Advice

Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in September 2014. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

Lurasidone (Latuda, Sunovion Pharmaceuticals Europe Ltd) is licensed for treating schizophrenia in adults aged 18 years and over. It was launched in the UK in August 2014. Evidence from 5 short-term and 3 long‑term studies suggests that lurasidone is effective at treating psychotic symptoms, and at preventing relapse in adults with schizophrenia. The European Public Assessment Report [EPAR] for lurasidone states that the adverse event profile of lurasidone is similar to that for other second-generation antipsychotics, the most common adverse events being akathisia and somnolence. NICE published an evidence summary on lurasidone for schizophrenia in April 2013 (ESNM15). However, a further long‑term study has been published in full since that summary was prepared, and another long‑term study is described in the EPAR for lurasidone. These have been reviewed in this evidence summary, which now updates and replaces the earlier evidence summary on lurasidone.

Effectiveness

  • In 292 adults with schizophrenia, lurasidone was found to be non-inferior to quetiapine prolonged release for preventing relapse of schizophrenia at 12 months. Probability of relapse was 23.7% with lurasidone compared with 33.6% with quetiapine prolonged release, (hazard ratio [HR] 0.728, 95% confidence interval [CI] 0.410 to 1.295, log-rank p=0.280).

  • In 285 adults with a primary diagnosis of schizophrenia, the probability of relapse up to week 28 was 42.2% with lurasidone and 51.2% with placebo. There was a statistically significant increase in time to relapse with lurasidone compared with placebo (p=0.039).

Safety

  • The EPAR states that lurasidone has a spectrum of adverse events that is similar to that for other second-generation antipsychotics.

  • From pooled safety data, there was some evidence of a dose-related effect on the incidence of extrapyramidal symptoms such as dystonia, tremor, Parkinsonism and salivary hypersecretion. These occurred most frequently in the lurasidone 111 mg daily group.

  • Lurasidone should be used with caution in people at high risk of suicide; people with Parkinson's disease; people with an increased risk of QT-interval prolongation; people with a history of seizures; people who are older and have dementia; people who already have diabetes or who are at high risk of developing it; people at an increased risk of hypotension; and people with renal and hepatic impairment.

  • Concomitant administration of lurasidone is contraindicated with strong inhibitors (for example clarithromycin) or inducers (for example carbamazepine) of the CYP3A4 enzyme. Dose adjustment of lurasidone is needed if used with moderate CYP3A4 inhibitors or inducers.

User factors

  • In 285 adults with a primary diagnosis of schizophrenia, the rate of discontinuation due to all causes was statistically significantly higher in the lurasidone group compared with the risperidone group (64% compared with 52% respectively, p=0.004).

  • The most common adverse events observed with lurasidone are akathisia and somnolence (both occurring with an incidence 1 in 10 or more).

  • People should avoid drinking grapefruit juice whilst taking lurasidone as it may increase the serum concentration of lurasidone.

Resource implications

  • The cost for 28 days' treatment with lurasidone at a dose of 37−148 mg daily is estimated to be £90.72 to £181.44 (MIMS, September 2014).

  • The cost for 28 days' treatment with alternative second-generation antipsychotics ranges from £0.97 to £194.56 depending on the drug and dose. See the alternative treatments section for more information.

Introduction and current guidance

The NICE clinical guideline on psychosis and schizophrenia in adults describes schizophrenia as a major psychiatric disorder, or cluster of disorders, characterised by psychotic symptoms that alter a person's perception, thoughts, mood and behaviour.

The NICE clinical guideline recommends that people with a first episode of schizophrenia, or an acute exacerbation or recurrence of schizophrenia, should be offered oral antipsychotic medication in conjunction with psychological interventions. The choice of antipsychotic medication should be made by the service user and healthcare professional together, taking into account the views of the carer if the service user agrees. Information should be provided on, and there should be discussion about, the likely benefits and possible side effects of each drug, including metabolic, extrapyramidal, cardiovascular, hormonal and other side effects (including unpleasant subjective experiences).

Full text of Introduction and current guidance.

Product overview

Lurasidone (Latuda, Sunovion Pharmaceuticals Europe Ltd) is licensed for treating schizophrenia in adults aged 18 years and over. It was launched in the UK in August 2014.

The recommended starting dose is 37 mg once daily. Dose increases should be based on physician judgement and observed clinical response. Lurasidone is effective at a dose range of 37−148 mg daily, and the maximum dose should not exceed 148 mg daily. It should be taken once daily together with a meal.

For people with moderate or severe renal impairment, end-stage renal disease, moderate or severe hepatic impairment, or people taking moderate CYP3A4 inhibitors, the recommended starting and maximum doses of lurasidone are lower.

The cost for 28 days' treatment with lurasidone at a dose of 37−148 mg daily is estimated to be £90.72 to £181.44 (MIMS, September 2014).

Full text of Product overview.

Evidence review

  • The EPAR for lurasidone discusses the short- and long-term studies supporting the marketing authorisation for lurasidone for treating schizophrenia in adults. The EPAR states that overall, short-term efficacy of lurasidone has been sufficiently demonstrated for the dose range 37−148 mg lurasidone daily for treating psychotic symptoms in adults with schizophrenia.

  • This evidence summary discusses in further detail, the 3 studies that provide the best long-term evidence of efficacy and safety for lurasidone for treating schizophrenia in adults.

  • Loebel et al. (2013a) was a 12-month, double-blind, active comparator, non-inferiority study in 292 adults with a diagnosis of schizophrenia, using a previously randomised population from a 6-week double-blind RCT. Lurasidone (at a mean modal dose of 124.2 mg lurasidone hydrochloride daily) was found to be non-inferior to quetiapine prolonged release (XR; at a mean modal dose of 637.6 mg daily) for preventing relapse of schizophrenia at 12 months. The probability of relapse was 23.7% with lurasidone compared with 33.6% with quetiapine prolonged release (HR 0.728, 95% CI 0.410 to 1.295, log-rank p=0.280). The upper limit of the 95% CI was less than the pre-specified margin of 1.93; therefore lurasidone was shown to be non-inferior to quetiapine prolonged release in terms of relapse prevention. Compared with people in the quetiapine prolonged release group, people in the lurasidone group had a statistically significantly greater improvement in the secondary efficacy outcomes of change from 6-week study baseline at 12 months in Positive and Negative Syndrome Scale (PANSS) total score, and PANSS positive subscale score. For PANSS negative subscale score and Clinical Global Impressions Severity scale (CGI-S) score there was no significant difference between lurasidone and quetiapine (p value not stated).

  • Citrome et al. (2012) was a 12-month, double-blind, active comparator RCT in 629 adults with schizophrenia or schizoaffective disorder. The trial was primarily a safety and tolerability study and efficacy measures were secondary outcomes. The rate of discontinuation due to all causes was statistically significantly higher in the lurasidone group compared with the risperidone group (64% compared with 52% respectively, p=0.004).

  • Study D1050238 (NCT01435928; reported in the EPAR for lurasidone) was a double-blind, placebo-controlled randomised withdrawal study of lurasidone (37 mg or 74 mg lurasidone daily, dosed flexibly) in adults with a primary diagnosis of schizophrenia. The first part of the study consisted of a screening phase and an open-label stabilisation phase (up to a maximum of 24 weeks, n=676). Participants whose schizophrenia responded to lurasidone treatment and met stabilisation criteria for at least 12 consecutive weeks were eligible to enter a randomised double-blind, withdrawal phase (up to a maximum of 28 weeks, n=144 randomised to lurasidone, n=141 randomised to placebo). Overall 30% of people in the lurasidone group, and 41% of people in the placebo group experienced relapse at some point during the study. Up to week 28, the probability of relapse was 42.2% in the lurasidone group, and 51.2% in the placebo group, and there was a statistically significant increase in time to relapse with lurasidone compared with placebo (p=0.039). PANSS total score and CGI-S increased (worsened) statistically significantly less in people in the lurasidone compared with the placebo group (p=0.019 for PANSS total score, and p=0.002 for CGI-S).

  • The EPAR for lurasidone concluded that overall, taking the results from all 3 long-term studies into account, the long-term efficacy for lurasidone has been sufficiently demonstrated.

  • The EPAR for lurasidone pooled safety data from studies including a total 5068 participants (3502 treated with lurasidone, 724 with placebo and 842 with other medications). The EPAR concluded that lurasidone has a spectrum of adverse events that is similar to that for other second-generation antipsychotics. The incidence of some common adverse events including akathisia, somnolence and dizziness was dose related. In addition there was some evidence of a dose-related effect on the incidence of extrapyramidal symptoms such as dystonia, tremor, Parkinsonism and salivary hypersecretion. These adverse events occurred most frequently in the lurasidone 111 mg daily group. Nausea and vomiting occurred with a higher incidence for lurasidone than for the comparators. Effects of lurasidone on blood lipids, glucose and glycated haemoglobin (HbA1c) were limited, and the effect on weight increase was moderate, which is considered to indicate a relatively favourable metabolic profile.

  • The summary of product characteristics for lurasidone (Latuda) states that in clinical studies, the most common adverse events occurring in at least 1 in 10 participants were akathisia and somnolence which were dose-related up to 111 mg daily.

  • For a full list of cautions and contraindications with lurasidone, see the summary of product characteristics for lurasidone (Latuda).

Full text of Evidence review.

Context

The NICE clinical guideline on psychosis and schizophrenia in adults recommends that the choice of antipsychotic medication should be made by the service user and healthcare professional together, taking into account the views of the carer if the service user agrees. Information should be provided on, and there should be discussion about, the likely benefits and possible side effects of each drug, including metabolic, extrapyramidal, cardiovascular, hormonal and other side effects (including unpleasant subjective experiences).

The second-generation antipsychotics currently listed in the British national formulary (September 2014) are amisulpride, aripiprazole, clozapine, olanzapine, paliperidone, quetiapine, and risperidone.

The BNF chapter on antipsychotic drugs describes the relative efficacy and adverse effects of different antipsychotics. A National Prescribing Centre patient decision aid provides a guide to the relative adverse effects of different antipsychotics, based on information available at that time (2009).

Full text of Context.

Estimated impact for the NHS

It is likely that lurasidone may represent an additional treatment option alongside existing antipsychotics for adults with schizophrenia. Local decision makers will need to consider the available evidence on efficacy and safety, as well as the higher cost of lurasidone compared with some existing antipsychotic medications (see the alternative treatments section for more information). As with choice of all antipsychotic medicines, individual factors for people with schizophrenia are a key factor when making treatment decisions.

Full text of Estimated impact for the NHS.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.