Animal studies suggest that the antibiotic and microglial activation inhibitor, minocycline, is likely to have a protective effect against the emergence of psychosis but evidence from human studies is lacking. The aim of this study is to examine the effects of exposure to minocycline during adolescence on the later incidence of severe mental illness (SMI).
Methods:
A historical cohort study using electronic primary care data was conducted to assess the association between exposure to minocycline during adolescence and incidence of SMI. The Incidence Rate Ratio (IRR) was measured using Poisson regression adjusted for age, gender, time of exposure, socioeconomic deprivation status, calendar year and co-medications.
Results:
Early minocycline prescription (n=13,248) did not affect the incidence of SMI compared with non-prescription of minocycline (n=14,393), regardless of gender or whether or not the data were filtered according to a minimum exposure period (minimum period: IRR 0.96; 95% CI 0.68–1.36; p=0.821; no minimum period: IRR 1.08; 95% CI 0.83–1.42; p=0.566).
Conclusions:
Exposure to minocycline for acne treatment during adolescence appears to have no effect on the incidence of SMI.
AkhondzadehSTabatabaeeMAminiHet al (2007) Celecoxib as adjunctive therapy in schizophrenia: A double-blind, randomized and placebo-controlled trial. Schizophr Res90: 179–185.
2.
AustinPC (2009) Using the standardized difference to compare the prevalence of a binary variable between two groups in observational research. Commun Stat Simul Comput38: 1228–1234.
3.
BossongMGNiesinkRJM (2010) Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia. Prog Neurobiol92: 370–385.
4.
BumpJMEnningFLewekeFM (2013) Repurposed drugs for the treatment of schizophrenia and bipolar disorders. Curr Top Med Chem13: 2364–2385.
5.
CastleDJMcGranthJKulkarniJ (2000) Women and Schizophrenia. Cambridge: Cambridge University Press.
6.
ChaudhryIBHallakJHusainNet al (2012) Minocycline benefits negative symptoms in early schizophrenia: A randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J Psychopharmacol26: 1185–1193.
7.
ChaudhryIBHusainNur RahmanRet al (2015) A randomised double-blind placebo-controlled 12- week feasibility trial of methotrexate added to treatment as usual in early schizophrenia: Study protocol for a randomised controlled trial. Trials16: 9.
8.
ChavesCMarqueCRMaia-de-OliveiraJPet al (2015) Effects of minocycline add-on treatment on brain morphometry and cerebral perfusion in recent-onset schizophrenia. Schizophr Res161: 439–445.
9.
DomercqMMatuteC (2004) Neuroprotection by tetracyclines. Trends Pharmacol Sci25: 10–13.
10.
García RodríguezLAPérez GutthannS (2002) Use of the UK General Practice Research Database for pharmacoepidemiology. Br J Clin Pharmacol45: 419–425.
11.
GarnerSEEadyEAPopescuCet al (2003) Minocycline for acne vulgaris: Efficacy and safety. Cochrane Database Syst Rev1: CD002086.
12.
Garrido-MesaNZarzueloAGálvezJ (2013) Minocycline: Far beyond an antibiotic. Br J Pharmacol169: 337–352.
13.
GhanizadehADehbozorgiSOmraniSigaroodiMet al (2014) Minocycline as add-on treatment decreases the negative symptoms of schizophrenia; A randomized placebo-controlled clinical trial. Recent Pat Inflamm Allergy Drug Discov8: 211–215.
14.
GiovanoliSEnglerHEnglerAet al (2013) Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice. Science339: 1095–1099.
15.
GiovanoliSEnglerHEnglerAet al (2016) Preventive effects of minocycline in a neurodevelopmental two-hit model with relevance to schizophrenia. Transl Psychiatry6: e772.
16.
HardoonSHayesJFBlackburnRet al (2013) Recording of severe mental illness in United Kingdom primary care, 2000–2010. PLoS One8: e82365.
17.
HerrettEThomasSLSchoonenWMet al (2010) Validation and validity of diagnoses in the General Practice Research Database: A systematic review. Br J Clin Pharmacol69: 4–14.
18.
Hoirisch-ClapauchSNardiAE (2013) Psychiatric remission with warfarin: Should psychosis be addressed as plasminogen activator imbalance?Med Hypotheses80: 137–141.
19.
HusainMIChaudhryIBRahmanRRet al (2017) Minocycline as an adjunct for treatment-resistant depressive symptoms: Study protocol for a pilot randomised controlled trial. J Psychopharmacol31: 1166–1175.
JonesCWatsonDFoneK (2011) Animal models of schizophrenia. Br J Pharmacol164: 1162–1194.
22.
KellerWRKumLMWehringHJet al (2013) A review of anti-inflammatory agents for symptoms of schizophrenia. J Psychopharmacol27: 337–342.
23.
KellyDLSullivanKMMcEvoyJPet al (2015) Adjunctive minocycline in clozapine-treated schizophrenia patients with persistent symptoms. J Clin Psychopharmacol35: 374–381.
24.
Khodaie-ArdakaniM-RMirshafieeOFarokhniaMet al (2014) Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: Randomized double-blind placebo-controlled study. Psychiatry Res215: 540–546.
25.
KirkbrideJBErrazurizACroudaceTJet al (2012) Incidence of schizophrenia and other psychoses in england, 1950–2009: A systematic review and meta-analyses. PLoS One7: e31660.
26.
LaanWGrobbeeDESeltenJ-Pet al (2010) Adjuvant aspirin therapy reduces symptoms of schizophrenia spectrum disorders: Results from a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry71: 520–527.
27.
LevkovitzYLeviUBrawYet al (2007) Minocycline, a second-generation tetracycline, as a neuroprotective agent in an animal model of schizophrenia. Brain Res1154: 154–162.
28.
LevkovitzYMendlovichSRiwkesSet al (2010) A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry71: 138–149.
29.
LiuFGuoXWuRet al (2014) Minocycline supplementation for treatment of negative symptoms in early-phase schizophrenia: A double blind, randomized, controlled trial. Schizophr Res153: 169–176.
30.
LuM-LPanJ-JTengH-Wet al (2002) Metoclopramide-induced supersensitivity psychosis. Ann Pharmacother36: 1387–1390.
31.
LudotMMouchabacSFerreriF (2015) Inter-relationships between isotretinoin treatment and psychiatric disorders: Depression, bipolar disorder, anxiety, psychosis and suicide risks. World J Psychiatry5: 222–227.
32.
MiyaokaTWakeRFuruyaMet al (2012) Minocycline as adjunctive therapy for patients with unipolar psychotic depression: An open-label study. Prog Neuropsychopharmacol Biol Psychiatry37: 222–226.
33.
MonjiAKatoTAMizoguchiYet al (2013) Neuroinflammation in schizophrenia especially focused on the role of microglia. Prog Neuropsychopharmacol Biol Psychiatry42: 115–121.
34.
MonteASde SouzaGCMcIntyreRSet al (2013) Prevention and reversal of ketamine-induced schizophrenia related behavior by minocycline in mice: Possible involvement of antioxidant and nitrergic pathways. J Psychopharmacol27: 1032–1043.
35.
National Institute for Health and Care Excellence (2014) Clinical Knowledge Summaries: Acne vulgaris. Available at: http://cks.nice.org.uk/acne-vulgaris (accessed 6 November 2015).
36.
National Institute for Health and Care Excellence (2015) Key Therapeuctic Topics: Minocycline. Available at: https://www.nice.org.uk/advice/ktt11 (accessed October 2016).
37.
National Institute for Health and Care Excellence (2016). Available at: https://www.nice.org.uk/guidance (accessed October 2016).
38.
OyaKKishiTIwataN (2014) Efficacy and tolerability of minocycline augmentation therapy in schizophrenia: A systematic review and meta-analysis of randomized controlled trials. Hum Psychopharmacol29: 483–491.
39.
PedersenCBMorsOBertelsenAet al (2014) A comprehensive nationwide study of the incidence rate and lifetime risk for treated mental disorders. JAMA Psychiatry71: 573–581.
40.
ShyuYYuanSLeeS-Yet al (2015) Attention-deficit/hyperactivity disorder, methylphenidate use and the risk of developing schizophrenia spectrum disorders: A nationwide population-based study in Taiwan. Schizophr Res168: 161–167.
41.
SuissaSGarbeE (2007) Primer: administrative health databases in observational studies of drug effects–advantages and disadvantages. Nat Clin Pract Rheumatol3: 725–732.
42.
SweetmanS (2016) Martindale: The Complete Drug Reference (online). London: Pharmaceutical Press. Available at: http://www.medicinescomplete.com/ (accessed 4 October 2016).
43.
TakahashiYYuZSakaiMet al (2016) Linking activation of microglia and peripheral monocytic cells to the pathophysiology of psychiatric disorders. Front Cell Neurosci10: 144.
44.
WilliamsTvan StaaTPuriSet al (2012) Recent advances in the utility and use of the general practice research database as an example of a UK primary care data resource. Ther Adv Drug Saf3: 89–99.
45.
XiangY-QZhengWWangS-Bet al (2016) Adjunctive minocycline for schizophrenia: Ameta-analysis of randomized controlled trials. Eur Neuropsychopharmacol27: 8–18.
46.
ZaengleinALPathyALSchlosserBJet al (2016) Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol74: 945–973.e33.
47.
ZhangLShirayamaYIyoMet al (2007) Minocycline Attenuates hyperlocomotion and prepulse inhibition deficits in mice after administration of the NMDA receptor antagonist dizocilpine. Neuropsychopharmacology32: 2004–2010.
48.
ZhangLZhaoJ (2014) Profile of minocycline and its potential in the treatment of schizophrenia. Neuropsychiatr Dis Treat10: 1103–1111.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
