Lithium Versus Quetiapine in Treatment Resistant Depression

Depressive Disorder, Treatment-Resistant Clinical Trial

— LQD  

Official title:

A Randomised Pragmatic Trial Comparing the Clinical and Cost Effectiveness of Lithium and Quetiapine Augmentation in Treatment Resistant Depression

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03004521
• Other study ID #: HTA 14/222/02
• Status: Recruiting
• Phase: Phase 4
• 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
• 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.

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Treatment-Resistant

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

External Links

•   Study website link