Imipramine serum level

Most antipsychotic drugs as well as tricyclic antidepressants (TCAs) are inhibitors of the chytochrome P450 liver catabolic enzymes, thus potentially increasing each other s serum levels. Chlorpromazine increases imipramine serum levels. Levomepromazine can cause a significant increase in clomipramine serum levels. Perphenazine has been reported to increase the serum levels of amitriptyline, desipramine, imipramine, and nortriptyline. Thioridazine has also been shown to increase TCA serum levels (mainly desipramine). Marked extrapyramidal side-effects have been reported in a few cases with fluphenazine or perphenazine when fluoxetine was added to the regimen. The mechanism is not known. A mutual increase in serum levels of both thioridazine and paroxetine is evident when these agents are... 

Though not used clinically, the therapeutic serum level for imipramine is 225 to 300 ng/ml the toxic serum level is greater than 500 ng/ml... 

Loof et al. (1995) reported the use of carbamazepine (300-1200 mg/day, serum levels 10-11.5 pg/mL) in 28 children and adolescents with sexual abuse histories. By treatment end, 22 of 28 patients were asymptomatic of PTSD. The remaining six were significantly improved in all PTSD symptoms except for continued abuse-related nightmares. Half of this cohort had com-orbid ADHD, depression, ODD or polysubstance abuse and were treated with concomitant medications, e.g., methylphenidate, clonidine, sertraline, fluoxetine, or imipramine. 

CBZ s molecular structure is similar to imipramine. It is primarily metabolized by the liver and, like lithium, has a narrow therapeutic index, predisposing to toxicity with elevated serum levels. 

Do not exceed plasma concentration of 225 mg/ml (imipramine plus its desipramine metabolite) in children, due to increased risk of cardiovascular effects at higher serum levels. 

While ASMase-deficient mice survive lethal doses of LPS (see above), the serum levels of TNF-a-induced by sublethal doses of LPS are similar to those in WT mice (Haimovitz-Friedman et ak, 1997) isolated ASMase-deficient macrophages respond to LPS with a normal pattern of cytokine secretion (Manthey and Schuchman, 1998). Thus, there is no evidence that ASMase is important for LPS-induced inflammatory responses. A recent report showed that imipramine, an inhibitor of cellular ASMase activity, blocked LPS-induced TNF-a secretion from differentiated human monocyte-like THP-1 cells (Cuschieri et ak, 2007). However, in our hands imipramine has no effect on cytokine secretion from these cells or from monocytes isolated from human blood (A.Billich, unpublished observations). 

Most studies have revealed no significant interactions with TCAs. Anecdotal reports suggest that alprazolam might increase the serum levels of imipramine by up to 30%. Clonazepam can decrease desipramine levels, while diazepam can increase amitriptyline serum levels in a few cases. 

Fluvoxamine inhibits the cytochrome P450 liver catabolic enzymes (predominantly this is inhibition of N-demethylation), leading to an increase in tricyclic antidepressant (TCA) serum levels. Plasma levels of several antidepressant drugs (e.g. amitriptyline, clomipramine, desipramine, imipramine, maprotiline, and nortriptyline) have been reported to increase by up to 4-fold during co-administration with fluvoxamine. Fluvoxamine at a daily dose of 50-100 mg causes a 3-4-fold increase in the plasma concentration of mirtazapine. 

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. 

Tricyclic antidepressants Alprazolam has been found to increase imipramine and desipramine serum levels by about 25%. The mechanism is unknown. ... 

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 phenytoin levels of 2 patients rose over a 3-month period when they were given imipramine 75 mg daily. One of them had an increase in phenytoin levels from about 7.6 to 15 micrograms/mL and developed mild toxicity (drowsiness and uncoordination). These signs disappeared and the phenytoin serum levels of both patients fell when the imipramine was withdrawn. One of them was also taking nitrazepam and clonazepam, and the other sodium valproate and carbamazepine, but were stable on these combinations before the addition of imipramine. ... 

A falsely elevated imipramine level was recorded when HPLC was used to determine serum imipramine levels in a patient taking imipramine, quetiapine, fluvoxamine, lithium and docusate. The abnormal readings were found to have been caused by a metabolite of quetiapine, and normal readings were obtained by altering the wavelength for detection of imipramine. Nortriptyline levels have been found to be falsely elevated in a patient also taking quetiapine when blood was analysed using fluorescence polarisation immunoassay, but were normal when an HPLC... 

In vitro experiments with human liver slices indicate that methylphenidate inhibits the metabolism of imipramine, resulting in raised blood levels. The accelerated response to tricyclic antidepressants may also be partly due to increased serum levels in the presence of methylphenidate, although the adverse effects observed were not entirely consistent with elevated levels of tricyclics. There are also reports suggesting that... 

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. 

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. 

Troleandomycin increases the plasma levels of imipramine, and an isolated report suggests that josamydn may possibly increase amitriptyline serum levels. Erythromycin may possibly raise clomipramine levels, but was not found to interact with other tricyclic antidepressants in one study. 

Quinidine can reduce the clearance of desipramine, imipramine, nortriptyline and trimipramine, and quinine can reduce the clearance of desipramine, thereby increasing their serum levels. 

Terbinafme markedly increased the AUC of desipramine in a pharmacokinetic study. Case reports describe increases in the serum levels of amitriptyline, desipramine, imipramine and nortriptyline, with associated toxicity, in patients additionally given oral terbinafme. 

A lack of correlation of serum levels with clinical effects previously observed for chlorpromazine and imipramine was also observed for meprobamate, tybamate and pentobarbital sodium ... 

TCAs ANTIDIABETIC DRUGS Likely to impair control of diabetes. TCAs may t serum glucose levels by up to 150%, t appetite (particularly carbohydrate craving) and i metabolic rate Be aware and monitor blood sugar weekly until stable. Generally considered safe unless diabetes is poorly controlled or is associated with significant cardiac or renal disease. Amitriptyline, imipramine and citalopram are also used to treat painful diabetic neuropathy... 

Evidence from two patients suggests that imipramine can raise serum phenytoin levels but nortriptyline and amitriptyiine appear not to do so. Phen i oin possibiy reduces serum desipramine iev-els. Note that the tricyciics aiso iower the convuisive threshoid. 

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