Famotidine Augmentation in Schizophrenia: Hope or Hype?

Andrade, Chittaranjan

doi:10.4088/jcp.13f08707

Cited by 6 publications

(2 citation statements)

References 20 publications

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“…Nevertheless, H 2 R agonists hold great potential as they may cover both the positive and negative symptoms of schizophrenia and may be feasible for direct clinical application. Moreover, there is evidence of H 2 R antagonist famotidine augmentation of antipsychotic medications in schizophrenia patients, but some randomized controlled trials of famotidine did not show consistent efficacy in treating the symptoms of schizophrenia ( 55 – 58 ). Some evidence suggests that the benefits of famotidine for schizophrenia may not arise from H 2 R antagonism ( 11 , 59 ).…”

Section: Discussionmentioning

confidence: 99%

Histamine H ₂ receptor deficit in glutamatergic neurons contributes to the pathogenesis of schizophrenia

Jiang

Chen

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Schizophrenia is a serious mental disorder, and existing antipsychotic drugs show limited efficacy and cause unwanted side effects. The development of glutamatergic drugs for schizophrenia is currently challenging. Most functions of histamine in the brain are mediated by the histamine H 1 receptor; however, the role of the H 2 receptor (H 2 R) is not quite clear, especially in schizophrenia. Here, we found that expression of H 2 R in glutamatergic neurons of the frontal cortex was decreased in schizophrenia patients. Selective knockout of the H 2 R gene ( Hrh2 ) in glutamatergic neurons ( CaMKIIα-Cre; Hrh2 fl/fl ) induced schizophrenia-like phenotypes including sensorimotor gating deficits, increased susceptibility to hyperactivity, social withdrawal, anhedonia, and impaired working memory, as well as decreased firing of glutamatergic neurons in the medial prefrontal cortex (mPFC) in in vivo electrophysiological tests. Selective knockdown of H 2 R in glutamatergic neurons in the mPFC but not those in the hippocampus also mimicked these schizophrenia-like phenotypes. Furthermore, electrophysiology experiments established that H 2 R deficiency decreased the firing of glutamatergic neurons by enhancing the current through hyperpolarization-activated cyclic nucleotide-gated channels. In addition, either H 2 R overexpression in glutamatergic neurons or H 2 R agonism in the mPFC counteracted schizophrenia-like phenotypes in an MK-801-induced mouse model of schizophrenia. Taken together, our results suggest that deficit of H 2 R in mPFC glutamatergic neurons may be pivotal to the pathogenesis of schizophrenia and that H 2 R agonists can be regarded as potentially efficacious medications for schizophrenia therapy. The findings also provide evidence for enriching the conventional glutamate hypothesis for the pathogenesis of schizophrenia and improve the understanding of the functional role of H 2 R in the brain, especially in glutamatergic neurons.

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Section: Discussionmentioning

confidence: 99%

Histamine H ₂ receptor deficit in glutamatergic neurons contributes to the pathogenesis of schizophrenia

Jiang

Chen

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…A previous article in this column suggested that famotidine augmentation may not be of much benefit. 2 The present article examines 2 other innovative augmentation treatments: nonsteroidal anti-inflammatory drugs (NSAIDs) and 5-HT 3 serotonin receptor antagonists.…”

Section: Introductionmentioning

confidence: 99%

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

Andrade

2014

J. Clin. Psychiatry

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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.

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Targeting the Central Histamine H2 Receptor: New Hope for Schizophrenia?

Lin,

Yu,

Zhu

2023

Neurosci. Bull.

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Famotidine Augmentation in Schizophrenia: Hope or Hype?

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.

Cited by 6 publications

References 20 publications

Histamine H ₂ receptor deficit in glutamatergic neurons contributes to the pathogenesis of schizophrenia

Histamine H ₂ receptor deficit in glutamatergic neurons contributes to the pathogenesis of schizophrenia

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

Targeting the Central Histamine H2 Receptor: New Hope for Schizophrenia?

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Famotidine Augmentation in Schizophrenia: Hope or Hype?

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.

Cited by 6 publications

References 20 publications

Histamine H 2 receptor deficit in glutamatergic neurons contributes to the pathogenesis of schizophrenia

Histamine H 2 receptor deficit in glutamatergic neurons contributes to the pathogenesis of schizophrenia

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

Targeting the Central Histamine H2 Receptor: New Hope for Schizophrenia?

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Histamine H ₂ receptor deficit in glutamatergic neurons contributes to the pathogenesis of schizophrenia

Histamine H ₂ receptor deficit in glutamatergic neurons contributes to the pathogenesis of schizophrenia

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