The Collaborative Lithium Trials (CoLT): specific aims, methods, and implementation

Robert L Findling, Jean A Frazier, Vivian Kafantaris, Robert Kowatch, Jon McClellan, Mani Pavuluri, Linmarie Sikich, Stefanie Hlastala, Stephen R Hooper, Christine A Demeter, Denise Bedoya, Bernard Brownstein, Perdita Taylor-Zapata, Robert L Findling, Jean A Frazier, Vivian Kafantaris, Robert Kowatch, Jon McClellan, Mani Pavuluri, Linmarie Sikich, Stefanie Hlastala, Stephen R Hooper, Christine A Demeter, Denise Bedoya, Bernard Brownstein, Perdita Taylor-Zapata

Abstract

Background: Lithium is a benchmark treatment for bipolar illness in adults. However, there has been relatively little methodologically stringent research regarding the use of lithium in youth suffering from bipolarity.

Methods: Under the auspices of the Best Pharmaceuticals for Children Act (BPCA), a Written Request (WR) pertaining to the study of lithium in pediatric mania was issued by the United States Food and Drug Administration (FDA) to the National Institute of Child Health and Human Development (NICHD) in 2004. Accordingly, the NICHD issued a Request for Proposals (RFP) soliciting submissions to pursue this research. Subsequently, the NICHD awarded a contract to a group of investigators in order to conduct these studies.

Results: The Collaborative Lithium Trials (CoLT) investigators, the BPCA-Coordinating Center, and the NICHD developed protocols to provide data that will: (1) establish evidence-based dosing strategies for lithium; (2) characterize the pharmacokinetics and biodisposition of lithium; (3) examine the acute efficacy of lithium in pediatric bipolarity; (4) investigate the long-term effectiveness of lithium treatment; and (5) characterize the short- and long-term safety of lithium. By undertaking two multi-phase trials rather than multiple single-phase studies (as was described in the WR), the feasibility of the research to be undertaken was enhanced while ensuring all the data outlined in the WR would be obtained. The first study consists of: (1) an 8-week open-label, randomized, escalating dose Pharmacokinetic Phase; (2) a 16-week Long-Term Effectiveness Phase; (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. The second study consists of: (1) an 8-week, double-blind, parallel-group, placebo-controlled Efficacy Phase; (2) an open-label Long-Term Effectiveness lasting either 16 or 24 weeks (depending upon blinded treatment assignment during the Efficacy Phase); (3) a 28-week double-blind Discontinuation Phase; and (4) an 8-week open-label Restabilization Phase. In December of 2006, enrollment into the first of these studies began across seven sites.

Conclusion: These innovative studies will not only provide data to inform the labeling of lithium in children and adolescents with bipolar disorder, but will also enhance clinical decision-making regarding the use of lithium treatment in pediatric bipolar illness.

Trial registration: NCT00442039.

Figures

Figure 1
Figure 1
Study 1 of CoLT.
Figure 2
Figure 2
Study 2 of CoLT.

References

    1. U.S. Food and Drug Administration: Best Pharmaceuticals for Children Act
    1. Best Pharmaceuticals for Children Act
    1. Ferrier IN. Developments in mood stabilisers. Br Med Bull. 2001;57:179–192. doi: 10.1093/bmb/57.1.179.
    1. Geddes JR, Burgess S, Hawton K, Jamison K, Goodwin GM. Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry. 2004;161:217–222. doi: 10.1176/appi.ajp.161.2.217.
    1. Muzina DJ, Calabrese JR. Maintenance therapies in bipolar disorder: focus on randomized controlled trials. Aust NZ J Psychiatry. 2005;39:652–661. doi: 10.1111/j.1440-1614.2005.01649.x.
    1. Cousins DA, Young AH. The armamentarium of treatments for bipolar disorder: a review of the literature. Int J Neuropsychopharmacol. 2007;10:411–431. doi: 10.1017/S1461145706007413.
    1. Kafantaris V, Coletti DJ, Dicker R, Padula G, Kane JM. Lithium treatment of acute mania in adolescents: a large open trial. J Am Acad Child Adolesc Psychiatry. 2003;42:1038–1045. doi: 10.1097/01.CHI.0000070247.24125.24.
    1. Findling RL, Pavuluri MN. Lithium. In: Geller B, DelBello MP, editor. Treatment of Bipolar Disorder in Children & Adolescents. New York, NY: Guilford Press;
    1. Kowatch RA, Fristad M, Birmaher B, Wagner KD, Findling RL, Hellander M, Child Psychiatric Workgroup on Bipolar Disorder Treatment guidelines for children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2005;44:213–235. doi: 10.1097/00004583-200503000-00006.
    1. Carlson GA, Jensen PS, Findling RL, Meyer RE, Calabrese J, DelBello MP, Emslie G, Flynn L, Goodwin F, Hellander M, Kowatch R, Kusumakar V, Laughren R, Leibenluft E, McCracken J, Nottelmann E, Pine D, Sachs G, Shaffer D, Simar R, Strober M, Weller EB, Wozniak J, Youngstrom EA. Methodological issues and controversies in clinical trials with children and adolescent patients with bipolar disorder: report of a consensus conference. J Child Adolesc Psychopharmacol. 2003;13:13–27. doi: 10.1089/104454603321666162.
    1. National Institute of Mental Health Clinical Global Impressions Scale. Psychopharmacol Bull. 1985;21:839–843.
    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. doi: 10.1192/bjp.133.5.429.
    1. Amdisen A. Serum concentration and clinical supervision in monitoring of lithium treatment. Ther Drug Monit. 1980;2:73–83.
    1. Smarty S, Findling RL. Psychopharmacology of pediatric bipolar disorder: a review. Psychopharmacol. 2007;191:39–54. doi: 10.1007/s00213-006-0569-y.
    1. Scahill L, McCracken J, McDougle CJ, Aman M, Arnold LE, Tierney E, Cronin P, Davies M, Ghuman J, Gonzalez N, Koenig K, Lindsay R, Martin A, McGough J, Posey DJ, Swiezy N, Volkmar F, Ritz L, Vitiello B, Research Units on Pediatric Psychopharmacology (RUPP), Autism Network Methodological issues in designing a multisite trial of risperidone in children and adolescents with autism. J Child Adolesc Psychopharmacol. 2001;11:377–399. doi: 10.1089/104454601317261555.
    1. Patel NC, Patrick DM, Youngstrom EA, Strakowski SM, DelBello MP. Response and remission in adolescent mania: signal detection analyses of the Young Mania Rating Scale. J Am Acad Child Adolesc Psychiatry. 2007;46:628–635. doi: 10.1097/chi.0b013e3180335ae4.
    1. Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36:980–988. doi: 10.1097/00004583-199707000-00021.
    1. Klein RG, Slomkowski C. Treatment of psychiatric disorders in children and adolescents. Psychopharmacol Bull. 1993;29:525–535.
    1. Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand. 1970:11–19. doi: 10.1111/j.1600-0447.1970.tb02066.x.
    1. Lingjaerde O, Ahlfors UG, Bech P, Dencker SJ, Elgen K. The UKU side effect rating scale. A new comprehensive rating scale for psychotropic drugs and a cross-sectional study of side effects in neuroleptic-treated patients. Acta Psychiatr Scand. 1987;334:1–100. doi: 10.1111/j.1600-0447.1987.tb10566.x.
    1. Greenhill LL, Vitiello B, Fisher P, Levine J, Davies M, Abikoff H, Chrisman AK, Chuang S, Findling RL, March J, Scahill L, Walkup J, Riddle MA. Comparison of increasingly detailed elicitation methods for the assessment of adverse events in pediatric psychopharmacology. J Am Acad Adolesc Psychiatry. 2004;43:1488–1496. doi: 10.1097/01.chi.0000142668.29191.13.
    1. Lazarus JH, McGregor AM, Ludgate M, Darke D, Creagh FM, Kingswood CJ. Effect of lithium carbonate therapy on thyroid immune status in manic depressive patients: a prospective study. J Affect Disord. 1986;11:155–160. doi: 10.1016/0165-0327(86)90023-6.
    1. Johnson GF. Lithium in depression: a review of the antidepressant and prophylactic effects of lithium. Aust NZ J Psychiatry. 1987;21:356–365.
    1. Gracious BL, Findling RL, Seman C, Youngstrom EA, Demeter CA, Calabrese JR. Elevated thyrotropin in bipolar youths prescribed both lithium and divalproex sodium. J Am Acad Child Adolesc Psychiatry. 2004;43:215–220. doi: 10.1097/00004583-200402000-00018.
    1. Gitlin MJ. Lithium-induced renal insufficiency. J Clin Psychopharmacol. 1993;13:276–279.
    1. Amdisen A. Serum level monitoring and clinical pharmacokinetics of lithium. Clin Pharmacokinet. 1977;2:73–92. doi: 10.2165/00003088-197702020-00001.
    1. Carson SW. Lithium. In: Evans WE, Schentag JJ, Jusko WJ, editor. Applied Pharmacokinetics: Principles of Therapeutic Drug Monitoring. 3. Vancouver, WA: Applied Therapeutics; 1992.
    1. Rosenqvist M, Bergfeldt L, Aili H, Mathé AA. Sinus node dysfunction during long-term lithium treatment. Br Heart J. 1993;70:371–375. doi: 10.1136/hrt.70.4.371.
    1. Hsu CH, Liu PY, Chen JH, Yeh TL, Tsai HY, Lin LJ. Electrocardiographic abnormalities as predictors for over-range lithium levels. Cardiology. 2005;103:101–106. doi: 10.1159/000082471.
    1. Pandey GN, Sarkadi B, Haas M, Gunn RB, Davis JM, Tosteson DC. Lithium transport pathways in human red blood cells. J Gen Physiol. 1978;72:233–247. doi: 10.1085/jgp.72.2.233.
    1. Ostrow DG, Pandey GN, Davis JM, Hurt SW, Tosteson DC. A heritable disorder of lithium transport in erythrocytes of a subpopulation of manic-depressive patients. Am J Psychiatry. 1978;135:1070–1078.
    1. Pandey GN, Goel I, Davis JM. Effect of neuroleptic drugs on lithium uptake by the human erythrocyte. Clin Pharmacol Ther. 1979;26:96–102.
    1. Wechsler DA. Wechsler Abbreviated Scale of Intelligence Manual. San Antonio, TX: The Psychological Corporation; 1999.
    1. Overholser JC, Brinkman DC, Lehnert KL, Ricciardi AM. Children's Depression Rating Scale–Revised: Development of a short form. J Clin Child Psychol. 1995;24:443–452. doi: 10.1207/s15374424jccp2404_8.
    1. Hughes CW, Rintelmann J, Emslie GJ, Lopez M, MacCabe N. A revised anchored version of the BPRS-C for childhood psychiatric disorders. J Child Adolesc Psychopharmacol. 2001;11:77–93. doi: 10.1089/104454601750143500.
    1. Shaffer D, Gould MS, Brasic J, Ambrosini P, Fisher P, Bird H, Aluwahlia S. A Children's Global Assessment Scale (CGAS) Arch Gen Psychiatry. 1983;40:1228–1231.
    1. Tarter RE, Hegedus AM. The drug use screening inventory: its applications in the evaluation and treatment of alcohol and other drug abuse. Alcohol Health Res World. 1991;15:65–75.
    1. Snaith RP, Constantopoulos AA, Jardine MY, McGuffin P. A clinical scale for the self-assessment of irritability. Br J Psychiatry. 1978;132:164–171. doi: 10.1192/bjp.132.2.164.
    1. The Research Units on Pediatric Psychopharmacology (RUPP) Anxiety Study Group The Pediatric Anxiety Rating Scale (PARS): Development and psychometric properties. J Am Acad Child Adolesc Psychiatry. 2002;41:1061–1069. doi: 10.1097/00004583-200209000-00006.
    1. John K, Gammon GD, Prusoff BA, Warner V. The Social Adjustment Inventory for Children and Adolescents (SAICA): Testing of a new semistructured interview. J Am Acad Child Adolesc Psychiatry. 1987;26:898–911.
    1. Posner K, Melvin GA, Stanley B, Oquendo MA, Gould M. Factors in the assessment of suicidality in youth. CNS Spectr. 2007;12:156–162.
    1. Youngstrom EA, Findling RL, Danielson CK, Calabrese JR. Discriminative validity of parent report of hypomanic and depressive symptoms on the General Behavior Inventory. Psychol Assess. 2001;13:267–276. doi: 10.1037/1040-3590.13.2.267.
    1. DuPaul GJ, Power TJ, Anastopoulos AD, Reid R. ADHD Rating Scale – IV: Checklists, norms, and clinical interpretation. New York: The Guilford Press; 1998.
    1. Pavuluri M, Henry D, Devineni B, Carbray J, Birmaher B. Child Mania Rating Scale (CMRS): Development, Reliability and Validity. J Am Acad Child Adolesc Psychiatry. 2006;45:550–560. doi: 10.1097/01.chi.0000205700.40700.50.
    1. Aman MG, Tasse MJ, Rojahn J, Hammer D. The Nisonger CBRF: A child behavior rating form for children with developmental disabilities. Res Dev Disabil. 1996;17:41–57. doi: 10.1016/0891-4222(95)00039-9.
    1. Brannan AM, Heflinger CA, Bickman L. The caregiver strain questionnaire: measuring the impact of the family of living with a child with serious emotional disturbance. Journal of Emotional and Behavioral Disorders. 1997;5:212–222.
    1. Moos R, Moos E. Family Environment Scale Manual. Palo Alto, CA: Consulting Psychologist Press; 1984.
    1. Matthews CG, Klove H. Instruction manual for the adult neuropsychology test battery. Madison, WI: University of Wisconsin Medical School; 1964.
    1. Matthews CG, Kløve H. Wisconsin Motor Steadiness Battery Administration manual for child neuropsychology battery. Madison: University of Wisconsin Medical School, Neuropsychology Laboratory; 1978.
    1. Francis DJ, Fletcher JM, Rourke BP. Discriminant validity of lateral sensorimotor tests in children. J Clin Exp Neuropsychol. 1988;10:779–799. doi: 10.1080/01688638808402814.
    1. Delis DC, Kaplan E, Kramer JH. Delis-Kaplan Executive Function System. San Antonio: The Psychological Corporation; 2001.
    1. Delis DC, Kramer JH, Kaplan E, Holdnack J. Reliability and validity of the Delis-Kaplan Executive Function System: an update. J Int Neuropsychol Soc. 2004;10:301–303. doi: 10.1017/S1355617704102191.
    1. Vigil W. Continuous Performance Test: User and Technical Manual. NH: For Thought Ltd; 1996.
    1. Hartman DE. Test review: Wide Range Assessment of Memory and Learning-2 (WRAML-2): WRedesigned and WReally Improved. Appl Neuropsychol. 2007;14:138–140.
    1. Williams JM, Mathews A, MacLeod C. The emotional Stroop task and psychopathology. Psychol Bull. 1996;120:3–24. doi: 10.1037/0033-2909.120.1.3.
    1. Kane MJ, Conway ARA, Miura TK, Colflesh GJH. Working memory, attention control, and the n-back task: a question of construct validity. J Exp Psychol Learn Mem Cog. 2007;33:615–622. doi: 10.1037/0278-7393.33.3.615.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel