Criteria Schizophrenia Author The Florida Center For Behavioral Health Improvements and Solutions
Criteria Schizophrenia Author The Florida Center For Behavioral Health Improvements and Solutions
Criteria Schizophrenia Author The Florida Center For Behavioral Health Improvements and Solutions
Box 5.
F Two (or more) of the following, each present for a significant portion of time during
a 1-month period (or less if successfully treated). At least one of these must be
delusions, hallucinations or disorganized speech:
Delusions
Hallucinations
Disorganized speech (e.g., frequent derailment or incoherence)
Grossly disorganized or catatonic behavior
Negative symptoms (i.e., diminished emotional expression or avolition)
F Continuous signs of the disturbance persist for at least 6 months. This 6-month period
must include at least 1 month of symptoms (or less if successfully treated) that meet
the above criteria (i.e., active phase symptoms) and may include periods of prodromal
or residual symptoms. During these prodromal or residual periods, the signs of the
disturbance may be manifested only be negative symptoms or by two or more
symptoms listed above present in an attenuated form.
F For a significant portion of time since the onset of the disturbance, level of
functioning in one or more major areas, such as work, interpersonal relations, or self-
care is markedly below the level achieved prior to the onset (or when the onset is in
childhood or adolescence, there is a failure to achieve expected level of interpersonal,
academic, or occupational functioning).
F Schizoaffective disorder and depressive or bipolar disorder with psychotic features
have been ruled out.
F The disturbance is not attributable to the physiological effects of a substance (e.g., a
drug of abuse, a medication) or another medical condition.
F If there is a history of autism spectrum disorder or a communication disorder
of childhood onset, the additional diagnosis of schizophrenia is made only if
prominent delusions or hallucinations, in addition to the other required symptoms of
schizophrenia, are also present for at least 1 month (or less if successfully treated).
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Treatment of Schizophrenia
Note: Treatment recommendations are based on levels of evidence and expert opinion. For a description
of the criteria for each level, see page 4.
Most importantly, assess social support system (housing, family, other caregivers) and
evaluate threats to continuity of care (access to medication, adherence, etc.).
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Table 4. Recommended Medications for the Treatment of
Schizophrenia: Oral Antipsychotics
Chlorpromazine Acute Maintenance
Medication Equivalentsa Therapy Therapyb
First Generation Antipsychotics (FGAs)
Chlorpromazine 100 300–1,000 mg/day 300–800 mg/day
Fluphenazine HCl 2 5–20 mg/day 5–15 mg/day
Haloperidol 2 5–20 mg/day 6–12 mg/day
Loxapine 10 30–100 mg/day 30–60 mg/day
Molindone 10 30–100 mg/day 30–60 mg/day
Perphenazine 8 16–80 mg/day 16–64 mg/day
Thiothixene 5 15–50 mg/day 15–30 mg/day
Trifluoperazine 5 15–50 mg/day 15–30 mg/day
Second Generation Antipsychotics (SGAs)
Aripiprazole N/A 10-30 mg/day 10–30 mg/day
Asenapine N/A 10–20 mg/day 10–20 mg/day
Brexpiprazole N/A 2–4 mg/day 2–4 mg/day
Cariprazine N/A 1.5–6 mg/day 3–6 mg/day
Clozapine N/A 150–800 mg/day 150–800 mg/day
Iloperidone N/A 12–24 mg/day 12–24 mg/day
Lurasidone N/A 40–160 mg/day 40–160 mg/day
Olanzapine N/A 10–30 mg/day 10–20 mg/day
Paliperidone N/A 3–12 mg/day 3–12 mg/day
Quetiapine N/A 300–800 mg/day 300–800 mg/day
Risperidone N/A 2–8 mg/day 2–8 mg/day
Ziprasidone N/A 80–240 mg/day 80–160 mg/day
Notes:
Recommendations may be below FDA maximum approved doses but are based on current evidence and
expert consensus.
Consider lower doses for first episode due to better response and higher side effects to medications in
pharmaceutically naïve patients. Use atypical antipsychotics and avoid haloperidol completely due to
well-documented neuronal cell death caused by haloperidol (and also fluphenazine and perphenazine).
Thioridazine is not recommended due to concerns about ventricular arrhythmias (Torsades de Pointes).
a
Approximate dose equivalent to 100 mg of chlorpromazine (relative potency); it may not be the same at
lower versus higher doses. Chlorpromazine equivalent doses are not relevant to the second generation
antipsychotics and therefore are not provided for these agents.
b
Drug-drug interactions (DDIs) can impact dosing. Maintenance dose should generally be no less than
half of the initial clinically effective dose, as that can result in reduced effectiveness of relapse prevention.
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Treatment of Schizophrenia with Long-Acting Injectable
Antipsychotic Medications (LAIs)
Note: Treatment recommendations are based on levels of evidence and expert opinion. For a description
of the criteria for each level, see page 4.
Assess social determinants (housing, family, other caregivers) and evaluate threats to
continuity of care (access to medication, adherence, etc.).
Page 43
Figure 1. Management of Breakthrough Psychosis with
Long-Acting Injectable Antipsychotics (LAIs)
Options to consider
• Rule out / address medical illness or substance use as a contributing factor
• Address stressors and optimize non-pharmacological treatments
• Treat comorbidities
• Ensure proper LAI administration
• Address missed LAI doses appropriately
• Increase LAI dose
• Shorten LAI injection interval (increase LAI AP dose) *
Symptoms
persist
Symptoms
stabilize or Supplement Symptoms
Slowly discontinue oral AP abate LAI with low dose of persist Increase oral AP to
(≥2 weeks after start of corresponding oral AP optimum effective dose†
oral AP coverage) formulation for fast
symptom control†
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Table 5. Recommended Medications for the Treatment of Schizophrenia:
Page 46
Long-Acting Injectable Antipsychotics (continued)
Dosage
Dose Maintenance Oral Time to
Medication Strengths/ Starting Dose Steady State
Interval Dose Supplementation Peak
Forms
Aripiprazole Once at the 675 mg 675 mg Not applicable 1 day (aripiprazole 30 mg 27 days With single IM
lauroxil (Aristada beginning (N/A) tablet) —therapeutic levels injection of
Initio®) to initiate in 4 days Aristada initio®
aripiprazole and 30 mg oral
lauroxil aripiprazole at time
(Aristada®) of first Aristada®
treatment dose, aripiprazole
concentration
reaches therapeutic
levels within 4 days
Olanzapine 2 to 4 weeks 210, 300, 405 mg Varies, up to Varies, up to No 4 days 3 months
pamoate‡ vial kits 300 mg every 300 mg every
(Zyprexa 2 weeks 2 weeks
Relprevv®)
Paliperidone Monthly 39, 78, 117, 156, 234 234 mg (day 1) + 117 mg No 13 days 7 to 11 months
palmitate (Invega mg prefilled 156 mg (day 8) (39 to 234 mg)
Sustenna®) syringes Deltoid only
Paliperidone Once every 3 273, 410, 546, Depends on Varies, 273 to No 30 to 33 Continues steady
palmitate (Invega months 819 mg prefilled once-monthly 819 mg days state at equivalent
Trinza®) syringes paliperidone dose
palmitate (Invega
Sustenna®) dose
Dosage
Dose Maintenance Oral Time to
Medication Strengths/ Starting Dose Steady State
Interval Dose Supplementation Peak
Forms
Risperidone Once every two 12.5, 25, 37.5, 50 mg Varies, 12.5 mg to Varies, 12.5 mg to 3 weeks 4-6 weeks Steady state
microspheres weeks vial kits 25 mg 50 mg reached after 4
(Risperdal Consta®) injections and
maintained for 4-6
weeks after last
injection
Risperidone Monthly 90 mg, 120 mg 90 mg, 120 mg 90 mg, 120 mg No 4-48 hours 4-6 weeks
extended release powder and liquid
subcutaneous filled syringes
injectable
(Perseris®)
Adapted and updated from: Correll CU, Kane JM, Citrome LL. Epidemiology, Prevention, and Assessment of Tardive Dyskinesia and Advances in Treatment. J Clin
Psychiatry. 2017 Sep/Oct;78(8):1136-1147.
Notes:
For the most updated Florida Medicaid Preferred Drug List, visit https://ahca.myflorida.com/medicaid/Prescribed_Drug/pharm_thera/fmpdl.shtml.
*First-generation long-acting injectable antipsychotic medications (fluphenazine decanoate and haloperidol decanoate) have an oil base. Second-generation
long-acting injectable antipsychotic medications (aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, 1-month and 3-month paliperidone
palmitate, and risperidone microspheres) have a water base.
** Initial Aristada® dose is based on current oral aripiprazole dose as follows: If oral aripiprazole dose is 10 mg/day, initial Aristada® dose is 441 mg once monthly. If
oral aripiprazole dose is 15 mg/day, initial Aristada® dose is either 882 mg once monthly, 882 mg Aristada every 6 weeks, or 1,064 mg Aristada® every 2 months. If
oral aripiprazole dose is ≥20 mg/day, initial Aristada® dose is 882 mg once monthly.
‡Olanzapine pamoate (Zyprexa Relprevv) requires prescriber certification and patient enrollment with the Risk Evaluation and Mitigation Strategy (REMS) program.
Administration of olanzapine pamoate requires at least 3-hours of post-injection monitoring for post-injection delirium/sedation syndrome (PDSS). Olanzapine has
been found to cause more weight gain and related metabolic side effects than other SGAs.
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Summary: Treatment of Schizophrenia with LAIs
Main Questions:
n 1. Are LAIs more effective than placebo?
Yes.
All approved LAIs have demonstrated efficacy for people with schizophrenia. In the USA
(Correll et al., 2017), these agents include:
F First-generation antipsychotics:
Fluphenazine decanoate
Haloperidol decanoate
F Second-generation antipsychotics:
Aripiprazole monohydrate
Aripiprazole lauroxil
Olanzapine pamoate
Paliperidone palmitate
Risperidone microspheres
Risperidone extended release subcutaneous injectable
n 2. Are LAIs more effective than oral antipsychotics?
Yes, in many studies and settings, with some non-differential results, but very rare/virtually
no data indicating better efficacy for oral antipsychotics.
Efficacy of LAIs versus oral antipsychotics depends on the study design and included
population (Correll et al., 2016). In randomized clinical trials (RCTs) that include patients
with better illness insight, less severity/complexity of the disease and better/monitored
adherence, LAIs were not more efficacious than placebo (Kishimoto et al., 2014). In mirror
image studies (Kishimoto et al., 2013) and cohort/database studies (Kishimoto et al., 2018)
that enroll more generalizable patients, LAIs were superior to oral antipsychotics regarding
relapse, hospitalization, and all-cause discontinuation risk, despite greater illness severity in
patients started on LAIs versus oral antipsychotics in real-world studies. Additionally, LAIs
have been associated with a 20–30% reduced all-cause mortality versus oral antipsychotics
(Taipale et al., 2018).
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Summary: Treatment of Schizophrenia with LAIs
(continued)
Generally, the adverse effects of LAIs are predictable from knowledge of the adverse effect
potential of the oral counterpart and can be tested in an individual patient during lead in
treatment with the oral antipsychotic.
Comparing 119 adverse events in patients randomized to an LAI or the same medication
given in an oral formulation, 115 (97%) were not different, including discontinuation
due to adverse event or mortality. Regarding 3 adverse effects [akinesia, (stiffness)
with first generation antipsychotics (FGAs), increase in low density lipoprotein
cholesterol, and anxiety], oral antipsychotics had lower events, while prolactin levels and
hyperprolactinemia were lower in LAI treated patients (Misawa et al., 2016). Injection pain
and injection site reactions are generally mild and infrequent (Correll et al., 2016).
Based on data with FGA-LAIs, there is no current indication that the outcome of
neuroleptic malignant syndrome is worse when it occurs during LAI versus oral
antipsychotic treatment, as management is symptomatic (Glazer and Kane, 1992).
An exception from the rules above is olanzapine pamoate, which is highly blood soluble
and which can, in 1/1,100–1,200 injections, lead to a post-injection somnolence, sedation,
and coma syndrome (known as post injection delirium/sedation syndrome, or PDSS).
Therefore, at least 3 hours of post-injection observation for the duration of treatment with
olanzapine pamoate is required.
If the above does not resolve the issue or immediate action is needed, add the same
antipsychotic in oral formulation in an attempt to increase the dose. Generally, try to avoid
polypharmacy with different antipsychotics, as the evidence for efficacy and safety is
lacking (Galling et al., 2017; Correll et al., 2017).
If efficacy is reestablished and the higher dose is tolerated, at the next injection interval,
use a higher LAI dose that corresponds to that combined LAI + oral dose. If already at the
highest dose, consider changing injection site (deltoid injections lead to higher peak levels
but shorter half-life, gluteal injection leads to lower peak levels but longer half-life), change
to shortest FDA-approved injection interval (if not already done), or consider off-label
strategy of shortening the injection interval (Correll et al., 2016; Correll et al., 2018).
References:
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S, Carrus D, Ballerini A, Francomano A, Ducci G, Del Casale A, Girardi P. Model of Management (Mo.
Ma) for the patient with schizophrenia: crisis control, maintenance, relapse prevention, and
recovery with long-acting injectable antipsychotics (LAIs). Riv Psichiatr. 2016 Mar-Apr;51(2):47-59.
Correll CU, Citrome L, Haddad PM, Lauriello J, Olfson M, Calloway SM, Kane JM. The Use of Long-
Acting Injectable Antipsychotics in Schizophrenia: Evaluating the Evidence. J Clin Psychiatry.
2016;77(suppl 3):1-24.
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Summary: Treatment of Schizophrenia with LAIs
(continued)
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