The Antidepressant Efficacy of the Anticholinergic Scopolamine
Condition: Unipolar Depression; Bipolar Depression
MeSH terms: Depression; Depressive Disorder; Bipolar Disorder
Intervention: Scopolamine; Scopolamine
Intervention MeSH terms: Scopolamine; Butylscopolammonium Bromide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Cholinergic; Unipolar; Bipolar; Depression; Muscarinic; Scopolamine; Major Depressive Disorder; MDD; Bipolar Disorder; BP

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.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Two groups of subjects will be recruited for studies under this protocol: unipolar
        depressives and bipolar depressives. Subjects with unipolar or bipolar depression appear to
        exhibit abnormal cholinergic function during the depressed phase, and no differences are
        hypothesized to exist between MDD and BD depressives herein. However, while BD subjects are
        more difficult to recruit, the evidence for cholinergic abnormalities has been particularly
        compelling for BD. Moreover, observations from our pilot study suggest that scopolamine
        will improve symptoms in both MDD and BD, a particularly persuasive observation given BD
        notoriously has been difficult to treat. Thus, the magnitude of this serious clinical
        problem justifies the inclusion of BD subjects. Therefore both groups will be recruited.
        However, BD Type I subjects will be included only if they are currently stable on lithium
        or valproate to reduce the risks associated with possible precipitation of mania.

        The presence of inclusion and exclusion criteria will be established using both an
        unstructured clinical interview with a psychiatrist and the Structured Clinical Interview
        for DSM-IV (SCID). Family history of mental illness will be obtained from the subject using
        the Family Interview of Genetic Studies. We will recruit 24 subjects per group.

        DEPRESSED SAMPLES: Subjects (ages 18-55) currently suffering from a major depressive
        episode falling into one of the following subgroups:

          1. . 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.

          2. . 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.

        EXCLUSION CRITERIA:

        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.

        We are not excluding comorbid anxiety disorders. Exclusion of patients with comorbid
        anxiety disorders would affect the generalizability of our findings since a substantial
        percentage of patients with major depression have these comorbid diagnoses. Instead, we
        will exclude patients with this comorbid diagnosis only if it is believed to be of clinical
        significance. Allowing participation by patients with histories of comorbid anxiety
        disorders broadens the inclusion criteria to more closely approximate patients seen in real
        world settings.