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. Author manuscript; available in PMC: 2014 Feb 13.
Published in final edited form as: J Clin Psychiatry. 2010 Sep;71(9):1247–1249. doi: 10.4088/JCP.09l05805blu

Minocycline Augmentation of Pharmacotherapy in Obsessive-Compulsive Disorder: An Open-Label Trial

Carolyn I Rodriguez a,b, James Bender a, Sue M Marcus a, Michael Snape c, Moira Rynn a,b, Helen Blair Simpson a,b
PMCID: PMC3923525  NIHMSID: NIHMS526904  PMID: 20923629

Abstract

not applicable, since submission is “letter to the editor.”

Keywords: Anxiety Disorders, glutamate, obsessive-compulsive disorder, OCD, minocycline, Y-BOCS

To the editor

Most obsessive-compulsive disorder (OCD) patients treated with serotonin reuptake inhibitors (SRIs) show only partial reduction of symptoms.1 Data suggest that OCD may be caused in part by glutamatergic dysfunction in orbito-frontal/basal ganglia brain circuits.2, 3 and prior trials of glutamate modulators (e.g., riluzole, memantine) given as augmentation to SRIs suggest anywhere from 30% to 54% of OCD patients respond.4–8

We conducted a 12-week, prospective, open-label study to assess whether SRI augmentation with minocycline, a tetracycline derivative with putative glutamate modulating activity (i.e., enhancing glial glutamate transport)9 in addition to its antibiotic properties, would improve OCD symptoms.

Advantages of minocycline include low cost (riluzole is expensive) and FDA approval in adults and children >12 years (memantine is only FDA approved in adults). Minocycline is the most widely prescribed antibiotic for chronic acne because its antibiotic resistance is lower than that of other tetracyclines and antimicrobials.10 It has excellent side effect profile, even chronically: one study11 showed minocycline taken for 2 years is well-tolerated, with no serious adverse effects.

Methods

Adult outpatients (N=9) aged 18 to 65 years who met DSM-IV criteria for OCD and had a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS)12 score of ≥16 despite a therapeutic SRI dose were recruited from the community between July 2008 and July 2009 and gave informed consent after the study procedures were fully explained. Institutional review board approval was obtained for the study. Subjects’ SRI dose was stable for at least 12 weeks (and concomitant psychotropic medications for at least 4 weeks) prior to study entry. Subjects were excluded for current cognitive behavioral therapy, comorbid psychiatric or medical conditions that made participation unsafe, or use of medications that reduced the bioavailability of minocycline. Patients were assessed by an independent rater who administered the YBOCS (primary outcome measure), Hamilton Depression Inventory (HDRS, 17-item)13, and Hamilton Anxiety Inventory (HARS)14 every 2 weeks. Response was defined as at least a 30% reduction on the YBOCS.15

Subjects received minocycline at 50 mg bid for 3 days to ensure no allergic reaction, then at the FDA-approved adult dosing of 100 mg bid for 12 weeks in addition to their SRI. This dosing is expected to produce minocycline brain concentrations in the range that antagonize glutamate effects on neurons.16, 17 All subjects completed the study, supporting the fact that minocycline was well tolerated. Outcome was analyzed using mixed-effects regression to model symptoms as a function of time.18

Results

Patient clinical characteristics are shown in Table 1.19 OCD severity was moderate: mean (SD) YBOCS score at baseline was 28.2 (3.9), illness duration was 18.2 (10.4) years. Subjects were treatment-resistant: the mean number of prior SRI trials was 2.8 (1.6); 56% (5/9) had failed at least 1 adequate trial of antipsychotic augmentation, and 56% had failed an adequate trial of cognitive behavioral therapy. They had a range of OCD symptoms; one subject had hoarding as the primary symptom domain.

Table 1. Clinical Characteristics of OCD Subjects.

Clinical characteristics and treatment history of nine OCD patients treated with minocycline in addition to SRI/SNRI. Symptom dimensions were based on a 4-factor model19 and listed in order of clinical severity for each subject: Cont (contamination obsessions and cleaning compulsions); Forbid Tht, (forbidden thoughts including aggression, sexual, religious, and somatic obsessions and checking compulsions); Hrd (hoarding and saving obsessions and compulsions); Symmetry (symmetry obsessions and repeating, ordering, and counting compulsions). AA, African American; C, Caucasian; Dysth, Dysthymia; F, female; GAD, generalized anxiety disorder; GF, grandfather; HAM-A, Hamilton Anxiety Rating Scale; HAM-D, Hamilton Depression Rating Scale; M, male; m, maternal; MDD, major depressive disorder; OCD, obsessive-compulsive disorder; p, paternal; S, sister; SRI, serotonin reuptake inhibitor; SNRI, serotonin and norepinephrine reuptake inhibitor; Soc Phobia, social phobia; Speci Phobia, Specific Phobia; Substance Ab, Substance Abuse; Y-BOCS, Yale-Brown Obsessive-Compulsive Scale.

Pt No./Age/ Sex/Ethniticy Age of OCD Onset (y) OCD Symptom Domain Comorbid Diagnoses Psychiatric Family History Prior SRI Trials Previous Anti-psychotic /or CBT Current SRI /SNRI Daily Dose Concommittant Psych Meds Pre/Post YBOCS Score Pre/Post HAM-D Score Pre/Post HAM-A Score
#1/40/M/AA 30 Cont, Symmetry MDD None 4 No/Yes Fluoxetine 80mg None 24/30 7/0 8/0
#2/50/F/W 30 Cont, Hrd, Symmetry None GAD (mother) 6 Yes/Yes Duloxetine 60mg None 29/28 0/3 0/3
#3/24/M/W 22 Cont, Symmetry, Forbid Tht MDD Soc Phobia OCD (father, p uncle, p GF) Substance Ab (S) 2 No/No Escitalopram 40mg Zolpidem Clonazepam 29/26 12/10 9/7
#4/42/F/W 17 Symmetry, Forbid Tht MDD None 4 Yes/No Fluvoxamine 150mg None 34/35 27/28 33/42
#5/54/M/W 20 Symmetry, Forbid Tht, MDD OCD (daughter) 2 Yes/No Fluoxetine 80mg Lisdexamfetam ine dimesylate 29/25 8/14 12/18
#6/53/M/W 23 Cont, Symmetry, Forbid Tht, Hrd MDD OCD (father) 2 Yes/Yes Fluvoxamine 300mg None 29/29 0/3 0/2
#7/51/M/W 40 Hrd, Symmetry, Forbid Tht Soc Phobia, GAD Substance Ab (m cousin) 1 No/Yes Sertraline 100mg None 23/22 8/10 7/7
#8/38/F/AA 11 Hrd MDD, Dysth Speci Phobia Bipolar (mother, brother) 2 Yes/No Fluoxetine 80mg Buproprion Desvenlafaxine 33/20a 16/5 14/5
#9/19/M/W 4 Symmetry, Forbid Tht, Hrd None Bipolar (father, m uncle, p aunt, p GF) 2 No/Yes Fluoxetine 80mg Clonzaepam Lisdexamfetam ine dimesylate 24/13 a 3/1 1/2
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a

>30% reduction in YBOCS rating scale.

As a group, patients showed no significant differences in YBOCS, HDRS, or HARS rate of improvement over time (mixed effects regression: Y-BOCS, z = −1.14, p= .25; HAM-D, z = .60, p = .55; HAM-A, z = .12, p = .90). However, 2 of 9 patients (22%) met and exceeded treatment response criteria (40% and 46% Y-BOCS reduction). Both of these patients reported early onset of their OCD symptoms. One had primary hoarding, and 1 no longer met criteria for OCD at study end. Both chose to continue minocycline after study end.

These data suggest that minocycline augmentation of SRI pharmacotherapy may not improve OCD symptoms in all adult OCD patients, but may improve symptoms in those with early-onset OCD and those with primary hoarding. The robust response of 2 of 9 patients in this study coupled with the response of 2 other subjects (aged 16 and 17 years) with early-onset OCD in an identical parallel study of minocycline in adolescents (M.R., unpublished data, 2008) suggests that minocycline warrants further study. Early-onset OCD differs from later onset OCD in phenomenology, genetic risk, and SRI response.20 Future studies should target early-onset OCD as well as focus on minocycline’s mechanism of action.21

Acknowledgments

Funding support: This investigation was supported by the NARSAD Joan Grandlund Investigator Award (to Dr. Rodriguez) and by Neuropharm Ltd (to Drs. Rynn and Simpson).

Andrew Schmidt for data management and Kim Glazier for data analysis.

Footnotes

Previous Presentation: NCDEU, Hollywood, Florida, June 30, 2009 and ACNP, Hollywood Florida, December 8, 2009

Clinical Trials Registration:

“Pilot Study of NPL-2003 (Minocycline) in Adults With Obsessive-Compulsive Disorder (OCD);” http://www.clinicaltrials.gov/; registration number NCT00728923.

Financial disclosures: Dr. Simpson has been a consultant or scientific advisor for Jazz Pharmaceuticals (9/07-9/08) and for Pfizer, Ltd (9/09), receives medication at no cost for an NIMH-funded study from Janssen Pharmaceuticals, and received an unrestricted research grant from Neuropharm Ltd to explore novel medications for OCD. Dr. Rynn receives research support from Boehringer Ingelheim Pharmaceuticals, Inc., Wyeth Pharmaceuticals, Inc., and Neuropharm Ltd. Dr. Snape is the Chief Scientific Officer of Neuropharm Ltd and is a share holder in that company. Drs. Rodriguez, Bender, and Marcus report no additional financial or other relationships relevant to the subject of this letter.

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