Early use of clozapine for poorly responding first-episode psychosis
ABSTRACT Although most patients treated for first-episode schizophrenia will experience considerable improvement with initial antipsychotic therapy, a subgroup experiences significant ongoing positive symptoms. Clozapine has unique efficacy in improving treatment-resistant patients with chronic schizophrenia, but its role in the treatment of first-episode patients remains unclear. A standardized treatment algorithm was implemented in our First Episode Psychosis Program, with patients receiving 2 trials with 2 second-generation antipsychotics (olanzapine, quetiapine, or risperidone at low, medium, and high doses), followed by a trial of clozapine as early as 25 weeks into the start of their treatment. Patients progress along the algorithm according to their response as defined by clinical rating scales. To date, 123 patients with first-episode schizophrenia have been treated according to the algorithm. Of these, 93 (76%) responded to the first trial of an antipsychotic. Only 7 (23%) of the remaining 30 patients responded to a second antipsychotic trial; 13 of the remaining 23 individuals agreed to a trial of clozapine. We compared the clozapine-treated group with a group of 9 patients who refused clozapine and chose to continue the same antipsychotic treatment as before. Subjects who received clozapine experienced a mean Brief Psychiatric Rating Scale change of 19 points (from 53.5 to 34.5) and a change in the Clinical Global Inventory severity rating from 5.4 to 3.5 (from severely ill to mildly ill); those who refused clozapine had a 2-point increase in mean Brief Psychiatric Rating Scale (from 53 to 55) and a 0.6-point increase in the mean Clinical Global Inventory severity rating from 5.4 to 6 (remaining markedly to severely ill). In clinical practice, there is a hesitancy to switch individuals to clozapine given its side effect profile and position as treatment of "last resort." The present findings suggest that clozapine may have an important role in the early treatment of first-episode patients whose psychosis does not remit with other second-generation antipsychotics during the first months of treatment.
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ABSTRACT: Although the role of clozapine is well established for treatment-resistant schizophrenia, it is rarely used in pediatric populations, mainly due to its potentially serious adverse effects. To summarize practical aspects of use of clozapine in treating children with schizophrenia and management of associated adverse effects. Available studies in the literature using clozapine in the pediatric population are summarized and the NIMH experience in treating refractory childhood-onset schizophrenia cases with clozapine is discussed. Despite a higher incidence of adverse effects in children, clozapine appears to be a uniquely beneficial second-line agent for treating children with refractory schizophrenia.Expert Opinion on Pharmacotherapy 03/2008; 9(3):459-65. DOI:10.1517/14656518.104.22.1689 · 3.09 Impact Factor
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ABSTRACT: To describe the treatment pathway and patterns of clozapine use in patients with schizophrenia, including coprescribed psychotropic medications, and compare the extent of coprescribing of clozapine with that of non-clozapine schizophrenia treatment in community mental health services in the Auckland and Northland regions of New Zealand. A retrospective chart review was conducted for adult outpatients receiving care from community mental health services on October 31, 2004. Data collected for all patients prescribed an antipsychotic included demographics (sex, age, ethnicity); principal diagnosis (Diagnostic and Statistical Manual of Mental Disorders, 4th edition); comorbid conditions; duration of mental illness; psychiatric admissions; and treatment information (psychotropic medications, with dose and route of administration). If clozapine had been started after the introduction of full government prescription subsidy (February 1999), additional data, including year of initiation and prior antipsychotic history, were collected. Analysis included all outpatients with a diagnosis of schizophrenia (including schizoaffective disorder). Antipsychotics were prescribed for 2796 schizophrenia patients; 32.8% were prescribed clozapine, with a mean dose of 372 mg/day and an average duration of illness of 9.7 years before starting clozapine. Patients who had started treatment after clozapine was funded by the government (59.3%) had received a median of 3 antipsychotic drugs prior to starting clozapine; most of the treatment regimens included 1 second-generation antipsychotic (91.2%). Clozapine patients were less likely to be coprescribed another antipsychotic compared with non-clozapine patients (11.7% vs 17.6%; p < 0.001). Both the clozapine and non-clozapine groups had a low total number of psychotropic medications prescribed (median 2); for clozapine patients, the second drug was most likely to be for treatment of hypersalivation. Outpatients with treatment-resistant schizophrenia were prescribed clozapine at expected rates; however, treatment was delayed longer than recommended. There is some evidence that access to clozapine for treatment-resistant schizophrenia has improved, possibly as the result of the introduction of government subsidy, guideline dissemination, or increasing experience of clinicians with use of clozapine. In this real-world environment, the number of concomitant psychotropic medications for outpatients with schizophrenia was found to be low; when used concomitantly with clozapine, they were most commonly used to manage adverse effects.Annals of Pharmacotherapy 06/2008; 42(6):852-60. DOI:10.1345/aph.1K662 · 2.92 Impact Factor