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Abraham Weizman - One of the best experts on this subject based on the ideXlab platform.
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treatment of antipsychotic induced Akathisia role of serotonin 5 ht2a receptor antagonists
Drugs, 2020Co-Authors: Michael Poyurovsky, Abraham WeizmanAbstract:Akathisia is one of the most prevalent and distressing adverse effects associated with antipsychotic drug treatment. Propranolol, a non-selective beta-adrenergic receptor antagonist, is currently considered a first-line treatment for antipsychotic-induced Akathisia (AIA). Surprisingly, the evidence for its anti-Akathisia effect is modest. Propranolol’s side effects (e.g. orthostatic hypotension, bradycardia), contraindications (e.g. asthma) and increased complexity in titration schedules limit its use in some patients. Anticholinergic agents and benzodiazepines merely provide symptomatic relief in patients with AIA. Effective and well-tolerated treatment remains a major unmet need in Akathisia and warrants a search for new anti-Akathisia agents. Accumulating evidence during the last two decades indicates that agents with marked postsynaptic serotonin 5-HT2a receptor antagonism (ritanserin, cyproheptadine, trazodone, mianserin, mirtazapine) may represent a new class of potential anti-Akathisia remedies. Among these agents, low-dose mirtazapine (7.5 mg or 15 mg once daily) has demonstrated the most compelling evidence for therapeutic efficacy. In this narrative review we highlight the clinical significance of AIA, outline major approaches for its management and propose a practical algorithm for its treatment.
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Treatment of Antipsychotic-Related Akathisia Revisited: The Role of Serotonin 2A Receptor Antagonists.
Journal of clinical psychopharmacology, 2015Co-Authors: Michael Poyurovsky, Abraham WeizmanAbstract:Akathisia remains a prevalent, clinically significant, and therapeutically challenging adverse event associated with antipsychotic treatment. Compelling evidence supports therapeutic efficacy and clinical utility of agents with marked serotonin 2A receptor antagonism, primarily low-dose mirtazapine, as an effective and well-tolerated antiAkathisia treatment.
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trazodone for the treatment of neuroleptic induced acute Akathisia a placebo controlled double blind crossover study
Clinical Neuropharmacology, 2010Co-Authors: Rafael Stryjer, Abraham Weizman, Silvio Rosenzcwaig, Faina Bar, Ann Marie Ulman, Baruch SpivakAbstract:Introduction Neuroleptic-induced acute Akathisia (NIA) is a common and distressing extrapyramidal symptom usually resulting from the use of antipsychotic medication.Despite its high incidence (20%-45%), the underlying mechanism of NIA has not yet been adequately explained. Although treatment strategies for NIA have traditionally included anticholinergic agents, γ-aminobutyric acid agents, dopamine enhancers, and the β-adrenergic antagonists, many patients fail to respond. Trazodone (Trz) is an antidepressant agent demonstrating prominent serotonergic antagonistic properties. In a recent pilot open-label trial, Trz demonstrated to be strongly effective in the treatment of NIA in 9 female schizophrenic patients. Objective On the basis of the results of this pilot study, we investigate further the efficacy of Trz in the treatment of NIA in a double-blind, placebo (Pla)-controlled, crossover design. Methods Thirteen inpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia or schizo-affective disorder and with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition NIA with a severity of at least mild Akathisia according to the Barnes Akathisia Rating Scale participated in the study. Patients were randomly assigned to either the order Trz-Pla or the order Pla-Trz in the treatment periods. Each period lasted for 3 consecutive days (days 1-3 and 4-6). Eight patients were treated with the Trz-Pla order (100 mg/d before bedtime); and 5, with the opposite order (Pla-Trz). Results Statistically significant improvement in most symptoms of NIA, as measured by the Barnes Akathisia Rating Scale, was detected with Trz compared with Pla treatment. Conclusions The findings of this double-blind, placebo-controlled, crossover study indicate the efficacy of Trz in the management of NIA, corroborating the results of a preliminary pilot study. We suggest that Trz's property of serotonin 2A postsynaptic receptor antagonism may be its principal mechanism for the improvement of NIA.
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zolmitriptan compared to propranolol in the treatment of acute neuroleptic induced Akathisia a comparative double blind study
European Neuropsychopharmacology, 2009Co-Authors: Ayelet Avital, Abraham Weizman, Haggai Hermesh, Ruth Grossisseroff, Rafael Stryjer, Roni ShilohAbstract:Neuroleptic-induced Akathisia (NIA) is a common, sometimes incapacitating adverse effect of anti-psychotic medication. Zolmitriptan is a selective 5-HT1D agonist. We aimed to determine its anti-NIA efficacy in comparison to propranolol. Thirty-three neuroleptic-treated patients were randomly allocated in a double-blind design to receive either 7.5 mg/d of zolmitriptan or 120 mg/d of propranolol for 3 consecutive days, followed by 3 days without any anti-NIA treatment. Patients were assessed at baseline and on days 3 and 7 by the Barnes Akathisia Rating Scale (BARS), PANSS, HAMD, HAMA, Pulse, and Blood Pressure. Both groups showed improvement of Akathisia (BARS) along the treatment period, with significant effect for time but not for group. No significant differences were found between the groups in all other measurements. Taken together, zolmitriptan was found to be as effective as propranolol for the treatment of NIA. Further placebo-controlled studies are warranted.
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cyproheptadine versus propranolol for the treatment of acute neuroleptic induced Akathisia a comparative double blind study
Journal of Clinical Psychopharmacology, 2001Co-Authors: Tsvi Fischel, Haggai Hermesh, Dov Aizenberg, Z Zemishlany, Hanan Munitz, Yoav Benjamini, Abraham WeizmanAbstract:The purpose of this study was to investigate the efficacy of cyproheptadine, an antiserotonergic agent, in the treatment of neuroleptic-induced Akathisia (NIA), as compared with propranolol, the current gold standard. In a double-blind trial, 30 patients with schizophrenia and NIA received either cyproheptadine 16 mg/day (N = 18) or propranolol 80 mg/day (N = 12) for 4 days, followed by 3 days without any anti-NIA treatment. The Barnes Akahisia Scale, Simpson-Angus Extrapyramidal Effects Rating Scale, and Brief Psychiatric Rating Scale were used to assess the severity of NIA, parkinsonism, and psychosis, respectively. In both groups, the severity of NIA decreased significantly over time (cyproheptadine, -46%; propranolol, -42%), with no significant intergroup difference. The NIA symptoms worsened significantly when cyproheptadine and propranolol were discontinued. We conclude that cyproheptadine 16 mg/day is as effective as propranolol for the treatment of acute NIA. The antiakathisic effect of cyproheptadine may be mostly attributable to its serotonin antagonistic activity.
Michael Poyurovsky - One of the best experts on this subject based on the ideXlab platform.
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treatment of antipsychotic induced Akathisia role of serotonin 5 ht2a receptor antagonists
Drugs, 2020Co-Authors: Michael Poyurovsky, Abraham WeizmanAbstract:Akathisia is one of the most prevalent and distressing adverse effects associated with antipsychotic drug treatment. Propranolol, a non-selective beta-adrenergic receptor antagonist, is currently considered a first-line treatment for antipsychotic-induced Akathisia (AIA). Surprisingly, the evidence for its anti-Akathisia effect is modest. Propranolol’s side effects (e.g. orthostatic hypotension, bradycardia), contraindications (e.g. asthma) and increased complexity in titration schedules limit its use in some patients. Anticholinergic agents and benzodiazepines merely provide symptomatic relief in patients with AIA. Effective and well-tolerated treatment remains a major unmet need in Akathisia and warrants a search for new anti-Akathisia agents. Accumulating evidence during the last two decades indicates that agents with marked postsynaptic serotonin 5-HT2a receptor antagonism (ritanserin, cyproheptadine, trazodone, mianserin, mirtazapine) may represent a new class of potential anti-Akathisia remedies. Among these agents, low-dose mirtazapine (7.5 mg or 15 mg once daily) has demonstrated the most compelling evidence for therapeutic efficacy. In this narrative review we highlight the clinical significance of AIA, outline major approaches for its management and propose a practical algorithm for its treatment.
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Treatment of Antipsychotic-Related Akathisia Revisited: The Role of Serotonin 2A Receptor Antagonists.
Journal of clinical psychopharmacology, 2015Co-Authors: Michael Poyurovsky, Abraham WeizmanAbstract:Akathisia remains a prevalent, clinically significant, and therapeutically challenging adverse event associated with antipsychotic treatment. Compelling evidence supports therapeutic efficacy and clinical utility of agents with marked serotonin 2A receptor antagonism, primarily low-dose mirtazapine, as an effective and well-tolerated antiAkathisia treatment.
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serotonin based pharmacotherapy for acute neuroleptic induced Akathisia a new approach to an old problem
British Journal of Psychiatry, 2001Co-Authors: Michael Poyurovsky, Abraham WeizmanAbstract:Neuroleptic-induced Akathisia (NIA) is characterised by a subjective sense of inner restlessness and objective fidgety movements. It is a major extrapyramidal side-effect of conventional antipsychotic agents. Despite its high incidence (20-45%), the underlying mechanisms have not yet been adequately
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treatment of neuroleptic induced Akathisia with the 5 ht2 antagonist mianserin double blind placebo controlled study
British Journal of Psychiatry, 1999Co-Authors: Michael Poyurovsky, Marina Shardorodsky, Camil Fuchs, Michael Schneidman, Abraham WeizmanAbstract:BACKGROUND Serotonin (5-HT):dopamine imbalance may underlie neuroleptic-induced Akathisia. AIM To evaluate the efficacy of the 5-HT2 antagonist, mianserin in neuroleptic-induced Akathisia. METHODS Thirty neuroleptic-treated patients with schizophrenia were randomly allocated in a double-blind design to receive either mianserin (15 mg/day) or placebo for five days. Patients were assessed at baseline and on Days 3 and 5 by the Barnes Akathisia Scale (BARS), as well as by other relevant clinical rating scales. RESULTS Compared with the placebo group, the mianserin-treated patients showed a significant reduction in all four BARS subscales by Day 5, with mean reductions in the BARS global score of 9.9% and 52.2%, respectively (P = 0.006). Response to treatment (a reduction of at least two points on the BARS global subscale), was noted in six patients (40%) in the mianserin group and only one patient (9.1%) in the placebo group (P = 0.04, log odds ratio 2.23). CONCLUSIONS Mianserin at a low dose may be a promising therapeutic option for patients with acute neuroleptic-induced Akathisia.
John M Kane - One of the best experts on this subject based on the ideXlab platform.
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evaluation of Akathisia in patients with schizophrenia schizoaffective disorder or bipolar i disorder a post hoc analysis of pooled data from short and long term aripiprazole trials
Journal of Psychopharmacology, 2010Co-Authors: John M Kane, James M Eudicone, Robert D Mcquade, Thomas R E Barnes, Christoph U Correll, Gary S Sachs, Peter F Buckley, Quynh Van Tran, Andrei Pikalov, Sheila AssuncaotalbottAbstract:The objective of this article is to assess the clinical characteristics of Akathisia in patients with schizophrenia, schizoaffective disorder, or bipolar I disorder receiving aripiprazole, haloperidol, olanzapine, or placebo. We conducted post hoc analyses of pooled safety data from trials in patients with schizophrenia, schizoaffective disorder, and bipolar I disorder. Outcome measures included the incidence of Akathisia, time to onset, duration, severity, and discontinuation due to Akathisia, concomitant use of benzodiazepines and/or anticholinergics, Barnes Akathisia Rating Scale (BARS) scores, and the correlation between antipsychotic efficacy and Akathisia. The results for schizophrenia and schizoaffective disorder were as follows: Akathisia in 9% of aripiprazole- and 6% of placebo-treated patients; 12.5% of aripiprazole- versus 24% of haloperidol-treated patients; 11% of aripiprazole- versus 6% of olanzapine-treated patients. Bipolar I disorder: Akathisia in 18% of aripiprazole- and 5% of placebo-treated patients. The clinical characteristics of Akathisia were similar between each data set, regardless of disease. Akathisia was generally mild-to-moderate in severity. Discontinuation due to Akathisia was low in both the schizophrenia trials (aripiprazole 0.3%; placebo 0%; aripiprazole 0.9%; haloperidol 2.3%; aripiprazole 1.2%; olanzapine 0.2%) and the bipolar trials (aripiprazole 2.3%; placebo 0%). Treatment-emergent Akathisia was not associated with a poorer clinical response. In conclusion, Akathisia with aripiprazole occurred early in treatment, was mild-to-moderate in severity, led to few study discontinuations, and did not compromise therapeutic efficacy.
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Akathisia an updated review focusing on second generation antipsychotics
The Journal of Clinical Psychiatry, 2009Co-Authors: John M Kane, Andrei Pikalov, Wolfgang W Fleischhacker, Lars K Hansen, Roy H Perlis, Sheila AssuncaotalbottAbstract:Objectives: To provide a brief description of the pathophysiology of Akathisia, the challenges of diagnosing and treating this condition, and potential associated clinical issues. Also, to provide a review of the literature on the incidence of drug-induced Akathisia associated with the use of second-generation antipsychotics (SGAs) and first-generation antipsychotics (FGAs). Data Sources: English-language literature with no date restrictions cited in PubMed was searched for the keywords Akathisia, placebo, neuroleptic, or haloperidol, and the generic names of SGAs (clozapine, risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole). Study Selection: Limits were set to search clinical trials, meta-analyses, or randomized controlled trials reviewing data from adult schizophrenia or bipolar disorder clinical trials. Studies including SGA comparisons with placebo and with FGAs, and also between SGAs themselves, were selected. Studies that specifically assessed Akathisia (either subjectively or objectively or both) were included. Studies reporting generalized results pertaining to extrapyramidal symptoms (EPS) were excluded. Data Extraction: The incidence of Akathisia, EPS rating scores, and required medications for the management of movement disorders were reviewed. Data Synthesis: Seventy-seven trials were included in the comparative review. Akathisia was observed with the use of all the SGAs. The Akathisia incidence reported in bipolar disorder trials was generally higher compared with schizophrenia trials. The incidence reported for FGAs was consistently higher than that reported for SGAs, regardless of the patient population studied. Conclusions: Akathisia remains a concern with the use of SGAs. More accurate and standardized evaluations are required for a better understanding of the nature and incidence of Akathisia.
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an integrated analysis of acute treatment emergent extrapyramidal syndrome in patients with schizophrenia during olanzapine clinical trials comparisons with placebo haloperidol risperidone or clozapine
The Journal of Clinical Psychiatry, 2003Co-Authors: Christopher Carlson, P Cavazzoni, Paul Berg, Hank Wei, Charles M Beasley, John M KaneAbstract:Background: The frequency and severity of extrapyramidal syndrome (EPS) were evaluated in patients with DSM-III or DSM-IV schizophrenia in the acute phase (≤ 8 weeks) of randomized, double-blind, controlled trials from the integrated olanzapine clinical trial database. Method: This retrospective analysis included 23 clinical trials and 4611 patients from November 11, 1991, through July 31, 2001. Incidences of dystonic, parkinsonian, and Akathisia events were compared using treatment-emergent adverse-event data. Categorical analyses of Simpson-Angus Scale and Barnes Akathisia Scale (BAS) scores, use of anticholinergic medications, and baseline-to-endpoint changes in Simpson-Angus Scale and BAS scores were compared. Results: A significantly smaller percentage of olanzapine-treated patients experienced dystonic events than did haloperidol- (p <.001) or risperidone-treated patients (p =.047). A significantly greater percentage of haloperidol-treated patients experienced parkinsonian (p <.001) and Akathisia (p <.001) events than did olanzapine-treated patients. Categorical analysis of Simpson-Angus Scale scores showed significantly more haloperidol- (p <.001) or risperidone-treated patients (p =.004) developed parkinsonism than did olanzapine-treated patients. Olanzapine-treated patients experienced significantly greater reductions in Simpson-Angus Scale scores than did haloperidol-(p <.001), risperidone- (p <.001), or clozapine-treated (p =.032) patients. Categorical analysis of BAS scores showed significantly more haloperidol-treated patients experienced treatment-emergent Akathisia versus olanzapine-treated patients (p <.001). Significantly greater reductions in BAS scores were experienced during olanzapine treatment versus placebo (p =.007), haloperidol (p <.001), and risperidone (p =.004) treatments. A significantly smaller percentage of olanzapine-treated patients received anticholinergic medications compared with that of haloperidol-(p <.001) or risperidone-treated patients (p =.018). Compared with that in olanzapine-treated patients, the duration of anticholinergic cotreatment was significantly longer among haloperidol- (p <.001) or risperidone-treated patients (p =.040) and significantly shorter among clozapine-treated patients (p =.021). Conclusion: This analysis of available data from olanzapine clinical trials lends additional support to olanzapine's favorable EPS profile.
Fabrice Berna - One of the best experts on this subject based on the ideXlab platform.
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recommendations of the schizophrenia expert center network for the screening prevention and treatment of sleep disorders based on the results from the real world schizophrenia face sz national cohort
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2021Co-Authors: P Sunhary L De Verville, Fabrice Berna, Delphine Capdevielle, D Etchecoparetchart, Raphaelle Richieri, Ophelia Godin, F Schurhoff, Bruno Aouizerate, Isabelle ChereauAbstract:Abstract Background Sleep disorders associated factors are under explored in schizophrenia while the literature suggests high and heterogeneous frequency. Aims The objective of the present study was to determine the prevalence and risk factors of sleep disorders in the real-world FACE-SZ national cohort. Method Stabilized schizophrenic outpatients were recruited in 10 expert centers for schizophrenia. Sleep quality was explored with the Pittsburgh Sleep Quality Index (PSQI) and sleep disorders was defined by a PSQI score > 5. Psychosis severity was measured with the Positive and Negative Syndrome Scale, current major depressive episode with the Calgary Depression Scale for Schizophrenia, verbal aggressiveness with the Buss-Perry Aggression Questionnaire, adherence to treatment with the Medication Adherence Rating Scale, Akathisia with the Barnes Akathisia Scale. Current somatic comorbidities and body mass index were reported. Variables with P values Results Of the 562 included patients, 327 subjects (58.2%, IC95% [54.1% - 62.3%]) reported having sleep disorders. After adjustment, sleep disorders were significantly associated with migraine (adjusted odds ratio aOR = 2.23, p = 0.041), major depressive disorder (aOR 1.79, p = 0.030), poor adherence to treatment (aOR = 0.87, p = 0.006), Akathisia (aOR = 1.29, p = 0.042) and verbal aggressiveness (aOR = 1.09, p = 0.002). Conclusions More than one on two stabilized real-life outpatients with schizophrenia have been identified with sleep disorders. Combined with the literature data, we have yielded expert recommendations for the treatment and prevention of sleep disorders including treating undiagnosed comorbid depression and migraine and managing antipsychotic treatment to improve adherence and Akathisia.
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Akathisia prevalence and risk factors in a community dwelling sample of patients with schizophrenia results from the multi center face sz dataset
European Psychiatry, 2016Co-Authors: Fabrice Berna, D Misdrahi, L Boyer, P M Llorca, Guillaume Fond, W G FaceszAbstract:The main objective of this study was to determine the prevalence of Akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with Akathisia. Three hundred and seventy-two patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of Akathisia (as defined by a score of 2 or more on the global Akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of Akathisia and this result remained significant (adjusted odd ratio = 2.04, P = .025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of Akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of Akathisia, given the potential side effects of these medications.
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Akathisia prevalence and risk factors in a community dwelling sample of patients with schizophrenia results from the face sz dataset
Schizophrenia Research, 2015Co-Authors: Fabrice Berna, D Misdrahi, L Boyer, B Aouizerate, Lore Brunel, Delphine Capdevielle, Isabelle Chereau, J M Danion, Jeanmichel DoreyAbstract:Abstract The main objective of this study was to determine the prevalence of Akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with Akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of Akathisia (as defined by a score of 2 or more on the global Akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of Akathisia and this result remained significant (adjusted odd ratio = 2.04, p = .025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of Akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of Akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of Akathisia, given the potential side effects of these medications.
A Weizman - One of the best experts on this subject based on the ideXlab platform.
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serotonergic agents in the treatment of acute neuroleptic induced Akathisia open label study of buspirone and mianserin
International Clinical Psychopharmacology, 1997Co-Authors: M Poyurovsky, A WeizmanAbstract:It has been suggested that dopamine/serotonin (5-HT) imbalance, with relative enhancement of serotonergic activity, might be one of the possible pathophysiological mechanisms underlying neuroleptic-induced Akathisia. On the basis of preclinical data, which imply that the partial 5.HT 1A agonist buspirone possesses anti-5-HT activity,in the present open-label study we examined the putative antiakathitic effect of buspirone in 10 neuroleptic-treated patients with acute neuroleptic-induced Akathisia. Buspirone (up to 30 mg/day in divided doses) was administered for a trial period of 4 days (first part of the study). No significant changes in neuroleptic-induced Akathisia as rated using the Barnes Akathisia Scale were detected during buspirone treatment. Buspirone was effective in only two neuroleptic-induced Akathisia patients and caused worsening of Akathisia in the other two patients. According to the study design, eight buspirone non-responders were switched to the 5-HT 2A/2C antagonist mianserin (15 mg/day) for the other 4 days of treatment (second part of the study). Seven mianserin-treated patients improved and five revealed complete disappearance of neuroleptic-induced Akathisia. It seems that the 5-H 1A partial agonist buspirone is of limited value in the treatment of acute neuroleptic-induced Akathisia. In contrast, it appears that low-dose mianserin is therapeutically effective in acute neuroleptic-induced Akathisia.
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beneficial effect of low dose mianserin on fluvoxamine induced Akathisia in an obsessive compulsive patient
International Clinical Psychopharmacology, 1995Co-Authors: M Poyurovsky, I Meerovich, A WeizmanAbstract:Extrapyramidal side effects induced by some selective serotonin reuptake inhibitors (SSRIs), i.e. fluoxetine and sertraline, have been previously reported in patients with depression and obsessive-compulsive disorder (OCD). However, the occurrence and management of Akathisia induced by fluvoxamine have not been described. In the presented case fluvoxamine-induced Akathisia in an OCD patient was partially resistant to the anticholinergic agent biperiden, and was successfully treated with the 5-HT 2A /5-HT 2C antagonist mianserin. Mianserin (15 mg/day at 21.00 h) was discontinued and then reinstituted (off-on-off-on design). Biperiden was transiently effective in the acute Akathisia, while the more persistent Akathisia was alleviated by mianserin. Discontinuation of mianserin resulted in recurrence of Akathisia, while full amelioration of the symptoms of Akathisia was noted when mianserin was reinstituted. No aggravation of OCD symptoms was noted during mianserin administration.