Acute onset psychosis with complex neurobehavioural symptomatology following the intramuscular injection of hyoscine butylbromide: a case report with an overview of the literature

Abstract

Different compounds of hyoscine (scopolamine) are widely used for the treatment of a variety of conditions, ranging from motion sickness to colic spasms and smoking cessation. In some rare conditions, the administration of scopolamine may lead to severe idiosyncratic reactions, including central anticholinergic intoxication syndrome. Here, we present 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. Referred to psychiatry, detailed screening of her medical records and collateral information from the family revealed that the neurobehavioural manifestations were indeed preceded by severe peripheral anticholinergic toxicity, which were mostly overlooked during the initial evaluations. Started on olanzapine treatment, the patient’s symptoms gradually subsided over time, though it took several weeks to achieve full clinical recovery.

Background

As an antagonist of the muscarinic receptors with peripheral and central anticholinergic properties, hyoscine (scopolamine) inhibits the action of acetylcholine at postganglionic parasympathetic sites including secretory glands, gastrointestinal tract and smooth muscles, as well as the central nervous system (CNS).^{1 2} Different compounds of hyoscine are widely used for a variety of indications, ranging from motion sickness (hyoscine hydrobromide) to acute spasms as in renal or biliary colic (hyoscine butylbromide). Unlike other antimuscarinic agents, pharmacologically effective doses of hyoscine have been associated with CNS depressive effects, whereas overdoses and idiosyncratic reactions may lead to CNS overstimulation, presenting with psychomotor agitation, irritability, confusion and, in some cases, acute psychosis, which generally occurs late in the course of the intoxication syndrome.³

In this case report, we present a female patient who, after repeated intramuscular administration of hyoscine butylbromide to treat her menstrual cramps, developed a series of complex neuropsychiatric symptoms including ataxia, slurred and rambling speech, stereotypic movements, vivid visual and auditory hallucinations, and self-mutilative behaviours. As a striking and atypical example of scopolamine-induced psychosis with neurobehavioural manifestations, we aim to discuss the patient’s symptomatology and improve awareness of this rare condition through an overview of the literature.

Case presentation

A 23-year-old single female patient with no prior psychiatric history was referred to psychiatry from the neurology outpatient unit on account of the incoherence of her reported complaints and the peculiarity of her presenting symptoms. It was noted that she tended to exhibit childish behaviours and crying spells during the examination, and that her history of recurrent fainting was not consistent with epileptic phenomenology.

The patient’s symptoms had first appeared about 1 month ago, following the intramuscular administration of hyoscine butylbromide (two consecutive injections of 20 mg/mL ampoules, with around half an hour between them) in the emergency department to treat her menstrual cramps. Several hours after discharge, the patient had developed a series of neurological symptoms including severe headache, loss of balance, dry mouth, blurred vision, vertigo, and nausea with vomiting, which caused her to be brought back to the emergency department by her family. She had no history of relevant medical conditions, and did not receive any other medication prior to admittance. Her initial neurological examination revealed diplopia and hypoaesthesia in the right side of the face, as well as the right upper and lower limbs. Her vital signs and the results of detailed laboratory tests (including complete blood count, biochemical and serological tests, and urine analysis) were all within normal limits. Her brain diffusion-weighted imaging, cranial computed tomography (CT), contrasted cranial and orbital magnetic resonance imaging revealed no apparent pathology. The consultant ophthalmologist reported bilateral restriction of lateral gaze, while no pathology was found on funduscopy. The subsequent lumbar puncture, which was carried out to exclude CNS infection, also revealed no abnormality. The symptoms were assessed to be consistent with the prolonged anticholinergic effects of hyoscine, and the patient was discharged for further follow-up in the outpatient clinic. However, 4 weeks later the patient presented to the neurology clinic with dramatically exacerbated neuromotor and behavioural symptoms. Due to the absence of apparent organic causes and the seemingly exaggerated and fluctuating presentation of her complaints, the patient was referred to psychiatry.

During her first psychiatric examination, it was noted that the patient was in an extreme state of psychomotor agitation; she was moaning, crying and hitting her head with her fists at the slightest frustration. She tended to speak and behave in such a childish manner such that she gave the impression of suffering from an intellectual disability. She continuously kept waving her right hand in a stereotypic manner during the interview, and her speech was also slurred and rambling, which made it difficult to communicate with the patient. As her agitation calmed down a little and she became able to engage in verbal communication, it was noticed that the patient made many paraphasic errors, and also tended to consistently omit consonants from the beginning of words (as in the case of initial consonant deletion) during her speech. She mostly gave short and superficial answers to the questions asked, and her thought content was largely dominated by paranoid ideation. She believed that the doctor who administered an intramuscular injection in the emergency room had intended to harm her, and she had felt insecure and frightened ever since. On further questioning, she stated that she had been chased by a “dreadful man” for a while, which she described as a big, black-dressed, shadow-like creature with long sharp teeth and pointy ears. The creature appeared several times during the day, she said, and commanded her to hit herself until she obeyed, otherwise he would not let her free. She felt so tormented that she was never able to fight back, which resulted in her hitting her head against the walls on several occasions.

Investigations

A family interview was conducted with the mother of the patient and a close family friend of theirs, who both denoted that her symptoms appeared abruptly during the last month, within a few days following the injection. They also confirmed that the patient had no prior history of mental disorder, nor any suspected substance abuse. She was employed as a shift manager at a fast-food restaurant, and was fully functional and able to meet her family’s financial needs until recently. No acute stressor was defined except for her parents having divorced years ago and some long ongoing financial difficulties. A further elaboration of the history of the onset of the symptoms and the retrospective screening of her medical records revealed that after the administration of hyoscine butylbromide, the patient had indeed fully experienced the peripheral symptoms characteristic of anticholinergic intoxication syndrome, although some of these were overlooked during the initial evaluation. Within the 2-day period after the injection, the family said, the patient had been unable to recognise her acquaintances due to her blurred vision and confusion. Significant flushing of her face was noticed as soon as they arrived at home, which was followed by spells of fainting and daily fluctuations in the patient’s mental status. She also had suffered from constipation lasting for several days after discharge, and dry mouth which had resulted in significant polydipsia. As the confusion subsided, the patient’s aforementioned motor symptoms (ie, ataxia, dysarthria, stereotypical hand waving, etc.) and behavioural changes (ie, childish temper tantrums, crying spells, disinhibited behaviours such as shouting and swearing, and severe acts of self-mutilation, etc.) became gradually more prominent. Psychotic symptoms, including vivid visual and auditory hallucinations as well as paranoid ideation, had also become very significant in the last few weeks. The family reported occasionally coming across the patient talking to herself when alone in the room, or looking at some invisible object with her gaze fixated on a spot on the wall.

Treatment

With a prediagnosis of hyoscine-induced psychosis with neurobehavioural symptomatology, the patient was started on olanzapine 5 mg/day with the recommendation of close monitoring. The following week, as she was brought to the clinic for her second appointment, it was noticed that the patient had significant bruises around both eyes (bilateral periorbital ecchymoses) which, as reported by the family, were caused by her repeatedly hitting her head hard against the wall. Her visual hallucinations and paranoid delusions persisted, despite some slight improvement in her psychomotor agitation in the last few days. Her cervical and cranial CT scans revealed no apparent pathology except significant soft tissue swelling in the anterior frontal region. Her olanzapine dose having been increased to 10 mg/day, the patient’s next appointment was arranged for 5 days later.

Outcome and follow-up

During the follow-up, it was noted that the patient’s neuromotor and psychiatric symptoms subsided gradually, with the patient becoming increasingly cooperative between the sessions. A significant clinical remission was achieved by about the third week of treatment, while it was not until 1 month later that the patient was fully able to return to work. The olanzapine was tapered and discontinued over the course of 2 weeks, with no residual symptoms during the follow-up period (see figure 1 for the patient’s clinical time course).

Figure 1.

Timeline of the patient’s clinical course.

Discussion

We believe that our case constitutes a striking and exceptional example of hyoscine-induced psychosis and neurobehavioural symptoms, given a wide diversity of symptoms being simultaneously present, and the atypical course of the syndrome, which persisted for several weeks after the injection. Having significantly extended beyond the characteristic features of anticholinergic overdose (as reflected by the common mnemonic, “red as a beet, dry as a bone, blind as a bat, mad as a hatter, and hot as a hare”), we suggest that our case should be considered within the scope of a severe idiosyncratic reaction to hyoscine. The overall clinical features of the patient were indeed strikingly in line with the literature and many previous reports on anticholinergic intoxication syndrome.

It should be borne in mind that among the preclinical effects of hyoscine are reported neuropsychiatric symptoms including pervasive cognitive impairment, psychomotor agitation and confusional states with hallucinations and complex visual imagery. Although these effects have been noted to be mostly dose-dependent, they can become extremely problematic especially among abusers of antimuscarinic drugs, such that self-injury and death can occur within the context of neurobehavioural symptoms and psychotic experiences.¹

In their review of the English literature, Minton et al reported finding five cases of psychosis induced by transdermal scopolamine.² The patients’ ages ranged between 59 and 84, and they all had developed bizarre/paranoid behaviours, agitation, and vivid visual and auditory hallucinations in addition to the peripheral anticholinergic symptoms, in the days following the administration of scopolamine patch at various doses. The same authors also reported a 61-year-old man who developed auditory and visual hallucinations, together with altered mental status, during smoking cessation therapy with scopolamine and/or atropine.² Similarly, Ziskind reported a 60-year-old woman who after using a transdermal scopolamine patch for prevention of motion sickness, experienced vivid auditory, visual and tactile hallucinations, which resolved within 36 hours after removal of the patch.⁴ Van Sassenbroeck et al reported three cases of anticholinergic intoxication caused by the accidental substitution of hyoscine hydrobromide for hyoscine butylbromide in preparations for gastrointestinal spasms. Two of the patients presented with altered mental status, agitation and visual hallucinations, and experienced long-lasting symptoms of cognitive impairment. The other patient, who presented with sudden onset speech disturbances and right hemiparesis, had first been diagnosed and treated as if suffering from an acute cerebrovascular accident, although hyoscine intoxication syndrome would later be recognised.⁵

On some occasions hyoscine intoxication may also occur in the form of epidemics, due to the widespread use of psychoactive substances adulterated with scopolamine, as in the example of epidemic poisoning in the United States in 1995⁶ and in Barcelona in 1991.⁷ A striking clinical feature of the epidemic in Oslo in 2008 was the commonness of plucking behaviour among the patients, whereas few of them had abnormal vital signs.⁸

Lauwers et al also described eight patients who developed neuropsychiatric symptoms, including paraparesis, blurred vision, confusion, agitation and hallucinations, after drinking tea adulterated with scopolamine. Similarly, their vital signs were reported to be within normal limits.⁹ Marneros et al reported a young man who amputated his penis and his tongue after drinking Angel’s Trumpet tea, a plant containing alkaloids (especially scopolamine) in a relatively high concentration.¹⁰ Intoxications with other anticholinergic agents are also known to cause complex neuropsychiatric symptoms similar to scopolamine poisoning, as in the case of atropine¹¹ and oxybutynin.¹²

The most crucial intervention in the treatment of anticholinergic intoxication is without doubt the discontinuation of the suspected agent. Hospitalisation may be necessary for the close monitoring of severe cases. While physostigmine is commonly used as a specific antidote for anticholinergic toxicity, benzodiazepines and antipsychotics can prove to be useful in managing agitation, hallucinations, and agressive and self-mutilative behaviours as in our case.²

Learning points.

• Some patients may be particularly vulnerable to the anticholinergic effects of hyoscine butylbromide, which is extensively used in the emergency department for several indications.

• In some rare cases, idiosyncratic toxicity may present with full-blown psychosis and/or complex neurobehavioural symptomatology.

• An elaborate medical history and collateral information may be the key to achieving a correct diagnosis for patients with acute onset, atypical neurobehavioural symptoms.

• Clinicians should be aware of the potential side effects and idiosyncratic intoxication syndromes associated with the use of hyoscine compounds and other anticholinergic agents.

Data availability statement

There are no data in this work.

Ethics statements

Patient consent for publication

Obtained.