Abstract
Hyoscine butyl bromide, an anti-spasmodic is often used for alleviation
of colicky abdominal pain. Few studies have shown its safety and
efficacy in children. Apart from common side effects, acute psychosis
has been rarely reported. With this case report, we would like to
reflect a message that hyoscine butylbromide should be used carefully in
children, along with the emphasis on the correct dose, frequency and
competency of the practicing clinician.
Keywords: hyoscine butylbromide; psychosis; children; abdominal
pain; side effect
INTRODUCTION
Functional disorders of the gastrointestinal (GI) tract, not related
with any organic, infectious or parasitic illness, are a regular cause
of painful abdominal cramps, and have been estimated to occur in up to
30% of the adult population in Western countries (Sandler RS, Stewart
WF, et al. 2000) (Bommelaer G, Poynard T, et al. 2004). Although
abdominal cramping and pain is not life-threatening, it has a
substantial impact on patients’ quality of life (QOL) and considerable
socioeconomic consequences (Maxion-Bergemamnn S, Thielecke F, et al.
2006) (Simren M, Brazier J, et al. 2004). Anti-spasmodics, analgesics,
antacids, anti-diarrhoeals, laxatives and anti-gas products are the
major drug therapies used for the relief of upper and lower abdominal
symptoms (Quigley EMM, Locke GR, et al. 2006) (Poynard T, Regimbeau C,
et al. 2001).
Hyoscine butylbromide is a derivative of the tertiary ammonium compound
hyoscine (Evangelista S. 2004). Hyoscine, an alkaloid is present in the
plant genus Duboisia which is grown in South America and
Australia. It is chemically prepared by adding a butyl group to obtain a
quaternary ammonium structure. This adjustment results in a molecule
that still has anticholinergic activities comparable to those of
hyoscine. But, in contrast with hyoscine, quaternary ammonium compounds
such as hyoscine butyl- bromide should not be systemically absorbed.
Limited systemic absorption may improve the adverse events profile
compared with the parent compound hyoscine.
Herein, we report a case of hyoscine butylbromide associated psychosis
in a 9-year-old-female child, with no significant personal and family
history of mental disorder. She presented to OPD with a history of
colicky abdominal pain and was prescribed hyoscine butylbromide 20mg to
be taken three times a day. She experienced delusions and hallucinations
after her second dose. A diagnosis of drug induced psychosis was
established. She was asked to withdraw the medication and her psychotic
features gradually disappeared. She was on her usual state of health
after few days. On regular follow-up, she is free of symptoms.
CASE PRESENTATION
A 9-year-old female child was brought to the OPD with a chief complaint
of abdominal pain for 1 day. The abdominal pain was generalized, acute
in onset, colicky in nature without any aggravating and relieving
factors. The child had been passing faeces and flatus. She had normal
bladder habits. She did not give a history of vomiting. Her past medical
history was not significant. She had never had a psychological problem
before. Her family history was unremarkable. There were no psychiatric
issues among the family members. She is from an upper-middle-class
household. She eats two major and two minor meals every day as a
non-vegetarian.
On examination, her general condition was fair. She was well oriented to
time, place and person. On per abdominal examination, she had a soft,
non-tender abdomen, no palpable organomegaly and normal bowel sounds.
A provisional diagnosis of non-specific colicky abdominal pain was made.
She was then given a prescription for 20 mg hyoscine butylbromide to be
taken three times a day for three days. The patient returned home and
took her first medication at midday and her second dose before bedtime.
Suddenly, at midnight, she woke up and began behaving strangely. She
screamed and told that something was crawling over her back, which could
indicate tactile hallucination. She experienced visual and auditory
hallucinations as explained by her parents. Then, she was rushed to the
emergency department at the same hospital where she was clinically
assessed. At the emergency, she constantly attempted to pick things up
from the floor (which was empty). She could not recognise her own
relatives. She kept seeing her friends and often shouted at them to
bring her a ball. The on-duty doctor found her to have features of acute
psychosis in her and was referred to a psychiatrist.
A diagnosis of drug-induced psychosis was established. She was advised
to withdraw the drug and her psychotic features gradually disappeared
and was back to her usual state of health after a few days. On regular
follow-up, she is free of symptoms.
DISCUSSION
Abdominal pain is reported by a third of school-aged children
(Saps M, Seshadri R, et al. 2009). Although the use of analgesia to
treat acute abdominal pain is well-supported (Falch C, Vicente D, et
al. 2014), there is little evidence to lead the management of
nonspecific abdominal pain in the emergency department, which accounts
for two-thirds of cases of abdominal pain presenting to the emergency
department.
In the pediatric study, hyoscine butylbromide, 10 mg given orally, was
found to be beneficial compared to a homoeopathic preparation with no
serious adverse effects (Müller-Krampe B, Oberbaum M, et al. 2007). One
meta-analysis (Poynard T, Regimbeau C, et al. 2001) and one systematic
review (Jailwala J, Imperiale TF, et al. 2000) concluded that
antispasmodics, including hyoscine butylbromide, are effective in the
treatment of abdominal cramping and pain/IBS. However, authors of
another meta-analysis (Lesbros-Pantoflickova D, Michetti P, et al. 2004)
disagreed with this conclusion.
As hyoscine butylbromide is barely absorbed, it is generally
well-tolerated. In the two large-scale studies (Scha ̵̈fer E, Ewe K. 1990)
(Mueller-Lissner S, Tytgat GN, et al. 2006) that compared hyoscine
butylbromide 30 mg/day with placebo (and paracetamol), 597 patients
received hyoscine butylbromide and 592 patients received placebo. There
was no significant difference in adverse events between the two groups
including those commonly associated with anticholinergics such as
nausea, constipation, dry mouth, blurred vision, tachycardia and urinary
retention. Moreover, these adverse events not only occurred at a low
incidence (≤1.5%) but were also usually mild and self-limiting. No
serious side effects were reported.
Herxheimer and Haefeli (Herxheimer A, Harfeli L. 1966) conducted a study
in which three healthy volunteers received very high oral (single) doses
of hyoscine butylbromide (200mg, 350mg and 600mg). These doses did not
provoke anticholinergic effects, i.e. change in heart rate, vision or
salivary excretion. The highest dose of 600 mg/day also did not produce
CNS effects. For a subject weighing 60kg, this dose correlates into a
dose of 10 mg/kg. As the lowest lethal dose (LD50)- value in a
single-dose toxicity study in dogs, the most sensitive species, was 600
mg/kg, a safety factor of 60 for oral hyoscine butylbromide in humans
can be extrapolated.
Despite the fact that there are also no data to support a difference in
tolerability, one would expect that a locally active drug such as
hyoscine butylbromide, which does not cross the blood-brain barrier,
would induce a lower incidence of CNS/anticholinergic adverse events
than systemically available smooth-muscle relaxants or drugs that do
cross the blood-brain barrier (Tytgat GN. 2007). However, we report a
case of acute psychosis due to toxicity of hyoscine butybromide.
Bulut et al presented a young female patient who progressively developed
a series of complex neuropsychiatric symptoms including ataxia, slurred
and rambling speech, stereotypic movements, vivid visual and auditory
hallucinations, and self-mutilative behaviours in the days following the
injection of hyoscine butylbromide in the emergency room to treat her
menstrual cramps. A diagnosis of acute psychosis was established and was
started on olanzapine. After few weeks, her condition was resolved
(Bulut NS, Arpacıoğlu ZB. 2020).
Poonai et al randomly assigned children aged 8–17 years with
nonspecific colicky abdominal pain who presented to the pediatric
emergency department of London Health Sciences Centre, London, Ontario
to receive hyoscine butylbromide, 10 mg given orally, or acetaminophen,
15 mg/kg given orally (maximum 975 mg) (Poonai N, Kumar K, et al. 2020).
Hyoscine butylbromide was not excellent to acetaminophen in this
setting. Adverse effects in the emergency department were reported by
32/116 (27.6%) participants in the hyoscine butylbromide group. Common
side effects were nausea, vomiting, dizziness, and photosensitivity.
There were no serious adverse effects (Poonai N, Kumar K, et al. 2020).