Bingo! part 2. Psychosis: Six Steps rule out medical causes in kids

HousePart two in a series, sharing information you can use to empower yourself when dealing with health professionals who seem more interested in the speed of their diagnosis than on figuring out what’s really going on, today a differential diagnosis algorithm devised for docs to use to rule out other medical causes of psychosis in kids.

The diagnosis “Schizophrenia” is one that can itself cause great harm to the life of any person receiving it.
It is also a diagnosis of exclusion and of elimination – which means eliminating other possible causes before arriving at the last on  list. Many experienced clinicians with diagnose it only with “with great reluctance” or exercising “extreme caution”, or after many years, not minutes. This diagnosis It is never one to be arrived at with greatest speed  possible.

This algorithm for ruling our other causes of what “presents” as psychosis was first published in 2006…

The printer friendly  pdf is at the end of the post.

For part see 1 yesterday’s post ,  here….


Journal of Family Practice

Psychosis: 6 steps rule out medical causes in kids

Vol. 5, No. 2 / February 2006

David A. Fohrman, MD

Board-certified child, adolescent, and adult psychiatrist, Private practice, Children’s Hospital, San Diego

Martin T. Stein, MD

Professor of clinical pediatrics, Director, developmental and behavioral pediatrics, University of California, San Diego, Children’s Hospital, San Diego

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developed normally until 3 years ago, when he gradually lost interest in his favorite activities and became socially withdrawn.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 (<10 mg/dL is normal for adolescents). We do no additional diagnostic tests—such as an EEG, CT, or MRI—because John’s clinical presentation does not suggest a specific medical condition that could be causing or exacerbating his psychotic symptoms.

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 ❤ because determining conclusively that a 2-year-old is experiencing “psychotic symptoms” is very difficult.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 1Drugs that may cause psychotic symptoms

Drug class Psychotic symptoms
Bizarre behavior/delusions Auditory or visual hallucinations
Amphetamine-like drugs X X
Anabolic steroids X
Angiotensin-converting enzyme (ACE) inhibitors X
Anticholinergics and atropine X X
Antidepressants, tricyclic X
Antiepileptics X
Barbiturates X X
Benzodiazepines X X
Beta-adrenergic blockers X X
Calcium channel blockers X
Cephalosporins X X
Corticosteroids X
Dopamine receptor agonists X X
Fluoroquinolone antibiotics X X
Histamine H1 receptor blockers X
Histamine H2 receptor blockers X
HMG-CoA reductase inhibitors X
Nonsteroidal anti-inflammatory drugs X
Opioids X X
Procaine derivatives (procainamide, procaine penicillin G) X X
Salicylates X X
Selective serotonin reuptake inhibitors X
Sulfonamides X
Source: Adapted from reference 10.

Table 2Common medical conditions that may cause pediatric psychosis symptoms*

Category Conditions not to forget Common symptoms/comments
Rheumatologic Lupus erythematosus Joint pain, fever, facial butterfly rash, prolonged fatigue
Infectious Viral encephalitis Fever, headache, mental status change; may occur in perinatal period
Neurologic Multiple sclerosis Varied neurologic deficits, especially ophthalmologic changes and weakness
Neurosyphilis Personality 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
Toxicologic Carbon monoxide poisoning Shortness 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 3Medical conditions that rarely cause pediatric psychosis symptoms*

Category/condition Symptoms/comments
Hyperthyroidism Tachycardia, weight loss, excessive sweating, tiredness, inability to sleep, diarrhea, shakiness, muscle weakness
Thymoma/myasthenia gravis Shortness 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 disease Burning sensations in hands and feet that worsen with exercise and hot weather
Niemann-Pick disease, type C Vertical gaze palsy, hepatosplenomegaly, jaundice, ataxia
Prader-Willi syndrome Obesity, hyperphagia, mild to moderate mental retardation, hypogonadism, tantrums, obsessive-compulsive disorder
Epstein-Barr virus Fever, sore throat, adenopathy, fatigue, poor concentration
Lyme disease Target lesion, fever; high-risk geographic area
Malaria/typhoid fever Fever, mental status change; endemic area
Mycoplasma pneumonia Fever, mental status change; may occur in absence of pneumonia
Rabies History of exposure
Citrullinemia Mental status change, high plasma citrulline and ammonia
Tay-Sachs disease Unsteadiness of gait and progressive neurologic deterioration
Homocystinuria Dislocated lenses, blood clots, tall stature, some mental retardation
Juvenile metachromatic leukodystrophy Cognitive decline, ataxia, pyramidal signs, peripheral neuropathy, dystonia; 60% of cases present before age 3
Central pontine myelinolysis Suspect in patient with pathogenic polydipsia
Huntington’s disease Chorea, myoclonic seizures, poor coordination, emotional lability
Moyamoya disease Paresis, syncopal episodes
Narcolepsy Excessive daytime sleepiness, cataplexy
Subacute sclerosing panencephalitis Visual hallucinations, loss of developmental milestones
Traumatic brain injury Occurring 4 to 5 years after a loss of consciousness >30 minutes
Wilson’s disease Tremors, 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 intoxication Headache, fatigue, mental status change
Mercury poisoning Abdominal 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

Substance abuse

Substance abuse is common among adolescents and adults with psychotic illnesses.4 Drug-induced states can cause delusions, hallucinations, paranoia, and disorganized behavior,5 which are reported most commonly during intoxication and withdrawal.6 Diagnosis is often straightforward because of the temporal association between the substance abuse and onset of psychotic symptoms.

Little evidence supports a causal relationship between drug use and the development of chronic psychotic symptoms, however. Case reports link use of 3,4-methylenedioxymethamphetamine (“Ecstasy”), lysergic acid diethylamide (LSD), and marijuana to chronic schizophrenia-like symptoms.7 The strongest evidence links long-term methamphetamine and cocaine use to chronic psychotic symptoms.8,9


Side effects of at least 25 drug classes have been reported to mimic psychosis (Table 1),10 but little is known about the incidence and prevalence of this problem. Case reports and chart reviews provide the only data that associate most medications with psychotic symptoms. These disagree on what defines a “psychotic symptom,” and most fail to rule out delirium as a possible cause.

The relationship between glucocorticosteroids and psychotic symptoms has been studied extensively. A clear link has been found between corticosteroids at dosages >40 mg/d and a markedly elevated risk for transient psychotic symptoms.11

Medical conditions

We identified 27 medical conditions that may cause or worsen clinical symptoms of psychosis (Tables 2 and 3) by searching PubMed, psychiatric journals, and neuropsychiatry and consult-liaison textbooks. We included only conditions:

  • shown to cause significant morbidity in pediatric populations

  • shown to have a statistically significant association with psychotic symptoms, or patients’ symptoms consistently resolved when the condition was treated.

Neurologic conditions. Many neurologic conditions had been reported to cause psychotic symptoms,12 but only four met at least one of our inclusion criteria. Psychotic symptoms are statistically associated with epilepsy,13 Huntington’s disease,14 and Wilson’s disease;15 psychotic symptoms associated with multiple sclerosis resolve when the underlying medical condition is treated.16

Endocrine disorders. Behavioral disturbances (including psychosis) may be the earliest manifestation of an endocrine disorder.17 Cushing’s syndrome,18 hyperthyroidism,19 and hypothyroidism20—met our inclusion criteria.

Cushing’s syndrome—caused by long-term systemic glucocorticoids and thyroid disorders—is not uncommon in children and adolescents but rarely presents with psychotic behaviors. For each endocrine disorder we included, however, at least one case report described delayed diagnosis because of prominent psychosis. Treating the endocrinopathies resolved the psychotic symptoms.

Genetic disorders. Genetically determined neurodevelopmental disorders usually present in very young children, but some may appear later. Genetic conditions that co-occur with psychotic symptoms at rates significantly greater than the population prevalence include Prader-Willi syndrome,21 metachromatic leukodystrophy,22 Turner’s syndrome,21 velocardiofacial syndrome,23 and Wilson’s disease.15

Acute intermittent porphyria, GM2 gangliosidosis (Tay-Sachs disease), and homocystinuria are rare conditions with unknown prevalence in patients with psychotic disorders. Still, they are important to consider when evaluating youths with psychosis because case reports link their treatment with psychotic symptom resolution.24-26

Infectious disease. An infectious CNS disease does not usually present with psychotic symptoms only. When this does happen, making the correct diagnosis as soon as possible is critical because early treatment is associated with better outcomes.27 Misdiagnosis as a primary psychotic disorder may expose a patient to psychotropics that may adversely affect clinical outcome.

Viruses that affect the CNS (viral encephalopathies) are the infections most likely to cause psychotic symptoms. By decreasing frequency, they are human simian virus, HIV, influenza, measles, Epstein-Barr virus, mumps, and rabies.27,28 Bacterial infections that cause psychosis include mycoplasma pneumonia,29 syphilis,30 typhoid fever,31 and Lyme disease.32

Brain tumor. Childhood brain tumors often present with behavioral symptoms associated with headache, vomiting, visual changes, and motor and cognitive symptoms. A CNS tumor rarely presents with isolated neuropsychiatric symptoms.33 A few case reports describe intracranial tumors initially misdiagnosed as primary psychotic illness because of prominent psychotic symptoms.34,35 In each case, these symptoms resolved with tumor resection.

A temporal relationship does not necessarily equate to a “causal” relationship, however. Tatter et al36 describe a case of “reoccurrence” of manic symptoms initially thought to be caused by an arteriovenous malformation (AVM) 10 years after the AVM was successfully removed. The important point is that, although rarely, pediatric brain tumor can present with prominent psychotic symptoms.

Environmental toxin exposure may cause well-defined psychiatric syndromes,37 although frank psychosis is uncommon at presentation. Most often, environmental toxins produce an encephalopathic process of which psychosis may be one symptom. A few toxic exposures—such as lead,38 carbon monoxide,39 and elemental mercury40 —have presented with prominent psychotic symptoms without other encephalopathic symptoms.

Collagen vascular disease is associated with significantly elevated rates of psychiatric illness, especially depression, but only systemic lupus erythematosus (SLE) is known to be associated with prominent psychosis. Case series report delayed SLE diagnosis in patients with this presentation.41

High-dose pulse corticosteroids have been reported to effectively treat SLE-related psychotic symptoms,42 although high-dose corticosteroids can also cause psychotic symptoms. The timing and character of the symptoms can help you determine whether using corticosteroids is helping or making the patient worse.

Using the algorithm

John’s mother and father fear that the inpatient team’s diagnosis of a primary psychotic disorder means that a medical cause has been permanently “ruled out.” To reassure them, we use the algorithm to explain in concrete terms the thought process that led us to John’s psychiatric diagnosis. We walk them through the algorithm and its tables, explaining how we used evidence to rationally rule out all known medical causes of psychotic symptoms in pediatric patients.

John’s parents are relieved to know that the case is not closed, even though we found no medical cause for their son’s condition. If more clinical data become available, we remain open to considering the possibility that medical conditions could be causing or worsening their son’s symptoms.

Related resources

  • American Academy of Child and Adolescent Psychiatry. Practice parameter for the assessment and treatment of children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry 2001;40(7 Suppl):4S-23S.

  • Schiffer RB, Klein RF, Sider RC. The medical evaluation of psychiatric patients. New York: Plenum Medical Book Co.; 1998.

  • National Organization for Rare Disorders (NORD).


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2. Behrman RE (ed). Nelson textbook of pediatrics (17th ed). Philadelphia: WB Saunders; 2003:397-518.

3. Dalmau A, Bergman B, Brismar B. Psychotic disorders among inpatients with abuse of cannabis, amphetamine and opiates. Do dopaminergic stimulants facilitate psychiatric illness? Eur Psychiatry 1999;14(7):366–71.

4. Breslow RE, Klinger BI, Erickson BJ. Acute intoxication and substance abuse among patients presenting to a psychiatric emergency service. Gen Hosp Psychiatry 1996;18(3):183–91.

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9. Ujike H, Sato M. Clinical features of sensitization to methamphetamine observed in patients with methamphetamine dependence and psychosis. Ann NY Acad Sci 2004;1025:279–87.

10. Drugs that may cause psychiatric symptoms. Med Lett Drugs Ther 2002;44:29–62.

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12. Cummings JL. Organic psychosis. Psychosomatics 1988;29(1):16–26.

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14. Mendez MF. Huntington’s disease: update and review of neuropsychiatric aspects. Int J Psychiatry Med 1994;24:189–208.

15. Brewer GJ. Recognition and management of Wilson’s disease. Proc Soc Exp Biol Med 2000;223:39–46.

16. Mendhekar DN, Mehta R, Puri V. Successful steroid therapy in multiple sclerosis presented as acute psychosis. J Assoc Physicians India 2004;52:512–3.

17. Reus VI. Behavioral disturbances associated with endocrine disorders. Ann Rev Med 1986;37:205–14.

18. Hirsch D, Orr G, Kantarovich V, et al. Cushing’s syndrome presenting as a schizophrenia-like psychotic state. Isr J Psychiatry Relat Sci 2000;37(1):46–50.

19. Lu CL, Lee YC, Tsai SJ, et al. Psychiatric disturbances associated with hyperthyroidism: an analysis report of 30 cases. Zhonghua Yi Xue Za Zhi (Taipei) 1995;56(6):393–8.

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22. Hyde TM, Ziegler JC, Weinberger DR. Psychiatric disturbances in metachromatic leukodystrophy. Insights into the neurobiology of psychosis. Arch Neurol 1992;49(4):401–6.

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25. Ryan MM, Sidhu RK, Alexander J, Megerian JT. Homocystinuria presenting as psychosis in an adolescent. J Child Neurol 2002;17(11):859–60.

26. MacQueen GM, Rosebush PI, Mazurek MF. Neuropsychiatric aspects of the adult variant of Tay-Sachs disease. J Neuropsychiatry Clin Neurosci 1998;10(1):10–9.

27. Caroff SN, Mann SC, Gliatto MF, et al. Psychiatric manifestations of acute viral encephalitis. Psych Annals 2001;31(3):193–204.

28. Caplan R, Tanguay PE, Szekely AG. Subacute sclerosing panencephalitis presenting as childhood psychosis. J Am Acad Child Adolesc Psychiatry 1987;26(3):440–3.

29. Gillberg C. Schizophreniform psychosis in a case of mycoplasma pneumoniae encephalitis. J Autism Dev Disord 1980;10(2):153–8.

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31. Venkatesh S, Grell GA. Neuropsychiatric manifestations of typhoid fever. West Indian Med J 1989;38(3):137–41.

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33. Stein MT, Duffner PK, Wery JS, Trauner D. School refusal and emotional liability in a 6 year old boy. J Dev Behav Pediatr 2001;22(suppl):29–32.

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36. Tatter SB, Ogilvy CS. Recurrent manic episode 10 years after arteriovenous malformation resection. J Clin Psychiatry 1995;56(2):83.

37. Hartman DE. Missed diagnosis and misdiagnosis of environmental toxicants exposure: the psychiatry of toxic exposure and multiple chemical sensitivity. Psychiatr Clin North Am 1998;21(3):659–70.

38. Bahiga LM, Kotb NA, El-Dessoukey EA. Neurological syndromes produced by some toxic metals encountered industrially or environmentally. Z Ernahrungswiss 1978;17(2):84–8.

39. Olson KR. Carbon monoxide poisoning: mechanisms, presentation, and controversies in management. J Emerg Med 1984;1(3):233–43.

40. Fagala GE, Wigg CL. Psychiatric manifestations of mercury poisoning. J Am Acad Child Adolesc Psychiatry 1992;31(2):306–11.

41. Turkel SB, Miller JH, Reiff A. Case series: neuropsychiatric symptoms with pediatric systemic lupus erythematosus. J Am Acad Child Adolesc Psychiatry 2001;40(4):482–5.

42. Baca V, Lavalle C, Garcia R, et al. Favorable response to intravenous methylprednisolone and cyclophosphamide in children with severe neuropsychiatric lupus. J Rheumatol 1999;26(2):432–9.

Current Psychiatry ©2006 Quadrant HealthCom Inc.


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