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Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug/Lab Interactions Precautions/
Contraindications
Aripiprazole

(Abilify®)
(Abilify Discmelt®)
(Abilify Maintena™)
(Aristada®)
Abilify® - tablet
  • 2 mg
  • 5 mg
  • 10 mg
  • 15 mg
  • 20 mg
  • 30 mg

Abilify Discmelt®
Orally-disintegrating tablet

  • 10 mg
  • 15 mg

Abilify® - solution
  • 1 mg/ml
  • Comes in 150 ml bottle

Abilify Maintena™
Prefilled syringe and vial

  • 300 mg
  • 400 mg

Aristada™ (aripiprazole lauroxil)
Prefilled syringe

  • 441 mg
  • 662 mg
  • 882 mg
Abilify® (tablet/discmelt/solution)     

Schizophrenia/Bipolar I
  • Starting: 10 - 15 mg once daily
  • Maintenance: - 10 - 20 mg once daily
  • Max: 30 mg once daily
  • Increase dose at intervals of ≥ 2 weeks
  • Solution can be substituted for tablet on mg-to-mg basis up to 25 mg

Depression (adjunctive with antidepressant)
  • Starting: 2 - 5 mg once daily
  • Maintenance: 2 - 15 mg once daily
  • Increase dose by up to 5 mg a day at intervals of ≥ 1 week

Abilify Maintena™     

Schizophrenia
  • Dosing: 400 mg IM once a month
  • Patients should demonstrate tolerability of oral Abilify® before using
  • After initial injection, continue oral aripiprazole for 14 days
  • See Abilify Maintena™ PI for guidelines on missed injections

Aristada™     

Schizophrenia
  • Dosing: 441 - 882 mg IM once monthly. 882 mg dose may also be given every 6 weeks.
  • Patients should demonstrate tolerability of oral Abilify® before using
  • After initial injection, continue oral aripiprazole for 21 days
  • Converting from oral:
    • 10 mg/day = 441 mg/month
    • 15 mg/day = 662 mg/month
    • ≥ 20 mg/day = 882 mg/month
  • See Aristada PI sec 2.2 for guidelines on missed injections

See drug interactions for dosing guidelines with certain medications
Tablet
YES/$$$$

Discmelt
YES/$$$$

Solution
YES/$$$$

Abilify Maintena
NO/$$$$

Aristada
NO/$$$$
Other
Tablet and discmelt
  • May take without regard to food
  • Discmelt is placed on tongue where it dissolves

Solution
  • Once bottle is opened, good for 6 months
  • Store at room temperature

Abilify Maintena
  • For intramuscular injection in the deltoid or gluteal muscle
  • Store at room temperature

Aristada
  • For intramuscular injection in the deltoid (441 mg dose only) or gluteal muscle (all doses)
  • Store at room temperature

Pharmacokinetics (tablet)
  • Half-life (aripiprazole): 75 hours
  • Half-life (metabolite): 94 hours
Mechanism of action
  • Dopamine D2 receptor partial agonist
  • Serotonin 5-HT1A receptor partial agonist
  • Serotonin 5-HT2A receptor antagonist

FDA-approved indications

Abilify tablets/solution
  • Schizophrenia
  • Bipolar - acute mania and chronic
  • Depression- adjunct with antidepressants
  • Autism- irritability

Abilify Maintena and Aristada
  • Schizophrenia
  • Headache- 27%, P - 23%
  • Agitation- 19%, P - 17%
  • Insomnia- 18%, P - 13%
  • Anxiety- 17%, P - 13%
  • Nausea- 15%, P - 11%
  • Somnolence - 11%, P - 6%
  • Constipation - 11%, P - 7%
  • Vomiting - 11%, P - 6%
  • Dizziness - 10%, P - 7%
  • Akathisia - 10%, P - 4%
  • Extrapyramidal symptoms - 8 to 13% of patients in trials
  • Weight gain - up to 8% of patients
  • Orthostatic hypotension - 1% of patients
  • Difficulty swallowing - incidence not well-defined
  • Hyperprolactinemia (elevated prolactin levels) - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
Drug interactions
  • CYP3A4 strong inhibitors - reduce aripiprazole dose by one-half
  • CYP3A4 strong inducers - aripiprazole dose may need to be doubled
  • CYP2D6 inhibitors - reduce aripiprazole dose by one-half
  • CYP3A4 strong inhibitor + CYP2D6 inhibitor - reduce aripiprazole dose to one-quarter of usual dose
  • Any combination of strong, moderate, or weak CYP3A4 and CYP2D6 inhibitors - reduce aripiprazole to one-quarter the usual dose and adjust as needed.
  • Carbamazepine - carbamazepine is a strong CYP3A4 inducer. Double aripiprazole dose when taken together.
  • Alpha blockers - aripiprazole can block alpha receptors. It may potentiate the effects of alpha blockers.
  • Dopamine agonists (Mirapex®, Sinemet®, etc.) - aripiprazole may block the activity of dopamine agonists used in Parkinson's, RLS, etc.

Lab interactions
  • Urine drug screen - there have case reports of false-positive amphetamines on urine drug screens in children exposed to aripiprazole. Subsequent confirmatory testing with gas chromatography-mass spectrometry was negative. [PMID 26527556]
  • Poor CYP2D6 metabolizers - reduce dose by one-half and adjust as needed
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Suicide in depression - possible increase risk when starting therapy in patients ≤ 24 years old
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials lasting up to 24 weeks, aripiprazole had no significant effect on blood sugars. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials lasting up to 24 weeks, aripiprazole had no significant effect on lipid parameters. Long-term effects are unknown. See cholesterol below for ADA monitoring recommendations.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Impulse-control problems - cases of uncontrollable urges to gamble, binge eat, shop, and have sex have been reported in patients taking aripiprazole
  • Liver disease - no dose adjustment necessary
  • Kidney disease - no dose adjustment necessary

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Asenapine

(Saphris®)
Asenapine (Saphris®)
Sublingual tablet
  • 5 mg
  • 10 mg
Schizophrenia
    ADULTS
    • Starting: 5 mg twice a day
    • Maintenance: 5 - 10 mg twice a day
    • Max: 10 mg twice a day
    • Increase dose at intervals of 1 week

Bipolar mania
    ADULTS
    • Starting: 5 - 10 mg twice a day
    • Maintenance: 5 - 10 mg twice a day
    • Max: 10 mg twice a day

    CHILDREN (10 - 17 YEARS)
    • Starting: 2.5 mg twice a day
    • Maintenance: 2.5 - 10 mg twice a day
    • Max: 10 mg twice a day

Bipolar mania - adjunct to lithium or valproate
    ADULTS
    • Starting: 5 mg twice a day
    • Maintenance: 5 - 10 mg twice a day
    • Max: 10 mg twice a day
NO/$$$$ Other
  • Asenapine is a sublingual tablet that dissolves under the tongue

  • It should not be crushed, chewed, or swallowed

  • Patients should not eat or drink for 10 minutes after administration

Pharmacokinetics
  • Tmax: 1 hour
  • Half-life: 24 hours
Mechanism of action
  • Dopamine D2 receptor antagonist

  • Serotonin (5-HT2A) receptor antagonist

FDA-approved indications
  • Schizophrenia

  • Bipolar - acute mania
  • Somnolence- 24%, P - 6%
  • Weight gain (≥ 7% increase) - 15% after one-year of therapy
  • Headache- 12%, P - 11%
  • Dizziness- 11%, P - 3%
  • Akathisia- 4%, P - 2%
  • Extrapyramidal symptoms - up to 10% of patients in trials
  • Orthostatic hypotension - < 1% of patients
  • Difficulty swallowing - incidence not well-defined
  • Hyperprolactinemia (elevated prolactin level) - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
  • Prolonged QT syndrome - DO NOT USE. Asenapine may prolong the QT interval.
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials lasting up to 6 weeks, asenapine caused a slight increase in blood sugars. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. See cholesterol below for ADA monitoring recommendations.
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Liver disease
    • Mild to moderate (Child-Pugh A/B) - no dose adjustment necessary
    • Severe (Child-Pugh C) - DO NOT USE
  • Kidney disease - No dose adjustment necessary

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Brexpiprazole

(Rexulti®)
Brexpiprazole (Rexulti®)
Tablet

  • 0.25 mg
  • 0.5 mg
  • 1 mg
  • 2 mg
  • 3 mg
  • 4 mg
Schizophrenia
  • Starting: 1 mg once daily on Days 1 to 4, increase dose to 2 mg once daily on Days 5 to 7, then to 4 mg on Day 8 if needed
  • Maintenance: 2 - 4 mg once daily
  • Max: 4 mg once daily

Depression (adjunctive with antidepressant)
  • Starting: 0.5 - 1 mg once daily
  • Maintenance: 2 mg once daily
  • Max: 3 mg once daily
  • Increase dose at weekly intervals

Dosing with CYP2D6 and CYP3A4 modulators

Concurrent medication Brexpiprazole dose
Strong CYP2D6 inhibitor Half usual dose
Strong CYP3A4 inhibitor Half usual dose
Strong/moderate CYP2D6 inhibitor +
strong/moderate CYP3A4 inhibitor
Quarter of usual dose
Strong CYP3A4 inducer Double usual dose over
1 - 2 weeks

Dosing for CYP2D6 poor metabolizers
  • CYP2D6 poor metabolizer - half the usual dose

  • CYP2D6 poor metabolizer + strong/moderate CYP3A4 inhibitor - quarter the usual dose
NO/$$$$ Other
  • May take without regard to food

Pharmacokinetics
  • Time to max level: within 4 hours
  • Half-life: 91 hours
Mechanism of action
  • Dopamine D2 receptor partial agonist

  • Serotonin 5-HT1A receptor partial agonist

  • Serotonin 5-HT2A receptor antagonist

FDA-approved indications
  • Schizophrenia

  • Depression (adjunctive with antidepressant)
NOTE: most side effects listed are from trials in schizophrenics using 4 mg/day dose

  • Increase in triglycerides - 10%, P - 6%
  • Akathisia- 7%, P - 5%
  • Extrapyramidal symptoms (excluding akathisia) - 5%, P - 4%
  • Somnolence - 5%, P - 3%
  • Tremor - 3%, P - 1%
  • Sedation - 3%, P - 1%
  • Upset stomach - 3%, P - 2%
  • Diarrhea - 3%, P - 2%
  • Increase in CPK - 2%, P - 1%
  • Weight gain - in 6 week trials, patients on brexpiprazole gained an average of 2.6 lbs (1.2 kg) while patients on placebo gained 0.4 lbs (0.2 kg)
  • Difficulty swallowing - incidence not well-defined
  • CYP3A4 modulators - brexpiprazole is a CYP3A4 sensitive substrate. See Dosage for recommendations on concomitant dosing.
  • CYP2D6 modulators - brexpiprazole is a CYP2D6 sensitive substrate. See Dosage for recommendations on concomitant dosing.
  • Dopamine agonists (Mirapex®, Sinemet®, etc.) - brexpiprazole may block the activity of dopamine agonists used in Parkinson's, RLS, etc.
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Suicide in depression - possible increase risk when starting therapy in patients ≤ 24 years old
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials lasting up to 6 weeks, brexpiprazole had no significant effect on blood sugars. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials lasting up to 6 weeks, brexpiprazole had no significant effect on lipid parameters. Long-term effects are unknown. See cholesterol below for ADA monitoring recommendations.
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Liver disease
    • Moderate to severe (Child-Pugh B/C) - max of 2 mg/day in depression and 3 mg/day in schizophrenia
  • Kidney disease
    • CrCl < 60 ml/min - max of 2 mg/day in depression and 3 mg/day in schizophrenia

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indication
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Cariprazine

(Vraylar®)
Cariprazine - capsule
  • 1.5 mg
  • 3 mg
  • 4.5 mg
  • 6 mg
Schizophrenia
  • Starting: 1.5 mg once daily. May increase to 3 mg once daily on Day 2.
  • Maintenance: 1.5 - 6 mg once daily
  • Max: 6 mg once daily
  • Cariprazine has a long half-life and changes in dose will not be fully reflected in plasma for several weeks

Bipolar I - manic or mixed episode
  • Starting: 1.5 mg once daily. Increase to 3 mg once daily on Day 2.
  • Maintenance: 3 - 6 mg once daily
  • Max: 6 mg once daily
  • Cariprazine has a long half-life and changes in dose will not be fully reflected in plasma for several weeks

Dosing with CYP3A4 inducers and inhibitors

Initiating a strong CYP3A4 inhibitor while on stable cariprazine dose
  • Reduce cariprazine dose by half
  • For 1.5 mg dose, give every other day

Initiating cariprazine while taking a strong CYP3A4 inhibitor
  • Give cariprazine 1.5 mg on Day 1 and Day 3 with no dose on Day 2
  • From Day 4 onward, give 1.5 mg once daily
  • Maximum dose is 3 mg once daily

Cariprazine with a CYP3A4 inducer
  • Has not been studied
  • Not recommended
Vraylar®
NO/$$$$

Other
  • May take without regard to food

Pharmacokinetics
  • Cariprazine has 2 major, active metabolites - DCAR, DDCAR
  • Half-lives:
    • Cariprazine: 2 - 4 days
    • DDCAR: 1 - 3 weeks
    • DCAR: ?
Mechanism of action
  • Cariprazine is a partial agonist at dopamine D2 and serotonin 5-HT1A receptors
  • Cariprazine is an antagonist at serotonin 5-HT2A receptors

FDA-approved indication
  • Treatment of schizophrenia

  • Acute treatment of manic or mixed episodes associated with bipolar I disorder
NOTE: only side effects that occurred at an incidence of ≥ 2% and ≥ 2% more than placebo are listed. Side effects are for 4.5 - 6 mg/day dosing.

  • Extrapyramidal symptoms - 32%, P - 14%
  • Insomnia - 13%, P - 11%
  • Somnolence - 8%, P - 5%
  • Constipation - 7%, P - 5%
  • Nausea - 7%, P - 5%
  • Restlessness - 6%, P - 3%
  • Vomiting - 5%, P - 3%
  • Dizziness - 5%, P - 2%
  • Fatigue - 3%, P - 1%
  • Hypertension - 3%, P - 1%
  • Weight gain - in a 6-week trial, patients taking 4.5 - 6 mg of cariprazine gained an average of 2.2 pounds while placebo-treated patients gained an average of 0.66 pounds
  • Difficulty swallowing - incidence not well-defined
  • Late-occurring adverse reactions - steady-state for cariprazine and its active metabolites may not be achieved for a number of weeks. Because of this, adverse effects may not appear until weeks after the drug is initiated.
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials lasting up to 6 weeks, cariprazine had no significant effect on blood sugars. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials lasting up to 6 weeks, cariprazine had no significant effect on lipid parameters. Long-term effects are unknown. See cholesterol below for ADA monitoring recommendations.
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Liver disease
    • Mild to moderate (Child-Pugh A/B) - no dose adjustment necessary
    • Severe (Child-Pugh C) - DO NOT USE
  • Kidney disease
    • CrCl ≥ 30 ml/min - no dose adjustment necessary
    • CrCl < 30 ml/min - DO NOT USE

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
O = % of patients on olanzapine
who experienced side effect
Drug Interactions Precautions/
Contraindications
Clozapine

(Clozaril®)
(Fazaclo ODT®)
(Versacloz®)
Clozapine - tablet
  • 12.5 mg
  • 25 mg
  • 50 mg
  • 100 mg
  • 200 mg

Fazaclo ODT®
Orally disintegrating tablet
  • 12.5 mg
  • 25 mg
  • 100 mg
  • 150 mg
  • 200 mg

Versacloz® - suspension
  • 50 mg/ml
  • Comes in 100 ml bottle
Schizophrenia
  • Starting: 12.5 mg once or twice daily
  • Maintenance: 300 - 450 mg a day given in divided doses
  • Max: 900 mg a day
  • Increase in increments of 25 - 50 mg daily until target dose reached. Subsequently, the dose can be increased once or twice weekly in increments of up to 100 mg.
  • When stopping, reduce dose gradually over a period of 1-2 weeks to avoid cholinergic rebound
  • If ≥ 2 days lapse since last dose, reinitiate with 12.5-mg once daily or twice daily to prevent hypotension
  • See lab monitoring recommendations below
  • Providers and pharmacies must be registered in the Clozapine REMS program in order to prescribe or dispense clozapine

See Drug interactions for dosing with certain medications
Tablet
YES/$$-$$$

Fazaclo ODT®
NO/$$$$

Versacloz®
NO/$$$$ (1 bottle)
Other
  • May take without regard to food
  • The Fazaclo ODT® is an orally disintegrating tablet. It may also be chewed or swallowed

Versacloz®
  • Store at room temperature
  • Shake well for 10 seconds before use
  • Bottle good for 100 days after opening

Pharmacokinetics
  • Half-life (single dose): 8 hours
  • Half-life (steady state): 12 hours
Mechanism of action
  • Dopamine-2 receptor antagonist
  • Serotonin 5-HT2A receptor antagonist

FDA-approved indications
  • Treatment resistant schizophrenia
  • Reduction in risk of recurrent suicidal behavior in schizophrenia and schizoaffective disorder
NOTE: data only available for comparison with
olanzapine (O)


  • Salivary hypersecretion - 48%, O - 6%
  • Somnolence- 46%, O - 25%
  • Weight gain (≥ 7% increase) - 35%, O - 46%
  • Lightheadedness - 27%, O - 12%
  • Constipation- 25%, O - 10%
  • Insomnia- 20%, O - 33%
  • Nausea- 17%, O - 10%
  • Vomiting- 17%, O - 9%
  • Upset stomach - 14%, O - 8%
  • Orthostatic hypotension - incidence not well-defined
  • Difficulty swallowing - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
  • Clozapine Agranulocytosis
  • Prolonged QT syndrome - DO NOT USE. Clozapine may prolong the QT interval.
  • Eosinophilia - in trials, 1% of patients treated with clozapine developed eosinophilia. DRESS syndrome has also occurred in some patients.
  • Poor CYP2D6 metabolizers - may need to reduce dose
  • Orthostatic hypotension, bradycardia, and syncope - clozapine has been associated with hypotension, bradycardia, and syncope in some patients. The risk is highest when starting therapy. Titrate dose slowly to avoid hypotension.
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Myocarditis, cardiomyopathy, and mitral valve incompetence - myocarditis and cardiomyopathy have been reported in patients receiving clozapine. Myocarditis typically presents within the first 2 months of treatment, but may occur at any time. Nonspecific flu-like symptoms often precede overt heart failure. Clozapine-induced cardiomyopathy may lead to mitral valve incompetence.
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials, clozapine has been shown to raise blood sugars. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials, clozapine had an adverse effect on lipid parameters. See cholesterol below for ADA monitoring recommendations.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Glaucoma - may cause pupil dilation
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Hepatotoxicity - cases of hepatotoxicity and liver failure have been reported in patients taking clozapine. Monitor for signs of liver failure (e.g. fatigue, malaise, anorexia, nausea, jaundice) and check liver function tests periodically.
  • Liver disease - dose adjustment may be necessary. Manufacturer makes no specific recommendation.
  • Kidney disease -dose adjustment may be necessary. Manufacturer makes no specific recommendation.

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Iloperidone

(Fanapt®)
Fanapt® - tablet
  • 1 mg
  • 2 mg
  • 4 mg
  • 6 mg
  • 8 mg
  • 10 mg
  • 12 mg

Titration pack
  • 2 X 1 mg
  • 2 X 2 mg
  • 2 X 4 mg
  • 2 X 6 mg

Schizophrenia
  • Starting: 1 mg twice a day
  • Maintenance: 6 - 12 mg twice a day
  • Max: 12 mg twice a day
  • Increase dose daily as tolerated. Do not increase by more than 4 mg a day.
  • Orthostatic hypotension may occur if dose is increased too fast

See Drug Interactions for dosing with specific medications
NO/$$$$ Other
  • May take without regard to food
  • If ≥ 3 days lapse since last dose, reinitiate at 1 mg twice a day and titrate

Pharmacokinetics
  • Iloperidone has 2 active metabolites - P88 and P95
  • Half-lives for iloperidone, P88 and P95 in CYP2D6 extensive metabolizers are 18, 26, and 23 hours, respectively, and in poor metabolizers are 33, 37, and 31 hours, respectively
Mechanism of action
  • Dopamine D2 receptor antagonist
  • Serotonin type 2 (5-HT2) receptor antagonist

FDA-approved indications
  • Schizophrenia
  • Dizziness- 20%, P - 7%
  • Weight gain - 18%, P - 4%
  • Somnolence- 15%, P - 5%
  • Extrapyramidal symptoms - 15%, P - 11%
  • Rapid heart rate - 12%, P - 1%
  • Nausea- 10%, P - 8%
  • Dry mouth - 10%, P - 1%
  • Orthostatic hypotension - up to 5% of patients
  • Hyperprolactinemia (elevated prolactin level) - 26%, P - 12%
  • Difficulty swallowing - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
  • Drugs that prolong the QT interval - DO NOT COMBINE
  • Iloperidone is a CYP2D6 and CYP3A4 substrate
  • CYP2D6 strong inhibitors - reduce iloperidone dose by one-half
  • CYP3A4 strong inhibitors - reduce iloperidone dose by one-half
  • CYP3A4 substrates - in vitro studies have shown that iloperidone is a CYP3A4 inhibitor. Iloperidone may affect CYP3A4 substrates.
  • Alpha blockers - iloperidone can block alpha receptors. It may potentiate the effects of alpha blockers.
  • Dopamine agonists (Mirapex®, Sinemet®, etc.) - iloperidone may block the activity of dopamine agonists used in Parkinson's, RLS, etc.
  • Prolonged QT syndrome - DO NOT USE. Iloperidone may prolong the QT interval.
  • Poor CYP2D6 metabolizers - reduce dose by one-half
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials lasting 4 weeks, iloperidone was shown to raise blood sugars in some patients. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials lasting 4 weeks, iloperidone was shown to raise lipid parameters in some patients. Long-term effects are unknown. See cholesterol below for ADA monitoring recommendations.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Liver disease - has not been studied. Not recommended.
  • Kidney disease - No dose adjustment necessary

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Lurasidone

(Latuda®)
Latuda® - tablet
  • 20 mg
  • 40 mg
  • 60 mg
  • 80 mg
  • 120 mg
Schizophrenia    
Adults
  • Starting: 40 mg once daily
  • Maintenance: 40 - 160 mg once daily
  • Max: 160 mg once daily

Adolescents (13 - 17 years)
  • Starting: 40 mg once daily
  • Maintenance: 40 - 80 mg once daily
  • Max: 80 mg once daily

Bipolar I depression (monotherapy or adjunctive)    
Adults
  • Starting: 20 mg once daily
  • Maintenance: 20 - 120 mg once daily
  • Max: 120 mg once daily

See Drug Interactions for dosing with specific medications
NO/$$$$ Other
  • Take with food (at least 350 calories). Food increases absorption.

Pharmacokinetics
  • Half-life: 18 hours
Mechanism of action
  • Dopamine-2 receptor antagonist
  • Serotonin type 2 (5-HT2A) receptor antagonist

FDA-approved indications
  • Schizophrenia
  • Major depressive episodes associated with bipolar 1 as monotherapy or as adjunctive therapy with lithium or valproate
  • Extrapyramidal symptoms - 26%, P - 9% (80 mg/day dose)
  • Somnolence- 22%, P - 10%
  • Akathisia- 15%, P - 3%
  • Nausea- 12%, P - 6%
  • Parkinsonism- 11%, P - 5%
  • Weight gain (≥ 7% increase) - 5.6%, P - 4%
  • Orthostatic hypotension - 1.7% with 120 mg a day
  • Hyperprolactinemia (elevated prolactin level ≥ 5 X ULN) - 3.6% of patients
  • Difficulty swallowing - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
  • Lurasidone is a CYP3A4 substrate
  • CYP3A4 strong inhibitor - DO NOT COMBINE
  • CYP3A4 strong inducer - DO NOT COMBINE
  • CYP3A4 moderate inhibitor - dose of lurasidone should not exceed 40 mg a day
  • Dopamine agonists (Mirapex®, Sinemet®, etc.) - lurasidone may block the activity of dopamine agonists used in Parkinson's, RLS, etc.
  • Alpha blockers - lurasidone can block alpha receptors. It may potentiate the effects of alpha blockers.
  • Poor CYP2D6 metabolizers - reduce dose by one-half
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Suicide in depression - possible increase risk when starting therapy in patients ≤ 24 years old
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials, lurasidone had a mixed effect on blood sugars. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials, lurasidone had no significant effect on lipid parameters. Long-term effects are unknown. See cholesterol below for ADA monitoring recommendations.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Liver disease
    • Moderate to severe (Child-Pugh B/C) - do not exceed 40 mg a day
  • Kidney disease
    • CrCl 10 - 49 ml/min - do not exceed 40 mg/day

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Olanzapine

(Zyprexa®)
(Zyprexa Zydis®)
(Zyprexa Relprevv®)

Olanzapine + fluoxetine

(Symbyax®)
Zyprexa® - tablet
  • 2.5 mg
  • 5 mg
  • 7.5 mg
  • 10 mg
  • 15 mg
  • 20 mg

Zyprexa Zydis®
Orally disintegrating tablet
  • 5 mg
  • 10 mg
  • 15 mg
  • 20 mg

Zyprexa Relprevv® - Vial
  • 210 mg
  • 300 mg
  • 405 mg

Symbyax®
Fluoxetine(mg):Olanzapine(mg)
  • 25 : 3
  • 25 : 6
  • 25 : 12
  • 50 : 6
  • 50 : 12
Zyprexa®     

Schizophrenia
  • Starting: 5 - 10 mg once daily
  • Maintenance: 10 - 20 mg once daily
  • Max: 20 mg once daily
  • Increase dose by 5 mg a day at intervals of ≥ 1 week
  • Starting dose of 5 mg once daily is recommended in debilitated patients and slow metabolizers (nonsmoking female ≥ 65 years)

Bipolar I
  • Starting: 10 - 15 mg once daily
  • Maintenance: 5 - 20 mg once daily
  • Max: 20 mg once daily
  • Increase dose by 5 mg a day at intervals of not less than 24 hours
  • Starting dose of 5 mg once daily is recommended in debilitated patients and slow metabolizers (nonsmoking female ≥ 65 years)

Zyprexa Relprevv®     

Schizophrenia
  • Dosing: 150 - 300 mg IM every 2 weeks; or 300 - 405 mg every 4 weeks
  • Dosing based on current oral olanzapine dose
  • See Relprevv® PI for dosing recommendations

Fluoxetine + olanzapine (Symbyax®)     

Depression associated with Bipolar 1 and
treatment-resistant depression

  • Starting: 25/6 mg once daily in the evening
  • Maintenance: 25/6 mg - 50/18 mg once daily
  • Max: 75/18 mg once daily
  • NOTE: see also fluoxetine

See Drug Interactions for dosing with specific medications
Zyprexa®
YES/$

Zyprexa Zydis®
YES/$$-$$$

Symbyax®
YES/$$$$

Zyprexa Relprevv®
NO/$$$$
Other
Zyprexa®
  • May take without regard to food

Zydis®
  • Do not push tablet through foil
  • Rapidly disintegrates in mouth
  • Swallow with or without liquid

Relprevv®
  • Only available through restricted distribution program
  • To enroll, call 1-877-772-9390

Pharmacokinetics (oral)
  • Half-life: 21 - 54 hours
Mechanism of action
  • Dopamine-2 receptor antagonist
  • Serotonin type 2 (5-HT2A) receptor antagonist

FDA-approved indications

Zyprexa®
  • Schizophrenia
  • Bipolar - manic or mixed episodes

Zyprexa Relprevv®
  • Schizophrenia

Symbyax®
  • Treatment resistant depression
  • Bipolar I depression
  • Somnolence- 29%, P - 13%
  • Extrapyramidal symptoms - 25%, P - 16%
  • Weight gain (≥ 7% increase) - 22%, P - 3%
  • Insomnia- 12%, P - 11%
  • Dizziness- 11%, P - 4%
  • Fatigue- 10%, P - 9%
  • Constipation - 9%, P - 4%
  • Dry mouth- 6%, P - 1%
  • Orthostatic hypotension - 5%, P - 2%
  • Hyperprolactinemia (elevated prolactin level) - 30%, P - 11%
  • Difficulty swallowing - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
  • Olanzapine is a CYP1A2 (major) and CYP2D6 (minor) substrate
  • CYP1A2 inducers and inhibitors - olanzapine doses may need to be adjusted when taken with CYP1A2 inhibitors or inducers
  • OCT2 substrates - olanzapine is an OCT2 inhibitor
  • Alpha blockers - olanzapine can block alpha receptors. It may potentiate the effects of alpha blockers.
  • Dopamine agonists (Mirapex®, Sinemet®, etc.) - olanzapine may block the activity of dopamine agonists used in Parkinson's, RLS, etc.
  • Fluvoxamine (Luvox®) - increases olanzapine levels. Consider lower olanzapine doses.
  • Omeprazole (Prilosec®) - may increase olanzapine clearance
  • Rifampin - may increase olanzapine clearance
  • Lamotrigine - may reduce lamotrigine levels
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Suicide in depression - possible increase risk when starting therapy in patients ≤ 24 years old
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Serious skin reactions - serious skin reactions including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been reported. Patients taking olanzapine who develop a fever with a rash and swollen lymph glands, or swelling in the face, should seek medical care right away.
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials lasting at least 48 weeks, olanzapine-treated patients had an average increase in fasting blood sugar of 4.2 mg/dl. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials, olanzapine had an adverse effect on lipid parameters. See cholesterol below for ADA monitoring recommendations.
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Liver disease
    • Mild to moderate (Child-Pugh A/B) - no dose adjustment necessary
    • Severe (Child-Pugh C) - use caution
  • Kidney disease - no dose adjustment necessary

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Paliperidone

(Invega®)
(Invega Sustenna®)
Invega®
Extended-release tablet
  • 1.5 mg
  • 3 mg
  • 6 mg
  • 9 mg

Invega Sustenna®
Prefilled syringe
  • 39 mg
  • 78 mg
  • 117 mg
  • 156 mg
  • 234 mg
Invega®     

Schizophrenia/Schizoaffective
  • Starting: 6 mg once daily
  • Maintenance: 3 - 12 mg once daily
  • Max: 12 mg once daily
  • Increase dose by 3 mg a day at intervals of ≥ 5 days

Invega Sustenna®     

Schizophrenia/Schizoaffective
  • Starting: 234 mg IM on Day 1, and 156 mg IM on Day 8
  • Maintenance: 39 - 234 mg IM once a month
  • Administer first maintenance dose 5 weeks after first injection
  • The recommended maintenance dose for schizophrenia is 117 mg
  • See Sustenna PI® for more information on dosing and missed doses

Dosing in kidney disease

CrCl 50 - 79 ml/min
  • Starting: 3 mg once daily
  • Max: 6 mg once daily
CrCl 10 - 49 ml/min
  • Starting: 1.5 mg once daily
  • Max: 3 mg once daily
CrCl < 10 ml/min
  • Do not use
Invega
NO/$$$$

Invega Sustenna
NO/$$$$

Other
Invega®
  • May take without regard to food
  • Do not crush, chew, or divide tablet
  • Insoluble tablet may be seen in stool. This is normal.

Sustenna®
  • Give initial 2 doses in deltoid muscle. Following doses may be given in deltoid or gluteal muscle.
  • Tolerability of oral Invega® or risperidone should be established before using

Pharmacokinetics (oral)
  • Half-life: 23 hours
Mechanism of action
  • Dopamine-2 receptor antagonist
  • Serotonin type 2 (5-HT2A) receptor antagonist

FDA-approved indications
  • Schizophrenia
  • Schizoaffective disorder
NOTE: data is for 9 mg/day dose. Only side effects that occurred at an incidence ≥ 2% more than placebo are listed.

  • Extrapyramidal symptoms - 20%, P - 8%
  • Rapid heart rate - 12%, P - 7%
  • Headache- 14%, P - 12%
  • Somnolence- 10%, P - 7%
  • Weight gain (≥ 7% increase) - 9%, P - 5%
  • Akathisia- 8%, P - 4%
  • Orthostatic hypotension - 2%, P - 1%
  • Hyperprolactinemia (elevated prolactin level) - similar to risperidone which is up to 87% of patients (13 - 17 years old) in some studies
  • Difficulty swallowing - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
  • Prolonged QT syndrome - DO NOT USE. Paliperidone may prolong the QT interval.
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Potential for GI obstruction - paliperidone comes in a non-deformable extended-release tablet. Do not use in patients who are susceptible to obstruction (e.g. esophageal motility disorders, small bowel inflammatory disease, "short gut" syndrome due to adhesions or decreased transit time, past history of peritonitis, cystic fibrosis, chronic intestinal pseudoobstruction, or Meckel's diverticulum)
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials, paliperidone had a mixed effect on blood sugars. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials lasting 6 weeks, paliperidone did not have an adverse effect on lipid parameters. Long-term effects are unknown. See cholesterol below for ADA monitoring recommendations.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Liver disease
    • Mild to moderate (Child-Pugh A/B) - no dose adjustment necessary
    • Severe (Child-Pugh C) - has not been studied
  • Kidney disease -see Dosing

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Quetiapine

(Seroquel®)
(Seroquel XR®)
Seroquel® - tablet
  • 25 mg
  • 50 mg
  • 100 mg
  • 200 mg
  • 300 mg
  • 400 mg

Seroquel XR®
Extended-release tablet
  • 50 mg
  • 150 mg
  • 200 mg
  • 300 mg
  • 400 mg
Specific dosing recommendations are available in the PI
Seroquel® dosing
Seroquel XR® dosing

NOTE: Recommendations below are general guidelines. See PI for specific dosing recommendations.

Seroquel®     

Schizophrenia
  • Starting: 25 mg twice a day
  • Maintenance: 150 - 750 mg a day
  • Max: 800 mg a day
  • Give in 2 - 3 divided doses
  • Increase in increments of 50 - 100 mg a day at intervals ≥ 2 days

Bipolar
  • Starting: 50 - 100 mg a day
  • Maintenance: 300 - 800 mg a day
  • Max: 800 mg a day
  • Give in 1 - 2 divided doses

Seroquel XR®     

Schizophrenia
  • Starting: 300 mg once daily
  • Maintenance: 400 - 800 mg once daily
  • Max: 800 mg once daily
  • Increase in increments of 300 mg a day at intervals ≥ 1 day

Bipolar
  • Starting: 300 mg once daily
  • Maintenance: 300 - 800 mg once daily
  • Max: 800 mg once daily

See Drug Interactions for recommendations with certain drugs
Seroquel®
YES/$

Seroquel XR®
NO/$$$$
Other
Seroquel®
  • May take without regard to food

Seroquel XR®
  • Take without food or with a light meal (300 calories). High fat meals increase absorption (not recommended).
  • Do not crush, chew, or divide tablet

Pharmacokinetics
  • Quetiapine has an active metabolite, norquetiapine

  • Half-life (quetiapine): 7 hours
  • Half-life (norquetiapine): 12 hours
Mechanism of action
  • Dopamine-2 receptor antagonist
  • Serotonin type 2 (5-HT2) receptor antagonist

FDA-approved indications
  • Schizophrenia
  • Bipolar disorder - mania
  • Weight gain (≥ 7% increase) - 23%, P - 6%
  • Headache - 21%, P - 14%
  • Agitation- 20%, P - 17%
  • Somnolence- 18%, P - 8%
  • Dizziness- 11%, P - 5%
  • Dry mouth - 9%, P - 3%
  • Constipation- 8%, P - 3%
  • Orthostatic hypotension - 4%, P - 3%
  • Hyperprolactinemia (elevated prolactin level) - 3.6%, P - 2.6%
  • Extrapyramidal symptoms - incidence is low, similar to placebo in some studies
  • Difficulty swallowing - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
  • Drugs that prolong the QT interval - DO NOT COMBINE
  • Quetiapine is a CYP3A4 sensitive substrate
  • CYP3A4 strong inhibitors - quetiapine dose should be reduced to one-sixth of the original dose when taken with a strong CYP3A4 inhibitor
  • CYP3A4 strong inducers - quetiapine dose should be increased up to five-fold of the original dose when used in combination with a strong CYP3A4 inducer during chronic treatment (greater than 7-14 days)
  • Thioridazine - may increase clearance of quetiapine
  • Dopamine agonists (Mirapex®, Sinemet®, etc.) - quetiapine may block the activity of dopamine agonists used in Parkinson's, RLS, etc.
  • Alpha blockers - quetiapine can block alpha receptors. It may potentiate the effects of alpha blockers.
  • Prolonged QT syndrome - DO NOT USE. Quetiapine may prolong the QT interval.
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Hypothyroidism (low thyroid) - quetiapine may cause low thyroid in some patients (3 - 5% of patients)
  • Suicide in depression - possible increase risk when starting therapy in patients ≤ 24 years old
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials, the effects of quetiapine on blood sugars was neutral to a mild increase. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials, quetiapine had an adverse effect on lipid parameters. Long-term effects are unknown. See cholesterol below for ADA monitoring recommendations.
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Serious skin reactions - serious skin reactions including drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients taking quetiapine
  • Liver disease - clearance is decreased; start with 25 mg a day and increase by 25 - 50 mg/day; use caution
  • Kidney disease - no dose adjustment necessary

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Risperidone

(Risperdal®)

(Risperdal Consta®)
Risperdal® - tablet
  • 0.25 mg
  • 0.5 mg
  • 1 mg
  • 2 mg
  • 3 mg
  • 4 mg

Risperdal® M-Tab®
Orally disintegrating tablet
  • 0.25 mg
  • 0.5 mg
  • 1 mg
  • 2 mg
  • 3 mg
  • 4 mg

Risperdal® - solution
  • 1 mg/ml
  • Comes in 30 ml bottle

Risperdal® Consta® - vial
  • 12.5 mg
  • 25 mg
  • 37.5 mg
  • 50 mg
Risperdal®     

Schizophrenia
  • Starting: 2 mg a day
  • Maintenance: 4 - 8 mg a day
  • Max: 16 mg a day
  • Risperidone may be given once or twice daily
  • Increase dose in increments of 1 - 2 mg per day at intervals of ≥ 24 hours
  • Start low and go slow in patients at risk for orthostatic hypotension

Bipolar mania
  • Starting: 2 - 3 mg a day
  • Maintenance: 1 - 6 mg a day
  • Max: 6 mg a day
  • Risperidone may be given once or twice daily
  • Increase dose in increments of 1 mg per day at intervals of ≥ 24 hours
  • Start low and go slow in patients at risk for orthostatic hypotension

Risperdal® Consta®     

Schizophrenia
  • Starting: 25 mg IM every 2 weeks
  • Maintenance: 25 - 50 mg IM every 2 weeks
  • Max: 50 mg IM every 2 weeks
  • Increase dose at intervals ≥ 4 weeks
  • Oral risperidone should be continued for 3 weeks after initial injection, then discontinued

Bipolar mania
  • Starting: 25 mg IM every 2 weeks
  • Maintenance: 25 - 50 mg IM every 2 weeks
  • Max: 50 mg IM every 2 weeks
  • Increase dose at intervals ≥ 4 weeks
  • Oral risperidone should be continued for 3 weeks after initial injection, then discontinued

See Drug Interactions for dosing with certain medications
Risperdal® tablet
YES/$

Risperdal® solution
YES (60 ml)/$$ -$$$

Risperdal® Consta®
NO/$$$$
Other
Risperdal®
  • May take without regard to food
  • Store solution at room temperature

Orally disintegrating tablet
  • Once tablet is removed from blister packet, it cannot be stored. Take immediately.
  • Tablet disintegrates in mouth within seconds and can be swallowed with or without liquid
  • Do not attempt to chew or split tablet

Consta®
  • See Consta® PI for instructions on how to mix and inject

Pharmacokinetics
  • Risperidone has one, major active metabolite called 9-hydroxyrisperidone
  • The apparent half-life of risperidone is 3 hours in CYP2D6 extensive metabolizers and 20 hours in poor metabolizers. The apparent half-life of 9-hydroxyrisperidone is about 21 hours in extensive metabolizers and 30 hours in poor metabolizers.
Mechanism of action
  • Dopamine-2 receptor antagonist
  • Serotonin type 2 (5-HT2) receptor antagonist

FDA-approved indications
  • Schizophrenia
  • Bipolar mania
  • Irritability associated with autistic disorder
  • Hyperprolactinemia (elevated prolactin level) - up to 87% of patients (13 - 17 years old) in some studies
  • Insomnia - 32%, P - 27%
  • Extrapyramidal symptoms - 21%, P - 13% (10 mg/day)
  • Weight gain (≥ 7% increase) - 21%, P - 3%
  • Anxiety- 16%, P - 11%
  • Sedation- 10%, P - 2%
  • Nausea- 9%, P - 4%
  • Constipation- 8%, P - 6%
  • Dizziness- 7%, P - 2%
  • Orthostatic hypotension - 1 - 2% of patients
  • Difficulty swallowing - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
  • Risperidone is a CYP2D6 sensitive substrate
  • CYP2D6 strong inhibitors - may increase risperidone levels. Do not exceed 8 mg a day when taken together.
  • CYP3A4 inducers - may be necessary to increase risperidone dose.
  • Dopamine agonists (Mirapex®, Sinemet®, etc.) - risperidone may block the activity of dopamine agonists used in Parkinson's, RLS, etc.
  • Alpha blockers - risperidone can block alpha receptors. It may potentiate the effects of alpha blockers.
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials, risperidone had mixed effect on blood sugars. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials, risperidone had an adverse effect on lipid parameters. Long-term effects are unknown. See cholesterol below for ADA monitoring recommendations.
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Phenylketonuria - risperidone orally disintegrating tab contains phenylalanine
  • Liver disease
    • Severe (Child-Pugh C) - initial dose 0.5 mg twice a day, increase slowly; for doses > 1.5 mg twice daily, increase in intervals of 1 week or more
  • Kidney disease
    • CrCl < 30 ml/min - initial dose 0.5 mg twice a day, increase slowly; for doses > 1.5 mg twice daily, increase in intervals of 1 week or more

Drug Dosage form Dosage Generic/Price Other Mechanism of Action/
FDA-approved indications
Side Effects
P = % of patients on placebo
who experienced side effect
Drug Interactions Precautions/
Contraindications
Ziprasidone

(Geodon®)
Geodon® - capsule
  • 20 mg
  • 40 mg
  • 60 mg
  • 80 mg
Schizophrenia
  • Starting: 20 mg twice a day
  • Maintenance: 20 - 80 mg twice a day
  • Max: 80 mg twice a day
  • Increase dose at intervals of ≥ 2 days

Bipolar I
  • Starting: 40 mg twice a day
  • Maintenance: 40 - 80 mg twice a day
  • Max: 80 mg twice a day
YES/$-$$$ Other
  • Take with food. Food increases absorption.

Pharmacokinetics (oral)
  • Half-life: 7 hours
Mechanism of action
  • Dopamine-2 receptor antagonist
  • Serotonin type 2 (5-HT2) receptor antagonist

FDA-approved indications
  • Schizophrenia
  • Bipolar I disorder
  • Agitation in schizophrenia
  • Weight gain (≥ 7% increase) - 16%, P - 4%
  • Somnolence - 14%, P - 7%
  • Extrapyramidal symptoms - 14%, P - 8%
  • Nausea - 10%, P - 7%
  • Rash - ziprasidone causes a rash in 5% of patients. Stop therapy if occurs.
  • Orthostatic hypotension - up to 1% of patients
  • Hyperprolactinemia (elevated prolactin level) - incidence not well-defined
  • Difficulty swallowing - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
  • Drugs that prolong the QT interval - DO NOT COMBINE
  • CYP3A4 strong inhibitors and inducers - ziprasidone undergoes a small amount of metabolism by CYP3A4. Strong CYP3A4 inhibitors and inducers may affect levels.
  • Dopamine agonists (Mirapex®, Sinemet®, etc.) - ziprasidone may block the activity of dopamine agonists used in Parkinson's, RLS, etc.
  • Alpha blockers - ziprasidone can block alpha receptors. It may potentiate the effects of alpha blockers.
  • Prolonged QT syndrome - DO NOT USE. Ziprasidone may prolong the QT interval.
  • Recent Heart attack - DO NOT USE. Ziprasidone may prolong the QT interval.
  • Uncompensated heart failure - DO NOT USE. Ziprasidone may prolong the QT interval.
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Stroke and TIA in elderly patients with dementia-related psychosis - in placebo-controlled trials, elderly patients with dementia-related psychosis who were treated with risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and TIA
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Diabetes - atypical antipsychotics have been associated with weight gain and diabetes in some patients. In trials lasting up to 6 weeks, ziprasidone had a mixed effect on blood sugars. Long-term effects are unknown. See diabetes below for ADA monitoring recommendations.
  • Cholesterol - atypical antipsychotics have been associated with increases in cholesterol in some patients. In trials lasting up to 6 weeks, ziprasidone had a mixed effect on lipid parameters. Long-term effects are unknown. See cholesterol below for ADA monitoring recommendations.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Seizure - antipsychotics may increase seizure risk. Use caution in susceptible patients.
  • Orthostatic hypotension and syncope - atypical antipsychotics may cause orthostatic hypotension and syncope in some patients. Use caution in susceptible patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • DRESS syndrome - severe skin reactions including DRESS syndrome have occurred in some users. DRESS syndrome is a rare, but serious skin reaction marked by rash, fever, and swollen lymph nodes.
  • Liver disease - clearance is decreased; manufacturer makes no dose adjustment recommendation
  • Kidney disease - no dose adjustment necessary




Drug Dosage form Dosage Generic/Price Mechanism of Action/
FDA-approved indications
Side Effects
Incidence not well-defined
Drug Interactions Precautions/
Contraindications
Haloperidol

(Haldol®)

(Haldol® Decanoate)
Haloperidol - tablet
  • 0.5 mg
  • 1 mg
  • 2 mg
  • 5 mg
  • 10 mg
  • 20 mg

Haloperidol - solution
  • 2 mg/ml
  • Comes in 15 ml and 120 ml bottle

Haldol® Decanoate - vial
  • 50 mg
  • 100 mg
Haldol®     

Psychosis
  • Starting (moderate symptoms): 0.5 - 2 mg two to three times a day
  • Starting (severe symptoms): 3 - 5 mg two to three times a day
  • Maintenance: titrate to effect

Haldol® Decanoate     

Psychosis
  • Dose: 10 - 20 X the daily oral dose of haloperidol
  • Frequency: IM injection every 4 weeks
  • Max: 450 mg
Tablet
YES/$

Solution (120 ml)
YES/$

Vial
YES/$
Mechanism of action
  • Dopamine receptor antagonist

FDA-approved indications
  • Psychotic disorders
  • Tourette's syndrome - control of tics
  • Extrapyramidal symptoms - common
  • Sedation - common
  • Weight gain - incidence not well-defined
  • Hyperprolactinemia (elevated prolactin level) - incidence not well-defined
  • Priapism (erection lasting longer than 4 hours) - rare
  • Prolonged QT syndrome - DO NOT USE. Haloperidol may prolong the QT interval.
  • Cardiovascular disease - use with caution
  • Elderly with dementia-related psychosis - antipsychotics may increase the risk of death in elderly patients with dementia-related psychosis. In studies lasting 10-weeks, the incidence of death was 4.5% in antipsychotic-treated patients and 2.6% in placebo-treated patients.
  • Cognitive and motor impairment - antipsychotics may cause sedation. Use caution before driving or performing tasks that require mental alertness.
  • Neuroleptic Malignant Syndrome
  • Tardive dyskinesia
  • Falls - antipsychotics may cause somnolence, postural hypotension, and motor and sensory instability which can lead to falls. Use caution in susceptible patients.
  • Body temperature dysregulation - disruption in the body's ability to reduce core temperature has been reported with antipsychotics. Use caution in conditions that may elevate core temperature (e.g. strenuous exercise, extreme heat, etc.)
  • Leukopenia - antipsychotics have been associated with a decrease in white blood cells in some patients. Monitor closely in susceptible patients.
  • Liver disease - manufacturer does not make recommendation
  • Kidney disease - manufacturer does not make recommendation



  • NEUROLEPTIC MALIGNANT SYNDROME (NMS)

    • NMS is a rare condition caused by antipsychotic medications
    • NMS is more common with first generation antipsychotics
    • The exact incidence of NMS is unknown
    • NMS can be fatal

      • Symptoms of NMS include:
        • Fever
        • Muscle rigidity
        • Mental status changes
        • Elevated blood pressure
        • Rapid heart beat
        • Excessive sweating
        • Elevated creatine phosphokinase (CK)
        • Rhabdomyolysis
        • Elevated white count [2]



  • TARDIVE DYSKINESIA (TD)

    • TD is a condition that is caused by antipsychotic medications
    • TD is marked by intermittent, involuntary, jerky movements of the face, tongue, jaw, trunk, or limbs
    • In some cases, TD can be permanent
    • The risk for TD appears to increase with longer duration of antipsychotic use and higher doses
    • The risk is also higher in elderly patients
    • TD is more common with first generation antipsychotics
    • The annual incidence of TD with first generation antipsychotics is about 5% in adults and as high as 25 - 30% in elderly patients
    • The annual incidence of TD with second generation antipsychotics is around 1% in adults and 5.3% in patients ≥ 54 years [3]



  • DIABETES, CHOLESTEROL, AND ANTIPSYCHOTICS

    • Second generation antipsychotic may cause weight gain and diabetes in some patients. The may also have a negative effect on lipid parameters.
    • The mechanism of this effect is not completely understood
    • Some antipsychotics have a greater risk than others
    • In 2004, the ADA issued diabetes and cholesterol screening guidelines for patients taking second generation antipsychotics

      • ADA screening recommendations for patients starting second generation antipsychotics
        • Fasting blood sugar at baseline, 12 weeks, and annually thereafter
        • Fasting lipid profile at baseline, 12 weeks, and every 5 years thereafter [4]



  • EXTRAPYRAMIDAL SYMPTOMS (EPS)

    • EPS can occur with all antipsychotics
    • The incidence of EPS varies for each antipsychotic
    • EPS are more common with first generation antipsychotics
    • EPS is often treated with anticholinergic medications (ex. benztropine, Cogentin®)

      • Extrapyramidal symptoms include the following:
        • Akathisia - urge to move, or inability to sit still; inner restlessness
        • Parkinsonism - tremor, mask-like facies (expressionless), rigid body movements, slow body movements
        • Dystonias - involuntary, sustained, muscle contractions



  • CLOZAPINE AGRANULOCYTOSIS

    • Agranulocytosis is a decrease in the number of white blood cells called neutrophils (neutropenia)
    • Agranulocytosis occurs when the absolute neutrophil count (ANC) falls below 500/mm3
    • Agranulocytosis is a serious condition that can be life-threatening
    • Clozapine has been shown to cause agranulocytosis in 1.3% of patients after 1 year of use
    • Because of this risk, the FDA requires physicians and patients to enroll in the Clozapine REMS program in order to use clozapine
    • Constant and frequent monitoring of white blood cells is required in patients taking clozapine
    • The clozapine prescribing information has extensive guidelines on monitoring for agranulocytosis and adjusting therapy. Those guidelines are available here - Clozapine agranulocytosis guidelines [warnings section]
    • Monitoring guidelines for patients with normal lab values are presented below

      • CBC frequency for patients with normal WBC counts:
        • Initiation of therapy - check CBC weekly for 6 months
        • 6 - 12 months of therapy - every 2 weeks for 6 months
        • 12 months of therapy and on - check CBC monthly indefinitely
        • NOTE: Normal CBC defined as WBC ≥ 3500/mm3 and ANC ≥ 2000/mm3



  • PRICING

    • $ = 0 - $50
    • $$ = $51 - $100
    • $$$ = $101 - $150
    • $$$$ = > $151

    • Pricing based on one month of therapy at standard dosing in an adult
    • Pricing based on survey of GoodRX.com®, HEB®, and Costco®, [accessed 1/2015]
    • Pricing may vary by region and availability



  • References:

  • 1 - Manufacturer's Package Insert for each drug listed
  • 2 - PMID 10928001
  • 3 - PMID 14992963
  • 4 - PMID 14747245