Is it safe to start a patient on clorazepate (a benzodiazepine)?

Safety of Initiating Clorazepate Dipotassium

Clorazepate can be safely initiated in appropriate patients, but it carries significant risks of physical and psychological dependence, withdrawal symptoms, and is contraindicated in specific populations including pregnant/nursing women, patients with depressive neuroses, psychotic reactions, and children under 9 years of age. 1

Absolute Contraindications

Do not prescribe clorazepate in the following situations:

• Depressive neuroses or psychotic reactions - the FDA explicitly states clorazepate is not recommended for these conditions 1
• Pregnancy - benzodiazepines including clorazepate are associated with increased risk of congenital malformations, particularly during first trimester; use should "almost always be avoided" 1
• Nursing mothers - nordiazepam (active metabolite) is excreted in breast milk 1
• Children under 9 years of age - insufficient clinical experience 1

High-Risk Populations Requiring Extreme Caution

Patients with suicidal tendencies: If depression accompanies anxiety, suicidal tendencies may be present and protective measures are required; prescribe the least amount feasible 1

Elderly or debilitated patients: Start with lower doses and titrate gradually to prevent ataxia or excessive sedation, as this population shows greater sensitivity to all benzodiazepines 1

Impaired hepatic or renal function: Exercise usual precautions and consider dose adjustments 1

Patients with psychological potential for drug dependence: Use with caution as evidence of drug dependence has been demonstrated in animal studies 1

Critical Safety Warnings

Physical and psychological dependence develops with clorazepate use - withdrawal symptoms following abrupt discontinuation include convulsions, delirium, tremor, abdominal and muscle cramps, vomiting, sweating, nervousness, insomnia, irritability, diarrhea, and memory impairment 1. The more severe withdrawal symptoms typically occur in patients receiving excessive doses over extended periods, though milder symptoms can occur even at therapeutic levels after several months 1, 2.

After extended therapy, always taper gradually rather than abruptly discontinue to minimize withdrawal risk 1. A 1988 study demonstrated significant increase in symptom severity consistent with withdrawal reaction when clorazepate was abruptly stopped after six months of therapeutic dosing 2.

Required Patient Counseling

Inform patients that:

• Benzodiazepines produce psychological and physical dependence 1
• They must consult their physician before increasing dose or discontinuing the drug 1
• They should avoid hazardous occupations requiring mental alertness (operating machinery, driving) 1
• They must avoid simultaneous use of other CNS depressants and alcohol, as effects may be potentiated 1
• Women of childbearing potential should communicate immediately if they become pregnant or intend to become pregnant 1

Required Monitoring

For prolonged use, obtain:

• Periodic blood counts 1
• Liver function tests 1

Clinical Context from Research

Clorazepate demonstrated effectiveness as an anxiolytic when given as a single 15mg nighttime dose, with fewer side effects (particularly less daytime sedation) compared to divided-dose benzodiazepines 3, 4, 5. It has also shown efficacy in preventing alcohol withdrawal convulsions when used prophylactically 6.