Schizophrenia Bulletin Advance Access originally published online on May 20, 2008
Schizophrenia Bulletin 2008 34(4):611-612; doi:10.1093/schbul/sbn043
© The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.
Pharmacological Interventions for Clozapine-induced Hypersalivation
Rebecca J. Syed Sheriff1,2,
Katie Au3,
Caroline Cahill4,
Lorna Duggan5,
Yanling He6,
Victor Udu4 and
Jun Xia7
2 Health Services and Population Research Department, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK
3 King's College Hospital, Denmark Hill, London SE5 9RS, UK
4 St Andrew's Hospital, Spring Hill, Cliftonville, Northampton NNH1 5BE, UK
5 Developmental Disabilities Division, St Andrew's Hospital, Billing Road, Northampton, Northamptonshire NN1 5DG, UK
6 Department of Psychiatric Epidemiology, Shanghai Mental Health Center, Shanghai, China
7 Cochrane Schizophrenia Group, University of Leeds, Leeds, West Yorkshire LS2 9LT, UK
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Background
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Clozapine is widely used for people with schizophrenia. Agranulocytosis,
weight gain, and cardiac problems are serious problems associated
with clozapine use. Hypersalivation, sometimes of a gross and
socially unacceptable quantity, is also common (30%–80%).
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Objectives
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To determine the clinical effects of pharmacological interventions
for clozapine-induced hypersalivation.
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Search strategy
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The Cochrane Schizophrenia Group Trials Register (March 2007)
is compiled by systematic searches of major databases, journals,
and conference proceedings.
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Selection criteria
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All relevant randomized controlled trials.
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Data collection and analysis
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We selected and extracted data independently. For dichotomous
data (homogenous), we calculated relative risk (RR) with 95%
confidence intervals (CIs) and numbers needed to treat (NNT)
on an intention-to-treat basis.
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Main results
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In total 15 trials were identified. Fourteen trials were conducted
in China and14 trials were conducted in the hospital setting.
The quality of reporting was poor with no studies clearly describing
allocation concealment. Much data were missing or unusable due
to poor reporting. The primary outcome was often the diameter
of wet patch on the pillow. Antimuscarinics were commonly the
focus of these trials (astemizole, diphenhydramine, propantheline,
and doxepin). For the outcome of "no clinically important change,"
see
figure 1, astemizole and diphenhydramine were more effective
than placebo (astemizole: n = 97, 2 randomised controlled trials
[RCTs], RR 0.61, CI 0.47 to 0.81, NNT 3, CI 2 to 5; diphenhydramine:
n = 131, 2, RR 0.42, CI 0.31 to 0.58, NNT 2, CI 1.5 to 2.5),
but the doses of astemizole used were those that can cause toxicity.
Data involving propantheline were heterogeneous (
I2 = 86.6%),
but both studies showed a benefit over placebo. For the antimuscarinics,
there were no differences in adverse effects, compared with
either each other or placebo. More detailed findings are to
be reported in the full version of this review.
1
Of the other interventions, oryzanol (rice bran oil and rice
embryo oil extract) showed benefit over the antimuscarinic doxepin
in terms of "no clinically important change" (n = 104, 1 RCT,
RR 0.45, CI 0.27 to 0.75, NNT 4, CI 2 to 7). The Chinese medicine
Suo quo wan (comprises spicebush root, Chinese yam, and bitter
cardamom) showed benefit over doxepin (n = 70, 1 RCT, RR "no
clinically important change" 0.31, CI 0.16–0.59, NNT 3,
CI 1.5 to 3.7).
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Reviewers' conclusions
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Treatments for this problematic adverse effect are poorly investigated.
The studies are small, and the quality of reporting suggests
that the risk of bias is high.
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Implications for practice and research
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A few important trials exist but are insufficient to direct
clinical care. We found no trials of drugs such as hyoscine.
Considering the potency and potential toxicity of these adjunctive
treatments, trials investigating the value of any intervention
used for clozapine-induced hypersalivation are indicated.
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Footnotes |
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1 To whom correspondence should be addressed; tel: (0)20-7848-0136, fax: (0)20-7848-5450, e-mail: rebecca.syed{at}iop.kcl.ac.uk.
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References
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- Syed Sheriff RJ, Au K, Cahill C, Duggan L, He Y, Udu V, Xia J. Pharmacological interventions for clozapine-induced hypersalivation. Cochrane Database Syst Rev. (2008) (3).
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Background
Objectives