Treatment Resistant DepressionPhase 3MINDEP2NCT03947827
Minocycline as Adjunctive Treatment for Treatment Resistant Depression
A Phase 3 study testing Minocycline in people with Treatment Resistant Depression, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Minocycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteCanada
- Study dates
- 1 Feb 2020to 7 Jan 2025
- Phase
- Phase 3
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Outpatients
- Voluntary and competent to consent to treatment
- DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the SCID-5
- Male or female aged between 18-80
- Total score > 3 on ATHF
- Baseline HRSD-17 score > 14
Show all 10Show fewer
- Able to adhere to study schedule
- 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)
- Currently taking one of the following standard antidepressants: Escitalopram, Citalopram, Sertraline, Venlafaxine, Duloxetine, Mirtazapine or Bupropion
- Been on same dose of all psychotropic medications for > 4 weeks prior to enrolment
Who cannot join
- DSM-5 substance use disorder within past 3 months, moderate or severe, based on SCID-5
- Concomitant major unstable medical illness
- Pregnancy or intent to become pregnant during study period
- DSM-5 diagnosis of psychotic disorder, bipolar disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) within last year
- DSM-5 diagnosis of borderline personality disorder (BPD)
- Possible or probable dementia
Show all 10Show fewer
- Prior or current intolerance or contraindication to tetracyclines
- Abnormal readings in hematology, liver, or renal function tests
- Have Myasthenia Gravis
- Concomitant treatment with anticoagulants, diuretics, retinoids, ergot alkaloids, antacids containing aluminium/calcium/magnesium, bismuth and zinc salts, or quinapril
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Minocycline as Adjunctive Treatment for Treatment Resistant Depression: a Double Blind, Placebo-controlled, Randomized Trial
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
- Being tested
- Minocycline
- Keywords
- Treatment Resistant Depression, Minocycline, Neuroinflammation, Microglial Activation, Biomarker
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, cyclopia sequence, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called Apo-Minocycline
Participants will be randomized to receive either Minocycline or placebo added to standard oral antidepressants.
| Study group | Role | What they receive |
|---|---|---|
| Active | Active comparator | Minocycline will start at an oral dose of 100mg daily and will be increased after one week to 100mg twice daily. Receives: Drug: Minocycline |
| Placebo | Placebo comparator | Placebo capsules will start at one capsule daily, and will be increased after one week to one capsule twice daily Receives: Drug: Minocycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depressive symptoms
Changes from baseline to week 12 on the 17-item Hamilton Rating Scale for Depression (HRSD-17).
Measured: 12 weeks
Secondary outcomes (5)
Response rate
Reduction of 50% or more in HRSD score from baseline to week 12
Measured: 12 weeks
Remission rate
Final HRSD score < 8
Measured: 12 weeks
Anxiety symptoms
Changes from baseline to week 12 in Generalized Anxiety Disorder scale (GAD-7)
Measured: 12 weeks
Self-reported perception of quality of life
Changes from baseline to week 12 in World Health Organization Quality of Life Short Version (WHOQOL-BREF)
Measured: 12 weeks
Clinician-rated illness severity
Changes from baseline to week 12 in Clinical Global Impression scale (CGI)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2019
- Study start1 Feb 2020
- Primary completion7 Jan 2025
- Study completion7 Jan 2025
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 Treatment Resistant DepressionStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Responsible party
- Principal investigator, Ishrat Husain, Centre for Addiction and Mental Health
- Investigators
- Ishrat Husain, MBBS, MD(Res.), Principal investigator, CAMH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03947827
- Sponsor's protocol ID
- 135/2018
- Acronym
- MINDEP2
- Status last verified
- Mar 2026
- First submitted
- 9 May 2019
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32295565
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Minocycline as Adjunctive Treatment for Treatment Resistant Depression: a Double Blind, Placebo-controlled, Randomized Trial
- ClinicalTrials.gov ID
- NCT03947827
- Acronym / sponsor ID
- MINDEP2 / 135/2018
- Conditions
- Treatment Resistant Depression
- Keywords
- Treatment Resistant Depression, Minocycline, Neuroinflammation, Microglial Activation, Biomarker
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 7 Jan 2025 (actual)
- Study completion
- 7 Jan 2025 (actual)
- First posted
- 13 May 2019 (actual)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active | Active comparator | Drug: MinocyclineMinocycline will start at an oral dose of 100mg daily and will be increased after one week to 100mg twice daily. |
| Placebo | Placebo comparator | Drug: MinocyclinePlacebo capsules will start at one capsule daily, and will be increased after one week to one capsule twice daily |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Outpatients
- Voluntary and competent to consent to treatment
- DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the SCID-5
- Male or female aged between 18-80
- Total score > 3 on ATHF
Key exclusion criteria (10 listed)
- DSM-5 substance use disorder within past 3 months, moderate or severe, based on SCID-5
- Concomitant major unstable medical illness
- Pregnancy or intent to become pregnant during study period
- DSM-5 diagnosis of psychotic disorder, bipolar disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) within last year
- DSM-5 diagnosis of borderline personality disorder (BPD)
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 |
|---|---|---|
| MinocyclineAlso: Apo-MinocyclineParticipants will be randomized to receive either Minocycline or placebo added to standard oral antidepressants. | Drug | Active, Placebo |
Primary outcome
Depressive symptoms
Time frame: 12 weeks
Changes from baseline to week 12 on the 17-item Hamilton Rating Scale for Depression (HRSD-17).
5 secondary outcomes
Response rate
Time frame: 12 weeks
Remission rate
Time frame: 12 weeks
Anxiety symptoms
Time frame: 12 weeks
Self-reported perception of quality of life
Time frame: 12 weeks
Clinician-rated illness severity
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Derived from this study: PubMed 32295565Husain 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.
- Individual participant dataSharing planned: No
Related trials for Treatment Resistant Depression
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant
Active, not recruiting
CET- REM (Correlating ECT Response to EEG Markers)
ECT, Treatment Resistant Depression
Active, not recruiting
rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression
Depression, Treatment Resistant
Recruiting
A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy® System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression
Treatment Resistant Depression
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.
Ishrat Husain, MBBS, MD(Res.) principal investigator
CAMH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Minocycline in people with Treatment Resistant Depression, run by Centre for Addiction and Mental Health at 1 site in Canada.
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 10 inclusion and 10 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: finished, as of the sponsor's last update on 27 Mar 2026. 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 Canada. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Depressive symptoms (time frame: 12 weeks). 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 NCT03947827, 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 27 Mar 2026.