Examining the potential preventative effects of minocycline prescribed for acne on the incidence of severe mental illnesses: A historical cohort study

Herrero-Zazo, María; Brauer, Ruth; Gaughran, Fiona; Howard, Louise M.; Taylor, David; Barlow, David J.

doi:10.1177/0269881117743483

Cited by 6 publications

(9 citation statements)

References 45 publications

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“…For instance, two studies concluded that taking minocycline for acne has no protective effect for any mental health conditions including psychosis, while raising the possibility that the observed increase in overall psychiatric morbidity could be due to the “experience of severe acne” itself. [ 23,28 ] Thus, Sellgren et al. wisely cautioned that their study did not provide direct evidence supporting that the observed in vitro effects of minocycline caused the decreased incidence of SZ in their EHR‐based analyses, and that “it is fully possible that minocycline modestly reduces the risk of transition to psychosis… through another as‐yet‐unidentified mechanism”; we concur with this assessment.…”

Section: Is Minocycline's Positive Effect Really Direct or Is It Medmentioning

confidence: 53%

“…Trials of minocycline and other anti‐inflammatory agents as add‐ons for treating SZ have at‐best produced ambiguous results. [ 22–24 ] Minocycline exerts anti‐inflammatory effects on microglia, but because it also affects other cells of the innate and adaptive immune systems through multiple mechanisms, the experimental use of minocycline to examine a causal role for microglia is problematic. [ 25 ] It remains unknown whether microglia changes observed in individuals with SZ are part of its etiology and pathophysiology or instead a downstream response to some other causal process (see refs.…”

Section: Is Minocycline's Positive Effect Really Direct or Is It Medmentioning

confidence: 99%

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Synaptic Pruning in Schizophrenia: Does Minocycline Modulate Psychosocial Brain Development?

2020

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Recent studies suggest that the tetracycline antibiotic minocycline, or its cousins, hold therapeutic potential for affective and psychotic disorders. This is proposed on the basis of a direct effect on microglia‐mediated frontocortical synaptic pruning (FSP) during adolescence, perhaps in genetically susceptible individuals harboring risk alleles in the complement component cascade that is involved in this normal process of CNS circuit refinement. In reviewing this field, it is argued that minocycline is actually probing and modulating a deeply evolved and intricate system wherein psychosocial stimuli sculpt the circuitry of the “social brain” underlying adult behavior and personality. Furthermore, this system can generate psychiatric morbidity that is not dependent on genetic variation. This view has important ramifications for understanding “pathologies” of human social behavior and cognition as well as providing long‐sought potential mechanistic links between social experience and susceptibility to mental and physical disease.

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Section: Is Minocycline's Positive Effect Really Direct or Is It Medmentioning

confidence: 53%

Section: Is Minocycline's Positive Effect Really Direct or Is It Medmentioning

confidence: 99%

Synaptic Pruning in Schizophrenia: Does Minocycline Modulate Psychosocial Brain Development?

2020

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“…Moreover, Sellgren et al added analyses of 22,027 electronic health records from two large US medical centers and found an inverse association (HR 0.58, 95% confidence interval (CI) 0.39-0.88) between minocycline and/or doxycycline exposure during adolescence for a minimum of 90 days (3811 individuals) and risk of later diagnosis of nonaffective psychosis, including schizophrenia (F20-F29) [24]. This contrasts an earlier electronic healthcare register study from UK by Herrero-Zazo et al who compared 13,248 minocycline exposed for a minimum of 42 days with 14,393 matched controls and found no preventive effect on SMI from early minocycline prescription [25]. Comparing exposure between these two studies is not entirely trivial.…”

Section: Introductionmentioning

confidence: 71%

Doxycycline exposure during adolescence and future risk of non-affective psychosis and bipolar disorder: a total population cohort study

et al. 2021

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Doxycycline has been hypothesized to prevent development of severe mental illness (SMI) through the suppression of microglia, especially if administered during the intense synaptic pruning period of adolescence. However, results from register studies on potential benefits differ considerably. The aim of the present study was to determine whether doxycycline exposure during adolescence is associated with reduced SMI risk, and to investigate if a direct and specific causality is plausible. This is a Swedish national population register-based cohort study of all individuals born from 1993 to 1997, followed from the age of 13 until end of study at the end of 2016. The primary exposure was cumulative doxycycline prescription ≥3000 mg and outcomes were first diagnosis of non-affective psychosis (F20–F29) and first diagnosis of bipolar disorder (F30–F31). Causal effects were explored through Cox regressions with relevant covariates and secondary analyses of multilevel exposure and comparison to other antibiotics. We found no association between doxycycline exposure and risk of subsequent non-affective psychosis (adjusted hazard ratio (HR) 1.15, 95% CI 0.73–1.81, p = 0.541) and an increased risk of subsequent bipolar disorder (adjusted HR 1.95, 95% CI 1.49–2.55, p < 0.001). We do not believe the association between doxycycline and bipolar disorder is causal as similar associations were observed for other common antibiotics.

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“…Although case reports and case series (Kelly et al, 2011; Qurashi et al, 2014; Sura and Bobrin, 2012) and open-label studies (Miyaoka et al, 2008; Miyaoka et al, 2012; Murrough et al, 2018; Soczynska et al, 2014; Soczynska et al, 2017; Vyas et al, 2013) have found adjunctive minocycline to be efficacious and safe for major mental disorders, results of randomized controlled trials (RCTs) have been mixed (Chaudhry et al, 2012; Deakin et al, 2018; Dean et al, 2017; Ghanizadeh et al, 2014; Hu et al, 2017; Husain et al, 2017; Kelly et al, 2015; Khodaie-Ardakani et al, 2014; Levkovitz et al, 2010; Liu et al, 2014; Savitz et al, 2018; Song and Li, 2017; Weiser et al, 2018; Zeng, 2015; Zhang, 2015; Zhang et al, 2018). Furthermore, a study found that minocycline prescribed for acne did not reduce the risk of major mental disorders (Herrero-Zazo et al, 2018). Another study found minocycline had no protective effect on severe psychiatric symptoms in adolescence (Brauer et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Adjunctive minocycline for major mental disorders: A systematic review

et al. 2019

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Objectives: This meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of minocycline for three major mental disorders: schizophrenia, bipolar disorder and major depressive disorder (MDD). Methods: A systematic literature search of major electronic databases was conducted. Meta-analysis of clinical efficacy as defined by the respective studies, all-cause discontinuation, adverse drug reactions (ADRs) with standardized mean difference (SMD) and risk ratios (RRs) and their 95% confidence intervals (CI) was conducted using random-effects model. Quality assessment was performed with the Jadad scale and Cochrane risk of bias. Results: Sixteen RCTs ( n=1357) on minocycline (50–300 mg/day) for schizophrenia (13 RCTs, n=1196), bipolar depression (1 RCT, n=49), and MDD (2 RCTs, n=112) were analyzed separately by diagnosis. Twelve RCTs mentioned randomized allocation specifically; the weighted Jadad scores were 4.0. Adjunctive minocycline outperformed placebo in improving total psychopathology [SMD: −0.45 (95%CI: −0.73, −0.16), p=0.002; I2=77%], positive [SMD: −0.15 (95%CI: −0.28, −0.02), p=0.02; I2=0%], negative [SMD: −0.62 (95%CI: −0.95, −0.28), p=0.0003; I2=85%] and general psychopathology scores [SMD: −0.28 (95%CI: −0.53, −0.03), p=0.03; I2=59%] in schizophrenia. Minocycline showed no significant effect on depressive and manic symptoms in both bipolar depression and MDD. Minocycline caused significantly less headache ( p=0.02, number-needed-to-harm=14, 95%CI=5–14) than placebo in schizophrenia. All-cause discontinuation and other ADRs were similar between minocycline and placebo in each diagnostic category. Conclusion: In this meta-analysis, adjunctive minocycline appeared to be efficacious and safe for schizophrenia. However, the efficacy of adjunctive minocycline for bipolar depression or MDD could not be demonstrated. Review registration: PROSPERO: CRD42018102483

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Examining the potential preventative effects of minocycline prescribed for acne on the incidence of severe mental illnesses: A historical cohort study

Abstract: Exposure to minocycline for acne treatment during adolescence appears to have no effect on the incidence of SMI.

Cited by 6 publications

References 45 publications

Synaptic Pruning in Schizophrenia: Does Minocycline Modulate Psychosocial Brain Development?

Synaptic Pruning in Schizophrenia: Does Minocycline Modulate Psychosocial Brain Development?

Doxycycline exposure during adolescence and future risk of non-affective psychosis and bipolar disorder: a total population cohort study

Adjunctive minocycline for major mental disorders: A systematic review

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