cognitive behavioural therapy, behavioural activation, mindfulness-based treatment, interpersonal psychotherapy, counselling or short-term psychodynamic psychotherapy as appropriate. Do not routinely offer an antidepressant first line for a new episode of less severe depression unless the person prefers medication, has previously benefited, psychological treatment was ineffective or unsuitable, or there is a risk of progression.1,2 | NICE NG222 recommendations for a new episode of less severe depression |
| Offer shared first-line choices for more severe depression | For more severe depression, discuss the NICE treatment options and choose collaboratively. Common options include an antidepressant plus individual CBT, individual CBT alone, an antidepressant alone or another NICE-recommended high-intensity psychological intervention such as behavioural activation or interpersonal therapy, taking account of urgency, prior response, comorbidity, access and preference. More severe illness usually needs closer follow-up and coordinated care.1,2 | NICE NG222 recommendations for a new episode of more severe depression |
| Prescribe an antidepressant safely when indicated | SSRIs are generally the first-choice class for most adults, but choose the individual drug and dose using current BNF and local formulary guidance, previous response, interactions, physical health, pregnancy or reproductive factors and overdose toxicity. Explain expected benefits, usual time to effect, early adverse effects, sexual and other possible persistent effects, withdrawal, alcohol or medicine interactions and when to seek urgent help. Avoid unopposed antidepressant treatment when bipolar disorder is suspected.1,3,7 | NICE NG222, NICE CG185 and BNF antidepressant guidance |
| Review early and monitor suicide risk, activation and harms | Review treatment response, adherence, side effects, suicidal ideation and activation between 2 and 4 weeks after starting treatment. Review after 1 week for people aged 18 to 25 or where there is particular concern about suicide, and more frequently if clinically needed. Explain that early adverse effects or suicidal thoughts can emerge and tell the person how to obtain urgent help; risk is clinical and dynamic rather than captured by a score.1,5 | NICE NG222 and MHRA SSRI/SNRI safety guidance |
| Escalate psychotic, life-threatening or treatment-resistant depression | Refer urgently to specialist mental-health services for psychotic depression, severe self-neglect, persistent high concern about suicide, diagnostic uncertainty or inadequate response. For psychotic depression, specialist teams may use an antidepressant with an antipsychotic. Consider ECT when a rapid response is needed, for example when the depression is life-threatening because the person is not eating or drinking, or when other treatments have failed. After limited response, check diagnosis, adherence and adequate treatment before switching, adding psychological therapy or considering specialist augmentation.1,4 | NICE NG222 recommendations on psychotic depression, ECT and further-line treatment |
| Treat bipolar depression as bipolar disorder | If assessment identifies bipolar disorder, involve specialist services and follow the bipolar pathway rather than treating it as unipolar depression. If mania or hypomania develops while taking antidepressant monotherapy, consider stopping the antidepressant and offer an appropriate antipsychotic through the NICE bipolar pathway. Discuss toxicity in overdose and limit medication quantities when suicide risk is high.3,1 | NICE CG185 |
| Continue effective treatment after remission and prevent relapse | If an antidepressant is effective, continue it for at least 6 months after remission, with regular review. Consider longer continuation when relapse risk is higher, such as recurrent episodes, residual symptoms or ongoing risk factors. Agree a relapse-prevention plan covering early warning signs, psychological skills, sleep and activity, support, crisis contacts and how medication will be reviewed.1,2 | NICE NG222 recommendations on preventing relapse |
| Taper antidepressants and safety-net the transition | Do not stop antidepressants abruptly unless an urgent clinical reason requires it. Agree a staged reduction tailored to the drug, treatment duration, dose, previous withdrawal and the person's preferences; withdrawal may take weeks or months. Monitor for withdrawal and returning depression, reassure about mild time-limited symptoms, and consider reinstating the previous dose followed by a slower taper if severe withdrawal occurs. Communicate the plan to primary and secondary care.1,7 | NICE NG222 recommendations on stopping antidepressants |
Illustrations
Differentials
Bipolar depression
Past or current mania or hypomania, reduced need for sleep, episodic increased activity, impulsivity or elevated or irritable mood; treatment follows the bipolar pathway.
Psychotic depression
Mood-congruent or incongruent delusions or hallucinations, severe self-neglect or marked functional decline; urgent specialist assessment is needed.
Adjustment disorder or grief
Symptoms linked to an identifiable stressor or loss but assess carefully for pervasive anhedonia, neurovegetative symptoms, functional impairment and suicide risk.
Generalised anxiety or trauma-related disorder
Anxiety, worry, hyperarousal or trauma symptoms dominate, although comorbidity with depression is common.
Physical or medication-related disorder
Symptoms and examination suggest thyroid, haematological, endocrine, neurological, inflammatory, substance-related or drug-induced illness.
Delirium or neurocognitive disorder
Acute fluctuation, inattention or altered consciousness suggests delirium; chronic progressive cognitive decline suggests dementia, with depression potentially coexisting.
Complications
- Suicide and self-harm
- Severe self-neglect, malnutrition or dehydration
- Substance misuse and medication toxicity
- Functional, occupational and relationship impairment
- Relapse, chronicity and residual symptoms
- Worse outcomes in comorbid physical illness
Prognosis
Many depressive episodes improve with appropriate psychological, behavioural or pharmacological treatment, but recurrence, residual symptoms and social or physical comorbidity are common. Ongoing review, relapse prevention and a clear safety plan are part of treatment rather than optional aftercare.
Guidelines
- Depression in adults: treatment and management (NG222) (NICE, 2022)
- Bipolar disorder: assessment and management (CG185) (NICE, 2025)
- Self-harm: assessment, management and preventing recurrence (NG225) (NICE, 2022)
References
- NICE NG222, Depression in adults: treatment and management, recommendations (NG222)
- NICE NG222, information for the public (NG222 public information)
- NICE CG185, Bipolar disorder: assessment and management, recommendations (CG185)Updated 2 Sept 2025
- NICE NG225, Self-harm: assessment, management and preventing recurrence, recommendations (NG225)
- MHRA, Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs): use and safety (MHRA SSRI/SNRI safety)
- NHS, sudden confusion (delirium) (NHS sudden confusion)
- BNF, sertraline (BNF sertraline)
- NICE NG222, update information (NG222 update)
Evidence checked: 2026-08-03
This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.