Depressive Disorder, Treatment-ResistantPhase 4LQDNCT03004521
Lithium Versus Quetiapine in Treatment Resistant Depression
A Phase 4 study testing Quetiapine and Lithium in people with Depressive Disorder, Treatment-Resistant, run by King's College London at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depressive Disorder, Treatment-Resistant
- What is being tested?
- Quetiapine and Lithium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 276 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Nov 2016to Aug 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Lindsey Marwood contact
United Kingdom1 site, 1 recruiting
- Recruiting
Institute of Psychiatry, Psychology and Neuroscience, King's College London
London, SE5 8AF
Helena Tee, helena.tee@kcl.ac.uk
About this study
Official title: A Randomised Pragmatic Trial Comparing the Clinical and Cost Effectiveness of Lithium and Quetiapine Augmentation in Treatment Resistant Depression
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.
Read the detailed 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.
- Conditions
- Depressive Disorder, Treatment-Resistant
- Being tested
- Quetiapine, Lithium
- Keywords
- Lithium, Quetiapine, Augmentation
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QuetiapineDrug
Quetipatine prescribed in addition to the patient's existing antidepressant treatment.
LithiumDrug
Lithium prescribed in addition to the patient's existing antidepressant treatment.
| Study group | Role | What they receive |
|---|---|---|
| Lithium | Active comparator | Lithium will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment. Receives: 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. Receives: Drug: Quetiapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Longitudinal depressive symptom severity
QIDS-SR
Measured: 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.
Measured: 12 months
Secondary outcomes (14)
Change in clinician rated depression severity
MADRS
Measured: From baseline to weeks 8 and 52
Response rates
Assessed using the MADRS questionnaire
Measured: 8 weeks and 52 weeks
Remission rates
Assessed using the MADRS questionnaire
Measured: 8 and 52 weeks
Health related quality of life
Assessed using the EuroQol-5D questionnaire
Measured: Measured at 8 and 52 weeks
Social functioning
Measured using the WSAS self rated questionnaire
Measured: Measured at baseline, 8 and 52 weeks
Adherence to treatment
Assessed using the MARS-5 questionnaire
Measured: Measured at weeks 8 and 52
Change in weight in kilograms
Assessed by weighing participants
Measured: Measured at 8 and 52 weeks
Change in diastolic blood pressure
Assessed by measuring blood pressure
Measured: Change from baseline to 8 and 52 weeks
Change in systolic blood pressure
Assessed by measuring blood pressure
Measured: Change from baseline to 8 and 52 weeks
Time to uptake of a new intervention (pharmacological or non-pharmalogical)
Assessed by recording all pharmacological and non-pharmacological interventions
Measured: 12 months
Time to initiation of treatment
Assessed using treatment initiation form
Measured: Up to 12 months
CGI Global Improvement
CGI
Measured: Measured at 8 and 52 weeks
Side effects
PRISE total score
Measured: Measured at 8 and 52 weeks
Serious Adverse Events
Serious adverse events will be monitored and reported throughout the patient's participation in the trial.
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2016 (estimated)
- Study startNov 2016
- Primary completionApr 2021 (estimated)
- Study completionAug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Depressive Disorder, Treatment-ResistantStudies of the same condition, open and under way.
- More trials run by King's College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 276 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College London
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford, Newcastle University, Oxford Health NHS Foundation Trust, Northumberland, Tyne and Wear NHS Foundation Trust, South London and Maudsley NHS Foundation Trust, Tees, Esk and Wear Valleys NHS Foundation Trust, Sussex Partnership NHS Foundation Trust, Avon and Wiltshire Mental Health Partnership NHS Trust
- Responsible party
- Sponsor
- Investigators
- Anothony Cleare, Principal investigator, Professor of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03004521
- Sponsor's protocol ID
- HTA 14/222/02
- Acronym
- LQD
- Status last verified
- Mar 2021
- First submitted
- 17 Nov 2016
- Last updated
- 5 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: The decision to share IPD to other researchers will be made by the CI on a case by case basis.
Publications
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.
PubMed 28651526
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Pragmatic Trial Comparing the Clinical and Cost Effectiveness of Lithium and Quetiapine Augmentation in Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT03004521
- Acronym / sponsor ID
- LQD / HTA 14/222/02
- Conditions
- Depressive Disorder, Treatment-Resistant
- Keywords
- Lithium, Quetiapine, Augmentation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 276 participants (estimated)
- Lead sponsor
- King's College LondonUniversity, hospital or other
- Collaborators
- University of Oxford, Newcastle University, Oxford Health NHS Foundation Trust, Northumberland, Tyne and Wear NHS Foundation Trust, South London and Maudsley NHS Foundation Trust, Tees, Esk and Wear Valleys NHS Foundation Trust, Sussex Partnership NHS Foundation Trust, Avon and Wiltshire Mental Health Partnership NHS Trust
- Study start
- Nov 2016 (actual)
- Primary completion
- Apr 2021 (estimated)
- Study completion
- Aug 2021 (estimated)
- First posted
- 29 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lithium | Active comparator | Drug: LithiumLithium will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment. |
| Quetiapine | Experimental | Drug: QuetiapineQuetiapine will be prescribed to patients in this arm as an augmenter on top of a patient's existing antidepressant treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QuetiapineQuetipatine prescribed in addition to the patient's existing antidepressant treatment. | Drug | Quetiapine |
| LithiumLithium prescribed in addition to the patient's existing antidepressant treatment. | Drug | Lithium |
Primary outcome
Longitudinal depressive symptom severity
Time frame: 52 weeks
QIDS-SR
Difference in time to all-cause treatment discontinuation
Time frame: 12 months
The difference in the time at which patients stop taking the medication for any reason between the two treatment arms.
14 secondary outcomes
Change in clinician rated depression severity
Time frame: From baseline to weeks 8 and 52
Response rates
Time frame: 8 weeks and 52 weeks
Remission rates
Time frame: 8 and 52 weeks
Health related quality of life
Time frame: Measured at 8 and 52 weeks
Social functioning
Time frame: Measured at baseline, 8 and 52 weeks
Adherence to treatment
Time frame: Measured at weeks 8 and 52
Change in weight in kilograms
Time frame: Measured at 8 and 52 weeks
Change in diastolic blood pressure
Time frame: Change from baseline to 8 and 52 weeks
Change in systolic blood pressure
Time frame: Change from baseline to 8 and 52 weeks
Time to uptake of a new intervention (pharmacological or non-pharmalogical)
Time frame: 12 months
Time to initiation of treatment
Time frame: Up to 12 months
CGI Global Improvement
Time frame: Measured at 8 and 52 weeks
Side effects
Time frame: Measured at 8 and 52 weeks
Serious Adverse Events
Time frame: 52 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2021.
- Derived from this study: PubMed 28651526Marwood 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.
- Study website linkLink provided by the sponsor.
- Individual participant dataSharing planned: No. The decision to share IPD to other researchers will be made by the CI on a case by case basis.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lindsey Marwood contact
Anothony Cleare principal investigator
Professor of Psychiatry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Quetiapine and Lithium in people with Depressive Disorder, Treatment-Resistant, run by King's College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lindsey Marwood (LQDstudy@kcl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Longitudinal depressive symptom severity (time frame: 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03004521, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2021.