Chlordiazepoxide is a long-acting benzodiazepine and is an FDA approved medication for adults with mild-moderate to severe anxiety disorder, preoperative apprehension and anxiety, and withdrawal symptoms of acute alcohol use disorder. It is also FDA approved for pediatric patients greater than six years old for anxiety. Off-label, it can be used in the treatment of catatonia. It was synthesized and developed in 1956 and approved for use in 1960. It is among the least harmful of the effective psychopharmacological benzodiazepine composites. Like other medications in the benzodiazepine class, it serves as an augmenting agent for antipsychotics, mood stabilizers, SSRI, and SNRI for the treatment of psychotic disorder, bipolar disorder, and anxiety disorders. Clinicians should not combine chlordiazepoxide with other benzodiazepines.[1][2]

Chlordiazepoxide has anti-anxiety, sedative, appetite-stimulating, and weak analgesic actions. It binds to benzodiazepine receptors at the GABA-A ligand-gated chloride channel complex and enhances the inhibitory effects of GABA. Also, it increases chloride conductance through GABA-regulated channels. Moreover, its therapeutic benefits in anxiety disorder come from the inhibition of neuronal activity in amygdala-centered fear circuits. Additionally, it blocks EEG arousal from stimulation of the brain stem reticular formation. It is common to see some immediate relief of anxiety symptoms with first dosing, but to see the maximal therapeutic benefit several weeks with daily dosing is needed. It is metabolized by the liver microsomal pathway, first by hepatic oxidation, then by glucuronidation. The elimination half-life of this medication is 24 to 48 hours, and its excretion is via the urine.[3][4]

Chlordiazepoxide is available as a capsule with three different strengths: 5, 10, and 25 mg for oral dosing, and as an injectable with a concentration of 100 mg/5 ml. It is usually in the form of a gelatin capsule, and storage should be at 68 F to 77 F (20 C to 25 C). For pediatric patients over six years old and geriatric patients, the recommendation is to use the lowest effective dose. Moreover, for pediatric patients, injectable forms are not recommended, and there is no data on long term effects of this medication in this age group.

Treatment of mild to moderate anxiety:

• Oral: 15 to 40 mg/day in 3 to 4 doses

Treatment of severe anxiety:

• Oral: 60 to 100 mg/day in 3 to 4 doses

Treatment of acute to severe anxiety:

• Injectable: initially 50 to 100 mg, then 25 to 50 mg 3 to 4 times/day if necessary

Treatment of alcohol withdrawal:

• Oral: initially 50 to 100 mg, then repeat after 2 hours as needed until agitation or withdrawals are controlled and can increase up to 300 mg/day

Treatment of preoperative apprehension and anxiety:

• Oral: 5 to 10 mg/day 3 to 4 doses preceding surgery
• Injectable: 50 to 100 mg IM 1 hour before surgery

Treatment of renal impairment, hepatic impairment:

• Oral: initially 10 to 20 mg/day in 2 to 4 doses then increase as needed
• Injectable: 25 to 50 mg

Treatment for geriatric patients, or with existing debilitating disease:

• 5 mg/day, 2 to 4 doses

Discontinuation of this medication because of side effects is rare, but some common adverse effects exist that can occur, particularly in the elderly and debilitated. Most of the side effects associated with these medications are preventable by correct dose adjustment. Common side effects include fatigue, sedation, depression, dizziness, ataxia, slurred speech, weakness, confusion, forgetfulness, nervousness, hyperexcitability, and pain at the injection site. Some of the rare side effects include mania, weight gain, hallucination, hypotension, skin eruptions, menstrual irregularity, dry mouth, and hyper-salivation. Life-threatening side effects are blood dyscrasias, renal dysfunction, hepatic dysfunction, and respiratory depression, particularly when taken with CNS depressants in overdose. Hyperactive pediatric patients require monitoring for the paradoxical effect.[5][6]

There is an absolute contraindication in patients with known hypersensitivity to chlordiazepoxide, other benzodiazepines or its components, and the patient who has angle-closure glaucoma. Strong drug interactions exist with the use of another CNS depressant or opioid medications. Respiratory depression, increased sedation, coma, and death can occur if taking these two drugs at the same time. If it is necessary to use an opioid and chlordiazepoxide together, using the lowest possible dose with the shortest duration would help decrease the likelihood of respiratory depression. Clinicians should use this medication cautiously in people with pulmonary disease. An increased risk of suicidal ideation exists in a patient with major depressive disorder. It is not recommended for a patient who is pregnant or planning to get pregnant due to the potential risk of congenital anomalies, especially during the first trimester. Chlordiazepoxide may reduce the mental and physical abilities needed for the performance of some tasks, including driving a vehicle or operating heavy machinery. Likewise, it may diminish mental alertness in children.[7]