A Practitioner’s Guide to Prescribing Clonazepam for Adults with Intellectual Disabilities

Abstract

We developed this clonazepam guideline using drug prescribing information and reviewing the available literature on relevant neuropsychiatric ­disorders in populations without intellectual disabilities because of the dearth of available literature on the population with intellectual disabilities. This guideline includes indications; contraindications; assessments prior to and during treatment; dosing with particular focus on dosing modifications required by drug–drug interactions, personal characteristics, or genetic variants; and adverse drug reactions. The procedures contained in this guideline may not fully account for all of the possible risks of treatment in this population because of the limited studies available; thus, there will be a need to periodically update this guideline as new information becomes available. Nevertheless, we believe that this guideline provides a useful resource for clinicians who treat epilepsy, anxiety, or catatonia in adult individuals with intellectual disabilities. A clonazepam drug utilization review that summarizes this guideline is described.

Appendix Drug Utilization Review: Clonazepam

DRUG UTILIZATION REVIEW CRITERIA				CRITERIA MET			CLONAZEPAM FOR ADULTS WITH IDs
				YES	NO	NA
1) Indication: Check one of the following indications for use
‫	Epilepsy: Alone ___ or as an adjunct ___ in the treatment of the Lennox–Gastaut syndrome (petit mal variant), akinetic ___ and myoclonic seizures ___. In patients with absence seizures (petit mal) who have failed to respond to succinimides.
‫	Panic disorder.
‫	Other (other anxiety disorders, treating or preventing ethanol withdrawal, catatonia, and antipsychotic-induced akathisia). Specify _______________. When clonazepam is used for off-label indications, the chart specifically includes an explanatory note (Y ___ N ___).
To meet indication criteria, at least one indication is present and documented.				‫	‫
2) Dose:_____
	Dose was divided in two to three administrations (Y __, N ___) or justification was provided (Y __).			‫	‫	‫
	Epilepsy: Initial dose was ≤ 1.5 mg (Y __, N ___) unless recommended otherwise by a consultant with expertise in the area (Y __).			‫	‫	‫
	Epilepsy: Maximum dose was ≤ 20 mg/day (Y __, N ___) unless recommended otherwise by a consultant with expertise in the area (Y __).			‫	‫	‫
	Panic disorder: Initial dose was ≤ 0.5 mg (Y __, N ___) or justification was provided (Y __).			‫	‫	‫
	Panic disorder: Maximum dose was ≤ 4 mg (Y __, N ___) or justification was provided (Y __).			‫	‫	‫
	Taking phenytoin __, carbamazepine __, ­phenobarbital __, primidone __, or other inducer ____________________. The chart documents the interaction (Y ___ N ___). The dosage of clonazepam may need to be increased when an inducer was added and the discontinuation of the inducer may need to be followed by a decrease of clonazepam dosage.			‫	‫	‫
	Taking potent CYP3A inhibitors (e.g., ketoconazole ___, itraconazole ___, fluconazole ___, ­erythromycin ___, fluoxetine ___, fluvoxamine ___, clarithromycin ___ or diltiazem ___). Other ________. The chart documents the interaction (Y ___ N ___). The dosage of clonazepam may need to be decreased when an inhibitor was added, and the discontinuation of the inhibitor may need to be followed by an increase of clonazepam dosage.			‫	‫	‫
	Hepatic impairment ____. The chart documents that lower doses are used (Y ___ N ___).			‫	‫	‫
	Geriatric patient ____. The chart documents that lower initial dose was used (Y ___ N ___).			‫	‫	‫
To meet dose criteria, all are Yes or NA.				‫	‫
3) Relative contraindications: Check any present.
‫	Pregnancy (Category D) or breast feeding.
‫	Elderly or debilitated.
‫	Hepatic or renal impairment.
‫	Compromised respiratory function (e.g., COPD, sleep-apnea syndrome, limited pulmonary reserve).
‫	Impaired gag reflex or swallowing problems.
‫	Depression with suicide risk. Be sure that patient is taking appropriate antidepressant treatment.
‫	History of drug dependence or alcoholism.
‫	Epilepsy treated with valproate.
If any of the above are checked, rationale is documented in chart to meet relative contraindication criteria. If none are present, check NA.				‫	‫	‫
4) Baseline monitoring studies:
‫	Liver function tests.
‫	In patients with epilepsy, serum concentrations of concomitantly administered antiepileptics, which are usually followed with therapeutic drug monitoring.
‫	If a female patient has potential to be pregnant, a pregnancy test is completed.
Answer Yes or No. If information is not applicable, check NA.				‫	‫	‫
5) Discontinuation:
	Clonazepam is or was withdrawn slowly to minimize the potential of increased seizure frequency (Y ___ N ___). Abrupt withdrawal was justified by a major medical reason (Y ___ N ___).			‫	‫	‫
6) Adverse drug reactions (ADRs) due to clonazepam: Check left boxes to indicate which ADRs are present.
6.1) Common ADRs:
‫	Sedation, drowsiness, memory difficulties, fatigue, muscle weakness, or cognitive impairment.	‫	Common in patients with IDs: Aggression, irritability, hyperactivity, or agitation.
6.2) Relatively uncommon ADRs:
‫	Dysarthria, confusion, abnormal coordination, ataxia, depression or worsening of mood, slurred speech, dizziness, or tremor.	‫	Dry mouth, constipation, or nausea.
‫	Paradoxical reaction, including increased talkativeness, emotional release, excitement, and excessive movements.	‫	Psychological and physical dependence.
‫	ADRs due to rapid decrease or abrupt withdrawal include agitation, heightened sensory perception, paresthesias, muscle cramps, muscle twitching, diarrhea, reduced concentration, worsening of mood, anxiety, nervousness, restlessness, sleeping difficulties, insomnia, tremors, or in rare cases seizures and hallucinations.	‫	Benzodiazepine intoxications manifest similarly to intoxications with other CNS depressants (e.g., alcohol).
‫	Worsening of swallowing problems.	‫	Other ___________
6.3) Potentially lethal ADRs:
‫	Suicidal ideation or behavior.
Answer Yes (intervention or benefit/risk discussion after ADRs developed) or No (neither intervention nor benefit/risk discussion after ADRs developed) or NA (no abnormality developed).				‫	‫	‫