Best Practice: Assessment of psychosis
The evaluation of the acutely psychotic patient includes a thorough history and physical examination, as well as laboratory tests. Based on the initial findings, further diagnostic tests may be warranted.
Organic causes must be considered and excluded before the psychosis is attributed to a primary psychotic disorder.
The most common cause of acute psychosis is drug toxicity from recreational, prescription, or OTC drugs.
Patients with structural brain conditions, or toxic or metabolic process presenting with psychosis, usually have other physical manifestations that are readily detectable by history, neurological examination, or routine laboratory tests.
Brain imaging is reserved for patients with specific indications, such as head trauma or focal neurological signs. The routine use of such imaging is unlikely to reveal an underlying organic cause and is not recommended.
A careful medical history should be taken to identify possible organic causes of the psychosis. This should be considered even if the patient has a known primary psychotic disorder, as organic and psychiatric causes can co-exist. Key features of the history include:
- History of recent or past head trauma: a recent head trauma should raise suspicion of a subdural haematoma. Previous head trauma may cause a seizure disorder and increases the risk of schizophrenia.
- Recent seizures or a known history of a seizure disorder: it is important to establish the timing of psychosis in relation to seizure activity (postictal, ictal, and interictal).
- Neurological symptoms: key symptoms that should prompt suspicion of organic CNS disease include new-onset headaches or changes in headache pattern, focal weakness or sensory loss, visual disturbance (double vision or partial vision loss), and speech deficits, including dysarthrias and aphasias. Abnormal body movements, memory loss, and tremor in older patients should prompt suspicion of dementia. Fluctuating consciousness suggests that delirium is present.
- Recreational drug use: any recent use of alcohol, cocaine, cannabis, amphetamines, or phencyclidine should prompt suspicion of drug-induced psychosis. A history of heavy alcohol, benzodiazepine, or barbiturate use followed by abrupt cessation should raise suspicion of a withdrawal syndrome, especially if the onset is abrupt.
- Prescription medications: common offending medications include anticholinergic drugs, dopamine agonists, corticosteroids, adrenergic drugs (stimulants, propranolol, clonidine), and thyroid hormones. It is important to establish when any new drugs were started, or when doses were changed, and how the timing relates to the onset of symptoms.
- OTC medications: common offending drugs include dextromethorphan, antihistamines, and medications containing phenylpropanolamine, especially if used chronically or at very high doses.
- Exposure to heavy metals: if the main water supply is from a well or the patient has any occupation or hobby that involves chemical or heavy metal exposure, heavy metal poisoning should be suspected. Physical symptoms of lead toxicity include nausea, vomiting, diarrhoea, anaemia, weakness in limbs, and convulsions. Common symptoms of arsenic poisoning are vomiting, diarrhoea, kidney failure, pigmentation of soles and palms, hypersalivation, and progressive blindness. Mercury toxicity presents with symptoms of metallic taste, hypersalivation, gingivitis, tremors, and blushing. Psychosis with mercury toxicity is rare.
- Exposure to organophosphates: a history of the use of pesticides (especially in farm workers) should prompt suspicion of organophosphate poisoning. The diagnosis is clinical. There is often an initial acute cholinergic crisis and an intermediate phase of respiratory paralysis (24 to 96 hours), followed at 1 to 3 weeks by neuropathy. Physical symptoms and signs include bronchospasm, nausea and vomiting, blurred vision, diaphoresis, confusion, anxiety, respiratory paralysis, and extrapyramidal symptoms.
- Dietary history: the use of extreme diets (such as vegan diets), eating disorders, or malnutrition related to alcoholism, drug dependence, or deprivation increases risk of vitamin deficiencies. Deficiencies of vitamin B12, folate, thiamine, and niacin can all cause psychosis. A malabsorption syndrome may produce changes in bowel habit.
- Recent surgery: hypoxia should be considered if an acute psychosis occurs during the postoperative period.
- Family history may reveal a genetic-based neurological, metabolic, or autoimmune disorder in a first-degree relative. Wilson’s disease is the most common inherited cause of psychosis. A history of a primary psychotic disorder in a first-degree relative may also be present.
- Travel history: if infectious encephalitis is suspected as the cause, a travel history is important to assess the risk of exposure to infectious causes, such as parasites (rare in the US).
Initial assessment should consist of vital signs and a mental state examination. Important features in the general examination that may help to identify specific causes of psychosis include:
- Fluctuations in the level of consciousness, suggesting delirium
- The presence of tachycardia and hypertension, strongly suggesting either drug intoxication or an acute drug withdrawal syndrome
- The presence of a fever, prompting suspicion of encephalitis. Characteristic rashes may be noted on general inspection for some causes of encephalitisView imageView image
- Evidence of malnutrition: vitamin deficiencies should be considered as the cause
- Signs of hypo- or hyperthyroidism or cushingoid features,View image prompting suspicion of an endocrine cause
- Noticeable joint deformities, rashes, or other specific signs associated with an underlying autoimmune disorder
- Dysmorphic body features, prompting consideration of the rare genetic and chromosomal causes.
A thorough neurological examination should be undertaken. Focal neurological signs are a common feature of encephalitis. Possible signs include:
- Brisk tendon reflexes
- Babinski’s sign
- Cranial nerve deficits
- Neuropathy with weakness and decreased vibrational and position sense: may be seen in vitamin B deficiencies
- Signs of raised intracranial pressure: may be present in patients with subdural haematoma or intracranial tumours.
The aim of initial tests is to identify patients with an organic cause, as well as exclude the most common organic causes. All patients require:
- Serum electrolytes
- Liver function tests (including gamma-GT)
- Serum creatinine
- Urine drug screen
- Vitamin B12 and folate levels
- Thyroid function tests (TSH, free T4)
- Consideration of ANA and ESR.
CBC findings are non-specific. Leukocytosis should prompt suspicion of infection. Serum electrolytes may be abnormal if there is an underlying metabolic or endocrine disturbance. Liver function tests may be abnormal in a range of conditions, including chronic alcohol abuse and Wilson’s disease. Renal function tests may detect underlying renal failure.
Recreational drugs are the most common causes of acute psychosis. Urine drug testing is required in all patients to screen for amphetamines, cocaine, cannabis, and benzodiazepines. If other drugs, such as hallucinogens, are suspected based on the history and clinical features, a blood or hair drug screen is also necessary. Known causative medications should be discontinued. If symptoms resolve, a diagnosis of medication-induced psychosis can be made retrospectively. Withdrawal syndromes are diagnosed clinically. Blood alcohol levels are useful if alcohol is suspected as being a contributing factor, although a positive result is not diagnostic of alcohol abuse.
Vitamin B12 and folate levels should be measured to exclude nutritional deficiency. Thyroid function tests (TSH and T4) should be measured to exclude hypo- or hyperthyroidism. ANA and ESR, although non-specific, may be useful to screen for autoimmune disorders. If ANA is positive or the ESR is elevated, specific investigations for the suspected disorder should be performed, guided by clinical findings.
When a patient presents with delirium with psychosis, a wide range of urgent initial tests need to be performed to elicit the underlying cause, including all of the blood tests already mentioned to be performed in all patients, as well as the following:
- Blood glucose
- Blood alcohol
- Urine microscopy and culture
- Blood culture
Patients with suspected Cushing’s syndrome are initially investigated by a 24-hour urinary free cortisol test. Those with suspected hyperparathyroidism require a serum calcium and serum parathyroid hormone test. When porphyria is considered it is investigated by performing a spot urine sample for porphobilinogen during acute attack, and 24-hour urine for porphyrins, porphobilinogen, and delta-aminolevulinic acid. Another metabolic condition, Wilson’s disease, is investigated by checking the serum ceruloplasmin. This may be followed up with a 24-hour copper excretion test. Lysosomal storage diseases require specific diagnostic tests, but these may include a skin biopsy, genetic tests, and the detection of alpha-galactosidase enzyme in plasma or serum. Homocystinuria is diagnosed using quantitative tests for homocystine in urine and blood and molecular genetic testing. Metachromatic leukodystrophy is diagnosed by checking arylsulfatase A enzyme activity in WBCs or in cultured skin fibroblasts. Where the diagnosis of a chromosomal disorder is being considered, specific genetic tests are required.
Further tests are guided by the clinical presentation. In situations of suspected acute drug toxicity, further investigations may be required. These may include:
- Serum CK
- Blood glucose
- Cardiac troponin
- Prothrombin time and activated partial thromboplastin time
- Serum phosphorous
- Serum calcium
- Urine dextromethorphan
- Serum paracetamol.
In addition to recreational drugs and medications, other toxic exposures may be present and should also be excluded if suggested by clinical features. Organophosphate toxicity is a clinical diagnosis. Measuring cholinesterase activity in red blood cells correlates with CNS acetylcholinesterase and is a useful marker of organophosphate poisoning but is not readily available. Where heavy metal toxicity is considered, a urine heavy-metal screen is performed.
Patients presenting with extreme malnourishment may have pellagra due to niacin deficiency or Korsakoff’s psychosis due to thiamine deficiency. Niacin and/or thiamine levels should be measured if these conditions are suspected. An erythrocyte transketolase activity test and a 24-hour urinary thiamin excretion test may also be requested in suspected thiamine deficiency. Where folate deficiency is being considered, serum homocysteine may also be measured subsequently to the folate and serum vitamin B12 tests. The following tests may also be performed, having checked the serum niacin level, if deficiency is suspected: serum tryptophan, serum nicotinamide adenine dinucleotide, and serum nicotinamide adenine dinucleotide phosphate.
HIV testing (if HIV neurological complications are suspected) and a treponemal test (if neurosyphilis is suspected) should be considered if clinical features suggest the diagnoses, known risk factors are present, or the patient comes from a population where syphilis, HIV, or other STDs are common.
Screening for Wilson’s disease should be considered in patients with abrupt-onset psychosis. Tests include ceruloplasmin, total serum copper concentration, 24-hour urine copper excretion, and a slit-lamp ophthalmological examination to detect Kayser-Fleischer rings.
MRI or CT scan of the brain should be ordered if an organic CNS cause is suspected. Indications for MRI or CT scanning include:
- A history of head trauma (to detect intracranial bleeding or haematoma)View imageView imageView image
- Presence of focal neurological signs
- Suspicious headache or change in headache patternView image
- Late age of onset or pronounced cognitive deficits, suggestive of dementia.
MRI brain scan with gadolinium is used when the diagnosis of multiple sclerosis is being considered.View image A lumbar puncture and CSF analysis (including a differential cell count, culture, and serology) should be performed if encephalitis is suspected and a mass lesion in the brain has been excluded. It is also performed with suspected multiple sclerosis along with an evoked potentials test. CT scan of the chest is useful to diagnose thymoma following a CXR.
An EEG should be considered if temporal lobe epilepsy or encephalopathy is suspected, due to confusion and poor memory about reported psychotic episodes or other symptoms of infection. Genetic testing may be indicated in specific situations, such as testing for Huntington’s disease in people with dementia.
Further investigations in people with suspected Cushing’s syndrome include blood glucose, low-dose dexamethasone suppression test, evening salivary cortisol, and the dexamethasone-corticotropin-releasing hormone test. People with abnormal thyroid initial tests may be followed up with a free T3 level and thyroid autoantibodies ELISA for anti-thyroid peroxidase.
Psychiatric causes of psychosis can only be diagnosed once organic causes have been excluded. A careful psychiatric history is required to diagnose primary psychotic disorders. The criteria for diagnosing these conditions are as follows:
- A. Characteristic symptoms: ≥2 of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated): delusions, hallucinations, disorganised speech (e.g., frequent derailment or incoherence), grossly disorganised or catatonic behaviour, or negative symptoms (i.e., affective flattening, alogia, or avolition). Note that only 1 criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on the person’s behaviour or thoughts or ≥2 voices conversing with each other.
- B. Social/occupational dysfunction: for a significant portion of the time since the onset of the disturbance, ≥1 major areas of functioning such as work, interpersonal relations, or self-care are markedly below the level achieved before the onset (or when the onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement).
- C. Duration: continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meet criterion A (i.e., active-phase symptoms) and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or ≥2 symptoms listed in criterion A present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences).
- D. Schizoaffective and mood disorder exclusion: schizoaffective disorder and mood disorder with psychotic features have been ruled out because either (1) no major depressive episode, manic episode, or mixed episode has occurred concurrently with the active-phase symptoms; or (2) if mood episodes have occurred during active-phase symptoms, their total duration has been brief relative to the duration of the active and residual periods.
Schizoaffective disorder 
- Meets criteria for diagnosis of schizophrenia with a duration of symptoms >6 months.
- Associated symptoms that meet criteria for a mood episode (major depressive episode, manic episode, or mixed episode) are present for a substantial portion of the total duration of the active and residual periods of the illness.
- During the same period of illness, there have been delusions or hallucinations for at least 2 weeks in the absence of prominent mood symptoms.
Brief psychotic disorder 
- Presence of ≥1 of delusions, hallucinations, disorganised speech, or grossly disorganised or catatonic behaviour. A symptom is not included if it is a culturally sanctioned response pattern.
- Duration of an episode of at least 1 day but <1 month, with eventual full return to premorbid level of functioning.
- The disturbance is not better accounted for by a mood disorder with psychotic features, schizoaffective disorder, or schizophrenia and is not due to the direct physiological effects of a substance or a general medical condition.
Schizophreniform disorder 
- Meets criteria for diagnosis of schizophrenia, but the duration, including prodromal, active, and residual phases, is >1 month but <6 months.
Depression with psychotic features 
- Sleep pattern is abnormal. The patient reports having trouble falling asleep, waking up too early, or sleeping too much without feeling rested.
- Subjective thought disorder: patient reports that thoughts come more slowly.
- Objective thought disorder: the patient’s speech may be slowed, and thought blocking may be present.
- The patient has reduced interest in and ability to enjoy usual activities.
Bipolar disorder 
- Alternating episodes of mania and depression.
- Sleep pattern: the patient reports needing significantly fewer hours of sleep to feel rested.
- Subjective thought disorder: the patient reports thoughts coming too fast to keep up with and often reports improved clarity of thinking.
- Objective thought disorder: speech is pressured for most conversations.
- Participation in usual activities is increased and often inefficient, and the patient does not complete tasks.
Delusional disorder 
- Non-bizarre delusions of at least 1 month’s duration.
- The patient has never met the criteria for the diagnosis of schizophrenia. However, tactile and olfactory hallucinations may be present in delusional disorder if they are related to the delusional theme.
- Apart from the impact of the delusions or its ramifications, functioning is not markedly impaired and behaviour is not obviously odd or bizarre.
- If mood episodes have occurred concurrently with delusions, their total duration has been brief relative to the duration of the delusional periods.
- The disturbance is not due to direct physiological effects of a substance or a general medical condition.
Shared psychotic disorder (folie a deux) 
- A delusion develops in a person in the context of a close relationship with another person or people who have an already established delusion.
- The delusion is similar in content to that of the person who already has an established delusion.
- The disturbance is not better accounted for by another psychotic disorder (e.g., schizophrenia) or a mood disorder with psychotic features and is not due to the direct physiological effects of a substance (e.g., drug abuse, medication) or a general medical condition.
The diagnostic criteria for substance-induced psychotic disorder are: 
- Prominent hallucinations or delusions are present.
- It is common to have psychotic symptoms while intoxicated with many drugs of abuse (cocaine, phencyclidine, amphetamines, dextromethorphan). In addition, chronic cannabis use can lead to a persistent psychotic illness that does not go away even with abstinence from cannabis.
- Psychotic symptoms are not better accounted for by another mental disorder.
- Psychotic symptoms do not occur exclusively during the course of a delirium