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 pliance^1,16.

Pimavanserin (Nuplazid) is an oral atypical antipsychotic that is indicated for use to manage hallucinations and delusions seen with Parkinson’s disease psychosis^1,17. Olanzapine combination therapy is FDA-approved for use in managing treatment-resistant depression as well as acute depressive episodes associated with bipolar I disorder^1,18. 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 patients^1,20.

Maximum recommended adult doses for atypical antipsychotics are summarized in Table 1. Dosages exceeding these recommendations will be reviewed.

Table 1. Oral Atypical Antipsychotics (Monotherapy) - Adult Maximum Recommended Dosages^1-17,19,20
Drug Name	Available Dosage Strengths	Treatment Indication	Maximum Recommended Dosage
Aripiprazole (Abilify, Abilify MyCite system, generics)	2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg immediate-release (IR) tablets 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, 30 mg IR tablets with sensor# 10 mg, 15 mg orally disintegrating tablets (ODTs) 1 mg/ml oral solution	Schizophrenia, BD	oral tablets & oral solution : 30 mg/day oral solution: 25 mg/day
		MDD	15 mg/day
Asenapine (Saphris®, Secuado® Transdermal System, generics)	2.5 mg, 5 mg, 10 mg sublingual tablets 3.8 mg/24 hr, 5.7 mg/24 hr, 7.6 mg/24 hr transdermal patch	Schizophrenia, BD	20 mg/day, in two divided doses 7.6 mg/24 hr transdermally
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)	25 mg, 50 mg, 100 mg, 200 mg IR tablets 12.5 mg, 25 mg, 100 mg, 150 mg, 200 mg ODTs 50 mg/ml oral suspension	Schizophrenia (treatment-resistant), reducing recurrent suicidal behavior in schizophrenia and schizoaffective disorder (SD)	900 mg/day, in divided doses
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)	25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg IR tablets 50 mg, 150 mg, 200 mg, 300 mg, 400 mg ER tablets	Schizophrenia, BD (acute manic episodes, maintenance)	IR: 800 mg/day, in two or three divided doses ER: 800 mg/day, as a single dose
		Schizophrenia	750 mg/day, in two or three divided doses
		Bipolar depression	IR: 300 mg/day, at bedtime ER: 300 mg/day, as a single dose
Quetiapine (Seroquel XR®, generics)		MDD	ER: 300 mg/day, as a single dose
Risperidone (Risperdal®, Risperdal M-TAB®, generics)	0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg IR tablets 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg ODTs 1 mg/ml oral solution	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 schizophrenia^1,21. 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 drug^{1, 21}. Doses exceeding the maximum adult recommended doses summarized in Table 2 will be reviewed.

Table 2. Oral Atypical Antipsychotics (Combination Therapy) – Adult Maximum Recommended Dosages^1,18,21
Drug Name	Available Dosage Strengths	Treatment Indication	Maximum Recommended Dosage
Olanzapine/ fluoxetine (Symbyax, generics )	Olanzapine 3 mg/fluoxetine 25 mg olanzapine 6 mg/fluoxetine 25 mg olanzapine 6 mg/fluoxetine 50 mg olanzapine 12 mg/fluoxetine 25 mg olanzapine 12 mg/fluoxetine 50 mg	Bipolar depression, treatment-resistant depression	Olanzapine 18 mg/ fluoxetine 75 mg once daily in evening, without regard to meals
Olanzapine/ samidorphan (Lybalvi®)	Olanzapine 5 mg/ samidorphan 10 mg olanzapine 10 mg/ samidorphan 10 mg olanzapine 15 mg/ samidorphan 10 mg olanzapine 20 mg, samidorphan 10 mg	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 age^1,6. 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 age^1,9. 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 fluoxetine^1,18. 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 age^1,11,12. Paliperidone is approved FDA for the management of schizophrenia in adolescents 12 to 17 years of age^1,8. 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 age^1,13. 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 population^{1-3,5,7,15-17,20}.

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.

Table 3. Atypical Antipsychotics (Monotherapy) – Pediatric Maximum Recommended Dosages^1-6,8-14
Drug Name	Available Dosage Strengths	Treatment Indication	Literature Based Maximum Dosage	FDA Approved Maximum Recommended Dosage
Aripiprazole (Abilify,generics)	2 mg, 5 mg, 10mg, 15 mg, 20 mg, 30 mg immediate-release (IR) tablets 10 mg, 15 mg orally disintegrating tablets (ODTs) 1 mg/ml oral solution	Schizophrenia	Age 4-11 years: 15 mg/day Age greater than or equal to 12 years: 30 mg/day	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: Less than 50 kg: 10 mg/day Greater than or equal to 50 kg: 20 mg/day
		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)	25 mg, 50 mg, 100 mg, 200 mg IR tablets 12.5 mg, 25 mg, 100 mg, 150 mg, 200 mg ODTs 50 mg/ml oral suspension	Reserved for treatment resistant psychosis, following two failed trials of antipsychotic therapy with adequate dose/ duration	Age 8-11 years: 150- 300 mg/day Age greater than or equal to 12 years: 600 mg/day Target serum clozapine level of 350 ng/mL for optimal efficacy	Not approved for children or adolescents
Lurasidone (Latuda®)	20 mg, 40 mg, 60 mg, 80 mg IR tablets	Schizophrenia, BD	Schizophrenia (age 13-17 years): 80 mg/day Bipolar I Depression (age 10-17 years): 80 mg/day	13 to 17 years of age: 80 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 5 mg, 10 mg, 15 mg, 20 mg orally disintegrating tablets	Schizophrenia, BD	Age 4-5 years: 12.5 mg/day Age 6-17 years: 20 mg/ day	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: Weight less than 51 kg: 6 mg/day Weight greater than or equal to 51 kg: 12 mg/day	12-17 years of age: Less than 51 kg: 6 mg/day Greater than or equal to 51 kg: 12 mg/day
Quetiapine (Seroquel, generics, Seroquel XR)	25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg IR tablets 50 mg, 150 mg, 200 mg, 300 mg, 400 mg ER tablets	BD - acute manic episodes	Age 5- 9 years: 400 mg/day Age 10-17 years: 800 mg/day	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)	0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg IR tablets 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg ODTs 1 mg/ml oral solution	Bipolar mania	Age 4-11 years: 3 mg/day Age greater than or equal to12 years:6 mg/day	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) Weight less than or equal to 45 kg: 80 mg/day Weight greater than 45 kg	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 BD^1,18. Recommended pediatric dosages are summarized in Table 4.

Table 4. Oral Atypical Antipsychotics (Combination Therapy) – Pediatric Maximum Recommended Dosages^1,18
Drug Name	Available Dosage Strengths	Literature Based Maximum Dosage	Treatment Indication	Maximum Recommended Dosage per Age Group
Olanzapine/ fluoxetine (Symbyax, generics)	Olanzapine 3 mg/fluoxetine 25 mg olanzapine 6 mg/fluoxetine 25 mg olanzapine 6 mg/fluoxetine 50 mg olanzapine 12 mg/fluoxetine 25 mg olanzapine 12 mg/fluoxetine 50 mg	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