Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Mirtazapine added to SSRIs for treatment resistant depression in primary care: a placebo controlled randomised controlled trial

    Summary
    EudraCT number
    		 2012-000090-23
    Trial protocol
    		 GB  
    Global end of trial date
    19 Dec 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Mar 2019
    First version publication date
    14 Mar 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    UoB1651
    Additional study identifiers
    ISRCTN number
    		 ISRCTN06653773
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University of Bristol
    Sponsor organisation address
    One Cathedral Square, Bristol, United Kingdom, BS1 5DD
    Public contact
    Rachel Davies, University of Bristol, +44 1174284021 , rachel.davies@bristol.ac.uk
    Scientific contact
    Rachel Davies, University of Bristol, +44 1174284021 , rachel.davies@bristol.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    02 Dec 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Dec 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    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).
    Protection of trial subjects
    usual standard operating procedures in the event of disclosure of ideas of suicide or self harm.
    Background therapy
    		 not applicable
    Evidence for comparator
    		 not applicable
    Actual start date of recruitment
    26 Aug 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 480
    Worldwide total number of subjects
    480
    EEA total number of subjects
    480
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    406
    From 65 to 84 years
    74
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Recruitment took place from August 2013 to October 2015 in four centres, all in the United Kingdom

    Pre-assignment
    Screening details
    		 751 patients assessed for eligibility 481 eligible, 270 ineligible (Not depressed) 480 randomised

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst
    Blinding implementation details
    The treatment allocation schedule was computer generated by a statistician independent of the trial team in a 1:1 ratio, stratified by centre and minimised by baseline depression score, sex and whether the participant was receiving a psychological intervention. Packs contained encapsulated mirtazapine 15mg or identical placebo.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Mirtazapine
    Arm description
    		 participants treated with the active medication
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Mirtazapine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were asked to take one capsule daily for 2 weeks and then increase to 2 capsules daily thereafter

    Arm title
    		 Placebo
    Arm description
    		 Patients treated with placebo
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Participants were asked to take one capsule daily for 2 weeks and then increase to 2 capsules daily thereafter

    Number of subjects in period 1
    		Mirtazapine Placebo
    Started
    241
    239
    Completed
    214
    217
    Not completed
    27
    22
         Lost to follow-up
    27
    22

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Mirtazapine
    Reporting group description
    		 participants treated with the active medication

    Reporting group title
    Placebo
    Reporting group description
    		 Patients treated with placebo

    Reporting group values
    		 Mirtazapine Placebo Total
    Number of subjects
    		 241 239 480
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 197 209 406
        From 65-84 years
    		 44 30 74
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        geometric mean (standard deviation)
    		 50.4 ± 13.8 49.9 ± 12.5 -
    Gender categorical
    Units: Subjects
        Female
    		 168 164 332
        Male
    		 73 75 148
    Baseline Beck Depression Inventory Score
    Units: Subjects
        14-25
    		 77 79 156
        26-34
    		 78 78 156
        >34
    		 86 82 168
    ICD-10 Diagnosis of Depression
    Units: Subjects
        mild
    		 38 44 82
        moderate
    		 138 144 282
        severe
    		 65 51 116
    Mean BDI score
    Units: scale 0-63
        geometric mean (standard deviation)
    		 31.5 ± 10.2 30.6 ± 9.6 -
    General Anxiety Disorder (GAD7)
    Units: scale 0-21
        geometric mean (standard deviation)
    		 11.3 ± 4.8 10.7 ± 4.8 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Mirtazapine
    Reporting group description
    		 participants treated with the active medication

    Reporting group title
    Placebo
    Reporting group description
    		 Patients treated with placebo

    Primary: mean BDI score

    		 Close Top of page
    End point title
    		 mean BDI score
    End point description
    End point type
    Primary
    End point timeframe
    12 weeks
    End point values
    		 Mirtazapine Placebo
    Number of subjects analysed
    214
    217
    Units: scale 0-63
        geometric mean (standard deviation)
    18 ± 12.3
    19.7 ± 12.4
    Statistical analysis title
    		 Change in mean BDI score analysed as a continuous
    Comparison groups
    Mirtazapine v Placebo
    Number of subjects included in analysis
    431
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.09
    Method
    		 Regression, Linear
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.92
         upper limit
    		 0.27

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All AEs were reported from the time a signed and dated informed consent form was obtained until completion of the last trial related procedure (collection of follow-up data 12 months after randomisation)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 SMPC and BNF
    Dictionary version
    latest
    Reporting groups
    Reporting group title
    Mirtazapine group
    Reporting group description
    		 Participants randomised to Mirtazapine

    Reporting group title
    Placebo group
    Reporting group description
    		 Participants randomised to placebo

    Serious adverse events
    		 Mirtazapine group Placebo group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 241 (3.32%)
    3 / 239 (1.26%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    0
    0
    Cardiac disorders
    Ischaemia
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Dental care
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Hysterectomy
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis acute
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    chest infection
         subjects affected / exposed
    1 / 241 (0.41%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    2 / 241 (0.83%)
    0 / 239 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    trauma
         subjects affected / exposed
    0 / 241 (0.00%)
    2 / 239 (0.84%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    infected ulcer
         subjects affected / exposed
    0 / 241 (0.00%)
    1 / 239 (0.42%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Mirtazapine group Placebo group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    180 / 241 (74.69%)
    89 / 239 (37.24%)
    Nervous system disorders
    psychiatric
    Additional description: This includes drowsiness, headache, TIA, unpleasant dreams, sleep disturbance
         subjects affected / exposed
    70 / 241 (29.05%)
    27 / 239 (11.30%)
         occurrences all number
    70
    27
    General disorders and administration site conditions
    see below
    Additional description: includes anticholinergic effects, allergic reactions, minor endocrine, ENT, Dental, dermatological, ophthalmological, haematological and infective disorders
         subjects affected / exposed
    27 / 241 (11.20%)
    26 / 239 (10.88%)
         occurrences all number
    27
    26
    Gastrointestinal disorders
    Appetite disorder
    Additional description: this includes appetite changes, nausea and weight gain
         subjects affected / exposed
    34 / 241 (14.11%)
    18 / 239 (7.53%)
         occurrences all number
    34
    18
    Reproductive system and breast disorders
    minor disorders
         subjects affected / exposed
    2 / 241 (0.83%)
    1 / 239 (0.42%)
         occurrences all number
    2
    1
    Respiratory, thoracic and mediastinal disorders
    minor respiratory disorders
         subjects affected / exposed
    6 / 241 (2.49%)
    3 / 239 (1.26%)
         occurrences all number
    6
    3
    Musculoskeletal and connective tissue disorders
    minor injury
         subjects affected / exposed
    15 / 241 (6.22%)
    17 / 239 (7.11%)
         occurrences all number
    15
    17

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/30442772
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 26 17:29:19 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA