Your activity: 21 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

Lumateperone: Drug information

Lumateperone: Drug information
(For additional information see "Lumateperone: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Increased mortality in elderly patients with dementia-related psychosis:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Lumateperone is not approved for the treatment of patients with dementia-related psychosis.

Suicidal thoughts and behaviors:

Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adults in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors. The safety and effectiveness of lumateperone have not been established in pediatric patients.

Brand Names: US
  • Caplyta
Pharmacologic Category
  • Second Generation (Atypical) Antipsychotic
Dosing: Adult

Note: Due to the drug's potential sedating effect, bedtime dosing may be preferred in some patients (Jibson 2021).

Bipolar disorder: Bipolar major depression (monotherapy or adjunctive therapy): Oral: 42 mg once daily.

Schizophrenia: Oral: 42 mg once daily.

Switching antipsychotics: An optimal universal strategy for switching antipsychotic agents 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 (Cerovecki 2013; Remington 2005; Takeuchi 2017). Because lumateperone is only available in a 42 mg capsule, gradual tapers are not possible, making abrupt discontinuation the only option when switching to a new treatment.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

Mild impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate to severe impairment (Child-Pugh class B and C): Avoid use.

Dosing: Older Adult

Refer to adult dosing. Note: Use of lumateperone in geriatric patients has not been studied.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as tosylate:

Caplyta: 42 mg [contains brilliant blue fcf (fd&c blue #1)]

Generic Equivalent Available: US

No

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/209500s005s006lbl.pdf#page=22, must be dispensed with this medication.

Administration: Adult

Oral: Administer with or without food.

Use: Labeled Indications

Bipolar disorder: As monotherapy or as an adjunct to lithium or valproate for treatment of depressive episodes associated with bipolar disorder I or II in adults.

Schizophrenia: Treatment of schizophrenia in adults.

Medication Safety Issues
Geriatric Patients: High-Risk Medication:

Beers Criteria: Antipsychotics are identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years of age and older due to an increased risk of cerebrovascular accidents (stroke) and a greater rate of cognitive decline and mortality in patients with dementia. Antipsychotics may be appropriate for schizophrenia, bipolar disorder, other mental health conditions, or short-term use as antiemetic during chemotherapy, but should be given in the lowest effective dose for the shortest duration possible. 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 or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria [AGS 2019]).

Adverse Reactions (Significant): Considerations
Dyslipidemia

Antipsychotics are associated with dyslipidemia, which is a component of the metabolic syndrome observed with this pharmacologic class (Ref). Increased LDL cholesterol, increased serum cholesterol, and increased serum triglycerides have been reported with lumateperone.

Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).

Onset: Varied; metabolic alterations from antipsychotics can develop in as short as 3 months after the 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: Overall, metabolic disturbances appear to be the greatest with clozapine and olanzapine (Ref); further data will help elucidate risk associated with lumateperone.

Extrapyramidal symptoms

Lumateperone may cause extrapyramidal reaction (extrapyramidal symptoms [EPS]), also known as drug-induced movement disorders. Antipsychotics can cause 4 main EPS: Acute dystonia, akathisia, drug-induced parkinsonism, and 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; due to antagonism of dopaminergic D2 receptors in nigrostriatal pathways (Ref). Akathisia: Mechanism not completely understood, but possibly associated with the low activity of dopaminergic projections from the midbrain to the ventral striatum and imbalance between the dopamine and serotonin neurotransmitter system (Ref). Tardive dyskinesia: Time-related (delayed); results from chronic exposure to dopamine 2 receptor antagonists leading to up-regulation of these receptors over time (Ref). Of note, lumateperone is a novel second-generation antipsychotic that modulates serotonin, dopamine, and glutamate neurotransmission. It has a 60-fold higher affinity for 5HT2A receptors compared to D2 receptors. High D2 receptor occupancy (60% to 80%) is associated with increased risk of EPS; lumateperone (42 mg/day) is associated with a low D2 receptor occupancy (40%). In addition, lumateperone has lower affinity for nigrostriatal dopamine pathways compared to mesocortical and mesolimbic circuits (Ref).

Onset:

For antipsychotics in general:

Acute dystonia: Rapid; in the majority of cases, dystonia usually occurs 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).

Drug-induced parkinsonism: Varied; onset 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 2 receptor 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:

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 and generation: Lumateperone, a novel second-generation antipsychotic, has been associated with a low incidence of EPS-related adverse events in post-hoc analysis of available preliminary data (Ref).

Acute dystonia:

• Males (Ref)

• Young age (Ref)

Drug-induced parkinsonism:

• Females (Ref)

• Older patients (Ref)

Akathisia:

• Higher antipsychotic dosages (Ref)

• Polypharmacy (Ref)

• Mood disorders (Ref)

• Females (Ref)

• Older patients (Ref)

Tardive dyskinesia:

• Increasing age (Ref)

• Females (Ref)

• Comorbidities such as diabetes mellitus, intellectual disability, brain damage, smoking, alcohol and/or substance use disorders, mood disorders (Ref)

• High antidopaminergic drug dose or plasma level (Ref)

• Race (White or African descent) (Ref)

• Longer illness duration (Ref)

• Higher cumulative doses (Ref)

• Higher ratings of negative symptoms and thought disorder (Ref)

Esophageal dysfunction (associated with EPS):

• Certain comorbidities such as neurologic degenerative disease, dementia, stroke, Parkinson disease, or myasthenia gravis (Ref)

• Older adults >75 years of age (may be risk factor due to age-related muscle atrophy, cognitive impairment, reduced esophageal peristalsis) (Ref)

Hematologic abnormalities

Leukopenia and neutropenia have been reported with lumateperone. Agranulocytosis has also been reported with other antipsychotics.

Onset: Varied; in general, drug-induced neutropenia usually manifests after 1 or 2 weeks of exposure and agranulocytosis usually appears 3 to 4 weeks following initiation of therapy; however, the onset may be insidious (Ref).

Risk factors:

• History of drug-induced leukopenia/neutropenia or preexisting low white blood cell count/absolute neutrophil count

• Older adults (Ref)

Hyperglycemia

Antipsychotics are associated with hyperglycemia, to varying degrees, which is a component of the metabolic syndrome observed with this pharmacologic class. Glycemic abnormalities range from mild insulin resistance to new-onset diabetes mellitus and diabetic ketoacidosis, including fatal cases (Ref).

Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).

Onset: Varied; new-onset diabetes has been observed within the first 3 months to a median onset of 3.9 years of atypical antipsychotic use (lumateperone was not included) (Ref).

Risk factors:

Antipsychotics in general:

• African American race (Ref)

• Males (Ref)

• Age <35 years (Ref)

• 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: Metabolic disturbances appear to be the greatest with clozapine and olanzapine (Ref); further data will help elucidate risk associated with lumateperone.

Mortality in older adults

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 in older adults with dementia-related psychosis (Ref). Of note, lumateperone 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:

• Higher antipsychotic dosage (Ref)

• Dementia-related psychosis (eg, Lewy body dementia, Parkinson disease dementia)

• Older adults

Neuroleptic malignant syndrome

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).

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:

Antipsychotic 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)

Sedation

Sedated state (drowsiness) is common with use; may cause nonadherence and impair physical and mental abilities, resulting in subsequent falling, particularly in older adults (Ref).

Temperature dysregulation

Antipsychotics may impair the body's ability to regulate core body temperature, which may cause a potentially life-threatening heatstroke during predisposing conditions such as a heat wave or strenuous exercise. Antipsychotics have also been associated with potentially life-threatening hypothermia (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 (Ref).

Onset: Hypothermia: Varied; antipsychotic-induced hypothermia cases indicate a typical onset in the period shortly after initiation of therapy (first 7 days) (Ref).

Risk factors:

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: Older adults, cerebrovascular accident, preexisting brain damage, hypothyroidism, malnutrition, shock, sepsis, adrenal insufficiency, diabetes, disability, burns, exfoliative dermatitis, benzodiazepine use, alcohol intoxication, kidney or liver failure (Ref)

• Schizophrenia (regardless of antipsychotic use) (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Nervous system: Drowsiness (≤24%) (table 1), sedated state (≤24%) (table 2)

Lumateperone: Adverse Reaction: Drowsiness

Drug (Lumateperone)

Placebo

Dose

Number of Patients (Lumateperone)

Number of Patients (Placebo)

Comments

≤24%

≤10%

42 mg

406

412

Combined incidence, drowsiness and sedated state

Lumateperone: Adverse Reaction: Sedated State

Drug (Lumateperone)

Placebo

Dose

Number of Patients (Lumateperone)

Number of Patients (Placebo)

Comments

≤24%

≤10%

42 mg

406

412

Combined incidence, drowsiness and sedated state

1% to 10%:

Gastrointestinal: Decreased appetite (2%), nausea (9%), vomiting (3%), xerostomia (6%)

Hepatic: Increased serum transaminases (2%)

Nervous system: Dizziness (5%), extrapyramidal reaction (7%) (table 3), fatigue (3%)

Lumateperone: Adverse Reaction: Extrapyramidal Reaction

Drug (Lumateperone)

Placebo

Number of Patients (Lumateperone)

Number of Patients (Placebo)

7%

6%

N/A

N/A

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (4%)

<1%: Cardiovascular: Orthostatic hypotension

Frequency not defined:

Endocrine & metabolic: Hyperglycemia, increased LDL cholesterol, increased serum cholesterol, increased serum triglyceride

Hematologic & oncologic: Elevated glycosylated hemoglobin, leukopenia, neutropenia

Nervous system: Dystonia

Contraindications

Hypersensitivity (eg, pruritus, rash, urticaria) to lumateperone or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Anticholinergic effects: May cause anticholinergic effects (confusion, agitation, constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased GI motility, urinary retention, benign prostatic hyperplasia, xerostomia, or visual problems.

• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability.

Disease-related concerns:

• Hepatic impairment: Avoid use in patients with moderate to severe hepatic disease or impairment.

• Seizures: Use with caution in patients at risk of seizures or with conditions that lower the seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.

Metabolism/Transport Effects

Substrate of CYP1A2 (minor), CYP2C8 (minor), CYP3A4 (major), UGT1A1, UGT1A4, UGT2B15; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Risk C: Monitor therapy

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy

Amisulpride (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome may be increased. Risk X: Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect 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

Armodafinil: May decrease the serum concentration of Lumateperone. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect 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 enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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 enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy

Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Risk X: Avoid combination

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Ciprofloxacin (Systemic): May increase the serum concentration of Lumateperone. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

CycloSPORINE (Systemic): May increase the serum concentration of Lumateperone. Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Lumateperone. Risk X: Avoid combination

CYP3A4 Inducers (Strong): May decrease the serum concentration of Lumateperone. Risk X: Avoid combination

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Lumateperone. Risk X: Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Lumateperone. Risk X: Avoid combination

Daridorexant: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor therapy

Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor therapy

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Droperidol: May enhance the CNS depressant effect 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

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect 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

FluvoxaMINE: May increase the serum concentration of Lumateperone. Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect 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 enhance the adverse/toxic effect 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 enhance the adverse/toxic effect 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

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect 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

Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Risk D: Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect 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

Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect 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

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect 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

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect 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 combination

Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect 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

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Risk X: Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect 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

Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect 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

Food Interactions

Grapefruit juice may increase lumateperone serum concentrations. Management: Avoid grapefruit juice.

Reproductive Considerations

If treatment is needed in a woman planning a pregnancy, use of an agent other than lumateperone is preferred (Larsen 2015).

Pregnancy Considerations

Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization.

Safety data related to atypical antipsychotics during pregnancy are limited; as such, routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to an agent that the fetus has not yet been exposed to; consider risk:benefit (ACOG 2008). If treatment is initiated during pregnancy, use of an agent other than lumateperone is preferred (Larsen 2015).

Data collection to monitor pregnancy and infant outcomes following exposure to lumateperone is ongoing. Health care providers are encouraged to enroll females exposed to lumateperone during pregnancy in the National Pregnancy Registry for Atypical Antipsychotics (1-866-961-2388 or http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry).

Breastfeeding Considerations

It is not known if lumateperone is present in breast milk.

Failure to thrive, jitteriness, extrapyramidal symptoms, and sedation have been reported in infants exposed to other antipsychotics via breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer. Until additional information is available, use of agents other than lumateperone in breastfeeding women is preferred (Uguz 2016).

Dietary Considerations

Avoid grapefruit juice.

Monitoring Parameters

Frequency of Antipsychotic Monitoringa,b

Monitoring parameter

Frequency of monitoring

Comments

Adherence

Every visit

Blood chemistries (electrolytes, renal function, liver function, TSH)

Annually

CBC

As clinically indicated

Check frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia

Extrapyramidal symptoms

Every visit; 4 weeks after initiation and dose change; annually. Use a formalized rating scale at least annually or every 6 months if high risk.c

Fall risk

Every visit

Fasting plasma glucose/HbA1c

12 weeks after initiation and dose change; annually

Check more frequently than annually if abnormal. Follow diabetes guidelines.

Lipid panel

12 weeks after initiation and dose change; annually

Check more frequently than annually if abnormal. Follow lipid guidelines.

Mental status

Every visit

Metabolic syndrome history

Annually

Evaluate for personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease

Prolactin

Ask about symptoms at every visit until dose is stable. Check prolactin level if symptoms are reported.

Hyperprolactinemia symptoms: Changes in menstruation, libido, gynecomastia, development of galactorrhea, and erectile and ejaculatory function

Tardive dyskinesia

Every visit; annually. Use a formalized rating scale at least annually or every 6 months if high risk.d

Vital signs (BP, orthostatics, temperature, pulse, signs of infection)

Every visit (at least weekly during first 3 to 4 weeks of treatment); 4 weeks after dose change.

Weight/Height/BMI

8 and 12 weeks after initiation and dose change; quarterly

Consider monitoring waist circumference at baseline and annually, especially in patients with or at risk for metabolic syndrome.

Consider changing antipsychotic if BMI increases by ≥1 unit.

Some experts recommend checking weight and height at every visit.

a For all monitoring parameters, it is appropriate for check at baseline and when clinically relevant (based on symptoms or suspected ADRs) in addition to the timeline.

b ADA 2004; APA [Keepers 2020]; De Hert 2011; Gugger 2011; manufacturer's labeling.

c Risk factors for extrapyramidal symptoms (EPS) include prior history of EPS, high doses of antipsychotics, young age (children and adolescents at higher risk than adults), and dopaminergic affinity of individual antipsychotic.

d Risk factors for tardive dyskinesia include age >55 years; females; White or African ethnicity; presence of a mood disorder, intellectual disability, or central nervous system injury; and past or current EPS.

Mechanism of Action

Lumateperone is a second-generation antipsychotic with antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors. Lumateperone has high binding affinity for serotonin 5-HT2A receptors and moderate binding affinity for dopamine D2 receptors. Lumateperone also has moderate binding affinity for dopamine D1 and D4 and adrenergic alpha1A and alpha1B receptors but has low binding affinity for muscarinic and histaminergic receptors.

Pharmacokinetics

Onset of action: 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: Ingestion of a high-fat meal lowers the mean Cmax by 33% and increases mean AUC by 9%. In the presence of food, the median Tmax is delayed ~1 hour (from 1 hour at fasted state to 2 hours with food).

Distribution: Vd: 4.1 L/kg.

Protein binding: Plasma: 97.4%.

Metabolism: Extensive metabolism to >20 metabolites by multiple enzymes, including but not limited to uridine 5'-diphospho-glucuronosyltransferases (UDP-glucuronosyltransferase, UGT) 1A1, 1A4, and 2B15, aldoketoreductase (AKR)1C1, 1B10, and 1C4, and cytochrome P450 (CYP) 3A4, 2C8, and 1A2.

Bioavailability: 4.4%.

Half-life elimination: ~18 hours after IV administration; following oral administration, steady state is reached in ~5 days.

Time to peak: 1 to 2 hours.

Excretion: Urine: 58% (<1% as unchanged drug); feces: 29%.

Pricing: US

Capsules (Caplyta Oral)

42 mg (per each): $59.27

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.

REFERENCES

  1. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. doi:10.1111/jgs.15767 [PubMed 30693946]
  2. Agid O, Kapur S, Arenovich T, Zipursky RB. Delayed-onset hypothesis of antipsychotic action: a hypothesis tested and rejected. Arch Gen Psychiatry. 2003;60(12):1228-1235. doi:10.1001/archpsyc.60.12.1228 [PubMed 14662555]
  3. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin: clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (Replaces Practice Bulletin Number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008;111(4):1001-1020. [PubMed 18378767]
  4. American Diabetes Association (ADA); American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Obes Res. 2004;12(2):362-368. [PubMed 14981231]
  5. Anzai T, Takahashi K, Watanabe M. Adverse reaction reports of neuroleptic malignant syndrome induced by atypical antipsychotic agents in the Japanese Adverse Drug Event Report (JADER) database. Psychiatry Clin Neurosci. 2019;73(1):27-33. doi:10.1111/pcn.12793 [PubMed 30375086]
  6. Bark N. Deaths of psychiatric patients during heat waves. Psychiatr Serv. 1998;49(8):1088-1090. doi:10.1176/ps.49.8.1088 [PubMed 9712220]
  7. Belvederi Murri M, Guaglianone A, Bugliani M, et al. Second-generation antipsychotics and neuroleptic malignant syndrome: systematic review and case report analysis. Drugs R D. 2015;15(1):45-62. doi:10.1007/s40268-014-0078-0 [PubMed 25578944]
  8. Bouchama A, Dehbi M, Mohamed G, Matthies F, Shoukri M, Menne B. Prognostic factors in heat wave related deaths: a meta-analysis. Arch Intern Med. 2007;167(20):2170-2176. doi:10.1001/archinte.167.20.ira70009 [PubMed 17698676]
  9. Caplyta (lumateperone) [prescribing information]. New York, NY: Intra-Cellular Therapies Inc; December 2021.
  10. Caroff SN, Hurford I, Lybrand J, Campbell EC. Movement disorders induced by antipsychotic drugs: implications of the CATIE schizophrenia trial. Neurol Clin. 2011;29(1):127-viii. doi:10.1016/j.ncl.2010.10.002 [PubMed 21172575]
  11. Casey DE, Haupt DW, Newcomer JW, et al. Antipsychotic-induced weight gain and metabolic abnormalities: implications for increased mortality in patients with schizophrenia. J Clin Psychiatry. 2004;65 Suppl 7:4-20. [PubMed 15151456]
  12. Cerovecki A, Musil R, Klimke A, et al. Withdrawal symptoms and rebound syndromes associated with switching and discontinuing atypical antipsychotics: theoretical background and practical recommendations. CNS Drugs. 2013;27(7):545-572. doi: 10.1007/s40263-013-0079-5. [PubMed 23821039]
  13. Chen MH, Liou YJ. Aripiprazole-associated acute dystonia, akathisia, and parkinsonism in a patient with bipolar I disorder. J Clin Psychopharmacol. 2013;33(2):269-270. doi:10.1097/JCP.0b013e3182856826 [PubMed 23422384]
  14. Cooper D, Gupta V. Lumateperone. In: StatPearls. Treasure Island (FL): StatPearls Publishing; October 5, 2020. [PubMed 32809679]
  15. Corponi F, Fabbri C, Bitter I, et al. Novel antipsychotics specificity profile: a clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone. Eur Neuropsychopharmacol. 2019;29(9):971-985. doi:10.1016/j.euroneuro.2019.06.008 [PubMed 31255396]
  16. Correll CU. Assessing and maximizing the safety and tolerability of antipsychotics used in the treatment of children and adolescents. J Clin Psychiatry. 2008;69 Suppl 4:26-36. [PubMed 18533766]
  17. Crouse EL, Alastanos JN, Bozymski KM, Toscano RA. Dysphagia with second-generation antipsychotics: a case report and review of the literature. Ment Health Clin. 2018;7(2):56-64. doi:10.9740/mhc.2017.03.056 [PubMed 29955499]
  18. De Hert M, Detraux J, van Winkel R, Yu W, Correll CU. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2011;8(2):114-126. doi:10.1038/nrendo.2011.156 [PubMed 22009159]
  19. de Leon J, Susce MT, Johnson M, et al. A clinical study of the association of antipsychotics with hyperlipidemia. Schizophr Res. 2007;92(1-3):95-102. doi:10.1016/j.schres.2007.01.015 [PubMed 17346932]
  20. D'Souza RS, Hooten WM. Extrapyramidal Symptoms. In: StatPearls. Treasure Island (FL): StatPearls Publishing; November 20, 2020. [PubMed 30475568]
  21. Divac N, Prostran M, Jakovcevski I, Cerovac N. Second-generation antipsychotics and extrapyramidal adverse effects. Biomed Res Int. 2014;2014:656370. doi:10.1155/2014/656370 [PubMed 24995318]
  22. Durgam S, Satlin A, Davis RE, Vanover KE, Mates S, Kane JM. Lumateperone in the treatment of schizophrenia: evaluation of extrapyramidal and motor symptoms in 4 late-phase clinical trials [abstract]. Schizophrenia Bulletin. 2020;46(suppl 1):S310:abstract T205. doi:10.1093/schbul/sbaa029.765
  23. Ely SF, Neitzel AR, Gill JR. Fatal diabetic ketoacidosis and antipsychotic medication. J Forensic Sci. 2013;58(2):398-403. doi:10.1111/1556-4029.12044 [PubMed 23278567]
  24. Evcimen H, Alici-Evcimen Y, Basil B, Mania I, Mathews M, Gorman JM. Neuroleptic malignant syndrome induced by low dose aripiprazole in first episode psychosis. J Psychiatr Pract. 2007;13(2):117-119. doi:10.1097/01.pra.0000265770.17871.01 [PubMed 17414689]
  25. Flanagan RJ, Dunk L. Haematological toxicity of drugs used in psychiatry. Hum Psychopharmacol. 2008;23 Suppl 1:27-41. doi:10.1002/hup.917 [PubMed 18098216]
  26. Fraser LA, Liu K, Naylor KL, et al. Falls and fractures with atypical antipsychotic medication use: a population-based cohort study. JAMA Intern Med. 2015;175(3):450-452. doi:10.1001/jamainternmed.2014.6930 [PubMed 25581312]
  27. Gareri P, De Fazio P, Manfredi VG, De Sarro G. Use and safety of antipsychotics in behavioral disorders in elderly people with dementia. J Clin Psychopharmacol. 2014;34(1):109-123. doi:10.1097/JCP.0b013e3182a6096e [PubMed 24158020]
  28. Gill SS, Bronskill SE, Normand SL, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med. 2007;146(11):775-786. doi:10.7326/0003-4819-146-11-200706050-00006 [PubMed 17548409]
  29. Gugger JJ. Antipsychotic pharmacotherapy and orthostatic hypotension: identification and management. CNS Drugs. 2011;25(8):659-671. doi:10.2165/11591710-000000000-00000 [PubMed 21790209]
  30. Hansen A, Bi P, Nitschke M, Ryan P, Pisaniello D, Tucker G. The effect of heat waves on mental health in a temperate Australian city. Environ Health Perspect. 2008;116(10):1369-1375. doi:10.1289/ehp.11339 [PubMed 18941580]
  31. Hsu JH, Mulsant BH, Lenze EJ, et al. Clinical predictors of extrapyramidal symptoms associated with aripiprazole augmentation for the treatment of late-life depression in a randomized controlled trial. J Clin Psychiatry. 2018;79(4):17m11764. doi:10.4088/JCP.17m11764 [PubMed 29924506]
  32. Isaac M, Koch A. The risk of death among adult participants in trials of antipsychotic drugs in schizophrenia. Eur Neuropsychopharmacol. 2010;20(3):139-145. doi:10.1016/j.euroneuro.2009.12.002 [PubMed 20053539]
  33. Jackson JW, Schneeweiss S, VanderWeele TJ, Blacker D. Quantifying the role of adverse events in the mortality difference between first and second-generation antipsychotics in older adults: systematic review and meta-synthesis. PLoS One. 2014;9(8):e105376. doi:10.1371/journal.pone.0105376 [PubMed 25140533]
  34. Jibson MD. Second-generation antipsychotic medications: pharmacology, administration, and side effects. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 20, 2021.
  35. Jones ME, Campbell G, Patel D, et al. Risk of mortality (including sudden cardiac death) and major cardiovascular events in users of olanzapine and other antipsychotics: a study with the general practice research database. Cardiovasc Psychiatry Neurol. 2013;2013:647476. doi:10.1155/2013/647476 [PubMed 24416588]
  36. Jurivich DA, Hanlon J, Andolsek K. Neuroleptic-induced neutropenia in the elderly. J Am Geriatr Soc. 1987;35(3):248-250. doi:10.1111/j.1532-5415.1987.tb02317.x [PubMed 3819263]
  37. Kales HC, Kim HM, Zivin K, et al. Risk of mortality among individual antipsychotics in patients with dementia. Am J Psychiatry. 2012;169(1):71-79. doi:10.1176/appi.ajp.2011.11030347 [PubMed 22193526]
  38. Keepers GA, Fochtmann LJ, Anzia JM, et al. The American Psychiatric Association practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2020;177(9):868-872. doi:10.1176/appi.ajp.2020.177901 [PubMed 32867516]
  39. Kogoj A, Velikonja I. Olanzapine induced neuroleptic malignant syndrome--a case review. Hum Psychopharmacol. 2003;18(4):301-309. doi:10.1002/hup.483 [PubMed 12766935]
  40. Koro CE, Meyer JM. Atypical antipsychotic therapy and hyperlipidemia: a review. Essent Psychopharmacol. 2005;6(3):148-157. [PubMed 15869022]
  41. Kwok JS, Chan TY. Recurrent heat-related illnesses during antipsychotic treatment. Ann Pharmacother. 2005;39(11):1940-1942. doi:10.1345/aph.1G130 [PubMed 16174785]
  42. Langballe EM, Engdahl B, Nordeng H, Ballard C, Aarsland D, Selbæk G. Short- and long-term mortality risk associated with the use of antipsychotics among 26,940 dementia outpatients: a population-based study. Am J Geriatr Psychiatry. 2014;22(4):321-331. doi:10.1016/j.jagp.2013.06.007 [PubMed 24016844]
  43. Larsen ER, Damkier P, Pedersen LH, et al. Use of psychotropic drugs during pregnancy and breast-feeding. Acta Psychiatr Scand Suppl. 2015;(445):1-28. [PubMed 26344706]
  44. Lenzer J. FDA warns about using antipsychotic drugs for dementia [published correction appears in BMJ. 2005;330(7502):1258]. BMJ. 2005;330(7497):922. doi:10.1136/bmj.330.7497.922-c [PubMed 15845964]
  45. Levine SZ, Rabinowitz J. Trajectories and antecedents of treatment response over time in early-episode psychosis. Schizophr Bull. 2010;36(3):624-632. doi:10.1093/schbul/sbn120 [PubMed 18849294]
  46. Martinez M, Devenport L, Saussy J, Martinez J. Drug-associated heat stroke. South Med J. 2002;95(8):799-802. [PubMed 12190212]
  47. Maust DT, Kim HM, Seyfried LS, et al. Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm. JAMA Psychiatry. 2015;72(5):438-445. doi:10.1001/jamapsychiatry.2014.3018 [PubMed 25786075]
  48. Miller DD. Atypical antipsychotics: sleep, sedation, and efficacy. Prim Care Companion J Clin Psychiatry. 2004;6(suppl 2):3-7. [PubMed 16001094]
  49. Muench J, Hamer AM. Adverse effects of antipsychotic medications. Am Fam Physician. 2010;81(5):617-622. [PubMed 20187598]
  50. Nanasawa H, Sako A, Mitsutsuka T, et al. Development of diabetes mellitus associated with quetiapine: a case series. Medicine (Baltimore). 2017;96(3):e5900. doi:10.1097/MD.0000000000005900 [PubMed 28099349]
  51. Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs. 2005;19 Suppl 1:1-93. doi:10.2165/00023210-200519001-00001 [PubMed 15998156]
  52. Nielsen J, Skadhede S, Correll CU. Antipsychotics associated with the development of type 2 diabetes in antipsychotic-naïve schizophrenia patients. Neuropsychopharmacology. 2010;35(9):1997-2004. doi:10.1038/npp.2010.78 [PubMed 20520598]
  53. Nielsen RE, Wallenstein Jensen SO, Nielsen J. Neuroleptic malignant syndrome-an 11-year longitudinal case-control study. Can J Psychiatry. 2012;57(8):512-518. doi:10.1177/070674371205700810 [PubMed 22854034]
  54. Olfson M, Marcus SC, Corey-Lisle P, Tuomari AV, Hines P, L'Italien GJ. Hyperlipidemia following treatment with antipsychotic medications. Am J Psychiatry. 2006;163(10):1821-1825. doi:10.1176/ajp.2006.163.10.1821 [PubMed 17012695]
  55. O'Neill JL, Remington TL. Drug-induced esophageal injuries and dysphagia. Ann Pharmacother. 2003;37(11):1675-1684. doi:10.1345/aph.1D056 [PubMed 14565800]
  56. Pelonero AL, Levenson JL, Pandurangi AK. Neuroleptic malignant syndrome: a review. Psychiatr Serv. 1998;49(9):1163-1172. doi:10.1176/ps.49.9.1163 [PubMed 9735957]
  57. Perera MA, Yogaratnam J. De Novo delayed onset hypothermia secondary to therapeutic doses of risperidone in bipolar affective disorder. Ther Adv Psychopharmacol. 2014;4(2):70-74. doi:10.1177/2045125313507740 [PubMed 24688758]
  58. Post RM. Bipolar disorder in adults: choosing maintenance treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 3, 2020.
  59. Remington G, Chue P, Stip E, Kopala L, Girard T, Christensen B. The crossover approach to switching antipsychotics: what is the evidence? Schizophr Res. 2005;76(2-3):267-272. doi: 10.1016/j.schres.2005.01.009. [PubMed 15949658]
  60. Reus VI, Fochtmann LJ, Eyler AE, et al. The American Psychiatric Association practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia. Am J Psychiatry. 2016;173(5):543-546. doi:10.1176/appi.ajp.2015.173501 [PubMed 27133416]
  61. Rojo LE, Gaspar PA, Silva H, et al. Metabolic syndrome and obesity among users of second generation antipsychotics: a global challenge for modern psychopharmacology. Pharmacol Res. 2015;101:74-85. doi:10.1016/j.phrs.2015.07.022 [PubMed 26218604]
  62. Seitz DP, Gill SS. Neuroleptic malignant syndrome complicating antipsychotic treatment of delirium or agitation in medical and surgical patients: case reports and a review of the literature. Psychosomatics. 2009;50(1):8-15. doi:10.1176/appi.psy.50.1.8 [PubMed 19213967]
  63. Solmi M, Murru A, Pacchiarotti I, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag. 2017;13:757-777. doi:10.2147/TCRM.S117321 [PubMed 28721057]
  64. Solmi M, Pigato G, Kane JM, Correll CU. Clinical risk factors for the development of tardive dyskinesia. J Neurol Sci. 2018;389:21-27. doi:10.1016/j.jns.2018.02.012 [PubMed 29439776]
  65. Stevens DL. Association between selective serotonin-reuptake inhibitors, second-generation antipsychotics, and neuroleptic malignant syndrome. Ann Pharmacother. 2008;42(9):1290-1297. doi:10.1345/aph.1L066 [PubMed 18628446]
  66. Stroup TS, Gray N. Management of common adverse effects of antipsychotic medications. World Psychiatry. 2018;17(3):341-356. doi:10.1002/wps.20567 [PubMed 30192094]
  67. Stroup TS, Marder S. Pharmacotherapy for schizophrenia: acute and maintenance phase treatment. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 3, 2020.
  68. Szota AM, Araszkiewicz AS. The risk factors, frequency and diagnosis of atypical antipsychotic drug-induced hypothermia: practical advice for doctors. Int Clin Psychopharmacol. 2019;34(1):1-8. doi:10.1097/YIC.0000000000000244 [PubMed 30398998]
  69. Takeuchi H, Kantor N, Uchida H, Suzuki T, Remington G. Immediate vs gradual discontinuation in antipsychotic switching: a systematic review and meta-analysis. Schizophr Bull. 2017;43(4):862-871. doi: 10.1093/schbul/sbw171. [PubMed 28044008]
  70. Trollor JN, Chen X, Chitty K, Sachdev PS. Comparison of neuroleptic malignant syndrome induced by first- and second-generation antipsychotics. Br J Psychiatry. 2012;201(1):52-56. doi:10.1192/bjp.bp.111.105189 [PubMed 22626633]
  71. Uguz F. Second-generation antipsychotics during the lactation period: a comparative systematic review on infant safety. J Clin Psychopharmacol. 2016;36(3):244-252. [PubMed 27028982]
  72. van Harten PN, Hoek HW, Kahn RS. Acute dystonia induced by drug treatment. BMJ. 1999;319(7210):623-626. doi:10.1136/bmj.319.7210.623 [PubMed 10473482]
  73. van Marum RJ, Wegewijs MA, Loonen AJ, Beers E. Hypothermia following antipsychotic drug use. Eur J Clin Pharmacol. 2007;63(6):627-631. doi:10.1007/s00228-007-0294-4 [PubMed 17401555]
  74. van Winkel R, De Hert M, Wampers M, et al. Major changes in glucose metabolism, including new-onset diabetes, within 3 months after initiation of or switch to atypical antipsychotic medication in patients with schizophrenia and schizoaffective disorder. J Clin Psychiatry. 2008;69(3):472-479. doi:10.4088/jcp.v69n0320 [PubMed 18348593]
  75. Waln O, Jankovic J. An update on tardive dyskinesia: from phenomenology to treatment. Tremor Other Hyperkinet Mov (N Y). 2013;3:tre-03-161-4138-1. doi:10.7916/D88P5Z71 [PubMed 23858394]
  76. Wu CY, Mitchell SR, Seyfried LS. Quetiapine-induced hyperglycemic crisis and severe hyperlipidemia: a case report and review of the literature. Psychosomatics. 2014;55(6):686-691. doi:10.1016/j.psym.2014.07.002 [PubMed 25497507]
  77. Zonnenberg C, Bueno-de-Mesquita JM, Ramlal D, Blom JD. Hypothermia due to antipsychotic medication: a systematic review. Front Psychiatry. 2017;8:165. doi:10.3389/fpsyt.2017.00165 [PubMed 28936184]
Topic 126411 Version 73.0