Table 3.

Selected studies assessing the efficacy of antiinflammatory agents among patients with unipolar and bipolar depression, schizophrenia, and obsessive-compulsive disorder

Study	Study design	Group comparison	Number of subjects	Functional outcome
COX-2 inhibitors
Müller et al. 2006 [238]	RCT	Celecoxib (200 mg bid) + reboxetine versus placebo + reboxetine	40 MDD (acute)	Significantly greater decrease in depressive symptoms in the treatment group (P = 0.035)
Akhondzadeh et al. 2009 [239]	RCT	Celecoxib (200 mg bid) + fluoxetine versus placebo + fluoxetine	40 MDD	Significant improvement of depressive symptoms (P <0.001), and a greater percentage of responders (90% versus 50%, P = 0.01) and remission (35% versus 5%, P = 0.04) in the treatment group
Medlewicz et al. 2006 [240]	Open-label	Acetylsalicylic acid (160 mg qd) + SRI	24 MDD and BPD	52.4% responder rate, significant improvement within one week (P <0.0001) following treatment; sustained at four weeks
ClinicalTrials.gov http://www.clinicaltrials.gov/NCT00510822 completed, pending results	RCT	Cimicoxib (50 mg bid) + sertraline versus placebo + sertraline	169 MDD	Primary outcome measure is mean change in Hamilton Depression Rating Scale from baselineto six-week endpoint
Nery et al. 2008 [263]	RCT	Celecoxib versus placebo	28 BPD (depressive and mixed states)	No significant differences in depressive or manic symptoms.
Müller et al. 2002 [242]	RCT	Celecoxib (400 mg qd) + risperidone versus placebo + risperidone	50 (acute schizophrenia)	Significant improvement of positive and negative symptoms (P = 0.05), as well as cognition (P <0.06) in treatment group at five weeks
Müller et al. 2010 [244]	RCT	Celecoxib + amisulpride versus placebo + amisulpride	49 schizophrenia (first-episode)	Significant improvement of positive and negative symptoms in celecoxib plus amisulpride group relative to amisulpride alone (P <0.001) at six-weeks
Sayyah et al. 2011 [245]	RCT	Celecoxib (200 mg bid) + fluoxetine versus placebo + fluoxetine	50 OCD	Significantly greater reduction in YBOCS scores in the celecoxib treatment group at two weeks (P = 0.007) and at the eight week end-point (P = 0.037)
Minocycline
Levine et al. 1996 [264]	Case report	Minocycline (150 mg qd) started 20 years after disease onset	1 BPD	Marked decrease in depressive symptoms (HAM-D score went from 25 to 8) within one week following treatment, sustained at two weeks.
Levkovitz et al. 2009 [265]	RCT	Minocycline (200 mg qd) versus placebo	21 schizophrenia (early and acute-phase)	Significant improvement of negative symptoms and cognitive dysfunction in treatment group (P <0.01)
ClinicalTrials.gov NCT01433055 recruiting, estimated completion 7/15	RCT	Minocycline (100 mg bid) + clozapine versus placebo + clozapine	60 schizophrenia (refractory to ≥2 antipsychotics)	Primary outcome is the improvement in positive symptoms as measured by the four-item sub-factor of the Brief Psychiatric Rating Scale.
Miyaoka et al. 2007 [266]	Case series	Minocycline (150 mg qd) + stable antipsychotic regiment	2 schizophrenia	Complete resolution of positive and negative symptoms with minocycline, sustained for one to two years. Symptom exacerbation occurred one-week following minocycline discontinuation (in both cases). In one patient, the complete resolution of symptoms occurred at age 61, which was 41 years after disease onset.
Miyaoka et al. 2008 [267]	Open-label	Minocycline (150 mg tid)	22 schizophrenia	Significant improvement of positive and negative symptoms at four to eight weeks (P = 0.0001)
Rodriguez et al. 2010 [268]	Open-label	Minocycline (100 mg bid)	9 OCD	22% had a 40% to 46% YBOCS reduction at 12 weeks; the group as a whole did not have a significant change in YBOCS score.

ASA, acetylsalicylic acid; BPD, bipolar disorder; COX-2, cycloxygenase-2; HAM-D: Hamilton Depression Rating Scale; MDD, major depressive disorder; OCD, obsessive-compulsive disorder; SRI, serotonin reuptake inhibitor; RCT, randomized controlled trial; YBOCS: Yale-Brown Obsessive-Compulsive Scale.