Clinical trial NCT03899285: Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders
Official title: Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders: a Pilot Study (CRY-MOOD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: citalopram
major depressive disorder
non responder
MADRS
Lead sponsor: Ciusss de L'Est de l'Île de Montréal
Sponsor class: OTHER
First posted: 2019-04-02
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Preparation phase (Phase 1) : Every enrolled patients start with citalopram 10 mg daily for 3 days and 20 mg daily for 11 days.

Escalation phase (Phase 2) :This phase is split in two arms which are the responders and the non-responders. Responders will pursue their citalopram 20 mg for 14 days. Non-responders will be assigned randomly 1:1 in 2 groups. Patients in group A will be randomized to receive a pill of citalopram 20 mg and a capsule of citalopram 20 mg for 14 days. The total dose of citalopram will be 40 mg once daily. Patients in group B receive a pill of citalopram 20 mg and a capsule of placebo (a capsule without medication) for 14 days. The total dose of citalopram will be 20 mg once daily.

Follow-up phase (Phase 3) : Every responders will pursue their treatment of citalopram 20 mg daily for 28 days. It's possible that in this group, the treatment approach may vary depending the physician. Every non-responders (group A and B) will receive 40 mg of citalopram for 28 days.
Primary purpose: TREATMENT

Brief summary: Major depressive disorder is a common mental disorder and the leading cause of disability worldwide. According to the Canadian Network for Mood and Anxiety Treatment, early improvement following an antidepressant treatment is correlated with response and remission. Escalation of an antidepressant dose after 2 weeks, as opposed to 4 to 8 weeks, is proposed to favor early improvement. However, this has never been tested systematically in a controlled study involving major depressive disorder patients that are non-responders to their antidepressant treatment.

Detailed description: The investigators sought to assess whether it is feasible to perform a prospective randomized controlled double-blind feasibility study with a 2 week run-in period and 3 parallel groups randomized controlled study using citalopram. Citalopram has physicochemical properties compatible with over-encapsulation and a has a simple titration that allows the study of early dose increase.. It is among the most prescribed antidepressant in the province of Quebec and at the Hospital Maisonneuve-Rosemont - University family medicine group (U-FMG).

Since establishment of a randomized controlled trial is complex and expensive, a feasibility design is appropriate to identify all the obstacles and to minimize sources of possible bias (recruitment, follow up, resources).

Eligibility criteria: Inclusion Criteria:

* Understand french or english
* Primary diagnostic of major depressive disorder based on the Diagnostic and Statistical Manual of Mental Disorders criteria (5th edition)
* Prescription of citalopram
* Citalopram started less than 4 days ago
* Able to receive informed consent
* Not participating to another study

Exclusion Criteria:

* Pregnancy or breastfeeding
* Unable to participate to follow-up
* Hypersensitivity to citalopram or any component of the formulation
* Known QT interval prolongation or congenital long QT syndrome
* Hepatic impairment (Child Pugh A, B or C)
* Renal impairment (Clcr \< 30 ml/min)
* Known cytochrome P450 2C19 poor metabolizers
* History of non-response to citalopram
* Head trauma or severe cognitive impairment
* Substance-related and addictive disorders controlled less than 3 months or uncontrolled
* Schizophrenia or psychotic disorder
* Mixed depression
* History of manic/hypomanic episodes
* Use of prohibited drugs : monoamine oxidase inhibitors, cytochrome P450 2C19 inhibitors, drugs at risk of causing prolongation of the QT interval, cimetidine, pimozide and antidepressors taken for another psychiatric condition.

Primary outcomes:
measure: Primary outcomes determined by the proportion of non-responders (< 30 % improvement on the MADRS) after 2 weeks of treatment and the proportion of non-responders randomized patients who completed the study.
timeFrame: 8 weeks
Secondary outcomes:
measure: Proportion of eligible subjects
timeFrame: 8 weeks
measure: Recruitment rate
timeFrame: 8 weeks
measure: Retention rate
timeFrame: 8 weeks
measure: Adherence rate to treatment
timeFrame: 8 weeks
measure: Unblinding rate
timeFrame: 8 weeks
measure: Length of interviews
timeFrame: 8 weeks
measure: Side effects reported to the assessors and measured by the Frequency, Intensity, and Burden of Side Effect Rating (FIBSER).
timeFrame: 8 weeks
measure: Response curves for all patients according to the results from the MADRS.
timeFrame: 8 weeks
measure: Correlation between the results of Patient Health Questionnaire-9 (PHQ-9) and the MADRS at each follow-up (T2, T4, T6 and T8).
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Montréal-Est
country: Canada
facility: GMF-U Maisonneuve-Rosemont hospital
state: Quebec
Study officials:
affiliation: GMF-U Maisonneuve-Rosemont Hospital
name: Marie-Claude Lefebvre, MD
role: PRINCIPAL_INVESTIGATOR
References: