Doxepin serum level

An isolated report describes a reduction in doxepin serum levels attributed to the use of tamoxifen. 

Chronic abuse of alcohol can lead to enhanced activity of cytochrome P450 enzymes and a consequent decrease in tricyclic antidepressant (TCA) serum levels. Central receptor interactions between alcohol and TCAs can cause impaired motor abilities (evident with amitriptyline, clomipramine, doxepin, and nortriptyline). 

Phenytoin, a liver enzyme inducer, decreases serum levels of TCAs (especially desipramine and clomipramine). An increase in serum levels of nortriptyline and trazodone has also been reported. In these cases, the net effect of enzyme induction (by phenytoin) and enzyme inhibition (by TCAs) seem to be in favor of the inhibitory effects. Carbamazepine also induces liver enzymes, with a consequent reduction in serum levels of TCAs (amitriptyline, desipramine, doxepin, and nortriptyline). These effects of carbamazepine have not been observed with clomipramine, but have been reported with selective serotonin reuptake inhibitors (SSRIs). 

Most APDs, as well as TCAs, are inhibitors of the cytochrome P450 enzymes, thus potentially increasing each other s serum levels. For haioperidoi, an increase in serum levels of TCAs (by about 2-fold) is found in up to 10% of patients treated with ciomipramine or nortriptyiine (but is not found with desipramine). Levomepromazine can significantly increase ciomipramine serum levels. Perphenazine has been found to increase serum levels of amitriptyline, desipramine, and nortriptyiine, while thioridazine has been reported to increase desipramine serum levels. Thiothixene levels are usually increased by TCAs such as doxepin, nortriptyline, and clomipramine (the latter combination increases the risk for tardive dyskinesia). 

This lowers serum levels of TCAs (desipramine and doxepin), probably due to decreased gastrointestinal absorption of TCAs. 

Carbamazepine induces hepatic catabolic enzymes, with a consequent reduction in serum levels of antidepressants (mainly described with amitriptyline, desipramine, doxepin, imipramine, mianserin, and nortriptyline). A decrease in bupropion serum levels was also reported with carbamazepine. These effects were not observed with clomipramine. Fluoxetine and fluvoxamine inhibit the metabolism of carbamazepine and valproate (up to 30% and 50% increases in serum levels, respectively). No significant interaction has yet been found between paroxetine and carbamazepine or valproate. 

Thiothixene levels are usually increased by TCAs (doxepin and nortriptyline). Additive adverse effects have also been reported when co-administered with ciomipramine (rapid development of tardive dyskinesia). Marked extrapyramidal side-effects have been reported (a few cases only) with suipiride or thiothixene when fluoxetine is added to the regimen. Unlike the established interactions between most phenothiazines and TCAs, in which serum levels of both agents could increase, no apparent interaction is evident to date between fiupenthixoi and imipramine or any other TCA. 

Part of the explanation for the increased C3S1S depression is that both alcohol and some of the tricyclics, particularly amitriptyline, cause drowsiness and other CNS depressant effeets, which can be additive with the effects of alcohol. The sedative effects have been reported to be greatest with amitriptyline, then doxepin and imipramine, followed by nortriptyline, and least with amoxapine, clomipramine, desipramine, and protriptyline. In addition acute alcohol intake causes marked increases (100 to 200%) in the plasma levels of amitriptyline, probably by inhibiting its first pass metabolism. Alcohol-induced liver damage could also result in impaired amitriptyline metabolism. The lower serum levels of imipramine and desipramine seen in abstinent alcoholics are attributable to induction of the cytochrome P450 isoenzymes by alcohol. ... 

The serum levels of amitriptyline, desipramine, doxepin, imipramine and nortriptyline can be reduced (halved or more) by carbamazepine but there is evidence that this is not necessarily clinically important. In contrast raised clomipramine ievels have been seen in patients taking carbamazepine. An isolated report describes carbamazepine toxicity in a patient shortly after she started to take desipramine. 

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. 

Limited evidence siu esitsi that very high fibre diets can reduce the serum levels of doxepin and desipramine, and therefore decrease their effects. The bioavailability of amitriptyline may be... 

Roessner MD, Demling J, Bleich S. Doxepin increases serum cholesterol levels. Can J Psychiatry 2004 49 74-5. 

In another study cimetidine 600 mg twice daily was found to double the steady-state plasma levels of doxepin 50 mg daily, whereas ranitidine 300 mg daily had no effect. A patient taking doxepin complained that the normally mild adverse effects (urinary hesitancy, dry mouth and decreased visual acuity) became incapacitating when he also took cimetidine. His serum doxepin levels were found to be elevated. ... 

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