> Table of Contents > Psychosis
Robert A. Baldor, MD, FAAFP
image BASICS
Syndrome seen with schizophrenia, schizoaffective disorder, mood disorder, substance use, medical problems, delirium, and dementia; symptoms include the following:
  • Positive symptoms: hallucinations and delusions (fixed false and often paranoid beliefs created as the patient loses the ability to correct errors in thinking)
  • Negative symptoms: apathy, avolition, withdrawal
  • Disorganized speech/behavior
  • Cognition: decreased working memory, difficulty with attention, poor and slow information interpretation
  • Schizophrenia: peak onset 18 to 25 years in men; women peak onset 25 to 35 years
    • 1% of the U.S. population; thought to be similar worldwide
  • Delusional disorder: 0.03% of population
  • Bipolar type I: 1% of population
  • Prevalence in major depression not known
  • Neurodevelopmental predisposition plus 1st/3rd trimester in utero insult (e.g., 1st-trimester infection or 3rd-trimester birth hypoxia) leads to exaggerated neuronal apoptosis in late adolescence with subsequent thalamic sensory overload. Increased dopaminergic mesolimbic transmission may contribute to delusions and hallucinations in schizophrenia. Dopamine deficiency in mesocortical pathways may contribute to frontal lobe hypoactivity often associated with apathy and withdrawal in schizophrenia. Glutamate, neurosteroids, and neurodevelopmental abnormalities are active areas of research.
  • Postulated stress-diathesis model: Individuals biologically at risk develop psychosis when under stress.
Schizophrenia: 50% concordance for monozygotic twins, little or no shared environmental effect; multiple candidate genes involving disruption of neurodevelopment
Substance abuse (particularly marijuana), family history of psychosis, lower socioeconomic status
Community interventions for early detection and treatment of prodromal symptoms show promise.
  • Serious mental illness is associated with metabolic syndrome, autonomic dysfunction, and sudden cardiac death.
  • Cancer mortality: particularly breast and lung cancer
  • Substance abuse disorders, including nicotine dependence
First, rule out delirium: Psychosis should not have fluctuating consciousness/reduced clarity of awareness.
  • Mental status exam: disorganized idea sequencing and/or error correction, not incorrect thought content, is the condicio sine qua non of schizophrenia. Patients often have negative symptoms (e.g., social withdrawal, lack of initiative, poverty of thought) and disorganized behavior.
  • Attention to neurologic focalities, antipsychotic-induced parkinsonism, tardive dyskinesia, and akathisia
  • May rarely present with catatonia: extreme excitement/lack of movement; posturing, mutism, grimacing, waxy flexibility
  • Schizophrenia: positive symptoms (psychosis) and negative symptoms (flat affect), prodrome of social withdrawal, cognitive impairment; schizophreniform disorder: psychotic/prodromal symptoms in <6 months; schizoaffective disorder: manic/depressive mood disorder with hallucinations/delusions that persist even when euthymic; schizotypal personality disorder: no true psychosis but distance in relationships and odd beliefs; delusional disorder: nonbizarre delusion (e.g., erotomanic, grandiose, jealous, persecutory, somatic), no negative/mood symptoms
  • Mood disorder with psychotic features: can occur in mania/depression. Delusions often mood-congruent; psychosis remits when mood improves.
  • Substance-induced psychosis: alcohol and benzodiazepine withdrawal, intoxication with cocaine, bath salts, PCP, cannabis, amphetamines, hallucinogens, and alcohol. May persist beyond acute intoxication
  • Borderline personality disorder: During extreme stress, patients often experience auditory/visual hallucinations (psychosis NOS).
  • Posttraumatic stress disorder: psychosis associated with traumatic recollections. Often visual hallucinations (vs. more auditory in schizophrenia)
  • Psychosis due to general medical condition: delirium, stroke, infection, collagen vascular disease, head injury, tumor, interictal, porphyria, syphilis, and so forth
  • Medication-induced psychosis: common causes: steroids, L-dopa, anticholinergic medication, antidepressants in bipolar patients, interferon, digoxin, stimulants
Test for causes of delirium mimicking psychosis, if uncertain.
  • Broad screen for medical causes: CBC, metabolic panel, LFTs, thyroid-stimulating hormone (TSH), rapid plasma reagin (RPR), HIV, vitamin B12, U/A, and screens for subclinical infection in elderly
  • Screen for drugs of abuse.
  • No imaging necessary for diagnosis. Consider MRI/CT to evaluate for medical cause of symptoms, especially if new onset or in elderly. In research studies, schizophrenia is associated with enlarged lateral ventricles and less frontal activity.
Follow-Up Tests & Special Considerations
Because of elevated risk related to schizophrenia and psychotropic medications, screen for metabolic syndrome.
  • Consider Wilson disease, porphyria, metachromatic leukodystrophy, inflammatory conditions.
  • Consider ECG: Antipsychotics can prolong corrected QT (QTc) interval, particularly ziprasidone, thioridazine, droperidol, IV haloperidol
  • Consider lumbar puncture if unable to distinguish from delirium and/or unexplained rapid-onset psychosis.
  • Consider electroencephalogram (EEG) for partial complex seizures and psychosis associated with preictal and postictal events.
Before antipsychotic treatment, lipid profile, fasting blood sugar, LFTs, metabolic panel, weight (1)[B]
  • Antipsychotics are the mainstay of treatment (1)[B].
  • Classified as typical versus atypical. Dopamine-2 (D2) antagonists with varied affinity for the receptor. Atypicals also block serotonin 5-HT2A receptors. Help positive symptoms more than negative. Nonspecific effect on agitation begins early; antipsychotic effect takes 1 to 6 weeks.
  • For mania with psychotic features, a mood stabilizer may be used with an antipsychotic.
  • For major depression with psychotic features, antidepressant and antipsychotic medications yield better response rate than either medication alone.
  • In delirium, must treat underlying cause
  • Risks of antipsychotic medications include the following:
    • Acute dystonia: Use 1 to 3 mg IM/IV benztropine initially, then 0.5 to 2 mg BID-TID or diphenhydramine 50 to 100 mg IM/IV BID-TID max 400 mg/day.
    • Parkinsonism: Lower antipsychotic dose; switch to atypical (particularly, quetiapine, olanzapine, or clozapine) or add benztropine 0.5 to 2 mg PO BID-TID, diphenhydramine 25 to 50 mg BID-TID.
    • Akathisia: intense restlessness, especially legs. Lower antipsychotic dose; treat with &bgr;-blocker, anticholinergic, or benzodiazepine; may switch to antipsychotic with lower risk for akathisia such as quetiapine, olanzapine, iloperidone, or clozapine
    • Tardive dyskinesia: 20% of those treated long-term with typicals. Switch to clozapine or quetiapine. If cannot, minimize dose.
    • P.879

    • Neuroleptic malignant syndrome: potentially fatal; rigidity, tremor, fever, autonomic instability, mental status changes; discontinue neuroleptic; ICU; volume resuscitation; cooling blankets; no anticholinergics/antihistaminics; consider dantrolene, amantadine, bromocriptine electroconvulsive therapy (ECT).
    • Metabolic syndrome, sudden cardiac death (risk higher IM/IV droperidol, IV haloperidol), stroke (elderly), QTc prolonged, pulmonary embolus
First Line
  • Benefits of some of the atypical antipsychotics include low risk of extrapyramidal symptoms (quetiapine, olanzapine, iloperidone, or clozapine) and tardive dyskinesia (clozapine, quetiapine); possibly more effective for negative symptoms
  • Greater risk of weight gain, new-onset diabetes, and hyperlipidemia with olanzapine and clozapine compared with typicals and some of the other atypicals (ziprasidone, aripiprazole)
  • Acute psychotic agitation: olanzapine 5 to 10 mg IM with up to three 10-mg injections over a 24-hour period, care with subsequent benzodiazepines; ziprasidone 10 mg IM q2h or 20 mg q4h; max 40 mg over a 24-hour period; haloperidol/lorazepam 5 mg/2 mg IM often with 1 mg IM benztropine, max 20 mg haloperidol, and 8 mg lorazepam over a 24-hour period
  • Psychosis in schizophrenia
    • Olanzapine: Start 5 to 10 mg at bedtime, target dose 5 to 20 mg/day within 2 days and up to 40 mg/day in treatment-refractory schizophrenia. More likely weight gain, hyperlipidemia, and hyperglycemia than other oral atypicals except clozapine; may have lower rates of discontinuation and rehospitalization than several other atypicals but likely not more efficacy than clozapine. Sedation initially
    • Quetiapine: Start 25 mg BID 25 to 50 mg BID-TID on days 2 and 3, up to 300 to 400 mg in divided doses by day 4. Within 2 weeks, up to 400 to 800 mg/day divided BID-TID; less parkinsonism, useful in Parkinson disease psychosis; more weight gain than aripiprazole, lurasidone, ziprasidone; sedation, restless legs syndrome; more gradual titration tolerated better. Quetiapine XR can start 300 mg/day. Dose increases can be within 1 day and up to 300 mg/day, but slower start and titration may be better; target dose 300 to 800 mg at bedtime
    • Risperidone: Start 1 to 2 mg/day; target dose of 2 to 6 mg/day to be reached over 1 to 2 weeks; doses >6 mg rarely more effective and higher risk of parkinsonism. Higher risk of prolactinemia/parkinsonism than clozapine, quetiapine, olanzapine
    • Paliperidone: Start 3 to 6 mg/day target dose 6 to 12 mg/day; titrate over 1 to 2 weeks. Higher risk of prolactinemia/parkinsonism than clozapine, quetiapine, olanzapine
    • Ziprasidone: Start 20 to 40 mg PO BID, with target dose of 100 to 200 mg/day in divided doses over 2 weeks; prolongs QTc; less likely to cause weight gain than other atypicals; higher risk of akathisia/parkinsonism than clozapine, quetiapine, olanzapine. Requires meal. Often sedation
    • Aripiprazole: Start 10 to 15 mg/day, may increase up to 30 mg/day over a week or 2; less weight gain but higher rates of akathisia/parkinsonism than clozapine, quetiapine, olanzapine
    • Asenapine: Start 5 mg at bedtime or BID sublingually, increase to 10 mg BID if needed over a week or 2; less weight gain than some, higher rates of akathisia/parkinsonism than clozapine, quetiapine, olanzapine; sedation, orthostatic hypotension, numb tongue, nausea, bad taste
    • Lurasidone: Start 20 to 40 mg once daily with food (at least 350 calories), increase to 80/120 mg at bedtime if needed over 2 to 4 weeks. Less weight gain than some but higher rates of akathisia/parkinsonism than clozapine, quetiapine, olanzapine; not antihistaminic but &agr;-blocking sedation and serotonergic nausea
    • Iloperidone: Start 1 mg BID, may increase by 2 mg BID each day, but slower can be better due to significant orthostasis. Increase to max 12 mg BID. Little akathisia/parkinsonism, less weight gain than olanzapine or clozapine but slower efficacy due to long titration, orthostasis, sedation
Geriatric Considerations
Increased risk of cerebrovascular accident when antipsychotics are used in the elderly with dementia 3[B]
Second Line
  • Clozapine: more effective for reducing symptoms, preventing relapse, decreasing tardive dyskinesia, and decreasing suicidality than other antipsychotics but second line given risk of fatal agranulocytosis. National registry for all patients on clozapine, weekly CBC and absolute neutrophil count (ANC) for 6 months then every 2 weeks for 6 months, then every 4 weeks. More weight gain, hyperlipidemia, hyperglycemia, seizures, myocarditis, pulmonary embolus, and sedation but low rate of parkinsonism, tardive dyskinesia. Useful in treatment-refractory psychosis and in Parkinson disease psychosis
  • Despite association with more weight gain than other antipsychotics, clozapine and olanzapine do not appear to increase risk of cardiac and all-cause mortality (2,3)[B].
  • Long-acting preparations: available for 2 typicals (haloperidol and fluphenazine) and 4 atypicals (risperidone, paliperidone, olanzapine, aripiprazole; olanzapine requires registration due to rare delirium syndrome). Test tolerability with oral medication first. Long-acting antipsychotics promote compliance.
  • Long-acting haloperidol, paliperidone, olanzapine, aripiprazole administered every 4 weeks; long-acting risperidone and fluphenazine administered every 2 weeks.
Encourage contact with advocacy groups for families and patients (National Alliance for the Mentally Ill).
Cognitive-behavioral therapy (CBT) is an effective adjuvant to antipsychotics (1)[B].
Admission Criteria/Initial Stabilization
At risk for harm to self or others; extreme functional impairment; unable to care for self; new-onset psychosis
Discharge Criteria
No longer a danger to self or others and adequate outpatient treatment in place
Close follow-up for inpatient discharge (high risk for suicide), use CBT, exercise, teach smoking cessation
National Alliance on Mental Illness: www.nami.org/
Schizophrenia: Fluctuating course, 70% first-episode psychosis patients improve in 3-4 months; 7% will die of suicide; 20-40% will attempt suicide.
1. National Institute for Health and Care Excellence. Psychosis and schizophrenia in adults: prevention and management. http://www.nice.org.uk/guidance/cg178. Accessed 2014.
2. Tiihonen J, Lönnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet. 2009;374(9690):620-627.
3. Strom BL, Eng SM, Faich G, et al. Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18,154 patients with schizophrenia: the Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC). Am J Psychiatry. 2011;168(2):193-201.
Additional Reading
  • McEvoy JP, Lieberman JA, Stroup TS, et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry. 2006;163(4):600-610.
  • van Iersel MB, Zuidema SU, Koopmans RT, et al. Antipsychotics for behavioural and psychological problems in elderly people with dementia: a systematic review of adverse events. Drugs Aging. 2005;22(10):845-858.
See Also
Delirium; Schizophrenia
  • F29 Unsp psychosis not due to a substance or known physiol cond
  • F20.9 Schizophrenia, unspecified
  • F39 Unspecified mood [affective] disorder
Clinical Pearls
  • Antipsychotics are the mainstay of treatment; evidence corroborates decreased all-cause mortality in patients who are adherent to these medications.
  • Clozapine and long-acting preparations are likely underused in schizophrenia in the United States and may increase adherence, whereas newer atypicals (quetiapine, lurasidone, aripiprazole, olanzapine-fluoxetine combination) may help with depressive symptoms in psychosis.