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Abstract Background Risperidone ISM® is a newly developed long-acting injectable (LAI) treatment for schizophrenia in adults. In the absence of head-to-head comparisons with other similar antipsychotics, the objective of this study was to generate indirect evidence of some aspects of the safety and tolerability of Risperidone ISM compared to other LAI antipsychotics for treatment of patients with schizophrenia in the maintenance treatment setting. Methods A literature review was conducted systematically to identify maintenance treatment studies reporting safety and tolerability outcomes for LAI antipsychotic therapies. Following an assessment of between-trial heterogeneity, a matching-adjusted indirect comparison (MAIC) was performed to account for between-trial imbalances in patient characteristics and to generate comparative evidence for safety and tolerability endpoints. Results The analysis showed that incidence of extrapyramidal symptoms (EPS) was found to be numerically, but not statistically significantly, lower in patients receiving Risperidone ISM than in those receiving Paliperidone palmitate (PP) (OR [95% CI] 0.63 [0.29, 1.38], p = 0.253) and statistically significantly lower than with Aripiprazole monohydrate once-monthly (AOM) (OR [95% CI] 0.25 [0.12, 0.53], p

Background: Pisa syndrome, also known as pleurothotonus, is a neurological condition characterized by more than ten degrees of constant lateral curvature of the spine when upright. In this way, the present manuscript aims to systematically review Pisa syndrome secondary to drugs. Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction between January 1990 and June 2024. Results: The prevalence of Pisa syndrome varied from 0.037 to 9.3%. We found 109 articles containing 191 cases of drug-induced Pisa syndrome reported in the literature. The mean and median ages were 59.70 (SD = 19.02) and 67 (range = 12–98 years). The most prevalent sex was female, 56.91% (107/188). The most frequent medications associated with Pisa syndrome were acetylcholinesterase inhibitors in 87 individuals. Of 112 individuals in which the onset time from the medication to the movement disorder occurrence was reported, 59 took place within a month. In this way, a return to baseline was observed in 45.50% of the cases, and partial recovery was observed in 14.28%. Conclusion: We proposed new diagnostic criteria for Pisa syndrome based on previous findings in the literature. Moreover, multiple mechanisms are probably involved in balance control and the development of lateral trunk flexions.

Background: Risperidone ISM® is a newly developed long-acting injectable (LAI) treatment for schizophrenia in adults. In the absence of head-to-head comparisons with other similar antipsychotics, the objective of this study was to generate indirect evidence of some aspects of the safety and tolerability of Risperidone ISM compared to other LAI antipsychotics for treatment of patients with schizophrenia in the maintenance treatment setting. Methods: A literature review was conducted systematically to identify maintenance treatment studies reporting safety and tolerability outcomes for LAI antipsychotic therapies. Following an assessment of between-trial heterogeneity, a matching-adjusted indirect comparison (MAIC) was performed to account for between-trial imbalances in patient characteristics and to generate comparative evidence for safety and tolerability endpoints. Results: The analysis showed that incidence of extrapyramidal symptoms (EPS) was found to be numerically, but not statistically significantly, lower in patients receiving Risperidone ISM than in those receiving Paliperidone palmitate (PP) (OR [95% CI] 0.63 [0.29, 1.38], p = 0.253) and statistically significantly lower than with Aripiprazole monohydrate once-monthly (AOM) (OR [95% CI] 0.25 [0.12, 0.53], p < 0.001). Use of anticholinergic agents for the alleviation of EPS was also shown to be significantly lower in Risperidone ISM patients than in those receiving PP (OR [95% CI] 0.29 [0.10, 0.83], p = 0.021) or AOM (OR [95% CI] 0.01 [0.003, 0.06], p < 0.001), suggesting a superior tolerability profile for clinically relevant EPS. Results from the sensitivity analyses comparing stabilized and stable patients receiving Risperidone ISM to those receiving AOM yielded similarly favorable conclusions in line with the base case analyses. Conclusions: This MAIC is consistent with the safety and tolerability results obtained during the PRISMA-3 clinical trial in the long-term treatment of schizophrenia and suggests a favorable safety and tolerability profile in terms of EPS incidence and anticholinergic agent use, relative to other antipsychotic therapies used for treatment of patients with schizophrenia in the maintenance setting. [ABSTRACT FROM AUTHOR]

To test the effect of prophylactic use of benzhexol in schizophrenia patients after risperidone treatment. Sixty-nine drug naïve schizophrenia patients were recruited. All patients were administered risperidone. Patients in the benzhexol group were given a benzhexol tablet of 2 mg bid daily. The controls received a placebo tablet of 2 mg bid daily. The primary outcome measured using the Extrapyramidal Symptoms Rating Scale (ESRS). The Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) measured secondary outcome. There were significant time and group effects on the ESRS scores of the two groups. The post hoc analysis yielded significant differences at 1, 2, 4, and 8 weeks between the two groups. There was a significant time effect on the PANSS scores of the two groups. No significant group and interaction effects on the PANSS scores of the two groups. There was a significant time effect on the BPRS scores of the two groups. No serious adverse events were found in this study. Prophylactic use of benzhexol reduced extrapyramidal symptom in schizophrenia patients after risperidone treatment and did not affect the antipsychotic action of risperidone.

The clinical presentation of repetitive choreiform involuntary movements of the anterior abdominal wall was first introduced as “belly dancer’s dyskinesia.” Etiologies of this rare condition include idiopathic causes, medication inducement, or post-abdominal surgery. We report a case of orobuccal stereotypic movements and abdominal wall dyskinesia secondary to prochlorperazine intake. The movements began 2 weeks after cessation of prochlorperazine. The patient took this dopamine receptor-blocking medication for 6 months to treat nausea due to chemotherapy. To our knowledge, abdominal wall dyskinesia as a tardive syndrome of prochlorperazine has not been previously reported.

Background: Pisa syndrome, also known as pleurothotonus, is a neurological condition characterized by more than ten degrees of constant lateral curvature of the spine when upright. In this way, the present manuscript aims to systematically review Pisa syndrome secondary to drugs., Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction between January 1990 and June 2024., Results: The prevalence of Pisa syndrome varied from 0.037 to 9.3%. We found 109 articles containing 191 cases of drug-induced Pisa syndrome reported in the literature. The mean and median ages were 59.70 (SD = 19.02) and 67 (range = 12-98 years). The most prevalent sex was female, 56.91% (107/188). The most frequent medications associated with Pisa syndrome were acetylcholinesterase inhibitors in 87 individuals. Of 112 individuals in which the onset time from the medication to the movement disorder occurrence was reported, 59 took place within a month. In this way, a return to baseline was observed in 45.50% of the cases, and partial recovery was observed in 14.28%., Conclusion: We proposed new diagnostic criteria for Pisa syndrome based on previous findings in the literature. Moreover, multiple mechanisms are probably involved in balance control and the development of lateral trunk flexions.

The clinical presentation of repetitive choreiform involuntary movements of the anterior abdominal wall was first introduced as "belly dancer's dyskinesia." Etiologies of this rare condition include idiopathic causes, medication inducement, or post-abdominal surgery. We report a case of orobuccal stereotypic movements and abdominal wall dyskinesia secondary to prochlorperazine intake. The movements began 2 weeks after cessation of prochlorperazine. The patient took this dopamine receptor-blocking medication for 6 months to treat nausea due to chemotherapy. To our knowledge, abdominal wall dyskinesia as a tardive syndrome of prochlorperazine has not been previously reported. [ABSTRACT FROM AUTHOR]

The alcohol-abuse deterrent disulfiram (DSF) is shown to have a highly selective toxicity against melanoma in culture, inducing a largely apoptotic response, with much lower toxicity against several other cell lines. Melanoma cell lines derived from different stages (radial, vertical, and metastatic phase) were all sensitive to DSF treatment in vitro; melanocytes were only slightly affected. A required role of extracellular Cu is demonstrated for DSF toxicity. Low concentrations of DSF alone decreased the number of viable cells, and the addition of CuCl(2) significantly enhanced the DSF-induced cell death to less than 10% of control. Significantly, the intracellular Cu concentration of melanoma cells increased rapidly upon DSF treatment. Both the intracellular Cu uptake and the toxicity induced by DSF were blocked by co-incubation with bathocuproine disulfonic acid (BCPD, 100 muM), a non-membrane-permeable Cu chelator. Chemical studies demonstrated a complicated, extracellular redox reaction between Cu(II) and DSF, which forms the complex Cu(deDTC)(2) in high yield, accompanied by oxidative decomposition of small amounts of disulfiram. The Cu complex has somewhat higher activity against melanoma and is suggested to be the active agent in DSF-induced toxicity. The redox conversion of DSF was unique to Cu(II) and not engendered by the other common biological metal ions Fe(II or III), Mn(III), and Zn(II). The implications of this work are significant both in the possible treatment of melanoma as well as in limiting the known side-effects of DSF, which we propose may be diminished by cotreatment to decrease adventitious Cu.

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (α), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak D2 receptor bindings with strong binding to the 5-HT2A receptor, while typical antipsychotics block long-lasting, tight D2 receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components. [ABSTRACT FROM AUTHOR]

Tardive dystonia is one of the most serious adverse events that can be caused by antipsychotic treatment, but few studies have examined the etiology of tardive dystonia, and no genetic study using a next-generation sequencing technique has been performed to date. We conducted exome sequencing in three subjects with severe tardive dystonia. We analyzed the results focusing on candidate genes of primary dystonia, for example, TOR1A , GCH1 , TH , THAP1 , and SGCE. There were no single-nucleotide polymorphisms of these dystonia genes that were commonly shared among our subjects. Instead, the results revealed the presence of rare mutations (minor allele frequency <0.01) on the ZNF806 and SART3 genes in all three patients. This is the first study to analyze whole-exonic regions of the genomes of patients with tardive dystonia. These results were only preliminary, but they suggest that subjects presenting with tardive dystonia induced by antipsychotic treatment can have a genetic predisposition to tardive dystonia. [ABSTRACT FROM AUTHOR]

What is known and objective Long-acting formulations are an important therapeutic option for non-adherent patients with schizophrenia. There is a commonly held view that management of long-acting formulation-induced side effects is difficult. Case description We present a patient with schizophrenia who developed acute and persistent extrapyramidal symptoms requiring tracheostomy and long-term rehabilitation after long-acting injections of fluphenazine decanoate. Extrapyramidal symptoms improved with declining fluphenazine concentration and antiparkinsonian drug therapy with bromocriptine. What is new and conclusion Long-acting formulations may lead to severe persistent adverse effects. For preventing fluphenazine-induced side effects, a possible option might be the antiparkinsonian drug therapy with bromocriptine. [ABSTRACT FROM AUTHOR]

Purpose: Flunarizine (fz) and cinnarizine (cz) have well-known extrapyramidal side effects (EPSEs). The aim of this study was to evaluate the incidence and occurrence time of cz- and fz-related EPSEs. Method: Patients who took fz or cz for more than 1 month were identified from the longitudinal health insurance database 2005 and 2010. Excluded were patients with any of the underlying diseases that may cause parkinsonism. Drug-induced EPSEs were defined as the new diagnosis of parkinsonism, dyskinesia, or secondary dystonia during drug use or within 3 months after discontinuing the medication. Age- and sex-matched controls were included in this study. Results: Recruited for analysis were individuals who took fz ( n = 26,133) and cz ( n = 7186). The incidence rates of fz- and cz-induced EPSEs were 21.03 and 10.3 per 10,000 person-months, respectively. The hazard ratios (HRs) of EPSEs among fz and cz subjects were 8.03 (95% CI 6.55-9.84) and 3.41 (95% CI 2.50-4.63) when compared with the control individuals. Both fz and cz patients had a higher cumulative incidence of EPSEs than their control individuals ( p < 0.001). Among subjects who took fz, the incidence of EPSEs was higher in the second than first year of drug exposure (45.59 vs 21.03 per 10,000 person-months). Conclusions: Fz and cz significantly increased the risk of parkinsonism, dyskinesia, and dystonia. Potential benefits and risks should be weighed when considering long-term use of these drugs especially fz. [ABSTRACT FROM AUTHOR]

To test the effect of prophylactic use of benzhexol in schizophrenia patients after risperidone treatment. Sixty-nine drug naïve schizophrenia patients were recruited. All patients were administered risperidone. Patients in the benzhexol group were given a benzhexol tablet of 2 mg bid daily. The controls received a placebo tablet of 2 mg bid daily. The primary outcome measured using the Extrapyramidal Symptoms Rating Scale (ESRS). The Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) measured secondary outcome. There were significant time and group effects on the ESRS scores of the two groups. The post hoc analysis yielded significant differences at 1, 2, 4, and 8 weeks between the two groups. There was a significant time effect on the PANSS scores of the two groups. No significant group and interaction effects on the PANSS scores of the two groups. There was a significant time effect on the BPRS scores of the two groups. No serious adverse events were found in this study. Prophylactic use of benzhexol reduced extrapyramidal symptom in schizophrenia patients after risperidone treatment and did not affect the antipsychotic action of risperidone., Competing Interests: The authors declare no competing interests., (© 2023 Published by Elsevier Ltd.)

The author focuses on criticism of the issues related to the control of antipsychotics effects using chlorpromazine and cognition's relation with symptoms in schizophrenia antipsychotic-induced extrapyramidal . Topics discussed include system for antipsychotic dosage comparison yielding accurate results, benefits of using second-generation antipsychotics (SGAs) in lowering cognition as it prevents the need for anticholinergic drugs and a table on the effect on cognitive functions.

Aims The purpose of the present study was to investigate the correlation between cognitive function and clinical variables in people with schizophrenia. Methods The subjects were 61 stabilized outpatients with schizophrenia ( DSM-IV). Their mean age was 40.1 ( SD = 12.2) years. All subjects gave written informed consent to participate in the research. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale. Results The Positive and Negative Syndrome Scale Negative syndrome score was significantly correlated with verbal memory score (r = −0.37, P < 0.01), working memory score (r = 0.38, P < 0.01), attention and speed of information processing score (r = −0.51, P < 0.01), verbal fluency score (r = −0.39, P < 0.01), and composite score (r = −0.54, P < 0.01). In addition, the Drug-Induced Extrapyramidal Symptoms Scale score was significantly correlated with attention and speed of information processing (r = −0.45, P < 0.01), and composite score (r = −0.41, P < 0. 01). Dose of antipsychotics and anti-Parkinson drugs was not significantly correlated with the Brief Assessment of Cognition in Schizophrenia scores. Conclusions These results indicate that cognitive dysfunction of people with schizophrenia might be associated with negative and drug-induced extrapyramidal symptoms, suggesting that their minimization would be important for improving cognitive dysfunction. [ABSTRACT FROM AUTHOR]

This systematic review aimed to determine whether the risk of extrapyramidal side effects (EPS) differed between antipsychotic drugs used in first episode psychosis (FEP). We identified 11 RCTs comparing two or more antipsychotics in FEP and reporting on EPS. All trials assessed one or more second generation antipsychotics (SGAs), one assessed chlorpromazine, one zuclopenthixol and seven trials assessed haloperidol. Assessment and reporting of EPS varied. Compared with one or more SGA comparators, haloperidol was associated with significantly higher rates/severity of parkinsonism (seven trials) and akathisia (six trials) and greater use of anticholinergics (five trials) and beta-blockers (two trials). Two trials with low-dose haloperidol (≤ 4 mg) showed significantly worse EPS outcomes versus a SGA. Two of four long-term haloperidol trials (≥ 1 year) found a higher dyskinesia-risk with haloperidol versus olanzapine and risperidone respectively; the remaining two trials found no difference (various SGA comparators). There was an EPS advantage for clozapine versus chlorpromazine (one trial) and risperidone versus zuclopenthixol (one trial). There was little evidence of EPS-differences between SGAs, possibly reflecting use of low doses. We conclude that SGAs offer an EPS advantage over FGAs in FEP though the evidence largely relates to comparisons with haloperidol. Standardized assessment and reporting of EPS would assist future research. [ABSTRACT FROM AUTHOR]

Abstract: Extrapyramidal symptoms (EPS) commonly occur as side effects of antipsychotic drugs (APDs) and are most likely to arise when the occupancy of dopamine D2 receptors in the striatum by these drugs exceeds 80%. We aimed to characterize changes in the protein expression profile in the striatum of rats after chronic (4 week) supra-therapeutic (EPS-inducing) treatment with risperidone (RIS), an atypical antipsychotic drug. Administration of RIS (2.1 mg/kg/day, via subcutaneous osmotic minipumps) induced significant vacuous chewing movements and catalepsy in male Sprague–Dawley rats over a 28-day treatment period compared with a vehicle (VEH) control group (n =12) (Karl et al., unpublished observation). Using two-dimensional gel electrophoresis (2DE), total protein extracts from the rat brain striatum were separated and protein expression was analyzed by Phoretix 2D Expression and Image Beta V4.02 software followed by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). 2DE gels resolved up to 450 protein spots, presumably different proteins and/or their isoforms. There were 30 protein spots showing statistically significant different densities between the RIS- and VEH-treated groups. All 30 proteins were successfully identified by MALDI-TOF MS, 28 of these were divided into groups based on their known functions. These included metabolic, signaling, transport, protein metabolism, chaperone, DNA binding and cell cycle categories. We conclude that chronic risperidone treatment accompanied by an EPS-like behavioral phenotype results in alterations in the striatal protein profile possibly subsequent to blockade of dopaminergic systems. These results suggest that possible mechanisms involved in APD-induced EPS include metabolic dysfunction and oxidative stress. [Copyright &y& Elsevier]

Objectives: To evaluate extrapyramidal symptoms (EPS), including akathisia, with quetiapine in patients with bipolar mania. Methods: Data were analyzed from four similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies evaluated quetiapine monotherapy (up to 800 mg/day) (n = 209) versus placebo (n = 198), with lithium or haloperidol monotherapy as respective active controls. Two studies evaluated quetiapine (up to 800 mg/day) in combination with a mood stabilizer (lithium or divalproex, QTP + Li/DVP) (n = 196) compared to placebo and mood stabilizer (PBO + Li/DVP) (n = 203). Extrapyramidal symptoms were evaluated using the Simpson–Angus Scale (SAS), the Barnes Akathisia Rating Scale (BARS), adverse event reports and anticholinergic drug usage. Results: The incidence of EPS-related adverse events, including akathisia, was no different with quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS-related adverse events with QTP + Li/DVP (21.4%) were no different than with PBO + Li/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated with lithium (n = 98) monotherapy experienced adverse events related to EPS. The incidence of akathisia was low and similar with quetiapine monotherapy (3.3%) and placebo (6.1%), and with QTP + Li/DVP (3.6%) and PBO + Li/DVP (4.9%). Lithium was associated with a significantly higher incidence (p < 0.05) of tremor (18.4%) than quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of lithium, may have contributed to the elevated rate of tremor in patients receiving lithium therapy. Haloperidol induced a significantly higher incidence (p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and extrapyramidal syndrome (35.4% versus 5.9%) than quetiapine. No significant differences were observed between quetiapine and placebo on SAS and BARS scores. Anticholinergic use was low and similar with quetiapine or placebo. Conclusions: In bipolar mania, the incidence of EPS, including akathisia, with quetiapine therapy is similar to that with placebo. [ABSTRACT FROM AUTHOR]

The substituted benzamide amisulpride is currently administered in its racemic form. In the present study, the biochemical and cataleptogenic profiles of the two enantiomers (R+ and S−) were compared with those of the racemic mixture. Displacement binding studies showed that the (S−)-isomer possesses an higher affinity for dopamine D2-like receptor (Ki 5.2±0.4 nM) compared to (R+)-amisulpride (Ki 244±12 nM) and to (RS)-amisulpride (Ki 9.8±0.8 nM). In contrast, (S−)-amisulpride binds the α2-receptor with an affinity (Ki 1528±45 nM) lower than that of the (R+)-isomer (Ki 375±34 nM) and of (RS)-amisulpride (Ki 783±27 nM). The bar test was used to evaluate the catalepsy induced by each drug. (RS)-amisulpride induced catalepsy only at very high doses (>100 mg/kg, s.c.) whereas, (S−)-amisulpride produced a catalepsy at a lower dose (30 mg/kg, s.c.) and (R+)-amisulpride did not produce any catalepsy up to the dose of 75 mg/kg. Interestingly, (R+)-amisulpride reduced the catalepsy induced by (S−)-amisulpride (50 mg/kg, s.c.) or haloperidol (0.3 mg/kg, s.c.), at the doses of 50 or 30 mg/kg, respectively. These results indicate that the weak cataleptic properties of (RS)-amisulpride might partially rely on its (R+)-isomer and provide a further explanation for the atypical properties of amisulpride as an antipsychotic. [Copyright &y& Elsevier]

Abstract: Median nerve stimulated short-latency somatosensory evoked potentials (MN-SSEPs) were performed in two young children with extrapyramidal symptoms. Brain MRI showed bilaterally symmetric striatal lesions in both cases. The subcortical components (N9, N11, N13, N18, P11, and P13) and the parietal component (N20) were normally detected, whereas the frontal component (N30) was not detected bilaterally in either case. In conclusion, our findings suggest that frontal N30 disappearance could be observed since as early as young childhood and it may pathophysiologically reflect severe dysfunction in the extrapyramidal system. [Copyright &y& Elsevier]

Dopamine-receptor blocking agent-associated akathisia (DRBA-A) is an adverse effect that can significantly limit the use of these important medications for the treatment of a variety of psychiatric diseases, yet there is no unifying theory regarding its pathophysiology. This knowledge gap limits clinicians' ability to effectively manage DRBA-A and mitigate negative outcomes in an already vulnerable patient population. Based on a review of the current literature on the subject, it is hypothesized that dopaminergic and noradrenergic signaling is perturbed in DRBA-A. Accordingly, it is proposed that the optimal agent to manage this extrapyramidal symptom should increase dopamine signaling in the affected areas of the brain and counteract compensatory noradrenergic signaling via antagonism of adrenergic or serotonergic receptors., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)