Efficacy and tolerability of clozapine in Japanese patients with treatment-resistant schizophrenia: Results from a 12-week, flexible dose study using raters masked to antipsychotic choice

Kishi, Taro; Fujita, Kiyoshi; Furukawa, Osamu; Suzuki, Tatsuyo; Moriwaki, Masatsugu; Nitta, Mari; Hattori, Miho; Tsunoka, Tomoko; Chekuri, Raja; Kane, John M.; Correll, Christoph U.; Iwata, Nakao

doi:10.1016/j.ajp.2012.10.007

Cited by 23 publications

(21 citation statements)

References 19 publications

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“…The sample size of the studies ranged from 15 [ 56 ] to 202 [ 57 ]. The mean age (data unavailable from [ 58 , 59 ]) of participants was 39.2 years (range: 28.2 [ 60 ]–47.6 years [ 61 ]) and 71% were male (gender data unavailable from [ 59 ]). The mean clozapine dose used (data missing from [ 59 ]) was 381 mg (SD = 138 mg).…”

Section: Resultsmentioning

confidence: 99%

“…For our study, we extracted data from the Clozaril-alone arm of the crossover study [ 62 ], as the prevalence of constipation within both arms over the study was unclear and this arm provided more data. Additionally, eight prospective studies [ 17 , 49 , 58 , 61 , 65 , 66 , 67 , 68 ], six retrospective cohort studies [ 48 , 50 , 56 , 57 , 59 , 69 ], and four cross-sectional studies [ 24 , 70 , 71 , 72 ] were included. Of the 21 studies that reported on the prevalence rate of clozapine-associated constipation, one was carried out across more than one geographical region [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

“…Of the 21 studies that reported on the prevalence rate of clozapine-associated constipation, one was carried out across more than one geographical region [ 63 ]. Five studies were carried out in Europe [ 24 , 57 , 63 , 68 , 70 ], seven in North America [ 17 , 45 , 50 , 59 , 60 , 63 , 64 , 65 , 72 ], six in Asia [ 49 , 56 , 58 , 61 , 63 , 66 ], two in Africa [ 62 , 71 ], one in the Middle East [ 48 ], and one in Oceania [ 69 ]. Nine studies were conducted in in-patient settings ( n = 395) [ 17 , 48 , 49 , 50 , 58 , 59 , 60 , 61 , 65 ], 10 involved outpatients ( n = 627) [ 24 , 56 , 57 , 62 , 66 , 68 , 69 , 70 , 71 , 72 ], and two included patients from mixed settings ( n = 56) [ 63 , 64 ].…”

Section: Resultsmentioning

confidence: 99%

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Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis

Shirazi

Stubbs

Gómez

et al. 2016

IJMS

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Constipation is a frequently overlooked side effect of clozapine treatment that can prove fatal. We conducted a systematic review and meta-analysis to estimate the prevalence and risk factors for clozapine-associated constipation. Two authors performed a systematic search of major electronic databases from January 1990 to March 2016 for articles reporting the prevalence of constipation in adults treated with clozapine. A random effects meta-analysis was conducted. A total of 32 studies were meta-analyzed, establishing a pooled prevalence of clozapine-associated constipation of 31.2% (95% CI: 25.6–37.4) (n = 2013). People taking clozapine were significantly more likely to be constipated versus other antipsychotics (OR 3.02 (CI: 1.91–4.77), p < 0.001, n = 11 studies). Meta-regression identified two significant study-level factors associated with constipation prevalence: significantly higher (p = 0.02) rates of constipation were observed for those treated in inpatient versus outpatient or mixed settings and for those studies in which constipation was a primary or secondary outcome measure (36.9%) compared to studies in which constipation was not a specified outcome measure (24.8%, p = 0.048). Clozapine-associated constipation is common and approximately three times more likely than with other antipsychotics. Screening and preventative strategies should be established and appropriate symptomatic treatment applied when required.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis

Shirazi

Stubbs

Gómez

et al. 2016

IJMS

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“…However, Kishi et al reported efficacy and tolerability of clozapine in Japanese patients with TRS and described the incidence of seizure in Japanese patients as 5.26%. 17 Our study involved a small number of patients, so we cannot conclude that Japanese patients with schizophrenia have a higher risk of seizure with clozapine use; additional studies with larger samples are needed to verify our observation. White and Van Cott 18 described the treatment of clozapine-associated seizures with dosage reduction and/or the addition of an antiepileptic drug.…”

Section: Discussionmentioning

confidence: 82%

Clozapine-induced seizures, electroencephalography abnormalities, and clinical responses in Japanese patients with schizophrenia

Kikuchi¹,

Sato²,

Ataka³

et al. 2014

NDT

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PurposeWe describe electroencephalography (EEG) abnormalities and seizures associated with clozapine treatment in Japanese patients with schizophrenia and retrospectively compare EEG results and total Positive and Negative Syndrome Scale (PANSS [T]) scores before and after treatment.MethodsTwenty-six patients with treatment-resistant schizophrenia were enrolled in this study. EEG measurements were obtained prior to clozapine treatment and every 4 weeks thereafter. EEG measurements were also obtained at the time of seizure. After seizures or EEG abnormalities were noted, additional EEGs were performed every 2 weeks. PANSS (T) scores were used to determine clozapine treatment outcome.ResultsAll 26 patients had normal baseline EEG measurements, and ten patients (38.5%) later manifested EEG abnormalities. The mean age was significantly lower than in the abnormal EEG group. Six patients (23.1%) experienced seizures. The mean dose of clozapine at the first occurrence of seizure was 383.3 mg/day. Five of six patients who experienced seizures in this study were successfully treated with valproate or lamotrigine without discontinuation of clozapine. The one patient who continued to experience seizures was successfully treated without antiepileptic drugs. The mean baseline PANSS (T) scores were not significantly different between the normal and abnormal EEG groups, but the mean score in the abnormal EEG group was significantly lower than that in the normal EEG group at the final follow-up (P=0.02).ConclusionEEG abnormalities may appear in younger patients, and our findings indicate that there is no need to discontinue clozapine when seizures occur. EEG abnormalities that appeared after clozapine treatment were associated with a good clinical response.

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“… 1 ) Hypersalivation occurs in 31.0–97.4% of patients treated with CLZ. 2 , 3 ) It usually develops early in the course of treatment, but physicians often take longer to recognize hypersalivation than they do to detect agranulocytosis or other side effects. 4 ) For this reason, some patients find it difficult to continue with CLZ treatment.…”

Section: Introductionmentioning

confidence: 99%

Effect of Scopolamine Butylbromide on Clozapine-induced Hypersalivation in Schizophrenic Patients: A Case Series

Takeuchi

Suzuki²,

Kishi³

et al. 2015

Clin Psychopharmacol Neurosci

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Clozapine has been demonstrated to be useful for treating refractory schizophrenia. However, hypersalivation occurs in 31.0–97.4% of the patients treated with clozapine. Accordingly, some patients who are disturbed by their hypersalivation refuse to continue with clozapine treatment. This study investigated the efficacy of the anticholinergic agent scopolamine butylbromide against clozapine-induced hypersalivation. Five schizophrenia patients were coadministered scopolamine butylbromide (30–60 mg/day) for 4 weeks. At the baseline and after 4 weeks’ treatment, we subjectively evaluated hypersalivation using a visual analog scale and objectively assessed it using the Drooling Severity Scale and Drooling Frequency Scale. As a result, improvements in the patients’ Drooling Severity Scale and Drooling Frequency Scale scores, but no improvements in their visual analog scale scores, were observed after scopolamine butylbromide treatment. These results indicate that at least some schizophrenic patients with clozapine-induced hypersalivation would benefit from scopolamine butylbromide treatment. We conclude that clozapine-induced hypersalivation is one factor of stress to patients. Subjective hypersalivation was not improved, but objective hypersalivation was, by scopolamine butylbromide treatment. However, scopolamine butylbromide and clozapine possess anticholinergic effects so clinicians should closely monitor patients who take scopolamine butylbromide.

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Efficacy and tolerability of clozapine in Japanese patients with treatment-resistant schizophrenia: Results from a 12-week, flexible dose study using raters masked to antipsychotic choice

Cited by 23 publications

References 19 publications

Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis

Prevalence and Predictors of Clozapine-Associated Constipation: A Systematic Review and Meta-Analysis

Clozapine-induced seizures, electroencephalography abnormalities, and clinical responses in Japanese patients with schizophrenia

Effect of Scopolamine Butylbromide on Clozapine-induced Hypersalivation in Schizophrenic Patients: A Case Series

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