Chlordiazepoxide with amitriptyline

A 66-year old man became lethargic, confused, and disoriented after taking melatonin 24 mg with his usual amitriptyline and chlordiazepoxide (30). 

Tricyclic antidepressants are commoniy taken in overdose by suicidal patients and represent a major cause of poisoning hospitaiizations and deaths. Currently available tricyclic antidepressants are described in Table 11-7. Amitriptyline is also marketed in combination with chlordiazepoxide (Limbitrol ) or perphenazine (Etrafon or Tria-viF ). Cyclobenzaprine (FlexerilTW), a centrally acting muscle relaxant (see p 339), is structurally related to the tricyclic antidepressants but exhibits minimal cardiotoxic and variable CNS effects. Newer, noncyclic antidepressants are discussed on p 88. Monoamine oxidase inhibitors are discussed on page 269. 

Po and Irwin (1979) used TLC to separate numerous tricyclic neuroleptic tranquilizers. Samples were dissolved in ethyl acetate, and the mobile phase consisted of mixtures of different n-alcohols with water. Circular development in a Camag U chamber was used, and spots were detected by fluorescence quenching. The /Jp values of some of the better known drugs developed in methanol-water (90 10) were amitriptyline, 0.17 clopenthixol, 0.40 doxepin, 0.42 nortriptyline, 0.37 and promazine, 0.14. Shirke et al. (1994) determined amitriptyline and chlordiazepoxide in combined dosage forms using ethyl acetate-methanol-dieth-ylamine (9.5 0.5 0.05) mobile phase and scanning at 245 nm. 

A 68-year-old man, who had been taking lorazepam, perphenazine, and amitriptyline for many years, developed acute thrombocytopenic purpura after combination therapy of chlordiazepoxide 5 mg and clidinium 2.5 mg tds for irritable bowel syndrome (2). His disease improved after withdrawal of chlordiazepoxide and clidinium and treatment with intravenous prednisolone. 

Amitriptyline blocks reuptake of serotonin and norepinephrine in CNS. Chlordiazepoxide potentiates effects of GABA in CNS. The combination is indicated in the treatment of moderate to severe depression associated with moderate to severe anxiety. 

Trazodone is perhaps the most sedative antidepressant available, being more sedative than amitriptyline, trimi-pramine, doxepan, or imipramine. Therefore, death has occurred in patients taking trazodone with alcohol, chloral hydrate, diazepam, chlordiazepoxide, meprobamate, or amobarbital. 

General Practitioner Clinical Trials. Chlordiazepoxide with amitriptyline in neurotic depression. Practiticmer ( 969) 202,437-40. 

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