Treatment Psychiatric disorder Probands Trial design Outcome Authors Aspirin 1000 mg/day plus 40 mg/day pantoprazole, in addition to antipsychotic treatment Schizophrenia Patients with at least moderate symptom burden and a DSM-IV diagnosis for schizophrenia spectrum disorder for under 10 years Randomized controlled trial Mixed model improvement in overall psychopathology and in positive symptoms as measured by PANSS Laan et al., 2010 [158 ] Aspirin 1000 mg/day plus 40 mg/day pantoprazole, in addition to antipsychotic treatment Schizophrenia Patients with moderate or above on CGI score, moderate score on two of PANSS items: delusions, hallucinatory behaviors, conceptual disorganization or suspiciousness/persecution, and/or a total PANSS negative symptoms score above 18 Post hoc analysis of randomized controlled trial Improvements in patients with high CRP levels Weiser et al., 2014 [159 ] Celecoxib 200 mg bid in addition to 2–6 mg/day risperidone Schizophrenia Patients with acute exacerbation of schizophrenia Double-blind, Randomized Placebo-controlled Significant improvement of positive symptoms Müller et al., 2002 [160 ] Celecoxib in addition to olanzapine Schizophrenia Patients with acute exacerbation of schizophrenia Open-label, prospective, controlled Improvement of positive, negative, and general psychopathology and total scores as measured by PANSS Baheti et al., 2013 [161 ] Celecoxib (200 mg bid) in addition to risperidone (200 mg/day) Schizophrenia inpatients diagnosed with active phase schizophrenia Double-blind randomized placebo-controlled Significant improvement regarding positive symptoms as measured by PANSS Akhondzadeh et al., 2007 [162 ] Celecoxib Schizophrenia Patients with a first manifestation of schizophrenia Double-blind randomized placebo-controlled Significant improvement regarding positive and negative symptoms as measured by PANSS Müller et al., 2010 [163 ] Celecoxib (400 mg/day) in addition to antipsychotic treatment Schizophrenia Outpatients with a DSM-IV diagnosis of schizophrenia, experiencing persistent symptoms despite treatment for 3 months Double-blind, randomized, placebo-controlled, No difference in outcome, as measured by PANSS Rapaport et al. 2005 [164 ] Concomitant intake of NSAID or paracetamol Schizophrenia Schizophrenia patients Retrospective investigation Higher risk for relapse to active psychosis Köhler et al., 2016 [165 ] Previous NSAID use Schizophrenia Patients prescribed antipsychotics Case-control trial of antipsychotics prescription Significant reduction of risk to develop psychosis when NSAID had been taken, but only in male individuals Laan et al., 2007 [166 ] Use of COX-2 inhibitors Schizophrenia Case events indicating schizophrenia exacerbation in patients using antipsychotics Nested case-control study No increase of risk for schizophrenia exacerbation Stolk et al., 2007 [167 ] Minocycline in addition to usual treatment Schizophrenia Patients with early-stage schizophrenia Double-blind, randomized, placebo-controlled Significant improvement of negative symptoms as measured by PANSS Chaudhry et al., 2012 [168 ] Minocycline (200 mg/day) in addition to risperidone Schizophrenia Patients with DSM-IV diagnosis of early-phase (less than 5 years) schizophrenia who had been on a steady dosage of risperidone Double-blind, randomized, placebo-controlled Significant improvement in treatment response in the Scale for the Assessment of Negative Symptoms (SANS) total scores and PANSS for negative symptoms Liu et al., 2014 [169 ] Minocycline (200 mg/day) Schizophrenia Patients with DSM-IV diagnosis of schizophrenia, no treatment with therapeutics for one week before start of trial Randomized, placebo-controlled Significant decrease of SANS score after 8 weeks (though not 4 weeks) of treatment Ghanizadeh et al., 2014 [170 ] Minocycline (up to 200 mg/day) in addition to risperidone (up to 6 mg/day) Schizophrenia Chronic schizophrenia patients Double-blind, randomized, placebo-controlled Significant improvement of negative symptom as measured by PANSS Khodaie-Ardakani et al., 2014 [171 ] Minocycline Schizophrenia Early-phase schizophrenia patients Double-blind, randomized, placebo-controlled Significant improvement of negative symptoms and general outcome measured by PANSS, Clinical Global Impression (CGI) and insight score, and improvements of cognitive executive functions Levkovitz et al., 2009 [172 ] NSAID and paracetamol Bipolar disorder DSM-IV-TR diagnosis of bipolar disorder I or II and at least mild symptoms Secondary analysis from the Bipolar CHOICE study No difference as measured by CGI-BP Köhler-Forsberg et al., 2017 [173 ] Aspirin Bipolar disorder Patients taking lithium with erectile dysfunction Double-blind, randomized, placebo-controlled No differences in mania or depressive symptoms, significant improvement of erectile dysfunction Saroukhani et al., 2013 [174 ] Aspirin, low-dose of 30 or 80 mg per day and for an unspecified time or for more than 1, 45, 90, or 180 days, in addition to lithium Bipolar disorder Patients with at least five previous prescriptions for lithium and at least 1-year drug history Pharmacoepidemiological study on the PHARMO Record Linkage System (RLS) in the Netherlands Significantly fewer events of mood-stabilizer treatment alteration Stolk et al., 2010 [175 ] Celecoxib (400 mg/day) Bipolar disorder DSM-IV diagnosis of bipolar disorder during a depressive or mixed episode of the disease Double-blind, randomized, placebo-controlled Improvement of depressive symptoms (as measured by Hamilton Depression Rating Scale) found in the first week Nery et al., 2008 [176 ] Celecoxib in addition to sodium valproate Bipolar disorder Patients with diagnosis of acute bipolar mania with manic episode without psychotic features Double-blind, randomized, placebo-controlled Significantly higher remission rates as measured by young mania rating scale Arabzadeh et al., 2015 [177 ] Concomitant NSAID use in addition to escitalopram or nortriptyline Depression Patients with major depression disorder treated in the GENDEP study Retrospective on the GENDEP study No change of serotonin reuptake inhibitor treatment Uher et al., 2012 [178 ] Previous aspirin use as anti-platelet treatment Depression Men of older age (69–87 years) Retrospective analysis of aspirin use after assessment of mood disorder symptoms Significantly higher risk for depression in individuals who had used aspirin as antiplatelet agent drug in the past, but had stopped the treatment before the mood assessment (measured by Geriatric Depression scale) Almeida et al., 2010 [179 ] Regular aspirin or statin use in the past Depression Depression patients Population-based study No higher risk for development of depression Glaus et al., 2015 [180 ] Celecoxib in addition to antidepressants Depression Patients with depressive episodes Meta-analysis of 4 randomized controlled trials Improvements in Hamilton Rating Scale for Depression scores, remission and response rate Na et al., 2014 [181 ] Diclofenac (50 mg bid) versus celecoxib (200 mg bid) Depression Outpatients with breast cancer and concomitant depression Significant improvements by HDSR score in both, celecoxib significantly more successful than diclofenac, analgesic effect comparable Mohammadinejad et al., 2015 [182 ] Celecoxib (200 mg bid) Depression Patients with depression due to brucellosis Double-blind, randomized, placebo-controlled Significant improvements on HDRS Jafari et al., 2015 [183 ] Celecoxib (200 mg bid) or sodium naproxen (220 mg bid) Depression Individuals older than 70 years and with a family history of Alzheimer’s disease (though without any cognitive dysfunction) Alzheimer’s Disease Anti-Inflammatory Prevention Trial No significant change in individual or overall depression score measured by 30-item Geriatric Depression Scale Fields et al., 2012 [184 ] Minocycline (150 mg/day) as adjunctive therapy to fluvoxamine, paroxetine, or sertraline Depression Inpatients with a DSM-IV diagnosis of major depression with psychotic features Open-label study Significant improvement of depressive and psychotic symptoms as measured by Hamilton Depression Rating Scale and Brief Psychiatric Rating Scale Miyaoka et al., 2012 [185 ] 100 mg bid minocycline Depression HIV positive patients with mild-to-moderate scores of depression Double-blind, randomized, placebo-controlled Significant reduction of depression score (Hamilton Depression Rating Scale) Emadi-Kouchak et al., 2016 [186 ] Celecoxib 200 mg bid in addition to fluvoxamine OCD OCD outpatient Double-blind, randomized, placebo-controlled Significant improvement of symptoms Shalbafan et al., 2015 [187 ] N-Acetylcysteine (up to 2400 mg/day) OCD OCD patients, nonresponsive to serotonin reuptake inhibitors Double-blind, randomized, placebo-controlled 15% higher response rate Afshar et al., 2012 [188 ] Minocycline (100 mg/day) in addition to serotonin reuptake inhibitor OCD Treatment-resistant outpatients with OCD Open-label study No significant improvements in outcome in cohort as a whole, more than 30% reduction of the Yale–Brown Obsessive Compulsive Scale Rodriguez et al., 2010 [189 ] Minocycline (100 mg bid) as add-on to fluvoxamine (100 mg/day for the first two 200 mg/day for the remaining 6 weeks of the trial) OCD OCD patients Double-blind, randomized, placebo-controlled Significantly higher treatment response rate (either complete or partial) measured by the Yale-Brown Obsessive compulsive scale. Specifically patients scored significantly lower in total and on the obsessive subscale Esalatmanesh et al., 2016 [190 ] Celecoxib (up to 300 mg/day) in addition to risperidone Autism Children with autistic disorder Double-blind, randomized, placebo-controlled Significant improvements of scores in irritability, social withdrawal, and stereotypy Asadabadi et al., 2013 [191 ] Minocycline (1.4 mg/kg body weight) Autism Children with autism spectrum disorder Open-label No clinical improvements (Clinical Global Impression Severity Scale, Clinical Global Impression Severity Scale Improvement, and Vineland Adaptive Behavior Scales) Pardo et al., 2013 [192 ]
