<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02263872</url>
  </required_header>
  <id_info>
    <org_study_id>MINDEP001</org_study_id>
    <nct_id>NCT02263872</nct_id>
  </id_info>
  <brief_title>Minocycline as an Adjunct for the Treatment of Depressive Symptoms: Pilot Randomized Controlled Trial</brief_title>
  <official_title>Minocycline as an Adjunct for the Treatment of Depressive Symptoms: Pilot Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pakistan Institute of Living and Learning</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Pakistan Institute of Living and Learning</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this double blind randomised controlled pilot trial the investigators aim to determine the&#xD;
      efficacy of minocycline as an adjunct to treatment as usual in patients with major depressive&#xD;
      disorder. The investigators hypothesize that the multiple neuroprotective effects of&#xD;
      minocycline will lead to an improvement in depressive symptoms in participants that were&#xD;
      given minocycline plus treatment as usual&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Major depressive disorder is associated with significant morbidity and mortality. According&#xD;
      to the WHO, depression is the leading cause of disability worldwide in terms of years lost&#xD;
      due to disability [1]. Although depressive symptoms are amenable to antidepressant treatment,&#xD;
      a high proportion of patients does not respond or remit. For example in the Sequenced&#xD;
      Treatment Alternatives for the Relief of Depression (STAR*D) study the response and remission&#xD;
      rates with stage 1 treatment (citalopram) were 49% and 37% respectively and these rates&#xD;
      decreased to 16% and 13% respectively over the subsequent next three treatment steps [2].&#xD;
      Clearly there is a need for new treatment approaches.&#xD;
&#xD;
      Recently there has been significant preclinical and clinical study linking inflammatory&#xD;
      processes to a range of psychiatric illness including depression, schizophrenia, bipolar&#xD;
      disorder and Alzheimer's disease. The evidence that depression is an inflammatory related&#xD;
      disorder comes from multiple sources. Depression is associated with raised inflammatory&#xD;
      markers even in the absence of a medical illness [3]. More specifically depression has been&#xD;
      associated with higher levels of positive acute phase proteins (APPs) and low levels of&#xD;
      negative APPs [4] as well as increased levels of complement factors C3c and C4 and&#xD;
      immunoglobulin M (IgM) and IgG [5]. Inflammatory medical illness, both CNS and peripheral,&#xD;
      are associated with greater rates of depression. In patients with Crohns disease and comorbid&#xD;
      depression bouts of physical disease activity tend to co-occur with depressive episodes [6].&#xD;
      Finally, patients treated with cytokines for various illnesses have an increased risk of&#xD;
      developing depressive illness [7]. For example, treatment with cytokine IFN-α leads to the&#xD;
      development of depressive symptoms in up to 45% of patients [8].&#xD;
&#xD;
      With this in mind it would seem logical to hypothesise that the addition of an&#xD;
      anti-inflammatory medication may be a treatment option in depressive illness. Muller et al&#xD;
      [9] were successful in showing this when they used Celcoxib in addition to Reboxetine for the&#xD;
      treatment of major depressive disorder in a double-blind, randomised, placebo-controlled&#xD;
      pilot study. Other studies have shown that TNF (tumour necrosis factor) blocking agents such&#xD;
      as Infliximab and Ethanercept improve mood independent of improvement in inflammatory&#xD;
      condition [10]. However some studies have found that anti-inflammatories may in fact have an&#xD;
      antagonistic effect on the antidepressant actions of SSRIs [11]. Further work is needed in&#xD;
      this area to clarify the role of inflammatory processes and anti-inflammatories in the&#xD;
      treatment of depression.&#xD;
&#xD;
      Alongside the current interest in the use of anti-inflammatories as novel treatments in&#xD;
      psychiatric illness, the antibiotic minocycline has also been proposed for the treatment of&#xD;
      depressive symptoms as well as negative symptoms in schizophrenia [12, 13]. Preliminary data&#xD;
      from an open label study of patients with psychotic unipolar depression also suggested that&#xD;
      minocycline augmentation of antidepressant treatment was effective and well tolerated [14].&#xD;
      Minocycline is a pleiotropic agent that exerts effects on multiple interacting symptoms (e.g.&#xD;
      anti-inflammatory, anti-oxidant, anti-apoptotic, anti-gutamatergic, monaminergic) implicated&#xD;
      in the pathophysiology of mood disorders. Despite such neuroprotective properties, there have&#xD;
      been no clinical trials to date investigating the antidepressant effects of minocycline in&#xD;
      individuals. The investigators have previously shown that the addition of minocycline to&#xD;
      treatment as usual early in the course of schizophrenia leads to a predominant improvement in&#xD;
      negative symptoms.&#xD;
&#xD;
      In this double blind randomised controlled pilot trial the investigators aim to determine the&#xD;
      efficacy of minocycline as an adjunct to treatment as usual in patients with major depressive&#xD;
      disorder. The investigators hypothesise that the multiple neuroprotective effects of&#xD;
      minocycline will lead to an improvement in depressive symptoms in participants that were&#xD;
      given minocycline plus treatment as usual.&#xD;
&#xD;
      Aim To investigate whether the addition of minocycline to treatment as usual (TAU) for 3&#xD;
      months in patients with major depressive disorder will lead to an improvement in depressive&#xD;
      symptoms compared with TAU.&#xD;
&#xD;
      Methods&#xD;
&#xD;
      Double blind randomised, placebo-controlled pilot trial.&#xD;
&#xD;
      The study will be conducted in Karachi, Pakistan. Patients will be recruited from psychiatric&#xD;
      units in Karachi. All patients will give written informed consent after reading information&#xD;
      in Urdu, witnessed almost always by a relative.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">August 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The primary clinical outcome measures will be mean change from baseline on the Hamilton Depression Scale scores</measure>
    <time_frame>12 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>PHQ-9</measure>
    <time_frame>Baseline, Week 2, week 4, week 8, week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GAD-7</measure>
    <time_frame>Baseline, Week 2, week 4, week 8, week 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CGI</measure>
    <time_frame>Baseline, Week 2, week 4, week 8, week 12</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Depressive Disorder</condition>
  <condition>Mood Disorders</condition>
  <condition>Depressive Disorder, Treatment Resistant</condition>
  <condition>Antidepressive Agents</condition>
  <arm_group>
    <arm_group_label>Minocycline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Minocycline 200mg perday</description>
  </arm_group>
  <arm_group>
    <arm_group_label>comparison group with placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo provide</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Minocycline</intervention_name>
    <description>Minocycline 200mg perday</description>
    <arm_group_label>Minocycline</arm_group_label>
    <arm_group_label>comparison group with placebo</arm_group_label>
    <other_name>mesodrum</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. patients aged 18-65 years&#xD;
&#xD;
          2. Diagnostic and Statistical Manual-IV (DSM-IV) diagnosis of major depressive disorder&#xD;
&#xD;
          3. competent and willing to give informed consent&#xD;
&#xD;
          4. taking the current antidepressant medication for a minimum of 4 weeks prior to&#xD;
             baseline&#xD;
&#xD;
          5. the current episode of depression has failed to remit with at least two courses of&#xD;
             antidepressant treatment (one of which is the current course)&#xD;
&#xD;
          6. able to take oral medication&#xD;
&#xD;
          7. if female, willing to use adequate contraceptive precautions and to have monthly&#xD;
             pregnancy tests.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. relevant medical illness (renal, hepatic, cardiac, serious dermatological disorders&#xD;
             such as exfoliative dermatitis, systemic lupus erythematosis)&#xD;
&#xD;
          2. prior history of intolerance to any of the tetracyclines&#xD;
&#xD;
          3. concomitant penicillin therapy&#xD;
&#xD;
          4. concomitant anticoagulant therapy&#xD;
&#xD;
          5. presence of a seizure disorder&#xD;
&#xD;
          6. currently taking valproic acid&#xD;
&#xD;
          7. any change of psychotropic medications within the previous 4 weeks&#xD;
&#xD;
          8. diagnosis of substance abuse (except nicotine or caffeine) or dependence within the&#xD;
             last 3 months according to DSM-IV criteria&#xD;
&#xD;
          9. pregnant or breast-feeding&#xD;
&#xD;
         10. presence of primary psychotic disorder.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dr. Muhammad Ishrat</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of Psychiatry, Psychology and Neuroscience, Kings college London</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Abasi Shaheed Hospital</name>
      <address>
        <city>Karachi</city>
        <state>Sindh</state>
        <zip>72000</zip>
        <country>Pakistan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Civil hospital Karachi</name>
      <address>
        <city>Karachi</city>
        <state>Sindh</state>
        <zip>72000</zip>
        <country>Pakistan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karwan-e-Hayat</name>
      <address>
        <city>Karachi</city>
        <state>Sindh</state>
        <country>Pakistan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <reference>
    <citation>World Health Organization. The Global Burden of Disease. Geneva: WHO Press; 2012.</citation>
  </reference>
  <reference>
    <citation>Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.</citation>
    <PMID>17074942</PMID>
  </reference>
  <reference>
    <citation>O'Donovan A, Rush G, Hoatam G, Hughes BM, McCrohan A, Kelleher C, O'Farrelly C, Malone KM. Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder. Depress Anxiety. 2013 Apr;30(4):307-14. doi: 10.1002/da.22087. Epub 2013 Mar 15.</citation>
    <PMID>23504697</PMID>
  </reference>
  <reference>
    <citation>Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008 Jan;9(1):46-56. doi: 10.1038/nrn2297.</citation>
    <PMID>18073775</PMID>
  </reference>
  <reference>
    <citation>Song C, Dinan T, Leonard BE. Changes in immunoglobulin, complement and acute phase protein levels in the depressed patients and normal controls. J Affect Disord. 1994 Apr;30(4):283-8. doi: 10.1016/0165-0327(94)90135-x.</citation>
    <PMID>7516941</PMID>
  </reference>
  <reference>
    <citation>Mardini HE, Kip KE, Wilson JW. Crohn's disease: a two-year prospective study of the association between psychological distress and disease activity. Dig Dis Sci. 2004 Mar;49(3):492-7. doi: 10.1023/b:ddas.0000020509.23162.cc.</citation>
    <PMID>15139504</PMID>
  </reference>
  <reference>
    <citation>Van Gool AR, Kruit WH, Engels FK, Stoter G, Bannink M, Eggermont AM. Neuropsychiatric side effects of interferon-alfa therapy. Pharm World Sci. 2003 Feb;25(1):11-20. doi: 10.1023/a:1022449613907.</citation>
    <PMID>12661471</PMID>
  </reference>
  <reference>
    <citation>Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. 2011 May;130(2):226-38. doi: 10.1016/j.pharmthera.2011.01.014. Epub 2011 Feb 17.</citation>
    <PMID>21334376</PMID>
  </reference>
  <reference>
    <citation>Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Moller HJ, Arolt V, Riedel M. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006 Jul;11(7):680-4. doi: 10.1038/sj.mp.4001805. Epub 2006 Feb 21.</citation>
    <PMID>16491133</PMID>
  </reference>
  <reference>
    <citation>Krishnadas R, Cavanagh J. Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry. 2012 May;83(5):495-502. doi: 10.1136/jnnp-2011-301779. Epub 2012 Mar 15.</citation>
    <PMID>22423117</PMID>
  </reference>
  <reference>
    <citation>Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proc Natl Acad Sci U S A. 2011 May 31;108(22):9262-7. doi: 10.1073/pnas.1104836108. Epub 2011 Apr 25. Erratum In: Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11297.</citation>
    <PMID>21518864</PMID>
  </reference>
  <reference>
    <citation>Soczynska JK, Mansur RB, Brietzke E, Swardfager W, Kennedy SH, Woldeyohannes HO, Powell AM, Manierka MS, McIntyre RS. Novel therapeutic targets in depression: minocycline as a candidate treatment. Behav Brain Res. 2012 Dec 1;235(2):302-17. doi: 10.1016/j.bbr.2012.07.026. Epub 2012 Aug 10.</citation>
    <PMID>22963995</PMID>
  </reference>
  <reference>
    <citation>Chaudhry IB, Hallak J, Husain N, Minhas F, Stirling J, Richardson P, Dursun S, Dunn G, Deakin B. Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J Psychopharmacol. 2012 Sep;26(9):1185-93. doi: 10.1177/0269881112444941. Epub 2012 Apr 23.</citation>
    <PMID>22526685</PMID>
  </reference>
  <reference>
    <citation>Miyaoka T, Furuya M, Yasuda H, Hayashida M, Nishida A, Inagaki T, Horiguchi J. Yi-gan san as adjunctive therapy for treatment-resistant schizophrenia: an open-label study. Clin Neuropharmacol. 2009 Jan-Feb;32(1):6-9. doi: 10.1097/WNF.0b013e31817e08c3.</citation>
    <PMID>19471183</PMID>
  </reference>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>October 8, 2014</study_first_submitted>
  <study_first_submitted_qc>October 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>September 2, 2016</last_update_submitted>
  <last_update_submitted_qc>September 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Mood Disorders</mesh_term>
    <mesh_term>Depressive Disorder, Treatment-Resistant</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Minocycline</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02263872
org study id: MINDEP001
nct id: NCT02263872
lead sponsor: 
collaborator: 
has dmc: Yes
In this double blind randomised controlled pilot trial the investigators aim to determine the
      efficacy of minocycline as an adjunct to treatment as usual in patients with major depressive
      disorder. The investigators hypothesize that the multiple neuroprotective effects of
      minocycline will lead to an improvement in depressive symptoms in participants that were
      given minocycline plus treatment as usual
Major depressive disorder is associated with significant morbidity and mortality. According
      to the WHO, depression is the leading cause of disability worldwide in terms of years lost
      due to disability [1]. Although depressive symptoms are amenable to antidepressant treatment,
      a high proportion of patients does not respond or remit. For example in the Sequenced
      Treatment Alternatives for the Relief of Depression (STAR*D) study the response and remission
      rates with stage 1 treatment (citalopram) were 49% and 37% respectively and these rates
      decreased to 16% and 13% respectively over the subsequent next three treatment steps [2].
      Clearly there is a need for new treatment approaches.

      Recently there has been significant preclinical and clinical study linking inflammatory
      processes to a range of psychiatric illness including depression, schizophrenia, bipolar
      disorder and Alzheimer's disease. The evidence that depression is an inflammatory related
      disorder comes from multiple sources. Depression is associated with raised inflammatory
      markers even in the absence of a medical illness [3]. More specifically depression has been
      associated with higher levels of positive acute phase proteins (APPs) and low levels of
      negative APPs [4] as well as increased levels of complement factors C3c and C4 and
      immunoglobulin M (IgM) and IgG [5]. Inflammatory medical illness, both CNS and peripheral,
      are associated with greater rates of depression. In patients with Crohns disease and comorbid
      depression bouts of physical disease activity tend to co-occur with depressive episodes [6].
      Finally, patients treated with cytokines for various illnesses have an increased risk of
      developing depressive illness [7]. For example, treatment with cytokine IFN-α leads to the
      development of depressive symptoms in up to 45% of patients [8].

      With this in mind it would seem logical to hypothesise that the addition of an
      anti-inflammatory medication may be a treatment option in depressive illness. Muller et al
      [9] were successful in showing this when they used Celcoxib in addition to Reboxetine for the
      treatment of major depressive disorder in a double-blind, randomised, placebo-controlled
      pilot study. Other studies have shown that TNF (tumour necrosis factor) blocking agents such
      as Infliximab and Ethanercept improve mood independent of improvement in inflammatory
      condition [10]. However some studies have found that anti-inflammatories may in fact have an
      antagonistic effect on the antidepressant actions of SSRIs [11]. Further work is needed in
      this area to clarify the role of inflammatory processes and anti-inflammatories in the
      treatment of depression.

      Alongside the current interest in the use of anti-inflammatories as novel treatments in
      psychiatric illness, the antibiotic minocycline has also been proposed for the treatment of
      depressive symptoms as well as negative symptoms in schizophrenia [12, 13]. Preliminary data
      from an open label study of patients with psychotic unipolar depression also suggested that
      minocycline augmentation of antidepressant treatment was effective and well tolerated [14].
      Minocycline is a pleiotropic agent that exerts effects on multiple interacting symptoms (e.g.
      anti-inflammatory, anti-oxidant, anti-apoptotic, anti-gutamatergic, monaminergic) implicated
      in the pathophysiology of mood disorders. Despite such neuroprotective properties, there have
      been no clinical trials to date investigating the antidepressant effects of minocycline in
      individuals. The investigators have previously shown that the addition of minocycline to
      treatment as usual early in the course of schizophrenia leads to a predominant improvement in
      negative symptoms.

      In this double blind randomised controlled pilot trial the investigators aim to determine the
      efficacy of minocycline as an adjunct to treatment as usual in patients with major depressive
      disorder. The investigators hypothesise that the multiple neuroprotective effects of
      minocycline will lead to an improvement in depressive symptoms in participants that were
      given minocycline plus treatment as usual.

      Aim To investigate whether the addition of minocycline to treatment as usual (TAU) for 3
      months in patients with major depressive disorder will lead to an improvement in depressive
      symptoms compared with TAU.

      Methods

      Double blind randomised, placebo-controlled pilot trial.

      The study will be conducted in Karachi, Pakistan. Patients will be recruited from psychiatric
      units in Karachi. All patients will give written informed consent after reading information
      in Urdu, witnessed almost always by a relative.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The primary clinical outcome measures will be mean change from baseline on the Hamilton Depression Scale scores
time frame: 12 weeks
measure: PHQ-9
time frame: Baseline, Week 2, week 4, week 8, week 12
measure: GAD-7
time frame: Baseline, Week 2, week 4, week 8, week 12
measure: CGI
time frame: Baseline, Week 2, week 4, week 8, week 12
arm group label: Minocycline
arm group type: Experimental
description: Minocycline 200mg perday
arm group label: comparison group with placebo
arm group type: Placebo Comparator
description: Placebo provide
intervention type: Drug
intervention name: Minocycline
description: Minocycline 200mg perday
arm group label: Minocycline
arm group label: comparison group with placebo
other name: mesodrum
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Dr. Muhammad Ishrat
role: Principal Investigator
affiliation: Institute of Psychiatry, Psychology and Neuroscience, Kings college London
facility: 
facility: 
facility: 
country: Pakistan
citation: World Health Organization. The Global Burden of Disease. Geneva: WHO Press; 2012.
citation: Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.
PMID: 17074942
citation: O'Donovan A, Rush G, Hoatam G, Hughes BM, McCrohan A, Kelleher C, O'Farrelly C, Malone KM. Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder. Depress Anxiety. 2013 Apr;30(4):307-14. doi: 10.1002/da.22087. Epub 2013 Mar 15.
PMID: 23504697
citation: Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008 Jan;9(1):46-56. doi: 10.1038/nrn2297.
PMID: 18073775
citation: Song C, Dinan T, Leonard BE. Changes in immunoglobulin, complement and acute phase protein levels in the depressed patients and normal controls. J Affect Disord. 1994 Apr;30(4):283-8. doi: 10.1016/0165-0327(94)90135-x.
PMID: 7516941
citation: Mardini HE, Kip KE, Wilson JW. Crohn's disease: a two-year prospective study of the association between psychological distress and disease activity. Dig Dis Sci. 2004 Mar;49(3):492-7. doi: 10.1023/b:ddas.0000020509.23162.cc.
PMID: 15139504
citation: Van Gool AR, Kruit WH, Engels FK, Stoter G, Bannink M, Eggermont AM. Neuropsychiatric side effects of interferon-alfa therapy. Pharm World Sci. 2003 Feb;25(1):11-20. doi: 10.1023/a:1022449613907.
PMID: 12661471
citation: Capuron L, Miller AH. Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol Ther. 2011 May;130(2):226-38. doi: 10.1016/j.pharmthera.2011.01.014. Epub 2011 Feb 17.
PMID: 21334376
citation: Muller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Muller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Moller HJ, Arolt V, Riedel M. The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry. 2006 Jul;11(7):680-4. doi: 10.1038/sj.mp.4001805. Epub 2006 Feb 21.
PMID: 16491133
citation: Krishnadas R, Cavanagh J. Depression: an inflammatory illness? J Neurol Neurosurg Psychiatry. 2012 May;83(5):495-502. doi: 10.1136/jnnp-2011-301779. Epub 2012 Mar 15.
PMID: 22423117
citation: Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proc Natl Acad Sci U S A. 2011 May 31;108(22):9262-7. doi: 10.1073/pnas.1104836108. Epub 2011 Apr 25. Erratum In: Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11297.
PMID: 21518864
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responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Mood Disorders
mesh term: Depressive Disorder, Treatment-Resistant
mesh term: Minocycline