sertraline, Zoloft
A claims analysis comparing citalopram with sertraline as initial pharmacotherapy for a new episode of depression: impact on depression-related treatment charges.

McLaughlin TP, Eaddy MT, Grudzinski AN.

NDCHealth, Phoenix, Arizona 85016, USA. Trent.McLaughlin ndchealth.com

BACKGROUND: Citalopram, a selective serotonin reuptake inhibitor (SSRI) recently approved in the United States for treatment of depression, has similar efficacy to and a lower acquisition cost than other SSRIs. The impact of using citalopram (instead of other SSRIs) on total treatment costs has not been studied extensively. OBJECTIVE: The aim of this study was to compare depression-related treatment charges for the first 6 months of treatment among patients with newly diagnosed depression who received sertraline or citalopram. METHODS: This was a retrospective analysis of medical and pharmaceutical claims from 20 managed care organizations across the United States. This study population can be considered representative of a commercially insured US population. Patients aged >or= 18 years with newly diagnosed depression (ie, major depressive disorder, dysthymia, or depressive disorder not otherwise specified) who had a prescription claim for sertraline or citalopram (within 30 days of initial diagnosis) from July 1, 1998, through June 30, 1999, were included in the study. Patients with previous mental disorders and/or treatment with an SSRI (including patients diagnosed with an anxiety disorder before the first SSRI prescription) were excluded from the analysis. Log-transformed depression-related treatment charges for the first 6 months of therapy were compared across the 2 treatment cohorts with use of multivariate regression. Other outcomes measures included medication compliance and use of other antidepressant medications during the 6-month study period. Costs were measured in year-1999 US dollars. RESULTS: A total of 15222 sertraline and 3175 citalopram patients met the inclusion criteria. Mean disease-related medical charges were US dollars 931 per patient in the setraline group and US dollars 1035 in the citalopram group ( [P<0.001). The difference between groups may have been due to higher mean outpatient charges in the citalopram group (US dollars 414 vs US dollars 360; P<0.001). Citalopram patients had lower mean pharmacy charges than did sertraline patients (US dollars 255 vs Us dollars 267; 0.036). After the data were controlled for differences in age, sex, managed care plan, pretreatment history of resource use, physician specialty type, index prescription year, and switching/augmentation of the treatment drug, depression-related charges for the citalopram patients were 22% higher than those for the sertraline cohort (beta coefficient, -0.21925; P<0.001). CONCLUSION: Despite potential cost savings due to a lower acquisition cost, initial treatment of depression with citalopram was associated with higher depression-related charges than was sertraline in the population studied.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14996524&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Antidepressants, sex steroids and pituitary-adrenal response in sheep.

Broadbear JH, Nguyen T, Clarke IJ, Canny BJ.

Department of Physiology, Building 13F, Monash University, Clayton, Vic., 3800, Australia.

The importance of sex differences in major affective diseases such as depression is providing a new focus for investigating the interactions between sex, sex steroids and antidepressants. In this study, we examined the acute effects of sertraline, a selective serotonin reuptake inhibitor (SSRI) and imipramine, a tricyclic antidepressant (TCA) on the endocrine endpoints, adrenocorticotropin (ACTH) and cortisol secretion in gonadectomised male and female sheep. Each sheep was treated with an acute subcutaneous (s.c.) injection containing vehicle, sertraline (5 and 10 mg/kg), or imipramine (10 mg/kg) in the presence and absence of sex steroid replacement. In males, SSRI treatment consisted of testosterone (2 x 200 mg s.c. pellets), and in females, estradiol (1 cm s.c. implant) plus an intravaginal controlled internal drug release device containing 0.3 g progesterone. ACTH and cortisol were measured in jugular blood. Female sheep responded to sertraline treatment with dose-dependent ACTH and cortisol increases that were unchanged by sex steroid replacement. In castrated males, however, only the highest dose of sertraline increased ACTH and cortisol, and this increase was abolished in the presence of testosterone replacement. Imipramine affected neither ACTH nor cortisol secretion in either the sex or sex steroid condition. We conclude that the sex and sex steroid-related differences in the male and female responses to sertraline treatment may reflect sex and sex steroid dependent differences in serotonergic activation of the HPA axis. This highlights the potential significance of sex and circulating sex steroids in modulating neuroendocrine responses to antidepressants, and may have an impact on our understanding of the actions of these drugs in men and women.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14997276&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Dual effects of nitric oxide in the mouse forced swimming test: possible contribution of nitric oxide-mediated serotonin release and potassium channel modulation.

Inan SY, Yalcin I, Aksu F.

Department of Pharmacology, Faculty of Medicine, Cukurova University, TR-01330, Balcali, Adana, Turkey.

Recent findings have indicated that nitric oxide (NO) may change the duration of immobility biphasically in the forced swimming test, which is a useful experimental model for screening antidepressant-like activity in rodents. In the present study, we have investigated the role of serotonin and of potassium (K(+)) channels in the dual effects of NO in the mouse forced swimming test (MFST). For this purpose, we tested the effects of l-arginine, an NO precursor, the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME), and of K(+)-channel blockers tetraethylammonium (TEA) and 3,4-diaminopyridine (3,4-DAP). In addition, we used sertraline as a serotonin reuptake inhibitor and cyproheptadine as a serotonin antagonist. l-Arginine increased the duration of immobility in the MFST in low doses (25 mg/kg ip) but decreased it in higher doses (500 and 1000 mg/kg ip). Low doses of l-NAME (50 and 75 microg icv) decreased while higher dose of this drug (150 microg icv) increased the immobility time. TEA (5 microg icv) and 3,4-DAP (0.05 microg icv) significantly reduced the time, whereas K(+) channel opener pinacidil increased the duration of immobility. l-Arginine (100 mg/kg ip) significantly antagonised the effects of l-NAME (50 microg), 3,4-DAP and TEA. Higher dose of l-arginine (500 mg/kg ip) significantly potentiated the effects of 3,4-DAP and TEA, but reduced the effect of pinacidil. Low doses of l-arginine antagonized, but higher doses of l-arginine potentiated the antidepressant-like effect of sertraline. Sertraline potentiated the effects of 3,4-DAP and TEA, but reversed the effect of pinacidil. Cyproheptadine reduced the anti-immobility effect of l-arginine and 3,4-DAP. At the highest effective doses, drugs did not impair the motor functions. These data support the hypothesis that NO effects may involve the release of serotonin and/or modulation of K(+) channels.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15006455&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
From the Bench to the Trench: A Comparison of Sertraline Treatment of Major Depression in Clinical and Research Patient Samples.

Lydiard RB, Perera P, Batzar E, Clary CM.

Medical University of South Carolina School of Medicine, Charleston; and Pfizer Inc, New York, N.Y.

BACKGROUND: New medications that enter the marketplace have been tested almost exclusively in controlled clinical trials conducted in specialty research settings. There is some concern that these carefully selected patient samples may not provide information generalizable to the "real world" clinical population. The purpose of this investigation was to compare results from a large, open-label study of sertraline in the treatment of major depression in the clinical practice setting with pooled results from 2 multicenter, double-blind, placebo-controlled studies conducted in specialty research settings. METHOD: Clinical practice patients (N = 1482), aged 21 to 65 years, from 228 psychiatric clinical practice sites across the United States participated in the open-label treatment study (Clinical Practice sample). Patients who met DSM-III-R criteria for moderate-to-severe unipolar major depression (i.e., had pretreatment Hamilton Rating Scale for Depression [HAM-D] scores >/= 18) were treated for 8 weeks with sertraline in a flexible dosing fashion (50-200 mg daily). Outcomes on the HAM-D and Clinical Global Impressions-Improvement scale (CGI-I) were compared with the pooled results from 2 previously published placebo-controlled, multicenter treatment studies of sertraline in outpatients with major depression (N = 280). The overall response to sertraline in the Clinical Practice sample was compared with the outcome from the research study patient sample (Clinical Research sample). Additionally, comparison of outcomes of patients with common depressive subtypes (double depression, anxious depression, and melancholic ["endogenous"] depression) were examined. RESULTS: The percentage of sertraline-treated patients rated as responders on the CGI-I was significantly higher in the Clinical Practice sample compared with the Clinical Research sample (87% vs. 73%; p <.001). Sertraline was also much better tolerated in the Clinical Practice sample than in the Clinical Research sample as evidenced by significantly lower overall reports of adverse events (9.4% vs. 13.2%; p <.05) and lower patient dropout rates (17.5% vs. 34.3%; p <.01). Among clinical practice patients, sertraline was found to be equally effective in treating endogenous/melancholic and anxious subtypes and only mildly less effective in achieving a response in patients with double depression (chronic low-grade depression with a superimposed major depression). A regression analysis identified older age and double depression as being predictors of a slower time to response. More than 70% of patients who reported nonresponse to previous treatment with fluoxetine or a tricyclic antidepressant responded to sertraline. CONCLUSION: The effectiveness and tolerability of sertraline treatment was found to be significantly better in the Clinical Practice sample, suggesting that the results from controlled studies in research settings may represent an underestimate of the benefits of a drug. More effectiveness research is needed to confirm and extend these findings.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15014677&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Clastogenicity of selective serotonin-reuptake inhibitors.

Bozkurt G, Abay E, Ates I, Karabogaz G, Ture M, Savran FO, Palanduz S, Temocin K, Algunes C.

Department of Medical Biology, Trakya University Medical Faculty, 22030 Edirne, Turkey. gokayb hotmail.com

OBJECTIVE: Selective serotonin-reuptake inhibitors (SSRIs) are used in the treatment of various forms of psychiatric disorders. Preclinical studies in laboratory animals have indicated that SSRIs were not genotoxic, but clear results from in vitro testing of SSRIs in a human cell system are currently scarce. The purpose of this study was to investigate whether SSRIs might be genotoxic. Sertraline was chosen as model SSRI, since it appears to be at least as well-tolerated as other SSRIs and may even have a more favourable side-effect profile. Unlike fluoxetine, fluvoxamine and paroxetine, sertraline has low potential for pharmacokinetic drug interactions. So, sertraline would be considered first in the treatment of psychiatric disorders requiring SSRI therapy in the future. We therefore examined peripheral lymphocytes from sertraline-treated patients for both sister chromatid exchanges (SCEs), cells with a high frequency of SCEs (HFC) and chromosome aberrations (CA) to evaluate the clastogenicity of SSRIs. METHOD: Ten sertraline-treated patients meeting 'Structured Clinical Interview for DSM-IV' criteria for both generalized anxiety disorder and major depression were compared with 18 healthy volunteers and 18 non-treated patients with similar psychopathology. Sertraline hydrochloride was administered orally at 50 mg daily for 10 months to 1 year. The participants were selected on the basis of similar responses to a questionnaire assessing risk of genotoxicity related to other aspects of life. All participants had very similar lifestyles, medical histories, biological and dietary factors. All subjects were non-smokers. RESULT: A statistically significant difference between patients with both generalized anxiety disorder and major depression (sertraline-treated or non-treated) and healthy volunteer groups was found by both SCE frequencies and HFC percentages. Both patient groups showed higher frequencies of SCEs than the healthy controls. No statistically significant difference was found between SCE frequencies or HFC percentages observed in sertraline-treated and non-treated patient groups. No statistical difference was found between groups with respect to the frequency of CA. CONCLUSION: There are no adequate studies analysing the clastogenicity of SSRIs, in particular of sertraline. The SCE frequency, the percentage HFC and the frequency of CA in patients with both generalized anxiety disorder and major depression exposed to daily doses of sertraline do not indicate a possible clastogenic hazard. The increased SCE frequencies in patients with both generalized anxiety disorder and major depression in our study-irrespective of sertraline treatment-indicate a possible genotoxic effect. However, our observations were based on a limited number of patients; the results may be explained by psychogenic stress.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15036127&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
A pilot study of brief interpersonal psychotherapy for depression among women.

Swartz HA, Frank E, Shear MK, Thase ME, Fleming MA, Scott J.

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. swartzha msx.upmc.edu

A matched-case-control study compared eight-week outcomes between a group of 16 depressed women who received brief (eight-session) interpersonal psychotherapy and a group of 16 who received a selective serotonin reuptake inhibitor (sertraline). Women who met DSM-IV criteria for major depression and who had a score above 15 on the Hamilton Rating Scale for Depression were treated openly with brief interpersonal psychotherapy and were matched on key variables with women being treated with sertraline. Linear mixed-effects regression models were used to compare groups on measures of symptoms and functioning during eight weeks of treatment. Both groups improved significantly over time, with large effect sizes. However, contrary to expectations, the women who received psychotherapy improved more quickly than those who received sertraline.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15067162&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
A comparison of fluvoxamine, fluoxetine, sertraline and paroxetine examined by observational cohort studies.

Mackay FJ, Dunn NR, Wilton LV, Pearce GL, Freemantle SN, Mann RD.

Drug Safety Research Unit, Bursledon Hall, Southampton, UK.

OBJECTIVE: To compare the safety and side-effect profiles of the four selective serotonin reuptake inhibitor antidepressants (SSRIs), fluvoxamine, fluoxetine, sertraline and paroxetine. METHODS: The results from four observational cohort studies of the four SSRIs were compared. Each of these studies was conducted by Prescription-Event Monitoring (PEM). The exposure data were derived from general practitioner (GP) prescriptions confidentially supplied by the Prescription Pricing Authority (PPA) in England. Outcome data were obtained from questionnaires (green forms) on which the prescribing doctor recorded event data. The main findings comprised demographic information, including patients' date of birth and sex; the indication for prescribing the monitored drug; the effectiveness of the drug as perceived by the GP; the reasons for stopping treatment and all events recorded during and after treatment. RESULTS: The final cohort for each of the four SSRIs exceeded 10,000 patients. The sex, age distributions and indications for prescribing the four SSRIs were very similar. Only 36% of the GPs expressing an opinion reported fluvoxamine as effective, compared with approximately 60% for fluoxetine, sertraline and paroxetine. Fluvoxamine was associated with a higher incidence of adverse events than the other three SSRIs. Nausea/vomiting was both the most frequent clinical reason for stopping all four SSRIs and the most frequently reported clinical event. Adverse events reported in patients aged 70 years and over were comparable with the events reported for the total cohorts. Differences were identified between the four SSRIs for less frequently reported adverse events. Withdrawal symptoms were significantly more frequent with paroxetine than the other three SSRIs. CONCLUSIONS: The data from the four studies were comparable in terms of age distribution, sex of patients and indication for prescribing the drugs. Fluvoxamine had a considerably higher incidence of side-effects associated with its use than the other three SSRIs. The side-effect profiles of the four SSRIs were comparable for frequently reported events. Important differences were identified between the four SSRIs in respect of less frequently reported events. This study suggests that fluvoxamine compares unfavourably with fluoxetine, sertraline and paroxetine, both in terms of reported effectiveness and the incidence of adverse events. Biases possibly affecting the comparisons involved in this study are unlikely to account for the observed differences between fluvoxamine and the other three SSRIs. Copyright 1997 John Wiley & Sons, Ltd.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15073774&dopt=Abstract sertraline Zoloft