Health Condition 1: F313- Bipolar disorder, current episodedepressed, mild or moderate severity
Conditions
Interventions
Intervention1: Cannabidiol: Cannabidiol capsules 400-600 mg per day for 6 weeks
Control Intervention1: Placebo: Matching placebo capsules for 6 weeks
Sponsors
Canadian Institutes of Health Research
Eligibility
Inclusion criteria
Inclusion criteria: 1. Males or females aged 19 to 70 years (inclusive). 2. DSM-5 diagnosis of BD I or BD II, AND a current major depressive episode confirmed by MINI 7.0.2 . 3. All patients must be taking either a mood stabilizer (i.e. lithium or valproate; lamotrigine monotherapy as a mood stabilizer is acceptable for BD II patients only and not for BD I) OR an atypical antipsychotic OR a combination of these (two mood stabilizers or a mood stabilizer plus an atypical antipsychotic), at therapeutic doses. Medications and therapeutic doses are: lithium, serum level 0.6 to 1.2 mEqL; divalproex/sodium valproate, serum level 350 to 700 uML(45 to 125 mcgml); risperidone 2 to6 mg/day; olanzapine 5 to 30 mg/day; quetiapine IR or XR 300 to 900 mg/day; aripiprazole 10 to 30 mg/day; and ziprasidone 80-160 mg/day. Combinations of these medications as outlined above, or the combination of any of them with lamotrigine 100400 mg daily, or the combination of a mood stabilizer plus asenapine 5 to 20 mg/day are also permitted. 4. Have received a minimum of 6-weeks treatment at adequate doses for treatment of current depressive episode with at least one CANMAT recommended first-line treatment for bipolar I disorder (i.e. lithium, lamotrigine, lurasidone, or quetiapine either as monotherapy or adjunctive therapy), or at least one first or second-line treatment for bipolar II depression (i.e. a. quetiapine, lithium, lamotrigine, sertraline, or venlafaxine as monotherapy or adjunctive therapy, or bupropion adjunctive therapy). 5. A MADRS score of greater than or equal to 20 and a YMRS score of less than or equal to 12 (these cut off scores are standard in bipolar depression RCTs). 6. Inpatient or outpatient status. 7. All participants are required to agree to practice highly effective methods of contraception (i.e. a. hormonal contraceptives, intrauterine device or system, vasectomy and tubal ligation, or double barrier methods of contraception) OR agree to completely abstain from heterosexual intercourse. Females who do not have childbearing potential are required to be postmenopausal for at least 1 year before the screening visit (confirmed by an FSH test) OR surgically sterile. 8. The capability of understanding, consenting to and complying with study requirements. 9. All concomitant medication must be at a stable dose for two weeks prior to the randomization visit.
Exclusion criteria
Exclusion criteria: 1. Current depressive episode greater than 12 months. 2. A history of rapid cycling, defined as 4 or more mood episodes in the preceding 12 months. 3. Current unstable or inadequately treated medical illness with the exception of current depression. 4. Recently started taking a CANMAT-recommended treatment for the management of acute bipolar depressive episode, but has not had a trial for a minimum of 6 weeks with adequate doses. 5. Recently (i.e. within the past 8 weeks) began structured psychotherapy (i.e. cognitivebehavioral therapy, interpersonal psychotherapy, family-focused therapy, or interpersonal and social rhythm therapy). 6. Current use of stimulant medications. 7. A history of non-response or intolerance to CBD. 8. Current or past month daily use of CBD, or any product or drug that contains CBD. Occasional users will be included if they agree to refrain from using during the trial. 9. A history of non-response to electroconvulsive therapy for the current depressive episode. 10. A current diagnosis of other primary psychiatric disorders as assessed by a study investigator to be primary and causing greater impairment than BD. 11. A lifetime history of a primary psychotic disorder (e.g. schizoaffective disorder, bipolar subtype) according to DSM-5 criteria. 12. Patients who have met the DSM-5 criteria for a substance use disorder (except for nicotine or caffeine) within the past 6 months. 13. Significant active suicidal ideation (as evidenced by MADRS suicide item score of 4 for more). 14. Pregnancy or lactation. 15. Liver function tests (AST and ALT) three times the upper limit of normal.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Improvement in depressive symptoms, as measured by changes in Montgomery- sberg Depression Rating Scale (MADRS) scores from baseline to week 6.Timepoint: week 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Response rateTimepoint: week 6;Remission rateTimepoint: week 6;Treatment emergent manic/hypomanic eventsTimepoint: Week 0- 6;changes in Hamilton Depression Rating Scale 21- item (HAM-D)Timepoint: week 6;subjective depressive symptoms as measured by changes in the Quick Inventory of Depressive Symptomatology Self-report (QIDS-SR) and Dimensional Anhedonia Rating Scale (DARS);Timepoint: week 6;anxiety symptoms scores measured objectively with the Hamilton Anxiety Rating Scale (HAM-A), and subjectively with the General Anxiety Disorder-7 (GAD-7) and State-Trait Anxiety Inventory (STAI)Timepoint: week 6;global severity of symptoms as indicated by changes in Clinical Global Impressions Scale, Bipolar Version, Severity (CGI-BP-S) and global improvement in symptoms with Clinical Global Impressions Scale, Bipolar Version, Change (CGI-BP-C)Timepoint: week 6;psychotic symptoms as reflected by changes in Positive and Negative Symptoms Scale (PANSS scores)Timepoint: week 6;Subjective cognitive functioning will be assessed using the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) and Patient-Reported Outcomes Measurement Information System (PROMIS), and objective cognitive functioning as measured by Screen for Cognitive Impairment in Psychiatry (SCIP)Timepoint: week 6;sleep quality measured by Pittsburgh Sleep Quality Index (PSQI)Timepoint: week 6;suicidal thoughts and behaviours as measured by the Columbia Suicide Severity Rating Scale (C-SSRS)Timepoint: week 0-6;Quality of life assessed using The Brief Quality of Life in Bipolar Disorder Questionnaire (Brief QoL-BDTimepoint: week 6;Daily functioning based on Functioning Assessment Short Test (FAST)Timepoint: Week 6;health services utilization by self-reportTimepoint: week 6;Open ended adverse report form and b) the Frequency, Intensity, Burden of Side Effects Rating scale (FIBSER)Timepoint: week 6 | — |
Countries
Canada, India
Contacts
Public ContactYC Janardhan Reddy
National Institute of Mental Health and Neuro Science (NIMHANS)
Outcome results
None listed