This study will examine the feasibility and potential efficacy of augmenting SRIs with minocycline. The study will assess whether the addition of minocycline leads to measurable changes in striatal glutamate (Glu) levels. This study will recruit up to 45 youth ages 8-20 diagnosed with clinically significant OCD who have demonstrated no more than minimal response to SRI treatment and are currently on a stable dose of SRI medication for at least 12 weeks. Participants will be randomized to receive either 12 weeks of minocycline treatment or pill placebo. Randomization will be 2:1 so that 2 of 3 participants receive minocycline. Screening for eligibility will take place for 1-4 weeks. Participants will undergo magnetic resonance spectroscopy (MRS) scans to measure striatal Glu levels prior to randomization, and again immediately following the treatment period. During the treatment period, participants will meet initially weekly and then every other week with the study psychiatrist. All participants will be offered three months of open medication treatment following participation. The clinical trial will only be conducted at the New York State Psychiatric Institute (NYSPI) and the MRS scans may be conducted at Weill Cornell Medical Center or NYSPI.

Please see the brief summary for study description.

Inclusion Criteria:

• Participants must be ages of 8-20 at the time of consent
• Participants must weigh at least 25kg
• Participants and a parent/guardian must be able to read and understand English
• Participants must meet diagnostic criteria for obsessive-compulsive disorder with score ≥ 16 on the Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS)
• Participants must be on stable dose of serotonin reuptake inhibitor (SRI) medication, and must have had a minimal adequate trial of SRI medication
• Report of at least minimal, but not full, response to current SRI medication to warrant ongoing SRI treatment
• For participants younger than 18, written informed assent by the participant and consent by the parent. For participants 18 and older, written consent by the participant and permission for legal guardian/parent to provide information

Exclusion Criteria:

• Lifetime diagnosis of: psychotic disorder, bipolar disorder, eating disorder, pervasive developmental disorder, mental retardation, or substance/alcohol dependence
• Current diagnosis of major depressive disorder, Tourette's/Tic Disorder, or substance/alcohol abuse
• Positive urine screen for illicit drugs
• Medical or psychiatric conditions that would make participation in the study unsafe
• Active suicidal ideation
• Females who are using hormonal birth control
• Presence of metallic device or dental braces incompatible with MRS
• Intelligence quotient (IQ) <80
• OCD patients with primary symptoms of hoarding (determined by CYBOCS checklist)
• Current or past diagnosis of pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS)
• Individuals who are currently receiving Exposure and Response Prevention therapy and are in the acute phase of treatment.
• Documented history of hypersensitivity or intolerance to tetracycline antibiotics
• Use of medications that are contra-indicated with minocycline (e.g., concomitant use of antacids, iron, calcium, magnesium, aluminum, zinc salts as they impair minocycline absorption; of anti-coagulant drugs as minocycline has been shown to depress plasma prothrombin activity; of other antibiotics or Accutane due to the rare side effect of pseudotumor cerebri)
• Inability of participant or parent/guardian to read or understand English

12 weeks