The Tricyclic Antidepressants

Rudorfer, Matthew V.; Potter, William Z.

doi:10.1007/978-1-4684-1253-6_9

Cited by 33 publications

(62 citation statements)

References 67 publications

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“…However, drug concentration differences due to genotype are not exactly the same as drug concentration differences due to different preparations of a drug because the active metabolites also contribute to the overall drug effect or are responsible for adverse drug reactions. 22,33 Whenever possible, we based dose adjustments on the active moiety of drug exposure consisting of parent drug and active metabolites if prevalent in considerable concentrations.…”

Section: Metabolic Polymorphismsmentioning

confidence: 99%

Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response

et al. 2004

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Genetic factors contribute to the phenotype of drug response. We systematically analyzed all available pharmacogenetic data from Medline databases on the impact that genetic polymorphisms have on positive and adverse reactions to antidepressants and antipsychotics. Additionally, dose adjustments that would compensate for genetically caused differences in blood concentrations were calculated. To study pharmacokinetic effects, data for 36 antidepressants were screened. We found that for 20 of those, data on polymorphic CYP2D6 or CYP2C19 were found and that in 14 drugs such genetic variation would require at least doubling of the dose in extensive metabolizers in comparison to poor metabolizers. Data for 38 antipsychotics were examined: for 13 of those CYP2D6 and CYP2C19 genotype was of relevance. To study the effects of genetic variability on pharmacodynamic pathways, we reviewed 80 clinical studies on polymorphisms in candidate genes, but those did not for the most part reveal significant associations between neurotransmitter receptor and transporter genotypes and therapy response or adverse drug reactions. In addition associations found in one study could not be replicated in other studies. For this reason, it is not yet possible to translate pharmacogenetic parameters fully into therapeutic recommendations. At present, antidepressant and antipsychotic drug responses can best be explained as the combinatorial outcome of complex systems that interact at multiple levels. In spite of these limitations, combinations of polymorphisms in pharmacokinetic and pharmacodynamic pathways of relevance might contribute to identify genotypes associated with best and worst responders and they may also identify susceptibility to adverse drug reactions.

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Section: Metabolic Polymorphismsmentioning

confidence: 99%

Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response

et al. 2004

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“…Tricyclics undergo multiple biotransformation actions in the liver, producing progressively more polar metabolites which can be readily excreted by the kidneys [19]. Less than 5 % of a dose of a TCA is eliminated unchanged.…”

Section: Tricyclic Antidepressantsmentioning

confidence: 99%

Pharmacokinetics of Antidepressants in Patients with Hepatic Impairment

et al. 2014

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Appropriate use of antidepressant in patients with hepatic impairment requires careful consideration of how the hepatic illness may affect pharmacokinetics. This review aims to analyze pharmacokinetic profile, plasma level variations so as the metabolism of several antidepressants relating to their use in patients with an hepatic impairment. Due to the lack of data regarding hepatic impairment itself, the review is focused mainly on studies investigating pharmacokinetics in hepatic cirrhosis or alcohol-related conditions. More data on reduced hepatic metabolism can be extrapolated by drug studies conducted in elderly populations. Dose adjustment of antidepressants in these patients is important as most of these drugs are predominantly metabolized by the liver and many of them are associated with dose-dependent adverse reactions. As no surrogate parameter is available to predict hepatic metabolism of drugs, dose adjustment according to pharmacokinetic properties of the drugs is proposed. There is a need for a more balanced assessment of the benefits and risks associated with antidepressants use in patients with hepatic impairment, particularly considering pharmacokinetic profile of the drugs to ensure that patients, who would truly benefit from these agents, are not denied appropriate treatment. In conclusion, kinetic studies for centrally acting drugs including antidepressants with predominant hepatic metabolism should be carried out in patients with liver disease to allow precise dose recommendations for enhanced patient safety.

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“…Dies gilt aber nicht in gleichem Masse für die bei den hepatischen Stoffwechselreaktionen anfallenden glucuronidierten Metaboliten. Diese werden überwiegend renal ausgeschieden [73]. Die renale Clearance beispielsweise von Lithium ist unter ACE-Hemmern deutlich vermindert [74].…”

Section: Kardiovaskuläre Erkrankungenunclassified

Psychopharmacotherapy in somatic diseases – treatment principles in daily medical routine

Rothenhäusler

Kapfhammer

2005

Wien Med Wochenschr

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Up to 46.5% of general hospital inpatients suffer from clinically relevant psychiatric disorders. Appropriate psychopharmacotherapy of comorbid mental disorders in the medically ill can have positive effects on the course of somatic illness and can enhance quality of life in patients with medical or neurologic conditions. However, treating psychiatric disorders in this population can often be challenging, even for the most seasoned clinicians. An increasingly important issue in daily medical routine when prescribing medications is the possibility that a newly prescribed drug may interact with existing pharmacotherapy. Most often the concern is to avoid adverse consequences, such as undermining the effectiveness of previously stable drug therapy or precipitating the appearance of new adverse events. We have used the examples of Parkinson's disease, epilepsy and cardiovascular disease commonly associated with mental disorders to illustrate how these considerations affect the clinician's choice of a psychotropic drug in the medically ill.

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The Tricyclic Antidepressants

Cited by 33 publications

References 67 publications

Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response

Pharmacogenetics of antidepressants and antipsychotics: the contribution of allelic variations to the phenotype of drug response

Pharmacokinetics of Antidepressants in Patients with Hepatic Impairment

Psychopharmacotherapy in somatic diseases – treatment principles in daily medical routine

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