A Comparative Study between Lithium and Extended-release Carbamazepine in Acute Mania: A Double-blind Clinical Trial

Author(s): Saeed S. Shafti*, Hamid Kaviani

Journal Name: Current Psychopharmacology

Volume 10 , Issue 2 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Recently, numerous large clinical trials have been performed to evaluate the effectiveness and tolerability of extended-release formulations of carbamazepine in bipolar disorder.

Objective: In the current study, we compared lithium with a prolonged-release form of carbamazepine (Tegretol CR) to evaluate its efficiency and safety in a group of patients with a diagnosis of acute mania.

Methods: Fifty patients with the diagnosis of acute mania were selected for a three-week, doubleblind study, and were randomly administered lithium carbonate or tegretol CR. The main outcome measured in the present evaluation was the Manic State Rating Scale (MSRS), which was scored at baseline and weekly intervals up to the third week. Moreover, insight and overall illness severity and improvement were assessed using the Schedule for Assessment of Insight (SAI), the Clinical Global Impressions-Global Improvement scale (CGI-I), and the Clinical Global Impressions Severity Scale (CGI-S), respectively. The statistical significance was defined with a p-value ≤0.05, and the treatment efficacy was analyzed by independent samples t-test and repeated measures analysis of variance (ANOVA).

Results: Despite the fact that the mean total score of MSRS improved significantly with respect to both lithium carbonate and tegretol CR at the end of the third week, the between-group analysis showed a significant advantage of lithium, regarding both frequency and intensity of symptoms, at the end of the study. The mean total score of SAI, as well, showed significant improvement caused by both of them. Nevertheless, while the CGI-I demonstrated significant improvement in participants taking lithium and tegretol CR, the CGI-S showed significant progress only with lithium. Besides, Cohen’s effect size analysis showed a large improvement of MSRS by lithium and medium improvement by tegretol CR. Post-hoc power analysis showed an intermediate power of 0.42 on behalf of the current evaluation.

Conclusion: While both lithium carbonate and tegretol CR were found to be valuable for the improvement of manic symptoms, management with lithium appears to be more helpful.

Keywords: Acute mania, bipolar disorder, extended-release carbamazepine, lithium, tegreto CR, mood stabilizer.

American Psychiatric Association (APA) Diagnostic and Statistical Manual of Mental Disorders 5th ed Washington, DC American Psychiatric Association. 2013; 123-32.
Katona C. Claudia Cooper, Mary Robertson Psychiatry at a Glance 5th ed Oxford John Wiley & Sons Ltd.. 2012; 24-5.
Burton N. Psychiatry 2nd ed Oxford: John Wiley & Sons Ltd 2010; 89-120.
Kroon JS, Wohlfarth TD, Dieleman J, et al. Incidence rates and risk factors of bipolar disorder in the general population: a population-based cohort study. Bipolar Disord 2013; 15(3): 306-13.
[http://dx.doi.org/10.1111/bdi.12058 PMID: 23531096]
Ketter TA. Diagnostic features, prevalence, and impact of bipolar disorder. J Clin Psychiatry 2010; 71(6)e14
[http://dx.doi.org/10.4088/JCP.8125tx11c ] [PMID: 20573324]
Scherk H, Pajonk FG, Leucht S. Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials. Arch Gen Psychiatry 2007; 64(4): 442-55.
[http://dx.doi.org/10.1001/archpsyc.64.4.442 PMID: 17404121]
Cipriani A, Barbui C, Salanti G, et al. Comparative efficacy and acceptability of antimanic drugs in acute mania: a multiple-treatments meta-analysis. Lancet 2011; 378(9799): 1306-15.
[http://dx.doi.org/10.1016/S0140-6736(11)60873-8 ] [PMID: 21851976]
Grunze H, Vieta E, Goodwin GM, et al. WFSBP task force on treatment guidelines for bipolar disorders. the world federation of societies of biological psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: update 2010 on the treatment of acute bipolar depression. World J Biol Psychiatry 2010; 11(2): 81-109.
[http://dx.doi.org/10.3109/15622970903555881 PMID: 20148751]
Girardi P, Brugnoli R, Manfredi G, Sani G. Lithium in bipolar disorder: optimizing therapy using prolonged-release formulations. Drugs R D 2016; 16(4): 293-302.
[http://dx.doi.org/10.1007/s40268-016-0139-7 PMID: 27770296]
Benard V, Vaiva G, Masson M, Geoffroy PA. Lithium and suicide prevention in bipolar disorder. Encephale 2016; 42(3): 234-41.
[http://dx.doi.org/10.1016/j.encep.2016.02.006 PMID: 27000268]
Tondo L, Baldessarini RJ. Antisuicidal effects in mood disorders: are they unique to lithium? Pharmacopsychiatry 2018; 51(5): 177-88.
[http://dx.doi.org/10.1055/a-0596-7853 PMID: 29672801]
Weisler RH. Carbamazepine extended-release capsules in bipolar disorder. Neuropsychiatr Dis Treat 2006; 2(1): 3-11.
[PMID: 19412441]
Chen CH, Lin SK. Carbamazepine treatment of bipolar disorder: a retrospective evaluation of naturalistic long-term outcomes. BMC Psychiatry 2012; 12: 47.
[http://dx.doi.org/10.1186/1471-244X-12-47 PMID: 22620289]
Weisler RH, Kalali AH, Cutler AJ, Gazda TD, Ginsberg L. Safety of carbamazepine extended-release capsules used in combination with other psychotropic medications for the treatment of bipolar I disorder. Psychiatry (Edgmont Pa) 2008; 5(5): 49-60.
[PMID: 19727252]
Weisler RH, Hirschfeld R, Cutler AJ, et al. SPD417 Study Group Extended-release carbamazepine capsules as monotherapy in bipolar disorder: pooled results from two randomised, double-blind, placebo-controlled trials. CNS Drugs 2006; 20(3): 219-31.
[http://dx.doi.org/10.2165/00023210-200620030-00004 PMID: 16529527]
Weisler RH, Kalali AH, Ketter TA. SPD417 Study Group A multicenter, randomized, double-blind, placebo-controlled trial of extended-release carbamazepine capsules as monotherapy for bipolar disorder patients with manic or mixed episodes. J Clin Psychiatry 2004; 65(4): 478-84.
[http://dx.doi.org/10.4088/JCP.v65n0405 ] [PMID: 15119909]
Ginsberg LD. Carbamazepine extended-release capsules: a retrospective review of its use in children and adolescents. Ann Clin Psychiatry 2006; 18(1)(Suppl. 1): 3-7.
[http://dx.doi.org/10.1080/10401230600653304 PMID: 16754405]
Owen RT. Extended-release carbamazepine for acute bipolar mania: a review. Drugs Today (Barc) 2006; 42(5): 283-9.
[http://dx.doi.org/10.1358/dot.2006.42.5.985635 PMID: 16801991]
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013; 310(20): 2191-4.
[http://dx.doi.org/10.1001/jama.2013.281053 PMID: 24141714]
Taylor DM, Barnes TRE, Young AH. The Maudsley prescribing guidelines in Psychiatry 13th ed West Sussex, UK John Wiley & Sons Ltd. 2018; 205-25.
Beigel A, Murphy DL, Bunney WE Jr. The manic-state rating scale: scale construction, reliability, and validity. Arch Gen Psychiatry 1971; 25: 256-62.
David AS. Insight and psychosis. Br J Psychiatry 1990; 156: 798-808.
[http://dx.doi.org/10.1192/bjp.156.6.798 PMID: 2207510]
Clinical Global Impressions ECDEU Assessment manual for psychopharmacologyRockville: US Department of Health, Education, and Welfare, 1976, DHEW Publication NO (ADM) 1976.pp. 76-338.
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(3): 241-51.
[http://dx.doi.org/10.1001/archgenpsychiatry.2011.12 ] [PMID: 21383262]
Judd LL, Schettler PJ, Akiskal HS, et al. Residual symptom recovery from major affective episodes in bipolar disorders and rapid episode relapse/recurrence. Arch Gen Psychiatry 2008; 65(4): 386-94.
[http://dx.doi.org/10.1001/archpsyc.65.4.386 PMID: 18391127]
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(6): 530-7.
[http://dx.doi.org/10.1001/archpsyc.59.6.530 PMID: 12044195]
Morriss RK, Faizal MA, Jones AP, Williamson PR, Bolton C, McCarthy JP. Interventions for helping people recognise early signs of recurrence in bipolar disorder. Cochrane Database Syst Rev 2007; (1): CD004854
[http://dx.doi.org/10.1002/14651858.CD004854.pub2 ] [PMID: 17253526]
Fuller MA, Dostrow V, Gupta S, Gazda TD. Practical considerations for carbamazepine use in bipolar disorder. Expert Opin Drug Saf 2006; 5(4): 501-9.
[http://dx.doi.org/10.1517/14740338.5.4.501 PMID: 16774489]
Swainston Harrison T, Keating GM. Extended-release carbamazepine capsules: in bipolar I disorder. CNS Drugs 2005; 19(8): 709-16.
[http://dx.doi.org/10.2165/00023210-200519080-00006 PMID: 16097852]
Shafti SS. Olanzapine vs. lithium in management of acute mania. J Affect Disord 2010; 122(3): 273-6.
[http://dx.doi.org/10.1016/j.jad.2009.08.013 PMID: 19740546]
Shafti SS. Aripiprazole versus lithium in management of acute mania: a randomized clinical trial. East Asian Arch Psychiatry 2018; 28(3): 80-4.
[PMID: 30146495]
Shafti SS, Shahveisi B. Comparison between lithium and valproate in the treatment of acute mania. J Clin Psychopharmacol 2008; 28(6): 718-20.
[http://dx.doi.org/10.1097/JCP.0b013e31818ce5ba ] [PMID: 19011453]
Yildiz A, Vieta E, Leucht S, Baldessarini RJ. Efficacy of antimanic treatments: meta-analysis of randomized, controlled trials. Neuropsychopharmacology 2011; 36(2): 375-89.
[http://dx.doi.org/10.1038/npp.2010.192 ] [PMID: 20980991]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 16 June, 2020
Page: [155 - 161]
Pages: 7
DOI: 10.2174/2211556009999200616130803
Price: $65

Article Metrics

PDF: 486