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.

Intolerance to neuroleptics and susceptibility for malignant hyperthermia in a patient with proximal myotonic myopathy (PROMM) and schizophrenia.

We report a patient with proximal myotonic myopathy who was treated with neuroleptics because of exacerbating schizophrenia. Under therapy with fluanxol, the patient developed muscle stiffness and oculogyric cramps. Treatment with both amisulpride and olanzapine lead to markedly elevated serum creatine kinase levels. An in-vitro contracture test was positive for halothane. Thus, in patients with all kinds of multisystemic myotonic myopathies, a susceptibility for malignant hyperthermia and intolerance towards neuroleptics should be taken into account.

Síndrome neuroléptico maligno en postoperatorio tardío / Neuroleptic malignant syndrome in postoperative period

La aparición de fiebre en el postoperatorio puede señalar una potencial complicación. A veces ésta sólo puede estar originada por drogas, especialmente neurolépticos, como en este caso. Varón 24 años sometido a gran cirugía tóraco-abdominal, por escopetazo con intento suicida. Con evolución favorable se da de alta quirúrgica a los 14 días con Haldol para evaluacion por siquiatra que lo sustituye por Fluanxol. Comenzando una semana después con fiebre alta, taquicardia, hipotermia, sudoración, calofríos y desorientación. Después de descartar cuadro febril de origen quirúrgico se plantea SNM, suspendiéndose neuroléptico e iniciando tratamiento cediendo fiebre en 24 horas. Comentario: A pesar de lo escaso de su presentación se analiza un caso de fiebre por drogas que siempre se debe tener presente en cirugía

Decanoato de flupentixol versus otros neurolépticos en esquizofrénicos crónicos / Flupentixol decanoate versus other neuroleptics in chronic schizophrenia

El estudio fue realizado en 80 pacientes ambulatorios del Servicio de Psiquiatría del Hospital Salvador (Santiago, Chile) con diagnóstico de esquizofrenia crónica según los criterios del DSM-IV. 40 pacientes fueron tratados con decanoato de flupentixol (como monoterapia neuroléptica). Los 40 restantes (grupo control) fueron tratados con uno o más de los siguientes neurolépticos: clorpromazina, haloperidol, tioridazina, decanoato de flufenazina. Ambos grupos fueron evaluados en entrevistas psiquiátricas y psicológicas utilizando 7 escalas estandarizadas. El uso de decanoato de flupentixol redujo los síntomas positivos y negativos que caracterizan a la esquizofrenia, corroborado por escalas BPRS y CGI.La adhesión al tratamiento con decanoato de flupentixol fue mejor y los efectos colaterales fueron escasos. El grupo control requirió el uso de uno o más neurolépticos para lograr la estabilización o reducción de los síntomas, con la consecuente presentación de efectos colaterales en un mayor número de casos. Finalmente, los resultados positivos obtenidos con decanoato de flupentixol están relacionados con la intensidad de la sintomatología. La efectividad de la medicación fue interior en los pacientes que desarrollaron crisis psicóticas y/o en los pacientes resistentes al tratamiento neuroléptico

Convulsions after enflurane in a schizophrenic patient receiving neuroleptics.

A schizophrenic patient suffered from an episode of unexpected grand mal seizure following an enflurane unaesthetic for biopsy of an orbital lesion. The seizure was brief and subsided spontaneously. An assessment of the anaesthetic technique and a thorough neurological examination which included a CT scan and an EEG, failed to demonstrate any obvious cause for the convulsion. The patient was not an epileptic and was receiving neuroleptic drugs preoperatively for the treatment of schizophrenia. A synergistic role of enflurane and neuroleptic drugs is producing seizure activity in this patients is a distinct possibility. Caution is therefore recommended when administering enflurane to patients on neuroleptic drugs.

Rationalizing neuroleptic polypharmacy in chronic schizophrenics: effects of changing to a single depot preparation.

This study investigated the effects of transferring patients on combined depot and oral neuroleptics to a single depot preparation; a secondary objective was to assess the effects of transferring patients from one depot neuroleptic to another. It was found that, whereas transferring from one depot preparation (flupenthixol) to another (fluphenazine) had no clear disadvantage for the patients, changing over from a combined oral and depot (fluphenazine) regimen to equivalent doses of depot alone resulted in an unacceptably high rate of relapse. The reasons for this may relate to either the unique pharmacokinetics of these drugs or subtle qualitative differences between them. It is suggested that caution is necessary whenever attempts are made to rationalize polypharmacy in schizophrenic patients.

[Neuroleptic malignant syndrome associated with the inadequate antidiuretic hormone secretion syndrome]. / Síndrome neuroléptico maligno asociado a síndrome de inadecuada secreción de hormona antidiurética.

Neuroleptic malignant syndrome (NMS) is an adverse reaction of an idiosyncratic nature to drugs having antidopaminergic activity. Pathogenesis is largely disputed. An NMS case is presented which was triggered by flupentixol and was associated with severe hyponatremia (116 mmol/l upon admission). Both clinically and analytically, the hyponatraemia fulfills criteria to be considered secondary to an inappropriate secretion of antidiuretic hormone (SIADH). Other possible causes of hyponatraemia were ruled out. After early treatment with dopaminergic agonists and water restriction, both conditions improved in parallel. The different pathogenetic possibilities which may explain the temporal coexistence of both syndromes in the same patient are discussed. The association of these two conditions is in favour of a probable central pathogenetic cause for NMS. On the other hand, it is suggested that hyponatraemia may mask the diagnosis of NMS.

Neuroleptic malignant syndrome: another medical cause of acute abdomen.

We present a patient with neuroleptic malignant syndrome and intestinal pseudo-obstruction misdiagnosed as being secondary to septicaemia. The management of the patient is discussed with emphasis on the role of creatine kinase and liver function tests.

Structural features determining activity of phenothiazines and related drugs for inhibition of cell growth and reversal of multidrug resistance.

Phenothiazines and structurally related compounds inhibit cellular proliferation and sensitize multidrug-resistant (MDR) cells to chemotherapeutic agents. To identify more potent pharmaceuticals, we studied the structure-activity relationships of 30 phenothiazines and related compounds on cellular proliferation and MDR in sensitive MCF-7 and resistant MCF-7/DOX human breast cancer cells. Substitutions on the phenothiazine ring that increased hydrophobicity increased antiproliferative and anti-MDR activities. For example, -Cl and -CF3 groups increased whereas -OH groups decreased potency. Modifying the length of the alkyl bridge and the type of amino side chain also influenced potency. Compounds with increased activity against cellular proliferation and MDR possessed a four-carbon bridge rather than a three- or two-carbon bridge and a piperazinyl amine rather than a noncyclic amino group. Compounds with tertiary amines were better anti-MDR agents than those with secondary or primary amines but were equipotent antiproliferative agents. The effects of these substituents were unrelated to hydrophobicity. The structure-activity relationships suggest that an ideal phenothiazine structure for reversing MDR has a hydrophobic nucleus with a -CF3 ring substitution at position 2, connected by a four-carbon alkyl bridge to a para-methyl-substituted piperazinyl amine. We subsequently studied related compounds having certain of these properties. Substitution of a carbon for a nitrogen at position 10 of the tricyclic ring, with a double bond to the side chain (thioxanthene), further increased activity against MDR. For example, (trans)-flupenthixol, the most potent of these compounds, increased the potency of doxorubicin against MDR cells by 15-fold, as compared with its stereoisomer (cis)-flupenthixol (5-fold) or its phenothiazine homolog fluphenazine (3-fold). (cis)- and (trans)-flupenthixol were equipotent antiproliferative agents. (trans)-flupenthixol was not accumulated more than (cis)-flupenthixol in MDR cells, implying that their stereospecific anti-MDR effects were not the result of selective differences in the access of the drugs to intracellular targets. Both drugs increased the accumulation of doxorubicin in MDR cells, but not in sensitive cells, suggesting that they modulate MDR by interacting with a uniquely overexpressed cellular target in these resistant cells. The apparent lack of clinical toxicity of (trans)-flupenthixol makes it an attractive drug for further investigation.

Fatal recurrence of neuroleptic malignant syndrome.

The clinical features of a fatal case of the neuroleptic malignant syndrome are presented. The fatal episode was a recurrence of the syndrome after a milder episode 3 months earlier. Prescription of neuroleptics was continued unchanged following the latter, as a correct diagnosis was not made at the time. The case emphasises the importance of early recognition of the syndrome and the possibility of spontaneous remission of symptoms despite continued neuroleptic treatment.

The neuroleptic malignant syndrome. Case report with a review of the literature.

Following the administration of fluphenthixol (a depot phenothiazine) for a psychotic illness, a 44-year-old woman developed weakness, rhabdomyolysis and renal failure, together with hyperthermia (42 degrees C) and signs of both autonomic and central nervous system dysfunction. She died following massive intestinal haemorrhage, intra-abdominal sepsis and probable disseminated intravascular coagulation. A diagnosis of neuroleptic malignant syndrome had been made, but treatment with dantrolene sodium was probably instituted too late to prevent the progress of the complications she had developed. This syndrome, which follows the use of phenothiazines or butyrophenones, is rare, potentially fatal and probably underdiagnosed. It has been likened to malignant hyperthermia, but a review of the literature points to many differences. Both dantrolene sodium and dopaminergic drugs (bromocriptine, amantidine and L-dopa) have been shown to be efficacious and their continued use, despite a failure in this case, is advocated until more is known about this syndrome.