Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: Randomized double-blind placebo-controlled study

Khodaie‐Ardakani, Mohammad‐Reza; Mirshafiee, Omid; Farokhnia, Mehdi; Tajdini, Masih; Hosseini, Saeed; Modabbernia, Amirhossein; Rezaei, Farzin; Salehi, Bahman; Yekehtaz, Habibeh; Ashrafi, Mandana; Tabrizi, Mina; Akhondzadeh, Shahin

doi:10.1016/j.psychres.2013.12.051

Cited by 84 publications

(63 citation statements)

References 33 publications

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“…Liu et al [33] studied adjunct minocycline to risperidone in patients in the first five years of illness but with negative symptoms as the primary outcome. Lastly, Khodaie-Ardakanie et al [34] also added minocycline to risperidone and with negative symptoms as the primary outcome, but in a chronic population. This study we present is different in that it is the first study with minocycline treatment as adjunct to clozapine, the first to have positive and cognitive symptoms as the primary outcomes and only the second to test in a chronic population.…”

Section: Discussionmentioning

confidence: 99%

Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms

Kelly¹,

Sullivan²,

McEvoy³

et al. 2015

Journal of Clinical Psychopharmacology

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Objective Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia, yet many patients only partially respond. Accumulating preclinical and clinical data suggest benefits with minocycline. We tested adjunct minocycline to clozapine in a 10 week, double blind placebo-controlled trial. Primary outcomes tested were positive and cognitive symptoms, while avolition, anxiety/depression and negative symptoms were secondary outcomes. Methods Schizophrenia and schizoaffective participants (N=52) with persistent positive symptoms were randomized to receive adjunct minocycline (100 mg oral capsule twice daily) (N=29) or placebo (N=23). Results Brief Psychiatric Rating Scale (BPRS) psychosis factor (p=0.098, effect size ES=0.39) and BPRS total score (p=0.075, effect size 0.55) were not significant. A ≥30% change in total BPRS symptoms was observed in 7/28 (25%) among minocycline and 1/23 (4%) among placebo participants, respectively (p=0.044). Global cognitive function (MATRICS Consensus Cognitive Battery, MCCB) did not differ, although there was a significant variation in size of treatment effects among cognitive domains (p=0.03), with significant improvement in working memory favoring minocycline (p=0.023, ES 0.41). The SANS total score did not differ, but significant improvement in avolition with minocycline was noted (p=0.012, ES=0.34). Significant improvement in the BPRS anxiety/depression factor was observed with minocycline (p=0.028, ES=0.49). Minocycline was well tolerated with significantly fewer headaches and constipation compared to placebo. Conclusion Minocycline’s effect on the MCCB composite score and positive symptoms were not statistically significant. Significant improvements with minocycline were seen in working memory, avolition and anxiety/depressive symptoms in a chronic population with persistent symptoms. Larger studies are needed to validate these findings.

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Section: Discussionmentioning

confidence: 99%

Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms

Kelly¹,

Sullivan²,

McEvoy³

et al. 2015

Journal of Clinical Psychopharmacology

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Section: Introductionmentioning

confidence: 99%

“…To our knowledge, four randomized controlled trials (RCTs) of minocycline have been conducted for the treatment of schizophrenia. Of these, all four studies (Levkovitz et al, 2010;Chaudhry et al, 2012;Khodaie-Ardakani et al, 2014;Liu et al, 2014) showed that minocycline was superior to placebo when treating negative symptoms. However, the study of Levkovitz et al (2010) showed that minocycline was superior to placebo in the improvement of Scale for the Assessment of Negative Symptoms (SANS) (Andreasen, 1982) scores but not of Positive and Negative Syndrome Scale (PANSS) (Kay et al, 1987) negative subscale scores.…”

Section: Introductionmentioning

confidence: 99%

“…Considering this, we performed an updated meta-analysis of minocycline for the treatment of schizophrenia. This meta-analysis used only four published RCTs (Levkovitz et al, 2010;Chaudhry et al, 2012;Khodaie-Ardakani et al, 2014;Liu et al, 2014). It comprehensively evaluates the efficacy and safety of minocycline in the management of schizophrenia (including the discontinuation rate and individual side effects).…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and tolerability of minocycline augmentation therapy in schizophrenia: a systematic review and meta‐analysis of randomized controlled trials

Oya

Kishi

Iwata

2014

Human Psychopharmacology

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“…Interestingly, multiple randomized, double-blind, placebo-controlled studies of minocycline, a semisynthetic derivative of tetracycline that inhibits microglial activation, have shown some therapeutic effects in individuals with schizophrenia (Chaudhry et al, 2012;Kelly et al, 2015;Khodaie-Ardakani et al, 2014;Levkovitz et al, 2010;Liu et al, 2014;Oya et al, 2014). For example, acute and chronic administration of minocycline, in combination with antipsychotic medications, to individuals with schizophrenia has been consistently reported to improve negative symptoms (e.g., amotivation, poverty of speech, social withdrawal), but not positive symptoms (e.g., hallucinations and delusions) (Table 1).…”

Section: Evidence Of Microglia Disturbances In Schizophreniamentioning

confidence: 99%

Role of microglia disturbances and immune-related marker abnormalities in cortical circuitry dysfunction in schizophrenia

Volk

2017

Neurobiology of Disease

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Studies of genetics, serum cytokines, and autoimmune illnesses suggest that immune-related abnormalities are involved in the disease process of schizophrenia. Furthermore, direct evidence of cortical immune activation, including markedly elevated levels of many immune-related markers, have been reported in the prefrontal cortex in multiple cohorts of schizophrenia subjects. Within the prefrontal cortex in schizophrenia, deficits in the basilar dendritic spines of layer 3 pyramidal neurons and disturbances in inhibitory inputs to pyramidal neurons have also been commonly reported. Interestingly, microglia, the resident immune-related cells of the brain, also regulate excitatory and inhibitory input to pyramidal neurons. Consequently, in this review, we describe the cytological and molecular evidence of immune activation that has been reported in the brains of individuals with schizophrenia and the potential links between these immune-related disturbances with previously reported disturbances in pyramidal and inhibitory neurons in the disorder. Finally, we discuss the role that activated microglia may play in connecting these observations and as potential therapeutic treatment targets in schizophrenia.

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Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: Randomized double-blind placebo-controlled study

Cited by 84 publications

References 33 publications

Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms

Adjunctive Minocycline in Clozapine-Treated Schizophrenia Patients With Persistent Symptoms

Efficacy and tolerability of minocycline augmentation therapy in schizophrenia: a systematic review and meta‐analysis of randomized controlled trials

Role of microglia disturbances and immune-related marker abnormalities in cortical circuitry dysfunction in schizophrenia

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