paroxetine, Paxil
Effect of paroxetine on extracellular serotonin and dopamine levels in the prefrontal cortex.

Nakayama K.

Department of Psychiatry, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan. kazu-n yb3.so-net.ne.jp

Abstract. Paroxetine, a selective serotonin (5-HT) reuptake inhibitor, increased extracellular 5-HT and dopamine levels, as determined by microdialysis, in the medial prefrontal cortex (mPFC) of freely moving rats. There was a difference in the time course of the maximum response between the 5-HT and dopamine levels after paroxetine administration. The extracellular dopamine concentration reached its maximum 20 min after the peak effect of 5-HT had appeared. The paroxetine-induced increase in extracellular dopamine concentration, but not 5-HT concentration, was inhibited by the 5-HT(3)-receptor antagonist granisetron. These results suggest that the increase in extracellular dopamine concentration in the mPFC elicited by paroxetine is the result of stimulation of 5-HT(3) receptors by the extracellular accumulation of 5-HT in the mPFC.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11819027&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Effects of chronic paroxetine administration on measures of aggressive and impulsive responses of adult males with a history of conduct disorder.

Cherek DR, Lane SD, Pietras CJ, Steinberg JL.

Human Psychopharmacology Laboratory, Department of Psychiatry and Behavioral Science, University of Texas-Houston Health Science Center, 1300 Moursund Street, Houston, TX 77030-3497, USA. don.r.cherek uth.tmc.edu

RATIONALE:The role of serotonin in human aggression and impulsivity was evaluated by administering paroxetine or placebo for 3 weeks and comparing the effects on laboratory measures of aggression and impulsivity among male subjects with a history of conduct disorder. METHODS: Twelve male subjects with a history of criminal behavior participated in experimental sessions, which measured aggressive and impulsive responses. Six subjects were assigned to placebo treatment and six subjects to placebo and paroxetine treatment. Aggression was measured using the point subtraction aggression paradigm (PSAP), which provides subjects with an aggressive and monetary reinforced response options. Impulsive responses were measured using a paradigm that gives subjects choices between small rewards after short delays versus larger rewards after longer delays. RESULTS:Chronic administration of paroxetine (20 mg/day) for 21 days produced significant decreases in impulsive responses. Decreases in aggressive responses were evident only at the end of paroxetine treatment. Decreases in impulsive and aggressive responses could not be attributed to a non-specific sedative action because monetary reinforced responses were not decreased as has been observed following CNS sedation. CONCLUSIONS: Inhibition of serotonin reuptake by paroxetine is the possible mechanism for reductions in aggressive and impulsive responses. These results support other data linking serotonin function and aggression and impulsivity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11862359&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
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 paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Paroxetine: new indication. In social phobia: minimal assessment.

[No authors listed]

Social phobia is generally defined as an intense and persistent fear of one or several social situations, with important repercussions for occupational activity or social life. Cognitive psychotherapy and antidepressants have partial efficacy. There is no reference drug therapy. In France, paroxetine is the first drug to be granted a licence for patients with social phobia. Clinical evaluation consists of data from four placebo-controlled trials lasting only 12 to 24 weeks. Treatment with paroxetine was associated with a significant improvement in standard social-phobia scores, although most patients remained symptomatic. Paroxetine is the best assessed selective serotonin reuptake inhibitor in this setting. However, long-term data are lacking, and the disorder is chronic. Paroxetine has not been compared with cognitive therapy. About one-third of patients in clinical trials stopped taking paroxetine, mainly because of adverse events. Gastrointestinal upset, sleep disturbance and ejaculatory problems are frequent. Paroxetine also has the potential to interact with other drugs. In practice, paroxetine may help some patients, provided they are aware of its limitations. The long-term effects of paroxetine in this setting remain unknown.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12906023&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Effect of SB-243213, a selective 5-HT(2C) receptor antagonist, on the rat sleep profile: a comparison to paroxetine.

Smith MI, Piper DC, Duxon MS, Upton N.

Neurology-CEDD, GlaxoSmithKline, New Frontiers Science Park North, Third Avenue, Essex CM19 5AW, Harlow, UK. martin_i_smith gsk.com

5-HT(2) receptor antagonists promote slow wave sleep (SWS) in humans and rats, conversely 5-HT(2) agonists inhibit SWS in rats. These alterations are thought to be predominantly mediated via the 5-HT(2C) receptor subtype. It is evident that 5-HT(2) receptor function also plays an important role in depression. Here, we examine the acute effect of the selective 5-HT(2C) receptor antagonist 5-methyl-1-[[-2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-triflouromethylindoline hydrochloride (SB-243213-A) on rat sleep in comparison to the selective serotonin reuptake inhibitor (SSRI) paroxetine. Both SB-243213-A (10 mg/kg po) and paroxetine (3 mg/kg po) significantly increased deep SWS (SWS2) quantity (27% and 24%, respectively) and reduced paradoxical sleep (PS) quantity (35%) during the sleep period. Following SB-243213-A, SWS2 occurrence frequency was reduced (24.1%); however, elevated quantity of SWS2 can be attributed to an increase in occurrence duration (81%). Reduced PS quantity results from a decrease in occurrence frequency (46%). In comparison, paroxetine increased SWS2 occurrence frequency (50%), with decreased frequency (27%) and duration (21%) of PS. The data for SB-243213-A in the present study is consistent with that following ritanserin supporting 5-HT(2C) receptor subtype mediation of this response. The similar effect of SB-243213-A to paroxetine with regard to PS quantity provides further evidence that 5-HT(2C) receptor antagonists maybe beneficial in the treatment of depression/anxiety.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11888551&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
The selective serotonin re-uptake inhibitors fluvoxamine and paroxetine differ in sexual inhibitory effects after chronic treatment.

Waldinger MD, van De Plas A, Pattij T, van Oorschot R, Coolen LM, Veening JG, Olivier B.

Department of Psychopharmacology, Rudolf Magnus Institute for Neurosciences and Utrecht Institute for Parmaceutical Sciences, Faculty of Pharmacy, Utrecht University, Utrecht, The Netherlands.

RATIONALE: The selective serotonin re-uptake inhibitors (SSRIs) delay orgasm and ejaculation in men. In men with rapid ejaculation it was shown that, of the SSRIs, paroxetine exerted the strongest delay in ejaculation and fluvoxamine the weakest. OBJECTIVES: In the present study, we compared the acute and chronic effects of fluvoxamine and paroxetine on sexual behavior in the male rat in order to compare their differential inhibitory effects on sexual behavior. METHODS: During a 4-week period, 48 male Wistar rats, selected on the basis of their sexual performance, were repeatedly tested for sexual behavior. All male rats received vehicle (saline, n=12), fluvoxamine (30 mg/kg, n=12), or paroxetine (10 mg/kg, n=12) daily for 2 weeks. Sexual behavioral tests were performed on days 1 (acute), 7, and 14. RESULTS: After acute oral administration, fluvoxamine and paroxetine did not inhibit sexual behavior. After 7 days and 14 days treatment, fluvoxamine mildly inhibited certain parameters of sexual behavior but ejaculation was never delayed. In contrast, paroxetine, after 7 days and particularly after 14 days treatment, strongly inhibited sexual behavior, including ejaculation. CONCLUSIONS: These results strongly concur with clinical data, suggesting that paroxetine, but not fluvoxamine, delays ejaculation. Because fluvoxamine does not delay ejaculation it may serve as an optimal treatment for depressive illness when sexual side effects, such as a delayed ejaculation, are undesired. The mechanisms whereby paroxetine and fluvoxamine, both being selective serotonin uptake inhibitors, differentially inhibit sexual behavior are unclear.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11889497&dopt=Abstract paroxetine, Paxil, Paxil CR



paroxetine, Paxil
Evaluating changes in sexual functioning in depressed patients: sensitivity to change of the CSFQ.

Bobes J, Gonzalez MP, Bascaran MT, Clayton A, Garcia M, Rico-Villade Moros F, Banus S.

Department of Psychiatry, University of Oviedo, Oviedo, Spain.

Accurately evaluating alterations in sexual functioning requires a validated instrument that measures clinically relevant change over time. One-hundred one depressed patients from 15 Spanish out-patient clinics completed the Changes in Sexual Functioning Questionnaire (CFSQ; Clayton, McGarvey, & Clavet, 1997) at baseline and after 6 months of treatment with fluoxetine, nefazodone, paroxetine, or venlafaxine. Sexual desire/interest showed a nearly substantial floor effect (30% of patients indicated the maximum score) for women in the nefazodone group at baseline and in the paroxetine group at final visit. The percentage of dimensions recording change was greater for women (80%) than for men (20%) in the nefazodone group (improving changes) and greater for men (40%) than for women (20%) in the paroxetine group (worsening changes). Highest effect sizes were found on sexual desire/frequency with improvement in women in the nefazodone group (SES = 0.49), and on orgasm/ejaculation with worsening in men in the paroxetine group (SES = -1.45). In conclusion, the CSFQ is sensitive to bidirectional changes and is appropriate for measuring sexual dysfunction.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11894800&dopt=Abstract paroxetine, Paxil, Paxil CR