sertraline, Zoloft
Sertraline in paired blood plasma and breast-milk samples from nursing mothers.

Dodd S, Stocky A, Buist A, Burrows GD, Maguire K, Norman TR.

Department of Psychiatry, University of Melbourne, Austin & Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia.

Paired blood and breast-milk samples were collected from 10 nursing mothers receiving sertraline. Samples were collected at steady state when the patients had been taking stable doses of 50-150 mg/day over several weeks. Sertraline concentrations in both fluids were determined using a specific, validated HPLC method. Plasma and milk concentrations showed a wide inter-individual variability for the same dose. Mean plasma concentrations were linearly related to dose, but this was not the case for breast-milk concentrations. An overall milk to plasma ratio of 1.76+/-1.72 was recorded. The average dose to the infants ranged from 1.1 to 31.1 &mgr;g/kg, which is less than 2 per cent of the maternal dose per day. Further studies are necessary to determine if these doses are detrimental to the development of the infant. Copyright 2000 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12404316&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19.

Wang JH, Liu ZQ, Wang W, Chen XP, Shu Y, He N, Zhou HH.

Pharmacogenetics Research Institute, Hunan Medical University, China.

OBJECTIVE: Our objective was to evaluate the relationship between the disposition of sertraline and the presence of the CYP2C19 gene and to define the contribution of cytochrome P450 2C19 (CYP2C19) to sertraline N-demethylation. METHODS: A single oral 100-mg dose of sertraline was administered to 6 subjects who were extensive metabolizers and 6 subjects who were poor metabolizers recruited from 77 healthy Chinese volunteers whose genotypes were predetermined by polymerase chain reaction-based amplification, followed by restriction fragment length polymorphism analysis. Phenotypes were determined by use of the omeprazole metabolic rate. The plasma concentrations of sertraline and desmethylsertraline were determined by gas chromatography with electron-capture detection. RESULTS: Six poor metabolizers with m1 mutation had area under the plasma concentration versus time curve (AUC(0-infinity)) values (983.6 +/- 199.3 microg x h/L versus 697.6 +/- 133.0 microg x h/L; P <.05) and terminal elimination half-life values of sertraline (35.5 +/- 5.6 hours versus 23.5 +/- 4.4 hours; P <.01) that were significantly higher than the values in 6 extensive metabolizers who were either homozygous or heterozygous for CYP2C19*1. The oral clearance of sertraline in poor metabolizers (105.3 +/- 19.4 L/h) was significantly lower than that of extensive metabolizers (148.4 +/- 28.6 L/h). The area under the concentration-time curve from 0 to 144 hours and the maximum plasma concentration of desmethylsertraline in poor metabolizers were significantly lower than the values of extensive metabolizers (627.6 +/- 203.8 microg x h/L versus 972.1 +/- 270.3 microg x h/L; P <.05; and 23.6 +/- 6.5 nmol/L versus 32.4 +/- 8.2 nmol/L; P <.01; respectively). CONCLUSIONS: The polymorphic CYP2C19 appears to be a major enzyme involved in the N-demethylation of sertraline, and both extensive and poor metabolizers had marked differences in the disposition of sertraline.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11452243&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Preference for a cocaine-associated environment is attenuated by augmented accumbal serotonin in cocaine withdrawn rats.

Harris GC, Altomare K, Aston-Jones G.

Department of Psychiatry, University of Pennsylvania, VAMC, Philadelphia 19104, USA.

RATIONALE: Recent studies have found decreased serotonin (5-HT) transmission within the nucleus accumbens following withdrawal from chronic cocaine. OBJECTIVE: We sought to investigate whether increasing brain 5-HT levels would decrease behavioral responses that occur following cocaine withdrawal, namely increased preference for a cocaine environment and anxiety. METHODS: The conditioned place preference and the defensive burying paradigms were used to measure the behavioral responses that occur 1 week following cocaine withdrawal. RESULTS: We show that pharmacological agents that increase 5-HT transmission (sertraline or 5-hydoxytryptophan, 5-HTP) abolish the preference of subchronically cocaine-treated, abstinent rats for a cocaine-associated environment. Similar results were seen when sertraline was microinjected into the nucleus accumbens. Conversely, rats acutely conditioned with cocaine showed an increased preference for a cocaine-associated environment when pretreated with these drugs. Sertraline also decreased the heightened anxiety-like behaviors found in subchronically treated cocaine rats. CONCLUSIONS: These results indicate that drugs that augment 5-HT function may reduce the desire for cocaine following cocaine withdrawal, and thus facilitate cocaine abstinence in dependent subjects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11465629&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Fluvoxamine but not sertraline inhibits the metabolism of olanzapine: evidence from a therapeutic drug monitoring service.

Weigmann H, Gerek S, Zeisig A, Muller M, Hartter S, Hiemke C.

Department of Psychiatry, University of Mainz, Mainz, Germany.

Therapeutic drug monitoring data of the new atypical neuroleptic drug olanzapine were used to study interactions with the selective serotonin reuptake inhibitors fluvoxamine and sertraline. The distribution of the ratio of concentration/daily dose (C/D; ng/mL per mg/d) of olanzapine was compared in three groups: patients treated with olanzapine (n = 134), patients treated with olanzapine plus fluvoxamine (n = 10) concomitantly, and patients treated with olanzapine plus sertraline (n = 21) concomitantly. No significant difference was seen between the olanzapine and the olanzapine plus sertraline groups. Patients receiving fluvoxamine in addition to olanzapine had C/D ratios that were in the mean 2.3-fold higher than patients receiving olanzapine without additional fluvoxamine. This indicated that fluvoxamine inhibits the metabolism of olanzapine, probably because of inhibition of cytochrome P450 (CYP) 1A2, whereas sertraline is unlikely to interfere with the metabolism of olanzapine. Combination therapy of olanzapine and fluvoxamine should be used cautiously, and therapeutic drug monitoring should be instituted to avoid olanzapine-induced adverse effects or intoxications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11477325&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Use of sertraline, paroxetine and fluvoxamine by nursing women.

Hendrick V, Fukuchi A, Altshuler L, Widawski M, Wertheimer A, Brunhuber MV.

Department of Psychiatry, UCLA Neuropsychiatric Institute and Hospital, Los Angeles, California 90095, USA.

BACKGROUND: The pharmacological treatment of depression in nursing women requires information on the magnitude of medication exposure to the infant that may occur through breast milk. AIMS: To examine serum concentrations of antidepressants in infants exposed to these medications through breast-feeding. METHOD: Maternal and infant serum concentrations of sertraline, paroxetine and fluvoxamine were determined with high-performance liquid chromatography (limit of detection=1 ng/ml). RESULTS: No detectable medication was present in any infant exposed to paroxetine (n=16) or fluvoxamine (n=4). Among infants exposed to sertraline (n=30), detectable medication was present in 24% of serum samples. A significant negative correlation was found between infant age and infant serum concentration. Sertraline was significantly more likely to be detected in an infant if the mother's daily dose was 100 mg or higher. No adverse sequelae occurred in any infant. CONCLUSIONS: This study shows that paroxetine, fluvoxamine and sertraline produce minimal exposure to infants when taken by nursing mothers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11483479&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Effect of sertraline hydrochloride on cardiac autonomic dysfunction in patients with hemodialysis-induced hypotension.

Yalcin AU, Kudaiberdieva G, Sahin G, Gorenek B, Akcar N, Kuskus S, Bayrak F, Timuralp B.

Department of Nephrology, Osmangazi University Medical School, Eskisehir, Turkey. auyalcin ogu.edu.tr

BACKGROUND/AIMS: It was previously shown that sertraline hydrochloride treatment improved hemodynamic parameters of patients with dialysis induced hypotension (DIH). The aim of this study was to examine the effect of sertraline on the autonomic functions of patients with DIH. METHODS: Ten patients with DIH, 10 hemodialysis patients without DIH and 10 healthy control subjects were included into the study. All of the patients were treated with sertraline 50 mg per day for 4 weeks. Pre-treatment and post-treatment heart rate variability (HRV) in supine and tilt position was evaluated. In order to evaluate the autonomic response to tilt position, gap values were calculated by subtracting the HRV in supine position from the HRV in tilt position. RESULTS: Analysis of the HRV response to tilt, demonstrated a paradoxical reduction in the indices of sympathetic modulation and sympathovagal balance in the patients with DIH while there was an increase in normalized powers of low frequency components (LFNU) and low frequency to high frequency components ratio (LFP/HFP) in the patients without DIH and control group. The number of therapeutic interventions for restoration of DIH decreased significantly in the sertraline period (p < 0.001). The gap values of the patients with DIH in LFNU (sympathetic modulation) (p < 0.05) and LFP/HFP (sympathovagal balance) increased in the sertraline period (p < 0.01). The decrease in gap value of normalized powers of high frequency components (parasympathetic modulation) was pronounced in the sertraline period in the patients with DIH (p < 0.05). CONCLUSION: The preventive effect of sertraline on DIH might be related to the improvement of regulation of autonomic response to hypovolemia. Copyright 2003 S. Karger AG, Basel

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12411727&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
[Sertraline in child and adolescent psychiatry]

[Article in Russian]

Voloshina VM, Kashnikova AA, Tatarova IN, Kim LV, Koren' EV.

The aim of the study was to research the efficiency of sertraline (zoloft) in depressions, anxious states and obsessive-compulsive disorders. Diagnosis of the mental disorders was carried out according to ICD-10. 72 children (59 boys, 13 girls) aged 6-18 years were treated. There were 32 inpatients and 40 outpatients. Therapy with sertraline was performed during 8 weeks with a gradual increase (titration) and individual selection of the dose from 12.5 to 100 mg/day. During the therapy clinical observation was combined with the patients' examination using Hamilton Depression Scale and Hamilton Anxiety Scale (HAM-D and HAM-A), and a Clinical Global Impression Scale (CGI). It was established that sertraline was very effective and safe drug in children (it has no influence on cognitive functions, has neither myorelaxing or sedative effects). Activity of this drug is characterized by quick manifestation of thymoanaleptic and anxiolytic effects. It mild depressive states 50 mg/day is a significant dose; in more severe depressions and obsessive-compulsive disorders the dose in juveniles was to 100 mg, the duration of the therapy was more than 2 months.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11552629&dopt=Abstract sertraline Zoloft