Imipramine Disposition in Alcoholics

Ciraulo, Domenic A.; Alderson, Lloyd M.; Chapron, Dennis J.; Jaffe, Jerome H.; Subbarao, Bollepalli; Kramer, Paul A.

doi:10.1097/00004714-198202000-00002

Cited by 38 publications

(8 citation statements)

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“…Several reviews have indicated that antidepressant medications have little role in treating the usual alcoholic patient (63,64), while they have noted deficiencies in the investigations reviewed (63,65). Also, a recent 12-week study of antidepressants in 69 actively drinking alcohol-dependent outpatients (48) reported that imipramine had no effect on drinking outcome but was associated with greater improvement in depression for subjects with primary depression.…”

Section: Discussionmentioning

confidence: 99%

Comparison of induced and independent major depressive disorders in 2,945 alcoholics

Schuckit

Tipp²,

Bergman³

et al. 1997

AJP

329

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Section: Discussionmentioning

confidence: 99%

Comparison of induced and independent major depressive disorders in 2,945 alcoholics

Schuckit

Tipp²,

Bergman³

et al. 1997

AJP

329

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“…Today, there are at least 8 classes of antidepressants available and the options for the treatment of depression have increased tremendously. For example, in the last 6 years, 8 new antidepressants have been approved by the US Food and Drug Administration (FDA); this does not include a number of others that are either in the process of review or prereview.…”

Section: Discussionmentioning

confidence: 99%

“…Impaired hepatic function decreases clearance of imipramine as does acute alcohol intake; long term ingestion of alcohol increases clearance of imipramine. [8,9) Smoking also increases imipramine clearance)JO,IIJ There is significant penetration of the drug into breast milk (milk to plasma ratio = 0.86 : 1 ). [ 12) Blood concentrations (of imipramine plus desipramine) in the range of 150 to 250 Ilg/L appear to correlate with improved clinical response.…”

Section: Imipraminementioning

confidence: 99%

Pharmacokinetic Optimisation of Therapy with Newer Antidepressants

Goodnick

1994

Clinical Pharmacokinetics

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Since the early 1950s, when imipramine was first introduced, a whole series of antidepressants with differences in structures, neurochemical effects and pharmacokinetics have been developed. Structurally or functionally, they have been classified as tricyclic antidepressants (TCAs), tetracyclic antidepressants, monoamine oxidase inhibitors (MAOIs), or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). In addition, there is a series of antidepressants with unique structures. Many of the newer TCAs appear to have shorter half-lives than the standard TCAs (e.g. imipramine), allowing for the possibility of a more rapid response, but requiring the drugs to be given in multiple daily doses, which may reduce patient compliance. The short time to peak plasma concentration (tmax) can also lead to rapid onset of adverse effects. The tetracyclic antidepressants have longer elimination half-lives (t1/2) than the TCAs, but there is only very minimal evidence for a relationship between drug concentrations in the blood and clinical response. The triazolopyridines, like the newer TCAs, show pharmacokinetic evidence for rapid onset of adverse effects and the need for multiple daily doses due to short tmax and t1/2. The newer MAOIs are a significant addition to therapy, as the rapid binding action of these medications increases their safety margin with regard to tyramine interactions. Further information in this area is required. In addition, moclobemide has pharmacokinetic features that are clinically beneficial (e.g. aging and renal dysfunction have little effect on the elimination of the drug), but also features that are not beneficial (e.g. nonlinear pharmacokinetics). Among the SSRIs, there are a range of t1/2 values for the parent drugs, from relatively short t1/2 values of less than 24 hours (paroxetine, fluvoxamine) to among the longest found (e.g. 2 days for fluoxetine). Only 2 of the agents (sertraline and citalopram) have linear pharmacokinetics, and 1 drug has nonlinear pharmacokinetics within the usual therapeutic range (fluvoxamine). Once a therapeutic blood concentration is established, linearity is helpful in avoiding the small dose changes and repeated rechecking of concentrations of medications that would be required for those agents with nonlinear pharmacokinetics. Sertraline stands out as having the best effects on behaviour among all antidepressants. However, fluoxetine and fluvoxamine are least likely to penetrate into breast milk. All 3 of the structurally unique newer antidepressants [amfebutamone (bupropion), viloxazine venlafaxine] have relatively short tmax values (1 to 2 hours), which may relate to the early onset of adverse effects. Amfebutamone has the benefits of linear pharmacokinetics with potential for defined therapeutic blood concentrations, lack of effect of liver enzymes on metabolism of the drug, and lack of significant effects of either aging or hepatic dysfunction on elimination of the drug. Thus, the antidepressants best suited for pharmacokinetic optimisation of ...

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“…Apart from problems such as compliance and liver function, there are both pharmacodynamic and pharmakokinetic interactions between alcohol and psychoatropic drugs. For example, due to an increased clear ance the plasma levels of imipramine and amitriptyline and to a lesser extent desipramine are reduced in alcohol ics [5][6][7], Increased plasma levels of imipramine have been reported in alcoholics taking disulfiram [8] and imipramine, clomipramine and amitriptyline in vitro were found to inhibit the activity of alcohol dehydroge nase [9],…”

Section: Discussionmentioning

confidence: 99%