Citalopram Titration in Early Non-responder Patients With Major Depressive Disorders

NCT03899285 | Completed Phase 2

• 1 other identifier: 2018-1215
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder

Keywords

citalopram; major depressive disorder; non responder; MADRS

Outcome Measures

Primary Outcomes (1)

• 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.

  The efficacy of treatment was assessed by the Montgomery and Asberg Depression Rating Scale (MADRS).Threshold for non-responders : \< 30 % improvement on the MADRS between T2 and T0. This scale was completed by a trained assessor and measures the severity of depressive episodes in patients with mood disorders. The scale is in french and has 10 items, with an overall score ranging from 0 to 60 points. Higher score indicates more severe depression. Criteria for success of the randomization and completion of the study : * Sample size target : 24 non-responders randomized patients * Proportion of non-responders after 2 weeks of treatment (T2) : ≥ 0.45 (number of non-responders after 2 weeks of treatment divided by the number of enrolled patients). * Proportion of non-responders randomized patients who completed the full course of treatment (8 weeks) : ≥ 0.65 (number of non-responders randomized patients who completed the study divided by the total number of enrolled patients).

  8 weeks

Secondary Outcomes (9)

• Proportion of eligible subjects

  8 weeks

• Recruitment rate

  8 weeks

• Retention rate

  8 weeks

• Adherence rate to treatment

  8 weeks

• Unblinding rate

  8 weeks

Study Arms (3)

Citalopram increase (group A)

EXPERIMENTAL

At the end of the preparation phase, non-responders will be randomized to receive a pill of citalopram 20 mg and a capsule of citalopram 20 mg for a length of 14 days. The total dose of citalopram will be 40 mg once daily. Follow up will last 8 weeks in total.

Drug: Citalopram 20mg or 40 mg (phase 2)

Placebo (group B)

PLACEBO COMPARATOR

At the end of the preparation phase, non-responders will be randomized to receive a pill of citalopram 20 mg and a capsule of placebo (a capsule without medication) for a length of 14 days. The total dose of citalopram will be 20 mg once daily. Follow up will last 8 weeks in total.

Drug: Citalopram 20mg or 40 mg (phase 2)

Observational arm (group c)

NO INTERVENTION

Eligible patients to this arm are responders to citalopram. A diminution of at least 30% of the symptoms from baseline with the MADRS is required to enter this arm. At the end of the first phase, these patients will pursue their citalopram 20 mg for the rest of the study (=6 weeks). It's possible that in this group, the treatment approach may vary depending the physician. Follow up will last 8 weeks in total.

Interventions

Citalopram 20mg or 40 mg (phase 2) DRUG

For non-responders, a randomisation 1:1 was chosen. The group A will receive 40 mg and the group B will receive 20 mg once daily of citalopram for 14 days.

Citalopram increase (group A); Placebo (group B)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ciusss de L'Est de l'Île de Montréal: lead

Study Sites (1)

GMF-U Maisonneuve-Rosemont hospital

Montreal East, Quebec, H1T 2M4, Canada

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Citalopram; Clinical Trials, Phase II as Topic

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Clinical Trials as Topic; Clinical Studies as Topic; Epidemiologic Study Characteristics; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Marie-Claude Lefebvre, MD

  GMF-U Maisonneuve-Rosemont Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Over-encapsulation was performed to maintain blind. Every participant will have the same step (visits, follow up, questionnaire and interview).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: 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.

Study Record Dates

• First Submitted: August 24, 2018
• First Posted: April 2, 2019
• Study Start: January 8, 2018
• Primary Completion: December 8, 2018
• Study Completion: December 8, 2018
• Last Updated: April 4, 2019

Record last verified: 2019-04

Locations

CA (1)