Minocycline for Treatment-Resistant Depression

(MINDEP2 Trial)

Overseen By Mary (Lily) Kittur

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Centre for Addiction and Mental Health

Must be taking: Standard antidepressants

Must not be taking: Anticoagulants, Diuretics, Retinoids, others

Disqualifiers: Substance use, Psychotic disorder, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether minocycline, an antibiotic, can aid those with depression unresponsive to other treatments. Minocycline may reduce brain inflammation, which is believed to contribute to certain types of depression. The trial will compare minocycline with a placebo to determine which is more effective as an add-on treatment. Suitable participants have ongoing depression despite using medications like Escitalopram or Sertraline and have maintained the same medication dose for over four weeks. As a Phase 3 trial, this study represents the final step before FDA approval, providing an opportunity to contribute to a potentially groundbreaking treatment for depression.

Will I have to stop taking my current medications?

No, you won't have to stop taking your current antidepressants. The trial involves adding minocycline to your existing treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that minocycline is generally safe and well-tolerated. In past studies, most participants did not experience serious side effects. While its effectiveness in treating depression symptoms has varied, its safety remains consistently supported. As an antibiotic used for a long time, doctors are familiar with its effects on the body. When used for other health issues, it has proven safe, suggesting it might be a safe option for treating depression that hasn't improved with other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for depression?

Minocycline is unique because it offers a new approach to treating treatment-resistant depression by utilizing its anti-inflammatory properties. Unlike traditional antidepressants like SSRIs and SNRIs, which primarily target neurotransmitter imbalances, minocycline acts on neuroinflammation, which is increasingly recognized as a significant factor in depression. Researchers are excited because this could lead to relief for those who haven't responded to standard treatments, potentially opening up a new frontier in mental health care.

What evidence suggests that minocycline might be an effective treatment for treatment-resistant depression?

Research has shown that minocycline might improve symptoms in people with depression, even if their depression doesn't respond to other treatments. This trial will assign participants to receive either minocycline or a placebo. One study found that people who took minocycline felt significantly better compared to those who took a placebo, which contains no active medicine. However, another study found that minocycline did not outperform a placebo in reducing depression symptoms. Some evidence suggests that minocycline might be more beneficial for people with inflammation, where the body's tissues become swollen or irritated. Overall, the results are mixed, but minocycline could potentially help some people with treatment-resistant depression. ^{2 3 5 6 7}

Who Is on the Research Team?

Ishrat Husain, MBBS, MD(Res.)

Principal Investigator

CAMH

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 with non-psychotic major depressive disorder (MDD) who haven't responded to standard antidepressants. Participants must have a certain level of depression severity and be stable on their current medication dose. Women of childbearing age should use effective birth control, and all participants must be able to follow the study schedule.

Inclusion Criteria

I have been on a stable dose of my mental health medications for over 4 weeks.

I have been diagnosed with major depression without psychosis.

I am not currently hospitalized.

Exclusion Criteria

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

I have been diagnosed with a psychotic disorder, bipolar, OCD, or PTSD in the last year.

Concomitant major unstable medical illness

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive minocycline or placebo as an add-on treatment for 12 weeks

12 weeks

4 visits (in-person) at baseline, week 2, 6, and 12

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Minocycline

Trial Overview The trial tests if minocycline can help people with treatment-resistant depression when added to usual treatments. It's a double-blind study, meaning neither doctors nor patients know who gets minocycline or placebo. Assessments include depression scales and quality of life measures over 12 weeks, starting at a low dose that increases after two weeks.

How Is the Trial Designed?

Group I: Active Active Control 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

The Physicians' Services Incorporated Foundation

Collaborator

Trials

165

Recruited

31,700+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37342175/

Efficacy and tolerability of minocycline in depressive ... Minocycline may improve depressive symptoms and augment response to treatment in patients with depression irrespective of treatment-resistance.

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2796182

Effect of Minocycline on Depressive Symptoms in Patients ... 6 weeks of minocycline treatment did not show a statistically significant advantage compared with placebo on the overall course of depressive symptoms.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33504955/

results from a double-blind randomised clinical trial Our data show some evidence of efficacy of add-on treatment with minocycline in MDD patients but only in those with low-grade inflammation defined as CRP ≥3 mg ...

4. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1139273/full

Efficacy and tolerability of minocycline in depressive ... Patients with depression who received minocycline obtained significant improvement in HAMD-17 scores (SMD: −0.68, 95% CI: −1.20 to −0.15, P = ...

5. psychiatrist.com psychiatrist.com/pcc/role-minocycline-adjunct-neuroinflammatory-modulator-treatment-resistant-depression-systematic-review-randomized-controlled-trials/

Role of Minocycline as an Adjunct Neuroinflammatory ... Minocycline has shown inconsistent immunomodulator clinical effect in treatment-resistant depression.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7611693/

Minocycline in Major Depressive Disorder - PubMed Central Another important finding arising from ours and other research groups is that minocycline proved to be overall safe and well-tolerated in humans across studies.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37713730/

Role of Minocycline as an Adjunct Neuroinflammatory ... Objective: To assess the efficacy and safety evidence for adjunct minocycline in treatment-resistant depression (TRD). Data Sources: In this ...