What are the behavioural and psychological symptoms of dementia? Describe their types, etiology, investigations and line of management, including the modes of action, indications and side effect profile of the drugs used.

Definition. Neuropsychiatric symptoms (NPSs), also called behavioural and psychological symptoms of dementia (BPSD), are signs and symptoms of disturbed perception, thought content, mood or behaviour occurring in a person with dementia. They may appear before, during or after the diagnosis and may be the earliest sign of incipient cognitive decline.

Epidemiology. 90–98% of people with dementia develop at least one NPS over the disease course. NPSs occur in all dementia types and all stages. In AD the commonest is apathy, followed by depression, aggression, anxiety, sleep disturbance, irritability, appetite disturbance, motor problems, delusions, disinhibition, hallucinations and euphoria.

Types — five clusters. (i) Psychosis — delusions (commonly theft, infidelity, misidentification, phantom boarder) and hallucinations; (ii) Affective — depression, anxiety, apathy, elation; (iii) Hyperactive/agitation — aggression, restlessness, pacing, wandering, disinhibition, screaming; (iv) Vegetative — sleep–wake reversal, sundowning, appetite and eating change, hyperorality; (v) Care-related — rejection of care, resistance to bathing and dressing.

Aetiology — patient factors. Neurodegeneration with cholinergic, serotonergic and frontal–subcortical circuit disruption, plus acute medical issues — pain, infection (urinary, respiratory), constipation, urinary retention, dehydration, drug change, poor sleep and sensory impairment. Pain is a common and frequently missed cause of agitation, and sometimes a trial of scheduled analgesia is the only way to prove it.

Aetiology — caregiver and environmental factors. Unmet needs (hunger, boredom, toileting, need for company), pre-existing personality and psychiatric illness, caregiver factors (communication style, unrealistic expectations, countertherapeutic approach) and environmental factors (clutter, poor lighting, over- or under-stimulation, unfamiliar surroundings, lack of routine).

Investigations. Exclude delirium first using the Confusion Assessment Method (CAM) — acute onset and fluctuating course, plus inattention, plus disorganised thinking or altered consciousness. Then: urinalysis and culture, complete blood count, blood glucose, blood urea, electrolytes (sodium, potassium in mEq/L), calcium (mg/dL), liver function tests, TSH (µIU/mL), vitamin B12 (pg/mL), oxygen saturation, ECG (QTc before any antipsychotic), chest radiograph if indicated, and a full medication review. Pain assessment using observational tools (PAINAD, Abbey) in non-verbal patients, and imaging only if focal signs, head injury or rapid change.

Symptom assessment tools. Neuropsychiatric Inventory (NPI, NPI-Q, NPI-C) for the symptom profile; Cohen-Mansfield Agitation Inventory (CMAI) for agitation; Cornell Scale for Depression in Dementia (CSDD) for mood.

Management — the DICE framework. Describe the behaviour and its context and triggers; Investigate modifiable patient, caregiver and environmental causes; Create a plan built on five strategies — caregiver education, effective communication, meaningful activity, task simplification with structured routine, and a safe simplified environment; Evaluate effectiveness, caregiver distress and unintended effects, and consider dose reduction or withdrawal of any psychotropic used.

Non-pharmacological management is first line. Family and paid caregiver interventions have the strongest evidence and a greater effect size (0.34) than antipsychotics for behavioural symptoms. Efficacy is best in mild and moderate stages. Music therapy, exercise and tailored activity work best embedded within caregiver-directed programmes. Training and supervising paid caregivers in communication or person-centred care skills is effective for severe agitation, immediately and up to six months afterward.

Pharmacological principles. Drugs are reserved for three “medication as first-line” scenarios — major depression, psychosis, or aggression with risk of harm to self or others — and for acute safety crises. International Delphi consensus endorses an escalating approach: identify causes → caregiver training, environmental adaptation, person-centred care and tailored activities → then citalopram and analgesia before antipsychotics; but for psychosis specifically, risperidone is prioritised. Valproate and carbamazepine are ineffective and harmful; benzodiazepines are for crises only; cholinesterase inhibitors and memantine do not help NPS in AD but do help in DLB and PDD. Drug Table — Mode of Action, Indications and Side Effects Drug Mode of action Indication in BPSD Key adverse effects Risperidone D2 and 5-HT2A antagonist Best evidence for short-term Stroke, increased mortality, (6–12 wk) agitation and extrapyramidal symptoms, aggression; licensed in hyperprolactinaemia, sedation, EU/Canada for severe aggression falls Olanzapine Multi-receptor (D2, 5-HT2, H1, Agitation, psychosis Sedation, anticholinergic and M1) antagonist metabolic effects, weight gain, hyperglycaemia, stroke, mortality Quetiapine D2/5-HT2A antagonist, low D2 Agent of choice with clozapine Sedation, postural hypotension, affinity in DLB and PDD psychosis falls; least extrapyramidal risk Aripiprazole D2 partial agonist, 5-HT1A Agitation, psychosis Akathisia, sedation, stroke, partial agonist mortality Haloperidol Potent D2 antagonist Avoid in dementia; delirium Severe extrapyramidal effects; only, lowest effective dose catastrophic neuroleptic sensitivity in DLB; QTc prolongation Citalopram SSRI Agitation (CitAD trial, target 30 QTc prolongation and mg), anxiety, irritability cognitive decline at 30 mg; hyponatraemia (SIADH), falls, GI upset Sertraline SSRI Major depression in dementia Hyponatraemia, GI upset, (DIADS) bleeding risk with NSAIDs, tremor Trazodone Serotonin antagonist and Night-time agitation and Sedation, postural hypotension, reuptake inhibitor sleep disturbance; stabilises falls, rarely priapism circadian rhythm Lorazepam / oxazepam GABA-A positive allosteric Crisis use only, short- to Sedation, falls, paradoxical modulator intermediate-acting preferred agitation, respiratory depression, worsened cognition, dependence Cholinesterase inhibitors Inhibit acetylcholinesterase, Not for NPS in AD; effective for Nausea, vomiting, diarrhoea, raising synaptic acetylcholine psychiatric and cognitive bradycardia and syncope, symptoms in DLB and PDD weight loss; worsens tremor in PD Memantine Uncompetitive, voltage- Moderate–severe AD cognition; Dizziness, headache, confusion; dependent, low-affinity NMDA cognitive and global benefit in case reports of worsening receptor antagonist DLB but no psychiatric delusions and hallucinations benefit in DLB Pimavanserin Selective 5-HT2A inverse Parkinson’s disease psychosis QTc prolongation, peripheral agonist, no dopaminergic action only oedema, confusion Latest Updates (2023–Present)

Agitation in AD now has two licensed drugs. Brexpiprazole (Rexulti) — a serotonin–dopamine activity modulator (D2 and 5-HT1A partial agonist, 5-HT2A antagonist) — received FDA approval in May 2023, the first approval for any neuropsychiatric symptom of dementia, showing about 31% reduction in agitation versus placebo (CMAI effect size ~0.35), with benefit on CGI-S significant only at 3 mg. It retains the class boxed warning for increased mortality in elderly patients with dementia-related psychosis, plus akathisia, somnolence and weight gain.

The first non-antipsychotic option has arrived. Dextromethorphan–bupropion (AXS-05, Auvelity) was FDA-approved in 2026 for agitation in AD dementia: dextromethorphan is an NMDA receptor antagonist and sigma-1 agonist, while bupropion inhibits CYP2D6 to sustain dextromethorphan levels. ADVANCE-1 showed CMAI improvement versus placebo at week 5; ACCORD-2 showed delayed relapse (HR 0.276) and reduced relapse (8.4% vs 28.6%) over 26 weeks. It carries a boxed warning for suicidal thoughts and behaviours and is contraindicated in seizure disorder, eating disorders, recent alcohol or benzodiazepine withdrawal, and with MAOIs.

BPSD/NPS = disturbed perception, thought content, mood or behaviour in dementia; 90–98% of patients develop at least one, across all dementia types and stages; apathy is commonest in AD, followed by depression and aggression.

Five symptom clusters: psychosis (delusions, hallucinations), affective (depression, anxiety, apathy), hyperactive/agitation (aggression, wandering, disinhibition), vegetative (sleep reversal, sundowning, eating change) and care-related (rejection of care).

Aetiology is multifactorial: neurodegeneration; acute medical triggers — pain, infection, constipation, retention, dehydration, drug change, poor sleep, sensory loss; unmet needs; caregiver communication and expectations; and environmental over- or under-stimulation.

Investigations: rule out delirium with the CAM, then urinalysis and culture, CBC, glucose, urea, electrolytes (mEq/L), calcium (mg/dL), LFT, TSH (µIU/mL), B12 (pg/mL), oxygen saturation, ECG for QTc before any antipsychotic, medication review, and observational pain assessment (PAINAD, Abbey). Quantify with NPI, CMAI and Cornell Scale.

Non-pharmacological measures are first line and follow the DICE approach (Describe, Investigate, Create, Evaluate), with caregiver education, communication training, meaningful activity, task simplification with routine, and a safe simplified environment. Caregiver interventions (effect size 0.34) outperform antipsychotics.

Drugs are reserved for major depression, psychosis, or aggression risking harm. Risperidone has the best short-term evidence for agitation (stroke and mortality risk); quetiapine or clozapine in DLB/PDD; citalopram helps agitation but causes QTc prolongation and cognitive decline at 30 mg; trazodone for night-time agitation; benzodiazepines for crises only; valproate and carbamazepine are ineffective; ChEIs and memantine do not help NPS in AD but do in DLB and PDD.

Two drugs are now formally licensed for agitation in AD dementia: brexpiprazole (FDA 2023), a serotonin–dopamine activity modulator with an effect size of about 0.35 and a boxed mortality warning; and dextromethorphan–bupropion (AXS-05, FDA 2026) — NMDA antagonist plus sigma-1 agonist with CYP2D6 inhibition — the first non-antipsychotic option, which delayed relapse in ACCORD-2 (HR 0.276).

Constipation · Hydration/Hypoxia · Medication · Environment Numerical anchors: NPS in 90–98% · caregiver intervention effect size 0.34 · risperidone efficacy window 6–12 weeks · brexpiprazole effect size ~0.35 · ACCORD-2 relapse 8.4% vs 28.6% Named trials to quote: DIADS and DIADS-2 (sertraline) · HTA-SADD (sertraline vs mirtazapine) · CitAD and S-CitAD (citalopram, escitalopram) · WHELD (person-centred care) · ADVANCE-1 and ACCORD-2 (AXS-05) · HARMONY (pimavanserin) Examiner traps: 1. Reaching for an antipsychotic before excluding pain, infection, constipation and retention. 2. Forgetting that delirium must be excluded first — the CAM takes two minutes. 3. Prescribing haloperidol in DLB — potentially catastrophic neuroleptic sensitivity. 4. Claiming ChEIs help behaviour in AD — they do not; they help in DLB and PDD. 5. Omitting the ECG/QTc before citalopram or an antipsychotic. 6. Continuing psychotropics indefinitely — the “E” of DICE demands a withdrawal trial. 15-second answer skeleton: Define → 90–98% prevalence → five clusters → aetiology in three domains (patient, caregiver, environment) → exclude delirium and PINCH ME triggers with named investigations → DICE and caregiver-directed non-pharmacological care first → drugs only for depression, psychosis or dangerous aggression, with the mode-of-action/indication/side-effect table → the two new licensed agents → Indian context (family caregiving, DMHP, unregulated antipsychotic access).