Other Warnings/Precautions

• Use with caution in patients with conditions that predispose to hypotension (dehydration, overheating)

• Dysphagia has been associated with antipsychotic use, and lurasidone should be used cautiously in patients at risk for aspiration pneumonia

Do Not Use

• If patient is taking a strong CYP 3A4 inhibitor (e.g., ketoconazole) or inducer (e.g., rifampin)

• In patients with a history of angioedema

• If there is a proven allergy to lurasidone

LURASIDONE: SPECIAL POPULATIONS

Renal Impairment

• Moderate and severe impairment: initial 20 mg/day; maximum dose 80 mg/day

Hepatic Impairment

• Moderate impairment: initial 20 mg/day; maximum dose 80 mg/day

• Severe impairment: initial 20 mg/day; maximum dose 40 mg/day

Cardiac Impairment

• Should be used with caution because of theoretical risk of orthostatic hypotension, although low potency at alpha 1 receptors suggests this risk may be less than for some other antipsychotics

• Lurasidone does not have a warning for QTc prolongation

Elderly

• In general, no dose adjustment is necessary for elderly patients

• However, some elderly patients may tolerate lower doses better

• Although atypical antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with dementia-related psychosis

• Elderly patients with dementia-related psychosis treated with atypical antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

Children and Adolescents

• Safety and efficacy have not been established

• Children and adolescents using lurasidone may need to be monitored more often than adults

Pregnancy

• Risk Category B [animal studies do not show adverse effects; no controlled studies in humans]

• There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• Not teratogenic in rodents

• Psychotic symptoms may worsen during pregnancy and some form of treatment may be necessary

• Lurasidone may be preferable to anticonvulsant mood stabilizers if treatment is required during pregnancy

• Pregnancy exposure should be reported to the manufacturer and a national pregnancy registry, where available

Breast Feeding

• Unknown if lurasidone is secreted in human breast milk, but all psychotropics assumed to be secreted in breast milk

✽ Recommended either to discontinue drug or bottle feed unless the potential benefit to the mother justifies the potential risk to the child

• Infants of women who choose to breast feed while on lurasidone should be monitored for possible adverse effects

LURASIDONE: THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients requiring rapid onset of antipsychotic action without dosage titration

• Patients who wish to take an antipsychotic once a day

• Patients experiencing weight gain from other antipsychotics or who wish to avoid weight gain

Potential Disadvantages

• Patients who cannot take a medication consistently with food

Primary Target Symptoms

• Positive symptoms of psychosis

• Negative symptoms of psychosis

• Cognitive symptoms

• Unstable mood (both depression and mania)

• Aggressive symptoms

Pearls

• Clinical trials suggest that lurasidone is well tolerated with a favorable balance of efficacy and safety

• One of the few “metabolically friendly” antipsychotics

• Neutral for weight gain (1–2 pounds weight gain in short-term studies, with 1–2 pounds weight loss in long-term studies)

• Neutral for lipids (triglycerides and cholesterol)

• Neutral for glucose

• Only atypical antipsychotic documented not to cause QTc prolongation, and one of the few atypical antipsychotics without a QTc warning

• Seems to have low-level extrapyramidal side effects, especially when dosed at bedtime

• Somnolence and akathisia are the most common side effects in short-term clinical trials of schizophrenia that dosed lurasidone in the daytime, but these adverse effects were reduced in a controlled study of lurasidone administered at night with food

• Nausea and occasional vomiting occurred in bipolar depression studies especially at higher doses

• Nausea and vomiting generally rapidly abates within a few days or can be avoided by slow dose titration and giving lower doses

• Prolactin elevations low and generally transient

• Agitation experienced by some patients

• Receptor binding profile suggests favorable potential as an antidepressant

• 5HT7 antagonism is antidepressant in animal models and has pro-cognitive actions in animal models

• 5HT7 antagonism and 5HT1A partial agonism enhance serotonin levels in animals treated with SSRIs/SNRIs, suggesting use for lurasidone as an augmenting agent to SSRIs/SNRIs in depression

• 5HT7 antagonism plus the absence of D1, H1, and M1 antagonism suggest potential for cognitive improvement

• Lack of D1 antagonist, anticholinergic, and antihistamine properties may explain relative lack of cognitive side effects in most patients

• Not approved for mania, but almost all atypical antipsychotics approved for acute treatment of schizophrenia have proven effective in the acute treatment of mania as well

• Patients with inadequate responses to atypical antipsychotics may benefit from determination of plasma drug levels and, if low, a dosage increase even beyond the usual prescribing limits

• Patients with inadequate responses to atypical antipsychotics may also benefit from a trial of augmentation with a conventional antipsychotic or switching to a conventional antipsychotic

• However, long-term polypharmacy with a combination of a conventional antipsychotic with an atypical antipsychotic may combine their side effects without clearly augmenting the efficacy of either

• For treatment-resistant patients, especially those with impulsivity, aggression, violence, and self-harm, long-term polypharmacy with 2 atypical antipsychotics or with 1 atypical antipsychotic and 1 conventional antipsychotic may be useful or even necessary while closely monitoring

• In such cases, it may be beneficial to combine 1 depot antipsychotic with 1 oral antipsychotic

THE ART OF SWITCHING