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Clozapine dose for schizophrenia

Overview of attention for article published in Cochrane database of systematic reviews, June 2017
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (92nd percentile)
  • Good Attention Score compared to outputs of the same age and source (73rd percentile)

Mentioned by

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1 news outlet
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35 tweeters
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1 Facebook page

Citations

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12 Dimensions

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110 Mendeley
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Title
Clozapine dose for schizophrenia
Published in
Cochrane database of systematic reviews, June 2017
DOI 10.1002/14651858.cd009555.pub2
Pubmed ID
Authors

Selvizhi Subramanian, Birgit A Völlm, Nick Huband

Abstract

Schizophrenia and related disorders such as schizophreniform and schizoaffective disorder are serious mental illnesses characterised by profound disruptions in thinking and speech, emotional processes, behaviour and sense of self. Clozapine is useful in the treatment of schizophrenia and related disorders, particularly when other antipsychotic medications have failed. It improves positive symptoms (such as delusions and hallucinations) and negative symptoms (such as withdrawal and poverty of speech). However, it is unclear what dose of clozapine is most effective with the least side effects. To compare the efficacy and tolerability of clozapine at different doses and to identify the optimal dose of clozapine in the treatment of schizophrenia, schizophreniform and schizoaffective disorders. We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (August 2011 and 8 December 2016). All relevant randomised controlled trials (RCTs), irrespective of blinding status or language, that compared the effects of clozapine at different doses in people with schizophrenia and related disorders, diagnosed by any criteria. We independently inspected citations from the searches, identified relevant abstracts, obtained full articles of relevant abstracts, and classified trials as included or excluded. We included trials that met our inclusion criteria and reported useable data. For dichotomous data, we calculated the relative risk (RR) and the 95% confidence interval (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD) again based on a random-effects model. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. We identified five studies that could be included. Each compared the effects of clozapine at very low dose (up to 149 mg/day), low dose (150 mg/day to 300 mg/day) and standard dose (301 mg/day to 600 mg/day). Four of the five included studies were based on a small number of participants. We rated all the evidence reported for the main outcomes of interest as low or very low quality. No data were available for the main outcomes of global state, service use or quality of life. Very low dose compared to low doseWe found no evidence of effect on mental state between low and very low doses of clozapine in terms of average Brief Psychiatric Rating Scale-Anchored (BPRS-A) endpoint score (1 RCT, n = 31, MD 3.55, 95% CI -4.50 to 11.60, very low quality evidence). One study found no difference between groups in body mass index (BMI) in the short term (1 RCT, n = 59, MD -0.10, 95% CI -0.95 to 0.75, low-quality evidence). Very low dose compared to standard doseWe found no evidence of effect on mental state between very low doses and standard doses of clozapine in terms of average BPRS-A endpoint score (1 RCT, n = 31, MD 6.67, 95% CI -2.09 to 15.43, very low quality evidence). One study found no difference between groups in BMI in the short term (1 RCT, n = 58, MD 0.10, 95% CI -0.76 to 0.96, low-quality evidence) Low dose compared to standard doseWe found no evidence of effect on mental state between low doses and standard doses of clozapine in terms of both clinician-assessed clinical improvement (2 RCTs, n = 141, RR 0.76, 95% CI 0.36 to 1.61, medium-quality evidence) and clinically important response as more than 30% change in BPRS score (1 RCT, n = 176, RR 0.93, 95% CI 0.78 to 1.10, medium-quality evidence). One study found no difference between groups in BMI in the short term (1 RCT, n = 57, MD 0.20, 95% CI -0.84 to 1.24, low-quality evidence).We found some evidence of effect for other adverse effect outcomes; however, the data were again limited. Very low dose compared to low doseThere was limited evidence that serum triglycerides were lower at low-dose clozapine compared to very low dose in the short term (1 RCT, n = 59, MD 1.00, 95% CI 0.51 to 1.49). Low dose compared to standard doseWeight gain was lower at very low dose compared to standard dose (1 RCT, n = 27, MD -2.70, 95% CI -5.38 to -0.02). Glucose level one hour after meal was also lower at very lose dose (1 RCT, n = 58, MD -1.60, 95% CI -2.90 to -0.30). Total cholesterol levels were higher at very low compared to standard dose (1 RCT, n = 58, n = 58, MD 1.00, 95% CI 0.20 to 1.80). Low dose compared to standard doseThere was evidence of fewer adverse effects, measured as lower TESS scores, in the low-dose group in the short term (2 RCTs, n = 266, MD -3.99, 95% CI -5.75 to -2.24); and in one study there was evidence that the incidence of lethargy (RR 0.77, 95% CI 0.60 to 0.97), hypersalivation (RR 0.70, 95% CI 0.57 to 0.84), dizziness (RR 0.56, 95% CI 0.39 to 0.81) and tachycardia (RR 0.57, 95% CI 0.45 to 0.71) was less at low dose compared to standard dose. We found no evidence of effect on mental state between standard, low and very low dose regimes, but we did not identify any trials on high or very high doses of clozapine. BMI measurements were similar between groups in the short term, although weight gain was less at very low dose compared to standard dose in one study. There was limited evidence that the incidence of some adverse effects was greater at standard dose compared to lower dose regimes. We found very little useful data and the evidence available is generally of low or very low quality. More studies are needed to validate our findings and report on outcomes such as relapse, remission, social functioning, service utilisation, cost-effectiveness, satisfaction with care, and quality of life. There is a particular lack of medium- or long-term outcome data, and on dose regimes above the standard rate.

Twitter Demographics

The data shown below were collected from the profiles of 35 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 110 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 110 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 24 22%
Student > Bachelor 16 15%
Student > Ph. D. Student 15 14%
Researcher 12 11%
Other 10 9%
Other 18 16%
Unknown 15 14%
Readers by discipline Count As %
Medicine and Dentistry 39 35%
Psychology 12 11%
Nursing and Health Professions 12 11%
Social Sciences 7 6%
Pharmacology, Toxicology and Pharmaceutical Science 5 5%
Other 12 11%
Unknown 23 21%

Attention Score in Context

This research output has an Altmetric Attention Score of 30. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 January 2019.
All research outputs
#610,404
of 14,201,503 outputs
Outputs from Cochrane database of systematic reviews
#1,831
of 10,885 outputs
Outputs of similar age
#20,373
of 268,781 outputs
Outputs of similar age from Cochrane database of systematic reviews
#64
of 241 outputs
Altmetric has tracked 14,201,503 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 10,885 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 21.7. This one has done well, scoring higher than 83% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 268,781 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 92% of its contemporaries.
We're also able to compare this research output to 241 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.