Lurasidone for the Acute Treatment of Adults with Schizophrenia: What is the Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed?

New York Medical College, Valhalla, NY, USA.
Clinical Schizophrenia & Related Psychoses 07/2012; 6(2):76-85. DOI: 10.3371/CSRP.6.2.5
Source: PubMed


To describe the efficacy, safety and tolerability of lurasidone for the acute treatment of schizophrenia using the metrics number needed to treat (NNT) and number needed to harm (NNH).
Study data were pooled from six Phase II and III, 6-week, randomized, placebo-controlled trials that were conducted to test the efficacy and safety of lurasidone for the acute treatment of schizophrenia. Included were the following interventions: fixed doses of lurasidone 20, 40, 80, 120 and 160 mg/d; haloperidol 10 mg/d; olanzapine 15 mg/d; quetiapine extended-release 600 mg/d; placebo. The following outcomes were assessed: responder rates as defined by a reduction of ≥20, 30, 40 or 50% from baseline on the Positive and Negative Syndrome Scale (PANSS) total score; study completion; discontinuation due to an adverse event (AE); weight gain ≥7% from baseline; incidence of spontaneously reported AEs; incidence of total cholesterol ≥240 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, fasting triglycerides ≥200 mg/dL and glucose ≥126 mg/dL at endpoint. NNT for the efficacy outcomes were calculated after excluding one failed study. NNH for the safety/tolerability outcomes were calculated using all six studies. Likelihood of being helped or harmed (LHH) was also calculated to illustrate trade-offs between outcomes of improvement ≥30% on the PANSS vs. incidence of akathisia, nausea, sedation, somnolence and parkinsonism.
NNT vs. placebo for PANSS reductions ≥30% were 6, 6, 7 and 4 for lurasidone doses of 40, 80, 120 and 160 mg/d, respectively, and 4 and 3 for olanzapine 15 mg/d and quetiapine extended-release 600 mg/d, respectively. Lurasidone was not associated with any statistically significant disadvantages over placebo for weight gain or metabolic abnormalities; NNH vs. placebo for weight gain ≥7% from baseline was 4 for olanzapine and 9 for quetiapine extended-release in contrast to a NNH for this outcome ranging from 43 to 150 for lurasidone 40-160 mg/d. The 5 most consistently encountered adverse events attributable to lurasidone were akathisia, nausea, sedation, somnolence and parkinsonism, with NNH vs. placebo for lurasidone 40-120 mg/d ranging from 6 (akathisia with 120 mg/d) to 30 (parkinsonism with 80 mg/d). Lurasidone 160 mg/d appeared better tolerated than doses of 40, 80 or 120 mg/d for akathisia, nausea, sedation or somnolence, with no NNH values for these adverse events for 160 mg/d vs. placebo being statistically significant. LHH was favorable for lurasidone when contrasting PANSS reductions vs. adverse events.
NNT and NNH can help quantify efficacy, safety and tolerability outcomes and place lurasidone into clinical perspective. Advantages for lurasidone include a low propensity for weight gain and metabolic abnormalities. More commonly encountered adverse events include akathisia, nausea, sedation, somnolence and parkinsonism, but NNH values are generally in the double digits, reflecting an overall tolerable profile. Individual patient characteristics, values and preferences will need to be considered when selecting lurasidone over other antipsychotics.

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    • "Eligible patients were adults aged between 18 and 75 years with a diagnosis of schizophrenia (all studies) or schizoaffective disorder (Citrome et al., 2012). Other, more specific inclusion criteria, such as duration of illness and baseline disease severity, varied among studies. "
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    ABSTRACT: The objective of this analysis was to evaluate the effect of 12 months of treatment with lurasidone on weight in patients with schizophrenia. Post-hoc, observed-case analysis included pooled data from six studies on 40-160 mg/day lurasidone; two studies included active comparators (2-6 mg/day risperidone or 200-800 mg/day quetiapine XR). Overall, 593 patients completed 12 months of treatment (N=471 lurasidone, N=89 risperidone, N=33 quetiapine XR). The mean baseline weight was 72.8, 80.8, and 72.4 kg in the lurasidone, risperidone, and quetiapine XR groups, respectively. The mean weight change at month 12 was -0.4 kg with lurasidone, +2.6 kg with risperidone, and +1.2 kg with quetiapine XR. Weight gain of at least 7% from study baseline was observed in 16.0, 25.8, and 15.2% of patients, and weight loss of at least 7% was seen in 18.5, 6.7, and 9.1% of patients treated with lurasidone, risperidone, and quetiapine XR, respectively. A shift from normal/underweight baseline BMI status to overweight/obese at month 12 occurred in 10.2, 27.6, and 15.0% of patients in the lurasidone, risperidone, and quetiapine XR groups, respectively. Conversely, 14.3, 1.7, and 7.7% of patients, respectively, shifted from overweight/obese to normal/underweight. In summary, a low potential for clinically significant weight gain was observed in patients with schizophrenia treated continuously with lurasidone for 12 months.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
    Full-text · Article · Jul 2015 · International clinical psychopharmacology
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    • "Si les effets secondaires des APIG sont dominés par l'apparition d'effets extrapyramidaux, les APIIG sont souvent associés à un risque de survenue d'effets secondaires métaboliques (prise de poids, diabète, dyslipidémie). La lurasidone, comme l'aripiprazole, se distingue par son bon profil de tolérance métabolique contrairement à d'autres APIIG tels que l'olanzapine, la clozapine et de manière plus modérée avec la risperidone ou la quétiapine (Tableau 3) [31] [32]. La lurasidone possède également une bonne tolérance cardiovasculaire, sans hypotension orthostatique ni allongement de l'intervalle QT, qu'elle que soit la posologie utilisée. "
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    ABSTRACT: La lurasidone est un nouvel antipsychotique de deuxième génération approuvée par l’Agence européenne du médicament en mars 2014 dans le traitement de la schizophrénie. Comme les autres molécules de seconde génération, la lurasidone est un puissant antagoniste des récepteurs dopaminergiques D2 et sérotoninergiques 5HT2A, mais se différencie par son profil d’action sur certains récepteurs en ayant une importante affinité pour les récepteurs sérotoninergiques 5HT7, une faible affinité pour les récepteurs α1 et α2C-adrénergiques et sérotoninergiques 5HT2C, et aucune d’affinité pour les récepteurs histaminergiques H1 ou muscariniques M1. La lurasidone a démontré une efficacité à court terme, supérieure au placebo dans le traitement des épisodes aigus de patients schizophrènes dans plusieurs études contrôlées randomisées. D’action rapide, une différence significative avec le placebo était observée dès la première semaine de traitement (j3 à j7). Les résultats des études ne suggèrent pas de relation dose-efficacité pour des posologies comprises entre 40 et 160 mg/jour de lurasidone. Une réduction des symptômes dépressifs et une amélioration des troubles cognitifs associés à la schizophrénie ont aussi été observées mais dans des études de qualités méthodologiques moindres. La lurasidone se distingue des autres antipsychotiques de seconde génération par un profil de tolérance métabolique et cardiovasculaire favorable. Cependant, il semble exister un lien significatif quoique modéré avec l’apparition d’akathisie, de symptômes extrapyramidaux et d’hyperprolactinémie en début de traitement. D’autres perspectives thérapeutiques de la lurasidone ont récemment été étudiées, notamment dans la dépression bipolaire.
    Full-text · Article · Nov 2014 · L Encéphale
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    ABSTRACT: Lurasidone is a newer “atypical” or “secondgeneration” antipsychotic that has received regulatory approval in the US and Canada for the treatment of schizophrenia. Recent changes in lurasidone product labeling include an expansion of the recommended dose range from 40–80 mg/day to 40–160 mg/day, administered once-daily with food. The recommended starting dose is 40 mg/day. Initial dose titration is not required. Efficacy for the treatment of acute episodes of schizophrenia was established in five, 6-week, fixed-dose, randomized, placebo-controlled trials. Additional short-term studies in patients with schizophrenia include a 3-week, randomized, double-blind trial comparing lurasidone with ziprasidone on safety and tolerability outcomes, and a 6-week, randomized, open-label switch study. Available long-term data includes a 12-month, doubleblind safety and tolerability study comparing lurasidone with risperidone; a 6-month, openlabel extension study for one of the shortterm registration studies where patients were initially randomized to receive lurasidone, olanzapine, or placebo; and a 12-month, doubleblind extension study comparing lurasidone with quetiapine extended-release after having received lurasidone, quetiapine extendedrelease, or placebo for 6 weeks. The totality of the evidence supports the overall tolerability of lurasidone, with minimal weight gain and no clinically-meaningful alterations in glucose, lipids, or the electrocardiogram corrected QT (ECG QTc) interval. The most commonly encountered adverse events that can be observed with lurasidone are somnolence, akathisia, nausea, and parkinsonism. Additional clinical trials are underway for the use of lurasidone in patients with bipolar disorder, including major depressive episodes in patients with bipolar I disorder, and in bipolar and schizophrenia maintenance. Principal advantages over some other second-generation antipsychotics are lurasidone’s highly favorable metabolic profile and once-daily dosing regimen. Additional studies are desirable to directly compare and contrast lurasidone’s efficacy with other antipsychotic agents.
    No preview · Article · Oct 2012 · Advances in Therapy
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