Name:	CEQUEL
Title:	Comparative Evaluation of QUEtiapine-Lamotrigine combination versus quetiapine monotherapy (and folic acid versus placebo) in patients with bipolar depression.
Researchers:
Funding Body:	MRC
Funding Awarded:	£1,626,468
Start Date:	01/04/2008
End Date:	31/03/2011

 

Background

Much of the burden of bipolar disorder is caused by depressive symptoms. Bipolar depression is often treated in the same ways as major depressive disorder but there is little evidence that this is effective and concerns that some treatments will increase the risk of switch to a manic state.

CEQUEL

CEQUEL is designed to address the urgent need to identify effective treatments that:

• Provide safe, tolerable and rapid reduction of depressive symptoms
• Avoid induction of manic symptoms in the short-term
• Maintain continued remission from depressive symptoms and freedom from manic symptoms in the longer-term.

Interventions:

• The NICE guidelines on treatment of bipolar disorder include quetiapine, an atypical antipsychotic, as a first-line treatment for depression. Evidence from RCTs suggests that quetiapine provides rapid relief of acute depression but has a high incidence of sedation and study withdrawal indicating the need for alternative treatments.
• There is also evidence that lamotrigine, an anticonvulsant, is tolerable and may be moderately effective for bipolar depression but the need for slow titration can lead to delayed therapeutic response.
• CEQUEL will explore the possibility that the combination quetiapine and lamotrigine will be more effective that quetiapine alone both for acute treatment of depressive symptoms and for longer-term maintenance of remission and prevention of depressive or manic relapse because: -
1. acute phase use of quetiapine to reduce depressive symptoms might make the slow introduction of lamotrigine more acceptable
2. As the dose of lamotrigine increases, the efficacy of the combination is likely to exceed that of quetiapine alone
3. If quetiapine is not tolerated in the longer-term, it can be withdrawn to leave lamotrigine monotherapy at a therapeutic dose.
4. There is also evidence that folic acid, vitamin B9, can increase response to antidepressant treatments. Furthermore response to folic acid may depend upon baseline serum levels of folate and homocysteine and upon genotype for two separate genes.
5. CEQUEL will compare folic with placebo as adjunctive therapy and explore these subgroup effects.

Procedures:

All participants will enter 7 to 14 say active run-in phase during which they will be prescribed open-label quetiapine. The run-in phase will provide immediate treatment for bipolar depression and restrict randomisation to people who can tolerate quetiapine and whose symptoms are persistent and severe enough for additional treatment to be considered. Randomisation will be to lamotrigine or placebo and to folic acid or placebo. The randomised phase will last one year.

Outcome measures: The primary outcome

The primary outcome measure will be remission from depression at 12 weeks (defined as a score of <=5 on the Quick Inventory of Depressive Symptomatology (QIDS-SR16).

Secondary outcomes

Will include the proportion of time spent free from depressive and manic symptoms over 12 months (manic symptoms assessed using the Altman Self-Rating Mania Scale [ASRMI]); deliberate self-harm; quality of life and use of health and social care service resources. Participants will complete weekly self-assessments of depressive and manic symptoms and submit them to the trial office using mobile phone text-message, email, webform or paper forms.