Version July 2025
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Lurasidone is not approved for the treatment of patients with dementia-related psychosis.
Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors.
Bipolar disorder, depressive episode:
Children ≥10 years and Adolescents <18 years: Monotherapy: Oral: Initial: 20 mg once daily; may increase dose after 1 week based on response and tolerability; reported range: 20 to 80 mg/day; in the largest double-blind placebo-controlled trial (n=175 treatment group), the majority of patients (67%) responded to a dose of 20 or 40 mg once daily; the modal daily dose was 20 mg in 52.3% of patients and 40 mg in 26.2% of patients (Ref).
Adolescents ≥18 years: Monotherapy or as adjunct to lithium or divalproex: Oral: Initial: 20 mg once daily in the evening; may increase dose further based on response and tolerability in 20 mg increments every 2 to 7 days up to 120 mg/day (Ref).
Schizophrenia: Adolescents ≥13 years: Oral: Initial: 40 mg once daily; may increase dose further based on response and tolerability; age-dependent maximum recommended daily dose: for ages <18 years: 80 mg/day; for ages ≥18 years: 160 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Discontinuation of therapy: Children and Adolescents: American Academy of Child and Adolescent Psychiatry (AACAP), American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), National Institute for Health and Care Excellence (NICE), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (Ref); risk for withdrawal symptoms may be highest with highly anticholinergic or dopaminergic antipsychotics (Ref). When stopping antipsychotic therapy in patients with schizophrenia, the CPA guidelines recommend a gradual taper over 6 to 24 months and the APA guidelines recommend reducing the dose by 10% each month (Ref). Continuing antiparkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms (Ref). When switching antipsychotics, three strategies have been suggested: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic), overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic), and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). Evidence supporting ideal switch strategies and taper rates is limited and results are conflicting (Ref).
CrCl ≥50 mL/minute: Children ≥10 years and Adolescents: Oral: No dosage adjustment necessary.
CrCl <50 mL/minute:
Bipolar disorder, depressive episode: Children ≥10 years and Adolescents: Oral: Higher drug exposure occurs in patients with CrCl <50 mL/minute; based on adult information, reduce initial dose; do not exceed an initial dose of 20 mg daily; maximum daily dose: 80 mg/day. Note: For patients ≤17 years of age, manufacturer-recommended renal impairment dose does not reflect a change from recommended dose for this indication; use caution.
Schizophrenia: Adolescents ≥13 years: Oral: Initial: 20 mg daily; maximum daily dose: 80 mg/day.
Mild impairment: Children ≥10 years and Adolescents: Oral: No dosage adjustment necessary.
Moderate impairment:
Bipolar disorder, depressive episode: Children ≥10 years and Adolescents: Oral: Higher drug exposure occurs in patients with moderate to severe hepatic impairment; based on adult information, reduce initial dose; do not exceed an initial dose of 20 mg daily; maximum daily dose: 80 mg/day. Note: For patients ≤17 years of age, manufacturer-recommended hepatic impairment dose does not reflect a change from recommended dose for this indication; use caution.
Schizophrenia: Adolescents ≥13 years: Oral: Initial: 20 mg daily; maximum daily dose: 80 mg/day.
Severe impairment:
Bipolar disorder, depressive episode: Children ≥10 years to Adolescents: Oral: Higher drug exposure occurs in patients with moderate to severe hepatic impairment; based on adult information, reduce initial dose; do not exceed an initial dose of 20 mg daily; maximum daily dose: 40 mg/day. Note: For patients ≤17 years of age, manufacturer-recommended hepatic impairment dose does not reflect a change from recommended dose for this indication; use caution.
Schizophrenia: Adolescents ≥13 years: Oral: Initial: 20 mg daily; maximum daily dose: 40 mg/day.
(For additional information see "Lurasidone: Drug information")
Dosage guidance:
Safety: Antipsychotics are not indicated for use in catatonia and may worsen psychosis and increase risk for neuroleptic malignant syndrome in patients with catatonia (Ref).
Clinical considerations: Consult a psychiatry specialist for all management decisions; select antipsychotic carefully based on patient preference, clinical characteristics, history, comorbidities, and adverse effect profile (Ref).
Bipolar disorder:
Note: Not effective for treating acute bipolar mania or hypomania (Ref).
Depressive episode associated with bipolar disorder, acute, with mixed features (off label) or without (labeled use) (monotherapy or in combination with antimanic therapy): Oral: Initial: 20 mg once daily in the evening within 30 minutes of food (≥350 calories); may increase daily dose based on response and tolerability in increments of 20 mg every ≥2 days to a maximum dose of 120 mg/day (Ref).
Maintenance treatment for depressive episodes (off-label use): Oral: Continue dose and combination regimen that was used to achieve control of the acute episode (Ref). Maximum dose: 120 mg/day.
Major depressive disorder (unipolar) with mixed features (monotherapy) (off-label use): Oral: Initial: 20 mg once daily in the evening within 30 minutes of food (≥350 calories) for 7 days; may subsequently increase daily dose based on response and tolerability by 20 mg every 2 to 7 days up to 60 mg/day (Ref).
Postpartum psychosis (off-label use): Oral: Initial: 40 mg once daily in the evening within 30 minutes of food (≥350 calories); after 3 days, increase to 80 mg once daily; after 2 to 3 additional days, may then increase up to 160 mg/day over the course of 1 week based on response and tolerability. Continue treatment for 3 to 6 months (Ref).
Schizophrenia:
Oral: Initial: 40 mg once daily in the evening within 30 minutes of food (≥350 calories), or if this is a first episode of psychosis, consider initiating at a reduced dose (eg, 20 mg once daily) because these patients will be more sensitive to adverse effects. May increase daily dose based on response and tolerability in increments of 40 mg no sooner than every 3 days, monitor for akathisia, parkinsonism, and sedation during titration. Usual dose range: 40 to 80 mg/day; use lowest effective maintenance dose. Maximum: 160 mg/day (Ref).
Discontinuation of therapy: In the treatment of chronic psychiatric disease switching therapy rather than discontinuation is generally advised if side effects are intolerable or treatment is not effective. If patient insists on stopping treatment, gradual dose reduction (ie, over several weeks to months) is advised to detect a re-emergence of symptoms and to avoid withdrawal reactions (eg, agitation, alternating feelings of warmth and chill, anxiety, diaphoresis, dyskinesias, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, vertigo) unless discontinuation is due to significant adverse effects. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).
Switching antipsychotics: An optimal universal strategy for switching antipsychotic drugs has not been established. Strategies include cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients with schizophrenia at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (ie, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Initial: 20 mg daily; maximum: 80 mg/day
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Initial: 20 mg daily; maximum: 80 mg/day.
Severe impairment (Child-Pugh class C): Initial: 20 mg daily; maximum: 40 mg/day.
Antipsychotics are associated with dyslipidemia in adult and pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class. Compared to other antipsychotics, lurasidone is usually associated with a minimal to low risk for dyslipidemia in adults (data are too limited in pediatric patients), however, significant increased serum triglycerides and decreased HDL cholesterol have been observed in some trials (Ref). In addition, data from short-term and long-term trials (≥12 months) in adults suggest lurasidone may even lead to improvements in metabolic parameters in patients switched from certain antipsychotics associated with a high risk of metabolic syndrome to lurasidone (Ref).
Mechanism: The mechanism of antipsychotics effect on lipids is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; in general, metabolic alterations from antipsychotics (data do not include lurasidone) can develop in as short as 3 months after initiation (Ref).
Risk factors:
• Schizophrenia (regardless of medication use) is associated with a higher rate of morbidity/mortality compared to the general population primarily due to cardiovascular disease (Ref).
• Specific antipsychotic: Lurasidone is usually considered to have minimal to low risk for causing lipid abnormalities in adults (Ref).
Lurasidone is associated with extrapyramidal reaction (extrapyramidal symptoms [EPS]), also known as drug-induced movement disorders, in adult and pediatric patients. Antipsychotics can cause four main EPS: Acute dystonia, drug-induced parkinsonism, akathisia, and tardive dyskinesia. Of these, akathisia and drug-induced parkinsonism are associated with lurasidone, followed less frequently by dystonia and rarely by tardive dyskinesia (Ref). EPS presenting as dysphagia, esophageal dysmotility, or aspiration have also been reported with antipsychotics, which may not be recognized as EPS (Ref).
Mechanism:
EPS: Dose-related (Ref); due to antagonism of dopaminergic D2 receptors in nigrostriatal pathway (Ref).
Akathisia: Mechanism not completely understood, but possibly associated with an imbalance between the dopamine and serotonin/noradrenergic neurotransmitter system (Ref); however, since lurasidone displays strong antagonism at 5-HT2A receptors and is associated with akathisia, it has been suggested that the mechanism is multifactorial (Ref).
Tardive dyskinesia: Time-related (delayed); results from chronic exposure to D2 receptor-antagonists leading to up-regulation of these receptors over time (Ref). EPS-associated esophageal dysfunction has been attributed to drug-induced parkinsonism and tardive dyskinesia (Ref).
Onset:
Antipsychotics in general:
Dystonia: Rapid; in the majority of cases, dystonia occurs usually within the first 5 days after initiating antipsychotic therapy (and even with the first dose, particularly in patients receiving parenteral antipsychotics) or a dosage increase (Ref).
Parkinsonism: Varied; may be delayed from days to weeks, with 50% to 75% of cases occurring within 1 month and 90% within 3 months of antipsychotic initiation, a dosage increase, or a change in the medication regimen (such as adding another antipsychotic agent or discontinuing an anticholinergic medication) (Ref).
Akathisia: Varied; may begin within several days after antipsychotic initiation but usually increases with treatment duration, occurring within 1 month in up to 50% of cases, and within 3 months in 90% of cases (Ref).
Tardive dyskinesia: Delayed; symptoms usually appear after 1 to 2 years of continuous exposure to a dopamine antagonist, and almost never before 3 months, with an insidious onset, evolving into a full syndrome over days and weeks, followed by symptom stabilization, and then a chronic waxing and waning of symptoms (Ref).
Esophageal dysfunction (associated with EPS): Varied; ranges from weeks to months following initiation (Ref).
Risk factors:
Antipsychotics in general:
EPS (in general):
• Prior history of EPS (Ref)
• Higher doses (Ref)
• Younger age (in general, children and adolescents are usually at higher risk for EPS compared to adults) (Ref)
• Specific antipsychotic: Overall, lurasidone is associated with a moderate risk for EPS (Ref). Some data have observed a very high relative risk for akathisia (4.48) with lurasidone therapy (Ref).
Dystonia:
• Younger adult males (Ref)
Parkinsonism:
• Females (Ref)
• Older patients (Ref)
• Higher antipsychotic potency at antagonizing D2 receptors (Ref).
Akathisia:
• Higher antipsychotic dosages (Ref)
• Polypharmacy (Ref)
• Mood disorders (Ref)
• Females (Ref)
• Older patients (Ref)
Tardive dyskinesia:
• Age >55 years (Ref)
• Cognitive impairment (Ref)
• Concomitant treatment with anticholinergic medications (Ref)
• Diabetes (Ref)
• Diagnosis of schizophrenia or affective disorders (Ref)
• Females (Ref)
• Greater total antipsychotic exposure (especially first-generation antipsychotics) (Ref)
• History of extrapyramidal symptoms (Ref)
• Substance misuse or dependence (Ref)
• Race (White or African descent). Note: Although early literature supported race as a potential risk factor for tardive dyskinesia (Ref), newer studies have challenged this assertion (Ref).
Esophageal dysfunction (associated with EPS):
• Increasing age (≥40 years) (Ref)
Anemia, thrombocytopenia, leukopenia, and neutropenia have been reported with lurasidone (Ref).
Mechanism: Dose-related (potentially) (Ref); mechanism is unclear (Ref).
Onset: Varied; in general, drug-induced neutropenia usually manifests after 1 or 2 weeks of exposure; however, the onset may be insidious (Ref). In case reports with lurasidone, anemia has been reported from 2 to 10 months after initiation of treatment (Ref).
Risk factors:
Antipsychotics in general:
• History of antipsychotic-induced neutropenia (Ref)
• Older adults (Ref)
• History of drug-induced leukopenia/neutropenia or low white blood cell count/absolute neutrophil count
Antipsychotics are associated with hyperglycemia in pediatric and adult patients, to varying degrees, which is a component of the metabolic syndrome observed with this pharmacologic class. Lurasidone is associated with a minimal to low risk of causing hyperglycemia and diabetes in adults (data are too limited in pediatric patients); however, significant increase in fasting plasma glucose, elevated glycosylated hemoglobin, and increase in serum insulin have been observed in some trials (Ref). In addition, data from short-term and long-term trials (≤12 months) in adults suggest lurasidone may even lead to improvements in metabolic parameters in patients switched from certain antipsychotics associated with a high risk of metabolic syndrome to lurasidone (Ref).
Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).
Onset: Varied; new-onset diabetes has been observed within first 3 months to a median onset of 3.9 years with antipsychotics (data do not include lurasidone) (Ref).
Risk factors:
Antipsychotics in general:
• African American race (Ref)
• Males (Ref)
• Younger adults (Ref)
• Patients with preexisting obesity, poor exercise habits, or other risk factors for diabetes, including family history of diabetes (Ref)
• Exposure to other agents that also increase the risk of hyperglycemia (Ref)
• Specific antipsychotic: Lurasidone is usually considered to have a minimal to low risk for causing glycemic abnormalities in adults (Ref).
Lurasidone may cause mild to moderate, dose-dependent increased serum prolactin and, in some patients, hyperprolactinemia which may lead to gynecomastia, galactorrhea not associated with childbirth, amenorrhea, sexual disorder, acne, hirsutism, and infertility (Ref). Although long-term effects of antipsychotic-induced elevated prolactin levels have not been fully evaluated, some studies have also suggested a possible association between hyperprolactinemia and an increased risk for breast and/or pituitary tumors and osteopenia/osteoporosis in both men and women (Ref).
Mechanism: Dose-dependent; antagonism of dopamine D2 receptors in the tuberoinfundibular dopaminergic pathway which causes disinhibition of prolactin release resulting in hyperprolactinemia (Ref).
Onset: Varied; in general, onset of antipsychotic-induced hyperprolactinemia is typically within a few days or weeks following initiation or a dosage increase and usually persists throughout treatment (although partial tolerance may develop). Onset may also arise after long-term stable use (Ref).
Risk factors:
• Specific typical antipsychotic: Lurasidone is usually considered to have an intermediate effect on serum prolactin (Ref), although some authors consider it to have a low propensity for increasing serum prolactin or causing hyperprolactinemia (Ref)
• Higher doses, particularly in women of reproductive age and younger patients (Ref)
• Females, particularly of reproductive age (although both males and females are affected) (Ref)
Older adults with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature (Ref). In addition, an increased incidence of cerebrovascular effects (eg, cerebrovascular accident, transient ischemic attacks), including fatalities, have been reported in placebo-controlled trials (trials did not include lurasidone) in older adults with dementia-related psychosis (Ref). Of note, lurasidone is not approved for the treatment of dementia-related psychosis.
Mechanism: Unknown; possible mechanisms include arrhythmia, cardiac arrest, and extrapyramidal effects that may increase the risk of falls, aspirations, and pneumonia (Ref).
Risk factors:
Antipsychotics in general:
• Higher antipsychotic dosage (Ref)
• Dementia-related psychosis (eg, Lewy body dementia, Parkinson disease dementia)
• Older adults
All antipsychotics have been associated with neuroleptic malignant syndrome (NMS), although the incidence is less with second-generation (atypical) antipsychotics compared to first-generation (typical) antipsychotics (Ref). There are a few published case reports of NMS with lurasidone (Ref).
Mechanism: Non–dose-related; idiosyncratic. Believed to be due to a reduction in CNS dopaminergic tone, along with the dysregulation of autonomic nervous system activity (Ref).
Onset: Varied; in general, most patients develop NMS within 2 weeks of initiating an antipsychotic, and in some patients, prodromal symptoms emerge within hours of initiation; once the syndrome starts, the full syndrome usually develops in 3 to 5 days (Ref). However, there are many cases of NMS occurring months after stable antipsychotic therapy (Ref).
Risk factors:
Antipsychotics in general:
• Males (twice as likely to develop NMS compared to females) (Ref)
• Dehydration (Ref)
• High-dose antipsychotic treatment (Ref)
• Concomitant lithium or benzodiazepine (potential risk factors) (Ref)
• Catatonia (Ref)
• Polypharmacy (Ref)
• Pharmacokinetic interactions (Ref)
• IM administration (Ref)
• Rapid dosage escalation (Ref)
• Psychomotor agitation (Ref)
Sedating effects (eg, drowsiness) may occur in children, adolescents, and adults treated with lurasidone, and lead to nonadherence or discontinuation. Individual patient experience can vary depending on the person’s sensitivity toward sedation and the dose used. Sedation is typically transient with therapy (Ref).
Mechanism: Sedation: Dose-related (Ref); sedation from antipsychotics is believed to be due to H1 antagonism leading to potential CNS depressant effects; however, lurasidone displays little to no affinity for histamine H1 receptors suggesting a lower risk for sedation and CNS depressant effect (Ref).
Risk factors:
• Children and adolescents (Ref)
• Higher doses and concurrent use of somnolence-prone agents (Ref)
• Specific antipsychotic (lurasidone is generally considered to be mildly to moderately sedating at usual therapeutic doses in comparison with other antipsychotics) (Ref).
Antipsychotics may impair the body’s ability to regulate core body temperature, which may cause a potentially life-threatening heat stroke during predisposing conditions such as heat wave or strenuous exercise. Conversely, some antipsychotics have been associated with hypothermia; however, there are no published case reports with lurasidone to date (Ref).
Mechanism: Non–dose-related; idiosyncratic. Exact mechanism is unknown; however, body temperature is regulated by the hypothalamus with involvement of the dopamine, serotonin, and norepinephrine neurotransmitters. D2 antagonism may cause an increase in body temperature, while 5-HT2A (serotonin) receptor antagonism may cause a decrease in body temperature. In addition, antagonism of peripheral alpha-adrenergic receptors has also been suggested as a factor in the hypothermic effect, by inhibiting peripheral responses to cooling (vasoconstriction and shivering) (Ref).
Risk factors:
Antipsychotics in general:
Heat stroke:
• Psychiatric illness (regardless of medication) (Ref)
• Strenuous exercise (Ref)
• Heat exposure (Ref)
• Dehydration (Ref)
• Concomitant medication possessing anticholinergic effects (Ref).
Hypothermia:
• In general, predisposing risk factors include advanced age, a cerebrovascular accident or preexisting brain damage, hypothyroidism, malnutrition, shock, sepsis, adrenal insufficiency, diabetes, disability, burns, exfoliative dermatitis, benzodiazepine use, polypharmacy, alcohol intoxication, immobility, kidney, or liver failure (Ref)
• Schizophrenia (regardless of antipsychotic use) (Ref)
Antipsychotics are associated with weight gain, to varying degrees, which is a component of the metabolic syndrome observed with this pharmacologic class in adult and pediatric patients (Ref). Lurasidone is associated with a minimal to low risk of causing metabolic abnormalities and weight gain, but some short-term, placebo-controlled trials in adults have observed significant weight gain (increase of >7% from baseline) (Ref). However, some long-term (≤1 year) primarily observational data in adults has observed a decrease in weight, weight circumference, and/or BMI in lurasidone-treated patients (Ref). In addition, data from short-term and long-term trials (≤12 months) in adults suggest lurasidone may even lead to improvements in metabolic parameters in patients switched from certain antipsychotics associated with a high risk of metabolic syndrome to lurasidone (Ref).
Mechanism: Multiple proposed mechanisms, including actions at serotonin, dopamine, histamine, and muscarinic receptors, with differing effects explained by differing affinity of antipsychotics at these receptors (Ref). Of note, lurasidone exhibits weak affinity for 5-HT2C receptors (which is often implicated as a proposed mechanism) and no appreciable affinity for histamine H1 or muscarinic M1 receptors (Ref).
Risk factors:
Antipsychotics in general:
• Family history of obesity (Ref)
• Parental BMI (Ref)
• Children and adolescents (Ref)
• Rapid weight gain in the initial period: Younger age, lower baseline BMI, more robust response to antipsychotic, and increase in appetite; rapid weight gain of >5% in the first month has been observed as the best predictor for significant long-term weight gain (Ref)
• Duration of therapy (although weight gain plateaus, patients continue to gain weight over time) (Ref)
• Schizophrenia (regardless of medication) is associated with a higher prevalence of obesity compared to the general population due to components of the illness such as negative symptoms, sedentary lifestyles, and unhealthy diets (Ref)
• Specific antipsychotic: In adults, lurasidone is considered to have a minimal or low risk for weight gain (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise indicated.
>10%:
Endocrine & metabolic: Hypercholesterolemia (6% to 14%), increase in fasting plasma glucose (2% to 13% (table 1)), increased serum triglycerides (6% to 14%) (table 2)
|
Drug (Lurasidone) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Lurasidone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
6% |
4% |
Adults |
80 mg to 120 mg/day |
Bipolar disorder, depressive episode |
141 |
141 |
Shift to fasting serum glucose ≥126 mg/dL |
|
2% |
4% |
Adults |
20 mg to 60 mg/day |
Bipolar disorder, depressive episode |
138 |
141 |
Shift to fasting serum glucose ≥126 mg/dL |
|
13% |
8% |
Adults |
40 mg/day |
Schizophrenia |
449 |
628 |
Shift to fasting serum glucose ≥126 mg/dL |
|
12% |
8% |
Adults |
20 mg/day |
Schizophrenia |
60 |
628 |
Shift to fasting serum glucose ≥126 mg/dL |
|
10% |
8% |
Adults |
120 mg/day |
Schizophrenia |
260 |
628 |
Shift to fasting serum glucose ≥126 mg/dL |
|
7% |
8% |
Adults |
80 mg/day |
Schizophrenia |
472 |
628 |
Shift to fasting serum glucose ≥126 mg/dL |
|
6% |
8% |
Adults |
160 mg/day |
Schizophrenia |
108 |
628 |
Shift to fasting serum glucose ≥126 mg/dL |
|
Drug (Lurasidone) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Lurasidone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
10% |
5% |
Adults |
20 mg to 60 mg/day |
Bipolar disorder, depressive episode |
119 |
126 |
Shift to triglycerides ≥200 mg/dL |
|
10% |
5% |
Adults |
80 mg to 120 mg/day |
Bipolar disorder, depressive episode |
122 |
126 |
Shift to triglycerides ≥200 mg/dL |
|
14% |
10% |
Adults |
20 mg/day |
Schizophrenia |
49 |
526 |
Shift to triglycerides ≥200 mg/dL |
|
11% |
10% |
Adults |
40 mg/day |
Schizophrenia |
379 |
526 |
Shift to triglycerides ≥200 mg/dL |
|
11% |
10% |
Adults |
120 mg/day |
Schizophrenia |
209 |
526 |
Shift to triglycerides ≥200 mg/dL |
|
7% |
10% |
Adults |
160 mg/day |
Schizophrenia |
100 |
526 |
Shift to triglycerides ≥200 mg/dL |
|
6% |
10% |
Adults |
80 mg/day |
Schizophrenia |
400 |
526 |
Shift to triglycerides ≥200 mg/dL |
Gastrointestinal: Dyspepsia (6% to 11%), nausea (children, adolescents, adults: 7% to 17%)
Infection: Viral infection (adolescents: 10% to 11%)
Nervous system: Akathisia (adolescents: 9%; adults: 6% to 22%), drowsiness (children, adolescents: 11% to 15%; adults: 7% to 26%) (table 3), extrapyramidal reaction (children, adolescents: 6% to 14%; adults: 5% to 39%), insomnia (children, adolescents, adults: 5% to 11%), parkinsonism (adolescents: 4%; adults: 5% to 17%)
|
Drug (Lurasidone) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Lurasidone) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|
|
11% |
6% |
Children, adolescents |
20 mg to 80 mg/day |
Bipolar disorder, depressive episode |
175 |
172 |
|
15% |
7% |
Adolescents |
40 mg/day |
Schizophrenia |
110 |
112 |
|
13% |
7% |
Adolescents |
80 mg/day |
Schizophrenia |
104 |
112 |
|
14% |
7% |
Adults |
80 mg to 120 mg/day |
Bipolar disorder, depressive episode |
167 |
168 |
|
7% |
7% |
Adults |
20 mg to 60 mg/day |
Bipolar disorder, depressive episode |
164 |
168 |
|
26% |
7% |
Adults |
120 mg/day |
Schizophrenia |
291 |
708 |
|
16% |
7% |
Adults |
40 mg/day |
Schizophrenia |
487 |
708 |
|
15% |
7% |
Adults |
20 mg/day |
Schizophrenia |
71 |
708 |
|
15% |
7% |
Adults |
80 mg/day |
Schizophrenia |
538 |
708 |
|
8% |
7% |
Adults |
160 mg/day |
Schizophrenia |
121 |
708 |
1% to 10%:
Cardiovascular: Hypertension (≥1%), orthostatic hypotension (children, adolescents, adults: ≤3%), tachycardia (adolescents: 3%, adults: ≥1%)
Dermatologic: Pruritus (≥1%), skin rash (≥1%)
Endocrine & metabolic: Hyperprolactinemia (≥5 × ULN: females: ≤6%; males: ≤2%) (table 4), weight gain (children, adolescents, adults: 2% to 7%) (table 5)
|
Drug (Lurasidone) |
Placebo |
Population |
Indication |
Comments |
|---|---|---|---|---|
|
0.5% |
1% |
Adolescents |
Schizophrenia |
≥5 × ULN |
|
1% |
0% |
Adolescent females |
Schizophrenia |
≥5 × ULN |
|
0% |
2% |
Adolescent males |
Schizophrenia |
≥5 × ULN |
|
0.4% |
0% |
Adults |
Bipolar disorder, depressive episode |
≥5 × ULN |
|
3% |
1% |
Adults |
Schizophrenia |
≥5 × ULN |
|
0.6% |
0% |
Adult females |
Bipolar disorder, depressive episode |
≥5 × ULN |
|
6% |
2% |
Adult females |
Schizophrenia |
≥5 × ULN |
|
2% |
0.6% |
Adult males |
Schizophrenia |
≥5 × ULN |
|
Drug (Lurasidone) |
Placebo |
Population |
Dose |
Indication |
Number of Patients (Lurasidone) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|
|
7% |
2% |
Children, adolescents |
20 mg to 80 mg/day |
Bipolar disorder, depressive episode |
175 |
172 |
N/A |
|
4% |
5% |
Children, adolescents |
20 mg to 80 mg/day |
Bipolar disorder, depressive episode |
N/A |
N/A |
≥7% increase in body weight |
|
3% |
5% |
Adolescents |
N/A |
Schizophrenia |
N/A |
N/A |
≥7% increase in body weight |
|
2% |
0.7% |
Adults |
N/A |
Bipolar disorder, depressive episode |
N/A |
N/A |
≥7% increase in body weight |
|
5% |
3% |
Adults |
N/A |
Schizophrenia |
N/A |
N/A |
≥7% increase in body weight |
Gastrointestinal: Abdominal pain (children, adolescents: 3%; adults: ≥1%), decreased appetite (children, adolescents: 4%; adults: ≥1%), diarrhea (children, adolescents, adults: 3% to 5%), sialorrhea (1% to 4%), upper abdominal pain (children, adolescents: 3%), vomiting (children, adolescents, adults: 6% to 9%), xerostomia (adolescents, adults: 2% to 6%)
Genitourinary: Urinary tract infection (1% to 2%)
Infection: Influenza (2%)
Nervous system: Agitation (5% to 10%), anxiety (4% to 7%), dizziness (children, adolescents, adults: 4% to 6%), fatigue (children, adolescents: 3%), restlessness (2% to 3%)
Neuromuscular & skeletal: Back pain (3% to 4%), dyskinesia (adolescents: 1%), dystonia (adolescents: ≤1%; adults: 2% to 7%), increased creatine phosphokinase in blood specimen (≥1%)
Ophthalmic: Blurred vision (≥1%)
Renal: Increased serum creatinine (children, adolescents, adults: 2% to 7%)
Respiratory: Nasopharyngitis (4%), oropharyngeal pain (adolescents: ≤3%), rhinitis (adolescents: 8%)
<1%:
Cardiovascular: Angina pectoris, bradycardia, first degree atrioventricular block, syncope
Endocrine & metabolic: Amenorrhea, galactorrhea not associated with childbirth
Gastrointestinal: Gastritis
Genitourinary: Breast hypertrophy, dysmenorrhea, dysuria, erectile dysfunction, mastalgia, priapism
Hematologic & oncologic: Anemia
Hypersensitivity: Angioedema
Nervous system: Abnormal dreams, cerebrovascular accident, dysarthria, panic attack, psychomotor agitation (children, adolescents), sleep disturbance, vertigo
Neuromuscular & skeletal: Rhabdomyolysis
Renal: Kidney failure
Frequency not defined (any population): Nervous system: Suicidal ideation, suicidal tendencies, tardive dyskinesia
Postmarketing (any population):
Cardiovascular: Pedal edema (Ref), prolonged QT interval on ECG (Ref)
Dermatologic: Urticaria
Endocrine & metabolic: Decreased HDL cholesterol (Ref), elevated glycosylated hemoglobin (Ref), hyperinsulinism (Ref), hyponatremia
Genitourinary: Urinary retention (Ref)
Hematologic & oncologic: Leukopenia (Ref), neutropenia (Ref), thrombocytopenia (Ref)
Hypersensitivity: Tongue edema
Nervous system: Mania (Ref), neuroleptic malignant syndrome (Ref)
Respiratory: Dyspnea, pharyngeal edema
Hypersensitivity to lurasidone or any component of the formulation (including angioedema); concomitant use with strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil) and inducers (eg, rifampin, avasimibe, St. John's wort, phenytoin, carbamazepine).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Altered cardiac conduction: Antipsychotics may alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics (Haddad 2002). Relative to other antipsychotics, lurasidone has minimal effects on the QTc interval and therefore, risk for arrhythmias is low.
• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability.
• Orthostatic hypotension: May cause orthostatic hypotension and syncope; use with caution in patients at risk of this effect (eg, concurrent medication use which may predispose to hypotension/bradycardia or presence of dehydration or hypovolemia) or in those who would not tolerate transient hypotensive episodes. Use caution with history of cerebrovascular or cardiovascular disease (myocardial infarction, heart failure, or ischemic disease).
Disease-related concerns:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. Literature evaluating lurasidone use in bariatric surgery patients is not available. The association of lurasidone with weight loss or gain and with metabolic abnormalities varies in the general population (De Hert 2012; Leucht 2013; Solmi 2017). It is recommended to administer lurasidone with a meal (≥350 calories) to ensure absorption and improve tolerability. Bariatric surgery diets commonly limit calories. Monitor weight closely postoperatively; if weight loss goals are not met or bariatric surgery diet limits meals to <350 calories consider an alternative agent.
• Cardiovascular disease: Use with caution in patients with severe cardiac disease, hemodynamic instability, prior myocardial infarction or ischemic heart disease.
• Hepatic impairment: Use with caution in patients with hepatic disease or impairment; dosage reduction is recommended in moderate to severe impairment.
• Renal impairment: Use with caution in patients with renal disease; dosage reduction is recommended in moderate to severe impairment.
• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures or conditions that lower the seizure threshold such as Alzheimer disease. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.
Other warnings/precautions:
• Discontinuation of therapy: When discontinuing antipsychotic therapy, gradually taper antipsychotics to avoid physical withdrawal symptoms and rebound symptoms (APA [Keepers 2020]; WFSBP [Hasan 2012]). Withdrawal symptoms may include agitation, alternating feelings of warmth and cold, anxiety, diaphoresis, dyskinesia, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor and vertigo (Lambert 2007; Moncrieff 2020). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). Patients with chronic symptoms, repeated relapses, and clear diagnostic features of schizophrenia are at risk for poor outcomes if medications are discontinued (APA [Keepers 2020]).
Pediatric psychiatric disorders are frequently serious mental disorders which present with variable symptoms that do not always match adult diagnostic criteria. Conduct a thorough diagnostic evaluation and carefully consider risks of psychotropic medication before initiation in pediatric patients with schizophrenia or bipolar disorder. Medication therapy for pediatric patients with these disorders is indicated as part of a total treatment program that frequently includes educational, psychological, and social interventions. Long-term usefulness of lurasidone should be periodically reevaluated in patients receiving the drug for extended periods of time. Although other second-generation antipsychotics have shown efficacy in the management of autism, efficacy data for lurasidone is lacking (Loebel 2016; McClellan 2017); in a 6-week double-blind, placebo-controlled trial of 150 children and adolescents (age range: 6 to 17 years; n=49 lurasidone 20 mg treatment group, n=51 lurasidone 60 mg treatment group, and n=50 placebo), once daily lurasidone was not shown to be more effective than placebo in treatment of moderate to severe irritability associated with autistic disorder (Loebel 2016).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Latuda: 20 mg, 40 mg, 60 mg
Latuda: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Latuda: 120 mg
Generic: 20 mg, 40 mg, 60 mg, 80 mg, 120 mg
Yes
Tablets (Latuda Oral)
20 mg (per each): $56.75
40 mg (per each): $56.75
60 mg (per each): $56.75
80 mg (per each): $56.75
120 mg (per each): $84.71
Tablets (Lurasidone HCl Oral)
20 mg (per each): $0.27 - $51.07
40 mg (per each): $0.39 - $51.07
60 mg (per each): $0.47 - $51.07
80 mg (per each): $0.50 - $51.07
120 mg (per each): $0.80 - $76.24
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Latuda: 20 mg, 40 mg, 60 mg
Latuda: 80 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Latuda: 120 mg
Generic: 20 mg, 40 mg, 60 mg, 80 mg, 120 mg
Oral: Administer with food (≥350 calories). The manufacturer recommends to not split, crush, or cut the tablets because the effects of splitting or crushing the tablets has not been evaluated in clinical and pharmacokinetic studies (Ref).
Oral: Administer consistently at the same time every day with food (≥350 calories). Evening administration may help reduce adverse effects (Ref). The manufacturer recommends not to split, crush, or cut the tablets because the effects of splitting or crushing the tablets has not been evaluated in clinical and pharmacokinetic studies (Ref).
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Latuda: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/200603s041lbl.pdf#page=63
Treatment of depressive episodes associated with bipolar I disorder, both as monotherapy (FDA approved in ages ≥10 years and adults) and as an adjunct to lithium or divalproex (FDA approved in adults); treatment of schizophrenia (FDA approved in ages ≥13 years and adults).
Latuda may be confused with Lantus
Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of stroke and a greater rate of cognitive decline and mortality in patients with dementia. Evidence also suggests there may be an increased risk of mortality with use independent of dementia. Avoid antipsychotics for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults. Use of antipsychotics may be appropriate for labeled indications including schizophrenia, bipolar disorder, Parkinson disease psychosis, adjunctive therapy in major depressive disorder, or for short-term use as an antiemetic (Beers Criteria [AGS 2023]).
Substrate of BCRP, CYP3A4 (Major), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (Weak);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Agents With Seizure Threshold Lowering Potential: May increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of ALPRAZolam. Risk C: Monitor
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
Amisulpride (Oral): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome or increased QTc interval may be increased. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider Therapy Modification
Antidiabetic Agents: Hyperglycemia-Associated Agents may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Atazanavir: May increase serum concentration of Lurasidone. Management: Decrease lurasidone dose 50% if adding atazanavir. Start lurasidone 20 mg daily and increase to no more than 80 mg daily in patients already taking atazanavir. Use of ritonavir- or cobicistat-boosted atazanavir with lurasidone is contraindicated. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benzgalantamine-Galantamine: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Blood Pressure Lowering Agents: May increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Bornaprine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, tardive dyskinesia symptoms may be potentiated. Risk C: Monitor
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BuPROPion: May increase neuroexcitatory and/or seizure-potentiating effects of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cabergoline: May decrease therapeutic effects of Antipsychotic Agents. Risk X: Avoid
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of CycloSPORINE (Systemic). Risk C: Monitor
CYP3A4 Inducers (Moderate): May decrease serum concentration of Lurasidone. Management: After chronic treatment (7 days or more) with a moderate CYP3A4 inducer, lurasidone dose increases may be needed. Monitor closely for decreased lurasidone effects and increase the lurasidone dose as needed. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Strong): May decrease serum concentration of Lurasidone. Risk X: Avoid
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Lurasidone. Management: Reduce the lurasidone dose by half when initiating therapy with a moderate CYP3A4 inhibitor. If initiating lurasidone in a patient already receiving a moderate CYP3A4 inhibitor, start lurasidone at 20 mg/day with a max dose of 80 mg/day. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Strong): May increase serum concentration of Lurasidone. Risk X: Avoid
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Deutetrabenazine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may increase adverse/toxic effects of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dofetilide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Dofetilide. Risk C: Monitor
Donepezil: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Flibanserin. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Lurasidone. Risk X: Avoid
Guanethidine: Antipsychotic Agents may decrease therapeutic effects of Guanethidine. Risk C: Monitor
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Huperzine A: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Itraconazole: May increase serum concentration of Lurasidone. Risk X: Avoid
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider Therapy Modification
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lithium: May increase neurotoxic effects of Antipsychotic Agents. Lithium may decrease serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lomitapide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider Therapy Modification
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: Antipsychotic Agents may decrease therapeutic effects of Metergoline. Metergoline may decrease therapeutic effects of Antipsychotic Agents. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
MetyroSINE: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor
Midazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Midazolam. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pimozide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Pimozide. Risk X: Avoid
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Piribedil: Antipsychotic Agents may decrease therapeutic effects of Piribedil. Piribedil may decrease therapeutic effects of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Quinagolide: Antipsychotic Agents may decrease therapeutic effects of Quinagolide. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Rivastigmine: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
Serotonergic Agents (High Risk): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Simvastatin. CYP3A4 Inhibitors (Weak) may increase active metabolite exposure of Simvastatin. Risk C: Monitor
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase serum concentration of Sirolimus (Conventional). Risk C: Monitor
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider Therapy Modification
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
St John's Wort: May decrease serum concentration of Lurasidone. Risk X: Avoid
Sulpiride: Antipsychotic Agents may increase adverse/toxic effects of Sulpiride. Risk X: Avoid
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tetrabenazine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased. Risk C: Monitor
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Triazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Triazolam. Risk C: Monitor
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider Therapy Modification
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ziprasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Administration with food (≥350 calories) increased Cmax and AUC of lurasidone ~3 times and 2 times, respectively, compared to administration under fasting conditions. Lurasidone exposure was not affected by the fat content of the meal. Management: Administer with food (≥350 calories).
Lurasidone serum concentrations may be increased when taken with grapefruit or grapefruit juice. Management: Avoid concurrent use.
Should be taken with food (≥350 calories). Avoid grapefruit and grapefruit juice.
Evaluate pregnancy status and provide preconception counseling prior to initiating treatment in patients who could become pregnant (APA [Keepers 2020]; BAP [McAllister-Williams 2017]; CANMAT [Yatham 2018]). Patients effectively treated may continue their current antipsychotic medication when planning a pregnancy unless contraindications exist (ACOG 2023; BAP [McAllister-Williams 2017]); the lowest effective dose and avoidance of polytherapy is recommended (BAP [Barnes 2020]; BAP [McAllister-Williams 2017]; CANMAT [Yatham 2018]). Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment and the risks of discontinuing antipsychotic therapy (ACOG 2023; BAP [McAllister-Williams 2017]; CANMAT [Yatham 2018]).
Antipsychotic agents may be associated with sexual dysfunction. Some second generation (atypical) antipsychotics may cause hyperprolactinemia, resulting in menstrual disorders or impaired spermatogenesis. Consider changing to a medication that is prolactin-sparing in patients with clinical symptoms. Contraception should be provided if pregnancy is not desired, as unintended pregnancies may occur when changing to a prolactin-sparing medication (APA [Keepers 2020]; BAP [McAllister-Williams 2017]).
Outcome data following exposure to second generation (atypical) antipsychotics (SGAs) as a class do not show a significant increased risk of major congenital malformations (BAP [Barnes 2020]; Viguera 2021; Wang 2021); however, data specific to lurasidone are limited (ACOG 2023; Cohen 2023; Montiel 2022). Additional studies are needed for individual agents and specific outcomes (BAP [Barnes 2020]). Data related to the long-term effects of in utero antipsychotic exposure on infant neurodevelopment and behavior are limited (BAP [McAllister-Williams 2017]; Straub 2022; Swetlik 2024).
Antipsychotic use during the third trimester of pregnancy increases the risk for extrapyramidal symptoms and/or withdrawal symptoms in newborns following delivery (Viguera 2023). Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor. These effects may require prolonged hospitalization or resolve within hours or days without specific treatment. Tapering the dose late in pregnancy to reduce the risk of symptoms is not recommended (APA [Keepers 2020]).
Atypical antipsychotics are associated with metabolic changes and the risk varies by specific agent. Available studies that evaluated the risk of developing gestational diabetes mellitus (GDM) during antipsychotic therapy have conflicting results, possibly due to differences in study design (ACOG 2023; Uguz 2019). Pregnant patients with diabetes mellitus or GDM may continue antipsychotic treatment (ACOG 2023). Consider the metabolic risks of the specific antipsychotic if treatment is initiated for the first-time during pregnancy (Heinonen 2022). Screening for GDM should continue as part of standard prenatal care; early screening is not needed due to psychiatric medication exposure (ACOG 2023; BAP [McAllister-Williams 2017]).
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of lurasidone may be altered, including increased CYP3A4 activity. Data from one case report suggest maternal plasma concentrations of lurasidone may decrease during the third trimester (Montiel 2022).
Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes (ACOG 2023). Adverse obstetric and neonatal outcomes are associated with schizophrenia; however, comparisons between treated and untreated pregnancies are limited (BAP [McAllister-Williams 2017]). Untreated bipolar disorder is associated with fetal growth restriction, preterm birth, and adverse neurodevelopment, and may increase the risk of postpartum psychosis, worsening mood, and postpartum hospitalization. Discontinuing effective medications during pregnancy increases the risk of symptom relapse (ACOG 2023).
Patients effectively treated for schizophrenia or bipolar disorder pre-pregnancy may use the same medication during pregnancy unless contraindications exist (ACOG 2023; APA [Keepers 2020]). SGAs are better tolerated and have fewer extrapyramidal adverse effects than first-generation (typical) antipsychotics (ACOG 2023). Due to limited data, agents other than lurasidone may be preferred when treatment for bipolar disorder is initiated for the first-time during pregnancy (ACOG 2023, CANMAT [Yatham 2018]).
Management of mental health conditions should be made as part of a shared decision-making process (ACOG 2023; BAP [McAllister-Williams 2017]). Treatment should not be withheld or discontinued based only on pregnancy status. When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Close monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023).
Data collection to monitor pregnancy and infant outcomes following exposure to psychiatric medications is ongoing. Encourage pregnant patients 45 years and younger with a history of psychiatric illness to enroll in the National Pregnancy Registry for Psychiatric Mediations (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/).
Mental status; vital signs (as clinically indicated); blood pressure (baseline; repeat 3 months after antipsychotic initiation, then yearly); weight, height, BMI, waist circumference (baseline; repeat at 4, 8, and 12 weeks after initiating or changing therapy, then quarterly; consider switching to a different antipsychotic for a weight gain ≥5% of initial weight); CBC (as clinically indicated; monitor frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia); ECG, electrolytes, renal and liver function (annually and as clinically indicated); personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease (baseline; repeat annually); fasting plasma glucose level/HbA1c (baseline; repeat 3 months after starting antipsychotic, then yearly); fasting lipid panel (baseline; repeat 3 months after initiation of antipsychotic; if LDL level is normal repeat at 2- to 5-year intervals or more frequently if clinically indicated); changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function (at each visit for the first 12 weeks after the antipsychotic is initiated or until the dose is stable, then yearly); abnormal involuntary movements or parkinsonian signs (baseline; repeat weekly until dose stabilized for at least 2 weeks after introduction and for 2 weeks after any significant dose increase); tardive dyskinesia (every 12 months; high-risk patients every 6 months); ocular examination (yearly in patients >40 years; every 2 years in younger patients) (ADA 2004; Lehman 2004; Marder 2004).
Lurasidone is a benzoisothiazol-derivative atypical antipsychotic with mixed serotonin-dopamine antagonist activity. It exhibits high affinity for D2, 5-HT2A, and 5-HT7 receptors; moderate affinity for alpha2C-adrenergic receptors; and is a partial agonist for 5-HT1A receptors. Lurasidone has no significant affinity for muscarinic M1 and histamine H1 receptors. The addition of serotonin antagonism to dopamine antagonism (classic neuroleptic mechanism) is thought to improve negative symptoms of psychoses and reduce the incidence of extrapyramidal side effects as compared to typical antipsychotics (Huttunen 1995).
Note: Lurasidone exposure in pediatric patients 10 to 17 years was observed to be generally similar to adult data.
Onset of action:
Bipolar disorder, depressive episode: Initial effects may be observed within 1 week of treatment with continued improvements through 6 weeks (Cruz 2010).
Schizophrenia: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks (Agid 2003; Levine 2010).
Absorption: Increased in fed state.
Distribution: Vd: 6,173 L.
Protein binding: ~99%.
Metabolism: Primarily via CYP3A4; two active metabolites (ID-14283 and ID-14326) and two major nonactive metabolites (ID-20219 and ID-20220) produced.
Bioavailability: 9% to 19%.
Half-life elimination: 18 to 40 hours; Main active metabolite, ID-14283 (exo-hydroxy metabolite), exhibits a half-life of 7.5 to 10 hours (Citrome 2011).
Time to peak: 1 to 3 hours; steady state concentrations achieved within 7 days.
Excretion: Urine (~9%); feces (~80%).
Altered kidney function: In patients with mild, moderate, or severe renal impairment, mean Cmax increased by 40%, 92%, and 54%, respectively, and mean AUC0-∞ increased by 53%, 91%, and 2 times, respectively, compared with healthy matched subjects (Citrome 2011).
Hepatic function impairment: Mean AUC0-last was 1.5 times higher in subjects with mild hepatic impairment (Child-Pugh class A), 1.7 times higher in subjects with moderate hepatic impairment (Child-Pugh class B), and 3 times higher in subjects with severe hepatic impairment (Child-Pugh class C) compared with the values for healthy matched subjects. Mean Cmax was 1.3, 1.2, and 1.3 times higher for patients with mild, moderate, and severe hepatic impairment, respectively, compared with the values for healthy matched subjects (Citrome 2011).
