There is more to this fever than meets the eye: A case of neuroleptic malignant-like syndrome (NMLS) secondary to withdrawal of procyclidine and L-dopa on a background of long-standing flupenthixol depot use.

This case report highlights the risk of development of Neuroleptic Malignant-Like Syndrome secondary to withdrawal of procyclidine with brief withdrawal of L-dopa and long-term typical antipsychotic depot. The patient responded to reintroduction of procyclidine, sedation and supportive treatment. The mechanism and management of NMS and NMLS is also reviewed. This case emphasises that any changes in antipsychotic and antiparkinsonian medications should be undertaken with extreme caution and patient should be closely monitored for development of NMLS after alteration in these medications.

The management challenges of a case with Flupentixol-induced neuroleptic malignant syndrome.

BACKGROUND: Neuroleptic malignant syndrome (NMS) is a rare and life-threatening reaction. The incidence rate of NMS has dropped because of the higher use of atypical antipsychotics, compared with the typical ones. The mortality rate in patients taking injectable antipsychotics has been also by 38%. AIM: Here, a case developing the NMS symptoms following Flupentixol (FPX) use was reported. CASE PRESENTATION: The patient was a 46-year-old man with the history of schizoaffective disorder (SAD) and recently on six-weekly doses of long-acting (LA) typical antipsychotic drugs. He was referred with a fever, sweating, a food intolerance, mutism, and disorientation in 2019. He was presented with generalized rigidity, negativism, and neck stiffness. The patient's initial creatine phosphokinase (CPK) level was 1476 IU/L, which gradually elevated to 3997 IU/L on Day 26. NMS was further diagnosed, in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, and the score 9+ in the Naranjo Algorithm as the adverse drug reaction probability scale. Afterward, the patient was treated with bromocriptine at a dose of 5 mg 3 times a day, which progressively reached a maximum of 50 mg. He experienced sepsis and resistant respiratory infection several times. The case was finally discharged after 66 days of hospitalization, with a high level of consciousness, but limited verbal communication, in a fever-free condition with the oral administration of bromocriptine and lorazepam. CONCLUSION: In conclusion, there were suggestions for the management challenges of NMS in patients receiving LA injectable antipsychotic agents.

[Observation of Flupentixol and melitracen on curative effect of sudden deafness patients with anxiety and depression in different stages].

Objective:To investigate the efficacy of flupentixol melitracen on different stages of sudden deafness patients with anxiety and depression.Method:Totally one hundred and sixty-three sudden deafness patients with anxiety and depression were randomly divided into two groups: experimental group(81 cases) and control group (82 cases). All patients were given routine treatment for 2 weeks. The experimental group was given oral flupentixol melitracen (1 tablet/day)for a period of 3 months. The hearing, tinnitus effect and vertigo treatment course were observed and compared. Curing rate of tinnitus at 2 weeks, 3 months and 6 months after treatment, self-rating anxiety scale (SAS) and depressive state scale (self-rating depression scale, SDS) score were collected and compared.Result:Total efficiency of hearing and tinnitus of experimental group(86.42%,84.21%)were higher than that of the control group(67.07%,61.29%);the vertigo cured the average treatment time of experimental group days was less than that of the control groupdays,all the differences were statistically significant.After treatment,the average hearing threshold value of the two groups of patients were lower than that before treatment,the low frequency descent type, high-frequency descent type,flat down type and total deafness type thresholds of the experimental group were lower than of the control group,all the differences were statistically significant.The tinnitus cure rate of experiment group were higher than the control group at 3months and 6 months after treatment,the differences were statistically significant;and after 3months and 6 months treatment tinnitus cure rate higher of the experimental group than that of after 2 weeks the treatment,the difference was statistically significant.After 2 weeks,3 months and 6 months treatment,the SAS and SDS scores of two groups were lower than that before treatment.The SAS and SDS scores of the experimental group decreased after 2 weeks,3 months and 6 months treatment, and the difference was statistically significant at different time points,the SAS,SDS scores of experimental group after treatment were lower than the control group at the same time,the differences were statistically significant.Conclusion:For the sudden deafness patients with anxiety and depression , the combination of flupentixol melitracen on the basis of conventional therapy can improve the clinical efficacy, the patient's mental status and long-term therapeutic effect of tinnitus..

Modulating cancer cell survival by targeting intracellular cholesterol transport.

BACKGROUND: Demand for cholesterol is high in certain cancers making them potentially sensitive to therapeutic strategies targeting cellular cholesterol homoeostasis. A potential approach involves disruption of intracellular cholesterol transport, which occurs in Niemann-Pick disease as a result of acid sphingomyelinase (ASM) deficiency. Hence, a class of lysosomotropic compounds that were identified as functional ASM inhibitors (FIASMAs) might exhibit chemotherapeutic activity by disrupting cancer cell cholesterol homoeostasis. METHODS: Here, the chemotherapeutic utility of ASM inhibition was investigated. The effect of FIASMAs on intracellular cholesterol levels, cholesterol homoeostasis, cellular endocytosis and signalling cascades were investigated. The in vivo efficacy of ASM inhibition was demonstrated using melanoma xenografts and a nanoparticle formulation was developed to overcome dose-limiting CNS-associated side effects of certain FIASMAs. RESULTS: Functional ASM inhibitors inhibited intracellular cholesterol transport leading to disruption of autophagic flux, cellular endocytosis and receptor tyrosine kinase signalling. Consequently, major oncogenic signalling cascades on which cancer cells were reliant for survival were inhibited. Two tested ASM inhibitors, perphenazine and fluphenazine that are also clinically used as antipsychotics, were effective in inhibiting xenografted tumour growth. Nanoliposomal encapsulation of the perphenazine enhanced its chemotherapeutic efficacy while decreasing CNS-associated side effects. CONCLUSIONS: This study suggests that disruption of intracellular cholesterol transport by targeting ASM could be utilised as a potential chemotherapeutic approach for treating cancer.

[Antipsychotic agents in the treatment of somatoform disorders; a review]. / Gebruik van antipsychotica bij somatoforme stoornissen; een literatuuroverzicht.

BACKGROUND: Antipsychotics are regularly prescribed in the treatment of somatoform disorders. Up till now there has not been any systematic review of the literature on this subject. AIM: To provide a review of the literature on the use of antipsychotic agents in patients with somatoform disorders. METHOD: Publications listed in PubMed database were retrieved and studied. The search terms used were the somatoform disorders and functional disorders in combination with 'antipsychotic agent' and all individual antipsychotics. RESULTS: L-sulpiride was effective in the treatment of functional dyspepsia in four randomised, controlled trials (rcts). There is only limited evidence for the effectiveness of flupentixolmelitracen in the treatment of functional dyspepsia and of amisulprid in the treatment of glossodynia. The other studies report the ineffectiveness of antipsychotics (in the treatment of body dysmorphic disorder) or they are methodologically poor studies which do suggest a slight positive effect (in fibromyalgia and in hypochondria). CONCLUSION: Recommendations about the effectiveness of antipsychotics in the treatment of somatoform disorders need to be differentiated according to the type of subcategory. There have been very few RCTs and typical antipsychotics have been studied more than atypical antipsychotics. Antipsychotics have proved effective in the treatment of functional dyspepsia.

Clinical investigation on hypotensive patients with vertigo.

The aim of this study was to investigate the characteristic of hypotensive patients with vertigo. Twenty hypotensive patients with rotatory vertigo, 15 hypotensive subjects without vertigo, and 15 mitral valve prolapse subjects without vertigo underwent a battery of tests including audiometry, electronystagmography (ENG), and vestibular evoked myogenic potential (VEMP) test. The abnormal rates in terms of audiometry, eye tracking, optokinetic nystagmus, visual suppression, and caloric tests were 15, 35, 35, 10, and 42% for the first group; 13, 20, 33, 0, and 0% for the second group; and 7, 13, 60, 0, and 3% for the third group, respectively. Comparison of the first group with the other two control groups revealed that significant difference existed only in the abnormality of caloric responses. Fifteen (75%) of 20 hypotensive patients with vertigo having abnormal ENG results, asymmetric caloric responses, or delayed VEMPs were attributed to vertigo of central origin, possibly from ischemic disorder. In contrast, five patients (25%) had neither central signs in ENG nor abnormal VEMPs, but showing bilateral normal or hyperactive caloric responses were classified as autonomic dysfunction. After 3 months of medication, all patients with autonomic dysfunction had their vertigo and autonomic symptoms subsided, whereas 27% of the patients with ischemic disorder had vertigo persisted, showing a significant difference. In conclusion, hypotensive patients with vertigo could be due to either direct autonomic dysfunction or ischemic disorder mediated by autonomic deficits.

Delusional pregnancy in a patient with primary sterility.

The case of a patient suffering from primary sterility who developed a well-systemized delusion of pregnancy is described. The patient did not have a history of psychiatric disorder or organic cerebral pathology. No history of epilepsy was detected in this patient contrary to the reports in the literature, and these facts have pathogenic relevance in delusional pregnancy. The importance of psychological factors in the development of a delusion of pregnancy is discussed.

Effects of flupenthixol and quadazocine on self-administration of speedball combinations of cocaine and heroin by rhesus monkeys.

The simultaneous i.v. administration of heroin and cocaine, called "speedball," is often reported clinically, and identification of effective pharmacotherapies for polydrug abuse is a continuing challenge. This study compared the effects of treatment using combinations of dopamine and opioid antagonists with each antagonist alone on speedball self-administration by rhesus monkeys. Speedballs (0.01 mg/kg/inj cocaine and 0.0032 mg/kg/inj heroin) and food (1 g banana pellets) were available in four daily sessions on a second-order schedule of reinforcement [FR4 (VR16:S)]. Monkeys were treated for 10 days with saline or ascending 1:10 dose combinations of the dopamine antagonist flupenthixol and the opioid antagonist quadazocine. The combination of flupenthixol (0.018 mg/kg/day) + quadazocine (0.18 mg/kg/day) significantly reduced speedball self-administration in comparison to the saline treatment baseline (p < .05), whereas, the same doses of each antagonist alone had no significant effect on speedball-maintained responding. Treatment with 0.018 mg/kg/day flupenthixol + 0.18 mg/kg/day quadazocine produced a 3-fold rightward shift in the speedball (3:1 cocaine-heroin combination) dose-effect curve. Food-maintained responding was similar during treatment with saline and with flupenthixol + quadazocine combinations. These findings suggest that medication mixtures designed to target both the stimulant and opioid component of the speedball combination, may be an effective approach to polydrug abuse treatment.

Cocaína: bases biológicas da administraçäo, abstinência e tratamento / Cocaine: biological basis of administration, withdrawal and treatment

O aumento do consumo de cocaína nas últimas duas décadas foi acompanhado por uma melhora do conhecimento dos mecanismos biológicos relacionados ao uso, abuso e dependência desta droga. Entender esses mecanismos ajudará o clínico a compreender os comportamentos e sintomas dos usuários, bem como as possibilidades de tratamentos biológicos existentes. Os objetivos desta revisäo säo:1. Avaliar a neurobiologia da cocaína, as alteraçöes que provoca nos usos agudo e crônico, os possíveis mecanismos de dependência e da síndrome de abstinência, além das repercussöes neuroendócrinas do uso crônico. 2. Relacionar a farmacoterapia disponível, avaliando sua eficácia a partir de estudos já realizados e apontar novos estudos em andamento

Pharmacotherapy of schizophrenia patients with comorbid substance abuse.

Substance abuse worsens the course of schizophrenia and significantly impairs the relationship between the patient and the health care team. Recent advances in laboratory studies of substance abuse and the pharmacology of schizophrenia open up new possibilities for pharmacotherapy of substance abuse in schizophrenia patients. D1 dopaminergic receptor agonists may directly block the drive for stimulant use. D2 dopaminergic receptor antagonists may indirectly block the drive for stimulant and nicotine use, while opioid antagonists appear to reduce the drive to use alcohol. New generations of neuroleptics with serotonin (5-HT2) receptor antagonism and/or 5-HT1A agonist activity may reduce substance abuse in schizophrenia patients who self-medicate negative symptoms or neuroleptic side effects. Pharmacotherapy efficacy may be enhanced by adding contingency management, social skills training, and other manualized programs. Tables are provided of potentially useful medications. Preliminary results are presented of cocaine-abusing schizophrenia patient treated with desipramine and traditional neuroleptics.

Síntomas positivos y negativos de la esquizofrenia / Positive and negative symptoms of schizophrenia

Desde el siglo pasado se reconoce dos grupos de síntomas que se supone corresponden a dos tipos de procesos mórbidos en la esquizofrenia. El artículo presenta las ideas de los principales investigadores acerca de estos dos aspectos, junto con los hallazgos neuroquímicos y los estudios de imágenes cerebrales que las sustentan.

Treatment of depression with flupenthixol in terminally ill patients.

In recent years, there has been much interest in the psychological well-being of cancer patients (Buckberg et al., 1980; Plumb & Holland, 1977; Razavi et al., 1990; Grassi et al., 1989). It is recognized that if depression is detected and treated, the quality of life for the patient is improved (Holland, 1987; Valentine & Saunders, 1989). Many patients are treated with tricyclic anti-depressants which work well in some cases, but these drugs can have the disadvantage of taking 3 weeks before any improvement in the mood of the patient is observed. They can also cause unpleasant side-effects, e.g. dry mouth, urinary retention and constipation. These symptoms are often already present in the terminally ill and their exacerbation can make these drugs unacceptable to such patients. Two cases of depression which were detected on admission to a hospice and which were successfully treated with flupenthixol dihydrochloride are reported.

Outpatient treatment of 'crack' cocaine smoking with flupenthixol decanoate. A preliminary report.

"Crack" cocaine abuse often produces severe cocaine dependence that is refractory to available pharmacological and outpatient psychotherapeutic treatments. We conducted two preliminary investigations evaluating the efficacy of flupenthixol decanoate, a depot xanthene requiring infrequent intramuscular administration, in the treatment of cocaine withdrawal. Ten outpatient crack cocaine smokers with poor prognoses were administered flupenthixol decanoate in an open-label, open-ended trial. Flupenthixol decanoate was well tolerated and appeared to decrease cocaine craving and use markedly and rapidly, producing a 260% increase in the average time retained in treatment among these subjects. These promising but preliminary data, combined with the magnitude of problems presented by crack, warrant rapid, expanded double-blind assessment of flupenthixol decanoate in cocaine-abuse treatment.

Comparative determination of flupentixol in plasma by gas chromatography and radioimmunoassay in schizophrenic patients.

A new method of measuring flupentixol in plasma was developed using gas chromatography (GC) with a nitrogen-phosphorus detector. The minimal quantifiable concentration was 0.5 ng/ml and the day-to-day coefficient of variation was 9.4% at 2 ng/ml. A comparison of flupentixol concentrations measured with radioimmunoassay (RIA) and GC was undertaken on 100 plasma samples obtained from 50 schizophrenic patients. The RIA method tended to overestimate flupentixol concentrations compared with GC. The reasons for this discrepancy might be the presence in plasma of the inactive trans(E)-flupentixol isomer and metabolites of flupentixol, which would cross-react with the antibody. The results of this study show that GC can be used for therapeutic monitoring of flupentixol.