Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period

Abstract

-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 (χ 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.Key WordS: schizophrenia, antipsychotics drugs, long-term outcomes, clinical practice. Eficácia da clozapina, haloperidol e clorpromazina na esquizofrenia em um período de cinco anosResumo -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 f...

A systematic review of the evidence of clozapine's anti-aggressive effects

“…It may be that patients on clozapine experience fewer side-effects or that the side-effects they experience are better tolerated, monitored or managed (Leucht et al 2009a, b ;Ravanic et al 2009). However, adverse effects were rarely discussed or investigated in the vast majority of studies reviewed.…”

Human endogenous retroviruses and the nervous system

“…The disparity between previous reports showing increased HERV-W expression in schizophrenia (Karlsson et al, 2001, 2004) may reflect different experimental approaches (specifically choice of PCR primers) or differential use of anti-psychotic medications by schizophrenia patients, specifically haloperidol and clozapine, which are known to dampen retroviral expression (Jones-Brando et al, 1997; Schifitto et al, 2009). Clinically, long-term treatment of schizophrenia patients with clozapine showed better effectiveness than other typical antipsychotics (Ravanic et al, 2009; Agid et al, 2010), although it is not known if this has any relation to suppression of HERV activity in the CNS. Another group reported the increase in HERV-W in patients with schizophrenia being treated with valproate.…”

Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects

“…Occupancy of clozapine at D 2 receptors is between 38–63% at normal doses, which is below the threshold for inducing EPS. Long‐term clozapine therapy showed greater efficacy in the treatment of the positive symptoms and negative signs of schizophrenia compared with typical antipsychotic drugs (Ravanic et al. 2009).…”

“…Occupancy of clozapine at D 2 receptors is between 38-63% at normal doses, which is below the threshold for inducing EPS. Long-term clozapine therapy showed greater efficacy in the treatment of the positive symptoms and negative signs of schizophrenia compared with typical antipsychotic drugs (Ravanic et al 2009). Olanzapine, a clozapine-like antipsychotic, is classified as a thienobenzodiazepine, which is also effective for treating negative signs and positive schizophrenic symptoms but induces low incidence of EPS.…”