Medicines Q&As
Q&A 54.6
Drug-induced hypersalivation - what treatment options are
available?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
Before using this Q&A, read the disclaimer at www.ukmi.nhs.uk/activities/medicinesQAs/default.asp
Date prepared: 21st June 2012
Background
Hypersalivation, which may manifest as drooling (sialorrhoea), can be caused by medication. This
Q&A summarises published studies or case reports concerning the pharmacological treatment of
drug-induced hypersalivation, although none of the treatments described below are licensed for this
condition. The licensed use of antimuscarinic drugs (e.g. glycopyrronium bromide) as premedicants to
dry bronchial and salivary secretions peri-operatively is not included in this Q&A.
Table 1 lists treatments for clozapine-induced hypersalivation. Table 2 lists treatments for
hypersalivation caused by other drugs.
Answer
Clozapine-Induced Hypersalivation
Many antipsychotics can cause hypersalivation, but it affects around 30% of patients taking clozapine
(reported range 10-80%) (1,2,3). It usually develops early in treatment, is often more prominent at
night, and may reduce compliance (1,2,3,4). The exact mechanism of clozapine-induced
hypersalivation is unknown (2,3,5).
If clozapine dose reduction (in appropriate patients) has not alleviated symptoms and an alternative
antipsychotic is not an option, various pharmacological interventions have been used to manage
hypersalivation (see Table 1 for treatment options). Non-pharmacological strategies (e.g. sugarless
chewing gum) have been recommended first-line but they are often ineffective (2,6,7).
A Cochrane Review to determine the clinical effects of pharmacological interventions (including
traditional Chinese medicines) for clozapine-induced hypersalivation identified 15 trials. The authors
concluded that “There are currently insufficient data to confidently inform clinical practice” and that
“These trials, however, are invaluable guides for current and future study design”. They add that
“Current practice outside of well designed randomised trials should be clearly justified” (8).
Table 1 – Drug Interventions for Clozapine-Induced Hypersalivation.
Intervention
Antimuscarinics
Amitriptyline oral
Report Descriptions
[ref]
Dose of Intervention
(a) Case reports (n=4)
[9]
(b) Case report [10]
(a) 75-100mg per day.
Outcome and notes when
used in clozapine patients
Marked improvement.
(b) 25mg at night.
Beware additive side effects
(e.g. fits, hypotension)
[10,11].
From the NHS Evidence website www.evidence.nhs.uk
1
Medicines Q&As
Table 1 (continued)
Atropine eye
(a) Case report [12]
drops 1%
sublingually
(b) Case reports (n=3)
[6]
(c) Case report [13]
Benzatropine
oral*
(a) Retrospective chart
review (n=60; 15 pts in
each of 4 groups) [16]
(b) Case report [17]
Biperiden oral*
Glycopyrronium
oral* #
Hyoscine
hydrobromide
patch/oral
(a) Randomised,
double-blind crossover
trial vs.
glycopyrronium
(n=13)[18]
(b) Case report [19]
(a) Randomised,
double-blind crossover
trial vs. biperiden
(n=13)[18]
(a) 1-2 drops in the
morning.
(b) 1 drop at night (plus
top-up overnight dose
of 1 drop in water prn
(n=1)).
(c) 2 drops bd.
(a) Benzatropine 1mg
bd vs. terazosin 2mg
nocte vs. both
treatments together vs.
no treatment.
(b) 2mg per day plus
chewing gum.
(a) Biperiden 2mg twice
daily vs.
glycopyrronium 1mg
twice daily.
(b) Uptitrated to 6mg
per day.
(a) See biperiden
above.
(b) Case report [20]
(b) 500 micrograms bd,
increased to 2mg bd
over 10 days.
(c) Case series (n=3)
(aged 13-16) [21]
(c) Dose uptitrated to
2-4mg bd in 2 patients
and from 1mg tds to
2mg tds to 2mg bd in 1
patient.
(a) Case reports (n=4)
[15]
(b) Case report [23]
(a) Patch (dose not
given).
(b) Patch 1.5mg every
72hrs.
(c) 300 microgram
tablet nocte increased
to tds if necessary,
sucked & swallowed.
(c) Anecdotal [3,4]
(a) Resolution.
(b) “Immediate relief”.
(c) Resolution.
Fast relief [6] but may not be
sustained [14]; dropper can
be hard to use with risk of
accidental overdose [14].
Beware additive
anticholinergic side effects
[13] and bitter taste [15].
(a) At 12 weeks, combination
gave 100% satisfactory
response vs 67% for
benzatropine alone and 93%
for terazosin alone.
(b) Improved.
(a) At 4 weeks,
hypersalivation significantly
improved vs. baseline, but
less than glycopyrronium.
Cognitive function reduced.
(b) Hypersalivation
eliminated.
(a) At 4 weeks,
hypersalivation significantly
improved vs. baseline and vs.
biperiden. Cognitive function
unchanged.
(b) Hypersalivation
significantly reduced.
Constipation worsened at
higher dose.
(c) Marked reduction in saliva
flow (n=2). Hypersalivation
resolved (n=1). Extensive
constipation observed (n=1).
Dry mouth (n=1) which
resolved on dose reduction.
(a) Improvement, including
pts failing other treatments.
(b) Persistent improvement.
(c) Widely used in practice
(e.g. Kwells). Beware
cognitive impairment,
drowsiness.
* Not available in UK, but can be imported.
# Glycopyrronium oral solution (Cuvposa®) is licensed in the US (to reduce chronic severe drooling in patients aged 3-16 years
with neurological disorders) [22] and can be imported.
From the NHS Evidence website www.evidence.nhs.uk
2
Medicines Q&As
Table 1 (continued)
Ipratropium
(a) Randomised,
bromide nasal
double-blind, placebospray 0.03%
controlled, crossover
trial (n=20) [24]
(b) Non-comparative
study (n=10) for 6
months [5]
(c) Retrospective noncomparative study
(n=9) [25]
Oxybutynin oral
Pirenzepine oral*
Trihexyphenidyl
(benzhexol)
hydrochloride
oral
(d) Case series (n=10)
[14]. Pts failed on sublingual atropine drops
Case report [26]
(a) Randomised,
double-blind placebocontrolled cross-over
trial (20 Asian
patients) [27]
(b) Case reports
(n=120) [28]
(c) Non-comparative
study (n=29) for 3
days [29]
(a) Non-comparative
study (n=14) for 15
days [30]
(b) Case report with 3
month follow-up [31]
(a) 2 puffs sublingually
at bedtime.
(a) Ipratropium no better than
placebo after 2 weeks.
(b) One puff to each
nostril at bedtime.
(b) 7 improved. 2 withdrew
[Dry nose/bleeding (n=1) and
ineffectiveness (n=1)].
(c) Seven patients improved,
2 did not. Effect lasted 2-8
hours.
(c) 2 puffs sublingually
nocte increasing to tds
if necessary;
0.06% strength 2 puffs
up to tds if 0.03%
failed.
(d) 2 puffs sublingually
nocte (n=8) or bd
(n=2).
Oxybutynin 5mg daily
titrated to 10mg every
morning and 5mg nocte
then reduced to 5mg
bd according to
response.
(a) Pirenzepine
25mg/day increased by
25mg/week to
100mg/day for further 5
weeks.
(b) Daily dosages of
25-100mg pirenzepine.
(c) Pirenzepine 50mg
daily.
(a) 5mg nocte,
gradually increasing to
maximum of 15mg
nocte.
(b) 6mg per day in
divided doses.
(d) Reduction or resolution.
Easier to use than atropine
eye drops.
Marked improvement.
(a) Pirenzepine no better than
placebo.
(b) Improvement. Mild
diarrhoea observed.
(c) Reduced incidence of
hypersalivation. Serum
clozapine levels elevated in 3
pts and reduced in 1 pt with
concomitant pirenzepine, but
confounding factors also
present.
(a) 11 pts improved; 3 pts did
not.
(b) Marked reduction in
nocturnal hypersalivation and
disappearance of daytime
hypersalivation.
May impair cognitive function
[4].
* Not available in UK, but can be imported.
From the NHS Evidence website www.evidence.nhs.uk
3
Medicines Q&As
Table 1 (continued)
Adrenoceptor Agonists
Clonidine
(a) Case series (n=4)
patch/oral
[32]
(b) Case series (n=12)
[33] 4 weeks treatment
(a) Patch* 100-200
micrograms per week.
(b) Oral 50 micrograms
nocte increased to 100
micrograms after 2
weeks if ineffective.
Guanfacine* oral
Case report [35]
1mg in the morning.
Lofexidine oral
Case report [37]. 1
month’s treatment
200 micrograms bd.
(a) 2 pts showed marked and
sustained improvement. 1 pt
developed tolerance. 1 pt did
not respond.
(b) 11 pts had good or partial
response. 1pt did not
respond.
Caution: additive hypotension
with clozapine [2]. May cause
depression and may
exacerbate psychosis [11,33].
Tolerance may develop [33].
Avoid abrupt cessation [34].
Improvement.
Avoid abrupt cessation [36].
Significant improvement.
Avoid long-term use [37] and
abrupt cessation [36]. May
exacerbate psychosis and
depression [4].
Adrenoceptor Antagonists
Terazosin oral
Retrospective chart
review (n=60) [16]
See benzatropine
above.
Beware additive hypotension
[34].
Miscellaneous
Amisulpride oral
(a) Randomised,
double-blind, placebocontrolled, cross-over
study (n=20). 3 wks
active treatment [38]
(b) Open-label
crossover trial vs.
moclobemide (n=53)
[39]
(c) Case report;
patient also on
pirenzepine
throughout [40]
(d) Case report with 3
month follow-up [41]
(e) Case report [42]
(a) Amisulpride
100mg/day titrated up
to 400mg/day over 1
week.
(a) Statistically significant
improvement. Prolactin levels
rose in most patients and may
need monitoring.
b) Amisulpride
400mg/day vs.
moclobemide
300mg/day.
(c) Amisulpride up to
600mg daily with
clozapine dose
reduction.
(d) Amisulpride
50mg/day.
(e) Amisulpride
50mg/day increased
over 2 weeks to
150mg/day.
(b) At 2 weeks, 39 improved,
1 worsened and 13
unchanged. Less effective
than moclobemide.
(c) Enabled reduced
pirenzepine dose. Hypersalivation markedly improved.
(d) Significant improvement in
hypersalivation.
(e) Marked improvement in
daytime hypersalivation but
night-time hypersalivation still
present. Constipation and
tachycardia reported.
* Not available in UK, but can be imported.
From the NHS Evidence website www.evidence.nhs.uk
4
Medicines Q&As
Table 1 (continued)
Bupropion oral
Case report with 300
days follow-up [43].
Previous treatment
failure with six other
drugs
Moclobemide
oral
Sulpiride oral
Quetiapine oral
Botulinum toxin A
injection
(a) Non-comparative
study (n=14).
Treatment for 2 weeks
[44]
(b) Open-label
crossover trial vs.
amisulpride (n=53)
[39]
Non-comparative
study (n=18) for 21
days [45]
Retrospective chart
review (n=158) [46]
Case report [47]
Bupropion 100mg*/day
increased to bupropion
SR 150mg/day after 18
days.
(a) Moclobemide
150mg/day increased
to 300mg/day after 1
week if ineffective.
(b) See amisulpride
above.
Marked improvement in
daytime hypersalivation but
night-time hypersalivation still
present.
Clozapine and bupropion
lower the seizure threshold
[43].
(a) 9 patients improved; 5 did
not.
(b) At 2 weeks, 44 improved
and 9 unchanged. More
effective than amisulpride.
Sulpiride 150-300mg
per day.
Hypersalivation reduced in all
patients.
Bedtime quetiapine
dose as required
clinically, plus reduction
in clozapine dose by
about 25%.
Botulinum toxin 150
units into each parotid
gland.
Quetiapine was “beneficial in
some patients”. Adding
benzatropine or terazosin as
well resolved hypersalivation
in all patients.
Beneficial response at 2
weeks still apparent at 12
weeks.
* Not available in UK, but can be imported.
Miscellaneous Drugs Inducing Hypersalivation
Table 2 - Hypersalivation Caused by Other Medicines with Drug Interventions Used.
Drug causing
hypersalivation
Aripiprazole
Report Details
[ref]
Case report [48]
Risperidone oral
(a) Case report
[49]
(b) Case report
[50]
Quetiapine
Case report [51]
Bethanechol
Case report with
4 mth follow-up
[52]
Intervention
Oral trihexyphenidyl 2mg
daily.
(a) Oral clonidine
100micrograms nocte,
increased to 100 micrograms
bd over 3 days.
(b) Single dose of IM
biperiden* (dose not stated)
followed by oral biperiden*
2mg daily.
Oral benzatropine* 1mg twice
daily.
Atropine eye drops 0.1%
sublingually.
Ipratropium bromide MDI 2
puffs every 6 hrs onto buccal
mucosa.
Outcome
Significant reduction in
hypersalivation.
(a) Rapid and marked
improvement.
(b) Full remission of
hypersalivation.
No improvement with
benzatropine and atropine
so quetiapine discontinued
and hypersalivation
resolved.
Significant symptomatic
improvement.
* Not available in UK, but can be imported.
From the NHS Evidence website www.evidence.nhs.uk
5
Medicines Q&As
Table 2 (continued)
Irinotecan plus
Case report [53]
oxaliplatin
Lithium
Case report [56]
Subcutaneous atropine (no
dose given).
Propantheline bromide 15mg
bd.
Resolution.
Oxaliplatin might potentiate
irinotecan’s cholinergic
effects [54] so prophylaxis
has been given (atropine
250 micrograms
subcutaneously) a few
minutes before irinotecan
[55].
Satisfactory relief.
* Not available in UK, but can be imported.
Summary
Clozapine-Induced Hypersalivation




There are currently no drug treatments licensed for the management of clozapine-induced
hypersalivation.
If hypersalivation is troublesome, reduce clozapine dose or use a different antipsychotic if
feasible.
There is very limited comparative efficacy data to support the choice of one treatment for
clozapine-induced hypersalivation over another. In practice the potential risks and benefits of
each option should be considered on an individual basis. Some options have specific risks:
a) Some agents may have additive hypotensive effects with clozapine (e.g. amitriptyline,
terazosin, clonidine, lofexidine). Blood pressure should be monitored in these patients.
b) Some may cause drowsiness (e.g. hyoscine, benzatropine, amitriptyline).
c) Some may cause psychiatric side effects (e.g. depression with clonidine, agitation with
trihexyphenidyl).
d) Antimuscarinic agents will have additive side effects with clozapine. Cognitive function
may also be impaired. Pirenzepine, glycopyrronium and ipratropium are believed to have little
CNS penetration. Peripherally, anticholinergics can impair the gag reflex, compromising
swallowing and increasing the risk of aspiration (23).
e) Amitriptyline with clozapine may increase the risk of convulsions.
f) Amisulpride with clozapine may cause hyperprolactinaemia.
The authors of a Cochrane Review concluded that “There are currently insufficient data to
confidently inform clinical practice” and that “Current practice outside of well designed randomised
trials should be clearly justified” (8).
Miscellaneous Drugs Inducing Hypersalivation
Information on the treatment of hypersalivation induced by other drugs is limited to case reports and
management needs to be considered on an individual basis.
From the NHS Evidence website www.evidence.nhs.uk
6
Medicines Q&As
Limitations
 There are no major randomised placebo-controlled trials for any drug to treat drug-induced
hypersalivation, so the amount of published evidence is limited. The evidence for the use of some
of these drugs is limited to anecdotal reports only.
 The majority of the studies are short-term, so long-term data are not available.
 Most of the studies included small numbers of patients or are case reports.
 The majority of the studies rely on subjective outcome measurements since it is difficult to assess
saliva production objectively, particularly as there is inter-individual variation in saliva production.
No single “standard” method of measurement of salivary flow and outcome presentation is
available.
 None of the drugs investigated are licensed for the management of drug-induced hypersalivation.
The licensed use of antimuscarinic drugs (e.g. glycopyrronium bromide) as premedicants to dry
bronchial and salivary secretions peri-operatively is not included in this Q&A.
References
(1) Szabadi E, Tavernor S. Hypo- and hypersalivation induced by psychoactive drugs:
Incidence, mechanisms and therapeutic implications. CNS Drugs 1999;11(6):449-466.
(2) Bird AM, Smith TL, Walton AE. Current treatment strategies for clozapine-induced
sialorrhea. Ann Pharmacother 2011;45:667-75.
(3) Praharaj SK, Arora M and Gandotra S. Clozapine-induced sialorrhea: pathophysiology
and management strategies. Psychopharmacology 2006;185:265-273.
(4) Taylor D, Paton C, Kapur S. The South London and Maudsley NHS Foundation Trust,
Oxleas NHS Foundation Trust. The Maudsley Prescribing Guidelines in Psychiatry. 11 th
Edition. Chichester, Wiley Blackwell; 2012 pp75-78, 89-92.
(5) Calderon J, Rubin E, Sobota WL. Potential use of ipratropium bromide for the treatment
of clozapine-induced hypersalivation: a preliminary report. Int Clin Psychopharmacol
2000;15:49-52.
(6) Antonello C, Tessier P. Clozapine and sialorrhea: A new intervention for this bothersome
and potentially dangerous side effect (letter). J Psychiatry Neurosci 1999;24(3):250.
(7) Davydov L, Botts SR. Clozapine-induced hypersalivation. Ann Pharmacother
2000;34:662-665.
(8) Syed R, Au K, Cahill C, Duggan L, He Y, Udu V, Xia J. Pharmacological interventions for
clozapine-induced hypersalivation. Cochrane Database of Systematic Reviews 2008,
Issue 3. Art. No.: CD005579. DOI: 10.1002/14651858.CD005579.pub2.
(9) Copp PJ, Lament R, Tennent TG. Amitriptyline in clozapine-induced sialorrhoea (letter).
Br J Psychiatry 1991;159:166.
(10) Praharaj SK, Arora M. Amitriptyline for clozapine-induced nocturnal enuresis and
sialorrhoea (letter). Br J Clin Pharmacol 2007;63(1):128-129.
(11) Rogers DP, Shramko JK. Therapeutic options in the treatment of clozapine-induced
sialorrhea. Pharmacotherapy 2000;20(9):1092-1095.
(12) Comley C, Galletly C, Ash D. Use of atropine eye drops for clozapine induced
hypersalivation (letter). Aust N Z J Psychiatry 2000;34:1033-1034.
(13) Sharma A, Ramaswamy S, Dahl E et al. Intraoral application of atropine sulfate
ophthalmic solution for clozapine-induced sialorrhea (letter). Ann Pharmacother
2004;38:1538.
(14) Tessier P, Antonello C. Clozapine and sialorrhea: update (letter). J Psychiatry Neurosci
2001;26(3): 253.
(15) McKane JP, Hall C, Akram G. Hyoscine patches in clozapine-induced hypersalivation
(letter). Psychiatric Bulletin 2001;25(7):277.
(16) Reinstein MJ, Sirotovskaya LA, Chasanov MA et al. Comparative efficacy and tolerability
of benzatropine and terazosin in the treatment of hypersalivation secondary to clozapine.
Clinical Drug Investigation 1999;17(2):97-102.
(17) Bourgeois JA, Drexler KG, Hall MJ. Hypersalivation and clozapine (letter). Hospital and
Community Psychiatry 1991;42(11):1174
(18) Liang C-S, Ho P-S, Shen L-J et al. Comparison of the efficacy and impact on cognition of
glycopyrrolate and biperiden for clozapine-induced sialorrhea in schizophrenic patients: a
randomized, double-blind, crossover study. Schizophr Res 2010;119:138-144.
From the NHS Evidence website www.evidence.nhs.uk
7
Medicines Q&As
(19) Richardson C, Kelly DL, Conley RR. Biperiden for excessive sweating from clozapine
(letter). Am J Psychiatry 2001;158(8):1329-1330.
(20) Duggal HS. Glycopyrrolate for clozapine-induced sialorrhea (letter). Prog NeuroPsychopharmacol Biol Psychiatry 2007;31:1546-1547.
(21) Robb AS, Lee RH, Cooper EB et al. Glycopyrrolate for treatment of clozapine-induced
sialorrhea in three adolescents. J Child Adolesc Psychopharmacol 2008;18(1):99-107.
(22) Cuvposa (glycopyrrolate 1mg/5ml) oral solution. Prescribing Information. Accessed via
http://www.cuvposa.com/ on 28th June 2012.
(23) Gaftanyuk O, Trestman RL. Scopolamine patch for clozapine-induced sialorrhea (letter).
Psychiatr Serv 2004;55(3):318.
(24) Sockalingam S, Shammi C, Remington G. Treatment of clozapine-induced
hypersalivation with ipratropium bromide: a randomized, double-blind, placebo-controlled
crossover study. J Clin Psychiatry 2009;70(8):1114-1119.
(25) Freudenreich O, Beebe M, Goff DC. Clozapine-induced sialorrhea treated with sublingual
ipratropium spray: A case series (letter). J Clin Psychopharmacol 2004;24(1):98-100.
(26) Leung JG, Puri NV, Jacobson MJ. Immediate-release oxybutynin for the treatment of
clozapine-induced sialorrhea. Ann Pharmacother 2011;45:e45.
(27) Bai Y-M, Lin C-C, Chen J-Y et al. Therapeutic effect of pirenzepine for clozapine-induced
hypersalivation: A randomized, double-blind, placebo-controlled, cross-over study. J Clin
Psychopharmacol 2001;21(6):608-611.
(28) Fritze J, Elliger T. Pirenzepine for clozapine-induced hypersalivation (letter). Lancet
1995;346:1034.
(29) Schneider B, Weigmann H, Hiemke C et al. Reduction of clozapine-induced
hypersalivation by pirenzepine is safe. Pharmacopsychiatry 2004;37:43-45.
(30) Spivak B, Adlersberg S, Rosen L et al. Trihexyphenidyl treatment of clozapine-induced
hypersalivation. Int Clin Psychopharmacol 1997;12:213-215.
(31) Aggarwal A, Garg A, Jiloha R. Trihexyphenidyl (benzhexol) in clozapine-induced
nocturnal enuresis and sialorrhea (letter). Indian J Med Sci 2009;63(10):470.
(32) Grabowski J. Clonidine treatment of clozapine-induced hypersalivation (letter). J Clin
Psychopharmacol 1992;12(1):69-70.
(33) Praharaj SK, Verma P, Roy D et al. Is clonidine useful for treatment of clozapine-induced
sialorrhea? J Psychopharmacol 2005;19(4):426-428.
(34) Joint Formulary Committee. British National Formulary 63. March 2012. Electronic
edition. London: BMJ Group and Pharmaceutical Press. Accessed via
http://www.bnf.org/ on 19th July 2012.
(35) Webber MA, Szwast SJ, Steadman TM et al. Guanfacine treatment of clozapine-induced
sialorrhea (letter). J Clin Psychopharmacol 2004;24(6):675-676.
(36) Anon. Guanfacine treatment of clozapine-induced sialorrhea. Primary Psychiatry
2005;12(2):23-24.
(37) Corrigan FM, MacDonald S, Reynolds GP. Clozapine-induced hypersalivation and the
alpha2 adrenoceptor (letter). Br J Psychiatry 1995;167:412.
(38) Kreinin A, Novitski D, Weizman A. Amisulpride treatment of clozapine-induced
hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled
cross-over study. Int Clin Psychopharmacol 2006;21:99-103.
(39) Kreinin A, Miodownik C, Sokolik S et al. Amisulpride versus moclobemide in treatment of
clozapine-induced hypersalivation. The World Journal of Biological Psychiatry
2011;12:620-626.
(40) Croissant B, Hermann D, Olbrich R. Reduction of side effects by combining clozapine
with amisulpiride: case report and short review of clozapine-induced hypersalivation. A
case report. Pharmacopsychiatry 2005;38:38-39.
(41) Praharaj SK, Sarkar S, Sinha VK. Amisulpride treatment for clozapine-induced sialorrhea
(letter). J Clin Psychopharmacol 2009;29(2):189-190.
(42) Praharaj SK, Ray P, Gandotra S. Amisulpride improved debilitating clozapine-induced
sialorrhea. American Journal of Therapeutics 2011;18(3):e84-e85.
(43) Stern RG, Bellucci D, Cursi-Vogel N et al. Clozapine-induced sialorrhea alleviated by
bupropion – a case report (letter). Prog Neuropsychopharmacol Biol Psychiatry
2009;33:1578-1580.
From the NHS Evidence website www.evidence.nhs.uk
8
Medicines Q&As
(44) Kreinin A, Miodownik C, Libov I et al. Moclobemide treatment of clozapine-induced
hypersalivation: pilot open study. Clin Neuropharmacol 2009;32(3):151-153.
(45) Kreinin A, Epshtein S, Sheinkman A et al. Sulpiride addition for the treatment of
clozapine-induced hypersalivation: preliminary study. Israel Journal of Psychiatry and
Related Sciences 2005;42(1):61-63.
(46) Reinstein MJ, Sonnenberg JG, Mohan SC et al. Use of quetiapine to manage patients
who experienced adverse effects with clozapine. Clinical Drug Investigation
2003;23(1):63-67.
(47) Kahl KG, Hagenah J, Zapf S et al. Botulinum toxin as an effective treatment of clozapineinduced hypersalivation (letter). Psychopharmacology 2004;173:229-230.
(48) Praharaj SK, Jana AK, Sinha VK. Aripiprazole-induced sialorrhea (letter). Prog
Neuropsychopharmacol Biol Psychiatry 2009;33:384-385.
(49) Gajwani P, Franco-Bronson K, Tesar GE. Risperidone-induced sialorrhea (letter).
Psychosomatics 2001;42(3):276.
(50) Panagiotidis PT, Fountoulakis KN, Siamouli M et al. Risperidone-induced sialorrhea
responsive to biperiden treatment. Schizophr Res 2007;93:410-411.
(51) Allen S, Hoffer Z, Mathews M. Quetiapine-induced hypersalivation (letter). Primary Care
Companion Journal of Clinical Psychiatry 2007;9(3):233.
(52) Kunwar AR, Doufekias E, Nihalani N et al. Ipratropium bromide for treatment of
bethanechol-induced sialorrhea (letter). Ann Pharmacother 2003;37:1343.
(53) Valencak J, Raderer M, Kornek GV et al. Irinotecan-related cholinergic syndrome induced
by coadministration of oxaliplatin (letter). J Natl Cancer Inst 1998;90(2):160.
(54) Dodds HM, Bishop JF, Rivory LP. More about: Irinotecan-related cholinergic syndrome
induced by coadministration of oxaliplatin (letter). Journal of the National Cancer Institute
1999;91(1):91-92.
(55) Cvitkovic E, Marty M, Wasserman E et al. Re: Irinotecan-related cholinergic syndrome
induced by coadministration of oxaliplatin (letter). Journal of the National Cancer Institute
1998;90(13):1016-7.
(56) Donaldson SR. Sialorrhea as a side effect of lithium: a case report. Am J Psychiatry
1982;139(10):1350-1351.
Quality Assurance
Prepared by
Kate Pickett, Medicines Q&A Pharmacist, Wessex Drug and Medicines Information Centre, University
Hospital Southampton NHS Foundation Trust.
Date Prepared
21st June 2012
Checked by
Sue Gough (based on the Q&A originally checked by Simon Wills and Sandra Hicks), Wessex Drug
and Medicines Information Centre, University Hospital Southampton NHS Foundation Trust.
Date of check
31st August 2012
From the NHS Evidence website www.evidence.nhs.uk
9
Medicines Q&As
Search strategy
 Medline (NHS Evidence): exp SIALORRHEA/dt (limited to human and English language)
 Embase (NHS Evidence): exp HYPERSALIVATION/dt (limited to human and English
language and years 1998-2012)
 Embase (NHS Evidence): exp*HYPERSALIVATION/si (limited to human and English
language)
 Micromedex
 eMC (accessed via http://www.medicines.org.uk/emc/)
 Cochrane library (accessed via http://www.thecochranelibrary.com)
 NHS Evidence (accessed via https://www.evidence.nhs.uk/)
 eBNF (accessed via https://www.bnf.org/)
From the NHS Evidence website www.evidence.nhs.uk
10