UMLS:C0011570 - FACTA Search

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Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(-)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(-)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.
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PMID:Enantioselective analysis of citalopram and metabolites in adolescents. 1180

Recent studies indicate that the Tg2576 transgenic mouse model of Alzheimer's disease [tg(hAPP)] demonstrates disturbances in plasma glucose and neuroendocrine function reminiscent of Alzheimer's disease (AD). Alterations in any one of these systems can have a profound effect on hepatic cytochrome P450 (CYP) expression. Additionally, the recent discovery that amyloid beta 1-42 can induce the expression of CYP reductase in neuronal cultures further suggests that hepatic CYP-related metabolism may be affected by the expression of mutant human amyloid precursor protein in these tg(hAPP) mice. Therefore, the current study was conducted to investigate the activity and protein content of several CYP isoforms in the livers and kidneys of aged (20-month-old) tg(hAPP) mice. tg(hAPP) mice exhibit significant elevations in hepatic CYP2B, CYP2E1-, CYP3A- and CYP4A-associated activities and CYP4A immunoreactive protein compared with wild-type. In contrast to the liver, a significant depression in renal CYP2E1- and CYP4A-associated activities were demonstrated in tg(hAPP) mice. The presence of the mutant hAPP protein was detected in the brain, kidney and livers of tg(hAPP) mice.
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PMID:Elevated hepatic and depressed renal cytochrome P450 activity in the Tg2576 transgenic mouse model of Alzheimer's disease. 1184 64

This paper provides an updated review of the use of antidepressant drugs in dermatology. Some of the psychiatric disorders that are usually comorbid with dermatological disorders and respond to antidepressants include major depressive disorder, obsessive compulsive disorder, body dysmorphic disorder, social phobia and post-traumatic stress disorder usually secondary to trauma and abuse during early life. Cutaneous symptoms may be the feature of a primary psychiatric disorder, e.g. cutaneous body image problems, dermatitis artefacta, neurotic excoriations and trichotillomania, or psychiatric syndromes may be comorbid with a primary dermatological disorder such as the association of major depressive disorder or social phobia with psoriasis and obsessive compulsive disorder with acne excoriee. Some of the salient pharmacological properties of the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitor (SSRI) antidepressants are reviewed. The review indicates that the SSRI antidepressants are potentially beneficial in the management of all the major psychiatric syndromes that are encountered in dermatological disorders. The generally more favourable side-effect profile of the SSRIs, such as lower cardiotoxicity in contrast to the TCAs, has made them the first-line agents for the treatment of depression. Furthermore, some of the pharmacological properties of the antidepressant agents that are not related to their antidepressant activity, such as the histamine H1 blocking effect of TCAs, such as doxepin, amitriptyline and trimipramine, are of benefit in dermatological conditions such as urticaria and pruritus. This paper reviews the general guidelines for use of antidepressants and salient drug-drug interactions resulting mainly from the inhibition of the cytochrome P450 (CYP) 2D6 and 3A3/4 isoenzymes by some of the SSRI antidepressants. Before prescribing an antidepressant agent, the specific guidelines, side-effect profile, drug-drug interactions and most current indications should always be obtained.
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PMID:The use of antidepressant drugs in dermatology. 1184 9

The selective serotonin reuptake inhibitors (SSRIs) have become the most prescribed antidepressants in many countries. Although the SSRIs share a common mechanism of action, they differ substantially in their chemical structure, metabolism, and pharmacokinetics. Perhaps the most important difference between the SSRIs is their potential to cause drug-drug interactions through inhibition of cytochrome-P450 (CYP) isoforms. This paper provides an update on both the in vitro and in vivo evidence with respect to CYP-mediated drug-drug interactions with this class of antidepressants. The available evidence clearly indicates that the individual SSRIs display a distinct profile of cytochrome P450 inhibition. Fluvoxamine is a potent CYP1A2 and CYP2C19 inhibitor, and a moderate CYP2C9, CYP2D6, and CYP3A4 inhibitor. Fluoxetine and paroxetine are potent CYP2D6 inhibitors, whereas fluoxetine's main metabolite, norfluoxetine, has a moderate inhibitory effect on CYP3A4. Sertraline is a moderate CYP2D6 inhibitor; citalopram appears to have little effect on the major CYP isoforms. Fluoxetine deserves special attention as inhibitory effects on CYP-activity can persist for several weeks after fluoxetine discontinuation because of the long half-life of fluoxetine and its metabolite norfluoxetine. Drug combinations with SSRIs should be assessed on an individual basis. Knowledge regarding the CYP-isoforms involved in the metabolism of the co-administered drug may help clinicians to anticipate and avoid potentially dangerous drug-drug interactions. Anticipated interactions can usually be managed by appropriate dose adjustment and titration of the object drug. In some cases, therapeutic drug monitoring can be useful. Equally well, an SSRI with limited interaction potential may be selected to treat depression in patients that receive other medications.
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PMID:Selective serotonin reuptake inhibitors and cytochrome P-450 mediated drug-drug interactions: an update. 1187 75

The past decade has witnessed the introduction of a diverse group of antidepressants from a variety of distinct chemical classes, each with their own specificity for neurochemical transmitters, receptors, and cytochrome P450 isozymes. This review focuses on nefazodone, a distinct antidepressant with efficacy for the treatment of depression with depression-related anxiety symptoms, an established tolerability profile, and a multimodal mechanism of action. Relevant pharmacologic and pharmacodynamic effects are summarized that support nefazodone as an attractive choice for both the short- and long-term treatment of depression.
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PMID:Pharmacology of antidepressants: focus on nefazodone. 1189 May 60

St. John's wort (Hypericum perforatum L.) is a medicinal plant traditionally used, both externally and internally, in all Europe for many pathologies. Paracelsus named it "arnica of the nerves" because of its empirical use in nervous diseases. In the last two decades many studies have proved the efficacy of some St. John's wort extracts in mild to moderate depression and it has been successful as an antidepressant both in Europe and the US. Its high efficacy and tolerability is unquestionable and from the clinical studies the activity is comparable to other antidepressants while lacking major side effects, making it a safe antidepressant.However, recently its potential to induce the metabolism of co-administered medications has been reported because it may potentate certain enzymes of the cytochrome P450 enzyme system. This resulted in a lowering of serum concentration of a number of concomitant drugs, including warfarin, digoxin, theophylline, cyclosporin, and indinavir. Many drugs and also several common foods and drinks can influence this enzyme system. So, even if its safety has been well established, physicians should be aware that St. John's wort administration might significantly affect other prescribed medicines.
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PMID:St. John's wort and depression: efficacy, safety and tolerability-an update. 1200 92

Pharmacological treatment of depression in old age is associated with an increased risk of adverse pharmacokinetic and pharmacodynamic drug interactions. Elderly patients may have multiple disease states and, therefore, may require a variety of other drugs. In addition to polypharmacy, other factors such as age-related physiological changes, diseases, genetic constitution and diet may alter drug response and, therefore, predispose elderly patients to adverse effects and drug interactions. Antidepressant drugs currently available differ in their potential for drug interactions. In general, older compounds, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), have a higher potential for interactions than newer compounds, such as selective serotonin reuptake inhibitors (SSRIs) and other relatively novel agents with a more specific mechanism of action. In particular, TCAs and MAOIs are associated with clinically significant pharmacodynamic interactions with many medications frequently prescribed to elderly patients. Moreover, TCAs may be susceptible to pharmacokinetic interactions when given in combination with inhibitors or inducers of the cytochrome P450 (CYP) isoenzymes involved in their metabolism. Because of a more selective mechanism of action, newer antidepressants have a low potential for pharmacodynamic drug interactions. However, the possibility of the serotonin syndrome should be taken into account when drugs affecting serotonergic transmission, such as SSRIs, venlafaxine or nefazodone, are coadministered with other serotonergic agents. Newer agents have a differential potential for pharmacokinetic interactions because of their selective effects on CYP isoenzymes. Within the group of SSRIs, fluoxetine and paroxetine are potent inhibitors of CYP2D6, while fluvoxamine predominantly affects CYP1A2 and CYP2C19 activity. Therefore, these agents should be closely monitored or avoided in elderly patients treated with substrates of these isoforms, especially those with a narrow therapeutic index. On the other hand, citalopram and sertraline have a low inhibitory activity on different drug metabolising enzymes and appear particularly suitable in an elderly population. Among other newer antidepressants, nefazodone is a potent inhibitor of CYP3A4 and its combination with substrates of this isoform should be avoided.
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PMID:Clinically significant drug interactions with antidepressants in the elderly. 1203 80

The effect of fluoxetine on the steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was evaluated in 10 patients with schizophrenia or schizoaffective disorder. Patients stabilized on risperidone (4-6 mg/day) received additional fluoxetine (20 mg/day) to treat concomitant depression. One patient dropped out after 1 week due to the occurrence of akathisia associated with markedly increased plasma risperidone concentrations. In the other subjects, mean plasma concentrations of risperidone increased during fluoxetine administration from 12 +/- 9 ng/mL at baseline to 56 +/- 31 at week 4 (p < 0.001), while the levels of 9-OH-risperidone were not significantly affected. After 4 weeks of combined treatment, the levels of the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) increased by 75% (range, 9-204%, p < 0.01) compared with baseline. The mean plasma risperidone/9-OH-risperidone ratio also increased significantly. During the second week of adjunctive therapy, two patients developed Parkinsonian symptoms, which were controlled with anticholinergic medication. These findings indicate that fluoxetine, a potent inhibitor of the cytochrome P450 enzyme CYP2D6 and a less potent inhibitor of CYP3A4, reduces the clearance of risperidone by inhibiting its 9-hydroxylation or alternative metabolic pathways. This interaction may lead to toxic plasma risperidone concentrations. In addition to careful clinical observation, monitoring plasma risperidone levels may be of value in patients given adjunctive therapy with fluoxetine.
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PMID:Inhibition of risperidone metabolism by fluoxetine in patients with schizophrenia: a clinically relevant pharmacokinetic drug interaction. 1217 43

Escitalopram oxalate (S-citalopram, Lexapro), a selective serotonin re-uptake inhibitor antidepressant which is the S-enantiomer of citalopram, is in clinical development worldwide for the treatment of depression and anxiety disorders. Preclinical studies demonstrate that the therapeutic activity of citalopram resides in the S-isomer and that escitalopram binds with high affinity to the human serotonin transporter. Conversely, R-citalopram is approximately 30-fold less potent than escitalopram at this transporter. Escitalopram has linear pharmacokinetics, so that plasma levels increase proportionately and predictably with increased doses and its half-life of 27 - 32 h is consistent with once-daily dosing. In addition, escitalopram has negligible effects on cytochrome P450 drug-metabolising enzymes in vitro, suggesting a low potential for drug-drug interactions. The efficacy of escitalopram in patients with major depressive disorder has been demonstrated in multiple short-term, placebo-controlled clinical trials, three of which included citalopram as an active control, as well as in a 36-week study evaluating efficacy in the prevention of depression relapse. In these studies, escitalopram was shown to have robust efficacy in the treatment of depression and associated symptoms of anxiety relative to placebo. Efficacy has also been shown in treating generalised anxiety disorder, panic disorder and social anxiety disorder. Results also suggest that, at comparable doses, escitalopram demonstrates clinically relevant and statistically significant superiority to placebo treatment earlier than citalopram. Analysis of the safety database shows a low rate of discontinuation due to adverse events, and there was no statistically significant difference between escitalopram 10 mg/day and placebo in the proportion of patients who discontinued treatment early because of adverse events. The most common adverse events associated with escitalopram which occurred at a rate greater than placebo include nausea, insomnia, ejaculation disorder, diarrhoea, dry mouth and somnolence. Only nausea occurred in > 10% of escitalopram-treated patients.
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PMID:Escitalopram. 1238 7

We described the effects of nimesulide (N-[4-nitro-2-phenoxyphenyl]-methanesulfonamide) and its reduced metabolite in isolated rat hepatocytes. Nimesulide stimulated the succinate-supported state 4 respiration of mitochondria, indicating an uncoupling effect of the drug. Incubation of hepatocytes with nimesulide (0.1-1 mM) elicited a concentration- and time-dependent decrease in cell viability as assessed by lactate dehydrogenase leakage, a decrease of mitochondrial membrane potential as assessed by rhodamine 123 retention, and cell ATP depression. Nimesulide also decreased the levels of NAD(P)H and glutathione in hepatocytes, but the extent of the effects was less pronounced in relation to the energetic parameters; in addition, these effects did not imply the peroxidation of membrane lipids. The decrease in the viability of hepatocytes was prevented by fructose and, to a larger extent, by fructose plus oligomycin; it was stimulated by proadifen, a cytochrome P450 inhibitor. In contrast, the reduced metabolite of nimesulide did not present any of the effects observed for the parent drug. These results indicate that: 1) nimesulide causes injury to the isolated rat liver cells, 2) this effect is mainly mediated by impairment of ATP production by mitochondria due to uncoupling, and 3) on account of the activity of its nitro group, the parent drug by itself is the main factor responsible for its toxicity to the hepatocytes.
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PMID:The critical role of mitochondrial energetic impairment in the toxicity of nimesulide to hepatocytes. 1238 41

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