Atypical Anti-psychotics (oral)
Atypical Anti-psychotics (oral) - Index
Medications listed in the tables and non-FDA approved indications included in these retrospective criteria are not indicative of Texas Vendor Drug Program formulary coverage.
- Revision history
- Oct. 13, 2023
- Oct. 22, 2021
- Sept. 2019
- Sept. 2017
- Sept. 2015
- Dec. 2013
- Feb. 2012
- June 2010
- May 2010
- March 2007
- Dec. 2006
- Oct. 2006
- May 2003
- April 2002
- April 2001
- April 2000
- March 1999
- March 1998
- Initially developed
- Feb. 1997
1. Dosage
1.1. Adults
Oral atypical antipsychotics are FDA-approved for use in schizophrenia, bipolar I disorder (BD), bipolar disorder with mixed episodes or depressive episodes, bipolar mania, schizoaffective disorder (SD), adjunctive therapy in major depressive disorder (MDD), treatment-resistant schizophrenia, and irritability associated with autism.1-14 Cariprazine (Vraylar) is approved to treat schizophrenia and manic or mixed episodes associated with BD.1,15 Aripiprazole tablets with sensors (Abilify MyCite) are approved to track medication com pliance1,16.
Pimavanserin (Nuplazid) is an oral atypical antipsychotic that is indicated for use to manage hallucinations and delusions seen with Parkinson’s disease psychosis1,17. Olanzapine combination therapy is FDA-approved for use in managing treatment-resistant depression as well as acute depressive episodes associated with bipolar I disorder1,18. Secuado (asenapine) Transdermal System is a topical patch that is FDA approved for the management of schizophrenia in adult patients.1, 19 Additionally, Caplyta (lumateperone) is a once daily oral capsule that is FDA approved for the management of schizophrenia in adult patients1,20.
Maximum recommended adult doses for atypical antipsychotics are summarized in Table 1. Dosages exceeding these recommendations will be reviewed.
Drug Name | Available Dosage Strengths | Treatment Indication | Maximum Recommended Dosage |
---|---|---|---|
Aripiprazole (Abilify, Abilify MyCite system, generics) |
| Schizophrenia, BD |
|
MDD | 15 mg/day | ||
Asenapine (Saphris®, Secuado® Transdermal System, generics) |
| Schizophrenia, BD |
|
Brexpiprazole (Rexulti®) | 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg tablets | Schizophrenia | 4 mg once daily |
MDD | 3 mg once daily | ||
Agitation associated with dementia due to Alzheimer’s disease | 3 mg once daily | ||
Cariprazine (Vraylar®) | 1.5 mg, 3 mg, 4.5 mg 6 mg capsules | Bipolar major depression, BD (acute mixed/manic episodes), schizophrenia | 6 mg once daily |
BD (acute mixed/manic episodes), schizophrenia | 6 mg once daily | ||
Clozapine (Clozaril, generics, Versacloz) |
| Schizophrenia (treatment-resistant), reducing recurrent suicidal behavior in schizophrenia and schizoaffective disorder (SD) |
|
Iloperidone (Fanapt®) | 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg 12 mg IR tablets | Schizophrenia | 24 mg/day, in divided doses |
Lumateperone (Caplyta®) | 10.5 mg, 21 mg, 42 mg capsules | Schizophrenia, bipolar depression | 42 mg/day |
Lurasidone (Latuda®) | 20 mg, 40 mg, 60 mg, 80 mg, 120 mg IR tablets | Schizophrenia | 160 mg/day, with food (at least 350 calories) |
Bipolar depression | 120 mg/day, with food (at least 350 calories) | ||
Olanzapine (Zyprexa®, Zyprexa Zydis®, generics) | 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg IR tablets | Schizophrenia, BD, treatment-resistant depression | 5 mg, 10 mg, 15 mg, 20 mg ODTs 20 mg/day, as a single dose |
Paliperidone (Invega®) | 1.5 mg, 3 mg, 6 mg, 9 mg extended-release (ER) tablets | Schizophrenia, SD | 12 mg/day |
Pimavanserin (Nuplazid®) | 10 mg tablets, 34 mg capsules | Hallucinations and delusions associated with Parkinson’s disease psychosis | 34 mg once daily |
Quetiapine (Seroquel®, Seroquel XR®, generics) |
| Schizophrenia, BD (acute manic episodes, maintenance) |
|
Schizophrenia | 750 mg/day, in two or three divided doses | ||
Bipolar depression |
| ||
Quetiapine (Seroquel XR®, generics) | MDD | ER: 300 mg/day, as a single dose | |
Risperidone (Risperdal®, Risperdal M-TAB®, generics) |
| Schizophrenia | 8 mg/day in 1 or 2 divided doses * |
Bipolar mania | 6 mg/day | ||
Ziprasidone (Geodon®, generics) | 20 mg, 40 mg, 60 mg, 80 mg IR capsules | Schizophrenia | 200 mg/day, in two divided doses + |
BD | 160 mg/day, in two divided doses |
Legend:
- # ingestible event marker (IEM) embedded in each MyCite® tablet; to be dispensed with MyCite® patch (wearable sensor that detects signal frim IEM sensor) and MyCite App
- * doses up to 16 mg/day have demonstrated efficacy in clinical trials; however, doses of 4 to 8 mg/day tended to produce the maximal effect
- + doses up to 320 mg daily have been used safely but greater efficacy not noted with higher dosages
Lybalvi is an oral combination product containing olanzapine and samidorphan that is FDA approved for the management of acute mixed or manic episodes in bipolar 1 disorder, maintenance therapy in bipolar 1 disorder, and for the management of schizophrenia1,21. Samidorphan that binds to mu, kappa, and delta opioid receptors. Samidorphan is a mu-opioid receptor antagonist, and it demonstrates partial agonist activity on kappa, and delta-opioid receptors. The major metabolites of samidorphan also have an affinity for opioid receptors, however, neither metabolite is thought to contribute to the pharmacologic effects of the drug1, 21. Doses exceeding the maximum adult recommended doses summarized in Table 2 will be reviewed.
Drug Name | Available Dosage Strengths | Treatment Indication | Maximum Recommended Dosage |
---|---|---|---|
Olanzapine/ fluoxetine (Symbyax, generics ) |
| Bipolar depression, treatment-resistant depression | Olanzapine 18 mg/ fluoxetine 75 mg once daily in evening, without regard to meals |
Olanzapine/ samidorphan (Lybalvi®) |
| Schizophrenia, BD | Olanzapine 20 mg/ samidorphan 10 mg once daily |
1.2. Pediatrics
Risperidone is FDA-approved to manage symptoms of irritability in autistic children greater than 5 years of age and adolescents, and is approved for bipolar mania in children and adolescents 10 to 17 years of age and schizophrenia in adolescents 13 to 17 years of age1,6. Aripiprazole is FDA approved for treating Tourette’s disorder in pediatric patients 6 to 18 years of age, and is also FDA-approved for managing schizophrenia in adolescents 13 to 17 years of age, bipolar disorder with or without psychotic features in children 10 to 17 years of age, and irritability associated with autistic disorder in children 6 to 17 years of age1,9. Olanzapine is FDA approved for bipolar disorder and schizophrenia in adolescents 13 years of age and older.1,10 Olanzapine is also FDA approved to treat depressive episodes associated with bipolar 1 disorder in patients 10 years of age and older when used in combination with fluoxetine1,18. Quetiapine is FDA approved for acute treatment of bipolar disorder mania episodes in children and adolescents 10 to 17 years of age and schizophrenia management in adolescents 13 to 17 years of age1,11,12. Paliperidone is approved FDA for the management of schizophrenia in adolescents 12 to 17 years of age1,8. Lurasidone is approved for the management of depressed phase bipolar disorder in children 10 to 17 years of age, and it is approved for the management of schizophrenia in patients 13 to 17 years of age1,13. Cariprazine, clozapine, iloperidone, lumateperone, ziprasidone, and aripiprazole tablets with sensors (Abilify MyCite) are not recommended for use in pediatric patients as safety and efficacy have not been established in this patient population. Additionally, pimavanserin is not approved for use in pediatric patients as Parkinson’s disease is typically not observed in pediatric patients, and safety and efficacy data are not available for pimavanserin in the pediatric population1-3,5,7,15-17,20.
Atypical antipsychotic pediatric dosages are summarized in Table 3. An additional column reflecting literature-based dosing included in the Texas Health and Human Services Psychotropic Medication Utilization Parameters for Children and Youth in Texas Public Behavioral Health (6th Version) is included in Tables 3 and 422.
Drug Name | Available Dosage Strengths | Treatment Indication | Literature Based Maximum Dosage | FDA Approved Maximum Recommended Dosage |
---|---|---|---|---|
Aripiprazole (Abilify,generics) |
| Schizophrenia |
| 13-17 years of age: 30 mg once daily |
BD | 10-17 years of age: 30 mg once daily | |||
Tourette’s disorder | 6-18 years of age:
| |||
Irritability associated with autism | 6-17 years of age: 15 mg/day as a single dose | |||
Asenapine (Saphris®) | 2.5 mg, 5 mg, 10 mg sublingual tablets | BD | Age greater than or equal to 10 years: 10 mg twice daily | 10-17 years of age: 20 mg/day, in two divided doses |
Brexpiprazole (Rexulti) | 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg tablets | Schizophrenia | Age 13-17 years: 4 mg/ day | |
Clozapine (Clozaril, generics, Versacloz) |
| Reserved for treatment resistant psychosis, following two failed trials of antipsychotic therapy with adequate dose/ duration |
| Not approved for children or adolescents |
Lurasidone (Latuda®) | 20 mg, 40 mg, 60 mg, 80 mg IR tablets | Schizophrenia, BD |
| 13 to 17 years of age: 80 mg/day, with food (at least 350 calories) |
Olanzapine (Zyprexa®, Zyprexa Zydis®, generics) |
| Schizophrenia, BD |
| 13 to 17 years of age: 20 mg once daily |
Paliperidone (Invega®) | 1.5 mg, 3 mg, 6 mg, 9 mg extended-release (ER) tablets | Schizophrenia | Adolescents (age greater than or equal to 12 years), schizophrenia:
| 12-17 years of age:
|
Quetiapine (Seroquel, generics, Seroquel XR) |
| BD - acute manic episodes |
| 10 to 17 years of age: 600 mg daily, once daily (ER tablets) or in 2 to 3 divided doses (IR tablets) |
Schizophrenia | 13 to 17 years of age: 800 mg daily, once daily (ER tablets) or in 2 to 3 divided doses (IR tablets) | |||
Risperidone (Risperdal, generics) |
| Bipolar mania |
| 10-17 years of age: 6 mg daily |
Schizophrenia | 13-17 years of age: 6 mg daily | |||
Irritability in autistic disorder | 5-17 years of age: 3 mg/day (no dosing data available for pediatric patients less than 15 kg) | |||
Ziprasidone (Geodon, generics) | 20 mg, 40 mg, 60 mg, 80 mg IR capsules | BP | Bipolar Disorder (age10-17 years)
| Not approved for children or adolescents |
The olanzapine/fluoxetine combination has been approved for use in pediatric patients 10-17 years of age with depression associated with BD1,18. Recommended pediatric dosages are summarized in Table 4.
Drug Name | Available Dosage Strengths | Literature Based Maximum Dosage | Treatment Indication | Maximum Recommended Dosage per Age Group |
---|---|---|---|---|
Olanzapine/ fluoxetine (Symbyax, generics) |
| Age 10-17 years: 12 mg olanzapine/50 mg fluoxetine once daily | Bipolar depression | 10-17 years of age: olanzapine 12 mg/ fluoxetine 50 mg once daily in evening, without regard to meals |
2. Duration of Therapy
Atypical antipsychotics are indicated for use in the management of schizophrenia and psychotic disorders. Therefore, there is no basis for limiting treatment duration with these atypical antipsychotics as these agents are utilized in the management of chronic disorders 1-44.
3. Duplicative Therapy
Combined therapy with multiple antipsychotic medications were evaluated in patients with treatment-resistant schizophrenia. Open studies, case reports, and clinical trials have observed favorable results following concurrent therapy with either atypical antipsychotics plus conventional antipsychotic agents or clozapine in conjunction with an additional atypical antipsychotic in clozapine-refractory patients. Further, controlled trials are necessary to identify patients and circumstances in which combination therapy should be utilized and the risks and benefits of concurrent therapy.
Neuroleptics should be used concomitantly during transitional periods lasting up to four weeks when switching patients to a different antipsychotic agent 1-44.
4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. Drug interactions considered clinically relevant for atypical antipsychotics are summarized in Table 5 1-25. Only those drug-drug interactions classified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.
Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level # |
---|---|---|---|---|
Aripiprazole | Citalopram | Increased risk of QT prolongation and serotonin syndrome because aripiprazole is a partial agonist of 5-HT1A and citalopram is a selective serotonin reuptake inhibitor | Avoid use | major (CP) |
Atypical antipsychotics (AAs) | Antihypertensive agents | Potential for enhanced antihypertensive effects due to AA-associated alpha1-adrenergic receptor antagonism | Use cautiously together; monitor for amplified hypotensive effects | moderate (CP) |
AAs | CNS depressants | Potential for additive CNS effects | Use cautiously together; observe patients for enhanced CNS adverse effects | moderate (CP) |
AAs (except pimavanserin) | Drugs affecting seizure threshold (e.g., tramadol) | Increased seizure risk as AAs have been associated with seizures (incidence varies) | Avoid drug combination if possible; if combination necessary, closely monitor patients for seizure activity and discontinue therapy as indicated | major (CP) |
AAs | Metoclopramide | Adjunctive therapy enhances potential for increased extrapyramidal symptoms (EPS) and neuroleptic malignant syndrome (NMS) as both agents block dopamine receptors | Combination contraindicated by metoclopramide manufacturer; if combination necessary, monitor for signs/ symptoms of EPS or NMS-discontinue metoclopramide if symptoms develop | severe (CP) |
Clozapine | Myelopsuppressive (antineoplastic) drugs | Potential for additive bone marrow suppressive effects | Concurrent administration contraindicated | severe (CP) |
Clozapine | Carbamazepine | Increased risk of additive bone marrow-suppressing effects, including agranulocytosis | Avoid concurrent use; choose alternative anticonvulsant | major (CP) |
Samidorphan | Opioids | Concurrent use may decrease opioid efficacy and precipitate opioid withdrawal | Concurrent administration is contraindicated | severe (CP) |
Select AAs (clozapine, olanzapine) | CYP1A2 inducers (e.g., carbamazepine**, phenobarbital, phenytoin, ritonavir*, rifampin) | Potential for reduced clozapine, olanzapine serum concentrations and worsening of psychosis | Monitor clozapine, olanzapine efficacy in patients; adjust doses as necessary when CYP1A2 inducer added, deleted, or changed to therapeutic regimen | major (CP) |
Select AAs (asenapine, clozapine, olanzapine) | CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine) | Potential for decreased AA clearance, increased AA serum concentrations and enhanced pharmacologic/ adverse effects (seizures, hypotension) as clozapine, olanzapine metabolized by CYP1A2 | If drug combination necessary, used reduced clozapine dosages and closely monitor for adverse events | major (CP) |
Select AAs (aripiprazole, brexpiprazole, cariprazine, clozapine, iloperidone, pimavanserin, quetiapine, ziprasidone) | CYP3A4 inhibitors (e.g., ketoconazole, ritonavir*) | Potential for decreased AA clearance, increased AA serum concentrations, and enhanced pharmacologic/ adverse effects as select AAs metabolized by CYP3A4 | Monitor for enhanced AA pharmacologic/ adverse effects and adjust doses as necessary (50% dose reduction recommended for aripiprazole, brexpiprazole, iloperidone) | major, moderate (CP) |
Select AAs (aripiprazole, brexpiprazole, clozapine, olanzapine, pimavanserin, quetiapine, risperidone, ziprasidone) | CYP3A4 inducers (e.g., carbamazepine**, phenytoin) | Potential for significant reductions in AA plasma concentrations (by as much as 50%) due to enhanced AA hepatic microsomal metabolism | Monitor AA efficacy in patients; adjust doses as necessary when CYP3A4 inducer added, deleted, or changed to therapeutic regimen (brexpiprazole dose should be doubled over 1-2 weeks when prescribed with CYP3A4 inducer) | major, moderate (CP) |
Select AAs (aripiprazole, brexpiprazole, iloperidone, risperidone) | CYP2D6 inhibitors (e.g., quinidine, select SSRIs, ritonavir) | Potential for decreased AA clearance and increased AA serum concentrations and enhanced pharmacologic/ adverse effects as select AAs metabolized by CYP2D6 | Monitor for enhanced AA pharmacologic/ adverse effects and adjust doses as necessary (recommended to reduce aripiprazole, brexpiprazole, iloperidone doses by 50% when administered in conjunction with CYP2D6 inhibitor) | major, moderate (CP) |
Select AAs (aripiprazole, asenapine, clozapine, iloperidone, olanzapine, paliperidone, pimavanserin, quetiapine, risperidone, ziprasidone) | QTc interval-prolonging medications | Potential for increased cardiotoxicity (e.g., torsades de pointes, cardiac arrest) due to additive QT interval prolongation | Avoid concurrent use; if combination necessary, closely monitor cardiac function; discontinue therapy in patients with QTc measurements greater than 500 msec | severe, major (CP) |
Legend:
- # CP = Clinical Pharmacology
- * Ritonavir inhibits clozapine metabolism through CYP3A4 inhibition, but induces olanzapine metabolism through CYP1A2 enzyme induction.
- ** Carbamazepine induces olanzapine metabolism through CYP1A2 enzyme induction and induces clozapine metabolism through CYP3A4 induction.
5. References
- Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2023. Available at: http://clinicalpharmacology-ip.com.ezproxy.lib.utexas.edu/. Accessed September 8, 2023.
- Clozapine tablets (Clozaril®) package insert. HLS Therapeutics (USA), Inc., May 2023.
- Clozapine oral suspension (Versacloz®) package insert. TruPharma, LLC, March 2023.
- Asenapine sublingual tablets (Saphris®) package insert. Allergan USA, Inc., October 2021.
- Ziprasidone capsules (Geodon®) package insert. Roerig, February 2022.
- Risperidone tablets, orally disintegrating tablets, oral solution (Risperdal®) package insert. Janssen Pharmaceuticals, Inc., August 2022.
- Iloperidone tablets (Fanapt®) package insert. Vanda Pharmaceuticals Inc., September 2021.
- Paliperidone extended-release tablets (Invega®) package insert. Janssen Pharmaceuticals, Inc., March 2022.
- Aripiprazole tablet, orally disintegrating tablet, oral solution (Abilify®) package insert. Otsuka America Pharmaceutical, Inc., November 2022.
- Olanzapine tablet, orally disintegrating tablet (Zyprexa®, Zyprexa® Zydis®) package insert. Eli Lilly and Company, February 2021.
- Quetiapine tablets (Seroquel®) package insert. AstraZeneca Pharmaceuticals, January 2022.
- Quetiapine extended-release tablets (Seroquel XR®) package insert. AstraZeneca Pharmaceuticals, January 2022.
- Lurasidone tablets (Latuda®) package insert. Sumitomo Pharma America, Inc., May 2022.
- Brexpiprazole (Rexulti®) package insert. Otsuka America Pharmaceutical, Inc., May 2023.
- Cariprazine capsules (Vraylar®) package insert. Remedyrepack, Inc., July 2021.
- Aripiprazole tablets with sensor (Abilify MyCite®) package insert. Otsuka America Pharmaceutical, Inc., February 2023.
- Pimavanserin tablets (Nuplazid®) package insert. Acadia Pharmaceuticals, Inc., November 2020.
- Olanzapine and fluoxetine hydrochloride capsule (Symbyax®) package insert. Eli Lilly and Company, August 2023.
- Asenapine extended-release transdermal film (Secuado®). Noven Therapeutics, LLC., November 2022.
- Lumateperone (Caplyta®) oral capsules package insert. Intra-Cellular Therapies, Inc., June 2023.
- Olanzapine and samidorphan (Lybalvi®) oral tablets package insert. Alkermes Inc., May 2021.
- The Parameters Workgroup of the Psychiatric Executive Formulary Committee, Health and Specialty Care Division, Texas Health and Human Services Commission. Psychotropic medication utilization parameters for children and youth in Texas public behavioral health (6th version). (June 2019) Available at: https://hhs.texas.gov/sites/default/files/documents/doing-business-with-hhs/provider-portal/facilities-regulation/psychiatric/psychotropic-medication-utilization-parameters.pdf. Accessed September 8, 2023.