Tricyclic antidepressants + Benzodiazepines and related drugs - Drug Interactions

Concurrent use is not uncommon and normally appears to beuneventful. However,three patients became drowsy, forgetfuland appeared uncoordinated and drunk while taking amitriptyline and chlordiazepoxide. A combined preparation of amitriptyline and chlordiazepoxide (Limbitrol) is available but its advantages have been questioned: adverse effects have been seenin four patients. Diazepam may increase risks of carrying outcomplex tasks (e.g. driving) if added to amitriptyline,as may other combinations of benzodiazepines and tricyclics.

Chlordiazepoxide. Clinical studies in large numbers of patients have shown that incidence of adverse reactions while taking amitriptyline and chlordiazepoxide was no greater than might have been expected with either of drugs used alone,(See reference number 1-3) but a few adverse reports have been documented. A depressed patient taking amitriptyline 150mg and chlordiazepoxide 40mg daily became confused,forgetful and uncoordinated. He acted as though he was drunk (See reference number 4). Two other patients taking amitriptyline and chlordiazepoxide experienced drowsiness, memory impairment, slurring of speech and an inability to concentrate. Both were unable to work and one described himself as feeling drunk (See reference number 5). Four patients taking Limbitrol are reported to have experienced some manifestations of toxicity (delusions,confusion, agitation, disorientation, dry mouth, blurred vi-sion) (See reference number 6). Some of these effects seem to arise from increased CNS depression (possibly additive) and/or an increase in antimuscarinic adverse effects of tricyclic.

Diazepam. A study demonstrated an increase in amitriptyline levels when diazepam was given,(See reference number 7) and two others found that addition of diazepam to amitriptyline 50 to 75mg further reduced attention and performance of a number of psychomotor tests (See reference number 8,9). In contrast,two studies suggested that diazepam did not affect amitriptyline levels (See reference number 3,10).

Studies on effects of nitrazepam and oxazepam on steady-state plasma levels of amitriptyline;(See reference number 3)did not find any interactions

An in vitro study in human liver microsomes found that alprazolam does not affect metabolism (hydroxylation) of desipramine (See reference number 12)

tients taking imipramine, and does not reduce effects of antidepressant.16,17

Zaleplon. A single 75mg dose of imipramine had no effect on pharmacokinetics of zaleplon 20 mg, and psychomotor tests showed only short term additive effects lasting 1 to 2 hrs (See reference number 18).

Zolpidem. A single-dose study using zolpidem 20mg and imipramine 75mg found no effect on pharmacokinetics of either drug. However, imipramine increased sedative effects of zolpidem, and anterograde amnesia was seen (See reference number 19).

Lorazepam may be useful for anxiety or insomnia in elderly depressed patients without impairing response to treatment with nortriptyline (See reference number 20)

Studies on effects of alprazolam, chlordiazepoxide, diazepam, nitrazepam and oxazepam on steady-state plasma levels of nortriptyline(See reference number 3,12,21)found no interactions.

In a study in 10 healthy subjects, when zopiclone and trimipramine were given concurrently for a week, bioavailability of zopiclone was reduced by almost 14 % and bioavailability of trimipramine by almost 27%, but neither of these changes were statistically significant (See reference number 22).

There seems to be no reason for avoiding concurrent use of benzodiazepines and tricyclics although advantages and disadvantages remain subject of debate. Other combinations of tricyclic antidepressants and benzodiazepines would not be expected to behave differently from those described here. Some patients will possibly experience increased drowsiness and inattention with more sedative antidepressants such as amitriptyline, particularly during first few days, and this may be exaggerated by benzodiazepines such as diazepam. Driving risks may therefore be increased.

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