Schizophrenia

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

at risk of developing psychosis

1st line – cognitive behavioral therapy

ACUTE

acute psychotic episode

1st line – start or review oral antipsychotic medication

Back

1st line –

start or review oral antipsychotic medication

An acute psychotic episode may occur in one of three settings: the first psychotic episode, psychotic decompensation caused by treatment nonadherence or stressors, or inadequate response to current antipsychotic medication despite adequate dosing. The patient often requires hospitalization. Specific indicators include the patient posing a serious threat of harm to self or others or being unable to care for themself and needing constant supervision or support as a result; psychiatric or other medical issues that make outpatient treatment unsafe or ineffective; or new onset of psychosis that warrants initial inpatient stabilization to reduce acute symptoms and permit engagement in treatment.[65] Having the patient in a safe and predictable environment is important.

If the acute episode is the first presentation, the patient needs to be established on antipsychotic medication. As these patients are usually naive to antipsychotic medications and more prone to developing extrapyramidal symptoms they should be started on low doses.

If the acute episode was due to psychotic decompensation from the patient’s current antipsychotic medication, the medication dosage may need to be increased or a new antipsychotic medication started. If the patient has previously had a good response to a specific agent, the same medication can be reconsidered.

The minimum antipsychotic dose that controls symptoms should be utilized, with adequate follow-up for possible medication adjustments and adverse effect monitoring.[65][99] Medication should be continued indefinitely but titrated or discontinued if adverse effects are intolerable.[65] Intermittent, or discontinuation of, antipsychotic treatment may increase the risk for symptom exacerbation and relapse and is not recommended.[94][100] Benefits and adverse effects of treatment should be assessed on an ongoing basis to determine the need for adjustments to medication doses or changes in medications.[65] There is no correlation between the dose and therapeutic effect, but the risk of extrapyramidal signs (e.g., akathisia, parkinsonism, and dystonia) increases with increases in dose.

Antipsychotics are available in oral, inhalation, transdermal, and short- or long-acting intramuscular formulations, depending on location.

It may take between 2 and 4 weeks for antipsychotic medication to elicit an initial response, and longer periods for a full or optimal response.[65]

The minimum length of an adequately-dosed antipsychotic treatment trial is 2 weeks before a nonresponse can be determined.[101] Limited evidence suggests that patients showing not even a minimal improvement after 2 weeks of antipsychotic treatment are unlikely to respond later and may benefit from a treatment change.[101][102]

Until antipsychotic medications take effect, benzodiazepines may help relieve emotional distress, insomnia, and other behavioral disturbances secondary to psychosis.[94]

Long-term treatment with antipsychotic medications is associated with a greater incidence of weight gain, diabetes and hyperlipidemia, sedation, and movement disorders. It may be possible to mitigate these risks by preventive interventions (e.g., early intervention for weight gain, screening for lipid and glucose abnormalities) and careful monitoring for adverse effects of medication. As treatment proceeds, the benefits and risks of continuing treatment with an antipsychotic medication should be reviewed with the patient in the context of shared decision-making. It will typically be beneficial to include family members or other persons of support in such discussions.[65]

First-generation (typical) antipsychotics or second-generation (atypical) antipsychotics are the treatment of choice.[65]

The choice of a specific antipsychotic agent will typically occur in the context of discussion with the patient and should incorporate patient preferences; the patient's past responses to treatment (including therapeutic response and tolerability); the medication’s likely benefits and adverse-effect profile; the presence of physical health conditions that may be affected by medication adverse effects; and other medication-related factors such as available formulations, potential for drug-drug interactions, receptor-binding profiles, and pharmacokinetic considerations.[65]

Lower antipsychotic doses are typically required to treat a first episode than to treat chronically ill or relapsed patients.[94]

If symptoms improve with an antipsychotic medication, patients should continue to be treated with this medication. Medication should be continued indefinitely but titrated or discontinued if adverse effects are intolerable.[65]

If a woman becomes pregnant while taking an antipsychotic medication, consideration should be given to consulting an obstetrician-gynecologist or maternal/fetal medicine subspecialist.[65] For most pregnant women with schizophrenia, the benefits of continued treatment with antipsychotic medications in minimizing relapse will generally outweigh the potential for fetal risk.[65][177][178] For many women, the eighth week of gestation will already have passed before obstetric care begins, and stopping medication will not avoid or reduce teratogenic risk (3-8 weeks gestation is associated with greatest risk for teratogenesis). The American College of Obstetricians and Gynecologists recommends against withholding or stopping medications for mental health based on pregnancy or lactation status alone.[178]

Available data for first- and second-generation antipsychotics suggest that these medications have minimal risk of teratogenic or toxic effects on the fetus.[65][179][180]

There does appear to be a risk of withdrawal symptoms or neurologic effects of antipsychotic medications in a newborn if an antipsychotic medication is used in the third trimester.[181] Nevertheless, tapering of antipsychotic medication late in pregnancy is not advisable because of the associated risk of relapse.[65] In some newborns, the symptoms subside within hours or days and do not require specific treatment; others may require longer hospital stays.[65][181]

Some psychotropic medications that are commonly used in patients with schizophrenia are best avoided during pregnancy because of their teratogenic effects. For example, both valproic acid (and its derivatives) and carbamazepine carry an increased risk of fetus malformations, including neural tube defects, especially during the first trimester.[65][177][179] Valproate should not be used to treat women who are pregnant or who plan to become pregnant, or in women of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable.[182][183] In such situations, effective contraception should be used.[183]

Examples of suitable antipsychotics are listed here. However, other medications are available, and you should consult your local drug formulary.

Primary options

risperidone: 1 mg orally twice daily initially, increase gradually according to response, maximum 16 mg/day

paliperidone: 6 mg orally once daily in the morning initially, increase gradually according to response, maximum 12 mg/day

quetiapine: 25 mg orally (immediate-release) twice daily initially, increase gradually according to response, maximum 800 mg/day given in 2-3 divided doses; 300 mg orally (modified-release) once daily initially, increase gradually according to response, maximum 800 mg/day

ziprasidone: 20 mg orally twice daily initially, increase gradually according to response, maximum 160 mg/day

aripiprazole: 10-15 mg orally once daily initially, increase gradually according to response, maximum 30 mg/day

iloperidone: 1 mg orally twice daily initially, increase gradually according to response, maximum 24 mg/day

asenapine: 5 mg sublingually twice daily initially, increase gradually according to response, maximum 20 mg/day

lurasidone: 40 mg orally once daily initially, increase gradually according to response, maximum 80 mg/day

brexpiprazole: 1 mg orally once daily for 4 days, increase to 2 mg once daily for 3 days, then increase to 4 mg once daily according to response, maximum 4 mg/day

cariprazine: 1.5 mg orally once daily on day one, increase to 3 mg once daily on day 2, then increase by 1.5 to 3 mg/day increments according to response, maximum 6 mg/day

lumateperone: 42 mg orally once daily

Secondary options

olanzapine: 5-10 mg orally once daily initially, increase gradually according to response, maximum 20 mg/day

Tertiary options

haloperidol: 0.5 to 2 mg orally two to three times daily initially, adjust dose gradually according to response and tolerability, usual dose is 5-20 mg/day, maximum 30 mg/day

fluphenazine: 2.5 to 10 mg/day orally given in 2-3 divided doses initially, increase gradually according to response, maximum 40 mg/day

perphenazine: 4-8 mg orally three times daily initially, increase gradually according to response, maximum 64 mg/day

These drug options and doses relate to a patient with no comorbidities.