Switching Strategies

See the results of the 6-week, open-label LATUDA Switch Study.
Watch the three different dosing strategies utilized in the following video.


Joseph P. McEvoy, MD, is a
professor of Psychiatry and
Behavioral Sciences at Duke
University School of Medicine
Durham, NC.

What’s the role of switching in therapy?

We sat down with Dr. Joseph McEvoy and discussed the results of his trial of switching patients to LATUDA.

Q: Can you tell us a little about the extent of your experience with Latuda® (lurasidone HCl)?

I have an inpatient service at a state psychiatric hospital where I treat adult patients with schizophrenia, and I have a large outpatient service where I follow adult patients with schizophrenia. I have experience using LATUDA clinically for these patients. In addition, I had the opportunity to be the academic Principal Investigator for the Switch Study, looking at three reasonable pathways for transitioning patients from other antipsychotic medications to LATUDA.

Q: What was the motivation for conducting a Switch Study with LATUDA?

We know from long-term trials like the Clinical Antipsychotic Trials of Intervention Effectiveness study, or CATIE trial, that up to 75% of adult patients with schizophrenia will have to switch their prescribed primary antipsychotic medication.1* Even a patient who has had a reasonable therapeutic response may need to switch medicines. In addition, most of the registration trials for LATUDA looked at acutely psychotic patients at the point when LATUDA was being started. This trial took place where a lot of switches actually occur—in the outpatient clinic—and focused on outpatients whose illness was clinically stable and not acutely exacerbated. It was required that they have some degree of stability in their situation but still had an indication for a therapeutic switch. In a systematic study like this, you gain information about strategies in settings that closely reflect the settings that real-world patients are in.

Q: What is your preferred way to switch antipsychotics in adult patients with schizophrenia?

In my opinion, one approach that doesn’t tend to work well is stopping the current antipsychotic immediately and then starting the new antipsychotic at a low dose and building it up gradually. In general, we now take approaches where over a 1- to 4-week period—depending on the clinician and the patient—we taper, we start the new antipsychotic, and we get it immediately or rapidly to a therapeutic dose while simultaneously yet gradually taking away the current antipsychotic. In the Switch Study with LATUDA, all three dosing strategies employed were reasonable.

Q: How would you help the community psychiatrist understand the primary endpoint of the Switch Study?

When clinicians are switching treatments, there are two things they don’t want. They don’t want the patient to have an insufficient therapeutic response—either they don’t improve on the new drug or their psychopathology worsens on the new drug. And they don’t want the patient to experience distressing side effects that often lead to discontinuation of the medication. The primary endpoint for the Switch Study focused on time to treatment failure of LATUDA, defined prospectively as inadequate or insufficient clinical response or exacerbation (worsening of the underlying schizophrenia) or a discontinuation due to an adverse event.

Q: What were the main findings of the LATUDA Switch Study?

Over the 6-week period of the study, 82.5% of randomized patients completed the study, and there was no difference shown across three dosing strategies, supporting the proposition that LATUDA was delivering therapeutic efficacy for the majority of patients and was generally well tolerated.2 The safety and tolerability data in the Switch Study were in keeping with the safety and tolerability data from the registration trials.

Q: What advice would you have for the practicing clinician who is considering switching an adult patient with schizophrenia to LATUDA?

I think the Switch Study has shown that the majority of adult patients with schizophrenia who need to be switched can be successfully switched to LATUDA. When switching, the clinician would be wise to gradually reduce the dose of the current antipsychotic over at least a week or, perhaps, 2 weeks.

Dr. McEvoy is an investigator and has conducted scientific studies/ trials for PsychoGenics Inc.; Genentech, Inc., a member of the Roche Group; and Sunovion Pharmaceuticals Inc. He has served as a CME meeting participant/leader for Genentech, Inc., a member of the Roche Group. Dr. McEvoy has received honoraria for speaking on behalf of Eli Lilly and Company, Merck, and Sunovion Pharmaceuticals Inc.

*LATUDA was not available at the time CATIE was conducted and was not part of this study.

Past Publications

LATUDA Connections

Issue 1 | October 2012

Features commentary from Dr. Herbert Meltzer on Study 3 efficacy data and Study 3 Open-Label Extension findings. Also provides an overview of LATUDA safety data from the prescribing information. Plus an overview of recent prescribing information updates, including updated dosing recommendations.

LATUDA Connections

Issue 2

An in-depth interview with Dr. Joseph McEvoy about the results of the 6-week, open-label LATUDA Switch Study. Highlights from the trial results, and additional safety data from the prescribing information. Also included: Upcoming conventions to mark on your calendar.

LATUDA Reprints

Meltzer HY, et al. Am J Psychiatry. 2011;168:957-967.

Original publication of results from Study 3, a 6-week, randomized, double-blind, placebo- and olanzapine-controlled trial to evaluate the efficacy and safety of LATUDA 40 mg/day and 80 mg/day. Olanzapine 15 mg/day was included as an active control to assess sensitivity.

Nakamura M, et al. J Clin Psychiatry. 2009;70:829-836.

Original publication of results from Study 2, a 6-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of LATUDA 80 mg/day.

Past Videos


Study 3 Open-Label Extension

Issue 1 | October 2012

See the clinical profile of the Study 3 open-label extension come to life in
this video.



See full prescribing information for complete boxed warning.
  • Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.
  • LATUDA is not approved for the treatment of patients with dementia-related psychosis.


LATUDA is contraindicated in the following:

  • Any patient with a known hypersensitivity to lurasidone HCl or any components in the formulation. Angioedema has been observed with lurasidone.
  • Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole).
  • Concomitant use with strong CYP3A4 inducers (e.g., rifampin).


Cerebrovascular Adverse Reactions, Including Stroke: In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks) including fatalities compared to placebo-treated subjects. LATUDA is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS, a potentially fatal symptom complex, has been reported with administration of antipsychotic drugs, including LATUDA. NMS can cause hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available.

Tardive Dyskinesia (TD): TD is a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements that can develop in patients with antipsychotic drugs. There is no known treatment for established cases of TD, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses. Given these considerations, LATUDA should be prescribed in a manner that is most likely to minimize the occurrence of TD. If signs and symptoms appear in a patient on LATUDA, drug discontinuation should be considered.

Metabolic Changes

  • Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
  • Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.
  • Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

Hyperprolactinemia: As with other drugs that antagonize dopamine D2 receptors, LATUDA elevates prolactin levels. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. In short-term, placebo-controlled studies, the median change from baseline to endpoint in prolactin levels for LATUDA-treated females was –0.2 ng/mL and was 0.5 ng/mL for males. The proportion of female patients with prolactin elevations ≥5x ULN was 5.7% for LATUDA-treated patients versus 2.0% for placebo- treated female patients. The proportion of male patients with prolactin elevations >5x ULN was 1.6% versus 0.6% for placebo-treated male patients.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia has been reported during treatment with antipsychotic agents. Agranulocytosis (including fatal cases) has been reported with other agents in the class. Patients with a preexisting low white blood cell count (WBC) or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy, and LATUDA should be discontinued at the first sign of a decline in WBC in the absence of other causative factors.

Orthostatic Hypotension and Syncope: LATUDA may cause orthostatic hypotension. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension and in patients with known cardiovascular disease or cerebrovascular disease.

Seizures: LATUDA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold (e.g., Alzheimer's dementia).

Potential for Cognitive and Motor Impairment: In short-term, placebo-controlled trials, somnolence was reported in 17.0% (256/1508) of patients treated with LATUDA compared to 7.1% (50/708) of placebo patients, respectively. Patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy with LATUDA does not affect them adversely.

Body Temperature Regulation: Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing LATUDA for patients who will be experiencing conditions that may contribute to an elevation in core body temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.

Suicide: The possibility of suicide attempt is inherent in psychotic illness and close supervision of high-risk patients should accompany drug therapy. Prescriptions for LATUDA should be written for the smallest quantity of tablets consistent with good patient management in order to reduce the risk of overdose.

Dysphagia: Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer's dementia. LATUDA and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.


Commonly Observed Adverse Reactions: (incidence ≥5% and at least twice the rate of placebo) in patients treated with LATUDA were somnolence, akathisia, nausea and parkinsonism.

Before prescribing LATUDA, please read the full Prescribing Information, including Boxed Warning.

References: 1. Lieberman JA, Stroup TS, McEvoy JP, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med. 2005;353:1209-1223. 2. Data on file. Sunovion Pharmaceuticals Inc.