Anticholinergic use trends in 14,013 patients with schizophrenia from three national surveys on the use of psychotropic medications in China (2002–2012)

Su, Yun‐Ai; Feng, Yundi; Li, Qian; Xiang, Yu‐Tao; Shen, Liang; Yu, Xin; Ning, Yuping; Zhang, Kerang; Li, Tao; Mei, Qiyi; Li, Keqing; Si, Tianmei

doi:10.1016/j.psychres.2017.07.038

Cited by 10 publications

(10 citation statements)

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“…These principles were also reflected in the treatment approach to schizophrenia. To date, most drugs available to treat schizophrenia target either dopamine and or glutamate receptors in the brain (Amodeo et al, 2017; Su et al, 2017). However, these treatment methods have been plagued with receptor sensitivity problems that may arise from prolonged use of antipsychotics like dopaminergic receptor antagonist (haloperidol) and glutamate receptor blocker (ketamine) (Ostinelli et al, 2017; Nikvarz et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…NMDAR and D 2 R). Side effects of these drugs are a limitation as it often leads to depression, movement disorders and catalepsy (Amodeo et al, 2017; Nakata et al, 2017, Nikvarz et al, 2017; Freyberg et al, 2017; Ibi et al, 2017; Meltzer, 2017; Ostinelli et al, 2017; Su et al, 2017). Therefore, there is a need for assessment of other synaptic targets that can reduce synaptic and behavioral defects of schizophrenia while circumventing neurotransmitter receptor sensitivity (Yang and Tsai, 2017).…”

Section: Introductionmentioning

confidence: 99%

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CaMKIIα expression in a mouse model of NMDAR hypofunction schizophrenia: Putative roles for IGF-1R and TLR4

Ogundele

Lee

2018

Brain Research Bulletin

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Schizophrenia (SCZ) is a neuropsychiatric disorder that is linked to social behavioral deficits and other negative symptoms associated with hippocampal synaptic dysfunction. Synaptic mechanism of schizophrenia is characterized by loss of hippocampal N-Methyl-d-Aspartate Receptor (NMDAR) activity (NMDAR hypofunction) and dendritic spines. Previous studies show that genetic deletion of hippocampal synaptic regulatory calcium-calmodulin dependent kinase II alpha (CaMKIIα) cause synaptic and behavioral defects associated with schizophrenia in mice. Although CaMKIIα is involved in modulation of NMDAR activity, it is equally linked to inflammatory and neurotropin signaling in neurons. Based on these propositions, we speculate that non-neurotransmitter upstream receptors associated with neurotropic and inflammatory signaling activities of CaMKIIα may alter its synaptic function. Besides, how these receptors (i.e. inflammatory and neurotropic receptors) alter CaMKIIα function (phosphorylation) relative to hippocampal NMDAR activity in schizophrenia is poorly understood. Here, we examined the relationship between toll-like receptor (TLR4; inflammatory), insulin-like growth factor receptor 1 (IGF-1R; neurotropic) and CaMKIIα expression in the hippocampus of behaviorally deficient schizophrenic mice after we induced schizophrenia through NMDAR inhibition. Schizophrenia was induced in WT (C57BL/6) mice through intraperitoneal administration of 30mg/Kg ketamine (NMDAR antagonist) for 5days (WT/SCZ). Five days after the last ketamine treatment, wild type schizophrenic mice show deficiencies in sociability and social novelty behavior. Furthermore, there was a significant decrease in hippocampal CaMKIIα (p<0.001) and IGF-1R (p<0.001) expression when assessed through immunoblotting and confocal immunofluorescence microscopy. Additionally, WT schizophrenic mice show an increased percentage of phosphorylated CaMKIIα in addition to upregulated TLR4 signaling (TLR4, NF-κB, and MAPK/ErK) in the hippocampus. To ascertain the functional link between TLR4, IGF-1R and CaMKIIα relative to NMDAR hypofunction in schizophrenia, we created hippocampal-specific TLR4 knockdown mouse using AAV-driven Cre-lox technique (TLR4 KD). Subsequently, we inhibited NMDAR function in TLR4 KD mice in an attempt to induce schizophrenia (TLR4 KD SCZ). Interestingly, IGF-1R and CaMKIIα expressions were preserved in the TLR4 KD hippocampus after attenuation of NMDAR function. Furthermore, TLR4 KD SCZ mice showed no prominent defects in sociability and social novelty behavior when compared with the control (WT). Our results show that a sustained IGF-1R expression may preserve the synaptic activity of CaMKIIα while TLR4 signaling ablates hippocampal CaMKIIα expression in NMDAR hypofunction schizophrenia. Together, we infer that IGF-1R depletion and increased TLR4 signaling are non-neurotransmitter pro-schizophrenic cues that can reduce synaptic CaMKIIα activity in a pharmacologic mouse model of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CaMKIIα expression in a mouse model of NMDAR hypofunction schizophrenia: Putative roles for IGF-1R and TLR4

Ogundele

Lee

2018

Brain Research Bulletin

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“…Studies measuring exposure to drugs with anticholinergic effects in schizophrenia patients were most often focused on antiparkinsonian drugs prescribed for extra-pyramidal side effects (Chakos et al, 2006;Pristed et al, 2017;Su et al, 2017). The frequency ranged from 5.7% in a population-based Danish study (Pristed et al, 2017) to 27.4% in a Chinese study carried out in a large sample recruited in psychiatric hospitals (Su et al, 2017).…”

Section: Interpretation Of Findingsmentioning

confidence: 99%

“…Persons with schizophrenia are potentially exposed to high-anticholinergic load due to the frequent use of antiparkinsonian drugs prescribed for extra-pyramidal side-effects but also of many other psychotropic drugs with anticholinergic effects (Duran, Azermai, & Vander Stichele, 2013;Montastruc et al, 2018;Pristed, Correll, & Nielsen, 2017;Salahudeen et al, 2015;Su et al, 2017). The negative effect of high-anticholinergic load on quality of life (QoL) has been documented in elderly persons from the general population (Cossette et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Impact of anticholinergic load on functioning and cognitive performances of persons with psychosis referred to psychosocial rehabilitation centers

et al. 2020

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Background Few studies have explored whether high-anticholinergic load may hamper rehabilitation in persons with schizophrenia. We aim to explore the associations between anticholinergic load of psychotropic treatment and functioning or cognitive performances of persons with psychosis engaged in psychosocial rehabilitation. Methods The study was performed using data collected at baseline assessment in the REHABase cohort including persons referred to a French network of psychosocial rehabilitation centers. The composite-rating scale developed by Salahudeen et al. was used to rate the anticholinergic load of psychotropic drugs prescribed at baseline assessment. The associations between total anticholinergic load score (categorized as ‘low’ <3 v. ‘high’ ⩾3) and functioning or cognitive characteristics were explored using multivariate analyses. Results Of the 1012 participants with schizophrenia spectrum disorders identified in the REHABase, half used at least two psychotropic drugs with anticholinergic activity and one out of three was prescribed at least one psychotropic drug with high-anticholinergic activity. High-anticholinergic load was significantly associated with lower stage of recovery [odds ratio (OR) = 1.70, 95% confidence interval (CI) 1.05–2.76, p = 0.03], poor mental well-being (OR = 1.55, 95% CI 1.02–2.33, p = 0.04) and poor self-rated medication adherence (OR = 2.14, 95% CI 1.29–3.53, p = 0.003). Regarding cognition, a high-anticholinergic score was associated with poorer delayed-episodic memory (OR = 1.69, 95% CI 1.01–2.85, p = 0.05) and at the trend level with faster completion time on the test exploring executive performance (OR = 0.67, 95% CI 0.43–1.04, p = 0.07). Conclusions The psychosocial rehabilitation plan of persons with psychosis should integrate optimization of psychotropic treatment in order to lessen the functional and cognitive impact of high-anticholinergic load.

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“…The current treatment of EPS in China contains anticholinergics including benzoyl 6,7. However, the side effects of anticholinergics can deteriorate the physical condition and cognition of patients with schizophrenia, especially elderly patients, which strongly restrict its clinical application 8,9.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of low-dose D2/D3 partial agonist pramipexole on neuroleptic-induced extrapyramidal symptoms and symptoms of schizophrenia: a stage-1 open-label pilot study

Weng¹,

Wang²,

Zhu³

et al. 2019

NDT

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Objective Some lines of evidence show that D 2 /D 3 receptor partial agonist pramipexole may be effective in the treatment of extrapyramidal symptoms (EPS) and psychiatric symptoms of schizophrenia. Therefore, we analyzed whether a low dose of pramipexole (0.375–0.75 mg/day) has efficacy on EPS and symptoms of schizophrenia while maintaining tolerability. Methods Ten subjects with EPS [including drug-induced parkinsonism (DIP) and akathisia] were recruited in a stage-1, open-label pilot study. All the subjects were treated with a low dose of pramipexole. The evaluations were performed at baseline, day 3, week 1, week 2, week 4, week 6, and week 8. The ratings of SAS, BARS, PANSS, CDSS, and CGI-S and adverse effects (AE) were recorded in every visit. Results SAS total scores decreased significantly during the study in patients with DIP ( P <0.001), and mild AEs were detected. Treatments with pramipexole did not show an anti-akathisia effect during the study, while 2 subjects experienced deterioration of akathisia and mood symptoms. The psychiatric symptoms of schizophrenia showed a trend of improvement during the study, but there was no improvement in depressive mood. Conclusion A low dose of pramipexole can significantly relieve antipsychotic-induced parkinsonism, but not akathisia. Improvements in psychiatric symptoms of schizophrenia were found, but the results of this study need to be validated in a larger sample. No improvement of mood disorder was detected.

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Anticholinergic use trends in 14,013 patients with schizophrenia from three national surveys on the use of psychotropic medications in China (2002–2012)

Cited by 10 publications

References 22 publications

CaMKIIα expression in a mouse model of NMDAR hypofunction schizophrenia: Putative roles for IGF-1R and TLR4

CaMKIIα expression in a mouse model of NMDAR hypofunction schizophrenia: Putative roles for IGF-1R and TLR4

Impact of anticholinergic load on functioning and cognitive performances of persons with psychosis referred to psychosocial rehabilitation centers

<p>Efficacy of low-dose D<sub>2</sub>/D<sub>3</sub> partial agonist pramipexole on neuroleptic-induced extrapyramidal symptoms and symptoms of schizophrenia: a stage-1 open-label pilot study</p>

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