Mirtazapine for treatment resistant depression

INTERVENTION: The addition of Mirtazapine to SSRI antidepressants Added 27/07/2017: To investigate whether combining mirtazapine with Serotonin‐Noradrenaline Reuptake Inhibitor (SNRI) or Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants results in better patient outcomes and more efficient NHS care than SNRI or SSRI therapy alone in Treatment Resistant Depression (TRD). Design: MIR is a two‐parallel group, multi‐centre, pragmatic, placebo controlled, randomised trial with allocation at the level of the individual. Interventions: Participants are randomised to receive either oral mirtazapine or matched placebo, starting at 15mg daily for two weeks and increasing to 30mg daily thereafter, for up to 12 months to be taken in addition to their usual antidepressant. CONDITION: Depression ; Mental and Behavioural Disorders ; Depressive episode, unspecified PRIMARY OUTCOME: Change in Beck Depression Inventory score at 12 weeks (added 27/07/2017: measured using the BDI‐I) measured as a continuous variable SECONDARY OUTCOME: Current secondary outcome measureS:; The following are measured at 12, 24, and 52 weeks:; 1. Response; 2. Remission of depression symptoms; 3. Changes in anxiety symptoms; 4. Adverse Effects; 5. Quality of life; 6. Adherence to antidepressant medication; 7. Health and social care use; 8. Time off work ; 9. Cost effectiveness; All outcomes are analysed on an intention to treat basis.; ; Previous secondary outcome measures:; 1. 50% improvement in BDI score (remission); 2. A measure of anxiety (GAD7); 3. Quality of life (EQ‐5D‐5L); 4. Health care utilisation; INCLUSION CRITERIA: 1. Aged 18‐75 years 2. Currently taking any of the following SSRI or SNRI antidepressants, for at least 6 weeks at recommended (BNF) doses: 2.1. Fluoxetine 2.2. Sertraline 2.3. Citalopram 2.4. Escitalopram 2.5. Fluvoxamine 2.6. Paroxetine 2.7. Duloxetine 2.8. Venlafaxine and who have done so for at least 6 weeks at 3. Patients who score 14 or more on the Beck Depression Inventory (BDI) 4. Patients who have adhered to their medication and meet ICD‐10 criteria for depression (assessed using the Computerised Interview Schedule ? Revised version (CIS‐R))