Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content + Print Section ++ For further information, see CMDT Part 25-11: Schizophrenia Spectrum Disorders + Key Features Print Section ++ ++ Essentials of Diagnosis ++ Social withdrawal, usually slowly progressive, with decrease in emotional expression and/or motivation Deterioration in personal care with disorganized behaviors and/or decreased reactivity to the environment Disorganized thinking, often inferred from speech that switches topics oddly or is incoherent Auditory hallucinations, often of a derogatory nature Delusions, fixed false beliefs despite conflicting evidence, frequently of a persecutory nature ++ General Considerations ++ Schizophrenia is manifested by a massive disruption of thinking, mood, and overall behavior as well as poor filtering of stimuli Cause is believed to be multifactorial, with genetic, environmental, and neurotransmitter pathophysiologic components The characterization and nomenclature of the disorders are quite arbitrary and are influenced by sociocultural factors and schools of psychiatric thought There may or may not be a history of a major disruption in the individual's life (failure, loss, physical illness) before gross psychotic deterioration is evident Other psychotic disorders on this spectrum are conditions that are similar to schizophrenia in their acute symptoms but have a less pervasive influence over the long term + Clinical Findings Print Section ++ ++ Symptoms and Signs ++ A history of a major disruption in the individual's life may precede gross psychotic deterioration Gradual decompensation usually predates the acute episode Positive symptoms Delusions are often paranoid, involving perceived threat from others Hallucinations are typically auditory Hypersensitivity to environmental stimuli, with feelings of enhanced sensory awareness Negative symptoms Diminished sociability Restricted affect Impoverished speech Appearance: may be bizarre, often with deterioration in personal care, though usually patients are just mildly unkempt Motor activity: generally reduced, although a broad spectrum is seen Social function: marked withdrawal, disturbed interpersonal relationships Speech Neologisms (made-up words or phrases) Echolalia (repetition of others' words) Verbigeration (repetition of senseless words or phrases) Affect: flat, occasionally inappropriate Mood: depression in most patients, less apparent during acute psychosis, may have rapidly alternating mood shifts irrespective of circumstances Thought content Varies from paucity of ideas to rich delusions Concrete thinking with inability to abstract Inappropriate symbolism ++ Differential Diagnosis ++ Schizophrenia should be distinguished from other psychoses Delusional disorders are characterized by persistent delusions with minimal impairment on daily life Schizoaffective disorders fail to fit within the definitions of either schizophrenia or affective disorders Schizophreniform disorders have a duration of less than 6 months, but more than 1 month Brief psychotic disorders result from psychological stress, last less than 1 month, and have a much better prognosis “Other psychotic disorders” Patient usually attains higher levels of functioning than in schizophrenia Acute psychotic episodes tend to be less disruptive of the person's lifestyle, with a fairly quick return to previous levels of functioning Clues are precipitous onset and a good premorbid history Manic episodes Obsessive-compulsive disorder Psychotic depression Drug intoxication and abuse Thyroid, adrenal, and pituitary disorders Complex partial seizures and temporal lobe dysfunction may produce psychotic symptoms Drug toxicities, particularly overdoses of typical antipsychotics, can produce catatonia + Diagnosis Print Section ++ ++ Laboratory Tests ++ There is no laboratory method for confirming the diagnosis of schizophrenia ++ Imaging Studies ++ Ventricular enlargement and cortical atrophy on CT have been correlated with chronicity, cognitive impairment, and poor response to antipsychotics Decreased frontal lobe activity on positron emission tomography scan has been associated with negative symptoms MRI can exclude temporal lobe disorders + Treatment Print Section ++ ++ Medications ++ See Tables 25–4 and 25–5 Typical (first-generation) antipsychotic agents Phenothiazines Thioxanthenes Butyrophenones Dihydroindolones Dibenzoxazepines Benzisoxazoles Newer, atypical (second-generation) antipsychotics (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, asenapine, iloperidone, and lurasidone) Cause less tardive dyskinesia and extrapyramidal symptoms Are more effective than typical agents for managing negative symptoms Lurasidone Effective in treating acute decompensation in patients with chronic schizophrenia Has low incidence of weight gain, increased lipids, or prolonged QT interval Side effects include akathisia; elevated prolactin; and in higher doses, somnolence Cariprazine FDA approved for treatment of schizophrenia and bipolar disorder Side effects include akathisia, weight gain, and insomnia Less likely to increase prolactin levels than most antipsychotics Antidepressant drugs may be used with antipsychotics if significant depression is present Resistant cases may require addition of lithium, carbamazepine, or valproate Addition of benzodiazepine can resolve catatonic symptoms and allow a lower antipsychotic dose ++Table Graphic Jump LocationTable 25–4.Commonly used antipsychotic medications (listed in alphabetical order).View Table|Favorite Table|Download (.pdf)Table 25–4. Commonly used antipsychotic medications (listed in alphabetical order). Medication Usual Daily Oral Dose Usual Daily Maximum Dose1 Cost per Unit Cost for 30 Days of Treatment Based on Maximum Dosage2 Aripiprazole (Abilify) 10–15 mg 30 mg $45.35/30 mg $1360.50 Asenapine (Saphris) 10–20 mg 20 mg $24.02/10 mg $1441.20 Cariprazine (Vraylar) 1.5–6 mg 6 mg $48.03/6 mg $1440.90 Chlorpromazine (Thorazine; others) 100–400 mg 1 g $17.86/200 mg $2679.00 Clozapine (Clozaril) 300–450 mg 900 mg $2.73/100 mg $737.10 Fluphenazine (Permitil, Prolixin)3 2–10 mg 60 mg $1.15/10 mg $207.00 Haloperidol (Haldol) 2–5 mg 60 mg $2.76/20 mg $248.40 Iloperidone (Fanapt) 12–24 mg 24 mg $46.39/12 mg $2783.40 Loxapine (Loxitane) 20–60 mg 200 mg $2.57/50 mg $308.40 Lurasidone (Latuda) 40–80 mg 80 mg $48.94/80 mg $1468.20 Olanzapine (Zyprexa) 5–10 mg 20 mg $39.79/20 mg $1193.70 Paliperidone (Invega) 6–12 mg 12 mg $30.53/6 mg $1831.80 Perphenazine (Trilafon)3 16–32 mg 64 mg $3.90/16 mg $468.00 Quetiapine (Seroquel) 200–400 mg 800 mg $19.93/400 mg $1195.80 Risperidone (Risperdal)4 2–6 mg 10 mg $7.06/2 mg $1059.00 Thiothixene (Navane)3 5–10 mg 80 mg $3.36/10 mg $806.40 Trifluoperazine (Stelazine) 5–15 mg 60 mg $2.45/10 mg $441.00 Ziprasidone (Geodon) 40–160 mg 160 mg $10.76/80 mg $645.60 1Can be higher in some cases.2Average wholesale price (AWP, for AB-rated generic when available) for quantity listed. Source: IBM Micromedex Red Book (electronic version) IBM Watson Health, Greenwood, CO, USA. Available at https://www.micromedexsolutions.com (cited April 25, 2019). AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions.3Indicates piperazine structure.4For risperidone, daily doses above 6 mg increase the risk of extrapyramidal syndrome. Risperidone 6 mg is approximately equivalent to haloperidol 20 mg. ++Table Graphic Jump LocationTable 25–5.Relative potency and side effects of antipsychotic medications (listed in alphabetical order).View Table|Favorite Table|Download (.pdf)Table 25–5. Relative potency and side effects of antipsychotic medications (listed in alphabetical order). Medication Chlorpromazine:Drug Potency Ratio Anticholinergic Effects1 Extrapyramidal Effect1 Aripiprazole 1:20 1 1 Chlorpromazine 1:1 4 1 Clozapine 1:1 4 — Fluphenazine 1:50 1 4 Haloperidol 1:50 1 4 Iloperidone 1:25 1 1 Loxapine 1:10 2 3 Lurasidone 1:5 1 2 Olanzapine 1:20 1 1 Perphenazine 1:10 2 3 Quetiapine 1:1 1 1 Risperidone 1:50 1 3 Thiothixene 1:20 1 4 Trifluoperazine 1:20 1 4 Ziprasidone 1:1 1 1 11, weak effect; 4, strong effect. ++ Therapeutic Procedures ++ Social therapeutic interventions Board and care homes with experienced staff can improve functioning and limit hospitalizations Nonresidential self-help groups (Recovery, Inc.) should be used Vocational rehabilitation and work agencies (Goodwill Industries, Inc.) can provide structured work situations Psychotherapy Need for psychotherapy varies markedly with patient status and history Insight-oriented psychotherapy is often counterproductive Cognitive-behavioral therapy with medication management may be efficacious A form of psychotherapy called Acceptance and Commitment Therapy has shown value in helping prevent hospitalizations in schizophrenia Cognitive remediation therapy is another approach that shows promise in helping schizophrenic patients become better able to focus their disorganized thinking Family therapy may alleviate the patient's stress and assist relatives in coping Behavioral intervention Music from portable players with headphones can divert attention from auditory hallucinations + Outcome Print Section ++ ++ Follow-Up ++ Clozapine 1.6% risk of agranulocytosis Weekly white blood cell counts (WBCs) for 6 months, then every other week thereafter Weekly WBCs for 1 month after discontinuation of clozapine Ziprasidone Can cause QT prolongation Pretreatment ECG and cardiac risk factor screen are necessary Quetiapine Associated with cataracts Ophthalmologic examination at initiation and biannually May cause QT prolongation particularly when prescribed with other medications that effect the QT interval and in overdose Asenapine and paliperidone Increase the risk of QT interval prolongation Should be avoided in patients with risk factors for this ECG finding Asenapine carries a warning of possible serious allergic reaction (even after the first dose) including anaphylaxis, low blood pressure, and difficulty breathing ++ Complications ++ Antipsychotic malignant syndrome is an uncommon but serious side effect of antipsychotics Tardive dyskinesia may occur after long-term use of antipsychotics Anticholinergic and adrenergic side effects are more frequent with low-potency antipsychotics Extrapyramidal symptoms are seen with high-potency antipsychotics Olanzapine has been associated with significant weight gain Clozapine may cause adynamic ileus, a rare side effect that can be fatal The risk of diabetes mellitus is increased in patients taking clozapine and olanzapine ++ Prognosis ++ After removal of positive symptoms, prognosis is good in most patients Negative symptoms are more difficult to treat Prognosis is guarded when psychosis is associated with a history of serious drug abuse, owing to likely CNS damage Life expectancy is 20% shorter in schizophrenics, mostly because of higher mortality rates among young patients ++ When to Admit ++ Gross disorganization Risk of self-harm or harm to others + References Print Section ++ + +Arnedo J et al; Molecular Genetics of Schizophrenia Consortium. 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Efficacy and safety of antidepressants added to antipsychotics for schizophrenia: a systematic review and meta-analysis. Am J Psychiatry. 2016 Sep 1;173(9):876–86. [PubMed: 27282362] + +Howes OD et al. Treatment-resistant schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. Am J Psychiatry. 2017 Mar 1;174(3):216–9. [PubMed: 27919182] + +Jones R et al. Schizophrenia in a primary care setting. Curr Psychiatry Rep. 2015 Oct;17(10):84. [PubMed: 26341756] + +Owen MJ et al. Schizophrenia. Lancet. 2016 Jul 2;388(10039):86–97. [PubMed: 26777917] + +Remington G et al. Treating negative symptoms in schizophrenia: an update. Curr Treat Options Psychiatry. 2016;3:133–50. [PubMed: 27376016] + +Subramanian S et al. Clozapine dose for schizophrenia. Cochrane Database Syst Rev. 2017 Jun 14;6:CD009555. [PubMed: 28613395] + +Tseng PT et al. Significant effect of valproate augmentation therapy in patients with schizophrenia: a meta-analysis study. Medicine (Baltimore). 2016 Jan;95(4):e2475. [PubMed: 26825886] + +Vinogradov S et al. Behavioral and emerging pharmacologic treatment options for cognitive impairment in schizophrenia. J Clin Psychiatry. 2016 Feb;77(Suppl 2):12–6. [PubMed: 26919053] + +Yang AC et al. New targets for schizophrenia treatment beyond the dopamine hypothesis. Int J Mol Sci. 2017 Aug 3;18(8):E1689. [PubMed: 28771182]