Evidence-Based Reviews

Psychosis: 6 steps rule out medical causes in kids

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Time-saving algorithm combines efficiency with a thorough evaluation.



John, age 16, is admitted to our inpatient psychiatric unit, complaining of “a 2-week constant headache” caused by “voices arguing in my head.” He has lived in Mexico with an uncle for 6 months but returned home last week for medical evaluation of his headaches.

His parents report that John developed normally until 3 years ago, when he gradually lost interest in his favorite activities and became socially withdrawn. He has not attended school in 2 years. He has no history of illicit drug use and is not taking prescription or over the-counter medications.

Complete physical examination, neurologic exam, and routine screening lab test results are normal. Thinking that a high lead content of cookware used in Mexico might be causing John’s symptoms, we order a lead level: result-0.2 mg/dL (

We diagnose schizophreniform disorder, but John’s parents refuse to accept this diagnosis. They repeatedly ask if we can do more to identify a medical cause of their son’s psychiatric symptoms.

As in John’s case, young patients or their parents may resist the diagnosis of a chronic mental illness such as schizophrenia. Understandably, they may be invested in trying to identify “medically treatable” causes. You can address their anxieties by showing them that you have systematically evaluated medical causes of psychosis.

We offer such a tool: an algorithm and tables to help you identify common and rare medical conditions that may cause or exacerbate psychotic symptoms in patients ages 3 to 18.

An evidence-based algorithm

Multiple factors—developmental, psychological, family, environmental, or medical—typically cause psychotic symptoms in a child or adolescent. Evaluating all possibilities is essential, but guidelines tend to minimize medical causes. American Academy of Child and Adolescent Psychiatry guidelines, for example, recommend that “all medical disorders (including general medical conditions and substance-induced disorders) are ruled out,”1 but they do not specify which medical conditions to consider.

To supplement existing guidelines, we searched the literature and developed an evidence-based algorithm to help you systematically consider medical causes of pediatric psychotic symptoms. We excluded children age 2

How to use it. The algorithm walks you through a medical systems review. You begin with a complete history, then address six causes of psychotic symptoms: substance abuse, medication reactions, general medical conditions, unexplained somatic symptoms (such as from toxic environmental exposures), developmental and learning disabilities, and atypical presentations.

Don’t stop if you find one possible cause of psychotic symptoms; continue to the end of the algorithm. The more factors you identify, the greater your chance of finding a treatable cause that may ameliorate your patient’s symptoms.

To make the algorithm clinically useful, we listed conditions in order of decreasing probability of causing psychotic symptoms. For example, the first cause listed is substance-induced disorders,3 which are most common among adolescent patients. We also “triaged” medical conditions from common to rare (based on estimated prevalence of association with psychotic symptoms), listing rare causes only in cases of atypical presentation or treatment resistance.

Supporting tables. The following discussion summarizes data that support the algorithm and its tables:

  • medications reported to cause psychosis (Table 1)
  • medical conditions most likely to cause psychosis (Table 2)
  • medical conditions that rarely cause psychosis (Table 3).
Table 1

Drugs that may cause psychotic symptoms

Drug classPsychotic symptoms
Bizarre behavior/delusionsAuditory or visual hallucinations
Amphetamine-like drugsXX
Anabolic steroidsX
Angiotensin-converting enzyme (ACE) inhibitors X
Anticholinergics and atropineXX
Antidepressants, tricyclic X
Beta-adrenergic blockersXX
Calcium channel blockersX
Dopamine receptor agonistsXX
Fluoroquinolone antibioticsXX
Histamine H1 receptor blockers X
Histamine H2 receptor blockersX
HMG-CoA reductase inhibitorsX
Nonsteroidal anti-inflammatory drugsX
Procaine derivatives (procainamide, procaine penicillin G)XX
Selective serotonin reuptake inhibitors X
Sulfonamides X
Source: Adapted from reference 10.
Table 2

Common medical conditions that may cause pediatric psychosis symptoms*

CategoryConditions not to forgetCommon symptoms/comments
RheumatologicLupus erythematosusJoint pain, fever, facial butterfly rash, prolonged fatigue
InfectiousViral encephalitisFever, headache, mental status change; may occur in perinatal period
NeurologicMultiple sclerosisVaried neurologic deficits, especially ophthalmologic changes and weakness
NeurosyphilisPersonality change, ataxia, stroke, ophthalmic symptoms
Seizure (temporal lobe epilepsy, interictal psychosis)Paroxysmal periods of sudden change in mood, behavior, or motor activity with or without loss of consciousness
ToxicologicCarbon monoxide poisoningShortness of breath, mild nausea, headache, dizziness
* Clinically significant symptoms that meet DSM-IV-TR criteria for a primary psychiatric disorder.
Click here to view citations supporting statements in this table
Table 3

Medical conditions that rarely cause pediatric psychosis symptoms*

HyperthyroidismTachycardia, weight loss, excessive sweating, tiredness, inability to sleep, diarrhea, shakiness, muscle weakness
Thymoma/myasthenia gravisShortness of breath, swelling of face, muscle weakness (especially around eyes)
Porphyria (acute intermittent porphyria, porphyria variegate)Intermittent abdominal pain (severe) accompanied by dark urine
Fabry’s diseaseBurning sensations in hands and feet that worsen with exercise and hot weather
Niemann-Pick disease, type CVertical gaze palsy, hepatosplenomegaly, jaundice, ataxia
Prader-Willi syndromeObesity, hyperphagia, mild to moderate mental retardation, hypogonadism, tantrums, obsessive-compulsive disorder
Epstein-Barr virusFever, sore throat, adenopathy, fatigue, poor concentration
Lyme diseaseTarget lesion, fever; high-risk geographic area
Malaria/typhoid feverFever, mental status change; endemic area
Mycoplasma pneumoniaFever, mental status change; may occur in absence of pneumonia
RabiesHistory of exposure
CitrullinemiaMental status change, high plasma citrulline and ammonia
Tay-Sachs diseaseUnsteadiness of gait and progressive neurologic deterioration
HomocystinuriaDislocated lenses, blood clots, tall stature, some mental retardation
Juvenile metachromatic leukodystrophyCognitive decline, ataxia, pyramidal signs, peripheral neuropathy, dystonia; 60% of cases present before age 3
Central pontine myelinolysisSuspect in patient with pathogenic polydipsia
Huntington’s diseaseChorea, myoclonic seizures, poor coordination, emotional lability
Moyamoya diseaseParesis, syncopal episodes
NarcolepsyExcessive daytime sleepiness, cataplexy
Subacute sclerosing panencephalitisVisual hallucinations, loss of developmental milestones
Traumatic brain injuryOccurring 4 to 5 years after a loss of consciousness >30 minutes
Wilson’s diseaseTremors, muscle spasticity, possible liver inflammation
Pellagra (vitamin B6 deficiency)Redness, swelling of mouth and tongue, diarrhea, rash, abnormal mental functioning; seen with isoniazid treatment for tuberculosis
Cancers (pancreatic, CNS papilloma, germinoma)Postural headache, neurologic signs, increased intracranial pressure, early morning nausea, vomiting
Lead intoxicationHeadache, fatigue, mental status change
Mercury poisoningAbdominal pain, bleeding gums, metallic taste; history of exposure
* Clinically significant symptoms that meet DSM-IV-TR criteria for a primary psychiatric disorder.
Click here to view citations supporting statements in this table


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