<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03004521</url>
  </required_header>
  <id_info>
    <org_study_id>HTA 14/222/02</org_study_id>
    <nct_id>NCT03004521</nct_id>
  </id_info>
  <brief_title>Lithium Versus Quetiapine in Treatment Resistant Depression</brief_title>
  <acronym>LQD</acronym>
  <official_title>A Randomised Pragmatic Trial Comparing the Clinical and Cost Effectiveness of Lithium and Quetiapine Augmentation in Treatment Resistant Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Newcastle University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oxford Health NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Northumberland, Tyne and Wear NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>South London and Maudsley NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tees, Esk and Wear Valleys NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sussex Partnership NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Avon and Wiltshire Mental Health Partnership NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>King's College London</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      LQD is a multicentre randomised clinical trial comparing the clinical and cost effectiveness&#xD;
      of lithium versus quetiapine when used as add-on therapies to antidepressant medication for&#xD;
      patients with treatment resistant depression. The Lithium versus Quetiapine in Depression&#xD;
      (LQD) study will assess patients over 12 months to establish which (if any) treatment is more&#xD;
      likely to improve TRD over a long duration of time. Professor Anthony Cleare is the Chief&#xD;
      Investigator and recruitment began in November 2016.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This 12 month parallel group, multi-centre, patient randomised, pragmatic, open label trial&#xD;
      is comparing the clinical and cost-effectiveness of the decision to prescribe lithium versus&#xD;
      quetiapine add-on treatment to antidepressant medication. There will be two parallel groups:&#xD;
      1) Quetiapine add-on to existing antidepressant medication; 2) Lithium add-on to existing&#xD;
      antidepressant medication. 276 patients will be randomised 1:1 at baseline to the decision to&#xD;
      prescribe either lithium or quetiapine, and treatment will then be undertaken by clinicians&#xD;
      on a real world basis. All patients, regardless of their treatment status, will be followed&#xD;
      up in the trial for one year. This is a superiority design whereby we hypothesise that&#xD;
      quetiapine will be superior to lithium in terms of time to treatment discontinuation and&#xD;
      average symptom burden (QIDS-SR) over 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 2016</start_date>
  <completion_date type="Anticipated">August 2021</completion_date>
  <primary_completion_date type="Anticipated">April 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Longitudinal depressive symptom severity</measure>
    <time_frame>52 weeks</time_frame>
    <description>QIDS-SR</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Difference in time to all-cause treatment discontinuation</measure>
    <time_frame>12 months</time_frame>
    <description>The difference in the time at which patients stop taking the medication for any reason between the two treatment arms.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in clinician rated depression severity</measure>
    <time_frame>From baseline to weeks 8 and 52</time_frame>
    <description>MADRS</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rates</measure>
    <time_frame>8 weeks and 52 weeks</time_frame>
    <description>Assessed using the MADRS questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Remission rates</measure>
    <time_frame>8 and 52 weeks</time_frame>
    <description>Assessed using the MADRS questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health related quality of life</measure>
    <time_frame>Measured at 8 and 52 weeks</time_frame>
    <description>Assessed using the EuroQol-5D questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Social functioning</measure>
    <time_frame>Measured at baseline, 8 and 52 weeks</time_frame>
    <description>Measured using the WSAS self rated questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence to treatment</measure>
    <time_frame>Measured at weeks 8 and 52</time_frame>
    <description>Assessed using the MARS-5 questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in weight in kilograms</measure>
    <time_frame>Measured at 8 and 52 weeks</time_frame>
    <description>Assessed by weighing participants</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in diastolic blood pressure</measure>
    <time_frame>Change from baseline to 8 and 52 weeks</time_frame>
    <description>Assessed by measuring blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in systolic blood pressure</measure>
    <time_frame>Change from baseline to 8 and 52 weeks</time_frame>
    <description>Assessed by measuring blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to uptake of a new intervention (pharmacological or non-pharmalogical)</measure>
    <time_frame>12 months</time_frame>
    <description>Assessed by recording all pharmacological and non-pharmacological interventions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to initiation of treatment</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Assessed using treatment initiation form</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CGI Global Improvement</measure>
    <time_frame>Measured at 8 and 52 weeks</time_frame>
    <description>CGI</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side effects</measure>
    <time_frame>Measured at 8 and 52 weeks</time_frame>
    <description>PRISE total score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious Adverse Events</measure>
    <time_frame>52 weeks</time_frame>
    <description>Serious adverse events will be monitored and reported throughout the patient's participation in the trial.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in global severity</measure>
    <time_frame>Measured at 8, 26 and 52 weeks</time_frame>
    <description>Change in CGI severity score</description>
  </other_outcome>
  <other_outcome>
    <measure>Global efficacy</measure>
    <time_frame>Measured at 8, 26 and 52 weeks</time_frame>
    <description>Change in CGI efficacy score</description>
  </other_outcome>
  <other_outcome>
    <measure>Side effects</measure>
    <time_frame>Measured at 8 and 52 weeks</time_frame>
    <description>Frequency of individual items on the PRISE</description>
  </other_outcome>
  <other_outcome>
    <measure>Physical health changes</measure>
    <time_frame>Measured at baseline, 8, 26 and 52 weeks</time_frame>
    <description>Not completed for all participants. Will be reported if there is a sufficient number e.g. blood parameters and waist circumference</description>
  </other_outcome>
  <other_outcome>
    <measure>Satisfaction with lithium / quetiapine treatment</measure>
    <time_frame>Measured at 8, 26 and 52 weeks</time_frame>
    <description>Measured using TSQM subscales</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in self-report manic symptoms</measure>
    <time_frame>Measured at baseline, 8, 26 and 52 weeks</time_frame>
    <description>Measured using the Altman Mania Self Rating Scale</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in anxiety symptoms</measure>
    <time_frame>Measured at baseline, 8, 26 and 52 weeks</time_frame>
    <description>GAD-7 score</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to prescription</measure>
    <time_frame>0-52 weeks</time_frame>
    <description>First date participant is given a prescription for the treatment</description>
  </other_outcome>
  <other_outcome>
    <measure>Baseline adherence to antidepressant</measure>
    <time_frame>Measured at baseline</time_frame>
    <description>MARS-5 score</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in cognition</measure>
    <time_frame>Measured at baseline, 8, 26 and 52 weeks</time_frame>
    <description>Total DSCT score</description>
  </other_outcome>
  <other_outcome>
    <measure>Adherence of clinicians</measure>
    <time_frame>0-52 weeks</time_frame>
    <description>Clinician adherence to prescribing and monitoring guidelines</description>
  </other_outcome>
  <other_outcome>
    <measure>Proportion of participants having an adequate treatment trial</measure>
    <time_frame>0-8 weeks</time_frame>
    <description>Adequate treatment trial as defined in study protocol</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of hospital admissions for depressive episode</measure>
    <time_frame>52 weeks</time_frame>
    <description>Measured using psychiatric history assessment</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in personality measure</measure>
    <time_frame>Measured at baseline, 8, 26 and 52 weeks</time_frame>
    <description>SAPAS</description>
  </other_outcome>
  <other_outcome>
    <measure>Social functioning</measure>
    <time_frame>Measured weekly over 12 months</time_frame>
    <description>WSAS</description>
  </other_outcome>
  <other_outcome>
    <measure>Economic analysis</measure>
    <time_frame>52 weeks</time_frame>
    <description>Costs from the NHS and Personal Social Services perspective and from a societal perspective.</description>
  </other_outcome>
  <other_outcome>
    <measure>Predictors of treatment response</measure>
    <time_frame>52 weeks</time_frame>
    <description>Measured using the Maudsley Staging Model, HAM-D, MINI 7, IDS-C and SAPAS questionnaires.</description>
  </other_outcome>
  <other_outcome>
    <measure>Longitudinal depression severity until time to all cause treatment discontinuation</measure>
    <time_frame>52 weeks</time_frame>
    <description>Measured weekly using the QIDS-SR</description>
  </other_outcome>
  <other_outcome>
    <measure>Collection and analysis of biological samples for genetic, cytokine and cortisol analysis</measure>
    <time_frame>0-52 weeks</time_frame>
    <description>Blood/hair/saliva samples collected in collaboration with the BRC BioResource</description>
  </other_outcome>
  <other_outcome>
    <measure>Reliability and validity of the Maudsley VAS</measure>
    <time_frame>Measured at baseline, 8, 26 and 52 weeks</time_frame>
    <description>Measured using the Maudsley VAS, validated against the QIDS-SR and MADRS</description>
  </other_outcome>
  <other_outcome>
    <measure>Discrepancy between the self-rated and clinician-rated version of 16 item IDS</measure>
    <time_frame>Measured at baseline and 8 weeks</time_frame>
    <description>Assessed using QIDS and IDS</description>
  </other_outcome>
  <other_outcome>
    <measure>Relationship between quetiapine and lithium serum levels, prescribed dose and depressive symptom severity</measure>
    <time_frame>52 weeks</time_frame>
    <description>MADRS</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to new interventions for depression.</measure>
    <time_frame>52 weeks</time_frame>
    <description>Measured using concomitant medication and concomitant therapy questionnaires</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of new interventions for depression</measure>
    <time_frame>52 weeks</time_frame>
    <description>Measured using concomitant medication and concomitant therapy questionnaires</description>
  </other_outcome>
  <other_outcome>
    <measure>Patient rated experience of the True Colours weekly monitoring system</measure>
    <time_frame>8 / 26 / 52 weeks</time_frame>
    <description>Qualitative Interview in a subset of participants</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in cognitive function</measure>
    <time_frame>Baseline, 8, 26 and 52 weeks</time_frame>
    <description>THINC-it composite and individual tests scores in a subset of participants</description>
  </other_outcome>
  <other_outcome>
    <measure>12. Patient views and experiences of lithium and quetiapine</measure>
    <time_frame>52 week visit</time_frame>
    <description>Qualitative interviews in a subset of participants</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">276</enrollment>
  <condition>Depressive Disorder, Treatment-Resistant</condition>
  <arm_group>
    <arm_group_label>Lithium</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lithium will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Quetiapine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Quetiapine will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Quetiapine</intervention_name>
    <description>Quetipatine prescribed in addition to the patient's existing antidepressant treatment.</description>
    <arm_group_label>Quetiapine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lithium</intervention_name>
    <description>Lithium prescribed in addition to the patient's existing antidepressant treatment.</description>
    <arm_group_label>Lithium</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Under the care of a GP and/or adult mental health services&#xD;
&#xD;
          2. Current episode of depression meeting DSM-5 criteria for major depressive disorder&#xD;
             (MDD) - single or recurrent episode 3.17-item HAM-D score ≥ 14 - this cut-off reflects&#xD;
             a pragmatic minimum severity of depression as also chosen in comparable studies such&#xD;
             as STAR*D (Rush et al 2006, Trivedi et al 2006)&#xD;
&#xD;
        4.Any gender and aged 18 years or over 5.Meet criteria for treatment resistant depression&#xD;
        (Fekadu et al., 2009a; Cleare et al., 2015): current episode has not responded to at least&#xD;
        two antidepressants given for at least 6 weeks at minimum therapeutic dose defined as&#xD;
        fluoxetine ≥20mg/day, paroxetine ≥20mg/day, sertraline ≥50mg/day, citalopram ≥20mg/day,&#xD;
        escitalopram ≥10mg/day, venlafaxine ≥75mg/day, duloxetine ≥60 mg/day, mirtazapine&#xD;
        ≥15mg/day, tricyclic antidepressant ≥125mg/day, and dosage as guided by the national&#xD;
        Maudsley Prescribing Guidelines or BNF for any other antidepressant. Please note, relapse&#xD;
        whilst on an antidepressant also counts as a failed treatment trial 6.Current&#xD;
        antidepressant treatment has remained unchanged and at, or above, a therapeutic dose for ≥6&#xD;
        weeks 7.Provision of written, informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diagnosis of bipolar disorder (defined as meeting DSM-5 criteria for bipolar 1 or&#xD;
             bipolar 2) on the MINI 7.0 (as recommended treatments are different for bipolar&#xD;
             depression)&#xD;
&#xD;
          2. Diagnosis of current psychosis (as recommended treatments are different for current&#xD;
             psychosis - antidepressants plus antipsychotics is the first-line treatment&#xD;
             recommendation (NiCE, 2009; Cleare et al., 2015)&#xD;
&#xD;
          3. Adequate use of lithium or quetiapine during the current episode. An adequate dose of&#xD;
             lithium is defined as the patient taking lithium for at least 4 weeks at an adequate&#xD;
             dose (leading to a documented plasma concentration of &gt;0.4mmol/L) and for quetiapine,&#xD;
             prescription in the range of 150-300mg/d for 4 weeks or longer. Or, if the patient has&#xD;
             taken an inadequate dose of lithium or quetiapine in the current episode, the patient&#xD;
             and clinician are not willing to re-prescribe/take the medication.&#xD;
&#xD;
          4. Ongoing use of another atypical antipsychotic (discontinuation will be required before&#xD;
             study entry i.e. any time prior to randomisation)&#xD;
&#xD;
          5. Known contraindication to use of either lithium or quetiapine: known hypersensitivity&#xD;
             of lithium or quetiapine or any of their excipients; severe renal insufficiency /&#xD;
             impairment; untreated hypothyroidism; severe cardiac disease / insufficiency; low&#xD;
             sodium levels e.g. dehydrated patients or those on low sodium diets; Addison's&#xD;
             disease; Brugada syndrome or family history of Brugada syndrome; the rare hereditary&#xD;
             inborn errors of metabolism galactosaemia, the Lapp lactase deficiency or&#xD;
             glucose-galactose malabsorption; concomitant administration of cytochrome P450 3A4&#xD;
             inhibitors; or congenital QT prolongation.&#xD;
&#xD;
          6. We will not recruit any individual who is currently participating in a clinical trial&#xD;
             of an investigational medical product (CTIMP).&#xD;
&#xD;
          7. Insufficient degree of comprehension or attention to be able to engage in trial&#xD;
             procedures.&#xD;
&#xD;
          8. We will exclude women who are pregnant, actively trying for pregnancy, or currently&#xD;
             breastfeeding. This will be based on verbal report of the subject. Otherwise the&#xD;
             management will be as appropriate according to standard clinical practice within the&#xD;
             context of a pragmatic, open trial, for example adequate contraceptive precautions&#xD;
             decided on the clinical judgement of the prescriber.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anothony Cleare</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor of Psychiatry</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lindsey Marwood</last_name>
    <email>LQDstudy@kcl.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Institute of Psychiatry, Psychology and Neuroscience, King's College London</name>
      <address>
        <city>London</city>
        <zip>SE5 8AF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helena Tee</last_name>
      <email>helena.tee@kcl.ac.uk</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <link>
    <url>https://www.kcl.ac.uk/research/lqd-study</url>
    <description>Study website link</description>
  </link>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>March 3, 2021</last_update_submitted>
  <last_update_submitted_qc>March 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lithium</keyword>
  <keyword>Quetiapine</keyword>
  <keyword>Augmentation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Treatment-Resistant</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Quetiapine Fumarate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The decision to share IPD to other researchers will be made by the CI on a case by case basis.</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03004521
org study id: HTA 14/222/02
nct id: NCT03004521
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
LQD is a multicentre randomised clinical trial comparing the clinical and cost effectiveness
      of lithium versus quetiapine when used as add-on therapies to antidepressant medication for
      patients with treatment resistant depression. The Lithium versus Quetiapine in Depression
      (LQD) study will assess patients over 12 months to establish which (if any) treatment is more
      likely to improve TRD over a long duration of time. Professor Anthony Cleare is the Chief
      Investigator and recruitment began in November 2016.
This 12 month parallel group, multi-centre, patient randomised, pragmatic, open label trial
      is comparing the clinical and cost-effectiveness of the decision to prescribe lithium versus
      quetiapine add-on treatment to antidepressant medication. There will be two parallel groups:
      1) Quetiapine add-on to existing antidepressant medication; 2) Lithium add-on to existing
      antidepressant medication. 276 patients will be randomised 1:1 at baseline to the decision to
      prescribe either lithium or quetiapine, and treatment will then be undertaken by clinicians
      on a real world basis. All patients, regardless of their treatment status, will be followed
      up in the trial for one year. This is a superiority design whereby we hypothesise that
      quetiapine will be superior to lithium in terms of time to treatment discontinuation and
      average symptom burden (QIDS-SR) over 12 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Longitudinal depressive symptom severity
time frame: 52 weeks
description: QIDS-SR
measure: Difference in time to all-cause treatment discontinuation
time frame: 12 months
description: The difference in the time at which patients stop taking the medication for any reason between the two treatment arms.
measure: Change in clinician rated depression severity
time frame: From baseline to weeks 8 and 52
description: MADRS
measure: Response rates
time frame: 8 weeks and 52 weeks
description: Assessed using the MADRS questionnaire
measure: Remission rates
time frame: 8 and 52 weeks
description: Assessed using the MADRS questionnaire
measure: Health related quality of life
time frame: Measured at 8 and 52 weeks
description: Assessed using the EuroQol-5D questionnaire
measure: Social functioning
time frame: Measured at baseline, 8 and 52 weeks
description: Measured using the WSAS self rated questionnaire
measure: Adherence to treatment
time frame: Measured at weeks 8 and 52
description: Assessed using the MARS-5 questionnaire
measure: Change in weight in kilograms
time frame: Measured at 8 and 52 weeks
description: Assessed by weighing participants
measure: Change in diastolic blood pressure
time frame: Change from baseline to 8 and 52 weeks
description: Assessed by measuring blood pressure
measure: Change in systolic blood pressure
time frame: Change from baseline to 8 and 52 weeks
description: Assessed by measuring blood pressure
measure: Time to uptake of a new intervention (pharmacological or non-pharmalogical)
time frame: 12 months
description: Assessed by recording all pharmacological and non-pharmacological interventions
measure: Time to initiation of treatment
time frame: Up to 12 months
description: Assessed using treatment initiation form
measure: CGI Global Improvement
time frame: Measured at 8 and 52 weeks
description: CGI
measure: Side effects
time frame: Measured at 8 and 52 weeks
description: PRISE total score
measure: Serious Adverse Events
time frame: 52 weeks
description: Serious adverse events will be monitored and reported throughout the patient's participation in the trial.
measure: Change in global severity
time frame: Measured at 8, 26 and 52 weeks
description: Change in CGI severity score
measure: Global efficacy
time frame: Measured at 8, 26 and 52 weeks
description: Change in CGI efficacy score
measure: Side effects
time frame: Measured at 8 and 52 weeks
description: Frequency of individual items on the PRISE
measure: Physical health changes
time frame: Measured at baseline, 8, 26 and 52 weeks
description: Not completed for all participants. Will be reported if there is a sufficient number e.g. blood parameters and waist circumference
measure: Satisfaction with lithium / quetiapine treatment
time frame: Measured at 8, 26 and 52 weeks
description: Measured using TSQM subscales
measure: Change in self-report manic symptoms
time frame: Measured at baseline, 8, 26 and 52 weeks
description: Measured using the Altman Mania Self Rating Scale
measure: Change in anxiety symptoms
time frame: Measured at baseline, 8, 26 and 52 weeks
description: GAD-7 score
measure: Time to prescription
time frame: 0-52 weeks
description: First date participant is given a prescription for the treatment
measure: Baseline adherence to antidepressant
time frame: Measured at baseline
description: MARS-5 score
measure: Change in cognition
time frame: Measured at baseline, 8, 26 and 52 weeks
description: Total DSCT score
measure: Adherence of clinicians
time frame: 0-52 weeks
description: Clinician adherence to prescribing and monitoring guidelines
measure: Proportion of participants having an adequate treatment trial
time frame: 0-8 weeks
description: Adequate treatment trial as defined in study protocol
measure: Number of hospital admissions for depressive episode
time frame: 52 weeks
description: Measured using psychiatric history assessment
measure: Change in personality measure
time frame: Measured at baseline, 8, 26 and 52 weeks
description: SAPAS
measure: Social functioning
time frame: Measured weekly over 12 months
description: WSAS
measure: Economic analysis
time frame: 52 weeks
description: Costs from the NHS and Personal Social Services perspective and from a societal perspective.
measure: Predictors of treatment response
time frame: 52 weeks
description: Measured using the Maudsley Staging Model, HAM-D, MINI 7, IDS-C and SAPAS questionnaires.
measure: Longitudinal depression severity until time to all cause treatment discontinuation
time frame: 52 weeks
description: Measured weekly using the QIDS-SR
measure: Collection and analysis of biological samples for genetic, cytokine and cortisol analysis
time frame: 0-52 weeks
description: Blood/hair/saliva samples collected in collaboration with the BRC BioResource
measure: Reliability and validity of the Maudsley VAS
time frame: Measured at baseline, 8, 26 and 52 weeks
description: Measured using the Maudsley VAS, validated against the QIDS-SR and MADRS
measure: Discrepancy between the self-rated and clinician-rated version of 16 item IDS
time frame: Measured at baseline and 8 weeks
description: Assessed using QIDS and IDS
measure: Relationship between quetiapine and lithium serum levels, prescribed dose and depressive symptom severity
time frame: 52 weeks
description: MADRS
measure: Time to new interventions for depression.
time frame: 52 weeks
description: Measured using concomitant medication and concomitant therapy questionnaires
measure: Number of new interventions for depression
time frame: 52 weeks
description: Measured using concomitant medication and concomitant therapy questionnaires
measure: Patient rated experience of the True Colours weekly monitoring system
time frame: 8 / 26 / 52 weeks
description: Qualitative Interview in a subset of participants
measure: Change in cognitive function
time frame: Baseline, 8, 26 and 52 weeks
description: THINC-it composite and individual tests scores in a subset of participants
measure: 12. Patient views and experiences of lithium and quetiapine
time frame: 52 week visit
description: Qualitative interviews in a subset of participants
arm group label: Lithium
arm group type: Active Comparator
description: Lithium will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment.
arm group label: Quetiapine
arm group type: Experimental
description: Quetiapine will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment.
intervention type: Drug
intervention name: Quetiapine
description: Quetipatine prescribed in addition to the patient's existing antidepressant treatment.
arm group label: Quetiapine
intervention type: Drug
intervention name: Lithium
description: Lithium prescribed in addition to the patient's existing antidepressant treatment.
arm group label: Lithium
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Anothony Cleare
role: Principal Investigator
affiliation: Professor of Psychiatry
last name: Lindsey Marwood
email: LQDstudy@kcl.ac.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
url: https://www.kcl.ac.uk/research/lqd-study
description: Study website link
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Treatment-Resistant
mesh term: Quetiapine Fumarate
sharing ipd: No
ipd description: The decision to share IPD to other researchers will be made by the CI on a case by case basis.