The Antidepressant Efficacy of the Anticholinergic Scopolamine

NCT00369915 | Terminated Phase 2 Results

• 2 other identifiers: 06023406-M-0234
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

A previous study showed that the intravenous administration of scopolamine produces antidepressant effects. This study is designed to determine if other routes of administration of scopolamine produce antidepressant effects.

Conditions

Unipolar Depression; Bipolar Depression

Keywords

Cholinergic; Unipolar; Bipolar; Depression; Muscarinic; Scopolamine; Major Depressive Disorder; MDD; Bipolar Disorder; BP

Outcome Measures

Primary Outcomes (1)

• Change in Depression Severity

  The Montgomery-Asberg Depression Rating Scale (MADRS) has a range of scores from 0 to 60 where the highest values indicate the most depression.

  Outcome measures obtained at each of 12 sessions

Secondary Outcomes (1)

• Hamilton Anxiety Rating Scale

  Each of 12 sessions.

Study Arms (2)

Plac/Scop

EXPERIMENTAL

Placebo then scopolamine

Drug: Scopolamine

Scop/Plac

EXPERIMENTAL

Scopolamine then placebo

Drug: Scopolamine

Interventions

Scopolamine DRUG

Scop/Plac

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may not qualify if:

• DEPRESSED SAMPLES: Subjects (ages 18-55) currently suffering from a major depressive episode falling into one of the following subgroups:
• MAJOR DEPRESSIVE DISORDER (MDD): Subjects will be selected with primary MDD and are currently depressed as defined by DSM-IV criteria for recurrent MDD and current MADRS score in the moderately-to-severely depressed range (greater than or equal to 20). The duration of the index episode is greater than or equal to four weeks.
• BIPOLAR DISORDER TYPE II (BD): Subjects will be selected who meet DSM-IV criteria for bipolar disorder Type I or II and are currently depressed, with MADRS score in the moderately-to-severely depressed range (greater than or equal to 20). The duration of the index episode is greater than or equal to four weeks.
• Subjects will be recruited who are drug-naive or who have not received psychotropic drugs for at least 3 weeks (8 weeks for fluoxetine) prior to screening. Subjects also will be excluded if they have: a) serious suicidal ideation or behavior, or current delusions or hallucinations, b) inability to provide informed consent, c) serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease, endocrinologic, neurologic, immunologic, or hematologic disease, d) a history of drug or alcohol abuse within 6 months or alcohol or drug dependence in the last five years (DSM IV criteria), e) not using a medically accepted means of contraception and are a woman of childbearing potential, f) current pregnancy (documented by pregnancy testing prior to each brain scan to avoid exposing a fetus to radiation or to a research MRI scan that is not medically necessary), g) current breast feeding, h) history of ulcerative colitis or toxic megacolon, i) vision and/or hearing problems severe enough to interfere with testing, j) electrocardiographic evidence of ischemia, arrhythmia, conduction defect, or myocardial infarction, k) current blood pressure of greater than 160 mm Hg or less than 90 mm Hg systolic, or greater than 90 mm Hg diastolic, l) clinically significant cerebrovascular or cardiovascular disease, hypertension, congestive heart disease, angina pectoris, clinic evidence of cerebrovascular disease, gross neurological impairment, hyperthyroidism, known hypersensitivity or idiosyncracy to anticholinergic agents (e.g. skin rashes), glaucoma, renal or hepatic impairment, m) current nicotine use or nicotine dependence within last six months (due to the effects of nicotine on the cholinergic system) n) narrow angle glaucoma (due to the possibility of exacerbation of this condition by scopolamine) o) age greater than 55 years (to reduce the biological heterogeneity encompassed by the MDD and BD criteria, since subjects with a late age-at onset for depression have a far greater likelihood of having MRI correlates of cerebrovascular disease than age-matched, healthy controls or age-matched, early-onset depressives), p) exposure within two weeks to medications likely to affect mood or cognition or likely to interact with scopolamine (e.g. narcotics or anti-cholinergic agents)- as verified by history and urine drug screen, q) HIV positive status, r) history of gastric or intestinal obstructions, s) history of urinary retention or bladder obstruction. During the course of this study, participants will be unable to take some medications, including antidepressant or antianxiety agents, sleep aids, diphenhydramine (e.g. Benedryl) or cough/cold preparations that contain diphenhydramine or antihistamines. A detailed list of allowed and not allowed medications is provided in Appendix B in the protocol.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (6)

• Janowsky DS, el-Yousef MK, Davis JM. Acetylcholine and depression. Psychosom Med. 1974 May-Jun;36(3):248-57. doi: 10.1097/00006842-197405000-00008. No abstract available.

  PMID: 4829619 BACKGROUND

• Janowsky DS, el-Yousef MK, Davis JM, Hubbard B, Sekerke HJ. Cholinergic reversal of manic symptoms. Lancet. 1972 Jun 3;1(7762):1236-7. doi: 10.1016/s0140-6736(72)90956-7. No abstract available.

  PMID: 4113219 BACKGROUND

• Janowsky EC, Risch C, Janowsky DS. Effects of anesthesia on patients taking psychotropic drugs. J Clin Psychopharmacol. 1981 Jan;1(1):14-20. doi: 10.1097/00004714-198101000-00004.

  PMID: 6117578 BACKGROUND

• Park L, Furey M, Nugent AC, Farmer C, Ellis J, Szczepanik J, Lener MS, Zarate CA Jr. Neurophysiological Changes Associated with Antidepressant Response to Ketamine Not Observed in a Negative Trial of Scopolamine in Major Depressive Disorder. Int J Neuropsychopharmacol. 2019 Jan 1;22(1):10-18. doi: 10.1093/ijnp/pyy051.

  PMID: 30184133 DERIVED

• Szczepanik J, Nugent AC, Drevets WC, Khanna A, Zarate CA Jr, Furey ML. Amygdala response to explicit sad face stimuli at baseline predicts antidepressant treatment response to scopolamine in major depressive disorder. Psychiatry Res Neuroimaging. 2016 Aug 30;254:67-73. doi: 10.1016/j.pscychresns.2016.06.005. Epub 2016 Jun 20.

  PMID: 27366831 DERIVED

• Drevets WC, Furey ML. Replication of scopolamine's antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biol Psychiatry. 2010 Mar 1;67(5):432-8. doi: 10.1016/j.biopsych.2009.11.021. Epub 2010 Jan 15.

  PMID: 20074703 DERIVED

MeSH Terms

Conditions

Depressive Disorder; Bipolar Disorder; Depression; Depressive Disorder, Major

Interventions

Scopolamine

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Bipolar and Related Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Maura Furey, PhD
• Organization: NIMH/NIH

mfurey@mail.nih.gov

301-594-7773

Study Officials

• Maura L Furey, Ph.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2006
• First Posted: August 30, 2006
• Study Start: August 1, 2006
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: November 10, 2016
• Results First Posted: April 29, 2016

Record last verified: 2016-09

Locations

US (1)