Recognition and Differential Diagnosis of Psychosis in Primary Care

KIM S. GRISWOLD; PAULA A. DEL REGNO; ROSEANNE C. BERGER

KIM S. GRISWOLD, MD, MPH, PAULA A. DEL REGNO, MD, AND ROSEANNE C. BERGER, MD

Am Fam Physician. 2015;91(12):856-863

Author disclosure: No relevant financial affiliations.

Psychosis is a symptom complex that may include hallucinations, delusions, disorders of thought, and disorganized speech or behavior. Acute psychosis is primary if it is symptomatic of a psychiatric disorder, or secondary if caused by a specific medical condition. Patients with primary psychiatric disorders are likely to have auditory hallucinations, prominent cognitive disorders, and complicated delusions. If psychosis is caused by a medical condition, the patient may exhibit cognitive changes and abnormal vital signs, and may have visual hallucinations. Illicit drug use is the most common medical cause of acute psychosis. Clinicians should ask about recent head injury or trauma, seizures, cerebrovascular disease, or new or worsening headaches. A subacute onset of psychosis should raise suspicion for an oncologic cause. Collateral history from family members is helpful in establishing the presentation and course of the illness. The physical examination should include complete neurologic and mental status assessments. Tachycardia or severe hypertension may indicate drug toxicity or thyrotoxicosis; fever may suggest encephalitis or porphyria. Suggested initial laboratory tests include a complete blood count, metabolic profile, thyroid function tests, urine toxicology, and measurement of parathyroid hormone, calcium, vitamin B₁₂, folate, and niacin. Testing for human immunodeficiency virus infection and syphilis should also be considered. Prompt recognition of the etiology of psychosis may improve treatment, consultation, and prognosis.

Psychosis is a symptom complex that may include hallucinations, delusions, disorders of thought, and disorganized speech or behavior. Primary care is often the point of first contact for patients exhibiting psychotic symptoms, and family physicians must be alert to the distinguishing features that point to a psychiatric or medical etiology.^1–3

Clinical recommendation	Evidence rating	References
For non–English-speaking patients, the use of a trained, bicultural interpreter is recommended in the evaluation of mental status.	C	⁴³
A mental status examination should be performed as part of the diagnostic approach to psychosis.	C	¹¹, ¹⁸, ³⁷, ⁴⁴
Brain imaging in the evaluation of psychosis should be reserved for patients with new, severe, unremitting headache; focal neurologic deficits; or a history of recent significant head trauma.	C	¹⁸, ³⁷, ⁴⁰

Recommendation	Sponsoring organization
Do not prescribe antipsychotics to patients for any indication without appropriate initial evaluation and appropriate ongoing monitoring.	American Psychiatric Association

Epidemiology

In the general population, there is an approximate 3% lifetime prevalence of psychotic disorders, with 0.21% accounting for psychosis due to a general medical condition.⁴ A recent review found a prevalence of 0.5% to 4.3% for bipolar disorder in primary care populations, and approximately 9% for bipolar spectrum illnesses.⁵ In one urban primary care population, the prevalence of psychotic symptoms was most commonly associated with depressive, anxiety, and panic disorders (42.4%, 38.6%, and 24.8%, respectively), followed by substance use disorders (13.8%).⁶

Childhood-onset schizophrenia (12 years or younger) is uncommon, with a prevalence of 0.2 to 0.4 per 10,000.7 However, children may exhibit psychotic symptoms secondary to medication adverse effects, drug toxicity or poisons, metabolic defects, autoimmune disorders, or other psychiatric disorders.⁸ In a 10-year cohort study, adolescent use of marijuana increased the occurrence of incident psychosis and, with ongoing use, the risk of persistent psychotic episodes.⁹

The prevalence of depression in pregnancy has been estimated to be 13.6% at 32 weeks' gestation to 17% at approximately 36 weeks' gestation.¹⁰ Postpartum psychosis occurs after one in 500 to 1,000 births; risk factors include a history of premorbid depression or bipolar disorder, prior peripartum mood disorder, or a previous episode of postpartum psychosis.^11,12

Etiology

The role of dopamine in the pathophysiology of psychosis is supported by the effectiveness of dopamine receptor antagonists in treating symptoms, and from evidence that psychosis-producing drugs such as methamphetamine, cocaine, and levodopa enhance dopamine secretion. Hypofunction of the N-methyl-d-aspartate glutamate receptor may cause schizophrenia.^13,14 Psychotic presentations associated with autoimmune disorders raise the possibility of shared genetic features or common exposures to etiologic factors, such as infections.¹⁵

Differential Diagnosis

Acute psychosis is primary if it is symptomatic of a psychiatric disorder, or secondary if caused by a specific medical condition. A key diagnostic distinction must be made between psychotic symptoms caused by delirium, a psychiatric disorder, or a defined medical condition (Table 1).^11,16 For example, if substance use or withdrawal is suspected, it may be difficult to differentiate delirium from psychosis.¹⁷ Delirium, an often reversible or temporary state of confusion with a rapid onset from altered brain function, is most often diagnosed in older or hospitalized populations, but it must be ruled out before reaching a definitive diagnosis of psychosis.¹¹ Patients with existing cognitive deficits may present with mixed delirium and psychosis. In these cases, it is helpful to ask about the temporal course of their symptoms, signs of systemic illness, or recent environmental change, and to obtain collateral information from caregivers. These patients may be taking multiple medications with psychoactive effects.

Patients with primary psychiatric disorders are more likely to have auditory hallucinations, prominent cognitive disorders, and complicated delusions.¹⁸ Schizophrenia, bipolar disorder, major depression, schizoaffective disorder, and brief psychotic disorder are the most common psychiatric illnesses that present in primary care with psychotic features. Level of consciousness and awareness are usually—but not always—intact. Overall appearance may be normal, or disheveled and unkempt. According to the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5), diagnostic criteria for schizophrenia include symptoms persisting for at least six months and significant difficulty in one or more major functional capacities.¹¹ However, during a prodromal phase in schizophrenia, patients may relate unusual perceptions or odd thoughts, and may report that sounds seem louder or colors more intense; the clinician should recognize that these symptoms may be early features of schizophrenia.¹⁶

In the manic phase of bipolar I disorder, the patient may present with at least a seven-day history of elevated or expansive mood, hallucinations or delusions, extreme goal-directed activity, and decreased need for sleep.¹¹ In schizoaffective disorder, patients may have characteristics of both mania (bipolar type) and major mood disturbance (depressive type). With psychotic depression, a patient is likely to have decreased energy and delusions or hallucinations consistent with major depression, such as voices reinforcing the patient's feeling of guilt or worthlessness. Alternatively, patients with major depressive disorder may present with prominent symptoms of anxiety or even panic. Patients experiencing a brief psychotic episode display the cardinal symptoms of delusions, hallucinations, and disorganized speech, but for a shorter period of time and with eventual recovery. Postpartum psychosis is classified in DSM-5 as a brief psychotic disorder if it occurs during pregnancy or within four weeks after delivery. During a peripartum episode of psychosis, women have delusions, hallucinations, or disorganized speech, and may have hallucinations telling them to hurt or kill their baby.

In secondary psychosis, there may be cognitive difficulties, abnormal vital signs, and visual hallucinations. Several medical conditions may initially present with psychosis; thus, a systematic approach to diagnosis is required to identify the cause (Table 2).^{5,11,16,19–39} Illicit drug use is the most common medical cause of acute psychosis.⁴⁰

Diagnosis		Clinical characteristics	Tests	Comments
Endocrine conditions
Adrenocorticotropic hormone-producing lung carcinoma (see oncologic, p. 860)		Bruising, glucose intolerance, hyperlipidemia, hypertension, moon facies, truncal obesity	Brain CT or MRI, chest radiography	—
Exogenous steroid use
Pituitary adenoma (Cushing disease)
Steroid-producing tumors
Diabetes mellitus type 1 or 2		Abnormal glucose metabolism, blurry vision, fatigue; hyper- or hypoglycemia may present with psychotic symptoms	A1C, complete metabolic profile, urinalysis	Rule out delirium
Parathyroid disease¹⁹		Abdominal discomfort, bone disorders, confusion, depression, fatigue, hallucinations, kidney stones, paranoia	Calcium and parathyroid hormone levels	1.5% prevalence in persons older than 65 years; 3.4% prevalence in postmenopausal women
Genetic or inherited conditions
Huntington disease²⁰		Schizophrenia-like symptoms may occur before cognitive or extrapyramidal changes	CT or MRI, genetic testing	Autosomal dominant; chromosome 4
Lewy body disease²¹		Executive dysfunction, fluctuating awareness, Parkinsonian motor symptoms, visual hallucinations	—	Neuroleptic drugs may cause sudden death or worsen movement, and should be avoided
Parkinson disease (often described with Lewy body disease as a continuum of symptoms)^21,22		Forward gait, slowing, stiffness, tremor; delusions, hallucinations, and psychotic symptoms are common in later stages	National Institute for Health and Care Excellence guidelines	Basal ganglia affected
Wilson disease²³		Abdominal swelling, delusions, jaundice, Kayser-Fleischer rings, schizophrenia-like psychosis, tremor, vomiting	Serum ceruloplasmin testing	Autosomal recessive; chromosome 13
				Copper accumulation
Infections
Encephalitis^24,25		Bizarre behaviors, chills, decreased sensorium, fever, headache, low sodium levels	Antibody testing, electrolyte levels, lumbar puncture, MRI	Affects limbic area of the brain
Human immunodeficiency virus²⁶		Cachexia, cognitive changes, delusions	CT, serum antibody testing	Rule out delirium; may be medication adverse effect; new onset of antiretroviral therapy can cause psychosis
Neurosyphilis²⁷		Abnormal gait, cognitive deficits, headache, incontinence, seizures, visual disturbances	CT or MRI, lumbar puncture, treponemal antibody testing (e.g., fluorescent treponemal antibody absorption test)	May be asymptomatic
Metabolic conditions
Acute intermittent porphyria²⁸		Abdominal pain, fever, peripheral neuropathy, tachycardia; may have only psychotic symptoms	Urine porphyrins testing	Genetic enzyme defect; fasting and drugs affecting the cytochrome P450 system act as inducers
Tay-Sachs disease, adult onset²⁹		Dystonia, spinocerebellar signs; psychosis appears in one-third to one-half of patients	Serum hexosaminidase testing	Often misdiagnosed
Neurologic conditions
Brain tumors, benign or space occupying (see oncologic, p. 860)		Headache, seizures, unilateral neurologic signs, visual hallucinations	CT or MRI	—
Dementia^16,30		Psychosis in 16% to 23% of older adults	Mental status examination, clock drawing test, Mini-Cog test	May co-occur with delirium
	Alzheimer type	Prominent short-term memory loss; may have aggression, agitation, or paranoia; delusions may be mistaken for misperceptions because of cognitive changes	—	—
Epilepsy ³¹		Primarily temporal lobe epilepsy; déjà vu, dissociation, visual hallucinations	Electroencephalography	Psychosis in 7% to 11% of patients
Nutritional deficiencies^32–34
Niacin (vitamin B₃)		Delusions, hallucinations, history of alcoholism	Eating disorder screening, vitamin B complex testing	Dermatitis, dementia, diarrhea, death
Thiamine (vitamin B₁)		Confabulation, history of alcoholism, Korsakoff psychosis, older age, Wernicke encephalopathy	Complete blood count, serum folate and vitamin B₁ testing	—
Vitamin B₁₂		Psychotic symptoms in late childhood, early adolescence; in older adults, ataxia, glossitis, cogwheel rigidity, abdominal symptoms, persecutory delusions, hallucinations	Complete blood count, Helicobacter pylori testing, intrinsic factor antibody testing, serum folate and vitamin B₁₂ testing	Replace with vitamin B complex plus niacin
Oncologic conditions
Ovarian teratoma³⁵		Altered consciousness, cognitive deficits, pelvic pain, psychosis, seizures	Abdominal CT or ultrasonography	Anti–N-methyl-d-aspartate receptor encephalitis may be associated with teratomas
Paraneoplastic limbic encephalitis³⁶		Neuropsychiatric symptoms, peripheral neuropathy, personality changes	CT, MRI, or electroencephalography; lumbar puncture; anti-Hu antibody testing; consider carcinoembryonic antigen and cancer antigen 125 testing	80% of cases associated with small cell lung cancer; Lambert-Eaton myasthenic syndrome may occur
Pharmacologic conditions (Table 3)
Drug intoxication or withdrawal		Acute onset, agitation, altered mental status, delusions, hypertension, tachycardia, visual hallucinations	History, toxicology	—
Medication adverse effect		Gradual onset	—	—
Psychiatric conditions^{5,11,16,37,38}
Bipolar I disorder		Mania: decreased need for sleep, elevated or irritable mood, racing thoughts, risk taking	Mental status examination, Mood Disorder Questionnaire	May present with depression; inquire about prior manic symptoms; selective serotonin reuptake inhibitors should be used with caution; lifetime prevalence of 0.24%
		Depression: anhedonia, changes in sleep and appetite, depressed mood, guilt, hopelessness, suicidality	Clinical diagnosis of exclusion
Depression with psychotic features		Anhedonia, changes in sleep and appetite, delusions, depressed mood, guilt, hallucinations, hopelessness, paranoia, suicidality; may present with symptoms of panic and anxiety	Mental status examination, Patient Health Questionnaire	Lifetime prevalence of 0.35%
			Clinical diagnosis of exclusion
Psychotic disorder (brief)		Delusions and paranoia with hallucinations lasting one day to one month; if in peri- or postpartum phases, mother may have delusions that the baby is possessed, or hallucinations telling her to harm the baby	Mental status examination	Psychiatric emergency
			Clinical diagnosis of exclusion
Schizoaffective disorder		Auditory hallucinations, delusions, paranoia; overlap with schizophrenia and mood disorders; functional difficulty not a defining criterion	Mental status examination	Lifetime prevalence of 0.3%
			Clinical diagnosis of exclusion
Schizophrenia		Auditory hallucinations, delusions, paranoia; decline in ability to work, or maintain relationships or self-care; a prodromal phase occurs when patients report peculiar perceptual experiences	Mental status examination	First break often in late adolescence or early adulthood; prevalence of 0.87%; treatment in prodromal phase may attenuate course and ameliorate severity
			Clinical diagnosis of exclusion
Thyroid dysfunction
Myxedema³⁹		Auditory or visual hallucinations, Capgras syndrome (delusions of “impostors,” either of the patient or significant others), few cognitive deficits, lethargy, normal level of consciousness, paranoia	Thyroid-stimulating hormone and thyroxine levels, thyroid antibodies	Psychosis in 5% to 15% of patients

Medical conditions associated with psychosis include autoimmune, endocrine, neurologic, and nutritional disorders.³⁷ Suspected endocrine conditions include thyroid and parathyroid dysfunction. Hallmark neurologic conditions include temporal lobe epilepsy, Parkinson disease, and Lewy body disease. A subacute onset of psychosis should raise suspicion for an oncologic cause, such as a steroid-producing tumor, space-occupying brain lesion, or paraneoplastic etiology. Genetic or heritable diseases should be considered; for example, Huntington disease may first present with a psychotic episode.²⁰

Information on medication interactions and use of herbal, over-the-counter, and recreational drugs should be elicited, because drug toxicity is a common cause of acute psychotic reactions^18,37 (Table 3^18,37,40 ).

Diagnostic Strategy

HISTORY

Obtaining a history from a patient with psychotic symptoms may be challenging.⁴¹ Although the differential diagnosis of primary and secondary psychoses is broad, sensitive inquiry about the patient's recent illness can help to focus diagnostic thinking.³⁸ Clinicians should ask about recent head injury or trauma to rule out subdural hematoma and obtain other relevant neurologic history, such as seizures, cerebrovascular disease, or new or worsening headaches.⁴²

Recognition of psychosis by the primary care physician is facilitated by prior knowledge of a patient's family, medical, and cultural history. Individual cultures reflect a set of beliefs, values, and practices shared by members of a particular group. Delusional thinking and hallucinations should be considered within the patient's specific cultural context. What may appear delusional in one culture may be normal in another. Hallucinations relating to religious expressions may be accepted in certain groups.¹¹ If the patient is not proficient in English, a bicultural interpreter is essential to assess whether the patient's thought processes and use of language are culturally consistent.⁴³

The temporal relationship and course of psychotic symptoms, as well as the patient's age, background, and general medical condition, may provide diagnostic clues.¹⁶ For example, a first major break in schizophrenia usually occurs in late adolescence or early adulthood, although earlier signs may have been present for years. An onset of psychosis may occur acutely after recreational drug use or as a later presentation in multiple sclerosis. Whenever possible, collateral information should be collected from family members.

The social history should include recent stressors or significant changes in the patient's life, such as job loss, death of a significant other, educational stress, or other traumatic event. Family history may provide clues to suggest a psychiatric diagnosis or heritable condition. Travel history may suggest exposure to infection, such as malaria. A history of multiple sex partners may suggest human immunodeficiency virus infection or syphilis. A dietary history is important to identify potential nutritional deficits, which are common in frail older persons. Niacin deficiency can be a consequence of severe eating disorders. Occupational or environmental exposures should be noted.

PHYSICAL EXAMINATION

The physical examination should include a complete medical and mental status examination. Tachycardia or severe hypertension may indicate drug toxicity or thyrotoxicosis; fever may suggest encephalitis or porphyria.¹⁸ Physical signs suggestive of underlying diagnoses include cushingoid appearance in certain endocrinopathies, arthritic deformities in autoimmune disorders, or movement and gait disturbances in conditions such as multiple sclerosis and Parkinson disease.³⁷ The neurologic examination should assess for focal signs, sensory deficits, myoclonus, or tremors. Tendon reflexes, cranial nerve testing, and ophthalmologic examination are important if a brain lesion, infection, or metabolic disease is suspected.

The mental status examination was reviewed in a previous article in American Family Physician.⁴⁴ It combines elements of the history, direct observation, and assessment of the patient's general behavior, mood, affect, speech, and thought processes—particularly hallucinations.¹¹ For example, frequency and features of auditory hallucinations may clarify their diagnostic significance. The patient's insight and judgment should be assessed; does the patient think he or she is ill? Has the patient noticed changes in thinking? If yes, what changes? Direct inquiry about suicidal or homicidal thoughts and plans is essential to determine whether immediate referral or hospitalization is indicated.

LABORATORY TESTING

When diagnostic signs and symptoms suggest a medical condition, targeted laboratory tests can be obtained.^18,37 Suggested initial tests include a complete blood count to assess for anemia, elevated white blood cell count, or increased eosinophils; a metabolic profile to evaluate renal and hepatic function and electrolyte and glucose levels; thyroid function tests; urine toxicology testing; and measurement of parathyroid hormone, calcium, vitamin B₁₂, folate, and niacin. Testing for human immunodeficiency virus infection and syphilis should also be considered. If there is concern for an autoimmune cause, antinuclear antibody testing and determination of the erythrocyte sedimentation rate can be useful. Rare conditions, such as acute intermittent porphyria or adult Tay-Sachs disease, may be identified by urine testing for porphyrins, or serum testing for hexosaminidase A.

Emergency brain imaging is usually not required unless the patient presents with new, severe, unremitting headache; focal neurologic deficits; or a history of recent significant head trauma.^18,37,40,42

Subsequent Management

Psychotic symptoms are debilitating and can be terrifying to patients and their families. Prompt recognition of the etiology may improve treatment, consultation, and prognosis. The patient and family members can be given therapeutic support in the office, and provided with appropriate educational literature.

If the patient expresses suicidal ideation or intent, or manifests symptoms of mania, immediate referral to emergency care is warranted.

If the psychosis is secondary, the family physician has an opportunity to deliver timely intervention and management for acute causes, and to ameliorate symptoms by providing long-term patient- and family-centered support for more chronic conditions.

Any patient with a primary diagnosis of a psychotic disorder will benefit from close collaboration between behavioral health specialists and the primary care physician.^3,45,46 The early use of antipsychotics, particularly clozapine (Clozaril), can decrease the risk of suicide in patients with schizophrenia, which may be as high as 15%, particularly in the initial phase of the illness.^41,46,47 Other treatments for schizophrenia were reviewed in a previous article in American Family Physician.⁴⁸

Despite optimal treatment, patients with schizophrenia and other psychotic disorders often have deficits in social functioning, are unable to maintain employment, and lack appropriate housing. The stigma of mental illness and poor mental health literacy compounds the challenges that patients face.⁴⁹ Patients may lack insight into medical comorbidities and complex drug regimens, and the course of illness may be complicated by tobacco or other substance use.⁵⁰ New and developing models are providing promising approaches toward integrated, patient-centered care for individuals with primary psychotic disorders.^51,52

Data Sources: PubMed, Agency for Healthcare Research and Quality reports, Essential Evidence Plus, the Cochrane database, and the National Guideline Clearinghouse were searched using the terms psychosis, primary care presentations, psychosis in children, postpartum psychosis, early psychosis, treatment of early psychosis, and specific medical conditions crossed with psychosis (e.g., multiple sclerosis, seizures, endocrine disorders, medications, substances). Search dates: February 2014 through July 2014.

Miller BF, Druss B. The role of family physicians in mental health care delivery in the United States: implications for health reform. J Am Board Fam Med. 2013;26(2):111-113.

. What is primary care mental health?: WHO and Wonca Working Party on Mental Health. Ment Health Fam Med. 2008;5(1):9-13.

Gavin B, Turner N, O'Callaghan E; Irish College of General Practitioners. Early psychosis: diagnosis & management from a GP perspective. http://www.icgp.ie/go/library/catalogue/item/F70DD4C1-8E09-42CC-87428F0A18670101. Accessed February 7, 2015.

Perälä J, Suvisaari J, Saarni SI, et al. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry. 2007;64(1):19-28.

Cerimele JM, Chwastiak LA, Dodson S, Katon WJ. The prevalence of bipolar disorder in general primary care samples: a systematic review. Gen Hosp Psychiatry. 2014;36(1):19-25.

Olfson M, Lewis-Fernández R, Weissman MM, et al. Psychotic symptoms in an urban general medicine practice. Am J Psychiatry. 2002;159(8):1412-1419.

Courvoisie H, Labellarte MJ, Riddle MA. Psychosis in children: diagnosis and treatment. Dialogues Clin Neurosci. 2001;3(2):79-92.

Reimherr JP, McClellan JM. Diagnostic challenges in children and adolescents with psychotic disorders. J Clin Psychiatry. 2004;65(suppl 6):5-11.

Kuepper R, van Os J, Lieb R, Wittchen HU, Höfler M, Henquet C. Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study. BMJ. 2011;342:d738.

Carter D, Kostaras X. Psychiatric disorders in pregnancy. BC Med J. 2005;47(2):96-99.

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.5th ed. Washington, DC: American Psychiatric Association; 2013.

Topiwala A, Hothi G, Ebmeier KP. Identifying patients at risk of perinatal mood disorders. Practitioner. 2012;256(1751):15-18.

Leo RJ, Regno PD. Atypical antipsychotic use in the treatment of psychosis in primary care. Prim Care Companion J Clin Psychiatry. 2000;2(6):194-204.

Seeman P. Glutamate and dopamine components in schizophrenia. J Psychiatry Neurosci. 2009;34(2):143-149.

Benros ME, Eaton WW, Mortensen PB. The epidemiologic evidence linking autoimmune diseases and psychosis. Biol Psychiatry. 2014;75(4):300-306.

Byrne P. Managing the acute psychotic episode. BMJ. 2007;334(7595):686-692.

Kaplan PW. Delirium and epilepsy. Dialogues Clin Neurosci. 2003;5(2):187-200.

Levenson JL. Psychosis in the medically ill. Primary Psychiatry. 2005;12(8):16-18.

Coker LH, Rorie K, Cantley L, et al. Primary hyperparathyroidism, cognition, and health-related quality of life. Ann Surg. 2005;242(5):642-650.

Corrêa BB, Xavier M, Guimarães J. Association of Huntington's disease and schizophrenia-like psychosis in a Huntington's disease pedigree. Clin Pract Epidemiol Ment Health. 2006;2:1.

Weintraub D, Hurtig HI. Presentation and management of psychosis in Parkinson's disease and dementia with Lewy bodies. Am J Psychiatry. 2007;164(10):1491-1498.

Holt RJ, Sklar AR, Darkow T, Goldberg GA, Johnson JC, Harley CR. Prevalence of Parkinson's disease-induced psychosis in a large U.S. managed care population. J Neuropsychiatry Clin Neurosci. 2010;22(1):105-110.

Bidaki R, Zarei M, Mirhosseini SM, et al. Mismanagement of Wilson's disease as psychotic disorder. Adv Biomed Res. 2012;1:61.

Barry H, Hardiman O, Healy DG, et al. Anti-NMDA receptor encephalitis: an important differential diagnosis in psychosis. Br J Psychiatry. 2011;199(6):508-509.

Kennedy PG, Chaudhuri A. Herpes simplex encephalitis. J Neurol Neurosurg Psychiatry. 2002;73(3):237-238.

Owe-Larsson B, Säll L, Salamon E, Allgulander C. HIV infection and psychiatric illness. Afr J Psychiatry (Johannesbg). 2009;12(2):115-128.

Friedrich F, Aigner M, Fearns N, Friedrich ME, Frey R, Geusau A. Psychosis in neurosyphilis — clinical aspects and implications. Psychopathology. 2014;47(1):3-9.

Ellencweig N, Schoenfeld N, Zemishlany Z. Acute intermittent porphyria: psychosis as the only clinical manifestation. Isr J Psychiatry Relat Sci. 2006;43(1):52-56.

MacQueen GM, Rosebush PI, Mazurek MF. Neuropsychiatric aspects of the adult variant of Tay-Sachs disease. J Neuropsychiatry Clin Neurosci. 1998;10(1):10-19.

Targum SD. Treating psychotic symptoms in elderly patients. Prim Care Companion J Clin Psychiatry. 2001;3(4):156-163.

Irwin LG, Fortune DG. Risk factors for psychosis secondary to temporal lobe epilepsy: a systematic review. J Neuropsychiatry Clin Neurosci. 2014;26(1):5-23.

Wells JL, Dumbrell AC. Nutrition and aging: assessment and treatment of compromised nutritional status in frail elderly patients. Clin Interv Aging. 2006;1(1):67-79.

Tufan AE, Bilici R, Usta G, Erdog an A. Mood disorder with mixed, psychotic features due to vitamin b12 deficiency in an adolescent: case report. Child Adolesc Psychiatry Ment Health. 2012;6(1):25.

Prakash R, Gandotra S, Singh LK, Das B, Lakra A. Rapid resolution of delusional parasitosis in pellagra with niacin augmentation therapy. Gen Hosp Psychiatry. 2008;30(6):581-584.

Vitaliani R, Mason W, Ances B, Zwerdling T, Jiang Z, Dalmau J. Paraneoplastic encephalitis, psychiatric symptoms, and hypoventilation in ovarian teratoma. Ann Neurol. 2005;58(4):594-604.

Grisold W, Giometto B, Vitaliani R, Oberndorfer S. Current approaches to the treatment of paraneoplastic encephalitis. Ther Adv Neurol Disord. 2011;4(4):237-248.

Freudenreich O. Differential diagnosis of psychotic symptoms: medical “mimics”. Psychiatr Times. http://www.psychiatrictimes.com/schizophrenia-psychotic-features/differential-diagnosis-psychotic-symptoms-medical-%E2%80%9Cmimics%E2%80%9D/page/0/2 (free subscription required). Accessed February 7, 2015.

Saunders K, Brain S, Ebmeier KP. Diagnosing and managing psychosis in primary care. Practitioner. 2011;255(1740):17-20.

Heinrich TW, Grahm G. Hypothyroidism presenting as psychosis: myxedema madness revisited. Prim Care Companion J Clin Psychiatry. 2003;5(6):260-266.

Best practice: assessment of psychosis. What causes severe mental illness, psychosis and mania? http://psychoticdisorders.wordpress.com/bmj-best-practice-assessment-of-psychosis. Accessed February 7, 2015.

Buchanan RW, Kreyenbuhl J, Kelly DL, et al.; Schizophrenia Patient Outcomes Research Team (PORT). The 2009 schizophrenia PORT psychopharmacological treatment recommendations and summary statements. Schizophr Bull. 2010;36(1):71-93.

Fujii DE, Ahmed I. Psychotic disorder caused by traumatic brain injury. Psychiatr Clin North Am. 2014;37(1):113-124.

Cambridge J, Singh SP, Johnson M. Cambridge JSinghSPJohnsonMThe need for measurable standards in mental health interpreting: a neglected area. http://pb.rcpsych.org/content/36/4/121.full. Accessed February 7, 2015.

Snyderman D, Rovner B. Mental status exam in primary care: a review. Am Fam Physician. 2009;80(8):809-814.

Marshall M, Rathbone J. Early intervention for psychosis. Cochrane Database Syst Rev. 2011;6:CD004718.

Kuipers E, Yesufu-Udechuku A, Taylor C, Kendall T. Management of psychosis and schizophrenia in adults: summary of updated NICE guidance [published correction appears in BMJ. 2014;348:g2234]. BMJ. 2014;348:g1173.

Harkavy-Friedman JM. Risk factors for suicide in patients with schizophrenia. Psychiatr Times. http://www.psychiatrictimes.com/articles/risk-factors-suicide-patients-schizophrenia/page/0/2 (free subscription required). Accessed February 7, 2015.

Schultz SH, North SW, Shields CG. Schizophrenia: a review. Am Fam Physician. 2007;75(12):1821-1829.

International Early Psychosis Association Writing Group. International clinical practice guidelines for early psychosis. Br J Psychiatry Suppl. 2005;48:s120-s124.

Planner C, Gask L, Reilly S. Serious mental illness and the role of primary care. Curr Psychiatry Rep. 2014;16(8):458.

Cerimele JM, Strain JJ. Integrating primary care services into psychiatric care settings: a review of the literature. Prim Care Companion J Clin Psychiatry. 2010;12(6).

Wulsin LR, Söllner W, Pincus HA. Models of integrated care. Med Clin North Am. 2006;90(4):647-677.

Medical causes
Delirium (acute, transient disturbance in mental function)
	Hypo- or hyperglycemia
	Hypoxia
	“ICU psychosis”
	Medication interactions or withdrawal
	Sepsis
	Serum electrolyte or metabolic abnormalities
	Sleep deprivation
Other medical causes (chronic disturbance in mental function)
	Autoimmune disorders (e.g., multiple sclerosis, systemic lupus erythematosus)
	Endocrine disorders (e.g., Cushing disease, diabetes mellitus, thyroid disease)
	Genetic, heritable conditions
	Neurologic conditions (e.g., dementia, encephalitis, epilepsy, Parkinson disease)
	Nutritional conditions (e.g., vitamin B deficiency)
	Oncologic conditions (e.g., ovarian teratoma, small cell lung cancer)
	Pharmacologic causes (e.g., medication adverse effect, substance abuse or withdrawal)
Psychiatric causes^11,16
Bipolar I disorder
Depression with psychotic features
Psychotic disorder (brief), with or without marked stressors*
Schizoaffective disorder
Schizophrenia

Adrenergics
Alcohol, benzodiazepines, or barbiturates (withdrawal)
Antiarrhythmics
Antibiotics
Anticholinergics
Antihistamines
Antimalarials
Antituberculars
Cannabis, ketamine, or bath salts
Cocaine, methamphetamine, or 3,4-methylenedioxymeth-amphetamine (“Ecstasy”)
Corticosteroids
Dextromethorphan
Dopamine agonists
Heavy metals
Organophosphates
St. John's wort
Thyroid hormones