Lithium Versus Quetiapine in Treatment Resistant Depression

NCT03004521 | Unknown Phase 4 DMC

• 1 other identifier: HTA 14/222/02
• Study Type: interventional
• Target: 276
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Depressive Disorder, Treatment-Resistant

Keywords

Lithium; Quetiapine; Augmentation

Outcome Measures

Primary Outcomes (2)

• Longitudinal depressive symptom severity

  QIDS-SR

  52 weeks

• 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 Outcomes (14)

• Change in clinician rated depression severity

  From baseline to weeks 8 and 52

• Response rates

  8 weeks and 52 weeks

• Remission rates

  8 and 52 weeks

• Health related quality of life

  Measured at 8 and 52 weeks

• Social functioning

  Measured at baseline, 8 and 52 weeks

Other Outcomes (27)

• Change in global severity

  Measured at 8, 26 and 52 weeks

• Global efficacy

  Measured at 8, 26 and 52 weeks

• Side effects

  Measured at 8 and 52 weeks

Study Arms (2)

Lithium

ACTIVE COMPARATOR

Lithium will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment.

Drug: Lithium

Quetiapine

EXPERIMENTAL

Quetiapine will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment.

Drug: Quetiapine

Interventions

Quetiapine DRUG

Quetipatine prescribed in addition to the patient's existing antidepressant treatment.

Quetiapine

Lithium DRUG

Lithium prescribed in addition to the patient's existing antidepressant treatment.

Lithium

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Under the care of a GP and/or adult mental health services
• 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)
• 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.

You may not qualify if:

• 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)
• 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)
• 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.
• Ongoing use of another atypical antipsychotic (discontinuation will be required before study entry i.e. any time prior to randomisation)
• 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.
• We will not recruit any individual who is currently participating in a clinical trial of an investigational medical product (CTIMP).
• Insufficient degree of comprehension or attention to be able to engage in trial procedures.
• 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.

Sponsors & Collaborators

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

Study Sites (1)

Institute of Psychiatry, Psychology and Neuroscience, King's College London

London, SE5 8AF, United Kingdom

RECRUITING

Related Publications (1)

• Marwood L, Taylor R, Goldsmith K, Romeo R, Holland R, Pickles A, Hutchinson J, Dietch D, Cipriani A, Nair R, Attenburrow MJ, Young AH, Geddes J, McAllister-Williams RH, Cleare AJ. Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of lithium and quetiapine augmentation in treatment resistant depression (the LQD study). BMC Psychiatry. 2017 Jun 26;17(1):231. doi: 10.1186/s12888-017-1393-0.

  PMID: 28651526 DERIVED

Related Links

• Study website link

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Quetiapine Fumarate; Lithium

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Dibenzothiazepines; Thiazepines; Thiepins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Metals, Alkali; Elements; Inorganic Chemicals; Metals, Light; Metals

Study Officials

• Anothony Cleare

  Professor of Psychiatry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lindsey Marwood

CONTACT

LQDstudy@kcl.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2016
• First Posted: December 29, 2016
• Study Start: November 1, 2016
• Primary Completion: April 1, 2021
• Study Completion: August 1, 2021
• Last Updated: March 5, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)