sertraline, Zoloft
Antidepressant pharmacotherapy: economic evaluation of fluoxetine, paroxetine and sertraline in a health maintenance organization.

Sclar DA, Robison LM, Skaer TL, Galin RS, Legg RF, Nemec NL, Hughes TE, Buesching DP, Morgan M.

College of Pharmacy, Washington State University, Pullman, USA.

The present study was designed to compare direct health service expenditures, for the treatment of depression, among patients enrolled in a health maintenance organization, and prescribed one of three selective serotonin reuptake inhibitors, fluoxetine, paroxetine or sertraline. Information regarding depression-related health service use was derived from the computer archive of a network-model health maintenance organization system serving 700,000 beneficiaries. A total of 744 health maintenance organization beneficiaries were found to satisfy the study selection criteria. Multivariate regression analysis was used to determine the incremental influence of selected demographic, clinical, financial and provider characteristics on health service expenditures related to the treatment of depression (ICD-9-CM, or DSM-IV code 296.2) 1 year after the start of antidepressant pharmacotherapy. Multivariate findings indicate that treatment with paroxetine increases average expenditures for physician visits ($31.93; P < or = 0.05), psychiatric visits ($19.33; NS), laboratory tests ($2.35; P < or = 0.05), hospitalizations ($85.33; P < or = 0.05), psychiatric hospitalizations ($82.01; P < or = 0.05), and antidepressant pharmacotherapy ($63.72; P < or = 0.05), for a total per capita increase in health service use of $284.68 (P < or = 0.05), compared with treatment with fluoxetine. Sertraline treatment increases average expenditures for physician visits ($21.74; P < or = 0.05), psychiatric visits ($56.79; P < or = 0.05), laboratory tests ($1.21; P < or = 0.05), hospitalizations ($70.59; P < or = 0.05), psychiatric hospitalizations ($95.75; P < or = 0.05), and antidepressant pharmacotherapy ($69.85; P < or = 0.05), for a total per capita increase in health service use of $315.96 (P < or = 0.05), compared with treatment with fluoxetine. Economic comparisons between paroxetine and sertraline did not demonstrate any significant differences in expenditures for the health services examined.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8746607&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Sertraline in social phobia.

Munjack DJ, Flowers C, Eagan TV.

USC-LAC Medical Center 90033, USA.

Eleven consecutive SCID-diagnosed generalized social phobias without major depression, other prominent anxiety disorders, substance abuse, alcoholism or organic mental disorder, were treated, open label, with sertraline up to 200 mg daily for 12 weeks. There were seven completers. Of these, five showed substantial improvement, after being on sertraline 100 mg daily for two weeks (following no response to sertraline 50 mg daily for four weeks). There were few side effects among the completers. The four dropouts complained of side effects and loss of interest in continuing treatment. Final average dose for completers who responded was 170 mg daily.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9160574&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Long-term sertraline treatment and peripheral biochemical markers in female depressed patients.

Pivac N, Muck-Seler D, Sagud M, Jakovljevic M, Mustapic M, Mihaljevic-Peles A.

Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, Ruder Boskovic Institute, P.O. Box 180, HR-10002 Zagreb, Croatia.

Serotonergic system is implicated in the pathogenesis of depression. Peripheral biochemical markers, platelet serotonin (5-HT) and platelet monoamine oxidase (MAO) activity were determined spectrofluorimetrically at baseline and after 4 and 24 weeks of sertraline (a selective serotonin reuptake inhibitor (SSRI)) treatment in 15 female nonsuicidal, nonpsychotic patients with major depression and compared with 15 drug-free healthy women. The aim of the study was to determine the effects of 4 and 24 weeks of sertraline treatment on platelet 5-HT concentration and platelet MAO activity in depressed patients subdivided according to the treatment response into remitters, responders and nonresponders after 4 and 24 weeks of sertraline treatment based on the 70%, 50-69% and <49% reductions in baseline Montgomery-Asperg Depression Rating Scale (MADRS) scores, respectively. Platelet 5-HT concentration was significantly lower in all depressed patients at baseline than in healthy subjects. Among patients, platelet 5-HT concentration or platelet MAO activity did not differ before treatment. There was no significant correlation between MADRS scores and peripheral biochemical markers. The limitation of the study was in a small number of patients, but its advantage was in a long-term (24 weeks) follow-up of both patients and healthy controls. Our results show that long-term sertraline treatment induced remission and response in 87% patients, decreased platelet 5-HT concentration after 4 and 24 weeks of treatment and decreased platelet MAO activity after 24 weeks and suggest that pretreatment values of platelet 5-HT and platelet MAO might not predict therapeutic outcome to sertraline treatment in female depressed patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12921906&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Evaluation of cost savings to a state Medicaid program following a sertraline tablet-splitting program.

Vuchetich PJ, Garis RI, Jorgensen AM.

Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University Medical Center, Omaha, Neb. 68178, USA. philv creighton.edu

OBJECTIVES: To evaluate the economic impact of implementing a sertraline (Zoloft--Pfizer) tablet-splitting program on the Nebraska Medicaid program based on the change in total and per-member-per-month (PMPM) prescription drug costs and to identify any real or perceived problems with tablet splitting using switches among selective serotonin reuptake inhibitors (SSRIs) as a proxy indicator. DESIGN: Retrospective study of prescription claims before and after the tablet-splitting program was implemented. SETTING: Nebraska Medicaid. PATIENTS: All 14,520 patients who received an SSRI during the study period, including 5,466 patients who received at least one prescription for sertraline. INTERVENTIONS: The Nebraska Medicaid program implemented a mandatory tablet-splitting program for sertraline. Pharmacists were paid a supplemental fee to split tablets. MAIN OUTCOME MEASURES: Total costs, PMPM costs, and switches among SSRIs. RESULTS: Using regression analysis, sertraline was the only SSRI that showed a downward slope in total cost per month, although the decrease was not statistically significant (P = .1156). Fluoxetine (Prozac--Eli Lilly) and paroxetine (Paxil--GlaxoSmithKline) both showed an upward slope, but the increases were not statistically significant (P = .1164 and .0671, respectively). Citalopram (Celexa--Forest) and fluvoxamine showed significantly positive upward slopes (P = .0001 and .0391, respectively). Sertraline was also the only SSRI that showed a downward slope in PMPM costs (P = .0093). Citalopram, fluvoxamine, fluoxetine, and paroxetine all showed an upward slope in PMPM costs (P = .4494, .0008, .0448, and .0482, respectively). The tablet-splitting program was not associated with a net change in patients being switched to or from sertraline. CONCLUSION: Implementing the sertraline tablet-splitting program significantly decreased the PMPM cost of sertraline prescriptions, but it did not significantly decrease total costs of sertraline, nor did it result in disproportionate numbers of patients switching from sertraline to other SSRIs. Total costs and PMPM costs of the other four SSRI drugs did not decrease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12952314&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Adverse event reporting with selective serotonin-reuptake inhibitors.

Hartnell NR, Wilson JP, Patel NC, Crismon ML.

College of Pharmacy, Dalhousie University, Halifax, Nova Scotia, Canada.

OBJECTIVE: The Weber effect is a phenomenon which states that the number of reported adverse reactions for a drug increases until the middle to end of the second year of marketing. The purpose of this study was to examine the number of adverse event reports associated with specific selective serotonin-reuptake inhibitor (SSRI) use. METHODS: Data used in this study included voluntary adverse event reports submitted to the US federal government through the Spontaneous Reporting System and Adverse Event Reporting System. Adverse event reports were analyzed for the following SSRIs: citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. RESULTS: Adverse event reporting associated with fluvoxamine demonstrates the Weber effect. Adverse events related to fluoxetine, paroxetine, and sertraline do not exhibit the Weber effect. Fluoxetine-related adverse events peaked at year 3, with peaks also occurring during the 10th and 12th years after market entry. Adverse event reports associated with paroxetine and sertraline use increased 5-8 years after market entry. CONCLUSIONS: Within 1 class of medications, it is possible for a few agents to exhibit the Weber effect, while there is no definite pattern with others. A new observation in adverse event reporting is introduced and suggests that a peak in adverse event reporting occurs 1-2 years after a medication receives approval for a new indication. Future research is necessary to validate this effect and examine the generalizability to other medications.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14519041&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Long-term use of sertraline leads to alterations in contractility of rat isolated vas deferens.

Ozyavuz R, Kalyoncu NI, Karaoglu S.

Departments of Urology and Pharmacology, Karadeniz Technical University Medical School, 61187, Trabzon, Turkey. rozyavuz meds.ktu.edu.tr

Previous experiments with rat isolated vas deferens have shown that sertraline pretreatment inhibits contractile responses to noradrenaline, KCl, serotonin and electrical field stimulation. In the present study, the aim was to investigate the effects of long-term use of sertraline on contractile responses of rat isolated vas deferens. Fifteen Sprague-Dawley rats were given long-term (21 days) sertraline treatment, while another 15 were used as control. Both vas deferens were excised. Epididymal and prostatic segments of each underwent electrical field and chemical stimulation (noradrenaline, serotonin, acetylcholine, adenosine-triphosphate). Epididymal and prostatic segments had different contraction characteristics. Long-term sertraline treatment inhibited contractile responses of vas deferens segments to electrical field stimulation. The responses to noradrenaline were amplified with a left shift on both segments. Responses to serotonin had only a left shift on epididymal segments, while no contractile responses were observed on prostatic segments of the groups. Long-term treatment with sertraline had peripheral effects on rat vas deferens contractility, and some of the effects may be through mechanisms other than the inhibition of serotonin re-uptake.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14579107&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Maternal fluoxetine treatment in the postpartum period: effects on platelet serotonin and plasma drug levels in breastfeeding mother-infant pairs.

Epperson CN, Jatlow PI, Czarkowski K, Anderson GM.

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA. neill.epperson yale.edu

OBJECTIVE: Postpartum major depression, a frequently (10%) occurring complication of childbirth, adversely affects the mother's functioning, the mother-infant relationship, and the child's subsequent development and propensity for later psychopathology. Although selective serotonin reuptake inhibitors (SSRIs) are effective in treating postpartum depression, concerns have been raised regarding their use in lactating women. Although plasma drug levels of infants who are exposed to SSRIs through breast milk are low compared with those typically seen in patients, infant levels in some reports do seem to be at or near the drugs' reported affinities (K(D)s) and IC(50)s for inhibition at the serotonin (5-hydroxytryptamine [5-HT]) transporter. The impact of central serotonin 5-HT modulation by SSRIs during critical periods of brain development is unknown. These concerns have led our group to examine whether exposure through breast milk has a discernible effect on platelet 5-HT uptake. Taking advantage of the similarities between platelet and neuronal serotonin transporters, we previously used measurements of platelet 5-HT before and during maternal sertraline treatment to determine the degree of 5-HT transporter blockade in breastfed infants. We found that infants who were exposed to sertraline through their mothers' breast milk experienced little to no change in platelet 5-HT levels, suggestive of minimal effects on peripheral and central 5-HT transporter blockade. Compared with sertraline and most other SSRIs, fluoxetine and its active metabolite, norfluoxetine, have substantially longer plasma half-lives, and both compounds have been found in measurable quantities in plasma of nursing infants. Thus, to extend our previous work in this area, we measured platelet 5-HT levels and plasma drug levels in breastfeeding mother-infant pairs before and during maternal treatment with fluoxetine. METHODS: Maternal and infant transporter blockade was assessed by measurement of platelet 5-HT in 11 breastfeeding mother-infant pairs before and after 4 to 12 weeks of maternal fluoxetine (20-40 mg/d) treatment for postpartum depression. The study was approved by the Human Investigation Committee of Yale University School of Medicine, and each mother (mean age: 34.5 years; standard deviation [SD]: 5.3) gave written informed consent. Whole-blood 5-HT levels and plasma fluoxetine and norfluoxetine levels were determined by high-performance liquid chromatography. RESULTS: Five mothers were taking 20 mg of fluoxetine daily, 4 were taking 30 mg daily, and 2 were taking 40 mg daily. Mean infant age at the start of the study was 16.8 (SD: 8.8) weeks. All infants except 1 were <6 months of age and 4 were <3 months of age when their mothers began treatment. Six infants were breastfed exclusively; the remaining were breastfed between 3 and 8 times daily and were given supplemental feedings. Mean maternal postexposure 5-HT levels of 22.9 ng/mL (SD: 12.5) were markedly lower than mean preexposure (baseline) levels of 156.6 ng/mL (SD: 71.4; paired t = 6.9, df = 10). In contrast, the mean infant pre- and postexposure 5-HT concentrations of 217.1 (SD: 66.5) and 229.9 (SD: 83.5) ng/mL, respectively, were similar (paired t = -0.24, df = 10). However, the 1 infant with measurable plasma fluoxetine had a substantial decline in 5-HT to 40% of baseline. In samples obtained from the same infant 4 months later, plasma drug levels were undetectable (<1 ng/mL) and the platelet serotonin levels were no longer reduced (12% increase from baseline). CONCLUSIONS: The marked declines (to 9%-28% of baseline) in platelet 5-HT concentrations seen in mothers who were treated with the SSRI fluoxetine were similar to those observed in our study of sertraline in breastfeeding and other previous studies. In contrast, all but 1 infant experienced little or no decline in whole-blood (platelet) 5-HT concentrations after exposure to fluoxetine through breast milk. The substantial drop in platelet 5-HT seen in 1 infant and the coupling of this drop with measurable plasma fluoxetine leves drop with measurable plasma fluoxetine level raises some concern. Possible reasons for the infant's measurable plasma fluoxetine level include his mother's high plasma drug level and his being breastfed exclusively. However, the observations may be coincidental, and the infant experienced no discernible adverse effects. These data suggest that most infants may continue to breastfeed without experiencing meaningful changes in platelet 5-HT transport while their mothers are treated with 20 to 40 mg of fluoxetine daily. Given the limited data regarding occurrence and extent of SSRI exposure and the uncertainties concerning the possible effects of exposure, it is premature to propose treatment guidelines. Our own advice to women who are thinking of combining breastfeeding and SSRI treatment will weigh a range of factors, including severity of postpartum depression, any demonstrated preferential response to a specific SSRI, and the mother's commitment to breastfeeding. Additional research is needed to establish more definitively the frequency of physiologically meaningful infant SSRI exposure during breastfeeding and to determine the behavioral consequences of such exposure.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14595087&dopt=Abstract sertraline Zoloft