Minocycline as an adjunct for treatment-resistant depressive symptoms: A pilot randomised placebo-controlled trial

Husain, Muhammad Ishrat; Chaudhry, Imran B; Husain, Nusrat; Khoso, Ameer B; Rahman, Raza Ur; Hamirani, Munir; Hodsoll, John; Qurashi, Inti; Deakin, Bill; Young, Allan H.

doi:10.1177/0269881117724352

Cited by 111 publications

(108 citation statements)

References 42 publications

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“…To our knowledge, this is only the second RCT of minocycline for the treatment of TRD. It is intended to be a larger scale study than the previous pilot trial [27], led by the same principal investigator and with more than double the number of participants (n = 41 vs. n = 100). If this study leads to similar findings as the pilot trial, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Adverse effects will be monitored using a rating scale that has been specifically designed for minocycline. This rating scale has been used in previous studies [27].…”

Section: Methodsmentioning

confidence: 99%

“…This dose has been shown by substantial literature to produce consistent anti-inflammatory effects in inflammatory disorders. It was also the dose used in our pilot trial [27]. Treatment compliance will be assessed by the pharmacy at each dispensing visit using pill counts.…”

Section: Clinical Proceduresmentioning

confidence: 99%

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Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2)

et al. 2020

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Background: Available evidence suggests that adjunctive treatment with immunomodulatory medications may be effective in the treatment of major depressive disorder (MDD). A pilot trial of the tetracycline minocycline as adjunctive treatment in treatment-resistant depression (TRD), produced promising results, however, a larger scale trial is needed to confirm the antidepressant actions of this drug. Methods: This is a 12-week double blind, placebo-controlled, randomized trial of minocycline as an add-on to standard antidepressants for adults (age > 18) with DSM-5 major depressive episode, who have failed to respond to at least two adequate trials of antidepressant treatment. It is a parallel-arm study with 50 participants in each group. The primary outcome measure is change in 17-item Hamilton Depression Rating Scale (HRSD-17) total scores from baseline to week 12. Secondary measures include the Clinical Global Impression (CGI) scale, World Health Organization Quality of Life Short Version (WHOQOL-BREF) and the Generalized Anxiety Disorder scale (GAD-7). Peripheral inflammatory biomarkers will be collected at baseline, week 6 and 12.Discussion: If minocycline is well tolerated and effective in reducing depressive symptoms in patients with TRD, it would warrant genuine consideration as a treatment option for TRD. Additionally, if results demonstrate that minocycline has antidepressant properties, and that changes in inflammatory status are associated with its antidepressant action, it will inform the development of individualized treatment for a subset of patients with MDD. Trial registration: Clinicaltrials.gov identifier: NCT03947827. Registered 13th May, 2019.

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Section: Discussionmentioning

confidence: 99%

“…Adverse effects will be monitored using a rating scale that has been specifically designed for minocycline. This rating scale has been used in previous studies [27].…”

Section: Methodsmentioning

confidence: 99%

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Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2)

et al. 2020

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“…To date, several meta‐analyses have gathered the evidence on the antidepressant effects of NSAIDs, statins, and cytokine inhibitors ; however, several of these studies only investigated specific agents did not assess the risk for side‐effects , only included patients with MDD while excluding patients with a somatic disease and depressive symptoms , or failed to perform a thorough bias assessment . Furthermore, the field is evolving rapidly and several new RCTs of anti‐inflammatory treatment effects on depressive symptoms have been published since our proof‐of‐concept meta‐analysis in 2014, necessitating an updated assessment. In addition, it has been argued that many anti‐inflammatory drugs yield antidepressant effects, indicating a group effect, which also may be present among patients with depressive symptoms not meeting diagnostic criteria for MDD .…”

Section: Introductionmentioning

confidence: 99%

Efficacy of anti‐inflammatory treatment on major depressive disorder or depressive symptoms: meta‐analysis of clinical trials

Köhler‐Forsberg

Lydholm

Hjorthøj

et al. 2019

Acta Psychiatr Scand

270

186

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Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials K€ ohler-Forsberg O, Nicolaisen Lydholm C, Hjorthøj C, Nordentoft C, Mors O, Benros ME. Efficacy of anti-inflammatory treatment on major depressive disorder or depressive symptoms: meta-analysis of clinical trials Background: No study has gathered evidence from all randomized clinical trials (RCTs) with anti-inflammatory drugs measuring antidepressant effects including a detailed assessment of side-effects and bias. Methods: We performed a systematic review identifying RCTs published prior to January 1, 2018, studying antidepressant treatment effects and sideeffects of pharmacological anti-inflammatory intervention in adults with major depressive disorder (MDD) or depressive symptoms. Outcomes were depression scores after treatment, remission, response, and side-effects. Pooled standard mean differences (SMD) and risk ratios (RR) including 95% confidence intervals (95%-CI) were calculated. Results: We identified 36 RCTs, whereof 13 investigated NSAIDs (N = 4214), 9 cytokine inhibitors (N = 3345), seven statins (N = 1576), 3 minocycline (N = 151), 2 pioglitazone (N = 77), and 2 glucocorticoids (N = 59). Anti-inflammatory agents improved depressive symptoms compared to placebo as add-on in patients with MDD (SMD = À0.64; 95%-CI = À0.88, À0.40; I 2 = 51%; N = 597) and as monotherapy (SMD = À0.41; 95%-CI = À0.60, À0.22; I 2 = 93%, N = 8825). Antiinflammatory add-on improved response (RR = 1.76; 95%-CI = 1.44-2.16; I 2 = 16%; N = 341) and remission (RR = 2.14; 95%-CI = 1.03-4.48; I 2 = 57%; N = 270). We found a trend toward an increased risk for infections, and all studies showed high risk of bias. Conclusion: Anti-inflammatory agents improved antidepressant treatment effects. Future RCTs need to include longer follow-up, identify optimal doses and subgroups of patients that can benefit from anti-inflammatory intervention. Summations• Among 36 RCTs including almost 10 000 patients, five out of six anti-inflammatory drugs improved depression scores compared to placebo.• Short-term (i.e., weeks) anti-inflammatory add-on to antidepressants showed improved antidepressant effects in MDD without increasing the risk for side-effects.• The effect size for anti-inflammatory add-on to antidepressants was similar to the effect size of antidepressants alone, indicating the potential clinical benefit. Considerations• Few studies reported on side-effects and all studies were associated with risk of bias.• Few studies investigated biomarkers and none explored specific depressive symptoms to predict better response to anti-inflammatory treatment.• Hence, future studies need to include longer follow-up and measures of inflammation (blood, CSF, and brain scans) to identify subgroups of patients with specific depressive symptoms who could be offered anti-inflammatory treatment.

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“…However, no significant difference in the Montgomery‐Asberg Depression Rating Scale was observed between the two groups. A smaller double‐blind randomized clinical placebo‐controlled trail of adjuvant minocycline in depression (n = 41) found clinical improvement as per Hamilton Depression Rating Scale in addition to other measures (Husain et al, ). Lastly, a 6‐week open‐label study of adjuvant minocycline in combination with SSRI's to treat psychotic depression (n = 25) demonstrated minocycline's safety in this setting (Miyaoka et al, ).…”

Section: Resultsmentioning

confidence: 99%

Putative neuroprotective pharmacotherapies to target the staged progression of mental illness

Robertson

Coronado

Sethi

et al. 2019

Early Intervention Psych

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Aim: Neuropsychiatric disorders including depression, bipolar and schizophrenia frequently exhibit a neuroprogressive course from prodrome to chronicity. There are a range of agents exhibiting capacity to attenuate biological mechanisms associated with neuroprogression. This review will update the evidence for putative neuroprotective agents including clinical efficacy, mechanisms of action and limitations in current assessment tools, and identify novel agents with neuroprotective potential.Method: Data for this review were sourced from online databases PUBMED, Embase and Web of Science. Only data published since 2012 were included in this review, no data were excluded based on language or publication origin.Results: Each of the agents reviewed inhibit one or multiple pathways of neuroprogression including: inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling. Some demonstrate clinical efficacy in preventing neural damage or loss, relapse or cognitive/functional decline. Agents include: the psychotropic medications lithium, second generation antipsychotics and antidepressants; other pharmacological agents such as minocycline, aspirin, cyclooxygenase-2 inhibitors, statins, ketamine and alpha-2-delta ligands; and others such as erythropoietin, oestrogen, leptin, N-acetylcysteine, curcumin, melatonin and ebselen.Conclusions: Signals of evidence of clinical neuroprotection are evident for a number of candidate agents. Adjunctive use of multiple agents may present a viable avenue to clinical realization of neuroprotection. Definitive prospective studies of neuroprotection with multimodal assessment tools are required.

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Minocycline as an adjunct for treatment-resistant depressive symptoms: A pilot randomised placebo-controlled trial

Abstract: ClinicalTrials.gov identifier: NCT02263872, registered October 2014.

Cited by 111 publications

References 42 publications

Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2)

Minocycline as adjunctive treatment for treatment-resistant depression: study protocol for a double blind, placebo-controlled, randomized trial (MINDEP2)

Efficacy of anti‐inflammatory treatment on major depressive disorder or depressive symptoms: meta‐analysis of clinical trials

Putative neuroprotective pharmacotherapies to target the staged progression of mental illness

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