Long-term costs of treatment for depression: impact of drug selection and guideline adherence. Plasma insulin levels are increased by sertraline in rats under oral glucose overload. Direct agonists for serotonin receptors enhance locomotor function in rats that received neural transplants after neonatal spinal transection. Rx drugs

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Value Health. 2001 Jul-Aug;4(4):295-307.
Long-term costs of treatment for depression: impact of drug selection and guideline adherence.

Crown WH, Treglia M, Meneades L, White A.

MEDSTAT Group, Inc., Cambridge, MA, USA.

OBJECTIVES: This paper examines three processes: SSRI antidepressant choice, adherence to treatment guidelines, and long-term health care expenditures associated with antidepressant treatment for patients with a diagnosis of depression. METHODS: Patient records were abstracted from a medical claims database covering employer-provided health care plans. Treatment episodes required a 6-month antidepressant-free prior period; initial treatment with sertraline, paroxetine or fluoxetine; and data on direct medical costs over the 24 months following the initial prescription. The multivariate model of drug selection, patient adherence to antidepressant use guidelines, and cost was subjected to specification testing to rule out the possibility that nonrandom initial antidepressant selection might lead to sample selection bias. Further tests indicated that the results were free of bias due to a possible correlation between antidepressant selection and use of the medication, or because of the endogeneity of use patterns in the process driving cost. However, there was evidence of unobserved variables correlated with both achieving guideline adherent use and expenditures, which might have led to sample selection bias. RESULTS: Subjects who met the study criteria included 796 initiating therapy with sertraline, 352 with paroxetine, and 882 with fluoxetine. Fluoxetine patients were significantly more likely than sertraline or paroxetine patients to achieve a use pattern that was consistent with guidelines for treating depressive disorder (p < .05). There were no statistically significant differences between the three treatment cohorts in total direct health care expenditures over the 2-year period (p < .05), and depression-related expenditures, other mental health expenditures, and non-mental health care expenditures did not show significant differences across the treatments (p < .05). Natural logged values of antidepressant drug expenditures were predicted to be highest for fluoxetine, followed by sertraline, then paroxetine (p < .01). Predicted log values of mental health expenditures were lower for sertraline relative to fluoxetine. CONCLUSIONS: Fluoxetine patients had the highest likelihood of using antidepressant medication according to treatment guidelines that were developed to assure quality care. This benefit was achieved without incurring greater total health care expenditures.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11705297&dopt=Abstract

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Braz J Med Biol Res. 2001 Dec;34(12):1569-72.
Plasma insulin levels are increased by sertraline in rats under oral glucose overload.

Gomez R, Huber J, Lhullier F, Barros HM.

Divisao de Farmacologia, Fundacao Faculdade Federal de Ciencias Medicas de Porto Alegre, Rua Sarmento Leite 245, 90050-170 Porto Alegre, RS, Brazil.

Recognition and control of depression symptoms are important to increase patient compliance with treatment and to improve the quality of life of diabetic patients. Clinical studies indicate that selective serotonin reuptake inhibitors (SSRI) are better antidepressants for diabetic patients than other drugs. However, preclinical trials have demonstrated that not all SSRI reduce plasma glucose levels. In fact, fluoxetine increases and sertraline decreases glycemia in diabetic and non-diabetic rats. In the present study we evaluated plasma insulin levels during fasting and after glucose overload after treatment with sertraline. Adult male Wistar rats were fasted and treated with saline or 30 mg/kg sertraline and submitted or not to glucose overload (N = 10). Blood was collected and plasma insulin was measured. The mean insulin levels were: fasting group: 25.9 +/- 3.86, sertraline + fasting group: 31.10 +/- 2.48, overload group: 34.1 +/- 3.40, and overload + sertraline group: 43.73 +/- 5.14 microU/ml. Insulinemia was significantly increased in the overload + sertraline group. There were no differences between the other groups. No difference in glucose/insulin ratios could be detected between groups. The overload + sertraline group was the only one in which a significant number of individuals exceeded the upper confidence limit of insulin levels. This study demonstrates that sertraline increases glucose-stimulated insulin secretion without any change in peripheral insulin sensitivity.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11717710&dopt=Abstract

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J Neurosci. 1999 Jul 15;19(14):6213-24.
Direct agonists for serotonin receptors enhance locomotor function in rats that received neural transplants after neonatal spinal transection.

Kim D, Adipudi V, Shibayama M, Giszter S, Tessler A, Murray M, Simansky KJ.

Department of Neurobiology and Anatomy, MCP Hahnemann University, Philadelphia, Pennsylvania 19129, USA.

We analyzed whether acute treatment with serotonergic agonists would improve motor function in rats with transected spinal cords (spinal rats) and in rats that received transplants of fetal spinal cord into the transection site (transplant rats). Neonates received midthoracic spinal transections within 48 hr of birth; transplant rats received fetal (embryonic day 14) spinal cord grafts at the time of transection. At 3 weeks, rats began 1-2 months of training in treadmill locomotion. Rats in the transplant group developed better weight-supported stepping than spinal rats. Systemic administration of two directly acting agonists for serotonergic 5-HT(2) receptor subtypes, quipazine and (+/-)-1-[2, 5]-dimethoxy-4-iodophenyl-2-aminopropane), further increased weight-supported stepping in transplant rats. The improvement was dose-dependent and greatest in rats with poor to moderate baseline weight support. In contrast, indirectly acting serotonergic agonists, which block reuptake of 5-HT (sertraline) or release 5-HT and block its reuptake (D-fenfluramine), failed to enhance motor function. Neither direct nor indirect agonists significantly improved locomotion in spinal rats as a group, despite equivalent upregulation of 5-HT(2) receptors in the lumbar ventral horn of lesioned rats with and without transplants. The distribution of immunoreactive serotonergic fibers within and caudal to the transplant did not appear to correspond to restoration of motor function. Our results confirm our previous demonstration that transplants improve motor performance in spinal rats. Additional stimulation with agonists at subtypes of 5-HT receptors produces a beneficial interaction with transplants that further improves motor competence.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10407057&dopt=Abstract

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