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

Paroxetine is a new compound in the group of the selective serotonin-reuptake inhibitors. The results of several open and double-blind control-group studies demonstrate clear antidepressive efficacy of paroxetine. However, most data were collected in samples of outpatients. To overcome this restriction, a six-week double-blind control-group study, comparing 30 mg paroxetine with 150 mg amitriptyline per day, was performed in a sample of inpatients suffering from major depression. Generally speaking, the efficacy analysis of 160 patients was not able to demonstrate statistically significant differences in the antidepressive activity of paroxetine or amitriptyline, either with respect to the total score on the Hamilton Depression Scale (HAMD) and the Clinical Global Impressions or with respect to the subscores of the HAMD. One exception was the retardation subscore, in which amitriptyline showed a greater degree of reduction. Both drugs had a characteristic side-effect profile. Paroxetine was characterized by a lack of anticholinergic side-effects and a higher rate of nausea.
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PMID:Double-blind multicenter study of paroxetine and amitriptyline in depressed inpatients. 841 97

A randomized, double-blind, parallel-group, 6-week study was undertaken to compare the efficacy and tolerability of once or twice daily administration of the selective serotonin reuptake inhibitors paroxetine and fluoxetine. After a 1-week placebo wash-out, patients suffering from DSM-III major depression and with a score of 18 or more on the 21-item Hamilton Rating Scale for Depression (HRSD) received either paroxetine or fluoxetine. The patients were assessed for efficacy using the HRSD, Montgomery-Asberg Depression Rating Scale and Clinical Global Impression; for tolerability, adverse events were elicited by the use of a non-leading question and a side effects checklist. The groups of patients were comparable on entry to the study. One hundred patients were recruited into the study, of whom 78 were evaluable for the efficacy analysis. Paroxetine and fluoxetine showed comparable efficacy at the end of the 6-week treatment period, but a statistically significant difference in the number of responders at week 3 in favour of paroxetine was observed. This could suggest an earlier onset of action with paroxetine. Also, associated anxiety symptoms were significantly reduced on paroxetine compared with fluoxetine at week 3. Patients on paroxetine reported fewer adverse events than those on fluoxetine. The most commonly reported adverse events were nausea and vomiting in both groups.
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PMID:A double-blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients. 844 41

The combination of selective serotonin reuptake inhibitors with tricyclic antidepressants has proven useful in treatment-resistant depression but has the potential for adverse drug-drug interactions. In the present study, the metabolism of a single dose of imipramine was studied before and after treatment with paroxetine. Paroxetine induced significant elevations of approximately 50% in half-life, area under the curve, and Cmax of imipramine and decreased clearance twofold. The effects on desipramine pharmacokinetics were even more pronounced. These findings indicate a significant interaction of paroxetine with the CYP2D6 isoenzyme.
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PMID:Paroxetine shifts imipramine metabolism. 893 24

The recently introduced antidepressants, the selective serotonin reuptake inhibitors (SSRIs) [citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline], are known for their clinical efficacy, good tolerability and relative safety. They differ from each other in chemical structure, metabolism and pharmacokinetic properties. Therapeutic drug monitoring of these compounds is not widely used, as the plasma concentration ranges within which clinical response with minimal adverse effects appears to be optimal are not clearly defined. Almost all recent assays developed for the quantitative determination of SSRIs and their metabolites in blood are based either on the separation of SSRIs by high performance liquid chromatography (HPLC) or gas chromatography (GC). Citalopram and fluoxetine have been introduced as racemic compounds. There are some differences in the pharmacological profile, metabolism and pharmacokinetics between the enantiomers of the parent compounds and their demethylated metabolites. Stereoselective chromatographic methods for their analysis in blood are now available. With regard to the SSRIs presently available, no clearcut plasma concentration-clinical effectiveness relationship in patients with depression has been shown, nor any threshold which defines toxic concentrations. This may be explained by their low toxicity and use at dosages where serious adverse effects do not appear. SSRIs vary widely in their qualitative and quantitative interaction with cytochrome P450 (CYP) isozymes in the liver. CYP2D6 is inhibited by SSRIs, in order of decreasing potency paroxetine, norfluoxetine, fluoxetine, sertraline, citalopram and fluvoxamine. This may have clinical consequences with some but not all SSRIs, when they are taken with tricyclic antidepressants. Except for citalopram and paroxetine, little is known about the enzymes which control the biotransformation of the SSRIs. There have been many reports on marked pharmacokinetic interactions between fluoxetine and tricyclic antidepressants. Fluoxetine has a stronger effect on their hydroxylation than on their demethylation. Interactions observed between fluoxetine and alprazolam, midazolam and carbamazepine seem to occur on the level of CYP3A. Fluvoxamine strongly inhibits the N-demethylation of some tricyclic antidepressants of the tertiary amine type and of clozapine. This may lead to adverse effects but augmentation with fluvoxamine can also improve response in very rapid metabolisers, as it increases the bioavailability of the comedication. Fluvoxamine inhibits with decreasing potency, CYP1A2, CYP2C19, CYP2D6 and CYP1A1, but it is also an inhibitor of CYP3A. Fluoxetine and fluvoxamine have shown to increase methadone plasma concentrations in dependent patients. Some authors warn about a combination of monoamine oxidase (MAO) inhibitors with SSRIs, as this could lead to a serotonergic syndrome. Studies with healthy volunteers suggest, however, that a combination of moclobemide and SSRIs, such as fluvoxamine, should not present serious risks in promoting a serotonin syndrome. A combination of moclobemide and fluvoxamine has successfully been used in refractory depression, but more studies are needed, including plasma-concentration monitoring, before this combined treatment can be recommended. Paroxetine is a substrate of CYP2D6, but other enzyme(s) could also be involved. Its pharmacokinetics are linear in poor metabolisers of sparteine, and non-linear in extensive metabolisers. Due to its potent CYP2D6 inhibiting properties, comedication with this SSRI can lead to an increase of tricyclic antidepressants in plasma, as shown with amitriptyline and trimipramine. CYP3A has been claimed to be involved in the biotransformation of sertraline to norsertraline. Clinical investigations (with desipramine) confirmed in vitro findings that CYP2D6 inhibition by sertraline is only moderate. (ABSTRACT TRUNCATED)
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PMID:Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. 896 57

The selective serotonin reuptake inhibitor, paroxetine, has been reported to inhibit cytochrome P450 activity. Nitric oxide synthase (NOS) is structurally homologous to cytochrome P450. Accordingly, in our study, we observed the effects of paroxetine on NOS activity. Seventeen ischemic heart disease (IHD) patients received paroxetine and fourteen received nortriptyline for treatment of clinical depression defined by a score of 17 or higher on the Hamilton Rating Scale for Depression (HAM-D). Serum nitrite and nitrate levels were significantly decreased following paroxetine treatment but not nortriptyline treatment. Paroxetine was also a more potent inhibitor of NOS enzyme activity than nortriptyline, as measured by the conversion of [14C] arginine to [14C] citrulline by hamster brain cytosols. In addition, paroxetine reversed the force-frequency relationship in isolated hamster papillary muscles in a manner analogous to that of known NOS inhibitors. Thus, paroxetine appears to be a novel NOS inhibitor in vitro and in vivo.
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PMID:Paroxetine is a novel nitric oxide synthase inhibitor. 899 87

A drug monitoring of the antidepressant paroxetine was carried out in Germany from August 1992 to November 1993. The principal aim of this study was to collect demographic, diagnostic, efficacy, and medical-safety data regarding patients who were treated for up to 12 weeks with this SSRI. A secondary goal was the investigation of differences between patients who left treatment after 6 weeks or earlier and those who continued treatment. Evaluable data were obtained from 507 psychiatrists for 2817 patients, 1301 of whom extended treatment beyond 6 weeks. 64% of the patients had been pretreated for the current episode of depression. 50% were considered by their doctors to have either chronic or recurrent illness and 92% to possess moderate to severe symptomatology. Concomitant psychotropic medication was reported in 43% of cases, the most frequent medications being benzodiazepines, neuroleptics, and/or tricyclic antidepressants. Clear or complete improvement was noted for 63% of assessable patients by the end of week 6 and for 79% of the patients who extended treatment to 12 weeks. There were significantly more patients with DSM major depression and severe symptoms in the treatment-extender than in the 6-week treatment group. Paroxetine was tolerated well by most patients: of the 1009 adverse events reported, only 17 were considered "serious". There were no suicides or cases of overdose attributable to paroxetine. The discussion of these results is the basis for a critical appraisal of postmarketing-surveillance methodology. It is concluded that, despite its present structural weaknesses as compared to controlled investigations, drug monitoring of a new medication in the immediate postmarketing period can give insights into the treatment of large numbers of patients under private-practice conditions. However, drug monitoring as it is conducted in Germany can have different and perhaps conflicting functions which may limit its effectiveness. The authors recommend that all interested parties (physicians, the pharmaceutical industry, regulatory bodies) engage in a continuous dialog aimed at clearly formulating the goals and improving the methodology of drug monitoring.
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PMID:The treatment of depression with paroxetine in psychiatric practice in Germany: the possibilities and current limitations of drug monitoring. 903 23

Forty schizophrenic patients were included in a study of the relationship between serotonin function as measured by 3H-paroxetine binding to platelet membranes and aggressive behaviour. Patients classified as either aggressive or non-aggressive were paired by age, sex and duration of illness. 3H-Paroxetine binding variations were avoided by taking samples for each pair between 09:00 and 11:00 h, within 4 days of each other, and by assaying pair of samples together. The mean Kd for the aggressive group was 0.193 +/- 0.126 nM and the mean Kd for the non-aggressive group was 0.176 +/- 0.164 nM. The mean Bmax for the aggressive group was 1451 +/- 386 fmol/mg protein while the mean for the non-aggressive group was 1549 +/- 375 fmol/mg protein. There was no significant difference between the groups for either parameter, Kd or Bmax. There were no significant correlations between psychopathology rating including positive and negative symptoms, depression, suicidal thoughts, impulse control, as well as both past and present history of aggression, hostility and irritability traits, psychopathic deviance and either Bmax and Kd. This study finds no relationship between aggressive behaviour and peripheral serotonin function as measured by 3H-paroxetine binding to platelet membranes.
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PMID:Aggressive behaviour and platelet 3H-paroxetine binding in schizophrenia. 905 Jan 29

Paroxetine is a selective and potent serotonin reuptake inhibitor and its efficacy for the treatment of depression has been proven. Under acute and subchronical treatment regimens, disturbances of the regular sleep pattern are a reported side effect of the drug. The present study was therefore performed to investigate the impact of subchronic treatment with the selective serotonin reuptake inhibitor paroxetine on the microstructure of the sleep EEG. The study especially addressed the question of subchronic effects of paroxetine medication (30 mg/day) in eight healthy male volunteers in a double blind, placebo-controlled crossover design. Conventional sleep EEG parameters and a spectral power analysis for different sleep stages after 4 weeks of treatment were computed. Additionally, the correlation of certain EEG rhythms across the night was calculated in order to detect subtle dynamical EEG alterations, not necessarily obvious when regarding conventional EEG analysis. Although we could not detect any alterations of the spectral power values in certain frequency bands either during NREM nor during REM sleep following subchronic paroxetine medication, the dynamical EEG attributes across the night revealed a significant enhancement of the correlation between certain EEG rhythms mainly during NREM sleep.
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PMID:Analysis of sleep EEG microstructure in subchronic paroxetine treatment of healthy subjects. 927 58

The effect of paroxetine, a selective serotonin reuptake inhibitor used in the treatment of depression, on extracellular serotonin levels was evaluated in freely moving conscious rats. Microdialysis, a powerful in vivo technique to monitor the extracellular levels of neurotransmitters, was used to monitor the baseline changes in the levels of serotonin in rat brain anterior lateral striatum post paroxetine administration, which is a measure of the neuropharmacodynamic effect of the drug. Microdialysis sampling was performed for 210 min prior to and for 240 min after intraperitoneal administration of paroxetine (10 mg/kg). Paroxetine caused a statistically significant increase in the extracellular levels of serotonin in the anterior lateral striatum sampled by microdialysis. The present study demonstrates the utility of microdialysis for studying the in vivo neuropharmacodynamics of paroxetine in conscious rats.
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PMID:Evaluation of the neuropharmacodynamics of paroxetine in vivo utilizing microdialysis. 942 68

Paroxetine is a potent and selective inhibitor of the neuronal reuptake of serotonin (5-hydroxytryptamine; 5-HT), which was previously reviewed as an antidepressant in Drugs in 1991. Since then, more comparative trials with other antidepressants have become available, and its use in the elderly and as long term maintenance therapy has been investigated. Paroxetine has also been studied in several other disorders with a presumed serotonergic component, primarily obsessive compulsive disorder (OCD) and panic disorder. In short term clinical trials in patients with depression, paroxetine produced clinical improvements that were significantly greater than those with placebo and similar to those achieved with other agents including tricyclic antidepressants (TCAs), maprotiline, nefazodone and the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine and sertraline. Long term data suggest that paroxetine is effective in preventing relapse or recurrence of depression in patients treated for up to 1 year. In the elderly, the overall efficacy of paroxetine was at least as good as that of comparator agents. In short term clinical trials involving patients with OCD or panic disorder, paroxetine was significantly more effective than placebo and of similar efficacy to clomipramine. Limited long term data show that paroxetine is effective in maintaining a therapeutic response over periods of 1 year (OCD) and up to 6 months (panic disorder). Preliminary data suggest that paroxetine has potential in the treatment of social phobia, premenstrual dysphoric disorder and chronic headache. Like the other SSRIs, paroxetine is better tolerated than the TCAs, causing few anticholinergic adverse effects. The most commonly reported adverse event associated with paroxetine treatment is nausea, although this is generally mild and subsides with continued use. Fewer withdrawals from treatment due to adverse effects occurred with paroxetine treatment than with TCAs. The adverse events profile of paroxetine appears to be broadly similar to that of other SSRIs, although data from comparative trials are limited. Serious adverse effects associated with paroxetine are very rare. In conclusion, paroxetine is effective and well tolerated, and suitable as first-line therapy for depression. It also appears to be a useful alternative to other available agents for the treatment of patients with OCD or panic disorder.
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PMID:Paroxetine. An update of its pharmacology and therapeutic use in depression and a review of its use in other disorders. 946 92


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