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

Abstract

We developed this diazepam 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 diazepam drug utilization review that summarizes this guideline is described.

Appendix Drug Utilization Review: Diazepam

DRUG UTILIZATION REVIEW CRITERIA				CRITERIA MET
DIAZEPAM FOR ADULTS WITH IDs
				YES	NO	NA
1) Indication: Check one of the following indications for use
	Anxiety disorders.
	Ethanol withdrawal symptoms.
	Skeletal muscle relaxant for the relief of skeletal muscle spasm: Reflex spasm secondary to local pathology___, spasticity caused by upper motor neuron disorder (such as cerebral palsy and paraplegia)___, athetosis___, and stiff-man syndrome____.
	Adjunct therapy in epilepsy.
	Other (including insomnia, catatonia, and antipsychotic-induced akathisia). Specify_____________________. When diazepam 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 four administrations (Y__, N___) or justification was provided (Y__).					
	Anxiety or adjunctive treatment of epilepsy: Dose range 4–40 mg/day (Y__, N___) unless recommended otherwise by a consultant with expertise in the area (Y__).					
	Skeletal muscle spam: Dose range is 6–40 mg/day (Y__, N___) unless recommended otherwise by a consultant with expertise in the area (Y__).					
	Taking phenytoin__, carbamazepine__, phenobarbital__, primidone__, or other inducer____________________. The chart documents the interaction (Y___ N___). The dosage of diazepam may need to be increased when an inducer is added, and the discontinuation of the inducer may need to be followed by a decrease of diazepam dosage.					
	Taking potent CYP2C19 and/or CYP3A inhibitors (e.g., omeprazole__, ketoconazole___, itraconazole___, fluconazole___, erythromycin___, fluoxetine___, fluvoxamine___, clarithromycin___, diltiazem___ or disulfiram___). Other______________. The chart documents the interaction. The diazepam dosage may need to be decreased when an inhibitor is added and the discontinuation of the inhibitor may need to be followed by an increase of diazepam dosage.					
	Taking phenytoin__. The chart documents the interaction (Y___ N___). Patient is monitored closely for phenytoin toxicity.
	Hepatic impairment_____. The chart documents lower doses (Y___ N___).					
	Renal impairment_____. The chart documents lower doses (Y___ N___).					
	Elderly___ or debilitated patient____. The chart documents the prescription of a lower initial dose (Y___ N___).					
	East Asian ancestry___. The chart documents the increased risk that patient may be a CYP2C19 poor metabolizer and this is considered for dosing (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.
	Mild-to-moderate hepatic impairment.
	Renal impairment.
	Compromised respiratory function (e.g., COPD, sleep apnea syndrome, limited pulmonary reserve).
	Impaired gag reflex or swallowing problems.
	Depression with suicide risk.
	History of drug dependence or alcoholism.
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:
	Diazepam 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 diazepam: 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, or constipation, nausea.
	Paradoxical reaction, including increased talkativeness, emotional release, excitement, or excessive movements.		Psychological or physical dependence.
	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 as intoxication 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).