Clozapine is the only drug specifically indicated for treatment-resistant schizophrenia and also for treatment of patients with high risk o suicide and aggressive behavior. A meta-analysis of randomized clinical trials confirmed its superiority in this patient population compared with other antipsychotics, both
first- and second-generation. A growing number of reports suggest that clozapine may also have a role in other psychiatric conditions such as manic episode. Some patients, however, do not have an adequate response to clozapine. As with other medications, adherence and pharmacokinetic matters must be addressed. This project was a 24-months noninterventional and observational study from January 2009 to December 2010, conducted in Clinical Department for acute patients belonging to the Psychiatry and
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Neurology Hospital, the most important in the region. Patients with age above 18 years were considered for entry into the study if they were eligible according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) as having schizophrenia in acute exacerbation. Our study was designed to investigate the treatment management of a really heterogeneous patients with schizophrenia hospitalized for acute exacerbation in a naturalistic setting of acute psychiatric departments and to identify the patterns of treatment used by the psychiatrist when they decided to use clozapine.
Investigators recorded all the data about the patients (gender, age, age of onset of schizophrenia, marital status, education, type of assurance, number of days of hospitalization) and data regarding
pharmacotherapy that had been prescribed during hospitalization. Patient’s demographics and illness
characteristics were analyzed using descriptive statistics. We used Analysis of variance (ANOVA) including post-hoc comparisons to test the difference between means in first generation antipsychotics
(FGA) and second generation antipsychotics (SGA) groups. Categorical data were analyzed using Chi-square test. All calculations were made by Stat Soft Statistics v.4.5. Statistical significance was set at P value less than 0.05. A total of 273 patients hospitalized for an acute exacerbation of schizophrenia
entered into the study. The vast majority of patients met the criteria for paranoid schizophrenia (74.8%), followed by undifferentiated schizophrenia (21.3%), disorganized schizophrenia (1.2%) and catatonic type (0.08%). The mean age across the group was 42.67 years (SD=11.2) with significant difference between female and male (female mean age was 44.25 and male mean age was 41.1, p<0.001). It was also a difference between female and male regarding the age of onset schizophrenia; the mean age of onset of
schizophrenia in male was with 2.9 years earlier than in female cases (25.63 vs.28.52, p<0.001). The mean schizophrenia duration was 15.72 years (SD=9.4), being higher in women than men (16.91 vs.14.54). The level of education of the group was relatively high, with mean years of education above 10 years of studies, greater in male cases. The results of hospitalization indicated a mean of 22.25 days (SD=10.50), almost equal for female and male. The mean age of onset of schizophrenia was statistically significant lower in male patients treated with SGAs compared with those treated with FGAs (24.62 vs. 26.84, p<0.001). An important aspect of our study was to evaluate the combinations used in treatment of schizophrenia indicated at discharge after an acute episode. All patients with schizophrenia under
study were treated with first or second generation antipsychotics in different proportions. Of 273 patients treated with ,,atypical†received amisulpride (25.27%), aripiprazole (0.7%), clozapine (26.37%),
olanzapine (27.73%), quetiapine (7.32%) and risperidone (13.55%). There were only 14 patients who
received FGAs alone at discharge (6.70%) compared with 93 patients who received mono-therapy with SGAs (34.06%, p<0.0001). Combination between FGAs and benzodiazepine was indicated in 11.00% of
cases being lower than in SGAs and benzodiazepine with was prescribed in 19.41% of cases (p = 0.01). The number of patients who received antiparkinsonian compounds in combination with antipsychotics was significantly higher for FGA (p=0.0004). The combination antipsychoticbenzodiazepine-mood stabilizer triple combination was found in approximately equal proportions for the two types of
antipsychotics (p = 0.69). The number of patients who have had their treatment regimen at discharge with a combination included antipsychoticbenzodiazepine-mood stabilizer and antiparkinsonian was significantly greater in FGAs cases (16.27%) compared with SGAs (2.93%), p<0.0006. Analysis of
variance between the type of treatment chosen at discharge and the average length of hospitalization revealed no statistically significant differences between the group treated with FGAs and SGAs, the values obtained were approximately equal. It was a significant difference between atypical antipsychotics in terms of psychotropic added; amisulpride was prescribed alone in 4.35% cases and was associated most frequently with benzodiazepine, mood stabilizers or both of them compared with olanzapine and
clozapine (p<0.005). The treatment with clozapine alone was recorded in 50%. We observed many
similarities between treatment with clozapine and olanzapine (the almost same percentage regarding number of patients treated with those antipsychotics and the number of patients who needed
benzodiazepine and mood stabilizers). There were no significant differences regarding hospitalization, gender and type of antipsychotic treatment between the two groups. The mean duration of illness was greater in group treated with FGAs compared with SGAs group and it was significant for male (p<0.001). Our observational study was the first study in Romania who intended to explore the patterns in antipsychotic treatment with clozapine in patients with schizophrenia in terms of demographics, hospitalization duration and necessity of other psychotropic compounds. Despite treatment guidelines and consensus of experts in psychiatry, the severity of schizophrenia frequently required adaptation of treatment and therapeutic combinations that often exceed imposed boundaries. In our study we noted the high percentage of patients who received treatment with clozapine, often in attempting to resolve psychotic symptoms or extreme agitation. Although all antipsychotics have been used in therapeutic doses, most times the maximum recommended dose, lack of therapeutic response in many cases required a combination of a benzodiazepine or mood stabilizer even in a clozapine case. The challenge of treatment-resistant schizophrenia with agitation or high risk of aggressive behavior continues despite the advent of a second-generation class of antipsychotics. Further research in treatment of schizophrenia is clearly needed to address the needs of patients who remain substantially symptomatic and disabled even with the use of currently available antipsychotic agents. In Romania, psychiatrists exhibited different approach of clinical concepts and on prescription guidelines of antipsychotics and they are influenced by patient’s age and personal experience. It is necessary to reach a consensus to establish and standardize the treatment of schizophrenia, based on the information reported in naturalistic trials to avoid inadequate treatments in schizophrenia. 1062 words
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