E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment resistant depression |
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E.1.1.1 | Medical condition in easily understood language |
Depression which has not responded to at least six weeks of treatment with an SSRI or SNRI antidepressant |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045543 |
E.1.2 | Term | Unipolar depression |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the effectiveness of the addition of the antidepressant mirtazapine to an SSRI or SNRI in reducing depressive symptoms and improving quality of life at 12 weeks, 24 weeks and 12 months (compared to the addition of a placebo). |
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E.2.2 | Secondary objectives of the trial |
We aim to determine the cost-effectiveness of the intervention over 12 months. In addition, this study will incorporate a qualitative study to: (i) explore patients’ views and experiences of taking either two antidepressant medications or an antidepressant and a placebo; (ii) identify patients’ reasons for completing or not completing the study, including withdrawal from study medication; and (iii) to explore the views of general practitioners on prescribing a second antidepressant in this patient group. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Eligible patients are those aged 18 years or over, who are currently taking any of the following SSRI or SNRI antidepressants: fluoxetine, sertraline, citalopram, escitalopram, fluvoxamine, paroxetine, duloxetine, or venlafaxine; and who have done so for at least 6 weeks at recommended (BNF) doses. Patients who score 14 or more on the Beck Depression Inventory (BDI), have adhered to their medication, and meet ICD-10 criteria for depression (assessed using the Computerised Interview Schedule – Revised version (CIS-R), will be invited to participate. |
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E.4 | Principal exclusion criteria |
GPs will be asked to exclude patients who have bipolar disorder, psychosis, dementia, or alcohol/substance abuse/dependence or who are pregnant, planning to become pregnant or breastfeeding. In addition, we will exclude patients who: are not able to complete the study questionnaires or have a past history of an adverse reaction to mirtazapine. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in score using the Beck Depression Inventory (BDI) at 12 weeks compared to BDI score at baseline, measured as a continuous variable. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks post randomisation |
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E.5.2 | Secondary end point(s) |
BDI score as a binary variable representing response, defined as a reduction in depressive symptoms of at least 50% compared to baseline, a widely used definition of improvement Other secondary outcomes will include remission of symptoms, score on a measure of general anxiety, the GAD7 quality of life using the EQ-5D-5L and SF-12 and use of antidepressants, together with outcomes measured at 24 weeks and 12 months post-randomisation. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
all outcomes will be measured at 12 and 24 weeks and 12 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will occur when the data analysis is complete. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |