Comparison of Intramuscular Olanzapine and Intramuscular Haloperidol in Treatment of Acute Agitation in Patients of Schizophrenia.

Objectives: To determine the antipsychotic efficacy and extra pyramidal safety of intramuscular olanzapine and intramuscular haloperidol during the first 24 hours of treatment of acute agitation in schizophrenia. Methods: Patients (n = 29) with schizophrenia were randomly allocated to receive one to three injections of intramuscular olanzapine (10 mg, n =14), intramuscular haloperidol (10 mg, n = 14) over a 24-hour period. Agitation was measured with the excited component of the positive and negative symptom scale (PANSS) and agitation behavior scale (ABS). Results: After the first injection, IM olanzapine was comparable to IM haloperidol for reducing mean changes in scores from baseline on excited component of PANSS at 2 hours to ( -13.08 olanzapine, -8.07 haloperidol ) and at 24 hours (-9.86 olanzapine, -8.07 haloperidol ). Mean changes in the scores of ABS scale from baseline was at 2 hours (-9.78 olanzapine, -8.54 haloperidol) and at 24 hours (-6.14 olanzapine, -6.6 haloperidol). Patients treated with IM olanzapine had significantly fewer incidence of treatment emergent Parkinsonism (0% olanzapine versus 6.66% haloperidol, p = 4.55), no patient had akathisia with olanzapine as compared to 13.33% of patients with haloperidol, p = 2.03. No patient developed acute dystonia compared to 6.66% of patients with haloperidol, p = 2.59. Conclusion: IM olanzapine was comparable to IM haloperidol in reduction of symptoms of acute agitation in schizophrenia during first 24 hours of treatment, the efficacy of both being evident within 2 hours after first injection. More Extra pyramidal symptoms were observed during treatment with IM haloperidol than with IM olanzapine.

Serotonin [1A] receptor agonism in the expression of behavioral dopaminergic supersensitivity in subchronic haloperidol treated rats

The idea that serotonin [5-hydroxytryptamine; 5-HT] is contributed in schizophrenia has long been advocated and alterations in 5-HT neurotransmission has been hypothesized to modulate both the therapeutic and extrapyramidal symptoms [EPS] liability of conventional neuroleptics. The 8-hydroxy-2-[di-n-propylamino] tetralin [8-OH-DPAT], a preferential 5-HT1A ligand, has been reported to attenuate EPS functions of haloperidol in animals. In view of a possible role of 5-HT1A receptors in the management of EPS functions of a neuroleptic drug, the present study was designed to investigate behavioral responses of 8-OH-DPAT at a challenge dose of 0.5mg/kg in rats with subchronic haloperidol administration at a dose of 5mg/kg twice daily for 5 days. The intensity of 5-HT syndrome provoked by 8-OH-DPAT was taken as a measure of postsynaptic responses. In the present study administration of haloperidol at a dose of 5mg/kg twice daily for 5 days decreased locomotion significantly [p<0.01] in familiar [home cage] environment. Subchronic administration of haloperidol at the same dose elicited significant [p<0.01] cataleptic responses in rats when compared with saline treated rats. Results revealed that 8-OH-DPAT-induced hyperlocomotion [p<0.05] and forepaw treading [p<0.1] were significantly smaller in rats pre-treated with haloperidol for 5 days than repeatedly saline injected rats. Conversely, the other components of the syndrome i.e. flat body posture [p<0.001], hind limb abduction [p<0.001] and straub tail [p<0.01] were significantly greater in repeated haloperidol treated rats when compared with repeated saline injected rats. These findings help to demonstrate a causal link between the upregulation of DA-D2 receptors and the decrease in the effectiveness of presynaptic 5-HT1A receptors following subchronic haloperidol administration and this may further help to yield an antipsychotic agent with an improved profile of efficacy to EPS, thereby widening its therapeutic window

Neurochemical and behavioral effects of M-CPP in a rat model of tardive dyskinesia

Present study was designed to monitor the responsiveness of 5HT [5-Hydroxytryptamine] -2C receptors following the long-term administration of haloperidol in rats. Effects of m-CPP [meta-Chlorophenyl piperazine] were monitored 48h after withdrawal from repeated [twice a day for 5 week] administration of haloperidol [at the dose of 1mg/kg]. Vacuous chewing movements [VCMs] were monitored on weekly basis. Two days after withdrawal, animals were injected with saline [1ml/kg of body weight] or m-CPP [3mr/kg of body weight]. Activities in open field and light dark activity box were monitored 15 and 30 min post injection respectively. Animals were then decapitated [4h post injection] to collect dorsal striatum [DS] samples for the neurochemical analysis by HPLC-EC [High performance Liquid Chromatography with Electrochemical detection] method. Results from the present study showed significant hypolocomotive effect of m-CPP [p<0.05] in both repeated haloperidol as well as repeated saline injected rats. Neurochemical analysis of DS by HPLC-EC method showed that administration of m-CPP significantly [p<0.05] decreased 5-HIAA [5-Hydroxyindol acetic acid] in repeated haloperidol injected rats. In conclusion, present study provides evidence that 5HT-2C receptors become hypersensitive in a rat model of Tardive Dyskinesia [TD]. These findings have potential implication in the treatment of TD and attenuation of EPS induced by typical neuroleptics

Atypical antipsychotics side effects, an update review

Although the novels anti psychotic's drugs are usually grouped together as a category, they are significantly different in many aspects. One is there side effect property. In there affinity to cause, EPS, and Tardive Dyskinesia - the data are still out, although, Clozapine and Quetiapine will cause less TD as compared to Risperidone and Olanzapine. The diabetes mellitus and the weight gain, is an important issue with the atypical anti-psychotics, particularly with Olanzapine and Clozapine. In Japan, the government has issued a warning stating that, Olanzapine is contraindicated in patients with pre-existing diabetes. Patients should be informed of the risk of diabetes with Olanzapine and their blood glucose should be monitored. On 05/03/02, the authorities in the UK have initiated a review of diabetes with Olanzapine because of 40 cases of diabetes four were of diabetic acidosis and one death. The QTc prolongation story, however, in some opinions, is a marketing gimmick then the actually data supports the likelihood of QTc prolongation with Ziprasidone

Haloperidol, biperideno e parkinsonismo / Haloperidol, biperiden and parkinsonism

O autor fez uma extensa revisäo bibliográfica sobre os neurolépticos, em especial o haloperidol, bem como sobre as reaçöes extrapiramidais, com atençäo principal ao parkinsonismo, com descriçäo de quadros e tratamentos indicados

Bases farmacológicas para o tratamento dos efeitos extrapiramidais dos antipsicóticos / Pharmacological basis for the treatment of extrapyramidal effects of antipsychotics

Os efeitos extrapiramidais dos neurolépticos säo devido a sua açäo no sistema nigro-estriatal, causando aparecimento de desordens diversas, reversíveis e irreversíveis. A mais freqüente é o pseudo-parkinsonismo, e sua origem está em um desequilíbrio acetilcolina-dopamina e é inversamente proporcional à atividade anticolinérgica do medicamento. Na discinesia tardia, ao contrário do que ocorre no pseudo-parkinsonismo, há um aumento da transmissäo dopaminérgica em conseqüência de uma supersensibilidade de desnervaçäo. O tratamento, para o pseudo-parkinsonismo é feito com anticolinérgicos. Näo há, no entanto, consenso no tratamento ideal para a discinesia tardia