Management of clozapine-resistant schizophrenia

Kerwin, R. W.; Bolonna, A. A.

doi:10.1192/apt.11.2.101

Cited by 40 publications

(26 citation statements)

References 34 publications

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“…For clozapine-resistant schizophrenia, a variety of pharmacological and non-pharmacological approaches, including electroconvulsive therapy (ECT), have been tried as adjunct therapies 6. The reported advantages of various psychotropic drugs that is the most frequently attempted strategy have been known as modest or equivocal 56789. ECT augmentation has been continued ever since the re-introduction of clozapine in the 1990s10 and the effectiveness of ECT in patients on clozapine has been reported in two randomized controlled studies,411 as well as in case reports and open trials 51213141516171819.…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of Electroconvulsive Therapy Augmentation on Clozapine-Resistant Schizophrenia

Kim

Lee

et al. 2017

Psychiatry Investig

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ObjectiveThis retrospective case series study of the effectiveness of electroconvulsive therapy (ECT) augmentation on clozapine-resistant schizophrenia was conducted by EMR review.MethodsClozapine-resistance was defined as persistent psychotic symptoms despite at least 12 weeks of clozapine administration with blood levels over 350 ng/mL in order to rule out pseudo-resistance. Seven in-patients who were taking clozapine and treated with ECT were selected. We analyzed the psychopathology and subscales changed by ECT.ResultsThe average number of ECT sessions was 13.4 (±4.6). Total Positive and Negative Syndrome Scale (PANSS) score was significantly reduced by 17.9 (±12.8) points (p=0.0384) on average, which represented a reduction of 25.5% (±14.3). 71.4% (5/7) of patients were identified as clinical remission, with at least a 20% reduction in PANSS score. PANSS reduction was associated with number of ECT sessions, stimulus level in the final session, and blood clozapine levels before ECT. However, the negative subscale on the PANSS were not reduced by ECT in any patient. We did not observe any persistent adverse cognitive effects.ConclusionThis study supports that ECT augmentation on clozapine-resistant schizophrenia reveals clinically effective and safe. Further research should be done involving a larger number of patients to investigate the effectiveness of clozapine/ECT combination therapy.

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Section: Introductionmentioning

confidence: 99%

Effectiveness of Electroconvulsive Therapy Augmentation on Clozapine-Resistant Schizophrenia

Kim

Lee

et al. 2017

Psychiatry Investig

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“…Roughly 20% of people suffering from schizophrenia do not improve with first-line antipsychotics treatment and therefore are categorized as individuals with refractory schizophrenia. Some patients can only achieve remission with the use of clozapine (Kerwin and Bolonna, 2005). Although clozapine is well known for superior efficacy over other antipsychotics, it requires careful management of the potential side effects.…”

Section: Introductionmentioning

confidence: 99%

“…Clozapine was the first atypical antipsychotic available in the US market, and since then it has been used as the gold standard for the treatment of refractory schizophrenia (Kerwin and Bolonna, 2005). Clozapine works by decreasing positive symptoms such as hallucinations, delusions, and disorganized thought patterns as well as negative symptoms that include lack of motivation, pleasure, and diminished ability to communicate.…”

Section: Introductionmentioning

confidence: 99%

Maximizing clozapine utilization while minimizing blood dyscrasias

Demler

Morabito

Meyer

et al. 2016

International Clinical Psychopharmacology

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The aim of this study was to determine whether patient characteristics such as age, sex, race/ethnicity, and frequency of monitoring play a role in clozapine-related blood dyscrasias. This study examined all neutropenic events to identify any potential demographic qualities that may pose increased risk to individuals receiving clozapine treatment in accordance with the FDA guidelines released in 2005. These guidelines required the addition of absolute neutrophil count (ANC) tests in addition to white blood cell (WBC) counts to regular monitoring and a reduction in the frequency of testing to once monthly after 1 year of satisfactory WBC counts and ANCs. The previous schedule neither included ANC testing nor allowed for further reductions in the frequency of testing after 1 year, with patients continuing to be tested every 2 weeks indefinitely. This is a retrospective, closed chart review of all patients who received clozapine at the State Psychiatric Center and experienced a leukopenic/neutropenic event and/or who had a substantial drop in WBC/ANC from January 2009 to December 2011. A subset of patients who were identified as achieving 'non-rechallengeable' status with either an ANC and/or WBC threshold value from 2001 to 2014 were also examined. This protocol was approved by the New York State Psychiatric Institute Institutional Review Board. A total of 193 patients were included in the study. Males experienced more total events at 6.4 events per person compared with 5.2 events per woman. White patients had 6.5 total events per person compared with 4.2 total events per Black patient; however, Black patients experienced more moderate leukopenia/granulocytopenia events compared with Whites. Regardless of race or ethnicity, patients in the 40-49-year age range had the most events at 8.1 events per person and also presented with the highest number of moderate leukopenia/granulocytopenia events as did those scheduled for weekly monitoring. Conversely, the majority of patients with no recorded events were female and either 20-29 or 60-69 years of age. In total, 16 patients were exclusively designated as non-rechallengeable from 2001 to 2014 and only had one single blood event prompting this clozapine monitoring status. Of these 16 patient events, seven were White males, eight were White females, and one was a Black female with roughly 40% of those patients in the 50-59-year age group. Currently published predictions on possible demographic risk groups may not reflect clinical experience and may pose unnecessary treatment barriers in the provision of clozapine. Although the healthcare team should be aware of the possible demographic predictors of blood dyscrasias when using clozapine, treatment goals and monitoring strategies must be individualized to ensure successful clozapine therapy.

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“…The criteria employed by Kane et al to define treatment-resistant (or treatment-refractory) schizophrenia in the pivotal trial comparing clozapine to chlorpromazine is used frequently in clinical trials and audit settings 26,27. Kane et al classified participants as treatment-resistant if: improvement had not been demonstrated after 3 periods of treatment with antipsychotics (from 2 or more different chemical classes) in the previous 5 years equivalent to 1000 mg/day of chlorpromazine (CPZ) for 6 weeks and participants had had no episodes of good functioning in the previous 5 years, Brief Psychiatric Rating Scale (BPRS) total score ≥ 45, Clinical Global Impressions (CGI) score ≥ 4, and score ≥ 4 on 2 or 4 positive symptoms items 26.…”

Section: Introductionmentioning

confidence: 99%

Pharmacotherapy for treatment-resistant schizophrenia

McIlwain¹,

Harrison²,

Wheeler³

et al. 2011

NDT

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Schizophrenia is a disabling mental illness with a lifetime prevalence of 0.7% worldwide and significant, often devastating, consequences on social and occupational functioning. A range of antipsychotic medications are available; however, suboptimal therapeutic response in terms of psychotic symptoms is common and affects up to one-third of people with schizophrenia. Negative symptoms are generally less amenable to treatment. Because of the consequences of inadequate symptom control, effective treatment strategies are required for people with treatment-resistant schizophrenia. Clozapine has been shown to be more effective than other antipsychotics in treatment-resistant populations in several studies; however, the occurrence of adverse effects, some of which are potentially life-threatening, are important limitations. In addition to those who are intolerant to clozapine, only 30% to 50% experience clinically significant symptom improvement. This review describes the recent evidence for treatment strategies for people not responding to nonclozapine antipsychotic agents and people not responding or only partially responding to clozapine.

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Management of clozapine-resistant schizophrenia

Cited by 40 publications

References 34 publications

Effectiveness of Electroconvulsive Therapy Augmentation on Clozapine-Resistant Schizophrenia

Effectiveness of Electroconvulsive Therapy Augmentation on Clozapine-Resistant Schizophrenia

Maximizing clozapine utilization while minimizing blood dyscrasias

Pharmacotherapy for treatment-resistant schizophrenia

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