Dosing & Uses
Dosage Forms & Strengths
tablet: Schedule IV
Depression with Anxiety
1 tablet (5-10 mg chlordiazepoxide/12.5-25 mg amitriptyline) PO three/four times daily; may increase to 6 tablets if necessary; 2 tablets reported to be effective in some patients
Safety and efficacy not established
Avoid; strong anticholinergic and sedative effects; may cause orthostatic hypotension (Beers criteria)
Consider alternatives; if must use, initiate with lower initial dose; long-acting active metabolites
1 tablet (5 mg/12.5 mg) PO three times daily
Serious - Use Alternative
Significant - Monitor Closely
Frequency Not Defined
Blood dyscrasias (agranulocytosis)
Hepatic dysfunction (jaundice)
Black Box Warnings
Children and Antidepressants
- In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (age <24 yr) taking antidepressants for major depressive disorders and other psychiatric illnesses
- This increase was not seen in patients aged >24 yr; slight decrease in suicidal thinking was seen in adults >65 yr; risks must be weighed in children and young adults against the benefits of taking antidepressants
- Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; monitor during the initial 1-2 months of therapy and dosage adjustments
- Patient’s family should communicate to the healthcare provider any abrupt changes in behavior
- Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy
- Not approved for pediatric patients
Antipsychotics & Dementia
- Patients with dementia-related psychosis that are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials; deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature
- Not approved for treatment of dementia-related psychosis
Severe cardiovascular disorders
Angle clossure glaucoma
Within 14 days of MAOIs
Any drugs or conditions that prolong QT interval
Acute recovery post-MI
Caution in BPH, urinary/GI retention, increased IOP, thyroid dysfunction, open-angle glaucoma, seizure disorders, brain tumor, respiratory impairment, respiratory disease,
Clinical worsening & suicide ideation may occur despite medication in adolescents & young adults (aged 18-24 yr)
Write prescription for smallest effective dose
Risk of anticholinergic side-effects
May cause orthostatic hypotension
Paradoxical reactions including hyperactive or aggressive behavior reported
Both agents may cause sedation and impair ability to perform tasks requiring mental alertness
SIADH and hyponatremia reported with therapy
Some patients may experience a large increase in amitriptyline concentration in presence of topiramate; any adjustments in amitriptyline dose should be made according to patient's clinical response and not on basis of plasma level
Pregnancy & Lactation
Pregnancy Category: D
Lactation: Excretion in milk unknown; not recommended
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Mechanism of Action
Chlordiazepoxide: Antianxiety agent; depresses all levels of CNS, including limbic and reticular formation, possibly by increasing gamma-aminobutyric acid (GABA) activity, a major inhibitory neurotransmitter
Amitriptyline: Antidepressant; neurotransmitter (especially norepinephrine and serotonin) reuptake inhibitor; elicits anticholinergic effects
Bioavailability: Slow and erratic following IM admin (chlordiazepoxide)
Peak serum time: 4 hr (amitriptyline)
Peak serum time: 0.5-2 hr
Onset of action: 1-5 min (IV, chlordiazepoxide)
Onset of action: 6 weeks
Duration: 15-60 min (IV, chlordiazepoxide)
Vd: 3.3 L/kg (chlordiazepoxide)
Chlordiazepoxide: demoxepam, desmethylchlordiazepoxide, desmethyldiazepam, oxazepam
Amiptriptyline: hepatic metabolism via CYP2C19, CYP3A4; nortriptyline is an active metabolite
- Chlordiazepoxide: 6.6-28 hr
- Amitriptyline: 9-27 hr
- Chlordiazepoxide: Predominately urine
- Amitriptyline: Urine (25-50%), small amounts in bile
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