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Clonazepam is a benzodiazepine drug used for the acute treatment of panic disorder, epilepsy, and nonconvulsive status epilepticus. The drug also has many off-label indications, including restless leg syndrome, acute mania, insomnia, and tardive dyskinesia. Clonazepam is a long-acting and high-potency benzodiazepine; it behaves as a GABA-A receptor agonist. Benzodiazepines facilitate GABA-A action by increasing the frequency of chloride channel opening resulting in hyperpolarization of the neurons and reduced firing, thus producing calming effects on the brain by decreasing the excitability of neurons. Clonazepam also has serotonergic activity by increasing serotonin synthesis. This activity will highlight the indications, mechanism of action, administration, adverse event profile, contraindications, monitoring, and toxicity of clonazepam in the clinical settings pertinent for interprofessional team members in treating patients with panic and seizure disorders. Objectives: Identify the indications for using clonazepam therapy. Select patients who will benefit from clonazepam therapy. Coordinate the management of a patient with clonazepam toxicity. Collaborate with the interprofessional team to monitor patients for clonazepam overdose and/or toxicity to improve outcomes and prevent the risk of developing severe side effects. Access free multiple choice questions on this topic.

The therapeutic range of clonazepam is from 0.02 to 0.08 mcg/mL. Any level over 0.08 mcg/mL is considered toxic. The symptoms of overdose develop rapidly. Initial Presentation The initial symptoms appear within a few hours with symptoms of CNS depression such as: Somnolence Diplopia Slurred speech Motor impairment Severe Presentation If the overdose is severe, then it may result in severe symptoms such as: Respiratory depression Hypoxemia Apnea Hypotension Bradycardia Cardiac arrest Pulmonary aspiration Coma Severe consequences of clonazepam use alone are rare, but the toxicity increases significantly if other CNS depressants, such as opioids, ethanol, barbiturates, etc., are coadministered.[45] Treatment of Toxicity Supportive care and medical observation are the mainstays of the treatment. The supportive care includes monitoring vitals, IV fluids for hypotension, atropine for bradycardia, and maintaining the patency of the airway by intubation or artificial respiration if respiratory depression develops. The use of flumazenil, a competitive benzodiazepine receptor antagonist, as the antidote is controversial as its use correlates with lowered seizure threshold and widened QRS complex resulting in adverse effects. Flumazenil's side effects do not outweigh the potential benefits. It has no role in multidrug toxicity and should only be used following a consultation with a medical toxicologist.[46] The use of illicit benzodiazepines in combination with opioids is increasing, leading to synergistic toxicity and increased mortality. Consequently, increasing awareness among providers, patient education, and community involvement regarding hazards associated with illicit benzodiazepines is crucial.[47][48]

The concern lies in the healthcare community about the inappropriate long-term use of prescribed clonazepam and other BZD drugs despite their serious adverse effects profile, like the risk of falls, cognitive impairment, and addiction. Interventions to decrease the inappropriate use of clonazepam involve an interprofessional team that includes clinicians, nurses, pharmacists, and primary care providers. Clonazepam is usually started after an acute event or during the hospital stay by the clinicians. Once ordered by the clinicians, nurses often administer the drug. Following administration in hospital settings, its use may carry over to primary care without any indication; this is where a pharmacist performing medication reconciliation on discharge is invaluable. In primary care, patients also influence clinicians by having this conceived notion about clonazepam and BZD drugs being wonder drugs to make them feel and sleep better. These issues can result in poor patient outcomes from drug dependence, misuse, abuse, motor impairment, etc. Therefore, an interprofessional approach is required to develop ideas to reduce the use of hypnotics and develop interventions to prevent misuse in the hospital and at the primary and secondary care interface. The prescribing clinician, nurse, and pharmacist should use controlled substance prescription monitoring program (CSPMP) databases to ensure the safe and proper use of benzodiazepines, sedative-hypnotics, opioids, and other controlled substances. A study suggests that interprofessional teamwork between primary care physicians, mid-level practitioners, nurses, and pharmacists can enhance safe medication practices involving high-risk benzodiazepines.[49] [Level 5]