Bipolar depression Mental and Behavioural Disorders Bipolar affective disorder
Conditions
Interventions
1. Open-label quetiapine (oral) plus
2. Lamotrigine (oral) or placebo plus
3. Folic acid (oral) or placebo
The recommended dose of quetiapine is 300 mg/day but this can be reduced if the higher do
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For the active run-in phase: 1. Primary diagnosis of bipolar disorder type I or II (based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV] criteria for a hypomanic or manic episode) 2. Consent to participate in the trial 3. Aged 16 or over 4. Current depressive episode requiring new pharmacological treatment (either as add-on therapy or as a change of treatment) 5. Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) Score >= 14 Please note that, as of 15/09/2008, inclusion criterion "1. Diagnosis of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) bipolar disorder type I or II (assessed using the Mini-International Neuropsychiatric Interview [MINI])" has been replaced with "1. Primary diagnosis of bipolar disorder type I or II (based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV] criteria for a hypomanic or manic episode)" For the randomised phase: 1. Able to tolerate quetiapine at a dose of at least 150 mg/day 2. Uncertainty whether quetiapine plus lamotrigine would be more effective than quetiapine monotherapy 3. Acceptable adherence to quetiapine (>90%) and to self-report SMS text-messages satisfactory 4. QIDS-SR16 score of >=11 on day of randomisation 5. Willing to accept random allocation of treatments 6. In the opinion of the investigator, not currently experiencing manic or mixed episode
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 15/09/2008: 1. Definite indications or contraindications to lamotrigine, quetiapine or folic acid (Including pregnancy or planned pregnancy) 2. New course of specific psychosocial intervention started in the past four weeks 3. First appointment for specific psychosocial intervention booked within the next 14 weeks 4. Primary diagnosis of schizophrenia Plus, for women of child-bearing potential: 5. Currently breast feeding or not using adequate contraception Current exclusion criteria as of 28/04/2008: 1. Definite indications or contraindications to lamotrigine, quetiapine or folic acid (Including pregnancy or planned pregnancy) 2. New course of specific psychosocial intervention started in the past four weeks 3. First appointment for specific psychosocial intervention booked within the next 14 weeks 4. Currently meeting criteria for (hypo)mania (based on MINI) 5. Currently meeting criteria for schizophrenia 6. Eight or more mood episodes in the past year Plus, for women of child-bearing potential: 7. Not using adequate contraception Initial exclusion criteria: 1. Definite indications or contraindications to lamotrigine, quetiapine or folic acid (Including pregnancy or planned pregnancy) 2. New course of structured psychotherapy started in the past four weeks 3. First appointment for structured psychotherapy booked within the next 14 weeks 4. Currently meeting criteria for (hypo)mania (based on MINI) 5. Eight or more mood episodes in the past year Plus, for women of child-bearing potential: 6. Not using adequate contraception
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Remission of depressive symptoms at 12 weeks post-randomisation. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. The proportion of participants who both achieve remission by 12 weeks following randomisation (defined as a score of = 10 on two consecutive weekly ratings and manic relapse as an Altman Self-Rating Mania Scale (ASRM) score of >=10 on a single weekly rating. 2. New intervention (admission or drug treatment) for manic episode by 52 weeks. 3. New intervention (admission or drug treatment) for depressive episode by 52 weeks. 4. Proportion of time over 12 months when participants were free from manic symptoms (ASRM <= 5). 5. Proportion of time over 12 months when participants were free from depressive symptoms (QIDS-SR16 <= 5). 6. Death (all cause and cause-specific including suicide). 7. Deliberate self-harm. 8. Quality of life will be assessed 4-weekly over 52 weeks (timepoints added 28/04/2008) 9. Unexpected adverse events. 10 Withdrawal from quetiapine or lamotrigine due to adverse effects. 11. Use of health and social care service resources. 12. Social costs/benefits. | — |
Countries
United Kingdom
Outcome results
None listed