Minocycline As Adjunctive Treatment for Treatment Resistant Depression

NCT ID: NCT03947827

Last Updated: 2025-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-01
• Study Completion Date: 2025-01-07

Brief Summary

Major depressive disorder (MDD) is a leading cause of disability worldwide. Up to 50% of patients experience treatment resistant depression (TRD), which accounts for a vast majority of disease burden. Current medications for TRD have limited efficacy and can be associated with intolerable side effects. Therefore, there is a need for finding new treatment targets. Accumulating evidence suggests some patients with MDD including those with TRD, display brain inflammation. Thus, patients with TRD may benefit from medications that can reduce this inflammation. Minocycline is an antibiotic which can cross the blood-brain barrier and has effects on several systems implicated in depression. The principal investigator led the first pilot study of minocycline as an add-on treatment in TRD demonstrating that it led to a significant reduction in depressive symptoms compared to placebo and these findings require replication in a larger sample to confirm the efficacy and tolerability of this treatment approach.

This study is a 12 week, double-blind, placebo-controlled trial of minocycline as add-on treatment for patients suffering from a major depressive episode who have failed to respond to antidepressant treatment, confirmed by the Structured Clinical Interview for DSM-5 (SCID-5) and the Antidepressant Treatment History Form (ATHF) at screening. After screening and randomization to the two parallel arms of the trial, 50 patients will receive minocycline added to treatment as usual (TAU) and 50 patients will receive placebo added to TAU. Clinical assessment will include the Hamilton Depression Rating Scale (HRSD-17), Clinical Global Impression scale (CGI), World Health Organization Quality of Life Short Form (WHOQOL-BREF), and Generalized Anxiety Disorder scale (GAD-7), administered at each study visit (baseline, week 2, 6, and 12). Side effects checklists will be undertaken at each visit. Minocycline will be started at 100 mg once daily and will be increased to 100 mg twice daily at two weeks. Secondary outcomes include inflammatory biomarkers measured at baseline, weeks 6 and 12.

This trial will provide further evidence of minocycline's efficacy and acceptability as a treatment option for patients with TRD and provide insights into its mechanism of action.

Conditions

Treatment Resistant Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active

Minocycline will start at an oral dose of 100mg daily and will be increased after one week to 100mg twice daily.

Group Type: ACTIVE_COMPARATOR

Minocycline

Intervention Type: DRUG

Participants will be randomized to receive either Minocycline or placebo added to standard oral antidepressants.

Placebo

Placebo capsules will start at one capsule daily, and will be increased after one week to one capsule twice daily

Group Type: PLACEBO_COMPARATOR

Minocycline

Intervention Type: DRUG

Participants will be randomized to receive either Minocycline or placebo added to standard oral antidepressants.

Interventions

Minocycline

Participants will be randomized to receive either Minocycline or placebo added to standard oral antidepressants.

Intervention Type: DRUG

Other Intervention Names

Apo-Minocycline

Eligibility Criteria

Inclusion Criteria

1. Outpatients

2. Voluntary and competent to consent to treatment

3. DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the SCID-5

4. Male or female aged between 18-80

5. Total score > 3 on ATHF

6. Baseline HRSD-17 score > 14

7. Able to adhere to study schedule

8. If female of childbearing potential, currently on a medically acceptable form of birth control (oral contraceptives, contraceptive injections, IUD, contraceptive patch, male partner sterilization, abstinence, or barrier methods plus spermicide)

9. Currently taking one of the following standard antidepressants: Escitalopram, Citalopram, Sertraline, Venlafaxine, Duloxetine, Mirtazapine or Bupropion

10. Been on same dose of all psychotropic medications for > 4 weeks prior to enrolment

Exclusion Criteria

1. DSM-5 substance use disorder within past 3 months, moderate or severe, based on SCID-5

2. Concomitant major unstable medical illness

3. Pregnancy or intent to become pregnant during study period

4. DSM-5 diagnosis of psychotic disorder, bipolar disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) within last year

5. DSM-5 diagnosis of borderline personality disorder (BPD)

6. Possible or probable dementia

7. Prior or current intolerance or contraindication to tetracyclines

8. Abnormal readings in hematology, liver, or renal function tests

9. Have Myasthenia Gravis

10. Concomitant treatment with anticoagulants, diuretics, retinoids, ergot alkaloids, antacids containing aluminium/calcium/magnesium, bismuth and zinc salts, or quinapril

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Physicians' Services Incorporated Foundation

OTHER

Sponsor Role: collaborator

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Ishrat Husain

Clinician Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ishrat Husain, MBBS, MD(Res.)

Role: PRINCIPAL_INVESTIGATOR

CAMH

Locations

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Countries

Canada

References

Husain MI, Cullen C, Umer M, Carvalho AF, Kloiber S, Meyer JH, Ortiz A, Knyahnytska Y, Husain MO, Giddens J, Diniz BS, Wang W, Young AH, Mulsant BH, Daskalakis ZJ. Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2). BMC Psychiatry. 2020 Apr 15;20(1):173. doi: 10.1186/s12888-020-02553-9.

Reference Type: DERIVED

PMID: 32295565 (View on PubMed)

Other Identifiers

135/2018

Identifier Type: -

Identifier Source: org_study_id