Approach to acute psychosis in older adults

Opening Vignette

A 65-year-old Chinese woman with hypertension, gout and knee osteoarthritis was brought to the emergency department due to altered mentation, behavioural changes and food refusal over the past 3 weeks. The patient reported hearing voices and was increasingly paranoid with false persecutory beliefs. She had become socially withdrawn, refusing food and increasingly incapable of self-care. She was alert, slightly unkempt and fidgety and occasionally muttered to herself. Her speech was fairly tangential and incoherent, and she was suspicious that people were trying to kill her by poisoning her food. Clinical examination was otherwise unremarkable. Corroborative history from the family revealed no significant recent events and the patient was not taking any new drugs. Your clinical impression was that of first-episode acute psychosis in an older adult, and the patient was admitted to the general medicine ward for further evaluation.

WHAT IS PSYCHOSIS?

Psychosis is a clinical syndrome of altered perception of reality, characterised by one or more of the following features[1,2]:

1. Hallucinations: sensory percepts (visual, auditory, tactile, olfactory, gustatory) experienced in the absence of true external stimulus

2. Delusions: false and potentially bizarre beliefs held with great conviction despite evidence to the contrary (i.e. untrue, unshared, unshakeable)

3. Formal thought disorder: objectively manifest as incoherent, disordered speech that may comprise neologisms and word salad

4. Catatonia: psychomotor disorder comprising various abnormal movements and behaviours

5. Negative symptoms: anhedonia, alogia, asociality, avolition/apathy and affect blunting (five ‘As’)

Classically, Schneider’s first-rank symptoms,[3] which include audible hallucinations (thought echo, voices arguing or commenting), thought interference (withdrawal, insertion, broadcasting), delusions of control (made volitional acts, impulses and affect) and delusional perception, were used to describe patients with schizophrenia.

HOW COMMON AND RELEVANT IS THIS IN CLINICAL PRACTICE?

The estimated prevalence of psychosis in older adults was 5%–10% locally and internationally.[4,5,6] In a rapidly ageing population, acute care physicians need to be familiar with managing elderly patients with first-onset psychosis that may manifest in various ways, such as agitation/aggression, paranoia, food refusal or sudden inability for self-care.[7,8]

Older adults are persons aged ≥60 years, based on the United Nations definition of older persons[9] and a similar age cut-off to local studies like the WiSE study.[6] The evaluation and management of acute psychosis in older adults is different from those for young adults due to salient differences in clinical disease manifestations, underlying aetiologies and choice of treatment, influenced by factors such as disease epidemiology, age-related physiological changes and medical comorbidities. For example, primary psychotic disorders such as schizophrenia tend to occur more commonly in younger patients from late teens to early thirties, while organic psychoses feature more prominently in older adults due to higher burden of medical comorbidities that may predispose to neurological/metabolic disturbances, higher incidence of polypharmacy and use of traditional/complementary/herbal medicines. In addition, unlike younger patients with classical schizophrenia spectrum disorders who may present with florid first-rank symptoms,[3] late onset paraphrenia in older adults has a predominant delusional component without concomitant thought disorder or personality change.[10] Finally, the choice and dosing regimen of antipsychotics in older adults depends on the patients’ clinical profile and medical comorbidities, taking into consideration age-related changes in pharmacokinetics and pharmacodynamics.

WHAT ARE THE CAUSES OF ACUTE PSYCHOSIS?

The aetiologies of acute psychosis are shown in Box 1. In older adults, it is particularly important to first rule out organic causes of psychoses, as primary psychoses rarely present in this age group and elderly patients have a higher burden of medical comorbidities and polypharmacy that predispose to organic pathologies. In addition, organic psychoses may be reversible if the underlying precipitant is addressed in a timely manner. For example, in an elderly patient with altered mentation, delirium should always be considered, with underlying precipitants to be investigated. This is because atypical disease presentations are fairly common in the geriatric population due to age-related homeostatic changes, with a tendency for clinical insults to manifest first at the organ with least reserves, such as the brain which may have undergone age-related atrophy and neurodegenerative changes. As such, delirium can be the first presentation of an underlying illness such as pneumonia, and early detection of delirium with prompt treatment of the underlying precipitant can reduce the duration and severity of symptoms.[11] In addition, cerebrovascular disease and neurodegenerative disorders are common in the older population and interestingly, studies have reported the prevalence of psychoses in patients with previous stroke, Parkinson’s disease and Alzheimer’s dementia to be 5%,[12] 10%[13] and 41%,[14] respectively. Locally, older adults commonly consume traditional Chinese medicines or herbal supplements for health and wellness, and some of these products may be adulterated with exogenous steroids for their anti-inflammatory effect.[15] In such cases, it may be prudent to consider the possibility of steroid-induced psychosis, which is a rare but well-established dose-dependent adverse effect of systemic corticosteroids.[16]

Box 1.

Causes of acute psychosis in older adults.

Medical causes (secondary psychoses)
Acute brain dysfunction
• Deliriuma
Neurological conditions
• Cerebrovascular disease (vascular psychosis)a
• Subdural hemorrhagea
• Brain tumours
• Central nervous system infections (meningoencephalitis)a
• HIV/AIDSa
• Neurosyphilisa
• Traumatic brain injury
• Epilepsy (especially temporal lobe epilepsya)
• Autoimmune and paraneoplastic encephalitis (e.g. anti-NMDA receptor encephalitis, limbic encephalitis), neuropsychiatric systemic lupus erythematosus, vasculitis
• Neurodegenerative disorders — dementiaa (Alzheimer’s dementia, frontotemporal lobe dementia, Lewy body dementia), Parkinson’s diseasea, multiple sclerosis, motor neuron disease, Prion disease, Huntington’s disease
Metabolic/endocrine disorders
• Electrolyte disturbancesa (especially severe hypercalcemia, severe hyponatremia)
• Nutritional deficienciesa — folate, vitamin B12 deficiency
• Thyroid and parathyroid disordersa
• Adrenal gland disordersa
• Hypoglycemia/hyperglycemic crisesa
• Uremic encephalopathy
• Hepatic encephalopathy
• Wilson’s disease
• Acute intermittent porphyria
• Hypoxia/hypercapnia
Drugs/toxins/substance use
• Medicationsa — corticosteroids, sympathomimetics, anti-cholinergic drugs, anti-parkinsonian drugs, opioids, antimicrobials
• Recreational drugs — cannabis, stimulants (amphetamines, cocaine), hallucinogens (phencyclidine)
• Alcohol intoxication/Korsakoff psychosis and withdrawala
• Sedative (benzodiazepine) withdrawala
• Traditional medicationsa
• Heavy metal poisoning (arsenic, cadmium, lead, mercury)
Psychiatric causes (primary psychoses)
Primary psychiatric illness
• Brief psychotic disordera
• Schizophreniform disordera
• Schizophreniaa (late onset, very late onset)
• Schizoaffective disordera
• Schizotypal/schizoid personality disorder
• Delusional disordera
• Mood disorder (depression, bipolar disorder) with psychotic featuresa

^aRelatively more common causes of psychosis in older adults

In the realm of primary psychoses in elderly patients, ‘very late onset schizophrenia-like psychosis’ is used to describe elderly patients with onset of schizophrenic features.[17] Interestingly, ‘late paraphrenia’ was previously used to describe a unique entity of elder-onset psychosis that commonly occurs in females, with predominant features of paranoid delusions and hallucinations, in the absence of thought disorder, negative symptoms or personality change.[10,17] Nonetheless, it is important to recognise that the diagnosis of schizophrenia can be made only when the psychotic symptoms last for at least 6 months.

EVALUATING OLDER ADULTS FOR ACUTE PSYCHOSIS

Initial evaluation for acute psychosis in older adults involves taking a comprehensive psychiatric and clinical history, with corroborative history from the next-of-kin, and performing a targeted examination based on the likely differential diagnoses. Firstly, psychiatric history-taking involves characterising the nature of psychotic symptoms, identifying associated neuropsychiatric symptoms such as mood and cognitive changes and assessing the degree of functional and psychosocial impairment. A list of salient questions in the psychiatric history-taking is detailed in Supplementary Table 1 [Appendix]. Importantly, the nature of psychotic manifestations may favour certain aetiologies — the presence of bizarre delusions and thought disorders would be suggestive of schizophrenia spectrum disorders, while the presence of pseudohallucination (voices in the head) and mood congruent symptoms are associated with affective states, such as mood disorders (depression, bipolar disorder) or endocrine conditions (thyroid dysfunction). During the psychiatric interview, a mental state examination is usually concurrently performed by observing the patient’s overall appearance (e.g. grooming, posture), behaviour (e.g. eye contact, body language), psychotic manifestations (including hallucinations, delusions and thought/speech disorders), mood/affect, cognition, insight and risk assessment (of suicide/self-harm and harm to others). Patients who are deemed to pose significant risks to themselves or others might require involuntary admission to the Institute of Mental Health under Singapore’s Mental Health (Care and Treatment) Act 2008. Secondly, corroborative history should be obtained from the patient’s next-of-kin to document the spectrum of observed psychotic behaviours, delineate the timeline of symptoms, identify possible precipitating events and determine the veracity of patient’s delusional claims. Furthermore, performing a comprehensive geriatric assessment with the patient’s caregiver provides a holistic picture of the premorbid medical history, cognition, mood, function, ambulatory status and social set-up. In the context of psychopathology, it is useful to characterise the patient’s premorbid personality and adjustment, which may influence disease pathogenesis, psychiatric insight and eventual functional outcomes.[18] Thirdly, clinical history-taking and examination should be performed to identify symptoms and signs of an underlying organic pathology.

Supplementary Table 1.

Salient Questions in Psychiatric History-Taking for Older Adults with Acute Psychosis

1. Characterising Psychotic Symptoms and Other Psychiatric Manifestations
a) Hallucinations:
Types	-Auditory hallucinations: do you hear voices (human voices, inaudible sounds) when there isn’t anyone around?
	-Visual hallucinations: do you see things that other people are unable to see?
	-Olfactory hallucinations: do you smell anything strange that other people are unable to smell?
	-Gustatory hallucinations: do you experience any strange tastes in your mouth when consuming food/drinks?
	-Tactile (haptic) hallucinations: do you get strange sensations on your body e.g. someone touching you or insects crawling on you, although you do not see them? (tactile hallucinations)
Content	-How many voices do you hear? Who do they identify themselves as?
	-How do they address you? (in second or third person)
	-What do the voices say to you? (command to do something, echo patient’s thoughts, argue amongst themselves, comment on patient’s actions)
	-Is the content of the hallucination congruent with the patient’s mood state?
Where are the "voices" coming from?	- Are the "voices" coming from inside your head (pseudo- hallucination) or from an external location?
Time course	-How long has/have the symptom(s) been going on for? (< 1 month, 1-6 months, > 6 months)
	-Are the symptoms there all the time or only at particular times of the day (e.g. when going to sleep (hypnagogic) or waking up (hypnopompic))?
	-Are the symptoms becoming more frequent?
b) Delusions: 3 "Us"
Main types	-Persecutory delusions: do you think that there are people trying to do things to harm you?
	-Delusions of reference: when you listen to the radio or watch the television, do you get the sense that people are referring to you?
	-Delusions of grandeur: do you feel that you have certain special powers or abilities that other people do not have?
	-Delusions of guilt: do you keep feeling that you have done wrong things in the past that you deserve punishment for?
	-Delusional jealousy (Othello syndrome): do you feel that your spouse is having an affair?
	-Erotomania (de Clerambault syndrome): do you feel that someone (usually of a higher social status) is in love with you?
	-Delusions of control (somatic passivity): do you feel that someone is able to take control of your thoughts (thought insertion, thought withdrawal, thought broadcasting), feelings (made affect), urges (made impulses) and actions (made volition)
	-Nihilistic delusion: do you feel that your body, or a part of it, is no longer existent or dead?
Untrue	- Could you tell me why you think this is true / what is the evidence supporting such a belief?
Unshared	-Do other people around you also think the same way?
	-Obtain corroborative history from patient’s family, friends or colleagues if they share the same belief o However, beware of the rare entity of shared delusion (folie a deux)
Unshakeable	-How certain are you, from a scale of 1 to 10, that this claim is true?
	-Gently challenge the patient’s delusional belief with evidence that points to the contrary
c) Screening for Other Psychiatric Manifestations
Mood	Adapted from the Patient Health Questionnaire-2 [1]
	-Over the last two weeks, how often have you felt depressed or hopeless?
	-Over the last two weeks, how often have you felt little interest in doing things you used to like to do?
Anxiety	- Do you feel anxious or keep worrying that something bad is going to happen?
Sleep	- How has your sleep been? Do you have difficulties falling asleep, maintaining uninterrupted sleep throughout the night or early morning awakening?
Appetite	- How has your appetite been?
2. Risk assessment
Self-harm/suicide	-Do you have any active or previous thoughts of hurting yourself or ending your own life? -If so, have you made any plans?
Harm to others	-Do you have any active or previous thoughts of doing something to harm others (e.g. taking revenge against those you feel are trying to harm you)? -If so, have you made any plans?
3. Insight
Recognition of pathological nature of symptoms and need for treatment	Adapted from Professor Anthony David’s 3 concepts of insight [2]
	-Do you think you might be having an illness of the mind? (awareness of illness) -Do you think that the symptoms you are experiencing (hallucinations, delusions) are real? If not, could they be related to an underlying psychiatric condition? (awareness of psychotic experiences) -Do you think you might need treatment for these symptoms you are experiencing? (awareness of need for treatment)
4. Functional Impairment
Social	- Do you have any issues with your relationships with family and friends?
Occupational	- Do you have any issues at work or with keeping a job? (if patient is still in employment)
5. Family History of Psychiatric Illness
Psychotic disorders	- Do you know if any of your family members (biologically related) are suffering from a psychotic illness (e.g. hearing voices)?
Mood disorders	- Do you know if any of your family members (biologically related) are suffering from mood disorders such as depression?
Cognitive disorders	- Do you know if any of your family members (biologically related) are suffering from dementia?

In patients with an acute change in mentation with psychotic symptoms, the Confusion Assessment Method is a well-validated tool to screen for delirium, based on the presence of the following: (a) altered mentation as compared to patient’s baseline (acute onset and follows a fluctuating course); (b) inattention; and either (c) disorganised thinking or (d) altered level of consciousness.[19] Essentially, delirious patients typically demonstrate hyperactivity (e.g. agitation, aggression, restlessness) and/or hypoactivity (e.g. lethargy, drowsiness, psychomotor retardation), with features of inattention such as difficulty focusing in a conversation or distractibility, and disorganised thought process manifesting as tangential, incoherent or irrelevant speech. Besides diagnosing delirium, the underlying precipitant needs to be identified by looking for infective features and focal neurological deficits suggestive of intracranial event, checking for distended bladder or high post-void residual urine volume in acute urinary retention, performing a digital rectal examination for impacted stools and reviewing the drug chart for potential medications that may predispose to delirium (e.g. anticholinergics, opioids, sedatives).

Subsequently, to evaluate for neurological causes of psychiatric manifestations, patients should be assessed for focal neurological deficits (e.g. numbness, weakness, speech/swallowing difficulties, visual loss), cognitive impairment, executive dysfunction, pre-existing cardiovascular risk factors, and history of neurological disorders or head trauma. Red-flag features of raised intracranial pressure, such as early morning headache associated with nausea/vomiting that is worse on exertion/coughing/sneezing or lying supine, Cushing’s ‘triad’ of bradycardia, hypertension and irregular respiratory rate, papilloedema on fundoscopy and false localising cranial nerve VI palsy, should always be excluded. To assess for common metabolic/endocrine disorders, it is useful to take a dietary history, evaluate the patient’s nutritional status and screen for features of hyper/hypothyroid states, hypercortisolism, anaemia and uraemic/hepatic/hypercapnic encephalopathy.

Finally, a comprehensive review of all prescribed medications, traditional medicines and herbal supplements, and any alcohol or recreational drug use should be conducted with the patient and caregiver, and the process of drug identification and reconciliation can be facilitated by inpatient pharmacists.

WHAT ARE THE INVESTIGATIONS INVOLVED?

In general, investigations comprise blood and urine tests, neuroimaging, electrophysiological studies and/or procedures like lumbar puncture [Supplementary Table 2, Appendix]. The type and extent of evaluation depends on the clinical suspicion, goals of care and diagnostic objectives.

Supplementary Table 2.

Common Investigations for Older Adults with Acute Psychosis

Blood tests
Full blood count (FBC)	Routinely performed - to evaluate for blood cell abnormalities (e.g. leukocytosis may suggest infection, anemia may require workup for nutritional deficiencies, thrombocytosis may be noted in inflammatory states)
Electrolytes, urea, creatinine and serum glucose	Routinely performed - to evaluate renal function and any electrolyte abnormalities and/or hypoglycemia/hyperglycemia that may require correction
Liver function tests (LFT)	Routinely performed - to evaluate for liver enzyme derangements (e.g. in severe infection, chronic alcohol use, recreational drug use, Wilson’s disease)
Thyroid function test (TFT)	Commonly performed - to evaluate for severe hypothyroidism or hyperthyroidism that can both have neuropsychiatric manifestations
Intact parathyroid hormone (iPTH)	Consider if patient has unexplained hypercalcemia
8 am serum cortisol	Consider if clinically suspicious of adrenal insufficiency especially secondary to exogenous steroids/TCM use
Short synacthen test, with paired ACTH	Useful in cases of equivocal 8 am serum cortisol levels (100-500 nmol/L) to evaluate for adrenal insufficiency
Vitamin B12, folate levels	Routinely performed - to evaluate for nutritional deficiencies that may present with psychosis
HIV and syphilis screen	Commonly performed - primarily to rule out sexually transmitted infections that have known neurocognitive manifestations (which in the context of elderly who are nursing home residents or immobile, requires evaluation of sexual abuse)
Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)	Commonly performed - although non-specific, if significantly elevated may suggest inflammatory, infective, malignant states
Serum ceruloplasmin levels	Consider if suspicious of Wilson’s disease
Autoimmune and paraneoplastic workup (e.g. ANA, anti-dsDNA, anti-Sm, C3/C4, ANCA, anti- NMDA receptor antibody)	Consider if clinically suspicious of autoimmune (e.g. neuropsychiatric lupus, vasculitis) and paraneoplastic (e.g. anti-NMDA receptor encephalitis) aetiologies
Serum toxicology screena	Consider if suspecting unknown drug use
Serum ethanol levels	Consider if suspicious of alcohol intoxication
Serum ammonia levels	Consider if patient is encephalopathic
Arterial blood gas	Consider if patient is encephalopathic to evaluate for hypoxic state or carbon dioxide retention
Urine tests
Urine drug screen	Commonly performed - to rule out benzodiazepine, opioid (to note: common cough syrups like Dhasedyl may also contain sympathomimetics like ephedrine/pseudoephedrine) and stimulant use
Urine toxicology screena	Consider if suspecting unknown drug use
24h urinary copper excretion	Consider only if suspicious of Wilson’s disease
Urine porphobilinogen levels	Consider only if suspicious of acute intermittent porphyria
Drug testing
Testing of drug components and heavy metals in traditional medicines/herbal supplementsb	Consider if patient is reported or suspected to be taking traditional medicines or herbal supplements
Neuroimaging
CT brain	Commonly performed - to look for intracranial hemorrhage, infarcts or grossly apparent space-occupying lesions
MRI brain (contrasted)	Commonly performed - to look for cerebrovascular disease, structural brain lesions, neurodegenerative changes, demyelinating disease
Procedures
Electroencephalogram	Commonly performed - specifically looking for features suggestive of temporal lobe epilepsy
Lumbar puncture	Commonly performed - to look for CNS infections, neuroinflammatory conditions, neurodegenerative disorders, Prion disease
Baseline tests prior to initiation of antipsychotics
ECG	To check for baseline QTc interval (normal < 0.44s for males, < 0.46s for females), as antipsychotics are commonly associated with prolonging QTc which can lead to life-threatening arrhythmias like Torsades de Pointes
Fasting plasma glucose or HbA1c	To evaluate for presence of diabetes mellitus at baseline, as atypical antipsychotics commonly have metabolic side effects
Fasting lipid profile	To evaluate for presence of hyperlipidemia at baseline, as atypical antipsychotics commonly have metabolic side effects

^a Locally, toxicology testing of unknown drug compounds with blood or urine sample is a send-out test to HSA’s analytical toxicology laboratory that requires filling up a toxicology request form (https://www.hsa.gov.sg/about-us/applied-sciences/analytical-toxicology/test-samples)

^b Locally, screening for drug adulterants in TCM/herbal supplement samples and heavy metal testing (arsenic, cadmium, lead and mercury) are send-out tests to HSA's pharmaceutical laboratory that requires filling up a test report (https://www.hsa.gov.sg/docs/default-source/hprg-tmhs/chpb-tmhs/tmhs_testing_guidelines.pdf)

Routine blood tests performed include full blood count, urea/creatinine/electrolytes, liver function tests, serum glucose, thyroid function test, vitamin B₁₂ and folate levels. These tests are useful to easily identify reversible metabolic derangements, evaluate renal/liver function that may influence antipsychotic choice/dosing, depending on the drug pharmacokinetics, predominant site of metabolism and toxicity profile in renal/liver impairment, and potentially guide further lines of investigations. Other laboratory and urine tests may be performed depending on clinical suspicion. For example, in patients with chronic cough or insomnia/anxiety requiring frequent use of symptomatic medications or in those with known history of drug abuse/dependence, a urine drug screen for opiates, ephedrine/pseudoephedrine and benzodiazepines should be done. For patients who have consumed complementary medicine products from unlicensed providers, further testing for adulterated drug components and heavy metals may be considered.

Neuroimaging modalities such as computed tomography and magnetic resonance imaging of the brain are usually performed to rule out structural brain lesions. Interestingly, a systematic review of 16 studies by Forbes et al. in 2019 found inadequate evidence to support routine brain imaging in patients with acute psychosis in the absence of neurocognitive impairment.[20] However, the studies included in the review involve a disproportionately younger age group, possibly due to a higher prevalence of psychotic illness amongst them. Furthermore, given that many neurological conditions such as cerebrovascular events, intracerebral haemorrhage and neurodegenerative conditions become more prevalent with older age, it is prudent to have a lower threshold to performing neuroimaging in older adults when they present with first-onset psychosis. Electroencephalogram may be useful in patients with previous cerebrovascular events, structural brain pathologies or clinical concerns of ictal events, to look for epileptiform activity, in particular features of temporal lobe epilepsy, which has a known association with psychosis.[21]

Finally, lumbar puncture may be performed to assess for central nervous system infections, neuroinflammatory conditions such as autoimmune/paraneoplastic encephalitis, and neurodegenerative disorders including multiple sclerosis and Prion disease.[22] However, cerebrospinal fluid studies are not routinely recommended in proposed guidelines for the workup of psychosis,[22] likely due to the procedural risks involved. In addition, performing a lumbar puncture in an acutely psychotic and agitated patient is foreseeably difficult and will probably require the use of procedural sedation which carries additional risks.

MANAGING OLDER ADULTS WITH ACUTE PSYCHOSIS

Management principles for older adults with acute psychoses include addressing potentially reversible organic causes, attaining symptomatic control, and importantly, developing a targeted treatment and follow-up plan tailored to the patient’s clinical symptomatology, premorbid profile and overall goals of care.

Firstly, while establishing a definitive association between an organic derangement, such as a metabolic/electrolyte abnormality, and the acute psychotic event may be difficult, every effort should be made to identify and correct any potentially reversible organic precipitants as soon as possible. Secondly, for symptomatic control of psychotic symptoms, both non-pharmacological and antipsychotic medications can be trialled.

Non-pharmacological measures may include cognitive behavioural therapy (CBT) and other psychotherapies, verbal de-escalation in acute agitation, involvement of family in patient care and environmental modifications to optimise patient safety (e.g. placing patient near the nursing counter, removal of sharp/dangerous objects in the surroundings). Outside of formal CBT sessions by clinical psychologists, a simple CBT approach that frontline clinicians can adopt includes exploring the psychotic symptoms with the patients to help them gain insight and come up with coping strategies. For example, patients can be educated to recognise that ‘how they think will influence how they feel and behave’. When they hear voices about a false/delusional belief, they can find ways to come up with alternative explanations, test out the belief (reality testing) or attempt to normalise the experience. Effective methods of verbal de-escalation have been previously described, including engaging and listening attentively to the patient, responding in a manner that validates the patient’s feelings and concerns while avoiding verbal or non-verbal cues of provocation/confrontation, offering choices and setting limits.[23]

In most settings, however, pharmacological interventions in the form of antipsychotics are often required for symptomatic control. In particular, early initiation of antipsychotic treatment should be considered when the psychotic symptoms significantly impair the ability to provide necessary clinical care (e.g. vitals monitoring, performing scans/procedures) or lead to risk of self-harm or harm to others (e.g. in command hallucinations with violent content). The usual antipsychotics used in elderly patients, with their commonly prescribed doses and side effect profile, are detailed in Table 1. Antipsychotic medications can be classified into first-generation (typical) antipsychotics and second-generation (atypical) antipsychotics. There exists mechanistic differences between the two classes of medications — for instance, typical antipsychotics predominantly exert their effects through dopamine receptor antagonism, whereas atypical antipsychotics have a lower affinity for dopaminergic receptors and relatively high affinity for serotonergic receptors, with a wider range of receptor targets.[24,25] In general, prescription of oral antipsychotics to elderly patients should follow the old adage of ‘start low and go slow’, and as a rule of thumb, given at approximately half of standard adult dosing. In acutely agitated patients who refuse or are unable to tolerate oral medications, usage of intramuscular antipsychotics (e.g. haloperidol) when necessary can be considered. In the longer term, patients with medication compliance issues may benefit from a switch to long-acting depot injectable antipsychotics, but a psychiatrist referral would be warranted in such cases.

Table 1.

Antipsychotic medications for older adults.

Medication		Common side effects/remarks
First-generation oral antipsychotics (i.e. typical antipsychotics)
Haloperidol (oral)	Starting dose: 0.5–1 mg/day (divided doses) Maximum dose: 10–20 mg/day (divided doses)	• Extrapyramidal side effects (EPSEs)a, b • Hyperprolactinaemia • Anticholinergic side effectsc • Antihistaminergic side effectsd • Antiadrenergic side effectse • QTc prolongation • Neuroleptic malignant syndrome
Trifluoperazine (oral)	Starting dose: 2.5–5 mg/day Maximum dose: 15–20 mg/day
Second-generation antipsychotics (i.e. atypical antipsychotics)
Risperidone (oral)	Starting dose: 0.25–0.5 mg/day Maximum dose: 2–4 mg/day	• Metabolic side effectsa,f (highest risk of weight gain in olanzapine and clozapine) • EPSEs (less than first-generation antipsychotics; highest risk in risperidone) • Idiosyncratic reactions (agranulocytosis and myocarditis in clozapine) • Anticholinergic side effectsc • Antihistaminergic side effectsd • Antiadrenergic side effectse • QTc prolongation • Neuroleptic malignant syndrome
Olanzapine (oral)	Starting dose: 2.5–5 mg/day (divided doses) Maximum dose: 20 mg/day
Quetiapine (IR) (oral)	Starting dose: 25–50 mg/day Maximum dose: 300–400 mg/day
Aripiprazole (oral)	Starting dose: 5–10 mg/day Maximum dose: 30 mg/day
Clozapine (oral)	Starting dose: Referral to psychiatrist warranted Maximum dose: Referral to psychiatrist warranted
Intramascular antipsychotics (e.g. haloperidol 2–5 mg pro re nata)		Useful option in episodes of significant agitation where patients refuse or are unable to tolerate oral antipsychotics
Long-acting injectable depot antipsychotics		Useful option for long-term management in patients who have issues with treatment compliance; however, referral to psychiatrist is warranted

^aPredominant adverse effects in the drug class. ^bExtrapyramidal side effects include (from earliest to latest) acute dystonia (e.g. oculogyric crises), akathisia, pseudoparkinsonism and tardive dyskinesia. ^cAnticholinergic side effects include blurred vision, dry mouth, urinary retention and constipation. ^dAntihistaminergic side effects include sedation and weight gain. ^eAntiadrenergic side effects include postural hypotension (especially quetiapine, risperidone and clozapine). ^fMetabolic side effects include hypertension, hyperlipidaemia, diabetes mellitus and weight gain.

Ultimately, the treatment and follow-up plan should be tailored to the individual patient’s clinical profile, premorbid state and overall goals of care. For example, psychotherapies may be less effective in patients with comorbid personality disorders and poor clinical insight. In addition, certain antipsychotic drugs may not be suitable or require close monitoring when started in patients with particular medical comorbidities (e.g. haloperidol is contraindicated in Parkinson’s disease/Lewy body dementia, second-generation antipsychotics should be used with caution when there is prolonged QTc on electrocardiogram). Finally, goals of care should be determined by patient’s premorbid function and medical comorbidities, and there is a need to consider any previously documented advanced care planning discussions. Depending on the patient’s care needs and social set-up, appropriate siting of care needs to be arranged (such as institutionalisation in psychiatric nursing homes, engagement of home medical/nursing services).

In summary, we described a systematic approach to the older adult with acute psychosis [Figure 1]. A multidisciplinary team comprising various medical specialties, nursing staff and allied health professionals is necessary to provide the appropriate clinical care and facilitate the process of discharging and reintegration of these patients back into the community, through inpatient rehabilitation, caregiver training, behavioural management strategies, psychosocial support and community-based services. On discharge, longitudinal follow-up may be provided in an outpatient psychiatric, geriatric or general medicine clinic to monitor the disease trajectory and titrate antipsychotic medications based on the patients’ clinical response and side-effect profile.

Figure 1.

Chart shows the suggested algorithm for evaluation and management of older adults with acute psychosis.

TAKE-HOME MESSAGES

1. The causes of psychoses in older adults comprise organic (delirium, neurological, metabolic/endocrine, drugs/toxins) and primary psychotic aetiologies (schizophrenia spectrum disorders, mood disorders with psychotic features).

2. Clinical evaluation of an undifferentiated patient with acute psychosis involves detailed psychiatric history-taking, systemic review for features of organic conditions, corroborative history-taking from next-of-kin and a thorough medication review.

3. Relevant investigations for workup of acute psychosis in older adults may include blood and urine tests, neuroimaging, electrophysiological studies and invasive procedures like lumbar puncture, depending on clinical suspicion and diagnostic objectives.

4. Management principles include addressing potentially reversible organic precipitants, controlling psychotic symptoms with pharmacological and non-pharmacological methods, and developing a holistic and multidisciplinary treatment approach tailored to the individual patient’s clinical profile, social set-up and overall goals of care.

Closing Vignette

You performed a comprehensive workup that ruled out organic causes of the patient’s psychosis. Referrals to the departments of neurology and psychiatry were made during admission. In view of the short duration of symptoms, the patient was given a presumptive diagnosis of possible primary psychotic illness. She was started on oral quetiapine 25 mg/day, which was gradually uptitrated to 100 mg/day at the point of discharge. After two weeks of inpatient stay, comprising the process of clinical evaluation, initiation of antipsychotic treatment and inpatient rehabilitation and caregiver training, the patient was discharged with improvements in her symptoms. An outpatient psychiatric clinic appointment was provided for longitudinal follow-up and treatment of her condition.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

SMC CATEGORY 3B CME PROGRAMME

Online Quiz: https://www.sma.org.sg/cme-programme

Deadline for submission: 6 pm, 12 July 2023

Question	True	False
1. The two main symptoms of psychosis are hallucinations and delusions.
2. Hallucinations can be described as misinterpretations of external sensory stimuli.
3. Delusions refer to beliefs that are untrue, unshared and unshakeable.
4. The prevalence of psychotic symptoms in older adults is <1%.
5. Primary psychoses are more common in older adults than the younger age group.
6. Organic causes of psychoses can be broadly classified into neurological disorders, metabolic/endocrine abnormalities and drug/toxin exposure.
7. Recreational drugs that can cause drug-induced psychosis include cannabis, methamphetamine and phencyclidine.
8. In an older adult with a one-month history of florid psychotic symptoms and whom organic causes have been ruled out, very late onset schizophrenia can be diagnosed immediately.
9. For an older adult with acute psychosis, taking a corroborative history from the patient’s next-of-kin would suffice as the patient is unlikely to give a meaningful history.
10. The presence of command hallucinations in a psychotic patient is potentially a red-flag symptom that may pose greater risk of harm to oneself and others.
11. Psychiatric insight comprises an awareness of mental illness, correct attribution of psychotic symptoms with the underlying illness and understanding of the necessity of treatment.
12. Traditional Chinese medicines can be sent to any of the tertiary hospital laboratories to evaluate for drug adulterants.
13. Heavy metal testing of drug samples sent to Health Sciences Authority includes arsenic, cadmium, lead and mercury.
14. Neuroimaging is often a useful modality in older adults with acute psychosis to screen for central nervous system pathologies such as cerebral infarcts, haemorrhage, space-occupying lesions, neurodegenerative or demyelinating disease.
15. In patients with epilepsy, psychosis is most commonly seen in those with seizures originating from the occipital lobe.
16. Management of an older adult with acute psychosis should be based on the patient’s clinical profile and premorbid status, severity of psychotic symptoms and overall goals of care.
17. Antipsychotic drugs are usually initiated in elderly patients at much higher doses as compared to younger patients because elderly patients do not show clinical response at low doses.
18. Atypical antipsychotics tend to have fewer extrapyramidal side effects as compared to the typical antipsychotics due to lower affinity for serotonin receptors.
19. Clozapine is an atypical antipsychotic that carries a small but established risk of idiosyncratic drug-induced agranulocytosis.
20. Allied health professionals play an integral role in helping to rehabilitate and reintegrate older adults with psychosis back into the community and providing caregivers with psychosocial support and the necessary training in behavioural management.