Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis

Br J Psychiatry. 2011 Dec;199(6):508-9. Epub  2011 Oct 7.

Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis.


Department of Psychiatry, Royal College of Surgeons in Ireland, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.


We present four cases of confirmed anti-NMDA receptor encephalitis; three presented initially with serious psychiatric symptoms and the other developed significant psychiatric symptoms during the initial phase of illness. Brain biopsy findings of one patient are also described. Psychiatrists should consider anti-NMDA receptor encephalitis in patients presenting with psychosis and additional features of dyskinesias, seizures and catatonia, particularly where there is no previous history of psychiatric disorder.


Assessment of psychosis

Drug or toxin exposure

OTC drugs and supplements, prescription drugs, and recreational drugs may cause psychosis and other psychiatric symptoms. Examples of OTC drugs that may cause psychosis include:

  • Dextromethorphan
  • Antihistamines
  • Medications containing phenylpropanolamine.

Psychosis usually occurs with chronic use of these drugs or very high doses. Ephedra-containing herbal supplements, such as ma huang, can also trigger psychosis. Other kinds of centrally acting herbal supplements are also available, but it is unknown whether these can trigger psychosis.

Prescription drugs that can trigger psychosis include:

  • Anticholinergics
  • Dopamine agonists
  • Corticosteroids
  • Adrenergics (stimulants, propranolol, and clonidine)
  • Thyroid hormones.

Psychosis is a rare and relatively idiosyncratic adverse effect of many other medications. These include isotretinoin, indometacin, several antibiotics, and antiviral drugs.

Psychosis may be induced by intoxication with recreational drugs, such as:

  • Cocaine
  • Cannabis
  • Amphetamines
  • Phencyclidine
  • Alcohol
  • Inhalants (solvents, aerosols, gases, nitrites).

Cannabis use is an environmental risk factor for development of a persistent psychotic disorder. This occurs in a dose-related fashion, increasing the risk by 2 to 6 times for patients without other risk factors. [2] Cannabis use by age 15 years has been shown to increase the risk of developing schizophreniform disorder (odds ratio 1.95). [3] Cannabis intoxication can also cause a psychosis of short duration. Paradoxically, patients with psychotic disorders may report that acute use is associated with reduction of psychosis severity or of anxiety. Some studies report improvement in negative symptoms. However, there is a clear relationship between cannabis use and psychotic relapse. [4]

Withdrawal syndromes from benzodiazepines, barbiturates, and alcohol may also include psychosis. This may be a presenting sign.


Heavy metal exposure causes a wide range of psychiatric and physical (cardiovascular, renal, reproductive, GI, neurological) sequelae. The most common heavy metals responsible for toxic exposures in the US are arsenic, mercury, and lead. Any of these can cause psychosis as a rare symptom.

Continue reading “Assessment of psychosis”

Best Practice: Assessment of psychosis

BMJ:  helping doctors make better decisions

Step-by-step diagnostic approach

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.

Medical history

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).
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