Depressive Disorder, Treatment-Resistant Clinical Trial
— LQDOfficial title:
A Randomised Pragmatic Trial Comparing the Clinical and Cost Effectiveness of Lithium and Quetiapine Augmentation in Treatment Resistant Depression
Verified date | March 2021 |
Source | King's College London |
Contact | Lindsey Marwood |
LQDstudy[@]kcl.ac.uk | |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Institute of Psychiatry, Psychology and Neuroscience, King's College London | London |
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 |
United Kingdom,
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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