> Table of Contents > Schizophrenia
Maja Skikic, MD
Jeffrey G. Stovall, MD
image BASICS
Schizophrenia is a chronic, severe, and disabling psychiatric condition characterized by neurocognitive changes and impairment in reality testing.
  • Major psychiatric disorder characterized by prodrome, active, and residual psychotic symptoms involving disturbances in appearance, speech, behavior, perception, and thought that last for at least 6 months.
  • DSM-5 has eliminated subcategories of schizophrenia (1).
  • System(s) affected: central nervous system
  • 7.7 to 43/100,000 (2)
  • Predominant sex: male-to-female ratio = 1.4:1.0
  • Age of onset: typically <30 years, earlier in males (early to mid-20s) than females (late 20s), with a smaller peak that occurs in women >45 years (3)
  • Lifetime (1%): highest prevalence in lower socioeconomic classes and urban settings (2-fold higher risk) (2)
  • 1.1% of the population > 18 years old; similar rates in all countries
  • Stems from a complex interaction between genetic and environmental factors; higher incidence if prenatal infection or hypoxia, winter births, firstgeneration immigrants, advanced paternal age, drug use, and genetic (velocardiofacial) syndromes
  • Overstimulation of mesolimbic dopamine D2 receptors, deficient prefrontal dopamine, and aberrant prefrontal glutamate (NMDA) activity results in perceptual disturbances, disordered thought process, and cognitive impairments (4).
If first-degree biologic relative has schizophrenia, risk is 8-10%; a 10-fold increase (5).
  • Currently, no known preventive measures decrease the incidence of schizophrenia.
  • Interventions to improve long-term outcome and associated comorbid conditions are employed during management.
  • Substance use disorders and nicotine dependence are common and lead to significant long-term medical and social complications (6).
  • Metabolic syndrome, diabetes mellitus, obesity, and certain infectious diseases, including HIV, hepatitis B, and hepatitis C all occur in higher-than-expected rates in individuals with schizophrenia.
Focus on identifying an insidious social and functional decline per history with the onset of ≥2 of the following characteristic symptoms on mental status exam:
  • Delusions (fixed, false beliefs)
  • Hallucinations (auditory > visual perceptual disturbances)
  • Disorganized thought (derailed or incoherent speech)
  • Grossly disorganized/catatonic behavior (hyper- or hypoactive movements that are often repetitive)
  • Negative symptoms (affective flattening, amotivation, avolition, asociality) (1)
No physical findings characterize the illness; however, chronic treatment with neuroleptic agents may result in parkinsonism, tardive dyskinesia, and other extrapyramidal symptoms.
  • Psychotic disorder due to another medical condition
    • Disorientation, in particular, indicates delirium.
    • Possible medical illnesses include porphyria, TBI, infection, tumor, metabolic, endocrine, and intoxication, including withdrawal states and disorders that affect the CNS (i.e., epilepsy, Huntington disease, Wilson disease, lupus cerebritis, anti-NMDA limbic encephalitis, metachromatic leukodystrophy).
  • Substance-induced psychosis: secondary to substance use/abuse, such as cocaine, hallucinogens (amphetamines, LSD, phencyclidine), cannabis (including synthetic), bath salts, alcohol, or prescribed medications including steroids, anticholinergics, and opiates
  • Personality disorders (paranoid, schizotypal, schizoid, borderline personality disorder)
  • Mood disorders: bipolar disorder, major depressive disorders with psychotic features, or schizoaffective disorder
  • Delusional disorder
  • Posttraumatic stress disorder
  • Cultural belief system
  • No tests are available to indicate schizophrenia.
  • Imaging and laboratory tests are needed to rule out other causes.
Initial Tests (lab, imaging)
These are needed to rule out a medical etiology of psychotic symptoms and when starting antipsychotic medications; these may include the following:
  • Brain MRI, EEG, LP (as clinically indicated)
  • CBC, blood chemistries
  • Thyroid-stimulating hormone (TSH)
  • Blood glucose level, preferably fasting
  • Hemoglobin A1C
  • Fasting lipid panel
  • Vitamin levels (thiamine, vitamin D, B12)
  • Drug/alcohol screen of blood and urine
  • Urinalysis
  • Urine pregnancy test
  • Rapid plasma reagin (RPR), HIV
  • Heavy-metal exposure: lead, mercury
  • Ceruloplasmin, urine porphobilinogen as indicated
  • ECG, for baseline QTc
Follow-Up Tests & Special Considerations
Clinical and laboratory tests for routine monitoring, at least yearly, if using antipsychotic medications (7)[A]
  • Blood pressure, weight, and waist circumference
  • CBC, blood chemistries
  • Fasting blood glucose level, hemoglobin A1C
  • Lipid panel
  • TSH
  • Pregnancy test and prolactin level, if indicated
  • ECG, monitoring for QTc prolongation
Diagnostic Procedures/Other
  • Psychological: not a routine part of assessment
  • MRI and EEG to rule out seizure/neurologic disorder
  • Lumbar puncture if indicated by clinical presentation
Test Interpretation
No diagnostic pathologic findings; however, ventriculomegaly is frequently seen on MRI with whole brain grey matter loss and white matter loss in medial temporal lobe structures preferentially (8)[A].
First Line
  • Two classes of antipsychotic medications: typical and atypical. First-line treatment is with an atypical antipsychotic given lower potential for extrapyramidal side effects.
    • Atypical (2nd generation)
      • Risperidone, olanzapine, ziprasidone, aripiprazole, quetiapine, paliperidone, iloperidone, asenapine, lurasidone, clozapine
    • Typical (1st generation)
      • Haloperidol, chlorpromazine, fluphenazine, trifluoperazine, perphenazine, thioridazine, thiothixene, loxapine
  • Medication choice is based on clinical and subjective response and side effect profile (7)[A].
  • Sensitivity to extrapyramidal adverse effects: atypical
  • For least risk of tardive dyskinesia: quetiapine, clozapine
  • For least risk of metabolic syndrome: aripiprazole, ziprasidone, lurasidone
  • For poor compliance/high risk of relapse: injectable form of long-acting antipsychotic such as haloperidol, fluphenazine, risperidone, olanzapine, aripiprazole, or paliperidone
  • Usual oral daily dose (initial dose may be lower)
    • Chlorpromazine: 200 mg BID
    • Aripiprazole: 10 to 30 mg/day
    • Asenapine: 5 mg BID (sublingual)
    • Fluphenazine: 5 mg BID
    • Haloperidol: 5 mg BID
    • Lurasidone: 40 to 80 mg/day
    • Olanzapine: 15 to 30 mg/day
    • Paliperidone: 3 to 12 mg/day
    • Perphenazine: 24 mg/day divided BID or TID
    • Quetiapine: 200 to 300 mg BID
    • Risperidone: 3 mg/day
    • Ziprasidone: 60 to 80 mg BID (with meal)
    • Clozapine: 200 mg BID
      • Start 12.5 mg/day and increase daily by 25 mg until dose of 300 mg/day split into BID dosing; do not exceed 900 mg/day. Effective in treatment of refractory or suicidal patients (7)[A]
      • Serious risk of agranulocytosis mandates registration with National Clozapine Registry and monitoring regular periodic CBC with differential (weekly to once monthly).
      • Significant risk of seizure at higher doses
      • Side effects can include myocarditis, DVT, sialorrhea, tachycardia, and weight gain.

  • Managing adverse effects of antipsychotics
    • Dystonic reaction (especially of head and neck): Give diphenhydramine 25 to 50 mg IM or benztropine 1 to 2 mg IM.
    • Akathisia: propranolol 10 mg BID or lorazepam 0.5 mg BID
    • Pseudoparkinsonism: trihexyphenidyl 2 mg BID (may be increased to 15 mg/day if needed) or benztropine 0.5 BID (range 1 to 4 mg/day)
    • Akathisia (restlessness): propranolol (30 to 60 mg in divided doses) or lorazepam (range 1 to 2 mg/day)
    • Neuroleptic malignant syndrome: hyperthermia, autonomic dysfunction, and extrapyramidal symptoms; requires hospitalization and supportive management (IVF and cessation of offending neuroleptic)
  • Geriatric considerations: All antipsychotics carry a black box warning for increased mortality risk in elderly dementia patients.
  • Adjunctive treatments
    • Benzodiazepines
      • May be effective adjuncts to antipsychotics during acute phase of illness
      • Useful for the treatment of catatonia
      • Withdrawal reactions with psychosis or seizures
    • Mood stabilizers (valproic acid, lithium, lamotrigine, carbamazepine): may be effective adjuncts for those with agitated/violent behavior (7,9)[A]
    • Antidepressants: if prominent symptoms of depression are present
    • Metformin: helps minimize risk of metabolic SE with use of AP (10)[A]
  • Consider in cases of suicidality, coexistence of an addiction, difficulty in engagement, or poor self-care.
  • Patients with schizophrenia should receive multidisciplinary care from both a primary care physician and a psychiatrist.
  • Family members often benefit from referral to family advocacy organizations such as NAMI (11)[A].
Family and patient education and psychotherapy. These include specific treatments to reduce the impact of psychotic symptoms and to enhance social functioning. Cognitive-behavioral therapy has been shown to be effective for specific symptoms of schizophrenia (12)[C].
No alternative therapies are validated.
  • Electroconvulsive therapy (ECT): For patients presenting with catatonic features, the option of ECT should be considered early when insufficient response to benzodiazepines is observed (7)[B].
  • Surgical interventions are not available.
Initial stabilization focuses on maintaining a safe environment and reducing acute psychotic symptoms and agitation through the initiation of pharmacologic treatment.
Admission Criteria/Initial Stabilization
The decision to admit is usually based on the patient's risk of self-harm or harm to others and the inability to care for self as governed by local legal statute.
Monitor for safety concerns and establish a safe and supportive environment.
Discharge Criteria
Based on the patient's ability to remain safe in the community. It reflects a combination of suicide risk, level of psychotic symptoms, support systems, and the availability of appropriate outpatient services.
  • Long-term symptom management and rehabilitation depend on engagement in ongoing pharmacologic and psychosocial treatment.
  • Monitoring is based on evaluation of symptoms (including safety and psychotic symptoms), looking for the emergence of comorbidities, medication side effects, and prevention of complications.
  • Newer atypical antipsychotics confer a higher risk of metabolic side effects such as diabetes, hypercholesterolemia, and weight gain.
  • Although there are no specific dietary requirements, attention should be paid to the high risk of development of obesity and metabolic syndrome in individuals with schizophrenia.
  • National Institute of Mental Health: Schizophrenia, at www.nimh.nih.gov/health/topics/schizophrenia/index.shtml
  • Helping a Family Member with Schizophrenia: www.aafp.org/afp/20070615/1830ph.html
  • National Alliance on Mental Illness (NAMI): www.NAMI.org
  • Typical course is one of remissions and exacerbations. Although uncommon, there are known cases of complete remission and of refractory illness
  • Negative symptoms are often most difficult to treat.
  • Excessive mortality occurs due to suicide, accidents, coronary artery disease, pulmonary disease, or substance use disorders; guarded prognosis
1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Arlington, VA: American Psychiatric Association;2013.
2. McGrath JJ. Variations in the incidence of schizophrenia: data versus dogma. Schizophr Bull. 2006;32(1):195-197.
3. Riecher-Rössler A, Häfner H. Gender aspects in schizophrenia: bridging the border between social and biological psychiatry. Acta Psychiatr Scand Suppl. 2000;102(407):58-62.
4. Laruelle M, Kegeles LS, Abi-Dargham A. Glutamate, dopamine, and schizophrenia: from pathophysiology to treatment. Ann N Y Acad Sci. 2003;1003:138-158.
5. Norman RM, Manchanda R, Malla AK, et al. The significance of family history in first-episode schizophrenia spectrum disorder. J Nerv Ment Dis. 2007;195(10):846-852.
6. Fagerström K, Aubin HJ. Management of smoking cessation in patients with psychiatric disorders. Curr Med Res Opin. 2009;25(2):511-518.
7. Hasan A, Falkai P, Wobrock T, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry. 2012;13(5):318-378.
8. Shenton ME, Dickey CC, Frumin M, et al. A review of MRI findings in schizophrenia. Schizophr Res. 2001;49(1-2):1-52.
9. Essali A, Al-Haj Haasan N, Li C, et al. Clozapine versus typical neuroleptic medication for schizophrenia. Cochrane Database Syst Rev. 2009;(1):CD000059.
10. Mizuno Y, Suzuki T, Nakagawa A, et al. Pharmacological strategies to counteract antipsychoticinduced weight gain and metabolic adverse effects in schizophrenia: a systematic review and meta-analysis. Schizophr Bull. 2014;40(6): 1385-1403.
11. Mojtabai R, Nicholson RA, Carpenter BN. Role of psychosocial treatments in management of schizophrenia: a meta-analytic review of controlled outcome studies. Schizophr Bull. 1998;24(4):569-587.
12. Grant PM, Huh GA, Perivoliotis D, et al. Randomized trial to evaluate the efficacy of cognitive therapy for low-functioning patients with schizophrenia. Arch Gen Psychiatry. 2012;69(2):121-127.
13. Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry. 2007;64(10):1123-1131.
Additional Reading
Saks E. The Center Cannot Hold: My Journey Through Madness. New York, NY: Hyperion; 2007.
See Also
Algorithm: Delirium
  • F20.9 Schizophrenia, unspecified
  • F20.0 Paranoid schizophrenia
  • F20.1 Disorganized schizophrenia
Clinical Pearls
  • A debilitating chronic mental illness that affects all cultures
  • Schizophrenia is characterized by positive symptoms, including hallucinations such as voices that converse with/about the patient, delusions that are often paranoid, and negative symptoms, including flattened affect, loss of a sense of pleasure, loss of will/drive, and social withdrawal.
  • Multidisciplinary teams to enhance patient and family coping with serious and persistent mental illness, to prevent and treat comorbidities, and to promote recovery