Top

Trials

Published in:

Open Access 01-12-2022 | Antidepressant Drugs | Study protocol

Efficacy and safety of scopolamine compared to placebo in individuals with bipolar disorder who are experiencing a depressive episode (SCOPE-BD): study protocol for a randomised double-blind placebo-controlled trial

Authors: Cerena Miravalles, Ruán Kane, Eimear McMahon, Colm McDonald, Dara M. Cannon, Brian Hallahan

Published in: Trials | Issue 1/2022

Abstract

Background

Current treatment options for the management of depressive episodes in bipolar disorder are often sub-optimal, with some treatments either noted to be only partially effective or to require long durations of treatment prior to a therapeutic response. Therefore, pharmaco-therapeutic options that reduce depressive symptoms in a more rapid manner might provide a viable therapeutic option for some people. Intravenous (IV) scopolamine, a pan muscarinic antagonist, has been demonstrated in a number of studies to confer a rapid antidepressant effect, albeit no study to date has exclusively evaluated its potential therapeutic effect in a cohort consisting solely of individuals with bipolar disorder.

Methods

Individuals with bipolar disorder who are currently experiencing a depressive episode of at least moderate severity will be included in this study. Eligible participants will undergo a screening and placebo-run in visit and will be randomised at visit 3 to the treatment or placebo group. Participants will receive the three blinded infusions over the course of 2 weeks, with two subsequent follow-up visits, 1 and 3 weeks after the last infusion visit. The total duration of the study will be approximately 6 weeks. Patients will continue their regular treatment regime in addition to study medication. Objective and subjective mood questionnaires, cognitive assessments and other psychometric instruments will be administered and recorded.

Discussion

To our knowledge, this is the first study to investigate the antidepressant effects of IV scopolamine in an exclusively bipolar disorder cohort. Trial findings will contribute to the evidence base regarding the cholinergic hypothesis of mood disorders and specifically might result in an additional safe therapeutic option for the management of depressive episodes in bipolar disorder.

Trial registration

ClinicalTrials.gov NCT04211961. December 26, 2019. EudraCT Number 2017-003112-39

American Psychiatric A. Diagnostic and statistical manual of mental disorders: DSM-5. [DSM V]. 5th ed. Washington, DC: American Psychiatric Publishing; 2013. https://doi.org/10.1176/appi.books.9780890425596.CrossRef

Ferrari AJ, Stockings E, Khoo JP, Erskine HE, Degenhardt L, Vos T, et al. The prevalence and burden of bipolar disorder: findings from the Global Burden of Disease Study 2013. Bipolar Disord. 2016;18(5):440–50. https://doi.org/10.1111/bdi.12423.CrossRefPubMed

Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010;303(1):47–53. https://doi.org/10.1001/jama.2009.1943.CrossRefPubMedPubMedCentral

Yildiz A, Vieta E, Leucht S, Baldessarini RJ. Efficacy of antimanic treatments: meta-analysis of randomized, controlled trials. Neuropsychopharmacology. 2011;36(2):375–89. https://doi.org/10.1038/npp.2010.192.CrossRefPubMed

Drevets WC, Furey ML. Replication of scopolamine’s antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biol Psychiatry. 2010;67(5):432–8. https://doi.org/10.1016/j.biopsych.2009.11.021.CrossRefPubMedPubMedCentral

Ellis JS, Zarate CA Jr, Luckenbaugh DA, Furey ML. Antidepressant treatment history as a predictor of response to scopolamine: clinical implications. J Affect Disord. 2014;162:39–42. https://doi.org/10.1016/j.jad.2014.03.010.CrossRefPubMedPubMedCentral

Furey ML, Drevets WC. Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Arch Gen Psychiatry. 2006;63(10):1121–9. https://doi.org/10.1001/archpsyc.63.10.1121.CrossRefPubMedPubMedCentral

Janowsky DS. Serendipity strikes again: scopolamine as an antidepressant agent in bipolar depressed patients. Curr Psychiatry Rep. 2011;13(6):443–5. https://doi.org/10.1007/s11920-011-0239-6.CrossRefPubMed

Furey ML, Khanna A, Hoffman EM, Drevets WC. Scopolamine produces larger antidepressant and antianxiety effects in women than in men. Neuropsychopharmacology. 2010;35(12):2479–88. https://doi.org/10.1038/npp.2010.131.CrossRefPubMedPubMedCentral

10.

Furey ML, Nugent AC, Speer AM, Luckenbaugh DA, Hoffman EM, Frankel E, et al. Baseline mood-state measures as predictors of antidepressant response to scopolamine. Psychiatry Res. 2012;196(1):62–7. https://doi.org/10.1016/j.psychres.2012.01.003.CrossRefPubMedPubMedCentral

11.

Gillin JC, Sutton L, Ruiz C, Darko D, Golshan S, Risch SC, et al. The effects of scopolamine on sleep and mood in depressed patients with a history of alcoholism and a normal comparison group. Biol Psychiatry. 1991;30(2):157–69. https://doi.org/10.1016/0006-3223(91)90170-Q.CrossRefPubMed

12.

Newhouse PA, Sunderland T, Tariot PN, Weingartner H, Thompson K, Mellow AM, et al. The effects of acute scopolamine in geriatric depression. Arch Gen Psychiatry. 1988;45(10):906–12. https://doi.org/10.1001/archpsyc.1988.01800340028004.CrossRefPubMed

13.

Khajavi D, Farokhnia M, Modabbernia A, Ashrafi M, Abbasi SH, Tabrizi M, et al. Oral scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2012;73(11):1428–33. https://doi.org/10.4088/JCP.12m07706.CrossRefPubMed

14.

Apfel CC, Zhang K, George E, Shi S, Jalota L, Hornuss C, et al. Transdermal scopolamine for the prevention of postoperative nausea and vomiting: a systematic review and meta-analysis. Clin Ther. 2010;32(12):1987–2002. https://doi.org/10.1016/j.clinthera.2010.11.014.CrossRefPubMed

15.

Stankovic AS, Alvarenga DL, Coleman Daniels VR, Simmons RG, Buckey JC, Putcha L. Intranasal scopolamine for motion sickness. Aerosp Med Hum Perform. 2019;90(11):917–24. https://doi.org/10.3357/AMHP.5456.2019.CrossRefPubMed

16.

Takeuchi I, Suzuki T, Kishi T, Kanamori D, Hanya M, Uno J, et al. Effect of scopolamine butylbromide on clozapine-induced hypersalivation in schizophrenic patients: a case series. Clin Psychopharmacol Neurosci. 2015;13(1):109–12. https://doi.org/10.9758/cpn.2015.13.1.109.CrossRefPubMedPubMedCentral

17.

Bonner TI, Buckley NJ, Young AC, Brann MR. Identification of a family of muscarinic acetylcholine receptor genes. Science. 1987;237(4814):527–32. https://doi.org/10.1126/science.3037705.CrossRefPubMed

18.

Hulme EC, Birdsall NJ, Buckley NJ. Muscarinic receptor subtypes. Annu Rev Pharmacol Toxicol. 1990;30(1):633–73. https://doi.org/10.1146/annurev.pa.30.040190.003221.CrossRefPubMed

19.

Davis KL, Berger PA, Hollister LE, Defraites E. Physostigmine in mania. Arch Gen Psychiatry. 1978;35(1):119–22. https://doi.org/10.1001/archpsyc.1978.01770250121012.CrossRefPubMed

20.

Janowsky DS, el-Yousef MK, Davis JM, Sekerke HJ. A cholinergic-adrenergic hypothesis of mania and depression. Lancet. 1972;2(7778):632–5. https://doi.org/10.1016/S0140-6736(72)93021-8.CrossRefPubMed

21.

Nabulsi L, Farrell J, McPhilemy G, Kilmartin L, Dauvermann MR, Akudjedu TN, et al. Normalization of impaired emotion inhibition in bipolar disorder mediated by cholinergic neurotransmission in the cingulate cortex. Neuropsychopharmacology. 2022. https://doi.org/10.1038/s41386-022-01268-7.

22.

Cannon DM, Carson RE, Nugent AC, Eckelman WC, Kiesewetter DO, Williams J, et al. Reduced muscarinic type 2 receptor binding in subjects with bipolar disorder. Arch Gen Psychiatry. 2006;63(7):741–7. https://doi.org/10.1001/archpsyc.63.7.741.CrossRefPubMed

23.

Cannon DM, Klaver JK, Gandhi SK, Solorio G, Peck SA, Erickson K, et al. Genetic variation in cholinergic muscarinic-2 receptor gene modulates M2 receptor binding in vivo and accounts for reduced binding in bipolar disorder. Mol Psychiatry. 2011;16(4):407–18. https://doi.org/10.1038/mp.2010.24.CrossRefPubMed

24.

Rosenkranz GK. Remarks on designs enriching for placebo non-responders. Clin Trials. 2016;13(3):338–43. https://doi.org/10.1177/1740774515625186.CrossRefPubMed

25.

Babor TF. The Alcohol Use Disorders Identification Test : guidelines for use in primary health care. Geneva: World Health Organization; 2001.

26.

Guy W. ECDEU assessment manual for psychopharmacology, Rev. 1976. edn. Rockville, Md: U.S. Dept. of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976.

27.

Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO. The Fagerstrom Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991;86(9):1119–27. https://doi.org/10.1111/j.1360-0443.1991.tb01879.x.CrossRefPubMed

28.

Hall RC. Global assessment of functioning. A modified scale. Psychosomatics. 1995;36(3):267–75. https://doi.org/10.1016/S0033-3182(95)71666-8.CrossRefPubMed

29.

Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23(1):56–62. https://doi.org/10.1136/jnnp.23.1.56.CrossRefPubMedPubMedCentral

30.

Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134(4):382–9. https://doi.org/10.1192/bjp.134.4.382.CrossRefPubMed

31.

Costa PT. McCrae RR, Psychological Assessment Resources I: Revised NEO Personality Inventory (NEO PI-R) and NEO Five-Factor Inventory (NEO-FFI). Odessa, Fla: Psychological Assessment Resources; 1992.

32.

Rush AJ, Fava M, Wisniewski SR, Lavori PW, Trivedi MH, Sackeim HA, et al. Sequenced treatment alternatives to relieve depression (STAR* D): rationale and design. Control Clin Trials. 2004;25(1):119–42. https://doi.org/10.1016/S0197-2456(03)00112-0.CrossRefPubMed

33.

McNair DM, Lorr M, Droppleman LF. Manual for the profile of mood states. Educational & Industrial Testing Service: San Diego; 1971.

34.

First MB, Williams JBW, Karg RS, Spitzer RL, American Psychiatric Association P, American Psychiatric A. SCID-5-RV: structured clinical interview for DSM-5 disorders - research version. Arlington, VA: American Psychiatric Association Publishing; 2015.

35.

Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133(5):429–35. https://doi.org/10.1192/bjp.133.5.429.CrossRefPubMed

36.

Robbins TW, James M, Owen AM, Sahakian BJ, McInnes L, Rabbitt P. Cambridge Neuropsychological Test Automated Battery (CANTAB): a factor analytic study of a large sample of normal elderly volunteers. Dement Geriatr Cogn Disord. 1994;5(5):266–81. https://doi.org/10.1159/000106735.CrossRef

37.

Wechsler D. Manual for the Wechsler adult intelligence scale. New York: Psychological Corporation; 1955.

38.

ICH Good Clinical Practice E6 (R2). https://globalhealthtrainingcentre.tghn.org/ich-good-clinical-practice/. Accessed 10 Feb 2022.

Title: Efficacy and safety of scopolamine compared to placebo in individuals with bipolar disorder who are experiencing a depressive episode (SCOPE-BD): study protocol for a randomised double-blind placebo-controlled trial
Authors: Cerena Miravalles
Ruán Kane
Eimear McMahon
Colm McDonald
Dara M. Cannon
Brian Hallahan
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Antidepressant Drugs
Antidepressant Drugs
Published in: Trials / Issue 1/2022
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-022-06270-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Efficacy and safety of scopolamine compared to placebo in individuals with bipolar disorder who are experiencing a depressive episode (SCOPE-BD): study protocol for a randomised double-blind placebo-controlled trial

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2022

Effect of listening to music on anxiety, pain, and cardiorespiratory parameters in cardiac surgery: study protocol for a randomized clinical trial

Postoperative drainage for 6, 12, or 24 h after burr-hole evacuation of chronic subdural hematoma in symptomatic patients (DRAIN-TIME 2): study protocol for a nationwide randomized controlled trial

Correction: Prophylaxis in healthcare workers during a pandemic: a model for a multi-centre international randomised controlled trial using Bayesian analyses

Sterile water injections for relief of labour pain (the SATURN trial): study protocol for a randomised controlled trial

G-CuP: the effect of a forced oral glucose intake on alcohol craving and mesolimbic cue reactivity in alcohol dependence—study protocol of a randomized, double-blind, placebo-controlled crossover study

Feasibility, effectiveness and costs of a decision support intervention for consultees and legal representatives of adults lacking capacity to consent (CONSULT): protocol for a randomised Study Within a Trial