&lt;p&gt;Atypical antipsychotics for Parkinson’s disease psychosis: a systematic review and meta-analysis&lt;/p&gt;

Zhang, Han; Wang, Limin; Fan, Yafei; Yang, Liguo; Wen, Xiaobin; Liu, Yunyun; Liu, Zhonglin

doi:10.2147/ndt.s201029

Cited by 32 publications

(29 citation statements)

References 41 publications

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“…Clozapine, marketed as the prototype atypical antipsychotic Clozaril™, is FDA-approved and treats psychosis related to schizophrenia and Parkinson’s disease [ 25 , 26 ]. It is a dopamine receptor antagonist with an affinity for D 4 receptors ( K i = 39 n m ) and shows high affinity for serotonin 5-HT 2A receptors ( K i = 13 n m ) and muscarinic M 1 and M 3 receptors ( K i = 14 n m and 25 n m , respectively) [ 25 , 27 , 28 ].…”

Section: Methodsmentioning

confidence: 99%

Effect of chemogenetic actuator drugs on prefrontal cortex-dependent working memory in nonhuman primates

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Baxter

2020

Neuropsychopharmacol.

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The most common chemogenetic neuromodulatory system, designer receptors exclusively activated by designer drugs (DREADDs), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is insensitive to acetylcholine. It is crucial in studies using these systems to test the potential effects of DREADD actuators prior to any DREADD transduction, so that effects of DREADDs can be attributed to the chemogenetic system rather than the actuator drug, particularly in experiments using nonhuman primates. We investigated working memory performance after injections of three DREADD actuators, clozapine, olanzapine, and deschloroclozapine, in four male rhesus monkeys tested in a spatial delayed response task before any DREADD transduction took place. Performance at 0.1 mg/kg clozapine and 0.1 mg/kg deschloroclozapine did not differ from vehicle in any of the four subjects. 0.2 mg/kg clozapine impaired working memory function in three of the four monkeys. Two monkeys were impaired after 0.1 mg/kg olanzapine and two were impaired after 0.3 mg/kg deschloroclozapine. We speculate that the unique neuropharmacology of prefrontal cortex function makes the primate prefrontal cortex especially vulnerable to off-target effects of DREADD actuator drugs with affinity for endogenous monoaminergic receptor systems. These findings underscore the importance of within-subject controls for DREADD actuator drugs in the specific tasks under study to confirm that effects following DREADD receptor transduction are not owing to the actuator drug itself. They also suggest that off-target effects of DREADD actuators may limit translational applications of chemogenetic neuromodulation.

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Section: Methodsmentioning

confidence: 99%

Effect of chemogenetic actuator drugs on prefrontal cortex-dependent working memory in nonhuman primates

Upright

Baxter

2020

Neuropsychopharmacol.

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“…Quetiapine is used as the first line of treatment in psychosis in PD patients according to the UK National Institute for Health and Care Excellence (NICE) guidelines 45 because it has less impact on PD motor symptoms compared to other SGAs, such as olanzapine. 48 However, its association with all-cause mortality, as suggested by the current study, is a matter of concern that needs further investigation.…”

Section: Discussionmentioning

confidence: 66%

Cardiovascular Events Associated with Antipsychotics in Newly Diagnosed Parkinson’s Disease Patients: A Propensity Score Matched Cohort Study

Orayj

2021

IJGM

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Purpose Observational studies have examined the association between antipsychotics and ischemic heart disease (IHD) in general populations, but results did not take into account other comorbid diseases, such as Parkinson’s disease (PD). This study investigates the one-year risk of IHD, all cardiovascular events, and all-cause mortality among newly diagnosed PD patients who used antipsychotics compared to non-users. Materials and Methods This study included individuals aged 40 years or older with a first definitive PD diagnosis Read Code in the Secure Anonymised Information Linkage (SAIL) databank who had been initiated on any PD medication between 2000 and 2016. Antipsychotic users were matched 1:1 with non-users by a propensity score model to control the confounding effects of patients’ demographics, social deprivation status, comorbidities, and medication history. Cox regression was performed to calculate the hazard ratios (HR) and 95% CIs for the association between antipsychotics and study outcomes. Results A total of 1837 participants were included in the analysis. Users of first-generation antipsychotics (FGA) were significantly more likely to develop IHD compared to non-users, with an HR of 2.60 (95% CI 1.103–6.167). Among the FGAs, haloperidol had the highest likelihood of IHD developing, with an HR of 3.01 (95% CI 1.038–8.729). Any use of antipsychotics, regardless of whether they were FGA or second-generation antipsychotics (SGA), was linked to all-cause mortality, with an HR of 4.201 (95% CI 3.272–5.394). When subdividing antipsychotics into FGAs and SGAs, mortality was more likely in FGA users, with an HR of 7.557 (95% CI 5.633–10.139). Mortality also occurred in SGA users, but with a lower HR of 3.278 (95% CI 2.509–4.282). Conclusion FGAs were associated with an increased risk of IHD and all-cause mortality in newly diagnosed PD patients with psychosis. This finding emphasizes the need to use antipsychotics with caution in PD patients with psychosis.

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“…Zhang et al 62 included 13 RCT's in their systematic review performed in May 2017 of atypical antipsychotics for psychotic symptoms in PD (pimavanserin, clozapine, olanzapine, and quetiapine). They reported results for each antipsychotic separately and found a positive effect for clozapine and pimavanserin only.…”

Section: Discussionmentioning

confidence: 99%

Effect of biological treatments on psychotic symptoms in lewy body disease: A systematic review and meta‐analysis of randomized controlled trials

Ford

Almeida

2020

Int J Geriat Psychiatry

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Objectives Parkinson disease and dementia with Lewy bodies (collectively termed Lewy body disease) are common neurodegenerative conditions of later life and are frequently associated with distressing psychotic symptoms. The best approach to manage these symptoms is yet to be established and current treatments carry the risk of serious adverse effects. Methods We performed a systematic review and meta‐analysis of 19 randomized controlled trials investigating the efficacy of biological treatments for psychotic symptoms in Lewy body disease. Results The summary effect estimate did not show a statistically significant benefit of biological treatments for psychotic symptoms in Lewy body disease (SMD −0.48, 95%CI −1.01 to 0.04). This was irrespective of the choice of intervention (SMD −0.53, 95%CI −1.20 to 0.14 for antipsychotic trials) or disease status (SMD −0.59, 95%CI −1.24 to 0.05 for trials of Parkinson disease). There was a significant effect for biological treatments compared with placebo in trials that lasted at least 6 weeks (SMD −0.25, 95%CI −0.43 to −0.08) and those with sample sizes greater than 100 participants (SMD of −0.28 95%CI −0.45 to −0.11). Conclusions In this systematic review and meta‐analysis, treatment of psychotic symptoms by biological means did not improve symptoms compared with placebo. Small sample sizes, modest treatment durations, and other methodological differences across the trials do make it difficult to draw firm conclusions. Longer, adequately powered trials utilizing established and novel treatments are needed to provide more definitive evidence to guide clinicians in the best choice of agent to treat these distressing and often persistent symptoms.

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<p>Atypical antipsychotics for Parkinson’s disease psychosis: a systematic review and meta-analysis</p>

Cited by 32 publications

References 41 publications

Effect of chemogenetic actuator drugs on prefrontal cortex-dependent working memory in nonhuman primates

Effect of chemogenetic actuator drugs on prefrontal cortex-dependent working memory in nonhuman primates

Cardiovascular Events Associated with Antipsychotics in Newly Diagnosed Parkinson’s Disease Patients: A Propensity Score Matched Cohort Study

Effect of biological treatments on psychotic symptoms in lewy body disease: A systematic review and meta‐analysis of randomized controlled trials

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