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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT03004521
Other study ID # HTA 14/222/02
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date November 2016
Est. completion date August 2021

Study information

Verified date March 2021
Source King's College London
Contact Lindsey Marwood
Email LQDstudy@kcl.ac.uk
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 276
Est. completion date August 2021
Est. primary completion date April 2021
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Under the care of a GP and/or adult mental health services 2. Current episode of depression meeting DSM-5 criteria for major depressive disorder (MDD) - single or recurrent episode 3.17-item HAM-D score = 14 - this cut-off reflects a pragmatic minimum severity of depression as also chosen in comparable studies such as STAR*D (Rush et al 2006, Trivedi et al 2006) 4.Any gender and aged 18 years or over 5.Meet criteria for treatment resistant depression (Fekadu et al., 2009a; Cleare et al., 2015): current episode has not responded to at least two antidepressants given for at least 6 weeks at minimum therapeutic dose defined as fluoxetine =20mg/day, paroxetine =20mg/day, sertraline =50mg/day, citalopram =20mg/day, escitalopram =10mg/day, venlafaxine =75mg/day, duloxetine =60 mg/day, mirtazapine =15mg/day, tricyclic antidepressant =125mg/day, and dosage as guided by the national Maudsley Prescribing Guidelines or BNF for any other antidepressant. Please note, relapse whilst on an antidepressant also counts as a failed treatment trial 6.Current antidepressant treatment has remained unchanged and at, or above, a therapeutic dose for =6 weeks 7.Provision of written, informed consent. Exclusion Criteria: 1. Diagnosis of bipolar disorder (defined as meeting DSM-5 criteria for bipolar 1 or bipolar 2) on the MINI 7.0 (as recommended treatments are different for bipolar depression) 2. Diagnosis of current psychosis (as recommended treatments are different for current psychosis - antidepressants plus antipsychotics is the first-line treatment recommendation (NiCE, 2009; Cleare et al., 2015) 3. Adequate use of lithium or quetiapine during the current episode. An adequate dose of lithium is defined as the patient taking lithium for at least 4 weeks at an adequate dose (leading to a documented plasma concentration of >0.4mmol/L) and for quetiapine, prescription in the range of 150-300mg/d for 4 weeks or longer. Or, if the patient has taken an inadequate dose of lithium or quetiapine in the current episode, the patient and clinician are not willing to re-prescribe/take the medication. 4. Ongoing use of another atypical antipsychotic (discontinuation will be required before study entry i.e. any time prior to randomisation) 5. Known contraindication to use of either lithium or quetiapine: known hypersensitivity of lithium or quetiapine or any of their excipients; severe renal insufficiency / impairment; untreated hypothyroidism; severe cardiac disease / insufficiency; low sodium levels e.g. dehydrated patients or those on low sodium diets; Addison's disease; Brugada syndrome or family history of Brugada syndrome; the rare hereditary inborn errors of metabolism galactosaemia, the Lapp lactase deficiency or glucose-galactose malabsorption; concomitant administration of cytochrome P450 3A4 inhibitors; or congenital QT prolongation. 6. We will not recruit any individual who is currently participating in a clinical trial of an investigational medical product (CTIMP). 7. Insufficient degree of comprehension or attention to be able to engage in trial procedures. 8. We will exclude women who are pregnant, actively trying for pregnancy, or currently breastfeeding. This will be based on verbal report of the subject. Otherwise the management will be as appropriate according to standard clinical practice within the context of a pragmatic, open trial, for example adequate contraceptive precautions decided on the clinical judgement of the prescriber.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Quetiapine
Quetipatine prescribed in addition to the patient's existing antidepressant treatment.
Lithium
Lithium prescribed in addition to the patient's existing antidepressant treatment.

Locations

Country Name City State
United Kingdom Institute of Psychiatry, Psychology and Neuroscience, King's College London London

Sponsors (9)

Lead Sponsor Collaborator
King's College London Avon and Wiltshire Mental Health Partnership NHS Trust, Newcastle University, Northumberland, Tyne and Wear NHS Foundation Trust, Oxford Health NHS Foundation Trust, South London and Maudsley NHS Foundation Trust, Sussex Partnership NHS Foundation Trust, Tees, Esk and Wear Valleys NHS Foundation Trust, University of Oxford

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Change in global severity Change in CGI severity score Measured at 8, 26 and 52 weeks
Other Global efficacy Change in CGI efficacy score Measured at 8, 26 and 52 weeks
Other Side effects Frequency of individual items on the PRISE Measured at 8 and 52 weeks
Other Physical health changes Not completed for all participants. Will be reported if there is a sufficient number e.g. blood parameters and waist circumference Measured at baseline, 8, 26 and 52 weeks
Other Satisfaction with lithium / quetiapine treatment Measured using TSQM subscales Measured at 8, 26 and 52 weeks
Other Change in self-report manic symptoms Measured using the Altman Mania Self Rating Scale Measured at baseline, 8, 26 and 52 weeks
Other Change in anxiety symptoms GAD-7 score Measured at baseline, 8, 26 and 52 weeks
Other Time to prescription First date participant is given a prescription for the treatment 0-52 weeks
Other Baseline adherence to antidepressant MARS-5 score Measured at baseline
Other Change in cognition Total DSCT score Measured at baseline, 8, 26 and 52 weeks
Other Adherence of clinicians Clinician adherence to prescribing and monitoring guidelines 0-52 weeks
Other Proportion of participants having an adequate treatment trial Adequate treatment trial as defined in study protocol 0-8 weeks
Other Number of hospital admissions for depressive episode Measured using psychiatric history assessment 52 weeks
Other Change in personality measure SAPAS Measured at baseline, 8, 26 and 52 weeks
Other Social functioning WSAS Measured weekly over 12 months
Other Economic analysis Costs from the NHS and Personal Social Services perspective and from a societal perspective. 52 weeks
Other Predictors of treatment response Measured using the Maudsley Staging Model, HAM-D, MINI 7, IDS-C and SAPAS questionnaires. 52 weeks
Other Longitudinal depression severity until time to all cause treatment discontinuation Measured weekly using the QIDS-SR 52 weeks
Other Collection and analysis of biological samples for genetic, cytokine and cortisol analysis Blood/hair/saliva samples collected in collaboration with the BRC BioResource 0-52 weeks
Other Reliability and validity of the Maudsley VAS Measured using the Maudsley VAS, validated against the QIDS-SR and MADRS Measured at baseline, 8, 26 and 52 weeks
Other Discrepancy between the self-rated and clinician-rated version of 16 item IDS Assessed using QIDS and IDS Measured at baseline and 8 weeks
Other Relationship between quetiapine and lithium serum levels, prescribed dose and depressive symptom severity MADRS 52 weeks
Other Time to new interventions for depression. Measured using concomitant medication and concomitant therapy questionnaires 52 weeks
Other Number of new interventions for depression Measured using concomitant medication and concomitant therapy questionnaires 52 weeks
Other Patient rated experience of the True Colours weekly monitoring system Qualitative Interview in a subset of participants 8 / 26 / 52 weeks
Other Change in cognitive function THINC-it composite and individual tests scores in a subset of participants Baseline, 8, 26 and 52 weeks
Other 12. Patient views and experiences of lithium and quetiapine Qualitative interviews in a subset of participants 52 week visit
Primary Longitudinal depressive symptom severity QIDS-SR 52 weeks
Primary Difference in time to all-cause treatment discontinuation The difference in the time at which patients stop taking the medication for any reason between the two treatment arms. 12 months
Secondary Change in clinician rated depression severity MADRS From baseline to weeks 8 and 52
Secondary Response rates Assessed using the MADRS questionnaire 8 weeks and 52 weeks
Secondary Remission rates Assessed using the MADRS questionnaire 8 and 52 weeks
Secondary Health related quality of life Assessed using the EuroQol-5D questionnaire Measured at 8 and 52 weeks
Secondary Social functioning Measured using the WSAS self rated questionnaire Measured at baseline, 8 and 52 weeks
Secondary Adherence to treatment Assessed using the MARS-5 questionnaire Measured at weeks 8 and 52
Secondary Change in weight in kilograms Assessed by weighing participants Measured at 8 and 52 weeks
Secondary Change in diastolic blood pressure Assessed by measuring blood pressure Change from baseline to 8 and 52 weeks
Secondary Change in systolic blood pressure Assessed by measuring blood pressure Change from baseline to 8 and 52 weeks
Secondary Time to uptake of a new intervention (pharmacological or non-pharmalogical) Assessed by recording all pharmacological and non-pharmacological interventions 12 months
Secondary Time to initiation of treatment Assessed using treatment initiation form Up to 12 months
Secondary CGI Global Improvement CGI Measured at 8 and 52 weeks
Secondary Side effects PRISE total score Measured at 8 and 52 weeks
Secondary Serious Adverse Events Serious adverse events will be monitored and reported throughout the patient's participation in the trial. 52 weeks
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