Major depression Mental and Behavioural Disorders Depression
Conditions
Interventions
Metyrapone 500 mg twice a day or twice daily placebo for 21 days in addition to the patient's current ongoing psychotropic medication which will remain stable throughout the trial.
Sponsors
Northumberland, Tyne and Wear NHS Foundation Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 05/02/2013: 1. Males and females aged 18-65 years 2. Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) confirmed diagnosis of major depression 3. Severity - Patients must have a Hamilton Depression Rating Scale (HDRS17) score of 18 or greater, consistent with a moderate to severe episode. The stability of the patients' clinical state will also be confirmed with a 2 week baseline lead in period (week -2 to 0). A repeat HDRS17 score at time 0 is required to be 18 or greater. 4. Treatment refractoriness - assessed using the Massachusetts General Hospital (MGH) staging method. This defines minimum effective doses of all currently available antidepressants and an "adequate trial" as being for at least 6 weeks. For the trial to be considered as a "failure" it must have been considered by the clinical team to have been ineffective rather than the drug not taken or not tolerated. For inclusion, patients will have failed to have responded to at least their second trial of an antidepressant. This equates to a minimum score of 2 on MGH staging. The maximum MGH score for inclusion in the study will be 10. 5. At trial entry, patients must be taking monotherapy or combination antidepressant therapy that includes a serotonergic drug (a selective serotonin reuptake inhibitor [SSRI], a tertiary amine tricyclic, venlafaxine, duloxetine or mirtazepine). They must not be on noradrenergic antidepressant monotherapy eg. lofepramine, imipramine or reboxitene. At the point of randomisation, patients must have been on their current antidepressant medication, at the current dose, for a minimum of four weeks (protocol amendment approved 05/03/2012). Previous inclusion criteria until 05/02/2013: 5. At trial entry, patients must be taking monotherapy or combination antidepressant therapy that includes a serotonergic drug (a selective serotonin reuptake inhibitor [SSRI], a tertiary amine tricyclic, venlafaxine, duloxetine or mirtazepine). (Added 16/06/2011: They must not be on noradrenergic antidepressant monotherapy eg. lofepramine, imipramine or reboxitene). Previous inclusion criteria until 16/06/2011: 1. Males and females aged 18 - 70 years 3. Severity - Patients must have a Hamilton Depression Rating Scale (HDRS17) score of 18 or greater, consistent with a moderate to severe episode. The stability of the patients' clinical state will also be confirmed with a 2 week baseline lead in period (week 2 to 0). A repeat HDRS17 score at time 0 is required to be 18 or greater.
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 05/02/2013: 1. Any other DSM IV Axis I disorder other than an anxiety disorder unless the depressive episode is considered to be secondary to the anxiety disorder, confirmed using the Structured Clinical interview for DSM (SCID) (protocol amendment approved 15/08/20111) 2. Physical co-morbidity which would render the use of metyrapone inappropriate, including untreated hypothyroidism, disorders of steroid production, cardiac failure, angina, myocardial infarction within the last 3 years, renal failure 3. Pregnancy - determined by history and if indicated, urine pregnancy test 4. Mothers who are breastfeeding 5. Use of concomitant medication that would interfere in a pharmacodynamic or pharmacokinetic manner with metyrapone 6. Dependence on alcohol or other drug in the past 12 months and/or current harmful use of alcohol or other drug 7. Recently having taken part in another research study that could interfere with the results of this one Previous exclusion criteria until 05/02/2013: 1. Any other DSM IV Axis I disorder 2. Physical co-morbidity which would render the use of metyrapone inappropriate, including untreated hypothyroidism, disorders of steroid production, cardiac failure, angina, myocardial infarction within the last 3 years, renal failure 3. Pregnancy - determined by history and if indicated, urine pregnancy test 4. Mothers who are breastfeeding (Added 21/06/2011) 5. Use of concomitant medication that would interfere in a pharmacodynamic or pharmacokinetic manner with metyrapone 6. Dependence on alcohol or other drug in the past 12 months and/or current harmful use of alcohol or other drug 7. Recently having taken part in another research study that could interfere with the results of this one (Added 21/06/2011)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in clinical symptoms of depression from 0 to +5 weeks (i.e. two weeks after end of treatment), assessed by the Montgomery-Asberg Depression Research Scale (MADRS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 28/06/2013: 1. Mood as measured by the MADRS, YMRS and BDI at time 0, +3, +5, +8, +16, +24 weeks 2. Anxiety as measured by the CAS and STAI at time 0, +3, +5, +8, +16, +24 weeks 3. Quality of life, assessed using the EQ-5D at weeks 0, +3, +5, +8, +16, +24 4. Tolerability assessed using the TSES and self-report at weeks 0, +3, +5, +8 (additional self-report at weeks +1, +2 and +4) 5. Suicide risk assessed at weeks 0, +1, +3, +5, +8, +16, +24 6. Hypothalamic-Pituitary-Adrenal (HPA) axis function assessed by salivary cortisol awakening response (CAR) and sample at 11 pm at weeks 0, +3 and +5 7. Safety assessments including blood pressure, urea and electrolytes and plasma cortisol levels at weeks -2, +1 and +5 Previous secondary outcome measures until 28/06/2013: 1. Secondary outcomes related to mood will be the MADRS measured at time 0, +3, +5, +8, +16, +24 weeks relative to baseline (protocol amendement approved 15/08/2011) 2. Quality of lfe, assessed using the EQ-5D at weeks 0, +3, +5, +8, +16, +24 3. Cortisol awakening response (CAR) from salivary samples at weeks 0, +3 and +5 Previous secondary outcome measures until 05/02/2013: 1. Secondary outcomes related to mood will be the MADRS measured at time +3, +8, +16 and + 24 weeks relative to baseline Previous secondary outcome measures until 16/06/2011: 2. Quality of life, assessed using the EQ-5D at weeks 0, +3 and +5 | — |
Countries
United Kingdom
Outcome results
None listed