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Educational draft · awaiting clinical reviewUse Rapid for revision, not patient-care decisions. Check current national and local guidance and the BNF or BNFC before acting.

Differential diagnosis and physical-health screening

Psychiatry · UK scope · Sources checked 27 Aug 2026 · Clinical review pending

RapidFull
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Acute medical or neurological mimic

Fluctuating consciousness, focal neurology, seizure, fever, severe headache, hypoxia, hypoglycaemia, postpartum confusion, intoxication or dangerous withdrawal requires emergency medical assessment before a primary depressive explanation.

Action: Use ABCDE and bedside glucose, obtain observations and a focused exposure and neurological history, treat immediate abnormalities and escalate for acute medical, obstetric or neurological care. Maintain suicide precautions and obtain collateral baseline information while the organic work-up proceeds.

Synopsis

Distinguish unipolar depression from bipolar, psychiatric, neurological, endocrine, sleep, substance and medicine-related causes through chronology, examination and targeted tests while avoiding both diagnostic overshadowing and indiscriminate screening.

  • Build a dated timeline of mood, biological change, function, prior episodes, activation, medical illness, reproductive events, medicines and substances.
  • Screen lifetime mania and hypomania before antidepressant treatment; ask about reduced sleep need, increased activity, pressured speech, confidence, irritability and risky behaviour.
  • Differentiate grief, adjustment disorder, anxiety, PTSD, psychotic disorders, eating disorders, neurodevelopmental conditions and personality-related difficulties by dominant pattern and course.
  • Review alcohol, cannabis, stimulants, opioids, sedatives and withdrawal, plus corticosteroids, interferons, hormonal treatments and other relevant medicines.
  • Perform physical and neurological examination when symptoms, age, onset or treatment require it, including observations, weight and targeted endocrine or movement signs.
  • Choose FBC, renal and liver profiles, glucose, calcium, thyroid, B12, folate, pregnancy, infection or other tests from a stated clinical question.
  • Assess sleep apnoea, restless legs, chronic pain, inflammatory disease and social deprivation when fatigue and sleep disturbance dominate.
  • Use ECG when cardiac symptoms, overdose, electrolyte risk or a QT-prolonging medicine such as citalopram makes the result relevant.
  • Explain what normal tests do and do not exclude and reopen the differential when course or treatment response is discordant.

    • Key red flags

    A history of mania or hypomania, antidepressant activation or episodic reduced sleep need suggests bipolar depression and changes treatment risk.

    Abrupt late onset, cognitive fluctuation, new seizure, focal deficit, movement disorder or rapidly progressive personality change requires neurological investigation.

    Weight change, tremor, temperature intolerance, menstrual disturbance, constipation, anaemia symptoms or steroid exposure can signal endocrine, metabolic or medicine contributors.

    Postpartum psychosis, severe perinatal depression or thoughts of harming the baby requires urgent specialist perinatal assessment and safeguarding support.

    Routine normal blood tests do not exclude sleep apnoea, epilepsy, Parkinson disease, substance effects, trauma or bipolar disorder.

    Investigation priorities

    01
    Longitudinal mood and activation historyFirst step

    Distinguish unipolar, bipolar, substance-related and adjustment courses before treatment selection.

    Management branches

    Initial differentialUse course before tests

    A depressive syndrome is suspected or treatment has not yet begun.

    1. Establish chronology, previous activation, grief or trauma context, substances, medicines, physical symptoms and reproductive timing.
    2. Perform mental-state, suicide, functional and indicated physical or neurological assessment and obtain collateral baseline evidence.
    3. Rank unipolar, bipolar, psychiatric, medical and substance explanations and choose tests that could change management.
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    Sources and review status4 sources · checked 27 Aug 2026 · clinical review pending+
    Sources

    Sources and review status

    National guidance is shown before implementation-dependent detail. Apply principles in context and verify current guidance when a decision affects care. Source check completed 27 Aug 2026; clinical approval remains outstanding.

    • NICE NG222 depression in adults recommendationsComprehensive assessment, differential diagnosis and physical health.
    • NICE CG185 bipolar disorder recommendationsRecognition and assessment of mania, hypomania and bipolar depression.
    • NICE NG202 sleep apnoea recommendationsSymptoms and diagnostic pathway for sleep-disordered breathing.
    • NICE CG192 antenatal and postnatal mental health recommendationsPerinatal assessment, severe illness and treatment considerations.

    Editorial contact: Doctor’s Passport editorial team. Source-check date is separate from clinical approval. Report a content problem · Content changes

    Authoring stateRapid draftClinical stateAwaiting reviewJurisdictionUnited Kingdom