Minocycline as Adjunctive Treatment for Treatment Resistant Depression: a Double Blind, Placebo-controlled, Randomized Trial (MINDEP2)

  • End date
    Jan 17, 2023
  • participants needed
  • sponsor
    Centre for Addiction and Mental Health
Updated on 17 September 2022
adjunctive treatment
depressive disorder
depressive symptoms
depressive episode
a 12


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.

Condition Treatment Resistant Depression
Treatment Minocycline
Clinical Study IdentifierNCT03947827
SponsorCentre for Addiction and Mental Health
Last Modified on17 September 2022


Yes No Not Sure

Inclusion Criteria

Outpatients, voluntary and capable to consent
DSM-5 diagnosis of non-psychotic MDD, single or recurrent
Baseline HRSD score > 14
ATHF total score > 3
Current adequate trial of one of the following standard antidepressants: Escitalopram, Citalopram, Sertraline, Venlafaxine, Duloxetine, Mirtazapine or Bupropion
If female of childbearing potential, currently on a medically acceptable form of birth control

Exclusion Criteria

DSM-5 substance use disorder within past 3 months, moderate or severe
DSM-5 diagnosis of psychotic disorder, bipolar disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) within last year, or borderline personality disorder (BPD)
Major unstable medical illness
Intolerance or contraindication to tetracyclines
Pregnancy or intent to become pregnant during study period
Concomitant treatment with anticoagulants, diuretics, retinoids, ergot alkaloids, antacids containing aluminium, calcium or magnesium, bismuth and zinc salts, or quinapril
Abnormal readings in hematology, liver, or renal function tests
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