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Completed

NCT Number: NCT07545382

Rivastigmine as an Antidote for Clozapine and Other Anticholinergic-Induced CNS Depression and Delirium: A Study of 100 Cases

This study aims to evaluate the clinical efficacy and safety of rivastigmine in reversing the full spectrum of anticholinergic delirium including hypoactive delirium which is presented with CNS depression and hyperactive or agitated delirium.

The study was conducted on 100 patients at the Poison Control Center of Alexandria University Main Hospital. The primary objective is to assess the effectiveness of rivastigmine in restoring consciousness and improving cognitive function in patients presenting with delirium and depressed mental status using GCS and RASS score.

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Key information

Conditions

Anticholinergic Delirium Antipsychotic Toxicity CNS Depression Clozapine Poisoning Hypoactive Delirium Procyclidine Induced Delirium Tricyclic Antidepressant Poisoning

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Poison Control Center (PCC), Alexandria University Main Hospital

Alexandria, 21131, Egypt

About this study

This prospective clinical study assess the efficacy of rivastigmine in reversing the full spectrum of anticholinergic delirium. The study encompasses both hyperactive (agitated) and hypoactive (depressed mental status/CNS depression) presentations, with a specific focus on the hypoactive variant. While anticholinergic toxicity is traditionally associated with agitation, this research highlights its role in causing hypoactive delirium and assesses how rivastigmine facilitates the recovery of consciousness and cognitive function.

Participants:

The study includes 100 patients (aged ≥18 years) with Anticholinergic delirium-induced by exposure to drugs with anticholinergic properties-manifests either as agitated delirium (characterized by confusion, agitation, disorientation, and hallucinations) or hypoactive delirium (characterized by CNS depression). Patient status was assessed using the Glasgow Coma Scale (GCS) and the Richmond Agitation-Sedation Scale (RASS) upon admission to the Poison Control Center of Alexandria University Main Hospital (AUMH).

Intervention Protocol:

Administration: An initial enteral dose of 6 mg is administered orally or by nasogastric tube. Transdermal patch was administered when nasogastric route was non-feasible.

Dosing: Additional 6 mg doses are administered every 2 hours until achieving GCS 15 /RASS 0

Assessment & Resolution:

Awareness, cognition, consciousness, and the level of agitation or sedation were evaluated using the Glasgow Coma Scale (GCS) and the Richmond Agitation-Sedation Scale (RASS). These assessments were performed at baseline, 2 hours, and 6 hours for both the oral and transdermal groups, and at 12 hours exclusively for the transdermal group. Clinical success was defined as achieving a GCS score of 15 and a RASS score of 0.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Exposure: acute exposure to anticholinergic agents (e.g., clozapine, tricyclic antidepressants).

Clinical Presentation: Presence of anticholinergic delirium either hyperactive/agitated or hypoactive/CNS depression/coma).

Exclusion criteria

  • Non-Toxic Delirium: Delirium of multifactorial origin or other medical causes (e.g., sepsis, hepatic encephalopathy, alcohol withdrawal, or metabolic disturbances).
  • Cardiac Contraindications: Baseline bradycardia, Atrioventricular (AV) block, or significant QTc prolongation.
  • Patients who experienced pulmonary aspiration as a complication of overdose, necessitating endotracheal intubation and mechanical ventilation
  • Severe Organ Impairment: Known severe renal or hepatic impairment.
  • Neurological Conditions: History of pre-existing seizure disorders or epilepsy.
  • Respiratory Conditions: Severe asthma or Chronic Obstructive Pulmonary Disease (COPD) due to the risk of bronchoconstriction.
  • Obstructions: Mechanical bowel obstruction or urinary tract obstruction.
  • Hypersensitivity: Known history of hypersensitivity to rivastigmine or other carbamates.
  • Pregnancy/Lactation: Pregnant or lactating women.

Treatment and study plan

Rivastigmine

Drug

Initial Dose: A starting dose of 6 mg is administered either orally or via a Nasogastric Tube (NGT) for patients with impaired swallowing or depressed consciousness.

Titration: Additional 6 mg doses are repeated every 2 hours based on clinical need until the resolution of delirium.

Alternative Route: Transdermal patches (9.5 mg/24h) are applied in cases where enteral administration is not feasible or based on clinical judgment.

Primary outcomes

  1. Change in Glasgow Coma Scale (GCS) Score.

    Time frame: Baseline (0 hour), 2 hours post-administration (all patients), 6-8 hours, and 12 hours (transdermal group). For patients receiving additional oral/NGT doses, assessments were repeated 2 hours after each supplemental dose up to 6 hours after resolution.

    The Glasgow Coma Scale (GCS) is a clinical scale used to assess a patient's level of consciousness. The total score was recorded for all participants at baseline and subsequent intervals to evaluate the clinical response to rivastigmine. The GCS score ranges from a minimum of 3 to a maximum of 15, where higher scores indicate a better neurological outcome (improved consciousness). For the oral/NGT group, assessments were performed 2 hours after the initial dose and after each supplemental dose. For the transdermal group, monitoring included a 6 to 8-hour window and at 12 hours. Clinical resolution is defined as reaching a GCS score of 15 and a RASS score of 0.

  2. Change in Richmond Agitation-Sedation Scale (RASS) Score

    Time frame: Baseline, 2h (all), 6-8h & 12h (patch group), and up to 6h post-resolution (both groups)

    The Richmond Agitation-Sedation Scale (RASS) is used to evaluate the clinical response to rivastigmine. The RASS is a 10-point scale ranging from a minimum value of -5 (denoting unarousable/deep sedation) to a maximum value of +4 (denoting combative/extreme agitation). A score of 0 represents an alert and calm state, which indicates the best clinical outcome for this study. Scores were recorded for all participants at baseline and 2 hours to evaluate the initial response. For the oral/NGT group, additional assessments were performed 2 hours after each supplemental dose. For the transdermal group, monitoring focused on the 6 to 8-hour window and at 12 hours. Clinical resolution is defined as reaching a RASS score of 0 and a GCS score of 15.

Secondary outcomes

  1. Post-Resolution Clinical Stability and Safety Profile.

    Time frame: From initial administration up to 6 hours post-resolution of delirium.

    Monitoring for potential adverse effects related to rivastigmine, including cardiac complications (e.g., bradycardia, arrhythmias) and cholinergic side effects (e.g., excessive secretions, vomiting). Safety is further assessed by the absence of relapse during a mandatory 6-hour observation period following the resolution of delirium and CNS depression. Patients are deemed clinically stable if they remain symptom-free throughout this period prior to discharge.

  2. Time to Clinical Resolution.

    Time frame: From the time of initial administration until the achievement of clinical resolution.

    The duration (measured in hours) elapsed from the initial dose of rivastigmine until the patient achieves clinical resolution, defined as reaching a Glasgow Coma Scale (GCS) score of 15 and a Richmond Agitation-Sedation Scale (RASS) score of 0.

  3. Resolution of Peripheral Antimuscarinic Features.

    Time frame: From initial administration up to the point of CNS manifestation resolution (variable, typically within 2-12 hours).

    Monitoring the normalization of heart rate and the resolution of urinary retention (without the requirement for catheterization) in patients presenting with these features at baseline.

  4. The requirement for Additional Interventions

    Time frame: From Initiation of Rivastigmine Treatment Until 6 Hours After Recovery of Consciousness

    The percentage of patients requiring rescue therapy or escalation of care after receiving rivastigmine. This includes the need for benzodiazepines for sedation, the use of physical restraints, or clinical escalation to endotracheal intubation and intensive care unit (ICU) admission.

Sponsors and collaborators

Lead sponsor

Alexandria University

Other

Registry information

Official study title

Efficacy of Rivastigmine in the Management of Toxic Anticholinergic Delirium: A Prospective Study at Alexandria Poison Center

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Apr 22, 2026
Registry last updated
May 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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