sertraline, Zoloft
A placebo-controlled screening trial of tiagabine, sertraline and donepezil as cocaine dependence treatments.

Winhusen TM, Somoza EC, Harrer JM, Mezinskis JP, Montgomery MA, Goldsmith RJ, Coleman FS, Bloch DA, Leiderman DB, Singal BM, Berger P, Elkashef A.

Cincinnati VA/UC NIDA MDRU, VA Medical Center, Cincinnati, OH, USA.

ABSTRACT Aims To conduct a preliminary evaluation of the safety and efficacy of tiagabine, sertraline or donepezil versus an unmatched placebo control as a treatment for cocaine dependence. Design A 10-week out-patient study was conducted using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design. Setting This study was conducted at the Cincinnati Medication Development Research Unit (MDRU) and at an affiliated site in Dayton, Ohio. Participants Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty-seven participants were enrolled with 55 completing final study measures. Intervention The targeted daily doses of medication were tiagabine 20 mg, sertraline 100 mg and donepezil 10 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis. Measurements Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression Scale-Observer and self-report of cocaine use. Safety measures included adverse events, ECGs, vital signs and laboratory tests. Findings Subjective measures of cocaine dependence indicated significant improvement for all study groups. Generalized estimating equations analysis indicated that the tiagabine group showed a trend toward a significant decrease in urine BE level from baseline to weeks 5-8 (P = 0.10) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. Conclusions The present findings suggest that tiagabine may be worthy of further study as a cocaine dependence treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15730351&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Efficacy and Tolerability of Hypericum Extract STW3 in Long-term Treatment with a Once-daily Dosage in Comparison with Sertraline.

Gastpar M, Singer A, Zeller K.

General Psychiatric Hospital, Dept. of Psychiatry and Psychotherapy, University of Essen, Germany.

OBJECTIVE: The objective of this double-blind, multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression. METHODS: A total of 241 patients with a diagnosis of moderate depressive disorder (according to ICD-10 criteria) were randomized with either 50 mg sertraline or 612 mg hypericum extract (hypericum group n = 123; sertraline group n = 118). According to the study protocol, 200 patients were treated for at least 12 weeks ( n = 102 hypericum extract; n = 98 sertraline); 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks. Thus, most patients were treated for a period of 6 months. The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period. RESULTS: After the first 12-week treatment period, the HAMD score decreased from almost identical initial values (22.0 +/- 1.1 for hypericum and 22.1 +/- 1.1 points for sertraline) to 8.3 +/- 5.5 points (hypericum) and 8.1 +/- 5.6 points (sertraline) (mean +/- SD) in the patients treated per-protocol (PP) population. The statistical test for non-inferiority (boundary delta = 3) revealed that hypericum extract is not inferior to sertraline ( P < 0.0001). The mean difference between the treatments was 0.1995 points, with a corresponding one-sided 97.5 % confidence interval (-infinity, 1.3772). In patients who continued treatment in the follow-up phase, the HAMD score at the end of the study was 5.7 +/- 4.8 points (hypericum group) and 7.1 +/- 6.3 points (sertraline group). Comparable improvement was also found for the von Zerssen's Adjective Mood Scale (BfS) and CGI during the first and second 12-week treatment period in both treatment groups. With 68.6 % of patients in the hypericum group and 70.4 % in the sertraline group, the percentage of patients rated as responders did not differ significantly between treatment groups (12 weeks). The adverse events of 12 patients in the hypericum group (9.8 %) and of 16 patients in the sertraline group (13.6 %) were possibly related to study medication. No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented. In most cases , the investigators assessed the tolerability of hypericum extract and sertraline as "good" or "very good." CONCLUSIONS: The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression. These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15744631&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
The influence of 4-week treatment with sertraline on the combined T3/TRH test in depressed patients.

Schule C, Baghai TC, Alajbegovic L, Schwarz M, Zwanzger P, Eser D, Schaaf L, Moller HJ, Rupprecht R.

Department of Psychiatry, Ludwig-Maximilian-University, Nussbaumstr. 7, 80336, Munich, Germany, Cornelius.Schuele med.uni-muenchen.de.

In the present study, the influence of a 4-week treatment with sertraline on the regulation of hypothalamic-pituitary-thyroid (HPT) axis activity in depression was investigated, in particular the impact of sertraline on the thyroid receptor (TR)-mediated negative feedback control as measured by the combined T3/TRH test. In 20 drug-free patients (8 men,12 women) suffering from a major depressive episode according to DSM-IV criteria the single TRH-stimulation test (administration of 200 microg TRH at 09:00h) was carried out followed by a combined T3/TRH test (pre-treatment with 40 microg 3,5,3'-triiodothyronine [T3] the night before; administration of 200 microg TRH at 09:00h the next day). After 4 weeks of treatment with sertraline at a standard dosage of 50 mg/day, both the single TRH test and the combined T3/TRH test were repeated in the depressed patients. Using repeated-measures ANOVA for statistical analysis, antidepressant therapy with sertraline did not have any significant impact on the TRH-induced TSH and prolactin stimulation (DeltaTSH, DeltaPRL) during the single TRH test nor during the combined T3/TRH test, neither in responders (n = 10) nor in non-responders (n = 10). Moreover, the percentage suppression of TRH-induced TSH stimulation (DeltaTSH) after pre-treatment with 40 microg T3 was comparable before (-61.07 %) and after the 4-week treatment with sertraline (-58.92 %). Apparently, the therapeutic efficacy of antidepressants such as sertraline is not related to the regulation of HPT axis activity in depressed patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15747035&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Economic appraisal of citalopram in the management of single-episode depression.

Sclar DA, Skaer TL, Robison LM, Galin RS.

Pharmacoeconomics and Pharmacoepidemiology Research Unit, College of Pharmacy, Washington State University, Pullman 99164-6510, USA. sclar mail.wsu.edu

A retrospective intent-to-treat analysis (N = 1,339) was conducted to discern the natural course of antidepressant use and direct health service expenditures for the treatment of single-episode depression (DSM-IV code 296.20) among patients initiating antidepressant pharmacotherapy with either a tricyclic antidepressant (TCA) (amitriptyline, N = 237) or a selective serotonin reuptake inhibitor (SSRI) (citalopram, N = 71; fluoxetine, N = 411; paroxetine, N = 334; or sertraline, N = 286). Data were derived from the computer archive of a network-model health maintenance organization for the period of January 1, 1996, through April 30, 1999. Comparisons at the end of the 6-month post-period (180 days) were undertaken between cohorts initiating antidepressant pharmacotherapy with citalopram and each SSRI or TCA. Consistent with the intent-to-treat design, all accrued health service expenditures were assigned to the pharmacotherapeutic option initially prescribed. Multivariate models were adjusted for patient's age, gender, number of concomitant disease state processes, use of health services in the 6-month time frame (180 days) before initiating antidepressant pharmacotherapy, specialty of physician recording a diagnosis of single-episode depression, and the presence or absence of a previous diagnosis of single-episode depression and receipt of antidepressant pharmacotherapy. Patients initiating antidepressant pharmacotherapy with citalopram were far more likely to (1) have been diagnosed by a psychiatrist (37%; p < or = 0.05); (2) continue with the original pharmacotherapeutic option (79%) compared with patients originally prescribed amitriptyline (51%; chi2 = 17.29, df = 1, p < or = 0.05) or sertraline (65%; chi2 = 36.91, df = 1, p < or = 0.05); no significant difference was found compared with patients initiating antidepressant pharmacotherapy with paroxetine (72%; p = not significant [NS]) or fluoxetine (83%; p = NS); (3) obtain 90 days or more of antidepressant pharmacotherapy (86%) compared with those prescribed amitriptyline (69%; chi2 = 8.09, df = 1, p < or = 0.05); no significant difference was found compared with sertraline (77%), paroxetine (81%), or fluoxetine (84%); and (4) obtain 6 months (180 days) of antidepressant pharmacotherapy (68%) compared with those prescribed amitriptyline (39%; chi2 = 18.26, df = 1, p < or = 0.05) or sertraline (51%; chi2 = 6.02, df = 1, p < or = 0.05); no significant difference was found compared with paroxetine (56%) or fluoxetine (59%). Receipt of amitriptyline or sertraline as initial medication was associated with a per capita increase (p < or = 0.05) in health service utilization (17% and 9%, respectively) relative to citalopram. No significant difference (p > 0.05) in health service utilization was discerned between citalopram and either fluoxetine or paroxetine. Multivariate models adjusted for nonrandom assignment to the initial pharmacotherapeutic option confirmed these findings. Further research over a longer time course is warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10507508&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Evidence for involvement of polymorphic CYP2C19 and 2C9 in the N-demethylation of sertraline in human liver microsomes.

Xu ZH, Wang W, Zhao XJ, Huang SL, Zhu B, He N, Shu Y, Liu ZQ, Zhou HH.

Pharmacogenetics Research Institute, Hunan Medical University, Changsha, Hunan 410078, P.R. China. xu.zhenhua mayo.edu

AIMS: The present study was designed to define the kinetic behaviour of sertraline N-demethylation in human liver microsomes and to identify the isoforms of cytochrome P450 involved in this metabolic pathway. METHODS: The kinetics of the formation of N-demethylsertraline were determined in human liver microsomes from six genotyped CYP2C19 extensive (EM) and three poor metabolisers (PM). Selective inhibitors of and specific monoclonal antibodies to various cytochrome P450 isoforms were also employed. RESULTS: The kinetics of N-demethylsertraline formation in all EM liver microsomes were fitted by a two-enzyme Michaelis-Menten equation, whereas the kinetics in all PM liver microsomes were best described by a single-enzyme Michaelis-Menten equation similar to the low-affinity component found in EM microsomes. Mean apparent Km values for the high-and low-affinity components were 1.9 and 88 microm and V max values were 33 and 554 pmol min-1 mg-1 protein, respectively, in the EM liver microsomes. Omeprazole (a CYP2C19 substrate) at high concentrations and sulphaphenazole (a selective inhibitor of CYP2C9) substantially inhibited N-demethylsertraline formation. Of five monoclonal antibodies to various cytochrome P450 forms tested, only anti-CYP2C8/9/19 had any inhibitory effect on this reaction. The inhibition of sertraline N-demethylation by anti-CYP2C8/9/19 was greater in EM livers than in PM livers at both low and high substrate concentrations. However, anti-CYP2C8/9/19 did not abolish the formation of N-demethylsertraline in the microsomes from any of the livers. CONCLUSIONS: The polymorphic enzyme CYP2C19 catalyses the high-affinity N-demethylation of sertraline, while CYP2C9 is one of the low-affinity components of this metabolic pathway.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10510155&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Course and cost of treatment for depression with fluoxetine, paroxetine, and sertraline.

Russell JM, Berndt ER, Miceli R, Colucci S, Grudzinski AN.

University of Texas Medical Branch, Galveston 77555-0191, USA. jrussell utmb.edu

OBJECTIVE: To compare depression-related treatment costs and total healthcare costs for patients diagnosed with depression and treated with either sertraline, paroxetine, or fluoxetine. PATIENTS AND METHODS: Claims records from a national database of patients diagnosed with depression who began treatment with an SSRI in 1995, following an antidepressant medication-free period of at least 6 months, were included. Treatment course and associated depression-related treatment and total healthcare costs during the subsequent 12-month treatment period were examined using univariate and multivariate methods. RESULTS: Nine-hundred five (905) patients taking sertraline, 492 on paroxetine, and 945 on fluoxetine met inclusion criteria. The groups were similar and representative with respect to gender and age. Mean dose over the 12-month treatment period increased 24%, indicating significant titration in all cohorts. Patients treated with paroxetine had shorter treatment duration (157.0 days) than did patients treated with fluoxetine (192.6 days) or sertraline (166.9 days, P < 0.001). Patients receiving index treatment with paroxetine were most likely to switch to another SSRI (21.3%); those taking sertraline were second most likely to switch (16.1%); and those on fluoxetine were least likely (12.4%, P = 0.001). Mean costs for depression-related outpatient visits and hospitalizations were similar. Mean antidepressant prescription costs differed, being $586, $419, and $446 for fluoxetine, paroxetine and sertraline cohorts, respectively (P < 0.001). In this sample, the fluoxetine cohort did not have lower nonpharmaceutical healthcare costs to offset higher pharmaceutical acquisition costs. Conclusions from median and multivariate analyses were robust to these findings. CONCLUSIONS: During this study period when fluoxetine, paroxetine, and sertraline were all well-established agents, similar depression-related treatment courses and cost characteristics among all 3 drugs were observed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10537866&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
The behavioral effects of sertraline, fluoxetine, and paroxetine differ on the differential-reinforcement-of-low-rate 72-second operant schedule in the rat.

Sokolowski JD, Seiden LS.

Department of Neurobiology, Pharmacology and Physiology, University of Chicago, 947E. 58th St., Chicago, IL 60637, USA.

RATIONALE: Recent evidence indicates that specific serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) are not a clinically or experimentally homogeneous class of drugs. Because the differential- reinforcement-of-low-rates 72-second (DRL 72-s) operant schedule has been extensively used as a screen for antidepressant effects of drugs, different SSRIs were compared on the task to further examine their behavioral effects. OBJECTIVES: These experiments were designed with two main purposes in mind: first, to determine whether all three SSRIs tested would produce antidepressant-like effects on the DRL 72-s (as measured primarily by an increase in reinforcement rate) and, second, to identify differences between the drugs using peak-deviation analysis of inter-response times (IRTs). METHODS: Different groups of rats were injected with one of three SSRIs: fluoxetine, sertraline, or paroxetine. Following drug administration, rats were tested on the DRL 72-s operant schedule. RESULTS: All three SSRIs produced significant increases in reinforcement rate, but only sertraline and fluoxetine significantly decreased response rate. Additionally, paroxetine was observed to disrupt the pattern of responding as indicated by decreases in peak area (PkA). Sertraline and paroxetine, but not fluoxetine, produced increases in peak location (PkL). CONCLUSIONS: These results indicate that, although SSRIs are correctly identified as antidepressants by the DRL 72-s operant schedule, they may exert their effects in subtly different ways, as indicated by the differences observed to exist between the drugs. It appears unlikely that the behavioral effects of the SSRIs are attributable solely to 5-HT transporter binding. Instead, the differential behavioral effects may be the result of a combination of factors, including 5-HT transporter binding, 5-HT(1A) autoreceptor activation, and binding to other receptors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10591882&dopt=Abstract sertraline Zoloft