Parenteral Clozapine: Five Years of Experience

Lokshin, Pavel; Lerner, Vladimir; Miodownik, Chanoch; Dobrusin, M.; Belmaker, Robert H.

doi:10.1097/00004714-199910000-00018

Cited by 10 publications

(19 citation statements)

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“…This suggests that the prescription of intramuscular clozapine may achieve long-term clinical improvement and adherence to oral medication, even in those patients who are initially reluctant to engage with clozapine treatment, and that this is maintained even in a less restrictive setting. Consistent with previous studies, 9,11,13 our data found no evidence that intramuscular clozapine differs markedly from oral clozapine tolerability and adverse effects, with the one reported adverse event related to its formulation being swelling at the injection site. However, the lack of additional side-effects reported may be attributed to its short-term use, often during titration and therefore at low doses, and this study was not powered nor designed to assess safety.…”

Section: Discussionsupporting

confidence: 91%

“…Presently, few naturalistic studies have demonstrated the potential of intramuscular clozapine in initiating treatment, with a total enrolment of approximately 100 patients. [9][10][11][12][13] To our knowledge, this is the largest study in the UK to report the use of short-acting intramuscular clozapine for treatment initiation and maintenance in patients with a treatment-resistant psychotic disorder. Our study further adds to the evidence for intramuscular clozapine as a viable tool to allow patients whose illness is compromising their capacity to consent to appropriate treatment for their treatment-resistant psychotic disorder to access and benefit from clozapine.…”

Section: Discussionmentioning

confidence: 99%

“…Although compulsory administration of medication is not uncommon in psychiatric care, this is rarely used with clozapine treatment, with only a few facilities worldwide reporting the use of nasogastric 8 and intramuscular clozapine. [9][10][11][12][13] In this study, we present our 3-year experience with short-acting intramuscular clozapine in the South London and Maudsley NHS Foundation Trust (SLaM).…”

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confidence: 99%

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A retrospective study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis

et al. 2020

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BackgroundClozapine is uniquely effective in treatment-resistant psychosis but remains underutilised, partly owing to psychotic symptoms leading to non-adherence to oral medication. An intramuscular formulation is available in the UK but outcomes remain unexplored.AimsThis was a retrospective clinical effectiveness study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis over a 3-year period.MethodSuccessful initiation of oral clozapine after intramuscular prescription was the primary outcome. Secondary outcomes included all-cause clozapine discontinuation 2 years following initiation, and 1 year after discharge. Discontinuation rates were compared with a cohort prescribed only oral clozapine. Propensity scores were used to address confounding by indication.ResultsAmong 39 patients prescribed intramuscular clozapine, 19 received at least one injection, whereas 20 accepted oral clozapine when given an enforced choice between the two. Thirty-six (92%) patients successfully initiated oral clozapine after intramuscular prescription; three never transitioned to oral. Eight discontinued oral clozapine during the 2-year follow-up, compared with 83 out of 162 in the comparator group (discontinuation rates of 24% and 50%, respectively). Discontinuation rates at 1-year post-discharge were 21%, compared with 44% in the comparison group. Intramuscular clozapine prescription was associated with a non-significantly lower hazard of discontinuation 2 years after initiation (hazard ratio 0.39, 95% CI 0.14–1.06) and 1 year after discharge (hazard ratio 0.37, 95% CI 0.11–1.24). The only reported adverse event specific to the intramuscular formulation was injection site pain and swelling.ConclusionsIntramuscular clozapine prescription allowed transition to oral maintenance in an initially non-adherent cohort. Discontinuation rates were similar to patients only prescribed oral clozapine and comparable to existing literature.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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A retrospective study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis

et al. 2020

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“…When we identified a study that was eligible, but did not contain sufficient data to enable inclusion in the meta-analysis, we contacted the corresponding authors twice over a month to acquire the data [ 10 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ].…”

Section: Methodsmentioning

confidence: 99%

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

Shirazi

Stubbs

Gómez

et al. 2016

IJMS

102

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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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“…One patient continued with IM clozapine for 8 days. There were no adverse events reported, though patients were already established on clozapine for 'a few weeks' prior to the use of parenteral clozapine (Lokshin et al, 1999). Seventeen patients with TRS were identified for treatment with IM clozapine in a Dutch cohort (Schulte et al, 2007), of whom ten started IM injections, while 7 chose oral clozapine in preference.…”

Section: Clozapine Refusalmentioning

confidence: 99%

Treatment resistant schizophrenia – review and a call to action

Lally

Gaughran

2018

Ir. j. psychol. Med.

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Recovery rates in schizophrenia remain suboptimal with up to one-third resistant to standard treatments, a population prevalence of 0.2%. Clozapine is the only evidenced-based treatment for treatment resistant schizophrenia (TRS), yet there are significant delays in its use or it may not be trialled, potentially impacting the chance of recovery. Better outcomes with earlier use of clozapine may be possible. There is emerging evidence that early treatment resistance is not uncommon from the earliest stages of psychosis. In this review, we provide an update on TRS, its epidemiology and its management, with a specific focus on the optimal use and timing of clozapine and augmentation strategies for the one-third of patients who do not respond to clozapine.

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Parenteral Clozapine: Five Years of Experience

Cited by 10 publications

References 1 publication

A retrospective study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis

A retrospective study of intramuscular clozapine prescription for treatment initiation and maintenance in treatment-resistant psychosis

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

Treatment resistant schizophrenia – review and a call to action

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