Efficacy Study of Quetiapine Plus Topiramate for Reducing Cannabis Consumption and Bipolar Mania
Condition: Bipolar Disorder; Cannabis-Related Disorder
MeSH terms: Marijuana Abuse; Bipolar Disorder
Intervention: Quetiapine and placebo; Quetiapine and Topiramate
Intervention description: placebo (titrated to 150-300 mg/day) in combination with quetiapine (titrated to 400-800 mg/day).; topiramate (titrated to 150-300 mg/day) in combination with Quetiapine (titrated to 400-800 mg/day).
Intervention MeSH terms: Topiramate; Quetiapine Fumarate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 75.0
Sex: All
Minimum age: 12 Years
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Bipolar mania; Cannabis consumption

Summary:

      The objectives of this study are to determine whether this treatment may be useful for
      reducing cannabis consumption; reducing symptoms of bipolar mania; and weight mitigation
      therapy for individuals on psychopharmacotherapy.
    

Eligibility criteria:

        Inclusion/Exclusion Criteria Inclusion Criteria: To be included, all subjects must…

          -  have an authorized parent/legal guardian who understands the nature of the study and
             who provides written informed consent if the study subject is younger than 18 years of
             age. Additionally, each subject must provide assent to the study;

          -  be fluent in English;

          -  be 12 to 21 years of age, inclusive;

          -  be using a medically accepted means of contraception (i.e., oral contraceptives and
             barrier methods (diaphragm or condom), medroxyprogesterone acetate injectable
             suspension, abstinence) if female and of menarche. Oral contraceptives alone are not
             acceptable means of contraception because concomitant use of topiramate and low
             estrogen oral contraceptive pills may lead to oral contraceptive failure;

          -  have a diagnosis of bipolar I disorder in a current manic or mixed episode, in
             addition to a cannabis use disorder (which includes abuse or dependence) within 28
             days prior to screening, as determined by the WASH-U-KSADS;

          -  have an initial YMRS total score of >16 at screening and baselines;

          -  use cannabis a minimum of twice per week on average during the 28 days prior to
             screening.

        Exclusion Criteria: Subjects will not be eligible for participation if they…

          -  have a known history of mental retardation;

          -  are acutely intoxicated, and thus impaired;

          -  have manic or depressive symptoms resulting entirely from acute medical illness or
             acute intoxication or withdrawal from drugs or alcohol, as determined by medical
             evaluation and rapid symptom resolution;

          -  have clinically significant alcohol or other drug withdrawal symptoms, as determined
             by vital signs, The Clinical Institute Withdrawal Assessment for Alcohol Scale -
             Revised (CIWA-Ar)24, and physician interview;

          -  have any unstable medical or neurological illness as determined by a study physician;

          -  have laboratory abnormalities >3 times upper limits of established normal values;

          -  as females, have a positive serum (screening and week 16) or urine pregnancy test (at
             baseline and weeks 1-16), are lactating, or are not practicing a reliable form of
             birth control;

          -  have a history of nephrolithiasis, since topiramate has been associated with an
             elevated risk of kidney stones;

          -  require concurrent treatment with mood stabilizers, anticonvulsants, or
             antidepressants

          -  require concurrent treatment with carbonic anhydrase inhibitors.

          -  have significant suicidal ideation

          -  have been treated for a substance use disorder during 28 days prior to screening or
             are court-ordered to treatment for substance use to ensure that, if we detect a change
             in use with topiramate treatment, it is likely not due to these other confounding
             factors that might influence substance use. Peer support groups are not considered
             treatment for substance use. **Patients can be enrolled into the study that are
             already enrolled in a court ordered substance treatment, for at least 1 month prior to
             study enrollment, if they still meet the minimum cannabis use criterion.**

          -  have been diagnosed or treated for an eating disorder, to make sure any weight loss
             does not contribute to an already underlying condition

          -  have a family history of glaucoma, since topiramate has been associated with an
             elevated risk of glaucoma;

          -  have a history of non-response or hypersensitivity to quetiapine or topiramate;

          -  if scanning, have claustrophobia and/or contraindicated for magnetic resonance
             scanning (i.e. intraocular metallic objects, braces, cochlear implants, pacemakers, or
             other electrical, mechanical, or magnetically activated implants); and

          -  if scanning, have a history of significant head trauma (i.e. injury resulting in loss
             of consciousness for greater than five minutes).