Double-blind, placebo-controlled study of lurasidone monotherapy for the treatment of bipolar I depression

Tadafumi Kato, Jun Ishigooka, Mari Miyajima, Kei Watabe, Tomohiro Fujimori, Takahiro Masuda, Teruhiko Higuchi, Eduard Vieta, Tadafumi Kato, Jun Ishigooka, Mari Miyajima, Kei Watabe, Tomohiro Fujimori, Takahiro Masuda, Teruhiko Higuchi, Eduard Vieta

Abstract

Aim: Previous studies conducted primarily in the USA and Europe have demonstrated the efficacy and safety of lurasidone 20-120 mg/day for the treatment of bipolar I depression. The aim of the current study was to evaluate the efficacy and safety of lurasidone monotherapy for the treatment of bipolar I depression among patients from diverse ethnic backgrounds, including those from Japan.

Methods: Patients were randomly assigned to double-blind treatment for 6 weeks with lurasidone, 20-60 mg/day (n = 184) or 80-120 mg/day (n = 169), or placebo (n = 172). The primary end-point was change from baseline to Week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Results: Lurasidone treatment significantly reduced mean MADRS total scores from baseline to Week 6 for the 20-60-mg/day group (-13.6; adjusted P = 0.007; effect size = 0.33), but not for the 80-120-mg/day group (-12.6; adjusted P = 0.057; effect size = 0.22) compared with placebo (-10.6). Treatment with lurasidone 20-60 mg/day also improved MADRS response rates, functional impairment, and anxiety symptoms. The most common adverse events associated with lurasidone were akathisia and nausea. Lurasidone treatments were associated with minimal changes in weight, lipids, and measures of glycemic control.

Conclusion: Monotherapy with once daily doses of lurasidone 20-60 mg, but not 80-120 mg, significantly reduced depressive symptoms and improved functioning in patients with bipolar I depression. Results overall were consistent with previous studies, suggesting that lurasidone 20-60 mg/day is effective and safe in diverse ethnic populations, including Japanese.

Keywords: antipsychotic agents; bipolar disorder; depressive disorder; lurasidone hydrochloride.

© 2020 The Authors Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

Figures

Fig. 1
Fig. 1
Patient disposition.
Fig. 2
Fig. 2
(a) Change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) total score (mixed‐effects model for repeated measures [MMRM]) – intent‐to‐treat (ITT) population. *P < 0.05, **P < 0.01, ***P < 0.001 (vs placebo). Adjustments for multiple comparisons by Hochberg (only at Week 6) , Placebo (n = 171); , Lurasidone 20–60 mg/day (n = 182); , Lurasidone 80–120 mg/day (n = 169). (b) Change from baseline in Clinical Global Impression: Bipolar Version – Severity of Illness (CGI‐BP‐S) Depression score (MMRM) – ITT population. *P < 0.05, **P < 0.01, ***P < 0.001 (vs placebo). No adjustments for multiple comparisons , Placebo (n = 171); , Lurasidone 20–60 mg/day (n = 182); , Lurasidone 80–120 mg/day (n = 169).

References

    1. Merikangas KR, Jin R, He JP et al Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey initiative. Arch. Gen. Psychiatry 2011; 68: 241–251.
    1. Nishi D, Ishikawa H, Kawakami N. Prevalence of mental disorders and mental health service use in Japan. Psychiatry Clin. Neurosci. 2019; 73: 458–465.
    1. Vos T, Flaxman AD, Naghavi M et al Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2163–2169.
    1. Fajutrao L, Locklear J, Priaulx J, Heyes A. A systematic review of the evidence of the burden of bipolar disorder in Europe. Clin. Pract. Epidemiol. Mental Health 2009; 5: 3.
    1. Gardner HH, Kleinman NL, Brook RA, Rajagopalan K, Brizee TJ, Smeeding JE. The economic impact of bipolar disorder in an employed population from an employer perspective. J. Clin. Psychiatry 2006; 67: 1209–1218.
    1. Dean BB, Gerner D, Gerner RH. A systematic review evaluating health‐related quality of life, work impairment, and healthcare costs and utilization in bipolar disorder. Curr. Med. Res. Opin. 2004; 20: 139–154.
    1. Crump C, Sundquist K, Winkleby MA, Sundquist J. Comorbidities and mortality in bipolar disorder: A Swedish national cohort study. JAMA Psychiatry 2013; 70: 931–939.
    1. Correll CU, Solmi M, Veronese N et al Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: A large‐scale meta‐analysis of 3,211,768 patients and 113,383,368 controls. World Psychiatry 2017; 16: 163–180.
    1. Vancampfort D, Correll CU, Galling B et al Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: A systematic review and large scale meta‐analysis. World Psychiatry 2016; 15: 166–174.
    1. Walker ER, McGee RE, Druss BG. Mortality in mental disorders and global disease burden implications: A systematic review and meta‐analysis. JAMA Psychiatry 2015; 72: 334–341.
    1. Dilsaver SC. An estimate of the minimum economic burden of bipolar I and II disorders in the United States. J. Affect. Disord. 2011; 129: 79–83.
    1. Watanabe K, Harada E, Inoue T, Tanji Y, Kikuchi T. Perceptions and impact of bipolar disorder in Japan: Results of an internet survey. Neuropsychiatr. Dis. Treat. 2016; 12: 2981–2987.
    1. Calabrese JR, Hirschfeld RM, Frye MA, Reed ML. Impact of depressive symptoms compared with manic symptoms in bipolar disorder: Results of a US community based sample. J. Clin. Psychiatry 2004; 65: 1499–1504.
    1. Judd LL, Akiskal HS, Schettler PJ et al The long term natural history of the weekly symptomatic status of bipolar I disorder. Arch. Gen. Psychiatry 2002; 59: 530–537.
    1. Vieta E, Berk M, Schulze TG et al Bipolar disorders. Nat. Rev. Dis. Primers. 2018; 4: 18008.
    1. Kato T. Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies. Psychiatry Clin. Neurosci. 2019; 73: 526–540.
    1. Ishibashi T, Horisawa T, Tokuda K et al Pharmacological profile of lurasidone, a novel antipsychotic agent with potent 5‐hydroxytryptamine 7 (5‐HT7) and 5‐HT1A receptor activity. J. Pharmacol. Exp. Ther. 2010; 334: 171–181.
    1. Hedlund PB. The 5‐HT7 receptor and disorders of the nervous system: An overview. Psychopharmacology 2009; 206: 345–354.
    1. Cates LN, Roberts AJ, Huitron‐Resendiz S, Hedlund PB. Effects of lurasidone in behavioral models of depression: Role of the 5‐HT7 receptor subtype. Neuropharmacology 2013; 70: 211–217.
    1. Loebel A, Cucchiaro J, Silva R et al Lurasidone monotherapy in the treatment of bipolar I depression: A randomized, double‐blind, placebo‐controlled study. Am. J. Psychiatry 2014; 171: 160–168.
    1. Loebel A, Cucchiaro J, Silva R et al Lurasidone as adjunctive therapy with lithium or valproate for the treatment of bipolar I depression: A randomized, double‐blind, placebo‐controlled study. Am. J. Psychiatry 2014; 171: 169–177.
    1. Fountoulakis KN. The International College of Neuro‐Psychopharmacology (CINP) treatment guidelines for bipolar disorder in adults (CINP‐BD‐2017), Part 3: The clinical guidelines. Int. J. Neuropsychopharmacol. 2017; 20: 180–195.
    1. Malhi GS. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust. N. Z. J. Psychiatry 2015; 49: 1087–1206.
    1. Yatham LN. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018; 20: 97–170.
    1. Sheehan DV, Lecrubier Y, Sheehan KH et al The MINI‐International Neuropsychiatric Interview (MINI): The development and validation of a structured diagnostic psychiatric interview for DSMIV and ICD‐10. J. Clin. Psychiatry 1998; 59: 22–33.
    1. Montgomery SA, Åsberg M. A new depression scale designed to be sensitive to change. Br. J. Psychiatry 1979; 134: 382–389.
    1. Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: Reliability, validity and sensitivity. Br. J. Psychiatry 1978; 133: 429–435.
    1. Chappell P, Feltner DE, Makumi C, Stewart M. Initial validity and reliability data on the Columbia‐Suicide Severity Rating Scale. Am. J. Psychiatry 2012; 169: 662–663.
    1. Spearing MK, Post RM, Leverich GS, Brandt D, Nolen W. Modification of the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): The CGI‐BP. Psychiatry Res. 1997; 73: 159–171.
    1. Sheehan DV. The Anxiety Disease. Bantam Books, New York, NY, 1983.
    1. Hamilton M. The assessment of anxiety states by rating. Br. J. Med. Psychol. 1959; 32: 50–55.
    1. Bech P, Tanghøj P, Andersen HF, Overø K. Citalopram dose‐response revisited using an alternative psychometric approach to evaluate clinical effects of four fixed citalopram doses compared to placebo in patients with major depression. Psychopharmacology 2002; 163: 20–25.
    1. Inada T, Beasley CM Jr, Tanaka Y, Walker DJ. Extrapyramidal symptom profiles assessed with the Drug‐Induced Extrapyramidal Symptom Scale: Comparison with Western scales in the clinical double‐blind studies of schizophrenic patients treated with either olanzapine or haloperidol. Int. Clin. Psychopharmacol. 2003; 18: 39–48.
    1. Selle V, Schalkwijk S, Vázquez GH, Baldessarini RJ. Treatments for acute bipolar depression: Meta‐analyses of placebo‐controlled, monotherapy trials of anticonvulsants, lithium and antipsychotics. Pharmacopsychiatry 2014; 47: 43–52.
    1. Potkin SG, Keator DB, Kesler‐West ML et al D2 receptor occupancy following lurasidone treatment in patients with schizophrenia or schizoaffective disorder. CNS Spectr. 2014; 19: 176–181.
    1. de Haan L, Lavalaye J, van Bruggen M et al Subjective experience and dopamine D2 receptor occupancy in patients treated with antipsychotics: Clinical implications. Can. J. Psychiatry 2004; 49: 290–296.
    1. Viktorin A, Lichtenstein P, Thase ME et al The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer. Am. J. Psychiatry 2014; 171: 1067–1073.
    1. Ketter TA, Sarma K, Silva R, Kroger H, Cucchiaro J, Loebel A. Lurasidone in the long‐term treatment of patients with bipolar disorder: A 24‐week open‐label extension study. Depress. Anxiety 2016; 33: 424–434.
    1. Calabrese JR, Pikalov A, Streicher C, Cucchiaro J, Mao Y, Loebel A. Lurasidone in combination with lithium or valproate for the maintenance treatment of bipolar I disorder. Eur. Neuropsychopharmacol. 2017; 27: 865–876.
    1. Ketter TA, Miller S, Dell'Osso B, Calabrese JR, Frye MA, Citrome L. Balancing benefits and harms of treatments for acute bipolar depression. J. Affect. Disord. 2014; 169: S24–S33.
    1. Barton BB, Segger F, Fischer K, Obermeier M, Musil R. Update on weight‐gain caused by antipsychotics: A systematic review and meta‐analysis. Expert Opin. Drug Saf. 2020; 19: 295–314.
    1. Huhn M, Nikolakopoulou A, Schneider‐Thoma J et al Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi‐episode schizophrenia: A systematic review and network meta‐analysis. Lancet 2019; 394: 939–951.
    1. de Jong M, Belleflamme J, Dale C et al Metabolic syndrome in Dutch patients with bipolar disorder: A cross‐sectional study. Prim. Care Companion CNS Disord. 2018; 20: 18m02366.
    1. Vancampfort D, Vansteelandt K, Correll CU et al Metabolic syndrome and metabolic abnormalities in bipolar disorder: A meta‐analysis of prevalence rates and moderators. Am. J. Psychiatry 2013; 170: 265–274.
    1. Tohen M, McDonnell DP, Case M et al Randomised, double‐blind, placebo‐controlled study of olanzapine in patients with bipolar I depression. Br. J. Psychiatry 2012; 201: 376–382.
    1. Murasaki M, Koyama T, Kanba S et al Multi‐center, randomized, double‐blind, placebo‐controlled study of quetiapine extended‐release formulation in Japanese patients with bipolar depression. Psychopharmacology 2018; 235: 2859–2869.
    1. Reynolds GP, Kirk SL. Metabolic side effects of antipsychotic drug treatment–pharmacological mechanisms. Pharmacol. Ther. 2010; 125: 169–179.
    1. Kroeze WK, Hufeisen SJ, Popadak BA et al H1‐histamine receptor affinity predicts short‐term weight gain for typical and atypical antipsychotic drugs. Neuropsychopharmacology 2003; 28: 519–526.
    1. Wu C, Yuen J, Boyda HN et al An evaluation of the effects of the novel antipsychotic drug lurasidone on glucose tolerance and insulin resistance: A comparison with olanzapine. PLoS One 2014; 9: e107116.
    1. Srisawasdi P, Vanwong N, Hongkaew Y et al Impact of risperidone on leptin and insulin in children and adolescents with autistic spectrum disorders. Clin. Biochem. 2017; 50: 678–685.
    1. Burghardt KJ, Seyoum B, Mallisho A, Burghardt PR, Kowluru RA, Yi Z. Atypical antipsychotics, insulin resistance and weight; A meta‐analysis of healthy volunteer studies. Prog. Neuropsychopharmacol. Biol. Psychiatry 2018; 83: 55–63.
    1. Newcomer JW. Second‐generation (atypical) antipsychotics and metabolic effects: A comprehensive literature review. CNS Drugs 2005; 19: 1–93.
    1. Rummel‐Kluge C, Komossa K, Schwarz S et al Head‐to‐head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: A systematic review and meta‐analysis. Schizophr. Res. 2010; 123: 225–233.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅