Effects of adjunctive fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia: A 12-week, randomized, double-blind, placebo-controlled study

Lu, Mong Liang; Chen, Tzu Ting; Kuo, Po-Hsiu; Hsu, Ching‐Chi; Chen, Chun Hsin

doi:10.1016/j.schres.2017.06.030

Cited by 38 publications

(28 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, other genes (i.e., BDNF, DISC1 ) as well as neurotransmitters (i.e., glutamate, serotonin) and hormones (e.g., insulin) have also been shown to activate the PI3K–AKT–mTOR signaling pathway ( 41 – 43 ) and as such may contribute or confound the increase in P70S6K expression we have observed. However, most studies find decreased BDNF levels in the blood of people with schizophrenia ( 44 ) and suggest some degree of insulin resistance in clozapine-treated patients ( 45 ). Future investigations should attempt to account for these other signaling factors and the potential confounders of metabolic changes in people with schizophrenia being treated with clozapine, as doing so will further elucidate the suitability of P70S6K as a peripheral biomarker of over-activity in the NRG1 pathway in schizophrenia.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Transcription of NRG-ErbB Pathway Genes Are Upregulated in Treatment-Resistant Schizophrenia

et al. 2017

View full text Add to dashboard Cite

Investigation of peripheral gene expression patterns of transcripts within the NRG–ErbB signaling pathway, other than neuregulin-1 (NRG1), among patients with schizophrenia and more specifically treatment-resistant schizophrenia (TRS) is limited. The present study built on our previous work demonstrating elevated levels of NRG1 EGFα, EGFβ, and type I(Ig2) containing transcripts in TRS by investigating 11 NRG–ErbB signaling pathway mRNA transcripts (NRG2, ErbB1, ErbB2, ErbB3, ErbB4, PIK3CD, PIK3R3, AKT1, mTOR, P70S6K, eIF4EBP1) in whole blood of TRS patients (N = 71) and healthy controls (N = 57). We also examined the effect of clozapine exposure on transcript levels using cultured peripheral blood mononuclear cells (PBMCs) from 15 healthy individuals. Five transcripts (ErbB3, PIK3CD, AKT1, P70S6K, eIF4EBP1) were significantly elevated in TRS patients compared to healthy controls but only expression of P70S6K (Pcorrected = 0.018), a protein kinase linked to protein synthesis, cell growth, and cell proliferation, survived correction for multiple testing using the Benjamini–Hochberg method. Investigation of clinical factors revealed that ErbB2, PIK3CD, PIK3R3, AKT1, mTOR, and P70S6K expression were negatively correlated with duration of illness. However, no transcript was associated with chlorpromazine equivalent dose or clozapine plasma levels, the latter supported by our in vitro PBMC clozapine exposure experiment. Taken together with previously published NRG1 results, our findings suggest an overall upregulation of transcripts within the NRG–ErbB signaling pathway among individuals with schizophrenia some of which attenuate over duration of illness. Follow-up studies are needed to determine if the observed peripheral upregulation of transcripts within the NRG–ErbB signaling pathway are specific to TRS or are a general blood-based marker of schizophrenia.

show abstract

Section: Discussionmentioning

confidence: 99%

Peripheral Transcription of NRG-ErbB Pathway Genes Are Upregulated in Treatment-Resistant Schizophrenia

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Lu et al60 conducted a 12-week, randomized, double-blind, placebo-controlled study to evaluate the effects of fluvoxamine on metabolic parameters and psychopathology in subjects being started on clozapine (n = 85). Subjects were randomized to receive combination therapy of fluvoxamine 50 mg/d plus clozapine 100 mg/d or monotherapy of clozapine 300 mg/d.…”

Section: Methodsmentioning

confidence: 99%

Clozapine augmentation strategies

Roerig¹

2019

Mental Health Clinician

View full text Add to dashboard Cite

Clozapine is established as the gold standard for antipsychotic treatment of patients suffering from treatment-resistant schizophrenia. Over virtually 3 decades, the level of inadequate response to clozapine was found to range from 40% to 60%. A heightened interest developed in the augmentation of clozapine to try to achieve response or maximize partial response. A large variety of drug groups have been investigated. This article focuses on the meta-analyses of these trials to discover reasonable evidence-based approaches to the management of patients not responding to clozapine.

show abstract

“…Lu and colleagues followed their open-label study on the metabolic effects of fluvoxamine in patients taking clozapine with a double-blind, randomized, clinically controlled trial [44] (Table 1). Eighty-five patients were recruited and followed for 12 weeks, with 43 receiving clozapine monotherapy at a target dose of 300mg/day and 42 given fluvoxamine at 50mg/day and clozapine at 100mg/day.…”

Section: Ssris and Cardiovascular Risk In Patients With Schizophreniamentioning

confidence: 99%

SSRIs as Risk Reduction for Cardiovascular Disease in Patients with Schizophrenia

Bellon¹,

Nguyen²

2020

Preprint

View full text Add to dashboard Cite

Patients with schizophrenia (SCZ) are at high risk of cardiovascular disease (CVD) due to an inherited predisposition, a sedentary life style and the use of antipsychotic medications. Several approaches have been taken to minimize this risk but results continue to be unsatisfactory. A potential alternative is prescribing Selective Serotonin Reuptake Inhibitors (SSRIs). SSRIs decrease platelet aggregation and reduce the risk of coronary heart disease in patients with depression. We therefore aim to investigate whether there is evidence that supports the use of SSRIs to reduce the risk for CVD in SCZ. A systematic review of the literature revealed five published reports relating to the impact of SSRIs on CV risk in SCZ. Three trials assessed the influence on metabolic parameters of fluvoxamine when combined with clozapine. Two of those studies found improvements with fluvoxamine. Of the other two reports, one indicates SSRIs as a group caused minimal but statistically significant increments in total cholesterol, LDL and triglyceride. The second report suggests that when SSRIs are combined with antipsychotics, the metabolic impact depends on the antipsychotic prescribed. While there are promising results, further studies are needed to establish the impact of SSRIs on CV risk in SCZ.

show abstract

Effects of adjunctive fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia: A 12-week, randomized, double-blind, placebo-controlled study

Cited by 38 publications

References 52 publications

Peripheral Transcription of NRG-ErbB Pathway Genes Are Upregulated in Treatment-Resistant Schizophrenia

Peripheral Transcription of NRG-ErbB Pathway Genes Are Upregulated in Treatment-Resistant Schizophrenia

Clozapine augmentation strategies

SSRIs as Risk Reduction for Cardiovascular Disease in Patients with Schizophrenia

Contact Info

Product

Resources

About