Nonsteroidal Anti-inflammatory Drugs and 5-HT₃Serotonin Receptor Antagonists as Innovative Antipsychotic Augmentation Treatments for Schizophrenia

Abstract

Each month in his online column, Dr Andrade offers practical knowledge, ideas, and tips in psychopharmacology to JCP readers in psychiatric and general medical settings. Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, India (candrade@psychiatrist.com). Department of ABSTRACTAntipsychotic treatment is the mainstay in the management of schizophrenia. However, despite optimum use of antipsychotic drugs, many schizophrenia patients continue to exhibit residual positive, negative, cognitive, and other symptoms. Various antipsychotic augmentation strategies have been studied using non-antipsychotic augmenting agents; 2 innovative classes of drugs examined have been nonsteroidal anti-inflammatory drugs (NSAIDs) and 5-HT 3 serotonin receptor antagonists. Metaanalysis of the NSAID studies in schizophrenia patients with positive symptoms (8 randomized controlled trials [RCTs], pooled N = 774) shows that NSAID augmentation is associated with a significant decrease in positive symptom ratings (standardized mean difference [SMD] = 0.19), with no significant change in negative or total symptom ratings. Meta-analysis of the 5-HT 3 antagonist studies in stable schizophrenia patients (6 RCTs, pooled N = 311) shows that 5-HT 3 antagonist augmentation is associated with significant reduction in negative symptom (SMD = 1.10), general psychopathology (SMD = 0.70), and total symptom (SMD = 1.03) ratings without reduction in positive symptom ratings. Neither NSAID nor 5-HT 3 antagonist augmentation increases the dropout rate. Whereas the benefits with NSAID augmentation are, perhaps, too small to be clinically meaningful, antipsychotic augmentation with 5-HT 3 antagonists may be a possible strategy to reduce persistent negative symptoms in schizophrenia. Both fields of inquiry require further investigation.

Psychopharmacological Treatment of Obsessive-Compulsive Disorder (OCD)

“…Ondansetron is a 5-HT 3 serotonin receptor antagonist used primarily to reduce nausea and vomiting associated with chemotherapy, radiotherapy, post-surgery, and pregnancy. Since 5-HT 3 blockade produces a weak inhibitory effect on dopaminergic neurotransmission [213], ondansetron has been tested in the treatment of schizophrenia [214], Tourette's disorder [215] tardive dyskinesia [216], alcoholism [217] (Johnson et al, 2011), and OCD [218]. Both uncontrolled and placebo-controlled studies showed that ondansetron was safe and effective in treating refractory OCD, both in monotherapy and added on SSRIs.…”

17.4 STRATIFICATION AND PREDICTION OF REMISSION IN FIRST-EPISODE PSYCHOSIS PATIENTS: THE OPTiMISE COHORT STUDY

“…In support of a critical role of inflammation in psychiatric diseases, add-on treatments with antiinflammatory drugs have been tested in severe and treatment-resistant psychiatric patients [56][57][58][59][60][61][62][63][64] . For example, acetyl salicylic acid (Aspirin) which interrupts the immuno-inflammatory cascade by inhibiting cyclooxygenase (COX)-1 and COX-2 showed promising results as an add-on treatment of schizophrenia in comparison to treatment as usual 60,63 .…”

A Comperehensive Drug Repurposing Study for Covid19 Treatment: Novel Putative DHODH Inhibitors Show Association to Serotonin-Dopamine Receptors

“…In structural similarity analyzes, similar targets were found between leflunomide and 5-HT antagonist drugs, and 5-HT antagonist drugs were among the molecules with the highest binding affinity to the DHODH enzyme among the 7900 molecules. It has been demonstrated by other studies that 5-HT antigonists cause suppression of cytokine release in immune cells by causing serotonin blocking 83,[85][86][87][88][89] . However these studies did not consider or tested for DHODH inhibition that may be on the main pathway to the anti-inflammatory affect.…”