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

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

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.

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.

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:

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