Amitriptyline dosage

Mr. Hopkins has been severely depressed for several months. Two weeks ago the primary care provider prescribed amitriptyline 30 mg orally four times a day. His family is concerned because he is still depressed. They are requesting that the dosage be increased. Discuss what information you would give Mr. Hopkins and his family and what assessments you could make... 

Some studies compare dietary supplements to sub-therapeutic dosages of prescription medicine. For example, St. John s wort is compared to some of the tricyclic antidepressants. However, the given doses of amitriptyline and imipramine were below the recommended antidepressant doses. 

Determination of amitriptyline plasma concentrations is not routinely recommended but maybe useful in identifying toxicity, drug interactions, or noncompliance (adjustments in dosage should be made according to clinical response not... 

The Division of Drug Experience of the US Department of Health and Welfare issued a note on five cases of the syndrome of inappropriate antidiuretic hormone secretion and drugs to which it has been attributed (1137). All involved drugs with a tricyclic structure one patient was taking imipramine, three carbamazepine, and the others the closely related muscle relaxant cyclobenz-aprine. The dosage of imipramine was 50 mg/day for 3 weeks and the patient was a 72-year-old woman. Other cases have been reported, involving amitriptyline (1137), imipramine, and protriptyline (SEDA-17,17). 

A method of treating human mental disorders involving depression which comprises orally administering to a human affected by depression 5-(3-dimethylaminopropylidene) dibenzo[a,d][l,4]cycloheptadiene (amitriptyline) or its non-toxic salts in daily dosages of 25 to 250 mg of said compound. 

Amoxapine is less potent than other tricyclic antidepressants, with a therapeutic dosage range of 75-600 mg/day (usually 200-400 mg/day). Clinical effects have not been consistently correlated with plasma concentrations, but amoxapine has similar efficacy to other tricyclic antidepressants in heterogeneous populations of depressed patients. Controlled comparisons have shown that its clinical profile is very similar to that of imipra-mine (3) and that it is somewhat less sedative than amitriptyline (4-6). In two of these studies (4,6) the... 

Drugs that meet one or more of the criteria given above and have been shown to exhibit significant differences in the bioavailability of marketed dosage forms include digoxin, quinidine, furosemide, nitrofurantoin, prednisone, chloramphenicol, theophylline, chlorpromazine, phenytoin, amitriptyline, and phenylbutazone. 

A comparative study of 99 patients taking amitriptyline or nortriptyline alone, and 60 other patients also taking perphenazine 10 mg daily, found that although the tricyclic antidepressant dosages were the same, the plasma tricyclic antidepressant levels of the perphenazine group were up to 70% higher. ... 

A study in 12 schizophrenic patients found that amitriptyline 50 to 100 mg daily had no effect on the serum levels of risperidone 3 mg twice daily. However, a 26-year-old man taking amitriptyline 25 mg daily developed extrapyramidal reactions alter his dosage of risperidone was increased from 2 to 4 mg daily On another occasion extrapyramidal adverse effects developed after risperidone 2 mg daily was added to treatment with amitriptyline 25 mg and fluoxetine 20 mg daily. Both pharmacokinetic and pharmacodynamic reasons for this reaction have been suggested. The cases illustrate that there is the potential for an adverse interaction between these drugs, which should be borne in mind when prescribing both drugs. 

The interaction between clonidine and the trieyelics is established and clinically important. The incidence is uncertain but it is not seen in all patients. Avoid concurrent use unless the effects can be monitored. Increasing the dosage of clonidine may possibly be effective. The clonidine dosage was apparently successfully titrated in 10 out of 11 hypertensive patients already on amitriptyline or imipramine. Only clomipramine, desipramine and imipramine have been implieated so far, but other tricyclics would be expected to behave similarly (amitriptyline, nortriptyline and protriptyline have been shown to interact in animals ). The tetracyclic antidepressants maprotiline and mianserin do not generally appear to interact with clonidine. The isolated case of hypotension with trazodone is of unknown general importance. 

Amitriptyline. A woman who had been taking amitriptyline 10 mg at night and thioridazine developed the serotonin syndrome after taking half a tablet of nefazodone (dosage unspecified). ... 

A study found that carbamazepine reduced the serum levels of nortriptyi-ine by 58% and of amitriptyline plus its metabolite, nortriptyline, by 60% in 8 psychiatric patients. In 17 other patients carbamazepine reduced serum doxepin levels by 54% and doxepin plus its metabolite, nordox-epin, by 55%. A retrospective study of very large numbers of patients confirmed that carbamazepine approximately halves the serum levels of amitriptyline and nortriptyline. An elderly woman needed her nortriptyline dosage to be inereased from 75 to 150 mg daily to achieve effective antidepressant serum levels when carbamazepine 500 to 600 mg daily was added. ... 

The reduction in the serum levels of amitriptyline, desipramine, doxepin, imipramine and nortriptyline caused by the interaction with carbamazepine appears to be established but the clinical importance is very much less certain. Evidence from one study, that achieved a beneficial response in patients taking tricyclics and carbamazepine suggests that it is possibly not necessary to increase the tricyclic dosage to accommodate this interaction. The fact that a retrospective study found that increased imipramine doses were being given to those taking carbamazepine suggests that this interaction will be naturally accounted for. If carbamazepine is added to treatment with any of these tricyclics, be aware that the dose of the tricyclic may need to be titrated up to achieve the desired therapeutic response. Remember too that the tricyclics can lower the convulsive threshold and should therefore be used with caution in patients with epilepsy. 

The interactions with cimetidine are well established, well documented and of clinical importance. The incidence is uncertain hut most patients could be affected. Those taking amitriptyline, desipramine, doxepin, imi-pramine or nortriptyline who are given cimetidine should be warned that adverse effects such as mouth dryness, urine retention, blurred vision, constipation, tachycardia, postural hypotension may be more likely to occur. Other tricyclic antidepressants would be expected to be similarly affected. If symptoms are troublesome reduce the dosage of the antidepressant (33 to 50% has been suggested) or replace the cimetidine with ranitidine, which does not appear to interact. Other H2-ieceptor antagonists that do not cause enzyme inhibition (e.g. famotidine and nizatidine) would also not be expected to interact. 

A number of other reports and studies clearly confirm that marked increases occur in the levels of amitriptyline, " clomipramine, desipramine, " imipramine " and nortriptyline, " accompanied by toxicity, if fluoxetine is added without reducing the dosage of the tricyclic antidepressant. Delirium and seizures have also been described, and a death has been attributed to chronic amitriptyline toxicity caused by fluoxetine. The pharmacokinetics of fluoxetine appear not to be affected by amitriptyline. ... 

The amitriptyline plasma levels of 8 patients rose (range 15 to 233%) when they were also given fluvoxamine 100 to 300 mg daily. Even larger rises in plasma clomipramine levels occurred (up to eightfold) in four other patients given fluvoxamine 100 to 300 mg daily. The trieyelie dosages remained the same or were slightly lower. No toxieity was seen. " ... 

Information seems to be limited to these reports. It would seem prudent to monitor for trieyolie adverse effeets (sueh as dry mouth, blurred vision and urinary retention) in patients given valproate and amitriptyline, clomipramine, or nortriptyline and to reduee the dosage of the tricyclic if necessary. Where possible eonsider monitoring tricyclic levels. Information about other trieyelie antidepressants seems to be lacking. The occurrence of status epileptieus in another patient reinforces the fact that the tricyclics can lower the eonvulsive threshold and should therefore be used with caution in patients with epilepsy. 

When 6 healthy subjects took a single 75-mg dose of amitriptyline with a single 1-g dose of sucralfate, the AUC of the amitriptyline was reduced by 50%. Concurrent use should be monitored to confirm that the therapeutic effects of the antidepressant are not lost. An increase in the dosage may be needed. There seems to be nothing documented about other tricyclics. 

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