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Completed

NCT Number: NCT03947827

Minocycline as Adjunctive Treatment for Treatment Resistant Depression

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.

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Key information

Conditions

Treatment Resistant Depression Depressive Disorder Depressive Disorder, Treatment-Resistant Inflammation Mental Disorders Mood Disorders Nervous System Diseases Neuroinflammatory Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms cyclopia sequence

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centre for Addiction and Mental Health

Toronto, Ontario, M6J 1H4, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • 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

Exclusion criteria

  • 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
  • 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

Treatment and study plan

Minocycline

Drug

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

Other names: Apo-Minocycline

Primary outcomes

  1. Depressive symptoms

    Time frame: 12 weeks

    Changes from baseline to week 12 on the 17-item Hamilton Rating Scale for Depression (HRSD-17).

Secondary outcomes

  1. Response rate

    Time frame: 12 weeks

    Reduction of 50% or more in HRSD score from baseline to week 12

  2. Remission rate

    Time frame: 12 weeks

    Final HRSD score < 8

  3. Anxiety symptoms

    Time frame: 12 weeks

    Changes from baseline to week 12 in Generalized Anxiety Disorder scale (GAD-7)

  4. Self-reported perception of quality of life

    Time frame: 12 weeks

    Changes from baseline to week 12 in World Health Organization Quality of Life Short Version (WHOQOL-BREF)

  5. Clinician-rated illness severity

    Time frame: 12 weeks

    Changes from baseline to week 12 in Clinical Global Impression scale (CGI)

Sponsors and collaborators

Lead sponsor

Centre for Addiction and Mental Health

Other

Collaborators

  • The Physicians' Services Incorporated Foundation

Registry information

Official study title

Minocycline as Adjunctive Treatment for Treatment Resistant Depression: a Double Blind, Placebo-controlled, Randomized Trial

Acronym: MINDEP2

Important dates

Study start
2020
Primary completion
2025
Study completion
2025
First posted
May 13, 2019
Registry last updated
Mar 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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