sertraline, Zoloft
Is dopamine implicated in the antidepressant-like effects of selective serotonin reuptake inhibitors in the mouse forced swimming test?

Renard CE, Fiocco AJ, Clenet F, Hascoet M, Bourin M.

EA Neurobiologie de l'anxiete et de la depression, Faculte de Medecine, BP 53508, 1 rue Gaston Veil, 44035 Nantes Cedex 01, France.

RATIONALE: Microdialysis, binding and behavioural studies have shown that the dopaminergic system plays a role in antidepressant treatment. OBJECTIVES: The present study determined whether the antidepressant-like effects of selective serotonin reuptake inhibitors measured in the mouse forced swimming test are mediated via dopamine receptors. METHODS: Male Swiss mice were randomly assigned to groups of 24 animals and injected IP with citalopram, fluoxetine, fluvoxamine, sertraline, or paroxetine alone or in combination with the dopamine D(1)agonist SKF 38393, the D(1) antagonist SCH 23390, the D(2) agonist bromocriptine, the D(2) antagonist sulpiride, the D(3) agonist PD 128 907, or the D(3) antagonist nafadotride. RESULTS: The anti-immobility effects of paroxetine, fluvoxamine and citalopram were increased by co-administration of SKF 38393 (0.5 and 2 mg/kg), SCH 23390 (0.06 mg/kg), bromocriptine (0.5 and 2 mg/kg) or PD 128 907 (1 and 2 mg/kg), and were attenuated by SCH 23390 (0.5 mg/kg). The anti-immobility effects of paroxetine and fluvoxamine were also increased with sulpiride (0.5 and 2 mg/kg). The anti-immobility effect of fluoxetine was increased by SKF 38393 (2 mg/kg) and PD 128 907(1 and 2 mg/kg) co-administration. The anti-immobility effect of sertraline (16 mg/kg) was increased by SKF 38393 (0.5 mg/kg), bromocriptine (2 mg/kg) and PD 128 907 (2 mg/kg) and the effect of sertraline (2 mg/kg) was increased by bromocriptine (2 mg/kg). The anti-immobility effect of paroxetine (4 mg/kg) was increased by nafadotride (2 mg/kg). CONCLUSIONS: These data indicate that the antidepressant activity of various SSRIs involves different dopamine receptor subtypes and that the serotoninergic and dopaminergic systems interact with each other.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11797068&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Acute locomotor effects of fluoxetine, sertraline, and nomifensine in young versus aged Fischer 344 rats.

Stanford JA, Currier TD, Gerhardt GA.

Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536-0098, USA. jastan2 pop.uky.edu

Spontaneous locomotor activity was measured in young (6-8 months) and aged (24-26 months) Fischer 344 (F344) rats. Following habituation to the activity monitors, aged rats demonstrated significantly diminished motor activity as quantified by total distance traveled and vertical activity. Movement speed did not differ significantly between the two groups. Following habituation, rats were administered acute doses of fluoxetine, sertraline, or nomifensine (1.0, 3.0, and 10.0 mg/kg). Fluoxetine diminished all three behavioral measures in the young rats, while in the old rats, fluoxetine's effects were limited to a robust attenuation of vertical activity. Sertraline decreased movement speed and vertical activity, but not total distance traveled, in the young rats. Unlike fluoxetine, sertraline produced no significant effects on any of the three behavioral variables in the old rats. Nomifensine increased behavioral scores for both age groups. The results are discussed in relation to acute motor side effects of selective serotonin reuptake inhibitors (SSRIs) in motor-impaired aged individuals, as these effects may influence their eventual use in the clinic.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11812540&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Do bupropion SR and sertraline differ in their effects on anxiety in depressed patients?

Trivedi MH, Rush AJ, Carmody TJ, Donahue RM, Bolden-Watson C, Houser TL, Metz A.

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas 75390, USA. madhukar.trivedi utsouthwestern.edu

OBJECTIVE: To examine the effects of bupropion sustained release (SR) and sertraline on anxiety in outpatients with recurrent DSM-IV-defined major depressive disorder. METHOD: This retrospective analysis was conducted using pooled data from 2 identical, 8-week, acute-phase, double-blind, placebo-controlled, parallel-group studies of bupropion SR (N = 234), sertraline (N = 225), and placebo (N = 233). Symptoms of anxiety and depression were measured using the 14-item Hamilton Rating Scale for Anxiety (HAM-A) and the 21-item Hamilton Rating Scale for Depression (HAM-D-21), respectively. Percentage reduction in baseline HAM-A total score for each treatment week was calculated to determine whether the time to onset of anxiolytic activity differed among antidepressant responders to each agent. Central nervous system (CNS) adverse events were tabulated. RESULTS: Bupropion SR and sertraline were comparably effective, both were superior to placebo in reducing depressive symptoms. and they did not differ in their effect on anxiety symptoms. Antidepressant responders (> 50% reduction in baseline HAM-D-21 score) in both groups showed marked and comparable reductions in HAM-A scores (baseline to exit). There were no differences between bupropion SR and sertraline in the median time (4 weeks) to reach a clinically significant anxiolytic effect (> or = 50% reduction in baseline HAM-A score). CNS adverse events were comparable for bupropion SR and sertraline, except for somnolence, which was more common in sertraline-treated patients. CONCLUSION: Bupropion SR and sertraline had comparable antidepressant and anxiolytic effects and an equally rapid onset of clinically significant anxiolytic activity. There was no difference in the activating effects between the 2 antidepressants. Selection between these 2 agents cannot be based on either anticipation of differential anxiolytic activity or differential CNS side effect profiles.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11816866&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Complex modulation of human motor cortex excitability by the specific serotonin re-uptake inhibitor sertraline.

Ilic TV, Korchounov A, Ziemann U.

Department of Neurology, J.W. Goethe-University Frankfurt, Theodor-Stern-Kai 7, D-60590 Franfurt am Main, Germany.

Monoamines are powerful modulators of cortical function. Serotonin has complex excitatory and inhibitory effects on animal cortex. Here, the effects of a single oral dose (100mg) of the selective serotonin re-uptake inhibitor sertraline on human motor cortex excitability were investigated in healthy subjects. Transcranial magnetic stimulation was used to test motor threshold, motor evoked potential intensity curve, cortical silent period, paired-pulse inhibition and facilitation and I-wave facilitation. Sertraline resulted in a steeper intensity curve and in depressed paired-pulse facilitation (PPF). All other measures and spinal and neuromuscular excitability remained unaffected. The steeper intensity curve points to an increased excitability of the cortico-spinal neurone, while the depressed PPF suggests an enhanced control of the cortico-spinal neurone by inhibitory interneurones. These features may improve the signal-to-noise ratio of output cells in human motor cortex.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11825684&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Fibromyalgia: patient perspectives on symptoms, symptom management, and provider utilization.

Wassem R, McDonald M, Racine J.

University of Utah, Salt Lake City, Utah 84112-5880, USA.

Two surveys of individuals with fibromyalgia were conducted to assess the frequency and prevalence of symptoms (N = 99) as well as healthcare providers, medications, and self-care activities used to manage one's fibromyalgia (N = 54). The pervasiveness of symptoms was striking, with 24 various symptoms ranging from cognitive to intestinal problems occurring in at least 75% of the respondents. Significant correlations were present between health status and both physical (P = .002) and psychological (P =.008) symptoms. There was also a significant correlation between the total number of symptoms and the degree of life disruption attributed to fibromyalgia (P =.015). A variety of healthcare professionals were seen, with internists, family physicians, and rheumatologist most frequently used. Although at least 80% of the respondents reported difficulty with anxiety, confusion, irritability, depression, and cognitive difficulties, less than 10% of the respondents reported seeing a psychiatrist. Most frequently used medications were: amitriptyline, (fluoxetine HCl) Prozac, ibuprofen (Motrin), sertraline HCI (Zoloft), and zolpidem (Ambein). Self-care activities used with the most success were walking, stretching, and exercising. These studies indicate the need for more research and support for healthcare providers as well as patients with fibromyalgia.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11839925&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Duration of therapy and health care costs of fluoxetine, paroxetine, and sertraline in 6 health plans.

Polsky D, Onesirosan P, Bauer MS, Glick HA.

Division of General Internal Medicine and the Leonard Davis Institute of Health Economics, the University of Pennsylvania, Philadelphia, USA. polsky mail.med.upenn.edu

BACKGROUND: Previous studies comparing fluoxetine, paroxetine, and sertraline, the 3 most common selective serotonin reuptake inhibitors (SSRIs), in naturalistic settings have produced conflicting results. With this study, we provide new evidence as to the similarities and differences among these SSRI therapies with respect to the duration of use and health care costs. METHOD: Data from 6 health maintenance organizations were used to identify patients with new-onset major depression. number of days with filled prescriptions, and total health care and depression-related costs. The sample consisted of 1771 patients given initial prescriptions for sertraline (N = 386), fluoxetine (N = 840), or paroxetine (N = 545) in the period from July 1, 1994, to March 31, 1997. Analyses included Cox proportional hazards models (for duration of initial therapy) and ordinary least squares regression (for cost). RESULTS: Patients who initiated therapy with fluoxetine were more likely to have a later interruption of therapy than patients who initiated therapy with sertraline (p = .03) and paroxetine (p = .001). Total 1-year costs did not differ statistically between the treatment groups, but 1-year depression-related costs were significantly lower for patients who initiated therapy with sertraline or paroxetine than for those who initiated therapy with fluoxetine ($332 less for sertraline, 95% confidence interval [CI] = $125 to $562; $339 less for paroxetine, 95% CI = $144 to $416). LIMITATIONS: A limitation of this observational study, as well as of observational studies in general, is that unobserved characteristics of the patients may lead to biased estimates of the impact of treatment on adherence or cost, even with controls for observed characteristics. CONCLUSION: We found no significant differences in total health care costs among the 3 SSRIs, but noted significant differences in depression-related costs (the costs of fluoxetine are greater than those of sertraline and paroxetine). Importantly, there was no relationship between treatment interruption and increased health care or depression-related costs, in contrast to the findings of some, but not all, prior studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11874218&dopt=Abstract sertraline Zoloft



sertraline, Zoloft
Up-regulation of tryptophan hydroxylase expression and serotonin synthesis by sertraline.

Kim SW, Park SY, Hwang O.

Department of Biochemistry, University of Ulsan College of Medicine, Seoul, Korea.

The neurotransmitter serotonin is involved in a variety of brain functions, and abnormal changes in serotonin neurotransmission are associated with an array of psychiatric disorders, including depression. Sertraline is a selective serotonin reuptake inhibitor (SSRI) and an effective antidepressant. Sertraline increases the serotonin concentration in the synaptic cleft by a short-term action; however, clinical improvement is observed only after several weeks, suggesting that the therapeutic effect may be caused by long-term alterations in serotonin transmission. We determined the effects of sertraline on serotonin synthesis in vivo and in vitro. Long-term treatment of rats with sertraline up-regulated mRNA and protein levels of the serotonin-synthesizing enzyme tryptophan hydroxylase (TPH), as determined by in situ hybridization and immunocytochemistry, respectively. In vitro studies using RBL-2H3 cells also showed an increase in mRNA and protein levels of TPH by sertraline, as determined by Northern blot and immunoblot analyses, respectively. This was accompanied by increases in the levels of TPH enzymatic activity and total serotonin. These data demonstrate that in addition to the known short-term action as an uptake blocker, sertraline also exerts a long-term effect on the serotonin neurotransmission by enhancing serotonin synthesis. A similar effect was observed with another SSRI, fluoxetine, but not with the non-SSRI chlorpromazine. The up-regulation of TPH gene expression by sertraline was attenuated by the protein kinase A (PKA) inhibitor N-[2-(p-bromocinnamylamine)-ethyl]-5-isoquinolinesulfonamine, suggesting that a mechanism involving the PKA signaling pathway might at least in part mediate the long-term therapeutic action.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11901216&dopt=Abstract sertraline Zoloft