Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Psychotropic prescriptions for the treatment of schizophrenia in an outpatient clinic / Prescrições psicotrópicas para o tratamento da esquizofrenia em uma clínica ambulatorial

Abstract Introduction There is an unpredictable pattern in the prescription of antipsychotics and other psychotropic medications for the treatment of schizophrenia, particularly in resource-limited settings in developing countries. Objective To determine the psychotropic prescriptions given to patients with schizophrenia in an outpatient clinic of a tertiary hospital and to describe the choices and trends of these prescriptions. Methods This was a cross-sectional descriptive study of prescriptions for adults with schizophrenia. After clinical consultation, patients' case notes were randomly selected over a period of 2 years. Using a structured form, data were extracted from the case notes including biodemographic data, psychotropic medications prescribed and changes made to these prescriptions. Data were analyzed by means of descriptive statistics. Results A total of 103 patients were selected, with a mean age of 35.96±9.78 years; 48.5% were males and 51.5% were females; 33% were unemployed and 38% had been hospitalized in the past. There were 231 initial prescriptions and 228 current prescriptions, with about 2.2 prescriptions per patient. Haloperidol (mean dose 14.77±6.28mg and 11.44±5.55mg for initial and current) and other old-generation antipsychotics were the most commonly prescribed for new cases (98%). Mean duration of psychotropic use was 7.78±5.6 years. All the patients were prescribed trihexyphenidyl, and 56.3% of the patients had their medications changed as a result of side effects. Conclusion There was a very high preference for the use of first-generation antipsychotics for all treatment settings (in- and outpatients), a pattern that is likely to persist.

Resumo Introdução Existe um padrão imprevisível na prescrição de antipsicóticos e outros medicamentos psicotrópicos para o tratamento da esquizofrenia, especialmente em ambientes com limitação de recursos em países em desenvolvimento. Objetivo Determinar as prescrições psicotrópicas dadas a pacientes com esquizofrenia em uma clínica ambulatorial de um hospital terciário e descrever as escolhas e tendências dessas prescrições. Métodos Este foi um estudo descritivo transversal das prescrições dadas a adultos com esquizofrenia. Após consulta clínica, os prontuários dos pacientes foram selecionados aleatoriamente ao longo de um período de 2 anos. Usando um formulário estruturado, os dados foram extraídos dos prontuários, incluindo dados biodemográficos, medicamentos psicotrópicos prescritos e mudanças feitas a essas prescrições. Os dados foram analisados por meio de estatística descritiva. Resultados Um total de 103 pacientes foram selecionados, com idade média de 35,96±9,78 anos; 48,5% eram do sexo masculino e 51,5% do sexo feminino; 33% estavam desempregados e 38% haviam sido hospitalizados no passado. Houve 231 prescrições iniciais e 228 prescrições atuais, com aproximadamente 2,2 prescrições por paciente. O haloperidol (dose média de 14,77±6,28mg e 11,44±5,55mg para prescrições inicial e atual) e outros antipsicóticos de primeira geração foram os mais comumente prescritos para casos novos (98%). A duração média do uso de psicotrópicos foi de 7,78±5,6 anos. Todos os pacientes receberam prescrição de triexifenidil, e 56,3% dos pacientes tiveram seus medicamentos alterados como resultado de efeitos colaterais. Conclusão Houve uma alta preferência pelo uso de antipsicóticos de primeira geração para todos os regimes de tratamento (internação e ambulatorial), um padrão que provavelmente persistirá.

Obstrucción respiratoria alta secundaria a distonía laríngea recurrente inducida por haloperidol y ziprasidona / High airway obstruction secondary to recurrent laryngeal dystonia induced by haloperidol and ziprasidone

La distonía aguda por antipsicóticos es un efecto extrapiramidal frecuente con el uso de estos medicamentos y, aunque su prevalencia es menor con el uso de antipsicóticos atípicos, no dejan de suscitarse casos de dichas reacciones adversas. Entre ellas, la distonía laríngea es un problema que requiere tratamiento de urgencia y que incluso acarrea riesgo mortal. Reportamos el caso de una paciente joven de sexo femenino y con diagnóstico de esquizofrenia paranoide, quien se presentó a nuestro servicio de emergencia en agitación psicomotriz y presentó distonía laríngea inducida por uso de haloperidol, en primer lugar, y luego por ziprasidona, ambos administrados por vía intramuscular. Finalmente revisamos la bibliografía respectiva y recomendamos que, en caso de distonía laríngea, se evite el posterior uso de antipsicóticos parenterales por el importante riesgo de recurrencia. Con anterioridad al presente reporte había solamente cuatro casos publicados en la literatura científica sobre distonía laríngea aguda inducida por ziprasidona...

Antipsychotic-induced acute dystonia is a frequent extrapyramidal effect secondary to the use of these drugs and, although its prevalence is lower with the use of atypical antipsychotics, several cases of such adverse reactions still arise. One of these extrapyramidal effects, laryngeal dystonia, is a problem that requires urgent treatment and may even be life-threatening. We here report the case of a young female patient with the diagnosis of paranoid schizophrenia who presented to our emergency room with psychomotor agitation and was treated with parenteral antipsychotics. She presented laryngeal dystonia induced by use of haloperidol, in first time, and then induced by ziprasidone, both drugs intramuscularly administered. We review the relevant literature about this case and we recommend to avoid the subsequent use of parenteral antipsychotics if there is the antecedent of laryngeal dystonia, because of the significant risk of recurrence. Prior to this case report, there was only four cases of acute laryngeal dystonia induced by ziprasidone reported in the scientific literature...

Haloperidol Induced Neurolept Malignant Syndrome Complicated by Right Ventricular Myocardial Infarction.

A fatal case of right ventricular myocardial infarction in the absence of risk factors, concurrent with haloperidol induced neuroleptic malignant syndrome, is presented; suggesting the existence of a causal relation between the two. Possible pathophysiological mechanisms have been discussed

Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone / Tranquilização rápida para pacientes agitados nos serviços de emergência psiquiátrica: um ensaio clínico randomisado de olanzapina, ziprasidona, haloperidol mais prometazina, haloperidol mais midazolam e haloperidol em monoterapia

OBJECTIVE: To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD: One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage. RESULTS: All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control. CONCLUSION: Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.

OBJETIVO: Comparar a eficácia da olanzapina, ziprasidona, haloperidol associado ao midazolam, haloperidol associado à prometazina e haloperidol isoladamente por via intramuscular como primeira escolha no tratamento de pacientes em agitação e agressividade. MÉTODO: Cento e cinquenta pacientes com agitação psicomotora por transtorno psicótico ou transtorno bipolar foram recrutados para estudo duplo-cego e receberam olanzapina, ziprasidona, haloperidol associado a midazolam, haloperidol associado a prometazina ou haloperidol isoladamente. Foram aplicadas as escalas Overt Agitation Severity Scale, Overt Aggression Scale e Ramsay Sedation Scale no período de 12 horas após a primeira aplicação. RESULTADOS: Todas as medicações foram capazes de acalmar os pacientes após uma hora da administração. Apenas a olanzapina e o haloperidol reduziram a agitação para menos de 10 pontos e apenas a olanzapina reduziu a agressividade para menos de quatro pontos nesse período. Doze horas depois, apenas o haloperidol com midazolam apresentou valores altos para a agitação e agressividade, e também esteve relacionado com maior proporção de efeitos colaterais. A ziprasidona, a olanzapina e o haloperidol apresentaram resultados mais estáveis para o controle da agitação e a ziprasidona, haloperidol associado a prometazina e olanzapina para o controle da agressividade. CONCLUSÃO: A olanzapina, a ziprasidona, o haloperidol associado a prometazina, o haloperidol associado ao midazolam e o haloperidol isoladamente foram efetivos no controle da agitação e da agressividade secundária a transtornos mentais dentro de 12 horas. Todas as drogas apresentaram vantagens e desvantagens, exceto pela associação haloperidol e midazolam que demonstrou os piores resultados em todos os parâmetros.

Antipsychotic treatment and weight gain: does risperidone behave differently in Pakistani psychiatric patients?

Studies from the Western world have shown that antipsychotic medications in psychiatric patients result in weight gain and other metabolic diseases. This study was undertaken to investigate whether any one of the five most commonly prescribed antipsychotics, [risperidone, olanzepine, trifluoperazine, quetiapine and haloperidol] could behave differently in terms of causing weight gain among patients attending the psychiatric outpatient clinics in a tertiary care hospital in Karachi, Pakistan. For this retrospective cohort study, data were collected from outpatient records of the Aga Khan University Hospital, from 2003 to 2007. Demographic and clinical data were analysed. Repeated measures ANOVA, using a linear mixed model approach was used to assess weight gain over time due to the use of antipsychotic medications. A total of 124 subject records [68 males and 56 females] were evaluated. One-way ANOVA revealed that the groups being prescribed with antipsychotics were comparable with respect to age, duration of treatment and weight measurements. Frequencies were calculated which showed that weight increases significantly over time with respect to the prescribed antipsychotic medications, except for risperidone. Repeated measures ANOVA using the linear mixed model approach showed that the serial weight measurements were significantly different across the follow up times [p<0.05]. Four of the commonly prescribed antipsychotic drugs do result in an increase in weight; however risperidone has no such effect, making it an option in treating psychiatric disorders without worrying for any gain in weight. In view of the increased prevalence of obesity and other metabolic diseases, measures should be taken towards careful prescription of antipsychotic medications

Lesão hepática grave induzida por fármacos anticonvulsivantes: relato de casos / Serious liver injury induced by anticonvulsants drugs: case reports

JUSTIFICATIVA E OBJETIVOS: Inúmeros medicamentos empregados rotineiramente na prática médica podem apresentar como efeito adverso significativo a agressão hepática, manifestando-se, por vezes, com lesões graves irreversíveis, sendo possível causa de óbito em determinadas situações. O objetivo deste estudo foi relatar dois casos de pacientes que apresentaram hepatotoxicidade por fármacos anticonvulsivantes, suas consequências e possível prevenção. RELATO DOS CASOS: Caso 1: Paciente do sexo feminino, 12 anos, com história de epilepsia, em uso de carbamazepina (CBZ), haloperidol, clorpromazina e clobazan. Ao exame clínico apresentava-se sonolenta e confusa, com exames laboratoriais contendo dosagem de CBZ elevada e enzimas hepáticas alteradas. Apresentou piora progressiva com surgimento de icterícia, elevação de enzimas hepáticas e diminuição do nível de consciência. A paciente evoluiu com broncopneumonia, hemorragia pulmonar, insuficiência respiratória e óbito. Caso 2: Paciente do sexo masculino, 4 anos, em uso contínuo de depakene, foi encaminhado com quadro de sonolência, icterícia, diminuição do nível de consciência, náuseas e dor abdominal. Houve agravamento do quadro hemodinâmico, com abalos mioclônicos, choque hipovolêmico e óbito. Durante a internação apresentou elevação de enzimas hepáticas e, assim como no primeiro caso, as sorologias virais eram negativas e a tomografia de crânio não apresentava anormalidades. CONCLUSÃO: Nos últimos anos, lesões hepáticas induzidas por diferentes agentes têm sido cada vez mais observadas. E, progressivamente, a importância dada a esse fenômeno tem aumentado de maneira significativa. Sendo o fígado o principal órgão metabolizador corporal, é esperado um comprometimento proporcionalmente extenso à medida que um número crescente de substâncias farmacológicas é utilizado. Diante do exposto, destaca-se a importância do uso racional de interações medicamentosas, na tentativa de prevenir lesões possivelmente evitáveis.

BACKGROUND AND OBJECTIVES: Countless medicines employees routinely in medical practice can present as significant adverse effect the hepatic aggression, manifesting, sometimes, with serious irreversible injuries, being a possible cause of death in determined situations. The objective of this study was reported two cases of patients who presented hepatotoxicity by anticonvulsants, its consequences and possible prevention. CASE REPORTS: Case 1: Female patient, 12 years, with a history of epilepsy, in use of carbamazepine (CBZ), haloperidol, chlorpromazine and clobazam. On clinical examination the patient was drowsy and confused, with laboratory containing elevation of CBZ dosage and liver enzymes changed. There was progressive worsening, with appearance of jaundice, elevation of liver enzymes and decreased level of consciousness. The patient evolved with bronchopneumonia, pulmonary hemorrhage, respiratory failure and death.Case 2: Male patient, 4 years, in continuous use of depakene, was directed with drowsiness, jaundice, decreased level of consciousness, nausea and abdominal pain. There was aggravation of hemodynamic status, with myoclonic tremors, hypovolemic shock and death. During hospitalization in our department, presented liver enzymes elevated and, as in the first case, viral serology was negative and tomography of skull showed no abnormalities. CONCLUSION: In recent years, liver injury induced by different agents has been increasingly observed. And gradually, the importance given to this phenomenon has increased significantly. Being the liver the main metabolizing organ body is expected a proportionally extensive involvement as a growing number of pharmacological substances is used. Given the above, highlights the importance of rational use of drug interactions in an attempt to prevent possibly avoidable injuries.

Toxicological profile of typical and atypical anti-psychotic drugs in psychotic disorders

To evaluate the safety of antipsychotic drugs in psychotic patients. Randomized, comparative and categorical study. This study was conducted in the Department of Pharmacology, Faculty of Pharmacy, University of Karachi collaboration with Sir Cows Jee Jehangir Institute of Psychiatry Hyderabad and duration of study 1[st] Nov. 2007 to 3[rd] Jan. 2008. Patients were selected from OPD, Male and Female wards of Sir Cows Jee Jehangir Institute of Psychiatry Hyderabad. Total two hundreds patients were enrolled in the study out of them 192 patients continue through out study and eight lost follow up the study. The side effects were noticed according to UKU side effect scale. Same criteria was followed for both drugs in the study, assessments was done on the 07, 14, 28 and 42 days. Adverse effect of two drugs presented rigidity and tremors were the most common adverse effect in halopenridol 14.6% and 12.5% and in Risperidone 4.2% and 4.2% respectively. Overall Risperidone in our study proved efficacious and economical drug in psychotic patients. On the other hand haloperidol was also effective and cost effective but produced more side effects. Overall Risperidone in our study proved less toxic and cost effective drug in psychotic patients, on other hand halopendol was also effective and economical drug but should be more side effects

Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period / Eficácia da clozapina, haloperidol e clorpromazina na esquizofrenia em um período de cinco anos

OBJECTIVE: The aim of our study was to evaluate the effects of low doses of clozapine in flexible regime in comparison with haloperidol and chlorpromazine in long term. METHOD: The naturalistic study was prospective, active-controlled with 325 adult outpatients of both genders (140 females), with mean year age of 34.8 (range 21-57), suffering from chronic schizophrenia. The first onset of illness was at the mean of 27.9 years (range 17-38), and subjects had the mean year age of 4.1±0.5 previous relapses. The patients were allocated to receive haloperidol (105 subjects, dose range 2-15 mg), chlorpromazine (n=105, 100-400 mg) or clozapine (n=115, 75-600 mg). The scores of psychometric instruments (GWB, PANSS, CGI) were regularly assessed during 5 year period. RESULTS: The sixty-six responders were included in per-protocol analysis: 12, 10 and 16 with positive and 7, 6 and 15 with negative schizophrenic syndrome in haloperidol, chlorpromazine and clozapine group, respectively. The statistically significant differences in all psychometric scores was found, for both schizophrenic syndromes, favoring clozapine. The distribution of eighteen different types of adverse events, which we noted, were significantly different among treatment groups ( ÷2=315.7, df=34, p<0.001). Clozapine was safer and had fewer adverse effects (average of 0.9 adverse events per patient) than haloperidol (2.7) and chlorpromazine (3.2). CONCLUSIONS: Clozapine, in low doses of flexible regime, in long term (five years) showed better effectiveness in chronic schizophrenics with positive and negative symptoms than typical antipsychotics.

OBJETIVO: O propósito deste estudo foi avaliar os efeitos de baixas doses de clozapina em regime flexível comparando com o uso de haloperidol e clorpromazina por período de 5 anos. MÉTODO: Um estudo prospectivo naturalístico, ativo-controlado foi realizado com 325 pacientes com idade média de 34,8 (variância 21-57). Todos com diagnóstico de esquizofrenia. No primeiro surto da doença os pacientes apresentavam idade média de 27,9 anos (variância 17-38) e os surtos subsequentes apareceram em média 4,1±0,5 anos após. Os pacientes foram orientados a receberem haloperidol (105 pacientes com dose entre 2 e 15 mg), clorpromazina (105 pacientes com dose entre 100 e 400 mg) e clozapina (115 pacientes com dose entre 75 e 600 mg). Os instrumentos psicométricos utilizados (GWB, PANSS e CGI) foram regularmente empregados durante os 5 anos do estudo. RESULTADOS: Os 66 pacientes respondedores ao tratamento foram incluídos no protocolo de análise: 12, 10 e 16 apresentavam síndrome esquizofrênica positiva e 7, 6 e 15 síndrome negativa esquizofrênica com haloperidol, clorpromazina e clozapina, respectivamente. Diferenças estatísticas significantes foram observadas em todas as avaliações psicométricas em ambas síndromes esquizofrênicas favorecendo a clozapina. A distribuição de 18 tipos de efeitos colaterais observados foi diferente de modo significativo entre os 3 grupos estudados. A clozapina foi a droga que apresentou menos efeitos colaterais. CONCLUSÃO: A clozapina administrada por longo termo em pequenas doses em regime flexível apresenta melhor eficácia nas síndromes esquizofrênicas quando comparada a outras drogas antipsicóticas.

Dietary supplementations of amino acids: evidence for enhanced serotonergic functions following haloperidol withdrawal in rat medial prefrontal cortex

To investigate the effects of orally supplemented amino acids L-Tryptophan [Trp] and L-Valine [Val] in rats repeatedly injected with haloperidol following one week of drug withdrawal, with particular reference to extrapyramidal symptoms [EPS] and serotonin [5-hydroxytryptamine; 5-HT] metabolism in medial prefrontal cortex [mPFC]. Experimental study. Place and Duration of Study: Department of Biochemistry, University of Karachi from December 2007 to February 2008. The study was conducted on thirty six locally bred male Albino Wistar rats. Freshly prepared amino acids [Val and Trp] were added in the drinking water of rats on alternate days and haloperidol at doses of 5.0 mg/kg or saline were injected twice daily for three weeks following one week of withdrawal. Locomotor/ exploratory activities were scored in activity boxes and open field apparatuses. Catalepsy was monitored on an inclined surface. The animals tested for locomotor activity and catalepsy for two weeks follow-up post-injections plus one week of drug withdrawal were decapitated to collect mPFC regions of rat brain for neurochemical analysis by high performance liquid chromatography with electrochemical detection [HPLC-EC]. There was significant increase [p < 0.01] in locomotor activity in rats orally supplemented with Val and Trp following one week of drug withdrawal from repeated administration. Marked reduction in cataleptogenic effects of the drug was also observed. Significant [p < 0.01] increases in the brain Trp and mPFC 5-HT metabolism in Val and Trp supplemented animals were also noticed. These findings help to demonstrate the effect of dietary amino acids, in particular, Trp to potentiate mPFC serotonergic modulation of neuroleptic activity

Olanzapina versus Haloperidol: efectividad en la funcionalidad y estado de salud en una muestra de pacientes venezolanos con esquizofrenia / Olanzapine versus Haloperidol: effectiveness in functionality and health state in a sample of venezuelan patients with schizophrenia

Objetivo: comparar la efectividad de olanzapina versus haloperidol, en términos de tasas de recaída en pacientes venezolanos con esquizofrenia. Métodos: estudio abierto, aleatorizado, de 9 meses de seguimiento luego del alta hospitalaria o la estabilización clínica. El Medical Outcomes Study Form Health Survey (SF-36) y el Quality of Life Index from Mezzich & Cohen fueron usados para evaluar el estado de salud y la calidad de vida. Se registraron parámetros de seguridad. Resultados: se enrolaron 31 pacientes en olanzapina y 40 en haloperidol y las tasas de descontinuación fueron 65 y 68 respectivamente. Sólo un paciente en haloperidol recayó. El estado de salud mejoró más con olanzapina con diferencia estadística en 5 de los 8 dominios del SF-36. La olanzapina fue discretamente superior en mejorar la calidad de vida. Más eventos adversos se registraron con haloperidol (p = 0.036). Más síntomas extrapiramidales, acatisia e insomnio se reportaron con haloperidol y mayor aumento de peso con olanzapina sin diferencia estadística. Conclusiones: ambas medicaciones fueron similares en prevenir recaídas. El estado de salud y funcionalidad mejoró más con olanzapina vs. haloperidol. Los resultados de seguridad fueron consistentes con los perfiles conocidos de las drogas. Limitaciones en el diseño y conducción del estudio, acotan su generalización.

Objective: To compare olanzapine versus haloperidol effectiveness, in terms of relapse rates in Venezuela n patients with schizophrenia. Methods: A randomized, open label, follow-up study of 9-months after clinical stabilization or hospital discharged was conducted. The Medical Outcomes Study Form Health Survey (SF-36) and the Quality of Life Index from Mezzic & Cohen were used to evaluate the health state and quality of life. Safety parameters were collected. Results: Thirty-one patients in olanzapine and 40 in haloperidol were enrolled and discontinuation rates were 65 and 68 respectively. Only one patient in haloperidol relapsed. Health status improved more with olanzapine showing statistically significant improvement in five of the eight items of the SF-36. Olanzapine was slightly superior improving quality of life. More adverse events were registered with haloperidol (p = 0.036). More extrapyramidal symptoms, akathisia and insomnia were reported with haloperidol and more weight gain with olanzapine but the differences were not significant. Conclusions: Both medications were similar preventing relapses. Health status and functionality improved more with olanzapine versus haloperidol. Safety results are consistent with the known profile of the drug. Study limitations on design and conduction of this study restrict its generalization.

O uso de antipsicóticos em pacientes com diagnóstico de demência / The use of antipsychotics in patients with dementia

OBJETIVO: Revisar sistematicamente as evidências que sustentam o uso de antipsicóticos no tratamento dos sintomas comportamentais e psicológicos em pacientes com demência, assim como rever as controvérsias e desvantagens dessa prescrição, tendo em vista, por um lado, a elevada prevalência destas manifestações no curso clínico das demências e, por outro, a maior susceptibilidade do idoso aos eventos adversos desses medicamentos. MÉTODO: Revisão sistemática da literatura sobre o uso de antipsicóticos típicos e atípicos em pacientes portadores de síndromes demenciais. As bases de dados usadas para este fim foram o PubMed/Medline, Embase e SciELO. A busca por trabalhos se limitou aos anos de 1986 a 2007, selecionando-se ensaios clínicos randomizados e metanálises da literatura. RESULTADOS: Há evidências a partir de ensaios randomizados, duplamente encobertos, controlados por placebo, de que os antipsicóticos típicos e atípicos são eficazes no tratamento dos sintomas comportamentais que ocorrem nas síndromes demenciais, especialmente os quadros psicóticos e alterações do comportamento motor. Entretanto, o uso destas medicações está associado a eventos adversos importantes. Embora os antipsicóticos atípicos estejam menos associados aos efeitos colaterais extrapiramidais, comuns entre os neurolépticos de primeira geração, podem aumentar a incidência de eventos cerebrovasculares e do risco de morte, sobretudo em pacientes vulneráveis. CONCLUSÃO: Os antipsicóticos devem ser usados com cautela nos pacientes com demência, buscando otimizar o regime de dosagem e duração do tratamento, e avaliando-se individualmente a relação risco-benefício.

OBJECTIVE: The objective of the present study is to systematically review the supporting evidence for the use of antipsychotics in the treatment of behavioral and psychological symptoms in patients with dementia, as well as the controversies and limitations of this prescription. We discuss the available evidence in the light of the high prevalence of behavioral and psychological symptoms of dementia in this population, along with the greater susceptibility of elderly patients to adverse events. METHOD: Systematic literature review of the use of typical and atypical antipsychotics in patients with dementia was carried out in the databases PubMed/Medline, Embase and SciELO. The search was limited to clinical trials and meta-analysis of the literature published from 1986 to 2007. RESULTS: Evidence drawn from randomized, double-blind, placebo controlled trials support the use of both typical and atypical antipsychotics in the treatment of behavioral symptoms of dementia, especially psychotic symptoms and abnormal psychomotor activity. Nevertheless, the use of these drugs in demented patients is not devoid of important adverse events. Although the induction of extrapiramidal symptoms is not as frequent or severe with atypical antipsychotics as it is with first-generation neuroleptics, the former drugs may particularly increase the risk of cerebrovascular events and death. CONCLUSION: Although effective, antipsychotic drugs must be prescribed cautiously in patients with dementia. Dose regimens, duration of treatment and a cautious assessment of risk-benefit must be established for each patient.

Neuroleptic malignant syndrome. Diagnostic and therapeutic dilemmas in a general hospital setting

Neuroleptic malignant syndrome [NMS] is a rare life-threatening condition, usually induced by typical and atypical antipsychotics. A middle-aged woman with bipolar disorder and acute back pain due to multiple falls was admitted to the trauma ward of a general hospital. After 3 days, she suddenly developed signs and symptoms of NMS possibly caused by PRN injectable haloperidol, although the additional role of olanzapine could not be ruled out. A 3-day delayed diagnosis of NMS led to serious complications, which could be prevented by its prompt management contingent on its early diagnosis, even in the absence of certain diagnostic criteria. Although she improved substantially with treatment interventions and continued to have dialysis, she died later due to renal complications. The PRN administration of antipsychotic medications needs to be avoided among such psychiatric patients admitted to general hospitals

Behavioral effects of l-[m-chlorophenyl] piperazine [m-CPP] in a rat model of tardive dyskinesia

The present study was designed to monitor the responsiveness of 5-hydroxy tryptamine [5-HT]-2C receptor in rats treated with haloperidol exhibiting tardive dyskinesia [TD]. Results show that haloperidol injected at a dose of 1 mg/kg twice a day for two weeks elicited vacuous chewing movements [VCMs]. Which increased in a time dependent manner following the drug administration for 3-5 weeks. The behavioral effects of 1-[m-chlorophenyl]piperazine [m-CPP] a 5-HT-2C and 5-HT-1B agonist were monitored 2 days after 5 weeks of saline or haloperidol administration. The results show that hypophagic as well as anxiogenic-like effects of m-CPP are greater in repeated haloperidol than repeated saline injected animals, while hypolocomotive effects of m-CPP are not different in repeated saline and haloperidol injected animals. Results are discussed in the context of role of 5-HT-2C receptors in the regulation of the activity of dopaminergic neuron and its possible impact on elicitation of TD

Effect of NR-ANX-C (a polyherbal formulation) on haloperidol induced catalepsy in albino mice.

BACKGROUND & OBJECTIVE: Use of typical antipsychotics like haloperidol in treatment of schizophrenia is associated with a high incidence of extrapyramidal side effects. In rodents, administration of haloperidol leads to the development of a behavioural state called catalepsy, in which the animal is not able to correct an externally imposed posture. In the present study we evaluated the anticataleptic efficacy of NR-ANX-C, a polyherbal formulation containing bioactives of Withania somnifera, Ocimum sanctum, Camellia sinensis, triphala and shilajit in haloperidol induced catalepsy in mice. METHODS: Five groups (n = 6) of male albino mice were used in the study. Catalepsy was induced by ip administration of haloperidol (1mg/kg). The degree of catalepsy (cataleptic score) was measured as the time the animal maintained an imposed posture. We compared the anticataleptic efficacy of NR-ANX-C (10, 25 and 50 mg/kg) with scopolamine (1 mg/kg). The superoxide dismutase (SOD) level in brain tissue was also estimated to correlate the levels of oxidative stress and degree of catalepsy in the animal. RESULTS: Significant (P<0.01) reduction in the cataleptic scores was observed in all NR-ANX-C treated groups and maximum reduction was observed in the NR-ANX-C (25 mg/kg) treated group. Significant (P<0.05) reduction in SOD activity was observed in NR-ANX-C (25 and 50 mg/kg) treated groups and maximum reduction was observed in NR-ANX-C (25mg/kg) treated group. INTERPRETATION & CONCLUSION: In our study, maximum reduction in cataleptic score was observed in NR-ANX-C (25 mg/kg) treated group. The maximum reduction in SOD activity was also observed in the same group. These findings suggest a possible involvement of the antioxidant potential of NRANX- C in alleviating haloperidol induced catalepsy.

An open, randomized, comparative study of efficacy and safety of risperidone and haloperidol in schizophrenia.

OBJECTIVES: In the last decade there have been numerous randomized controlled trials comparing the efficacy and safety of second generation antipsychotics and conventional antipsychotics in the treatment of schizophrenia, but most of them have been conducted in the western population. This study compared the efficacy and safety of risperidone versus haloperidol in the Nepalese context, in order to add on to the very few literatures available on this topic in the South East Asia region and compare them. METHODS: Patients with the diagnosis of schizophrenia were randomly assigned to receive risperidone 4-6 milligrams (mg) per day and haloperidol 10-20 mg per day, and were followed up for 6 weeks. Assessment were done on the day of the diagnostic interview and days 7, 14, 28 and 42 (end point). During the assessment periods Positive and Negative Syndrome Scale (PANSS) was administered to monitor the progress in psychopathology and Udvalg for Kliniske Undersogelser (UKU) side effects rating scale was applied to rate the treatment emergent adverse effects. RESULTS: Both risperidone and haloperidol were associated with substantial baseline- to- endpoint reduction in symptom severity. After one week of treatment, the improvement in schizophrenia with risperidone was significantly better than haloperidol in terms of PANSS- total Score (-45.4 versus -29.5), negative subscale score (-14.3 versus -6.68) and general psychopathology subscale score (-20.9 versus -13.7). At the end point of the study, the benefit was maintained in total score (-52.1 versus -43.1), though the negative subscale score still showed tendency for greater improvement in psychopathology with risperidone. The side effects profile did not show significant differences except in extrapyramidal symptoms. Thirty-eight percent of risperidone treated patients had to resort to anti-parkinsonian treatment compared to 78% in haloperidol treatment group. CONCLUSION: Similar to the studies in the western countries, Asia and Indian subcontinent, both risperidone and haloperidol were effective in the reduction of psychopathological symptoms in this group of Nepalese population with the diagnosis of schizophrenia. However, risperidone was quicker and better then haloperidol and risperidone had a better safety profile. This is important, because extrapyramidal side effects of neuroleptics are responsible for non-compliance and increased cost in terms of us of anti-parkinsonian medication.

Antipsychotic Drugs and Sudden Death

Sudden, unexpected death may occur in apparently healthy individuals. Its occurrence in psychiatric patients has raised the concern that the use of psychotropics, especially antipsychotics, may be associated with an increased risk of sudden death. This concern is maintained even though not all psychiatric patients who have succumbed to sudden death have been on psychotropics. Early reports presented the concern that the use of chlorpromazine and thioridazine were associated with sudden death. More recently, the focus shifted to the more potent agents. Indeed, the FDA Advisory Committee discussed the possibility of a connection between sudden death and haloperidol. No decision could be reached by the FDA Committee because of the enormous complexity of the problem. Nonetheless, since sudden death continues to catastrophically complicate the course of some patients, the scope of this review is to further investigate the relationship between antipsychotic agents and sudden death

Increase in serotonin-1A receptor responsiveness following haloperidol, withrawal

In view of a role of 5-hydroxtryptamine [serotonin; 5-HT]-1A receptors in the elicitation of extrapyramidal symptoms [EPS], The present study was designed to monitor pre- and postsynaptic responses to a selective 5 HT-1A ligand, 8-hydroxy-2- [di-n-propylamino] tetralin [8-OH-DPAT] following single and repeated [two times a day for 9 days] administration of haloperidol [5 mg/kg] in rats. The intensity of 5 H-T syndrome elicited by 8-OH-DPAT [0.5 mg/kg] was taken as measure of postsynaptic response. 8-OH-DPAT induced decreases of 5-HT metabolism in the striatum and brain were taken as a measure of postsynaptic response. 8-OH-DPAT induced forepaw treading and hyperlocomotion were smaller in haloperidol than saline injected rats. The decreases were not observed following withdrawal from repeated administration of haloperidol. Flat body posture not altered by single injection of haloperidol was enhanced following withdrawal from repeated administration of haloperidol. Haloperidol plus 8OH-DPAT injected animals exhibited comparable levels of 5-HT metabolism in the striatum as well as in the brain. Administration of 8-OH-DPAT significantly decreased 5-HT metabolism in brain but not in striatum of repeated saline injected animals. Conversely, same dose of 8-OH-DPAT injected to haloperidol-injected animals did not decrease 5-HT metabolism in the brain but decreased it in the striatum. The results show an increase in the responsiveness of pre-and postsynaptic 5-HT-responsiveness of post and presynaptic 5-HT-1A receptors may be involved in the greater incidence of EPS in patients treated with neuroleptics such as haloperidol

Olanzapine-induced obesity and diabetes in Indian patients: a prospective trial comparing olanzapine with typical antipsychotics.

The association of hyperglycaemia and weight gain with the use of atypical antipsychotics has been documented. However, there is still not enough data from India. The fact that Indian patients usually have a lower body weight compared to European and American counterparts makes it difficult to extrapolate available data to the Indian context. The purpose of this study is: (a) To compare the prevalence of hyperglycaemia in schizophrenic patients taking olanzapine with those taking typical antipsychotics, and (b) to follow-up non-diabetic, non-obese schizophrenics on a stable regimen of antipsychotic monotherapy and determine the proportion of patients who develop weight gain, diabetes or impaired glucose tolerance; comparing the effects of olanzapine versus typical antipsychotics. Fifty-five schizophrenic patients attending psychiatry outpatients' department and on stable antipsychotic monotherapy for at least 6 weeks were included in the study. Those with a family or personal history of diabetes were excluded. There were 28 cases on olanzapine and 27 on either haloperidol or trifluoperazine. Fasting blood glucose estimation and body-mass Index (BMI) were recorded at baseline, at 6 weeks, and at 12 weeks. The two groups were comparable with respect to age, genderwise composition, and duration of illness. There was no significant difference in baseline glycaemic status or BMI. At the end of 12 weeks, olanzapine was not associated with any significant change in body weight, BMI or plasma fasting glucose. Duration of use of antipsychotic emerged as the only statistically significant risk factor for developing hyperglycaemia across both groups.