sertraline, Zoloft
Sertraline enhances the effects of cognitive-behavioral treatment on weight reduction of obese patients.

Ricca V, Mannucci E, Di Bernardo M, Rizzello SM, Cabras PL, Rotella CM.

Dipartimento di Scienze Neurologiche e Psichiatriche, Universita di Firenze, Italy.

Serotonin reuptake inhibitors, such as dexfenfluramine, fluoxetine and fluvoxamine, have been proposed as therapeutical tools for the treatment of eating disorders and obesity. Sertraline, a SSRI used in the treatment of depression, interferes with eating behavior in animal models, but it has not been tested in obese humans. Aim of this study is the assessment of the effects of sertraline on eating attitudes and body weight in obese patients with and without mood disorders. A consecutive series of 65 obese out-patients aged 18-65 years, with a body mass index (BMI) > 30 kg/m2, was treated for 6 months with sertraline 150 mg/day per os, in addition to a cognitive-behavioral treatment (CBT). A consecutive series of 60 obese patients with similar characteristics, who were treated with CBT only, were used as control group. A greater reduction of BMI (mean +/- SD) was observed in sertraline-treated patients when compared to controls (from 35.3 +/- 5.7 to 32.0 +/- 5.4 kg/m2 in sertraline-treated patients, from 37.1 +/- 7.0 to 36.0 +/- 7.1 kg/m2 in controls; 6.5 +/- 5.4% vs. 3.0 +/- 6.3%; p < 0.01), while a similar change in eating attitudes (evaluated through the BITE questionnaire) was observed in both groups. Effects of sertraline on eating attitude and body weight were similar in patients with and without mood disorders. In conclusion, sertraline, administered together with CBT, seems to be more effective in inducing weight loss in obese patients when compared with CBT alone, and therefore it could be a useful tool in the first months of CBT for severe obesity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9061505&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Pharmacokinetics of sertraline and its N-demethyl metabolite in elderly and young male and female volunteers.

Ronfeld RA, Tremaine LM, Wilner KD.

Pfizer Central Research, Groton, Connecticut, USA.

A nonblinded study was conducted to compare the pharmacokinetic properties of the selective serotonin reuptake inhibitor sertraline in 22 young (aged 18 to 45 years) and 22 elderly (> 65 years) volunteers, of whom half were male and half were female. In this study, sertraline was administered at a dosage of 200mg once daily (the maximum recommended daily dosage) for 21 days after upward dosage titration from 50 mg/day over a 9-day period. Thus, this study was designed to measure the effect of age and gender on the pharmacokinetic properties of sertraline at the maximum dosage recommended for clinical use. The terminal elimination half-life (t1/2 beta ) of sertraline was similar in young females, elderly males and elderly females (mean t1/2 beta ranged from 32.1 to 36.7 hours in these groups) but shorter (22.4 hours) in the young males. The mean maximum plasma sertraline concentration (Cmax) and the mean steady-state area under the plasma concentration-time curve from time zero to 24 hours postdose (AUC24) were also similar between the young females, elderly males and elderly females, but were approximately 25% lower in the young males. The time to Cmax was unaffected by age or gender and ranged from 6.4 to 6.9 hours. N-Demethylsertraline is the principal metabolite of sertraline and does not contribute significantly to its serotonergic actions. The mean values for N-demethylsertraline trough plasma concentrations, AUC24 and Cmax were comparable in elderly males and females and young females but lower in young males. The ratios of mean AUC24 and Cmax for N-demethylsertraline to the AUC24 and Cmax for sertraline were similar between the 4 groups.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9068932&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Behavioral profiles of SSRIs in animal models of depression, anxiety and aggression. Are they all alike?

Sanchez C, Meier E.

H. Lundbeck A/S, Copenhagen-Valby, Denmark.

The behavioral profiles of five clinically used selective serotonin reuptake inhibitors (SSRIs) citalopram, paroxetine, sertraline, fluvoxamine and fluoxetine, have been compared in animal models of antidepressant (mouse forced swim test), anxiolytic (exploration of black and white test box and foot-shock-induced ultrasonic vocalization in the rat) and antiaggressive (isolation-induced aggressive behavior in the mouse) activity. the results are discussed in relation to receptor binding data from the literature. Furthermore, affinities for the sigma 1 and sigma 2 binding sites are presented. Citalopram reversed the immobility induced by forced swimming with a potency similar to that of imipramine. Paroxetine, fluvoxamine and fluoxetine reversed swim-induced immobility less potently and with a maximum of 40-50% reversal. Citalopram produced a mixed anxiogenic-/anxiolytic-like response in rats tested in the two-compartment black and white box. Paroxetine induced an anxiogenic-like response at low doses and the other SSRIs were without major effects. Citalopram and paroxetine inhibited footshock-induced ultrasonic vocalization with high potencies. The dose-response curve was biphasic for citalopram with a maximum of 64% inhibition. Sertraline and fluvoxamine inhibited the vocalization less potently, and fluoxetine induced a weak inhibitory effect corresponding to a maximum of 32%. Sertraline, fluvoxamine and fluoxetine inhibited isolation-induced aggressive behavior, whereas citalopram and paroxetine were inactive. Both 5-HT1 and 5-HT2 receptors are involved, and there was a functional interaction between 5-HT1A and 5-HT2A or 5-HT2C receptors, as ritanserin potentiated the antiaggressive effect of 1,5-HTP as well as that of 8-OH-DPAT.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9084057&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Behavioral stimulation without alteration of beta and 5-HT receptors and adenylate cyclase activity in rat brain after chronic sertraline administration.

Tadokoro C, Kiuchi Y, Yamazaki Y, Nara K, Oguchi K, Kamijima K.

Department of Psychiatry, Showa University School of Medicine, Tokyo, Japan.

Effects of chronic treatment with selective 5-HT reuptake inhibitors (SSRIs) on the monoaminergic functions have not been much investigated in compared with tricyclic antidepressants. Therefore, we compared the effects of 3-week treatment with sertraline, a potent SSRI, to those of imipramine (10 mg/kg, IP, twice a day), on monoamine receptors and adenylate cyclase (AC) activity in rat brain. Two-week treatment with both sertraline and imipramine reduced immobility in the water wheel test to the comparable extent. Sertraline treatment did not affect Kd and Bmax of [3H]CGP12177 and [3H]ketanserin bindings or cAMP, accumulation by norepinephrine, isoproternol, 5'-guanylylimidodiphosphate [Gpp(NH)p] and forskolin in the cortical membrane compared with vehicle-treated rats. On the other hand, imipramine treatment decreased Bmax of both bindings and norepinephrine- or isoproternol-stimulated cAMP accumulation. Treatment with either antidepressant induced no apparent changes in [3H]8-OH-DPAT [2-(N, N-dipropylamino)-8-hydroxy-1,2,3,4-tetrahydronaphthalene] binding in the hippocampal membrane. These results suggested that chronic treatment of sertraline induced little effect on monoamine receptors and AC activity in the brain and that the alteration of these functions may not be primarily involved in antidepressive effects of antidepressants, at least of SSRIs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9106909&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Interaction of sertraline with Candida species selectively attenuates fungal virulence in vitro.

Lass-Florl C, Ledochowski M, Fuchs D, Speth C, Kacani L, Dierich MP, Fuchs A, Wurzner R.

Department of Hygiene and Social Medicine, University of Innsbruck, Fritz Pregl Str. 3, 6020 Innsbruck, Austria. cornelia.lass-floerl uibk.ac.at

This study investigated whether the interaction between isolates of Candida albicans (n=7), Candida parapsilosis (n=3), Candida krusei (n=2), Candida dubliniensis (n=1) and sertraline, a typical selective serotonin reuptake inhibitor, alters candidal virulence. Sertraline treatment of Candida spp. significantly (P<0.05) affected hyphal elongation, phospholipase activity, production of secreted aspartyl proteinases and fungal viability. In addition, monocyte-derived macrophages (MDMs) treated with sertraline reduced inhibition of blastoconidia germination in comparison to MDMs alone. In conclusion, our findings suggest that the interaction between sertraline and Candida spp. may also diminish the virulence properties of this fungal pathogen in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12589952&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
[Treatment of dysthymia with sertraline]

[Article in Spanish]

Chinchilla A, Cebollada A, Vega M, Diaz M, Guzman G, Montes JM.

Servicio de Psiquiatria, Hospital Ramon y Cajal, Madrid.

We studied 50 patients (40 females, 10 males) diagnosed of dysthymia according to 1CD-10 criteria (F34.1), retrospectively and prospectively. All were treated with Sertraline, with an initial dose of Sertraline 50-100 mg/day, allowing increases to a maximum of 200 mg/day during the follow up. The clinical and therapeutical evolution was measured by HDRS (Hamilton Depression Rating Scale) 21 items, HARS (Hamilton Anxiety Rating Scale), Clinical Global Impression (CGI), subjective patient impression, compliance, secondary effects, complementary treatments when needed, severity, evolution evaluated on days 15, 30, 60 and 90, from the patient and psychiatrist perspective. Seventy two percent of the sample completed the three months of treatment. We obtained a good clinical efficacy with sertraline observed by a statistical significant decrease (p < 0.01) in the scales in the second week of treatment, which continued in following weeks. The mean doses varted from 78 mg/day to 98.7 mg/day during the three months of follow up The tolerance to Sertraline in our sample was good and similar to other data in the literature. Fourteen patients withdrew, but only six (12%) were due to secondary effects In spite of the study's limitations due to the lack of a control group, we could affirm that sertraline was an effective treatment for dysthymic patients and it should be recommended as a first choice in the treatment of affective disorders, facilitating other psychotherapeutical approach due to its favourable tolerance profile.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9133155&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations.

Stowe ZN, Hostetter AL, Owens MJ, Ritchie JC, Sternberg K, Cohen LS, Nemeroff CB.

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta GA, USA.

BACKGROUND: The purpose of this study was to attain a new landmark in the area of selective serotonin reuptake inhibitor therapy during lactation by establishing a basis for interpreting infant serum concentrations and for minimizing infant exposure in the absence of treatment-emergent side effects. METHOD: Breast milk and paired maternal and infant sera were collected following maternal treatment with sertraline monotherapy (25-200 mg/day) administered once daily. Sertraline and its major metabolite were measured in breast milk and serum samples using high-performance liquid chromatography with UV detection (limit of detection = 2 ng/mL). RESULTS: Twenty-six nursing women with DSM-IV major depressive disorder participated in the study; the mean (SD) daily sertraline dose was 123.9 (62.8) mg/day. Fifteen women submitted 182 breast milk samples for analysis of gradient (foremilk to hindmilk) and time course of medication excretion. The milk/plasma ratio was highly variable (range, 0.42-4.81). A significant gradient and time course of excretion for both sertraline (p <.001 for both) and desmethylsertraline (p <.001 for gradient and p <.046 for time course) were observed, with the highest concentrations observed in the hindmilk 8 to 9 hours after maternal ingestion. Mathematical modeling of sertraline and desmethylsertraline excretion revealed that discarding breast milk 9 hours after maternal dose decreased the infant daily dose of sertraline by a mean of 17.1% (1.8%). Twenty-two mother/infant sera pairs were obtained. Sertraline was detectable in 4 infants (18% of sample), and desmethylsertraline was found in 11 infants (50% of sample). The mean (SD) maximum calculated nursing infant dose of sertraline, 0.67 (0.61) mg/day, and desmethylsertraline, 1.44 (1.36) mg/day, represented 0.54% (0.49%) of the maternal daily dose. The maximum infant dose of desmethylsertraline (p <.002) significantly correlated with infant serum desmethylsertraline concentrations (ng/mL). In contrast, maternal daily dose, duration of medication exposure, and infant age and weight at sampling did not correlate with either detectability (< 2 ng/mL vs. > or = 2 ng/mL) or absolute concentrations (ng/mL) in infant serum. No adverse events were reported or documented in any infant. CONCLUSION: These results extend previous studies by demonstrating the utility of breast milk analysis in interpreting infant serum concentrations and minimizing infant exposure.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12590627&dopt=Abstract sertraline Zoloft