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Objective: Prescribers' expectations of Zuclopethixol Acetate's (ZA) efficacy and tolerability are shaped by clinical experience and organisational culture; however, these expectations may not be consistent with current evidence and best practice., Methods: Quality improvement project (QIP) through a process audit of ZA prescribing, monitoring and patient outcomes (adverse events) in order to identify issues requiring intervention to align with service standards and practices., Results: QIP interventions resulted in a statistically significant shift in psychiatrist oversight, identifying high dose ZA with adverse outcomes and cessation of prescribing/administration within the Emergency Department. Clinically significant changes in patterns of prescribing were observed between pre-post intervention audits., Conclusion: Entrenching an evidence-based QIP approach to clinical practice can effect clinically significant patterns of practice change to improve safe prescribing and drug monitoring.

Introduction: Priapism is defined as a prolonged penile erection in absence of sexual arousal, leading also to serious sexual and urological problems such as erectile dysfunction and penile fibrosis. Amongst many different etiologies, priapism may be caused by a wide range of antipsychotic medications, mainly due to the α1-adrenergic receptor antagonism. On the other hand, only a couple of cases of opioid compounds have been linked to the onset of priapism, with evidence coming only from methadone and buprenorphine. Here we describe the case of a patient treated with antipsychotics who developed priapism four times following rapid discontinuation of buprenorphine/naloxone (Suboxone®)., Case Presentation: S.C. is a 30-year-old Caucasian man suffering from chronic buprenorphine/naloxone (Suboxone®) abuse, borderline personality disorder, antisocial traits, and multiple suicide attempts. During the acute and the first part of post-acute Suboxone® withdrawal, four episodes of priapism developed while he was treated with clotiapine, clozapine, and chlorpromazine. However, after the last episode of priapism, despite he was either on haloperidol or zuclopenthixol and chlorpromazine, no other urological event occurred during the following 6 months of observation., Conclusions: As opioids may have dampened the patient's sexual function due to chronic consumption, a rapid drug suspension coupled with an antipsychotic therapy might have created the conditions to facilitate the occurrence of close clustered priapism events.

Neuroleptic malignant syndrome (NMS) is a potentially lethal adverse drug reaction. We report a case of NMS potentially induced by dehydration in a female patient suffering from schizoaffective disorder. We discuss possible aetiologies and triggering factors alongside the existing literature., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Oral zuclopenthixol dihydrochloride (Clopixol) is an anti-psychotic treatment for people with psychotic symptoms, especially those with schizophrenia. It is associated with neuroleptic malignant syndrome, a prolongation of the QTc interval, extra-pyramidal reactions, venous thromboembolism and may modify insulin and glucose responses., Objectives: To determine the effects of zuclopenthixol dihydrochloride for treatment of schizophrenia., Search Methods: We searched the Cochrane Schizophrenia Group's Trials Register (latest search 09 June 2015). There were no language, date, document type, or publication status limitations for inclusion of records in the register., Selection Criteria: All randomised controlled trials (RCTs) focusing on zuclopenthixol dihydrochloride for schizophrenia. We included trials meeting our inclusion criteria and reporting useable data., Data Collection and Analysis: We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a random-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE., Main Results: We included 20 trials, randomising 1850 participants. Data were reported for 12 comparisons, predominantly for the short term (up to 12 weeks) and inpatient populations. Overall risk of bias for included studies was low to unclear.Data were unavailable for many of our pre-stated outcomes of interest. No data were available, across all comparisons, for death, duration of stay in hospital and general functioning.Zuclopenthixol dihydrochloride versus: 1. placeboMovement disorders (EPSEs) were similar between groups (1 RCT, n = 28, RR 6.07 95% CI 0.86 to 43.04 very low-quality evidence). There was no clear difference in numbers leaving the study early (2 RCTs, n = 100, RR 0.29, 95% CI 0.01 to 6.60, very low-quality evidence). 2. chlorpromazineNo clear differences were found for the outcomes of global state (average CGI-SI endpoint score) (1 RCT, n = 60, MD 0.00, 95% CI -0.49 to 0.49) or movement disorders (EPSEs) (3 RCTs, n = 199, RR 0.94, 95% CI 0.61 to 1.45), both very low-quality evidence. More people left the study early for any reason from the zuclopenthixol group (6 RCTs, n = 766, RR 0.54, 95% CI 0.36 to 0.81, low-quality evidence). 3. chlorprothixeneThere was no clear difference in numbers leaving the study early for any reason (1 RCT, n = 20, RR 1.00, 95% CI 0.34 to 2.93, very low-quality evidence). 4. clozapineNo useable data were presented. 5. haloperidolNo clear differences between treatment groups were found for the outcomes global state score (average CGI endpoint score) (1 RCT, n = 49, MD 0.13, 95% CI -0.30 to 0.55) or leaving the study early (2 RCTs, n = 141, RR 0.99, 95% CI 0.72 to 1.35), both very low-quality evidence. 6. perphenazineThose receiving zuclopenthixol were more likely to require medication in the short term for EPSEs than perphenazine (1 RCT, n = 50, RR 1.90, 95% CI 1.12 to 3.22, very low-quality evidence). Similar numbers left the study early (2 RCTs, n = 104, RR 0.63, 95% CI 0.27 to 1.47, very low-quality evidence). 7. risperidoneThose receiving zuclopenthixol were more likely to require medications for EPSEs than risperidone (1 RCT, n = 98,RR 1.92, 95% CI 1.12 to 3.28, very low quality evidence). There was no clear difference in numbers leaving the study early ( 3 RCTs, n = 154, RR 1.30, 95% CI 0.84 to 2.02) or in mental state (average PANSS total endpoint score) (1 RCT, n = 25, MD -3.20, 95% CI -7.71 to 1.31), both very low-quality evidence). 8. sulpirideNo clear differences were found for global state (average CGI endpoint score) ( 1 RCT, n = 61, RR 1.18, 95% CI 0.49 to 2.85, very low-quality evidence), requiring hypnotics/sedatives (1 RCT, n = 61, RR 0.60, 95% CI 0.27 to 1.32, very low-quality evidence) or leaving the study early (1 RCT, n = 61, RR 2.07 95% CI 0.97 to 4.40, very low-quality evidence). 9. thiothixeneNo clear differences were found for the outcomes of 'global state (average CGI endpoint score) (1 RCT, n = 20, RR 0.50, 95% CI 0.17 to 1.46) or leaving the study early (1 RCT, n = 20, RR 0.57, 95% CI 0.24 to 1.35), both very low-quality evidence). 10. trifluoperazineNo useable data were presented. 11. zuclopenthixol depotThere was no clear difference in numbers leaving the study early (1 RCT, n = 46, RR 1.95, 95% CI 0.36 to 10.58, very low-quality evidence). 12. Zuclopenthixol dihydrochloride (cis z isomer) versus zuclopenthixol (cis z/trans e isomer)There were no clear differences in reported side-effects ( 1 RCT, n = 57, RR 1.34, 95% CI 0.82 to 2.18, very low-quality evidence) and in numbers leaving the study early (4 RCTs, n = 140, RR 2.15, 95% CI 0.49 to 9.41, very low-quality evidence)., Authors' Conclusions: Zuclopenthixol dihydrochloride appears to cause more EPSEs than clozapine, risperidone or perphenazine, but there was no difference in EPSEs when compared to placebo or chlorpromazine. Similar numbers required hypnotics/sedatives when zuclopenthixol dihydrochloride was compared to sulpiride, and similar numbers of reported side-effects were found when its isomers were compared. The other comparisons did not report adverse-effect data.Reported data indicate zuclopenthixol dihydrochloride demonstrates no difference in mental or global states compared to placebo, chlorpromazine, chlorprothixene, clozapine, haloperidol, perphenazine, sulpiride, thiothixene, trifluoperazine, depot and isomers. Zuclopenthixol dihydrochloride, when compared with risperidone, is favoured when assessed using the PANSS in the short term, but not in the medium term.The data extracted from the included studies are mostly equivocal, and very low to low quality, making it difficult to draw firm conclusions. Prescribing practice is unlikely to change based on this meta-analysis. Recommending any particular course of action about side-effect medication other than monitoring, using rating scales and clinical assessment, and prescriptions on a case-by-case basis, is also not possible.There is a need for further studies covering this topic with more antipsychotic comparisons for currently relevant outcomes.

Background: We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms., Methods: Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [(123)I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n=13) or zuclopenthixol (n=9), 22 patients were reexamined., Results: Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P=.003) and planning time (r = -0.436, P=.048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P=.003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P=.016)., Conclusions: Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms., (© The Author 2016. Published by Oxford University Press on behalf of CINP.)

Background: Zuclopenthixol is an older antipsychotic that has three distinct formulations (zuclopenthixol dihydrochloride, zuclopenthixol acetate or Acuphase and zuclopenthixol decanoate). Although it has been in common use for many years no previous systematic review of its efficacy compared to placebo in schizophrenia has been undertaken., Objectives: To evaluate the effectiveness of all formulations of zuclopenthixol when compared with a placebo in schizophrenia., Search Methods: On 6 November 2013 and 20 October 2015, we searched the Cochrane Schizophrenia Group Trials Register, which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. We also checked the references of all included studies and contacted authors of included studies for relevant studies and data., Selection Criteria: We included all randomised controlled trials comparing zuclopenthixol of any form with placebo for treatment of schizophrenia or schizophrenia-like psychoses., Data Collection and Analysis: We extracted and cross-checked data independently. We identified only a small number of studies so we cross checked all studies. We calculated fixed-effect relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. We analysed by intention-to-treat. Where possible we converted continuous outcomes into dichotomous outcomes. When this was not possible we used mean differences (MD) for continuous variables. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table., Main Results: Only two studies, with a total of 65 participants, were eligible for inclusion in the review. Overall the quality of the two studies was low, with small study populations and significant sources of bias, so we were not able to use all the data in our comparisons. . The studies were old from 1968 and 1972, and would be unlikely to pass modern peer review standard. We were only able to find short-term data and only trials randomising zuclopenthixol dihydrochloride. We also hoped to identify data for zuclopenthixol acetate versus placebo and zuclopenthixol decanoate versus placebo comparisons. We were unable to identify any studies that included data on these two fairly widely used drugs.For our primary outcome of interest, clinically significant improvement, we found one study that provided useable data. Global state measured by clinical global impression scale (CGI) improvement showed different ratings when assessed by a psychiatrist or a nurse.The psychiatrist scores failed to achieve statistical significance, however when assessed by nursing staff, the difference favouring zuclopenthixol did reach statistical significance (1 RCT n = 29, RR 2.57 95% CI 1.06 to 6.20, very low quality data). There was also evidence of increased sedation with those treated with zuclopenthixol when compared with placebo (1 RCT n = 29, RR 4.67 95% CI 1.23 to 17.68, very low quality data). 'Leaving the study early' data were equivocal. No useable data were available for outcomes such as relapse, mental state, death, quality of life, service use or economic costs., Authors' Conclusions: For people with schizophrenia this review shows that zuclopenthixol dihydrochloride may help with the symptoms of schizophrenia. The review provides some trial evidence that, if taking zuclopenthixol dihydrochloride, people may experience some adverse effects and sedation compared with placebo. However this evidence is of very low quality and with some significant sources of bias. There are no data for zuclopenthixol decanoate or zuclopenthixol acetate.For clinicians, the available trial data on the absolute effectiveness of zuclopenthixol dihydrochloride do support its use but the limited nature of the data and significant sources of bias make conclusions hard to draw. Zuclopenthixol in all three forms is a commonly used antipsychotic and it is disappointing that there are so few data regarding its use.

Objective: Disruptive or challenging behavior problems pose a threat to children and adolescents with intellectual disabilities and their caregivers. Psychopharmacological treatment is mostly studied with new-generation antipsychotics and has been criticized for adverse side effects. This study examined the effect of the classic antipsychotic zuclopenthixol., Methods: A total of 39 boys (ages 8.0-17.11 years) with learning disabilities were included and examined for a response to zuclopenthixol during a 6 week period of open label treatment. Doses started low and were adapted individually. From responders, zuclopenthixol was randomly withdrawn for 12 weeks. Responses to withdrawal were observed by external raters using the Modified Overt Aggression Scale., Results: Of all patients included into the study, 15 were not randomized because of insufficient therapeutic effect, adverse event, or noncompliance. Kaplan-Meier estimations showed less aggressive behavior problems for the continuing subgroup (n=9) than in the placebo group (n=15). Individual doses stayed <10 mg/day., Conclusions: Zuclopenthixol proved to be effective in reducing challenging behavior in boys even at low doses.

Introduction: People with mental retardation often display aggressive behavior against themselves or others making care within institutions or foster families difficult. Due to a lack of viable alternatives, antipsychotics of the first and second generations are often used for long-term treatment despite the fact that only data about short-term treatment exist., Methods: A short-time withdrawal trial of 12 weeks (n = 39) was extended at open label to 2 years. 31 patients received zuclopenthixol after the end of the withdrawal and were examined using the same instruments as in the withdrawal period (DAS, MOAS, CGI)., Results: Patients still treated with zuclopenthixol after 2 years (n = 21) benefitted, compared to the drop-outs (n = 10). Analyses of time trends revealed an early effect of zuclopenthixol which could not be enhanced afterwards., Discussion: Zuclopenthixol proved to be safe and effective to keep a lower rate of aggressive behavior in adults with mental retardation also over a longer period of time., (© Georg Thieme Verlag KG Stuttgart · New York.)

A 41-year-old patient with schizophrenia was admitted to hospital following episodes of unexplained collapse attacks and on and off episodes of frontal headaches for 3 months. After three such episodes of loss of consciousness in 2 weeks duration and subsequent spontaneous recovery, his evaluation which included MRI scan of head revealed extensive cortical venous thrombosis. He was on zuclopenthixol (thioxanthene group) for several months for schizophrenia and was under regular psychiatric evaluation. He was treated for simple lower respiratory infection a week prior to admission. Other causes for any clotting disorders including vasculitic and thrombophilic screen were negative. There was no evidence of focal neurology on examination. Systemic examination was otherwise unremarkable. He was treated initially with unfractionated heparin and subsequently changed to warfarin with target international normalised ratio between two and three for at least 6 months and psychiatrist was advised to stop zuclopenthixol.

Background: Neuroleptic malignant syndrome (NMS) is a rare side-effect of neuroleptic medication. Most NMS reports have been on adults, and the incidence in children and adolescents is unknown., Objective: This report reviews cases of NMS to highlight possible risk factors for the development of NMS in adolescents., Method: Four cases of probable NMS in adolescents diagnosed in the Western Cape between February 2009 and March 2010 are presented., Results: Risk factors in the development of the syndrome in adolescents in the Western Cape may be male gender, polypharmacy, the use of zuclopenthixol acetate (clopixol acuphase), a previous history of extra-pyramidal side-effects or NMS, and a history of substance misuse - in particular methamphetamine., Conclusion: Caution must be applied in the apparent overuse of intramuscular antipsychotics, and especially zuclopenthixol acetate (clopixol acuphase), in neuroleptic-naïve and agitated psychotic adolescents where the short-term use of benzodiazepines is more appropriate.

Oculogyric crisis (OGC) is an acute dystonia which can occur after initiation of antipsychotic treatment. Stereotypic paroxysmal psychiatric symptoms have been described along with OGC that resolve spontaneously when the later remits. We report a case of tardive OGC associated with zuclopenthixol in which there were associated paroxysmal auditory pseudohallucinations.

Purpose: Long-term persistence of use, lack of co-prescribed anticholinergic antiparkinson drugs and low mortality may indicate effectiveness and safety of antipsychotic drugs. We aimed to assess 3-year prescription persistence, concomitant use of anticholinergics and mortality related to the use of all antipsychotic agents available in Norway., Methods: Data were drawn from the Norwegian Prescription Database on the sales of antipsychotic and anticholinergic antiparkinson agents in 2004 to a total of 52,427 patients. The primary study group was a subgroup of 34,494 patients who were prescribed only one antipsychotic agent in 2004. The patients were re-investigated in 2007. For each of the 13 antipsychotic agents studied, assumed prescription persistence was assessed in light of use of anticholinergic antiparkinson agents in 2004, and casualty rates were noted., Results: The highest persistence was demonstrated for zuclopenthixol (69.8%) and clozapine (88.4%). Zuclopenthixol was often co-prescribed with anticholinergics (22.2%), in contrast to clozapine (3.6%). Ziprasidone was associated with a low mortality (OR = 0.08), while chlorprotixene and haloperidol were associated with a high mortality (OR = 1.34 and 3.97, respectively) compared to levomepromazine., Conclusions: Clozapine demonstrated a high degree of continuity of prescription and a low level of concomitant use of anticholinergics. Zuclopenthixol also demonstrated a high degree of continuity of prescription, despite a considerable degree of co-prescribed anticholinergics. We did not find that any antipsychotic other than ziprasidone was associated with a low mortality. The use of haloperidol seemed to confer a mortality risk three times that of any of the other antipsychotic agents included.

Objective: Prescribers are warned to be vigilant for potential cytochrome P450 mediated drug interactions; guidelines separately highlight risks of toxicity associated with zuclopenthixol acuphase. We previously examined potential cytochrome P450 interactions with zuclopenthixol and here describe dangerous side effects in a patient receiving zuclopenthixol acuphase and the selective serotonin reuptake inhibitor fluoxetine at high dose., Method: We present the case of a patient established on fluoxetine 80 mg/day who subsequently received injected zuclopenthixol acuphase 100 mg., Results: Following zuclopenthixol acuphase administration, dangerous extra-pyramidal side effects were observed, including severe laryngeal dystonia necessitating emergency medical treatment., Conclusions: Our observations of symptoms of zuclopenthixol toxicity are consistent with a cytochrome P450 2D6/3A4 interaction with fluoxetine. Previous evidence demonstrating this interaction included only patients taking fluoxetine up to 60 mg/day. This case extends the evidence base. In patients taking high dose fluoxetine, we advise marked reductions in the prescribed dose of zuclopenthixol acuphase.

Objective: High prevalence of metabolic syndrome (MS) and related metabolic disturbances in patients with schizophrenia and bipolar affective disorder have been in main focus of interest in recent years since the introduction of second-generation antipsychotics. This study aims to examine these questions: 1) Is there a relation between antipsychotic treatment and MS prevalence? 2) Which antipsychotic users have higher MS prevalence? 3) Do patients on antipsychotic polytherapy have higher rates of MS than patients on antipsychotic monotherapy? 4) Which metabolic parameters are considerably disturbed on which antipsychotic users?, Methods: 242 Patients with schizophrenia, schizoaffective disorder and bipolar disorder without any other psychiatric comorbidity according to DSM-IV and using the same antipsychotic(s) and/or mood stabilizers at least for the last 6 months included to the final assessment., Results: The sample was divided into 7 drug groups. The MS prevalence was highest in the combined antipsychotic (AA) group (48.1%) according to ATP III criteria. According to IDF criteria clozapine (C) group had the highest MS prevalence (74%)., Conclusions: When metabolic parameters evaluated overall, metabolic risk with antipsychotics is found to be highest in clozapine group, followed by combined AP group. Olanzapine and risperidone have intermediate risk while zuclopentixole has lowest.

Aim: This naturalistic study aims to compare discontinuation rates for low-dose first-generation versus second-generation antipsychotics in first-episode psychotic patients., Methods: The prescription of antipsychotic medication in 301 consecutively admitted patients with first-episode psychosis from four catchment areas is described. For the first year of inclusion a first-generation antipsychotic in low dose was recommended as the first medication. From the second year a second-generation antipsychotic was recommended as first choice. Switching was allowed when any drug was judged to be ineffective or to have serious side-effects. Switching during the first 2 years after inclusion is described., Results: Switching from a low-dose first-generation antipsychotic was more frequent than from a second-generation antipsychotic (90.7 vs. 58.4%). Lack of therapeutic effect and side-effects were the more frequently recorded reasons for changing in the first-generation group. Akathisia, parkinsonism, dyskinesias, dystonia and dysphoria were more often reported in patients on first-generation drugs. Weight gain and sedation were more often reported in patients on second-generation drugs., Conclusion: The findings suggest a better adherence to and tolerability for second-generation antipsychotics than for low-dose first-generation antipsychotics in first-episode psychosis., (© 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Asia Pty Ltd.)

Poor response to antipsychotics is still an important problem in the treatment of many schizophrenia patients. N-acetylcysteine (NAC) is a compound that exerts anti-oxidant and scavenging actions against reactive oxygen species. This paper reports a case of poorly responsive schizophrenia patient who improved considerably with add-on NAC 600 mg/day. The NAC might work through activating cysteine-glutamate antiporters or reducing in nitric oxide (NO) metabolites, free radicals and cytokines or through both of these mechanisms.

Neuroleptic malignant syndrome (NMS) is a rare clinical condition and potentially life-threatening complication of antipsychotic medications. We report a patient with an atypical presentation of NMS. A 60-year-old man with schizophrenia was admitted to our hospital with disturbed consciousness, fever and marked extrapyramidal rigidity both in the upper and lower extremities. He had been given i.m. zuclopenthixol 200 mg/month but had not taken the last dose. Laboratory investigations showed that creatinine phosphokinase 428 IU/l (normal up to 130), lactate dehydrogenase 772 IU/l (normal up to 450), blood glucose 256 mg/dl (65-110). Urine analyses revealed ketonuria. White blood cell (WBC) count was 6100 cells/mm(3). Therefore, the patient was diagnosed as having NMS and antipsychotic medications were stopped. Adequate hydration was provided and bromocryptine 5 mg was started three times a day. Despite treatment, the patient died due to acute myocardial infarction after 3 days of hospitalization.

Introduction: Earlier studies showed risperidone to be effective in the treatment of aggression and self-injurious behaviour in adults with mental retardation but also having adverse side effects. This study was conducted to evaluate the effects of zuclopenthixol withdrawal., Methods: After open treatment with zuclopenthixol (n=49) responders were randomly assigned to continue (n=19) or discontinue (n=20) zuclopenthixol treatment during a 12-week double-blind, placebo-controlled period. Effects were measured using the Disability Assessment Schedule (DAS), improvement on the Clinical Global Impression Scale (CGI-I), and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE)., Results: Ten patients (20%) discontinued the study due to insufficient therapeutic effect or adverse events in the open period., Efficacy: The superiority of zuclopenthixol over placebo among all randomized patients was supported not only by primary efficacy measure but also by the comparisons of mean scores of all secondary efficacy measures tested in a step-down-procedure (DAS, p<0.001; CGI-I, p<0.002, NOSIE, p<0.005)., Safety: In both groups, one patient discontinued (5%) for adverse events. Adverse events were generally mild or moderate in severity., Discussion: Zuclopenthixol proved to be safe and effective to keep a low rate of aggressive behaviour in adults with mental retardation.

Background: Concern has been raised about the occurrence of venous thromboembolism (VTE) during treatment with antipsychotics. However, to date, clozapine is the only antipsychotic agent for which recurring evidence supports an association with VTE. Therefore, the aim of this study was to investigate the association between antipsychotic drugs, including clozapine and VTE., Study Design and Methods: Data mining of the WHO database of adverse drug reactions (ADRs) using Bayesian statistics is in routine use for early alerting to possible ADRs. An information component measure was used to investigate the association between antipsychotic drugs and VTE reactions in the database., Results: A total of 754 suspected cases of VTE related to treatment with antipsychotics had been reported. After excluding cases related to clozapine, 379 cases remained. A robust association was found for the second-generation antipsychotics group but not for the high-potency, first-generation antipsychotics group or the low-potency first-generation antipsychotics group. The individual compounds with statistically significant associations were olanzapine, sertindole and zuclopenthixol. A time-dependent analysis showed that the associations were positive for these drugs in 2002, 2001 and 2003, respectively. Case analyses were undertaken after excluding ten suspected duplicate reports. Of the remaining 369 cases, 91 cases were associated with olanzapine, 9 with zuclopenthixol and 6 with sertindole., Conclusions: VTE was more often reported with the antipsychotic drugs olanzapine, sertindole and zuclopenthixol than with other drugs in the WHO database. Further studies are warranted to explain this disproportional reporting. Since the associations found were based on incomplete clinical data, the results should be considered as preliminary and interpreted cautiously.

In past years, Zuclopenthixolacetate as well as Flupentixoldecanoate have each proven to be reliable and efficient in the treatment of schizophrenic psychoses. In a specially implemented psychiatric treatment unit (PTU) we administered a high-dose depot neuroleptic combination therapy initially consisting of both substances to seriously ill schizophrenic prisoners who exhibited highly aggressive behaviour (N=20). We initially used both antipsychotics at the same time as a simple regimen in order to restore the prisoners' health to enable them to return to their home prisons. A single coercive intervention was performed in 14 out of 20 prisoners which was followed by a second one in two cases according to Article 101 of the German Code of Criminal Procedure. On average, prisoners needed a treatment course of 30.4 days. Within this time PANSS global scores were reduced by approximately 40%. Side effects occurring as a consequence of neuroleptic treatment were negligible and could be dealt with.

Objective: To report a case of fatal exertional heat stroke associated with the use of zuclopenthixol, quetiapine and benztropine., Case Summary: A 36-year-old male with a history of schizophrenia and bipolar disease was working as a roofer during the third day of a heat wave. His medications included zuclopenthixol, quetiapine, benztropine, carbamazepine and levothyroxine. He developed loss of consciousness late in the day and presented to hospital with a Glasgow Coma Scale 3 and a rectal temperature of 42.2 degrees C. He progressed to severe multiple organ dysfunction and asystole, and expired the following morning. Neuroleptic and anticholinergic agents have long been associated with heat alteration, but there are few reports involving the newer antipsychotic agents. Physicians and pharmacists should ensure that appropriate counseling is given to patients receiving these medications regarding early recognition of signs and symptoms and prompt treatment of heat related illness and heat stroke.

Conventional antipsychotics are often associated with late-occurring undesirable movement effects. To gain more experience with newer antipsychotic agents, 151 patients in an acute admissions department were switched from treatment with conventional antipsychotics to sertindole between late 1996 and early 1998. Four of these patients had tardive dyskinesia, tardive dystonia and/or tardive akathisia. The effect of changing to sertindole was measured using specific rating scales for undesirable movement effects. Three of the four patients apparently recovered from the movement disorders after switching to sertindole. In one patient, sertindole monotherapy was not sufficient to reduce the movement effects, but combination treatment with tetrabenazine resulted in a greater reduction in extrapyrimidal symptoms. Because these are case reports, no direct conclusions can be drawn. However, the beneficial effect of sertindole on severe, late-occurring movement disorders, as observed in four difficult-to-treat patients, appears to be promising.

Objective: To report a case of recurrent heat-related illnesses associated with the use of benzhexol, chlorpromazine, and zuclopenthixol decanoate., Case Summary: During the summer of 2004, a 48-year-old man with a history of diabetes mellitus and schizophrenia was twice admitted to the hospital because of heat-related illnesses. On both occasions, he had been working under the sun in an open car park. His medications included benzhexol 2 mg twice daily, chlorpromazine 650 mg at bedtime, and zuclopenthixol decanoate intramuscular injection 600 mg every 4 weeks. In the first admission, the clinical diagnosis was heat stroke. He was discharged home on day 14, with precautionary advice against heat stroke. In the second admission, the clinical diagnosis was heat exhaustion. He was discharged home on day 4 and reminded of the precautions against heat stroke. An objective causality assessment revealed that the adverse event was possibly drug related in the first admission and probably drug related in the second admission., Discussion: Several drugs can impair thermoregulation during exercise or under conditions of environmental heat stress. Anticholinergic drugs or drugs with anticholinergic effects can inhibit sweating and reduce heat elimination. Neuroleptics (antipsychotics), such as phenothiazines, have combined anticholinergic and central thermoregulatory effects. The set point of the temperature regulation center can be elevated by the antidopaminergic effect of antipsychotics, such as phenothiazines and thioxanthenes., Conclusions: Certain drugs may induce or worsen heat-related illnesses. During a heat wave, special attention should be given to those most at risk, and the importance of preventive measures should be emphasized.

Background: Zuclopenthixol dihydrochloride, given orally, is commonly used for managing the signs and symptoms of schizophrenia., Objectives: To determine the effects of zuclopenthixol dhydrochloride for treatment of schizophrenia., Search Strategy: We searched the Cochrane Schizophrenia Group's register (December 2004). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. To identify further trials we also contacted a pharmaceutical company and authors of relevant studies., Selection Criteria: We included all randomised controlled trials comparing zuclopenthixol dihydrocodine with antipsychotics or with placebo (or no intervention) for treatment of schizophrenia and/or schizophrenia-like psychoses., Data Collection and Analysis: We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed articles and extracted data. For dichotomous data we calculated relative risks (RR) and the 95% confidence intervals (CI) and the number needed to treat (NNT) or number needed to harm statistics. For continuous data we calculated weighted mean differences with 95% CIs for non-skewed data., Main Results: We included eighteen trials involving 1578 people. Two trials compared zuclopenthixol with placebo and neither reported global or mental state outcomes. People allocated zuclopenthixol did have increased risk of experiencing extraparamydal symptoms compared with placebo (n=64, RR 5.37, CI 1.12 to 29.34 NNH 2 CI 2 to 31). Ten short trials (total n=478) compared zuclopenthixol with other typical antipsychotics. Risk of being unchanged or worse was decreased by allocation to zuclopenthixol (n=357, 7 RCTs, RR 0.72 CI 0.53 to 0.98, NNT 10 CI 6 to 131). No findings suggest any clear difference between zuclopenthixol and other typical antipsycotics across a whole range of adverse effects, including movement disorders (n=280, 6 RCTs, RR needing additional antiparkinsonian medication 1.07 CI 0.86 to 1.33) and general agitation (n=162, 3 RCTs, RR needing treatment with hypnotic/sedative drugs 1.09 CI 0.76 to 1.56). Fewer people allocated zuclopenthixol left in the short term compared with those given other typical antipsychotics (n=424, 22% vs 30%, 8 RCTs, RR 0.70 CI 0.51 to 0.95, NNT 12 CI 7 to 67). Three short trials (total n=233) compared zuclopenthixol with atypical antipsychotics. Zuclopenthixol was associated with no greater risk of being unchanged or worse compared with risperidone (n=98, 1 RCT, RR 1.30 CI 0.80 to 2.11). People allocated zuclopenthixol were prescribed antiparkinsonian medication more frequently compared to those treated with risperidone (n=98, 1 RCT, RR 1.92 CI 1.12 to 3.28, NNH 3 CI 3 to 17). Weight gain was equal for people allocated zuclopenthixol and those given sulpiride (n=61, 1 RCT, WMD 1.60 CI 8.35 to 5.15). Many people left these short studies early (45% zuclopenthixol vs 30% risperidone, n=159, 2 RCTs, RR 1.48 CI 0.98 to 2.22). The two isomers of zuclopenthixol, when compared in four short studies (total n=140), did not result in clearly different outcomes., Authors' Conclusions: There is an indication that zuclopenthixol causes movement disorders, perhaps more so than the newer generation of drugs, though no more frequently than the older generation of antipsychotics. There is some suggestion from this review that oral zuclopenthixol may have some clinical advantage, at least in the short term, over other older drugs in terms of global state. If an older drug is going to be prescribed, zuclopenthixol dihydrochloride is a viable option but may be best taken with additional medication to offset movement disorders that occur in about half the people taking this drug. There is no information on service, functional, behavioural outcomes and important outcomes such as relapse, for such a widely used drug this would indicate the need for further studies. We feel that it should remain a choice in the treatment of those for whom older generation drugs are indicated.

Acutely psychotic patients presenting as psychiatric emergencies with aggression or agitation are often administered conventional antipsychotics intramuscularly. However, patients view intramuscular administration as coercive, and conventional antipsychotics are often associated with adverse events. In this open study, consecutive adult patients presenting with an acute exacerbation of schizophrenia or other psychotic disorder were assigned to oral risperidone 2-6 mg/day (n = 48) or oral zuclopenthixol 20-50 mg/day (n = 27) for 7-14 days. Lorazepam (either oral or intramuscular) was administered to both groups as needed. Patients were assessed regularly until day 14 or discharge. Mean Positive And Negative Syndrome Scale (PANSS) aggression scores (sum of item scores on excitement, poor impulse control, hostility and uncooperativeness) decreased steadily and similarly in both groups; the mean changes from baseline were statistically significant at days 10 and 14 and at study end-point. The mean decrease at study end-point in the PANSS component score for hostility was statistically significant in the risperidone group, but not in the zuclopenthixol group. Social Dysfunction and Aggression Scale aggression scores and Clinical Global Impression scores decreased significantly and similarly in both groups. Overall, 18.7% of patients showed minor extrapyramidal symptoms during the study, but only 16.7% of risperidone-treated patients, compared to 59.3% of zuclopenthixol-treated patients, received anti-parkinsonian medication (p < 0.001). Lorazepam was administered to all of the patients assigned to risperidone and to 89% of those assigned to zuclopenthixol. Oral risperidone plus lorazepam is a convenient, effective and well-tolerated alternative to conventional antipsychotics for the treatment of acute psychosis in emergency psychiatry.

Introduction: In most patients diagnosed with psychotic depression or schizophrenia and treated with electroconvulsive therapy, parallelly administered antipsychotic medication cannot be stopped. Antipsychotic drugs can influence both seizure threshold and seizure activity in different ways., Patients and Method: The present study processes the data of 77 patients treated parallelly with electroconvulsive therapy and antipsychotic drugs. Oral doses of the antipsychotic medication administered the day before the electroconvulsive therapy, stimulus intensity, seizure durations, and impedance were analysed from session to session., Results: One group of antipsychotics (haloperidol, fluphenazine, risperidone, sulpirid) was not found to influence seizure activity: there was no significant difference in EEG and EMG registered seizure duration or in stimulus intensity between the treated and non-treated group. However, significant difference was found between the next treated and non-treated groups in 40% of the sessions in case of olanzapine, in 50% of the sessions in case of clozapine and in 57% of the sessions in case of zuclopenthixol in EEG or EMG registered seizure duration as well as in stimulus intensity. In the third group (quetiapine) there was a significant difference in each session (2nd session: EMG, p=0.02; 5th session: EEG, p=0.05, EMG, p=0.04). Most of the antipsychotics (olanzapine, clozapine, zuclopenthixol) have been shown to possess epileptogenic properties; only quetiapine reduces seizure activity., Conclusion: In the clinical use of olanzapine, clozopine and zuclopenthixol seems epileptogenic, whereas in the case of quetiapine seizure reducing properties must be taken into account. Together with the consideration of the accompanying somatic and neurologic disturbances and with the concomitant medications this can influence the treatment of choice.

Long-acting injectable risperidone was assessed in schizophrenia patients who were symptomatically stable on conventional depot antipsychotics and who were then switched to long-acting risperidone. Participants in this open-label, multicentre, 12-week trial had received flupenthixol decanoate, fluphenazine decanoate, haloperidol decanoate, or zuclopenthixol decanoate for 4 months or longer. Each was considered symptomatically stable by investigators. After receiving two cycles of their conventional depot antipsychotic during the run-in period, patients were switched to receive long-acting risperidone every 2 weeks for 12 weeks at an initial dose of 25 mg. This dose could be increased in 12.5-mg increments at 4-week intervals. Ninety-two percent of the patients received all six injections; 62% received the 25-mg dose throughout the treatment period. Adverse events related to movement disorders were reported in 3%. Severity of movement disorders decreased during long-acting risperidone treatment. Positive and Negative Syndrome Scale (PANSS) total and factor scores and scores on the Clinical Global Impressions severity scale were significantly reduced during treatment; 48% of these stable patients showed further symptom improvement (> or =20% decrease in PANSS score at endpoint). The results indicate that patients with schizophrenia who are symptomatically stable during treatment with a conventional depot antipsychotic can be safely and effectively switched to long-acting injectable risperidone without a prior transition to oral risperidone.

There is some evidence of ferropenia correlating with neuroleptic malignant syndrome and catatonic symptoms. The aim of this prospective and naturalistic study was to investigate the implications of ferremia in patients undergoing an intramuscular injection treatment of Zuclopenthixol-acetate in Visceolo. We recruited 59 catatonic patients (33 females). Age, sex, psychiatric and somatic diagnoses, body mass index (BMI), dosage and duration of Zuclopenthixol-acetate medication and the timing of the changeover from intramuscular to oral prescription, the single dosage of Clopenthixol if initially coadministered, incidence, onset and duration of transient benign hyperthermia, iron, ferritin, transferrin and saturation values, and white and red blood cell counts as well as liver function and electrolytes were registered. A transient and benign hyperthermic reaction (mean degrees: 37.5 + 0.3 degrees C) lasting for an average of 3.0 + 1.9 d was shown by 72.9% patients (N = 43, 22 females), during a mean treatment period of 5.8 + 3.1 d. These patients were medicated with significant different mean doses of Zuclopenthixol-acetate and compared to the patients with normal body temperature (ANOVA P < 0.01). The duration of Zuclopenthixol-acetate application did not vary between these patients groups. Furthermore, significant differences of iron (59.5 + 30.6 micromol/dl vs. 87.8 + 40.8 micromol/dl; ANOVA P < 0.006) and transferrin saturation values (18.3 + 10.4% vs. 27.2 + 17.0%; ANOVA P < 0.02) were found. Ferritin and transferrin were not implicated in the episode of hyperthermia. Diagnoses, sex, white and red blood cell counts also did not vary between these groups. Our findings indicate a possible involvement of ferropenia in catatonic patients, regardless of the diagnoses, and in the development of benign transient hyperthermia, also known as drug fever.

Objectives: To study the effectiveness, frequency of administration and side effects of zuclopenthixol acetate (ZPTA) and haloperidol (HAL) in the treatment of acute psychotic disturbance with aggression., Method: Purposive sampling method was employed in a group of psychotic patients with aggression admitted to Songkla Neuropsychiatric Hospital, they were randomly divided into 2 groups: ZPTA group and HAL group. All of the patients were evaluated daily for 7 consecutive days using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression Scale (CGI). Statistical analysis was performed by using the Student t-test and Linear regression., Results: There were 70 patients with diagnosis of schizophrenia, mania and acute psychosis. Thirty-eight patients were randomly assigned to the ZPTA group and were given 50-100 mg of the drug, while 32 patients received HAL 5-10 mg. The result showed a significant reduction in BPRS or CGI scores in both groups. Patients treated with ZPTA required less frequent administration than did those on HAL (p < 0.05). There was no statistically significant difference in the reduction in scores between the two groups. Nor was there a statistical difference in reduction of aggression based on BPRS rating. Each group of patients showed a few side effects of mild degree., Conclusion: Both ZPTA and HAL were effective in the treatment of acute psychosis with aggression, but frequency of administration was lower in the ZPTA group

Rationale: Several antipsychotic drugs are metabolised by the polymorphic cytochrome P(450) CYP2D6. The impact of the polymorphism on the plasma levels and the occurrence of side effects have not been clearly established., Objective: To investigate the impact of the CYP2D6 polymorphism on the steady-state plasma concentrations of zuclopenthixol and the occurrence of extrapyramidal side effects (EPS) and tardive dyskinesia (TD) during treatment with zuclopenthixol-decanoate., Methods: Fifty-two clinically stable schizophrenic outpatients on monotherapy with zuclopenthixol-decanoate (100-400 mg/4 weeks) were genotyped for the CYP2D6 variants CYP2D6*3 and CYP2D6*4. Steady-state plasma levels of zuclopenthixol were analysed using high-performance liquid chromatography. Assessments of EPS, TD and psychopathology were performed twice with an 8-week interval using the extrapyramidal symptoms rating scale, the abnormal involuntary movement scale and the brief psychiatric rating scale., Results: Thirty-five patients were homozygous extensive metabolisers (EMs), 13 were heterozygous EMs and 4 were poor metabolisers (PMs). While there were no significant genotype-related differences in the doses of zuclopenthixol decanoate, PMs as well as heterozygous EMs had significantly higher steady-state plasma levels of zuclopenthixol than homozygous EMs (median 9.5 nmol/l; 8.2 nmol/l and 5.9 nmol/l, respectively, P<0.05). The median dose-corrected plasma concentrations were 0.029, 0.038 and 0.048 nmol.l(-1).mg(-1) in homozygous EMs, heterozygous EMs and PMs, respectively, with statistically significant differences between homozygous EMs and heterozygous EMs ( P=0.014) and homozygous EMs and PMs ( P=0.03). Patients with neurological side effects were significantly older than patients without ( P=0.02 in case of parkinsonism and P=0.04 in case of TD). Mutant CYP2D6*3 and *4 alleles tended to occur more frequently in patients with neurological side effects. An odds ratio (OR) of 2.3 (95% confidence interval 0.7-6.9) for development of parkinsonism and an OR of 1.7 (95% confidence interval 0.5-4.9) for TD was calculated in an individual with at least one mutated allele. However, the ORs were not statistically significant., Conclusions: The higher zuclopenthixol steady-state plasma concentrations in heterozygous EM and PM schizophrenic patients receiving monotherapy with zuclopenthixol-decanoate than in homozygous EMs indicates a significant role of CYP2D6 in the systemic elimination of zuclopenthixol. The tendencies for patients carrying at least one mutated CYP2D6 gene to have an increased risk of parkinsonism and TD are in accordance with previous studies. Age was a significant risk factor for neurological side effects.

Objective: To present a single case of zuclopenthixol-induced priapism and a literature review., Case Summary: We report the case of a 31-year-old patient hospitalized due to behavioral alterations and treated with oral zuclopenthixol, an antipsychotic from the thioxanthene family, who developed an acute, painful erection., Discussion: The occurrence of priapism in our patient was related to zuclopenthixol. This adverse reaction is reported for the first time in a patient not concomitantly treated with other drugs associated with the appearance of priapism. The capacity of zuclopenthixol to induce priapism is thought to be due to its antagonist activity on alpha-adrenergic receptors., Conclusions: Priapism is an uncommon but potentially serious adverse effect of zuclopenthixol that practitioners, as with many other antipsychotics, should be aware of.

Colonic pseudo-obstruction is characterized by non-mechanical chronic colonic dilatation. It is an infrequent entity that can be provoked by multiple causes, among them pharmacological. We present the case of a 74-year-old female psychiatric patient who presented abdominal bloating, diarrhea, intense electrolytic alterations and marked radiographic colonic dilatation after treatment with a neuroleptic (zuclopenthixol decanoate). Organic obstruction and other causes were ruled out and the final diagnosis was chronic colonic pseudo-obstruction secondary to the use of neuroleptics. Cisapride (20 mg/8 h) produced a slight improvement in symptoms but colonic dilatation was permanent.

An 8 year-old boy with X-ALD under treatment with simvastatin developed a severe adverse reaction when the dose of his other medication, zuclopenthixol was increased. Both drugs were withdrawn after a diagnosis of neuroleptic malignant syndrome was made.

Two long-acting neuroleptics were used to tranquilize nine captive cheetahs (Acinonyx jubatus). Perphenazine enanthate (3.0 mg/kg) and zuclopenthixol acetate (0.6 mg/kg) were each administered to separate groups of three cheetahs in a double blind trial. Both products were administered together to a third group of three animals at the same dosages. Behavioral effect, duration of effect, and possible side effects were observed by a predefined protocol. Under standardized holding conditions, the cheetahs were observed 5 days before drug administration and 14 days after administration. Daily activity was defined and statistically evaluated by a U-test. A significant reduction of activity was observed after administration in all three trials. Zuclopenthixol acetate at 0.6 mg/kg alone and in combination with perphenazine enanthate caused inappetence, ataxia, extra pyramidal reactions, akathisia, and prolapse of the third eyelid. Zuclopenthixol acetate should not be used in cheetahs. Perphenazine enanthate did not cause inappetence, reduced appetite, or any of the previously mentioned side effects when used alone. It produced satisfactory tranquilization and is suitable and safe for cheetahs at 3.0 mg/kg. This dosage should be varied depending on health, age, and temperament of the individual cheetah.

cis(Z)-Clopenthixol and trans(E)-clopenthixol were determined by gas chromatography-mass spectrometry and high-performance liquid chromatography-diode-array detection in necropic samples from a postmortem case. The peripheral blood concentrations of cis(Z)-clopenthixol and trans(E)-clopenthixol were 278 and 177 ng/mL, respectively. The level of the active cis(Z)-isomer is within the toxic range. Other associated drugs' concentrations were within their therapeutic ranges. Postmortem redistribution of the drug and instability of the drug due to trans-isomerization were discussed.

Background: Case series and reviews have suggested the effectiveness of zuclopenthixol acetate in the acute management of disturbed behaviour caused by serious mental illnesses. This review investigates the trial-based evidence for these suggestions., Methods: All randomized clinical trials comparing zuclopenthixol acetate to other 'standard' treatments for the acute management of those with serious mental illnesses were identified and, if possible, their results summated., Results: Six trials were identified. All had methodological problems and one did not meet the minimal methodological inclusion criteria. The summary data do not demonstrate that zuclopenthixol acetate is better than 'standard care' for altering behaviour, decreasing the need for supplementary medication, avoiding side-effects, or postponing early discharge against medical advice. One trial, however, presented data that suggested an earlier, more intense level of sedation., Conclusions: Recommendations of reviews and open studies for the use of zuclopenthixol acetate in preference to 'standard' treatments in the psychiatric emergency are not supported by evidence from randomized controlled trials.