Prozac
Plasma Catecholamine Levels after Fluoxetine Treatment in Depressive Patients.

Blardi P, de Lalla A, Auteri A, Iapichino S, Dell'erba A, Castrogiovanni P.

Center of Clinical Pharmacology, Department of Clinical Medicine and Immunological Sciences, University of Siena, Siena, Italy.

It is known that selective serotonin reuptake inhibitors, widely used as antidepressive drugs, act by inhibiting the cell reuptake of serotonin, but their effect on the catecholaminergic system is not yet completely understood. In this study, we investigated plasma concentrations of norepinephrine, epinephrine and dopamine after acute and chronic administration of fluoxetine in depressive patients. Twelve patients affected by major depression received a single oral dose of fluoxetine in the morning, 5 mg in the first 5 days, 10 mg from the 6th to the 10th day and 20 mg from the 11th to the 40th day. Twelve healthy subjects received a placebo under identical testing procedures. Blood samples were collected at baseline and 7, 10 and 24 h after drug administration on the 1st day of fluoxetine administration at a dose of 5 mg, and on the 1st and the 30th day of fluoxetine administration at a dose of 20 mg (days 11 and 40 of treatment, respectively). We found that plasma norepinephrine, epinephrine and dopamine levels significantly increased after acute and chronic treatment (p < 0.001), reaching the highest concentrations on the last day. No significant changes of these parameters were observed in control patients. Copyright (c) 2005 S. Karger AG, Basel.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15741747&dopt=Abstract fluoxetine Prozac



Prozac


Brambilla P, Cipriani A, Hotopf M, Barbui C.

Department of Pathology and Experimental Medicine, Section of Psychiatry, University of Udine, Udine, Italy.

BACKGROUND: In the last ten years, SSRIs have increasingly replaced TCAs as comparators of newer antidepressants (ADs), because of their better tolerability profile. In particular, fluoxetine has become a reference drug for the treatment of depression, but the occurrence of individual side effects in depressed subjects treated with fluoxetine and each comparator AD have not been systematically investigated. METHODS: This meta-analysis investigated the frequency of side effects induced by fluoxetine or alternative ADs and compared the occurrence of individual side effects in depressed subjects. All randomised clinical trials (RCTs) comparing fluoxetine with any other AD drug in patients with major depression were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Controlled Trials Register. Two reviewers independently extracted information. RESULTS: Significantly less percentage of patients treated with fluoxetine experienced any side effects in comparison with TCAs (50.9 % vs 60.3 %, 29 RCTs; RR = 0.84, p = 0.003), but not in comparison with other SSRIs (59.4 % vs 59.3 %, 15 RCTs; RR = 1.00, p = 0.902). In addition, fluoxetine was better tolerated in comparison with TCAs and related ADs (RR 0.61, 95 % CI 0.52, 0.71), but not in comparison with other SSRIs. Regard to individual side effects, activating (insomnia, agitation, tremor and anxiety) and gastrointestinal adverse events (nausea, vomiting, diarrhoea, weight loss and anorexia) were significantly more frequent in fluoxetine-treated patients, whereas cholinergic side effects were significantly less frequent. CONCLUSIONS: Fluoxetine compared to other ADs had more activating and gastrointestinal adverse effects, which often require additional pharmacotherapy or other managements strategies, leading to discontinuation and non-compliance and increasing the costs. This information is relevant to base on evidence the prescription of ADs in everyday clinical practice.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15744630&dopt=Abstract fluoxetine Prozac



Prozac
Serotonin 5-HT(2C) receptor-mediated phosphoinositide hydrolysis in rat choroid plexus after fluoxetine and citalopram treatments.

Palvimaki EP, Majasuo H, Syvalahti E, Hietala J.

Department of Neurosurgery, Helsinki University Central Hospital, 00029 HUS, Finland.

Selective serotonin reuptake inhibitors (SSRIs) bind directly to various neurotransmitter receptors. The clinical effects of SSRIs appear gradually during weeks of treatment, suggesting a role for adaptive changes in neurotransmitter receptors. Most clinically used antidepressants, e.g. fluoxetine, bind to 5-HT(2C) receptors. When administered chronically, many antidepressants elicit adaptive regulation of 5-HT(2C) receptors. The present study was conducted in order to determine the effects of acute and chronic fluoxetine and citalopram treatments on the density and function of 5-HT(2C) receptors in the rat choroid plexus. Acute and chronic treatments followed by phosphoinositide (PI) hydrolysis assays and quantitative receptor autoradiography were performed. Acute (single-dose) treatment with neither drug significantly affected basal or 5-HT-stimulated PI hydrolysis, but acute citalopram (20mg/kg) treatment increased both agonist and antagonist binding to 5-HT(2C) receptors. Chronic (14 days) citalopram treatment (20mg/kg) increased the maximal PI hydrolysis response by 40%, but fluoxetine lacked this effect. The present data suggest that sensitisation of 5-HT(2C) receptor-mediated intracellular signal transduction may play a role in the effects of citalopram. In contrast, fluoxetine treatment does not functionally sensitise 5-HT(2C) receptors. Thus, functional 5-HT(2C) receptor sensitisation is not a common effect of antidepressants, but the differential effects may explain some of the pharmacodynamic differences seen with these drugs, especially upon repeated administration.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15749456&dopt=Abstract fluoxetine Prozac



Prozac
Economic impact of olanzapine plus fluoxetine combination therapy among patients treated for depression: a pilot study.

Corey-Lisle PK, Birnbaum H, Greenberg P, Marynchenko M, Dube S.

Eli Lilly and Company, Indianapolis, IN, USA.

Individuals with treatment-resistant depression (TRD) utilize more health care services and are significantly more costly. Drug treatments for TRD may include concomitant administration of multiple antidepressants or augmentation with mood stabilizers or antipsychotic agents. An augmentation strategy currently under investigation is the use of an olanzapine plus fluoxetine combination (OFC) therapy. The objectives for this pilot study were to use claims data to: (1) describe the extent of current use of OFC in patients with depressive disorders, and (2) compare health care utilization patterns and medical costs of patients receiving fluoxetine therapy before and after the initiation of olanzapine treatment. Data source consisted of medical, pharmaceutical, and disability claims from a Fortune 100 manufacturer from 1996 to 1998 (N>100,000). The sample included individuals with medical or disability claims for major depressive disorders treated with OFC (nOFC=36). Resource utilization and costs were compared for fluoxetine patients before and after the initiation of olanzapine treatment. Eleven percent of patients on combination therapy received olanzapine and fluoxetine. For patients on fluoxetine, there was a statistically significant reduction in health care utilization, and overall medical costs (20%), following initiation of olanzapine therapy. Overall, it appears the addition of olanzapine to ongoing fluoxetine therapy is effective in reducing outpatient, office, and inpatient utilization, as well as medical costs of patients treated for depression. Further research is needed to investigate combination therapy more fully.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14608242&dopt=Abstract fluoxetine Prozac



Prozac
Mechanism of block by fluoxetine of 5-hydroxytryptamine3 (5-HT3)-mediated currents in NCB-20 neuroblastoma cells.

Choi JS, Choi BH, Ahn HS, Kim MJ, Rhie DJ, Yoon SH, Min do S, Jo YH, Kim MS, Sung KW, Hahn SJ.

Department of Physiology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, South Korea.

The effect of fluoxetine (Prozac) on 5-hydroxytryptamine(3) (5-HT(3))-mediated currents in NCB-20 neuroblastoma cells was examined using the whole-cell patch-clamp technique. Fluoxetine produced a significant reduction of peak amplitude without altering the activation time course of 5-HT(3)-mediated currents. These effects were concentration-dependent, with an IC(50) value of 4.15 microM. No voltage dependence was evident in fluoxetine's block of 5-HT(3)-mediated currents over the entire voltage range tested. The extent of block by pre-application of fluoxetine was significantly greater than that by co-application. Fluoxetine also increased the apparent rate of current desensitization to 5-HT application. Using a first-order kinetics analysis, the open-channel blocking rate constants were 0.06 microM(-1)s(-1) (k(+1), association rate constant) and 0.05 s(-1) (k(-1), dissociation rate constant), with an apparent K(d) (=k(-1)/k(+1)) of 0.83 microM. This value is close to an IC(50) of 1.11 microM obtained from the reduction in tau, the time constant of desensitization. Intracellular application of fluoxetine for long durations had no effect on the amplitude or kinetics of 5-HT(3)-mediated currents. Similarly, norfluoxetine, the major metabolite of fluoxetine, reduced the peak current, and enhanced the rate of current desensitization in a concentration-dependent manner with an IC(50) of 2.66 microM, indicating that norfluoxetine is more potent than fluoxetine in blocking 5-HT(3)-mediated currents. These results indicate that, at clinically relevant concentrations, fluoxetine and its metabolite, norfluoxetine, block 5-HT(3)-mediated currents in NCB-20 neuroblastoma cells.

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Prozac
[Idendification of the drugs in the mixture using thin-layer chromatography in sudden poisoning cases]

[Article in Lithuanian]

Kazlauskiene D, Vainauskas P, Rakauskaite D.

Department of Analytical and Toxicological Chemistry, Institute of Pharmacy, Kaunas University of Medicine, A. Mickeviciaus 9, 3000 Kaunas, Lithuania. daivakazlauskiene centras.lt

The problem of acute intoxication has become very urgent now due to a great number of various chemical preparations accumulated during the last decades in the environment. Intoxications with psychotropic drugs and their mixtures form the significant part of the intoxications; there is an increasing tendency of intoxication with several preparations at a time. Amitriptyline and codeine are the preparations, which more frequently can cause intoxication. Fluoxetine is one of the newest and often used antidepressants. Under certain circumstances, like overdose, using all preparations together, long term using or using for suicide, these preparations can be even a cause of death. In such cases amitriptyline, fluoxetine and codeine become the objects of chemical-toxicological analysis. The possibility of the separation and identification of amitriptyline, fluoxetine and codeine in the mixture using thin-layer chromatography was established. Dragendorf reagent, modified by Munje, is most suitable for the spray-distinct of the chromatographic plates for all three substances. Amitriptyline research limit, using this developer, is 0.4 micro g, fluoxetine - 1.6 micro g, codeine - 0.8 micro g. Most acceptable for separation the components of the mixture are 5 mobile phases: 1. Diethyl acetate-methanol-ammonium hydroxide (concentrated solution) (85:10:5). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.94; 0.63; 0.51. 2. Buthylacetate-methanol-ammonium hydroxide (concentrated solution) (85:10:5). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.65; 0.24; 0.15. 3. Cyclohexane-diethyl acetate-diethyl amine (70:15:15). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.93; 0.75; 0.37. 4. Cyclohexane-buthylacetate-diethyl amine (70:15:15). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.92; 0.51; 0.25. 5. Acetone-1,4-dioxane-ammonium hydroxide (concentrated solution) (30:68:2). Amitriptyline, fluoxetine and codeine R(f) medium values respectively are 0.82; 0.62; 0.42. Recommended methodology for the separation and identification of amitriptyline, fluoxetine and codeine in the mixture using thin-layer chromatography is statistically reliable: when confidence level is 0.95, relative error is less than 0.05; standard deviation is from 0.007 to 0.03. Recommended methodology suits for mixture, extracted from biological liquids, components separation and identification.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14617874&dopt=Abstract fluoxetine Prozac



Prozac
[UV spectrophotometric research of drug mixture in sudden poisoning cases]

[Article in Lithuanian]

Kazlauskiene D, Vainauskas P, Marksiene R, Kiliuviene G.

Department of Analytical and Toxicological Chemistry, Faculty of Pharmacy, Kaunas University of Medicine, A. Mickeviciaus 9, 3000 Kaunas Lithuania. daivakazlauskiene centras.lt

The objective of this research - to develop the methodics for analysis of amitriptyline, fluoxetine and codeine in the mixture. RESULTS. The analytical method of amitriptyline, codeine and fluoxetine in the mixture identification and quantitative determination using ultraviolet spectrophotometry was established. Preparations in the mixture can't be separated, because material ultraviolet light peaks are in insufficient distance and therefore cover one another. The maximum of ultraviolet light absorption for amitriptyline is at 217-220 and 238-240 nm; fluoxetine - at 226-228 nm; codeine - at 224-248 and 284-286 nm. Using ultraviolet spectroscopy it's possible to identify amitriptyline, fluoxetine and codeine only after separating mixture components by thin-layer chromatography, the same time executing cleaning of extracts from blood and urine. Using ultraviolet spectroscopy can be identificated at least 0.5 micro g/ml amitriptyline, 1.5 micro g/ml fluoxetine and 1.0 micro g/ml codeine. The intervals of the quantitative determination: 5-25 micro g/ml amitriptyline; 5-30 micro g/ml fluoxetine; 100-300 micro g/ml codeine; relative error of the measurement, when confidence level is 95%, is from 0.66 to 1.2% for amitriptyline; from 0.66 to 1.45% for fluoxetine; from 0.33 to 0.88% for codeine. Standard deviation is from 1.15 to 2.08% for amitriptyline; from 1.15 to 2.52% for fluoxetine; from 0.57 to 1.53% for codeine. Molar absorption coefficients for all three preparations in distillated water were determinated. Conclusions: recommended methodology suits for mixture, extracted from biological liquids, components separation, identification and quantitative determination.

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Prozac
Chronic fluoxetine treatment partly attenuates the long-term anxiety and depressive symptoms induced by MDMA ('Ecstasy') in rats.

Thompson MR, Li KM, Clemens KJ, Gurtman CG, Hunt GE, Cornish JL, McGregor IS.

School of Psychology, University of Sydney, NSW, Australia.

Use of the drug 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') can have long-term adverse effects on emotion in both humans and laboratory animals. The present study examined whether chronic treatment with the antidepressant drug fluoxetine could reverse such effects. Male Wistar rats were briefly exposed to MDMA (4 x 5 mg/kg over 4 h) or vehicle on 2 consecutive days. Approximately 9-12 weeks later, half of the rats received a dose of approximately 6 mg/kg/day fluoxetine in their drinking water for a 5-week period. Fluoxetine administration reduced fluid intake and body weight in MDMA and vehicle pretreated rats. After several weeks of fluoxetine treatment, rats were assessed on the social interaction test, the emergence test of anxiety and the forced swim model of depression. MDMA pretreated rats showed reduced social interaction, increased anxiety on the emergence test, and increased immobility and decreased active responses in the forced swim test. Fluoxetine treatment reversed MDMA-induced anxiety in the emergence test and depressive-like effects in the forced swim test, yet exhibited no effects on the social interaction test. MDMA pretreated rats had decreased 5-HT and 5-HIAA levels in limbic and cortical regions, and decreased density of serotonin transporter sites in the cortex. Fluoxetine treatment did not greatly affect 5-HT levels in MDMA pretreated rats, but significantly decreased 5-HIAA levels in all brain sites examined. Postmortem blood serum levels of fluoxetine and norfluoxetine did not differ in MDMA and vehicle pretreated rats. These results indicate that fluoxetine may provide a treatment option for some of the deleterious long-term effects resulting from MDMA exposure.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14627999&dopt=Abstract fluoxetine Prozac