\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[T2A]{fontenc}
\usepackage[ngerman,polish,english]{babel}



\usepackage{float}








\begin{document}

\title{Hyoscine butylbromide associated psychosis: A case report}



\author[1]{Durga Neupane}%
\author[1]{Nimesh Lageju}%
\author[1]{Lokesh Jaiswal}%
\affil[1]{BP Koirala Institute of Health Sciences}%


\vspace{-1em}



  
  \date{June 17, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
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.%
\end{abstract}%



\sloppy


\textbf{Hyoscine butylbromide associated psychosis: A case report}

Durga Neupane\textsuperscript{1}, Nimesh Lageju\textsuperscript{1},
Lokesh Shekher Jaiswal\textsuperscript{2}

MBBS, B.P. Koirala Institute of Health Sciences, Dharan, Nepal

Department of Surgery (Division of CTVS), B.P. Koirala Institute of
Health Sciences, Dharan, Nepal

Authors

Durga Neupane

Email: neupanedurga26@gmail.com

ORCID iD

https://orcid.org/0000-0002-9736-9335

\emph{Nimesh Lageju}

\emph{Email:Nimesh.lageju@yahoo.com}

ORCID iD

https://orcid.org/0000-0002-1411-5867

Lokesh Shekher Jaiswal

Email: lokesh\_shekher@yahoo.com

ORCID ID

https://orcid.org/0000-0002-0813-8747

Corresponding author

Durga Neupane

Email: neupanedurga26@gmail.com

ORCID iD

https://orcid.org/0000-0002-9736-9335

\textbf{Word count:} 1469

\textbf{Running title:} Hyoscine induced psychosis

\textbf{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.

\textbf{Keywords:} hyoscine butylbromide; psychosis; children; abdominal
pain; side effect

\textbf{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 \emph{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.

\textbf{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.

\textbf{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 (M\selectlanguage{ngerman}üller-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~\selectlanguage{english}\selectlanguage{english}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, Arpac\selectlanguage{polish}ı\selectlanguage{english}o\selectlanguage{polish}ğ\selectlanguage{english}lu 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).

\textbf{Conclusion}

Only a few studies have shown the safety and efficacy of hyoscine
butylbromide in alleviating abdominal pain in children without any
severe adverse effects like acute psychosis being reported. The
aforementioned case was a rare side effect of the drug. 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 expertise of the practicing clinician.

\textbf{Consent for study}

As the patient was minor, a written informed consent was obtained from
her father for the reporting and publication of this case report.

\textbf{Funding}

None

\textbf{Conflict of interest}

None

\textbf{Ethical approval}

Not required

\textbf{Conflict of interests}

None

\textbf{REFERENCES}

\begin{enumerate}
\tightlist
\item
  Bommelaer G, Poynard T, Le Pen C, et al. Prevalence of irritable bowel
  syndrome (IBS) and variability of diagnostic criteria. Gastroenterol
  Clin Biol 2004; 28: 554-61
\item
  Bulut, N. S., \& Arpac\selectlanguage{polish}ı\selectlanguage{english}o\selectlanguage{polish}ğ\selectlanguage{english}lu, Z. B. (2020). Acute onset psychosis with
  complex neurobehavioural symptomatology following the intramuscular
  injection of hyoscine butylbromide: a case report with an overview of
  the literature.~\emph{European journal of hospital pharmacy : science
  and practice} , ejhpharm-2020-002583. Advance online publication.
  https://doi.org/10.1136/ejhpharm-2020-002583
\item
  Evangelista S. Quaternary ammonium derivatives as spasmolytics for
  irritable bowel syndrome. Curr Pharm Des 2004; 10: 3561-8
\item
  Falch, C., Vicente, D., H\selectlanguage{ngerman}äberle, H., Kirschniak, A., Müller, S.,
  Nissan, A., \& Brücher, B. L. (2014). Treatment of acute abdominal
  pain in the emergency room: a systematic review of the
  literature.~\emph{European journal of pain (London, England)}
  ,~\emph{18} (7), 902--913.
  https://doi.org/10.1002/j.1532-2149.2014.00456.x
\item
  Herxheimer A, Haefeli L. Human pharmacology of hyoscine butylbromide.
  Lancet 1966; 2: 418-21
\item
  Jailwala J, Imperiale TF, Kroenke K. Pharmacologic treatment of the
  irritable bowel syndrome: a systematic review of ran- domized,
  controlled trials. Ann Intern Med 2000; 133: 136-47
\item
  Lesbros-Pantoflickova D, Michetti P, Fried M, et al. Meta- analysis:
  the treatment of irritable bowel syndrome. Aliment Pharmacol Ther
  2004; 20: 1253-69
\item
  Maxion-Bergemann S, Thielecke F, Abel F, et al. Costs of irritable
  bowel syndrome in the UK and US. Pharmacoeco- nomics 2006; 24: 21-37
\item
  Mueller-Lissner S, Tytgat GN, Paulo LG, et al. Placebo- and
  paracetamol-controlled study on the efficacy and tolerability of
  hyoscine butylbromide in the treatment of patients with recurrent
  crampy abdominal pain. Aliment Pharmacol Ther 2006; 23: 1741-8
\item
  Müller-Krampe, B., Oberbaum, M., Klein, P., \& Weiser, M. (2007).
  Effects of Spascupreel versus hyoscine butylbromide for
  gastrointestinal cramps in children.~\emph{Pediatrics international :
  official journal of the Japan Pediatric Society} ,~\emph{49} (3),
  328--334. https://doi.org/10.1111/j.1442-200X.2007.02382.x
\item
  Poonai, N., Kumar, K., Coriolano, K., Thompson, G., Brahmbhatt, S.,
  Dzongowski, E., Stevens, H., Gupta, P., Miller, M., Elsie, S., Ashok,
  D., Joubert, G., Lim, R., Bütter, A., \& Ali, S. (2020). Hyoscine
  butylbromide versus acetaminophen for nonspecific colicky abdominal
  pain in children: a randomized controlled trial.~\emph{CMAJ : Canadian
  Medical Association journal = journal de l'Association medicale
  canadienne} ,~\emph{192} (48), E1612--E1619.
  https://doi.org/10.1503/cmaj.201055
\item
  Poynard T, Regimbeau C, Benhamou Y. Meta-analysis of smooth muscle
  relaxants in the treatment of irritable bowel syndrome. Aliment
  Pharmacol Ther 2001; 15: 355-61
\item
  Quigley EMM, Locke GR, Mueller-Lissner S, et al. Prevalence and
  management of abdominal cramping and pain: a multina- tional survey.
  Aliment Pharmacol Ther 2006; 24: 411-9
\item
  Sandler RS, Stewart WF, Liberman JN, et al. Abdominal pain, bloating,
  and diarrhea in the United States: prevalence and impact. Dig Dis Sci
  2000; 45: 1166-71
\item
  Saps, M., Seshadri, R., Sztainberg, M., Schaffer, G., Marshall, B. M.,
  \& Di Lorenzo, C. (2009). A prospective school-based study of
  abdominal pain and other common somatic complaints in
  children.~\emph{The Journal of pediatrics} ,~\emph{154} (3), 322--326.
  https://doi.org/10.1016/j.jpeds.2008.09.047
\item
  Scha~\selectlanguage{english}\selectlanguage{english}fer E, Ewe K. The treatment of irritable colon: efficacy and
  tolerance of buscopan plus, buscopan, paracetamol and place- bo in
  ambulatory patients with irritable colon {[}in German{]}. Fortschr Med
  1990; 108 (25): 488-92
\item
  Simre~\selectlanguage{english}n M, Brazier J, Coremans G, et al. Quality of life and illness
  costs in irritable bowel syndrome. Digestion 2004; 69: 254-61
\item
  Tytgat GN. Hyoscine butylbromide: a review of its use in the treatment
  of abdominal cramping and pain.~\emph{Drugs} . 2007;67(9):1343-1357.
  doi:10.2165/00003495-200767090-00007
\end{enumerate}

\selectlanguage{english}
\FloatBarrier
\end{document}

