Skip to main content
PMC home page
Current Therapeutic Research, Clinical and Experimental logoLink to Current Therapeutic Research, Clinical and Experimental
. 2007 Jul;68(4):280–290. doi: 10.1016/j.curtheres.2007.08.004

Comparison of the Addition of Siberian Ginseng (Acanthopanax senticosus) Versus Fluoxetine to Lithium for the Treatment of Bipolar Disorder in Adolescents: A Randomized, Double-Blind Trial

Shenhong Weng 1, Jihua Tang 1, Gaohua Wang 1, Xiaoping Wang 1, Hui Wang 2,a
PMCID: PMC3967289  PMID: 24683218

Abstract

Background: Bipolar disorder (BD) is a common, recurrent, and often life-long major psychiatric condition characterized by manic, depressive, and mixed episodes. Without treatment, there is substantial risk for morbidity and mortality, making BD a considerable public health problem.

Objective: The purpose of this study was to compare the relative effectiveness and tolerability of Acanthopanax senficosus (A senficosus)—an herb that is derived from eleutherosides and polysaccharides found in the plant's root— versus fluoxetine added to lithium in the treatment of BD in adolescents.

Methods: This was a double-blind, 6-week study. The patients were randomized into 2 treatment groups—A senticosus plus lithium (A senticosus group) and fluoxetine plus lithium (fluoxetine group). The patients underwent a baseline assessment using the 17-Item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS) during the screening period. Patients were scheduled for clinical visits at the end of weeks 1, 2, 4, and 6. At the end of the 6-week treatment period, each patient's condition was rated as follows: response (indicating an improvement of ≥50% in the HAMD-17 score from baseline); remission (a HAMD-17 score of ⪯7); and switching to mania (a YMRS score >16, and meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition, Text Revision] for a manic episode). At each visit (with the exception of the enrollment visit), the patients were queried as to whether they experienced any health problems since the previous visit, a Treatment Emergent Symptom Scale assessment was completed, and the serum lithium concentration was analyzed. The patients were instructed to report adverse events (AEs) at any time during the study. AEs were also observed by the investigator(s) at clinical visits.

Results: Seventy-nine Chinese adolescents were initially enrolled into the study. However, 76 adolescents were assessed for inclusion (45 females, 31 males; mean [SD] age, 15.4 [30.0] years; age range, 12–17 years) in the study. All included patients completed the study.

After 6 weeks of treatment, the response rate between the A senticosus and the fluoxetine groups was similar (67.6% vs 71.8%, respectively). The remission rate between both groups was also similar (51.4% vs 48.7%). Analyzed by a general line model, the HAMD-17 scores revealed there was a significant time effect (F = 183.06; P < 0.01), but not a significant group effect (F = 0.99) or group-by-duration of treatment interaction (F = 0.779). Three patients in the fluoxetine group experienced switching to mania compared with no patient in the A senticosus group. AEs reported by patients in the A senticosus group were as follows: nausea, 2 (5.4%); rash, 1 (2.7%); and diarrhea, 1 (2.7%). AEs reported by patients in the fluoxetine group were as follows: nausea, 4 (10.3%); anxiety, 3 (7.7%); insomnia, 3 (7.7%); constipation, 1 (2.6%); and tinnitus, 1 (2.6%).

Conclusion: Our study found no significant difference in these adolescents with BD treated with lithium plus adjunctive A senticosus or fluoxetine. All treatments were generally well tolerated.

Key words: Acanthopanax senticosus, bipolar disorder, adolescent, fluoxetine

Full Text

The Full Text of this article is available as a PDF (623.1 KB).

References

  • 1.Regier DA, Narrow WE, Rae DS. The de facto mental and addictive disorders service system. Epidemiological catchment area prospective 1-year prevalence rates of disorders and services. Arch Gen Psychiatry. 1993;50:85–94. doi: 10.1001/archpsyc.1993.01820140007001. [DOI] [PubMed] [Google Scholar]
  • 2.Goodwin G. Perspectives for clinical research on bipolar disorders in the new millennium. Bipolar Disord. 2000;2:302–304. doi: 10.1034/j.1399-5618.2000.020402.x. [DOI] [PubMed] [Google Scholar]
  • 3.McClellan J, Werry J. Practice parameters for the assessment and treatment of children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 1997;36(Suppl 10):157S–176S. doi: 10.1097/00004583-199710001-00010. [DOI] [PubMed] [Google Scholar]
  • 4.Findling RL, Gracious BL, McNamara NK. Rapid, continuous cycling and psychiatric co-morbidity in pediatric bipolar I disorder. Bipolar Disord. 2001;3:202–210. [PubMed] [Google Scholar]
  • 5.Geller B, Zimerman B, Williams M. Diagnostic characteristics of 93 cases of a pre-pubertal and early adolescent bipolar disorder phenotype by gender, puberty and comorbid attention deficit hyperactivity disorder. J Child Adolesc Psychopharmacol. 2000;10:157–164. doi: 10.1089/10445460050167269. [DOI] [PubMed] [Google Scholar]
  • 6.Pavuluri M, Henry D, Carbray J. Open-label prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric mania. J Affect Disord. 2004;82(Suppl 1):S103–S111. doi: 10.1016/j.jad.2004.05.017. [DOI] [PubMed] [Google Scholar]
  • 7.Wagner D, Weller E, Carlson G. An open-label trial of divalproex in children and adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2002;4:1224–1230. doi: 10.1097/00004583-200210000-00012. [DOI] [PubMed] [Google Scholar]
  • 8.Frazier JA, Biederman J, Tohen M. A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder. J Child Adolesc Psychopharmacol. 2001;11:239–250. doi: 10.1089/10445460152595568. [DOI] [PubMed] [Google Scholar]
  • 9.Emslie G, Judge R. Tricyclic antidepressants and selective serotonin reuptake inhibitors: Use during pregnancy, in children/adolescents and in the elderly. Acta Psychiatr Scand Suppl. 2000;403:26–34. doi: 10.1111/j.1600-0447.2000.tb10945.x. [DOI] [PubMed] [Google Scholar]
  • 10.Biederman J, Mick E, Spencer TJ. Therapeutic dilemmas in the pharmacotherapy of bipolar depression in the young. J Child Adolesc Psychopharmacol. 2000;10:185–192. doi: 10.1089/10445460050167296. [DOI] [PubMed] [Google Scholar]
  • 11.Cicero D, El-Mallakh RS, Holman J, Robertson J. Antidepressant exposure in bipolar children. Psychiatry. 2003;66:317–322. doi: 10.1521/psyc.66.4.317.25437. [DOI] [PubMed] [Google Scholar]
  • 12.Faedda GL, Baldessarini RJ, Glovinsky IP, Austin NB. Treatment-emergent mania in pediatric bipolar disorder: A retrospective case review. J Affect Disord. 2004;82:149–158. doi: 10.1016/j.jad.2003.12.011. [DOI] [PubMed] [Google Scholar]
  • 13.Craney J, Geller B. Clinical implications of antidepressant and stimulant use on switching from depression to mania in children. J Child Adolesc Psychopharmacol. 2003;13:201–204. doi: 10.1089/104454603322163925. [DOI] [PubMed] [Google Scholar]
  • 14.McMan's Depression and Bipolar Web. FDA antidepressant suicide warning. Available at: http://www.mcmanweb.com/FDA_suicide.htm. Accessed May 26, 2005.
  • 15.US Food and Drug Administration. Available at: http://www.fda.gov/cder/drug/antidepressants/antidepressants_label_change_2007.pdf. Accessed March 5, 2005.
  • 16.Li Shi Zhen. Ben Cao Gang Mu (An Outline of Herbs) Rev ed. Beijing, China: People's Health Press; 1596:2108
  • 17.Liu Qihua, Zhu Li, Li Wenlan. Progress of the pharmacodynamic researches on chemical components of Acanthopanax senticosus. Li Shi Zhen Medicine and Materia Medica Research. 1999;4:305–306. [Google Scholar]
  • 18.Wang Y, Sun J, Xing G. Study on the quality standard of Ciwujia tablet. Li Shi Zhen Medicine and Materia Medica Research. 2001;2:119–120. [Google Scholar]
  • 19.Hui Improvement of RP-HPLC analyzing eleutheroside B and E in extract of Acanthopanax senticosus. Chinese Traditional Herbal Drugs. 2003;1:39–40. [Google Scholar]
  • 20.Chinese Acanthopanax senticosus Studies. 1st ed. Heilongjiang Science and Technology Press; Haerbin, China: 1981. Heilongjiang Institute of Traditional Chinese Medicine; pp. 17–18. [Google Scholar]
  • 21.Weng S, Cheng Z, Wang H. An open-label study of capsule Acanthopanax senticosus for treatment of depression in patients. Hubei Journal of Chinese Traditional Medicine. 2001;6:8–9. [Google Scholar]
  • 22.Cai M, Peng X, Luo C. Effect of Ciwujia Injection on depression. Pharmacology and Clinics of Chinese Materia Medica. 2005;2:54–56. [Google Scholar]
  • 23.Zhao Y, Yang S. Study on chemical components of Acanthopanax Senticosus. China Journal of Chinese Materia Medica. 1993;7:428. [PubMed] [Google Scholar]
  • 24.Zeng C, Peng W, Wu H. Adverse drug reaction of injection Acanthopanax senticosus. Chinese Journal of Information on Traditional Chinese Medicine. 2004;2:172–173. [Google Scholar]
  • 25.World Medical Association Declaration of Helsinki Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects [WMA Web site] Ferney-Voltaire, France: WMA. 1989 http://www.wma.net Available at: Accessed October 5, 2005. [Google Scholar]
  • 26.European Agency for the Evaluation of Medicinal Products WHO; International Conference on Harmonisation-World Health Organization. Guideline for Good Clinical Practice [EMEA Web site]; Geneva, Switzerland: ICH Topic E6; 2002. Available at: Accessed October 5, 2005. [Google Scholar]
  • 27.American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition. American Psychiatric Association; Washington, DC: 2000. Text Revised. [Google Scholar]
  • 28.The Hamilton Rating Scale for depression. J Operational Psychiatry. 1979;10:149–165. [Google Scholar]
  • 29.Stokes M, Kocsis H, Arcuni J. Relationship of lithium chloride dose to treatment response in acute mania. Arch Gen Psychiatry. 1976;33:1080–1084. doi: 10.1001/archpsyc.1976.01770090070006. [DOI] [PubMed] [Google Scholar]
  • 30.Young RC, Biggs JT, Ziegler VE. A rating scale for mania: Reliability, validity, and sensitivity. Br J Psychiatry. 1978;133:429–435. doi: 10.1192/bjp.133.5.429. Abstract. [DOI] [PubMed] [Google Scholar]

Articles from Current Therapeutic Research, Clinical and Experimental are provided here courtesy of Elsevier

RESOURCES