Aspiration pneumonia induced by haloperidol – A case report

INTRODUCTION

Aspiration pneumonia arises mainly from lung infections due to the inhalation or aspiration of non-air substances such as liquid, saliva or food. Factors such as general anaesthesia, bedridden conditions and certain medications like antipsychotics can contribute. Dystonia, characterised by involuntary muscle contractions, results from disorganised motor activity, often linked to basal ganglia lesions. Antidopaminergic therapies can also trigger dystonia. It manifests as twisting movements and abnormal posture, categorised by age of onset and body distribution. Treatment may involve deep brain stimulation or surgical ablation. Understanding these conditions is crucial for effective management and minimising drug-induced adverse events.^[1] Reporting known adverse reactions is essential for pharmacovigilance and patient safety, as it allows for the identification of potential risks associated with medication usage. By documenting and disseminating such adverse reactions, healthcare professionals can enhance their understanding of drug safety profiles, improve patient care and contribute to the development of safer treatment strategies.

CASE REPORT

The young male, in his 20s, presented to the pulmonology outpatient department with breathing difficulty, cough, dysphagia and muscle stiffness in the neck and upper limbs for 2 days. He had a history of psychosis and was taking haloperidol 2.5 mg and alprazolam 0.5 mg at bedtime for the past 3 weeks. Physical examination revealed dystonia of neck and upper limb muscles, dyspnoea and bilateral lung basal crepitations. Chest X-ray showed bilateral lower zone heterogeneous opacities, diagnosing aspiration pneumonia and haloperidol-induced dystonia. Dechallenge was positive, indicating a probable adverse drug reaction (ADR), reported through World Health Organization (WHO) Vigiflow, where haloperidol was commonly associated with dystonia and aspiration pneumonia, with 36,122 and 283 cases reported, respectively, along with 2345 cases of haloperidol-induced dystonia.^[2] The patient’s symptoms improved post-haloperidol cessation, confirmed by positive dechallenge and ethical constraints prevented rechallenge. Permission for the publication of this case report has been obtained from the Institutional Ethics Committee affiliated with Rangaraya Medical College, associated with the Government General Hospital, Kakinada Andhra Pradesh. The Institutional Ethics Committee registration number is IEC/RMC/2024/1269. Assessment using both the WHO–Uppsala Monitoring Centre^[3] and the Naranjo ADR probability scale ^[4] categorises it as a probable reaction. Specifically, the Naranjo ADR probability scale yielded a score of +7, indicating a probable reaction [Table 1].^[5]

DISCUSSION

Drug safety is a primary concern of public health, and it can be continuously monitored by the pharmacovigilance ADR reporting system. We can quantify, qualify and decrease drug-related adverse events with the help of the pharmacovigilance ADR reporting system. For many years, adverse events related to antipsychotic drugs have been investigated using pharmacovigilance programs such as spontaneous reporting systems and electronic medical records. The reliability of the association between drug adverse reactions and drug use is strengthened by confirming the drug’s mechanism of action and drug-receptor interactions, especially in ‘type A’ adverse drug events, which are dose-dependent and based on the pharmacological properties of the drug effects.^[1]

The onset of aspiration pneumonia typically occurs within a range of 2–5 days, a timeframe that can vary depending on factors such as the patient’s age, underlying health conditions and additional contributing factors. Due to limitations in the patient’s history, a time-to-event analysis correlating the administration of haloperidol with the onset of aspiration pneumonitis could not be conducted in our study. The likelihood of developing aspiration pneumonia is elevated in patients undergoing combination therapy involving benzodiazepines, barbiturates and antihistamines alongside antipsychotics compared to those receiving antipsychotic monotherapy.^[6] In our case report, the patient was prescribed alprazolam, a benzodiazepine, which poses a considerably lower risk of causing aspiration pneumonitis compared to all other benzodiazepines, including diazepam and midazolam.^[7] Therefore, in our study, alprazolam was not discontinued due to its lower propensity to induce aspiration. Instead, haloperidol was ceased on hospital admission, and supportive treatment was administered. As a result, the patient’s symptoms improved, leading to discharge. Thus, in our investigation, haloperidol was identified as the primary cause of aspiration pneumonitis.

Haloperidol is commonly used for bipolar disorder, schizophrenia and psychosis.^[8] It is a potent typical antipsychotic drug that competitively blocks post-synaptic D₂ dopamine receptors and also blocks D₁, D₄, H₁, α₁, M₁ and 5HT_2A receptors.^[9,10] Haloperidol is the most important antipsychotic drug that causes more extrapyramidal symptoms, especially dystonia, due to its high affinity for D₂ receptors. It causes adverse effects such as dysphagia and aspiration pneumonia, leading to higher mortality.^[11,12] Patients prescribed haloperidol have a higher mortality rate than those prescribed other antipsychotic drugs.^[9] Moreover, this risk is further escalated among elderly individuals as opposed to younger patients.^[13,14]

Haloperidol can cause aspiration pneumonia through several mechanisms, including its high affinity toward D₂ dopamine receptor blockade, which leads to many extrapyramidal symptoms such as dystonia, dysphagia, dyskinesia of oropharyngeal muscles, rigidity and spasm of pharyngeal muscles and sedation.^[15] These effects suppress the cough reflex and increase the risk of aspiration pneumonia due to the aspiration of saliva, foreign bodies, food particles and gastric contents.^[16,17] D₂ receptor blockade also causes dry mouth in some patients, leading to impaired oropharyngeal bolus transport and contributing to the occurrence of aspiration pneumonia.^[12] Sometimes, antipsychotics paradoxically cause hypersalivation due to disrupted cholinergic function, increasing the risk of aspiration pneumonia in patients taking antipsychotic medications. Haloperidol has also been associated with a decreased level of substance P, which impairs the swallowing reflex and increases the risk of aspiration pneumonia.^[15] Its antihistamine effects, such as sedation and sometimes dysphagia, occur due to the H1 receptor-blocking activity of haloperidol, which also increases the risk of aspiration pneumonia. Thromboxane A2 receptor and platelet-activating factor receptor are novel antipsychotic drug target receptors potentially associated with pneumonia, with affinity observed for all antipsychotic drugs except amisulpride.^[1]

CONCLUSION

Haloperidol, the most commonly prescribed antipsychotic medication, poses numerous serious complications, including extrapyramidal symptoms, cardiovascular issues and aspiration pneumonia. Clinicians should evaluate patients for their susceptibility to pneumonia and cardiovascular events before prescribing haloperidol. Vigilant monitoring of patients on antipsychotic medications for haloperidol’s adverse effects is crucial. Health-care providers should thoroughly explain the potentially severe side effects of haloperidol treatment to both patients and their relatives. Given the potentially fatal complications such as dystonia and aspiration pneumonia associated with haloperidol, it is imperative to raise awareness among patients and their families regarding the symptoms of haloperidol-induced side effects.