Olanzapine intramuscular shows better efficacy than zuclopenthixol acetate intramuscular in reducing the need for restraint, but not in comparison to haloperidol intramuscular.

Many psychotic patients are treated with antipsychotic medications during acute agitation and aggressive behavior episodes in an attempt to achieve a rapid calming effect. Those medications include olanzapine, zuclopenthixol acetate, and haloperidol intramuscular administration. This study compared the effectiveness of these injections in reducing the need for restraint during agitated-psychotic episodes that include aggression. Sociodemographical and clinical data were retrieved from the electronic medical records of 179 patients who needed rapid calming while hospitalized in a mental health center with acute psychosis. The treatments administered were olanzapine intramuscular, zuclopenthixol acetate intramuscular, and haloperidol intramuscular. The assessed outcomes were rate of restraint and violent behavior. Olanzapine was found significantly more effective in reducing the need for restraint compared to zuclopenthixol acetate. No significant differences were found between haloperidol and the other two with regard to restraint. Neither were other significant differences found between the groups with regard to violent or self-harming behaviors. No significant differences were found in the rate of violent behavior and antipsychotic dosage at discharge. In conclusion, in inpatients with acute agitated psychosis, olanzapine intramuscular shows better efficacy in reducing the need for restraint, at least as compared to zuclopenthixol acetate intramuscular.

Paliperidone Palmitate-Induced Delirium in an Adolescent with Schizophrenia: Case report.

Schizophrenia is a serious long-term mental disorder which usually presents in adolescence or early adulthood. However, poor adherence to oral antipsychotics can lead to relapse and rehospitalisation. We report an adolescent male with schizophrenia who was referred to the South London & Maudsley National Health Service Foundation Trust, London, UK, in 2015 due to worsening psychotic symptoms. Following poor compliance with oral medications, a four-week regimen of paliperidone palmitate long-acting injections was initiated, with an initial positive response. However, 10 days after the second dose, the patient developed severe acute-onset delirium with fluctuating levels of consciousness. Paliperidone palmitate was discontinued and the patient instead underwent a course of zuclopenthixol decanoate long-acting injections with a favourable outcome.

Polysubstance-induced relapse of schizoaffective disorder refractory to high-dose antipsychotic medications: a case report.

BACKGROUND: The high prevalence of comorbid illicit drug use in persons with chronic psychotic illness represents a strong determinant of psychotic relapse and rehospitalization. Epidemiological studies indicate changing patterns of illicit drug use in Australia, which are concerning because of increased use of crystal methamphetamine, also known as "ice." An important complication of habitual use of crystal methamphetamine is the development of a dose-dependent acute psychotic reaction. We report a case of an acute psychotic relapse in response to polydrug use most notable for multiple recent binges of crystal methamphetamine. Unlike previously described case reports, our patient's acute psychosis was refractory to ultra-high doses of multiple antipsychotic medications. This presented safety challenges due to the risk of serious side effects with high-dose antipsychotic medications. CASE PRESENTATION: A 30-year-old white man with a past history of schizoaffective disorder was brought to our emergency department by the police in a state of extreme agitation, combativeness, and paranoia after use of cannabis and crystal methamphetamine. Despite existing compliance with zuclopenthixol decanoate depot medication, he required multiple emergency injections of zuclopenthixol acetate, and regular high-dose droperidol, chlorpromazine, and lorazepam. However, he remained severely agitated and psychotic with continuous threats of harm to others. A test of antipsychotic drug metabolism by cytochrome P450 enzymes did not reveal a pharmacogenetic cause for the poor therapeutic efficacy of antipsychotic medications. His psychosis did not appear to be modified by psychoactive medications but was instead self-limited to the presence of endogenous methamphetamine within his system. He fully recovered 96 to 120 hours post-presentation and was discharged home with out-patient clinic follow-up. CONCLUSIONS: The current case highlights the challenging nature of a severe psychotic relapse precipitated by illicit substances that is resistant to medical management. High doses of multiple antipsychotic medications may be required to manage dangerous behaviors associated with these acute psychotic relapses. These patients require close monitoring for adverse effects with adjustment of dosing to ensure the optimal balance of risk versus benefit while the patient is acutely psychotic. The results are of relevance for the management of psychiatric emergencies in emergency departments and acute mental health settings.

THE EFFECT OF A SLOW-RELEASE FORMULATION OF ZUCLOPENTHIXOL ACETATE (ACUNIL®) ON CAPTIVE BLUE WILDEBEEST (CONNOCHAETES TAURINUS) BEHAVIOR AND PHYSIOLOGICAL RESPONSE.

The study investigated the effect of a slow-release formulation of zuclopenthixol acetate (Acunil®) on blue wildebeest ( Connochaetes taurinus ) in captivity. Two groups of trials were conducted using either Acunil or a placebo (control). Animals (Acunil: n = 17; placebo: n = 12) were observed for a 12-hr period before the administration of Acunil or the placebo (pretreatment). After 24 hr, animals were administered Acunil (1.5 mg/kg) or a placebo (1.0-3.0 ml of sterile water) and observed again for 12 hr (posttreatment). During both treatments, animals were stimulated every 2 hr for 1 min by a person entering the enclosure (referred to as periods of stimulation). Behavioral observations and continuous heart rate, respiration rate, and motion measurements were taken throughout. Animals treated with Acunil spent more time lying with their heads folded back, eating and standing with their heads down, and less time being vigilant and exploring while walking around. Animals treated with the placebo also spent less time being vigilant and more time lying with heads up. Animals treated with Acunil groomed less while standing and performed less head shaking; no such changes were observed in the control group. Neither Acunil nor the placebo had any effect (P > 0.05) on heart rate. However, overall mean respiration rate was lowered (P = 0.02) when animals were treated with Acunil (pretreatment: 14.5 ± 0.82 breaths/min; posttreatment: 12.5 ± 0.83 breaths/min). Acunil also caused a lowered (P < 0.05) respiration rate during periods when animals were stimulated (pretreatment: 16.2 ± 0.87 breaths/min; posttreatment: 13.7 ± 0.87 breaths/min) and when animals were trotting and being vigilant. No such changes were observed with the placebo. Both placebo- and Acunil-treated animals spent more time being stationary during periods of stimulation. However, Acunil-treated animals also spent less time moving fast when they were stimulated.

Zuclopenthixol versus placebo for schizophrenia.

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.

Zuclopenthixol decanoate in pregnancy: successful outcomes in two consecutive offsprings of the same mother.

INTRODUCTION: Almost all individual antipsychotics are classified into the intermediate pregnancy risk category as no or limited data exist about human pregnancy outcomes. We presented the case of zuclopenthixol decanoate using in two successive pregnancies of the same woman, which had not been published in the available peer-reviewed literature. CASE REPORT: A middle-age female subject who suffered from schizophrenia received zuclopenthixol decanoate injection during her two consecutive pregnancies. About four and a half months before diagnosis of the first pregnancy (to approximately 3.5 years after psychosis emergence), zuclopenthixol decanoate (400 mg every other week, im injection) was introduced to the treatment protocol (due to previous non-compliance with haloperidol and risperidone). A significant clinical improvement was achieved and the dose during pregnancy was reduced to 200 mg once monthly and maintained to date. In both pregnancies the women gave birth to healthy girls who have been developing normally until now, at their ages of 6 months and of 3.5 years. During pregnancy and after giving birth to children the mothers' psychiatric status and her social functioning were significantly improved and are still stable. Close monitoring of the mother's health, a multidisciplinary approach to both her treatment and the monitoring of pregnancies as well as the complete compliance with the prescribed drug protocol were likely to be crucial for the therapeutic success. CONCLUSION: A favorable outcome of the present case suggests that the zuclopenthixol decanoate is a rational therapeutic option for pregnant women suffering from psychosis when the expected benefit exceed the potential risk, but a definitive evidence for its safety requires large, controlled studies.

Severe laryngeal dystonia in a patient receiving zuclopenthixol "Acuphase" and fluoxetine.

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.

Beneficial effects of N-acetylcysteine in treatment resistant schizophrenia.

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.

Zuclopenthixol-induced neuroleptic malignant syndrome presenting as fever of unknown origin, hyperglycaemia and acute myocardial infarction in a 60-year-old man.

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.

Antipsychotic polypharmacy in the emergency treatment of highly aggressive schizophrenic prisoners - a retrospective study.

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.

Quetiapine-induced leucopenia and thrombocytopenia.

Antipsychotic drugs can cause neutropenia, which can progress to life-threatening agranulocytosis if drug therapy is not interrupted. The newer atypical antipsychotics are reputedly without adverse hematological effects. Quetiapine is a recently introduced atypical antipsychotic. It is a dibenzothiazepine derivative and shows similarities with clozapine in that it is characterized by high 5-HT(2)-relative-to-DA(2) receptor affinity. Although adverse effects are usually mild, the author reports here a case of leucocytopenia and thrombocytopenia with quetiapine treatment that required its discontinuation.

Recurrent heat-related illnesses during antipsychotic treatment.

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.

Long-acting injectable risperidone: safety and efficacy in stable patients switched from conventional depot antipsychotics.

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.

Local-global processing in early-onset schizophrenia: evidence for an impairment in shifting the spatial scale of attention.

In this study we report the results of two experiments on visual attention conducted with patients with early-onset schizophrenia. These experiments investigated the effect of irrelevant spatial-scale information upon the processing of relevant spatial-scale information, and the ability to shift the spatial scale of attention, across consecutive trials, between different levels of the hierarchical stimulus. Twelve patients with early-onset schizophrenia and matched controls performed local-global tasks under: (1) directed attention conditions with a consistency manipulation and (2) divided-attention conditions. In the directed-attention paradigm, the early-onset patients exhibited the normal patterns of global advantage and interference, and were not unduly affected by the consistency manipulation. Under divided-attention conditions, however, the early-onset patients exhibited a local-processing deficit. The source of this local processing deficit lay in the prolonged reaction time to local targets, when these had been preceded by a global target, but not when preceded by a local target. These findings suggest an impaired ability to shift the spatial scale of attention from a global to a local spatial scale in early-onset schizophrenia.