Fluoxetine Response Research Articles

Potential antidepressant LY 367265 presynaptically inhibits the release of glutamate in rat cerebral cortex

Abnormality of glutamate, one of the excitatory neurotransmitters, has been implicated in psychiatric disorders such as depression. In this study, the effect of the potential antidepressant LY 367265, an inhibitor of the 5-hydroxytryptamine (5-HT) transporter and 5-HT2A receptor antagonist, on the release of endogenous glutamate was investigated in nerve terminals purified from rat cerebral cortex using an on-line enzyme-coupled fluorimetric assay. LY 367265 inhibited the release of glutamate evoked by 4-aminopyridine (4AP) in a concentration-dependent manner; no effect was seen on KCl-evoked glutamate release. Examination of the effect of LY 367265 on cytosolic [Ca(2+)] revealed that the attenuation of glutamate release could be attributed to a reduction in Ca(2+) influx. The inhibition of Ca(2+) influx by LY 367265 was most likely due to it decreasing synaptosomal excitability because LY 367265 significantly reduced the 4AP-evoked depolarization of the synaptosomal plasma membrane potential. Glutamate release induced by the Ca(2+) ionophore ionomycin was not affected by LY 367265, indicating that LY 367265-mediated inhibition of glutamate release is not a direct interference in the release process at some point subsequent to Ca(2+) influx. Together, these results suggest that LY 367265 effects a decrease in the nerve terminal excitability, which subsequent attenuates the Ca(2+) entry through voltage-dependent Ca(2+) channels to cause a decrease in evoked glutamate release. Additionally, compared with the clinically effective antidepressant fluoxetine, a selective serotonin reuptake inhibitor, LY 367265 seems to have a more potent inhibition on 4AP-evoked glutamate release. Furthermore, the finding that LY 367265 and fluoxetine responses were additive suggests that the simultaneous blockade of 5-HT(2A) receptors and 5-HT uptake transporters might have greater therapeutic efficacy than either action alone.

Association Analysis for Neuronal Nitric Oxide Synthase Gene Polymorphism with Major Depression and Fluoxetine Response

Nitric oxide (NO) is produced from its precursor L-arginine by the enzyme NO synthase (NOS), which includes at least three distinct isoforms – neuronal (nNOS), endothelial, and inducible NOS. Recent studies have implicated NOS in the mechanism that underlies the therapeutic efficacy of antidepressant medication. In addition, major depressive disorder (MDD) patients were found to have significantly higher plasma nitrate concentrations than normal subjects, an index of NO production, in comparison to normal subjects. In a population-based association study, we tested the hypothesis that the nNOS C276T polymorphism confers susceptibility to MDD. We also examined the association between this polymorphism and therapeutic fluoxetine response in 114 MDD patients who underwent a 4-week fluoxetine treatment. The results demonstrate that the nNOS variants are found at similar frequencies in MDD patients and healthy control subjects. Further, we did not discover any genetic variants that influenced the fluoxetine response in MDD patients treated with fluoxetine. Our findings suggest that this nNOS C276T polymorphism does not play a major role in the susceptibility to, or fluoxetine response in, MDD. However, the association between other NOS variants and MDD or antidepressant response, including sexual dysfunction, may warrant further investigation.

Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement.

Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement.

Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement

One hundred and twenty‐nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow‐up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

Fluoxetine response in children with autistic spectrum disorders: correlation with familial major affective disorder and intellectual achievement.

One hundred and twenty-nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

Initial conditions of serotonin transporter kinetics and genotype: influence on ssri treatment trial outcome

Background: Fifty-one patients with major depression were classified for 5-HTT promoter region polymorphism and platelet 5-HTT kinetics before treatment with fluoxetine, and then examined for treatment outcome. Methods: Dose was stratified from 1.25 mg to 40 mg per day to allow for the possibility that one genotype could express a lower-dose fluoxetine response. A repeated-measures analysis of variance of 24-item Hamilton depression change through baseline, 1-week placebo lead-in, and 6, 12, and 18 weeks treatment was done to test a genotype effect on outcome. Results: Genotype had a significant effect on outcome (F = 4.7, p < .02), with the initial affinity constant ( K m) (F = 11.9, p = .001), and dose (F = 6.0, p < .02) being significant covariates on outcome as well. The gene effect, however, was complex in that the 5-HTT promoter region insertion showed two effects: both a placebo response effect (F = 4, p < .025), and a drug dose response effect ( r = .40, p < .01). The long allele group was more responsive to placebo, as well as more responsive to drug dose than was the short allele group. Conclusions: This is the first study to examine the antidepressant dose-response relationship to 5-HTT kinetics and genetics. The findings indicate that both the initial affinity and genotype of 5-HTT may contribute in unique ways to the variation in the outcome of depression treatment trials.

P02.201 Ad early response and remission of venlafaxine (ven: effexor®) and fluoxetine (flu: prozac®) in geriatric outpatients

P02.201 Ad early response and remission of venlafaxine (ven: effexor®) and fluoxetine (flu: prozac®) in geriatric outpatients

Antidepressant early response and remission of venlafaxine and fluoxetine in geriatric outpatients

Antidepressant early response and remission of venlafaxine and fluoxetine in geriatric outpatients

Estrogen Replacement and Response to Fluoxetine in a Multicenter Geriatric Depression Trial

The estrogen decrease of the postmenopausal state may be a factor in both the pathogenesis of late-life depression and in therapeutic response. Studies of nondepressed women over 60 given estrogen replacement therapy (ERT) suggest improvement in mood. The authors compared clinical response of elderly depressed women outpatients entering a 6-week, randomized, placebo-controlled, double-blind, multicenter trial of fluoxetine (20 mg/day); 72 patients received ERT, and 286 did not. There was a significant interaction between ERT status and treatment effect (P = 0.015). Patients on ERT who received fluoxetine had substantially greater mean Ham-D percentage improvement than patients on ERT who received placebo (40.1% vs. 17.0%, respectively); fluoxetine-treated patients not on ERT did not show benefit significantly greater than placebo-treated patients not on ERT. ERT use may augment fluoxetine response in elderly depressed outpatients and should be considered as a factor in clinical trials in elderly women.

Correction

Back to table of contents Previous article Next article ArticleNo AccessCorrectionPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.153.5.740-bAboutSectionsView articleAbstractPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail View articleAbstractReference 5 in the review by Mark S. Gold, M.D., of Addiction Psychiatry: Current Diagnosis and Treatment in the Book Forum (March 1996, pp. 439-440) should have been as follows: Dalack GW, Glassman AH, Rivelli S, Covey L, Stetner F: Mood, major depression, and fluoxetine response in cigarette smokers. Am J Psychiatry 1995; 152:398-403. Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited ByNone Volume 153Issue 5 May 1996Pages 740-b-740 Metrics PDF download History Published online 1 April 2006 Published in print 1 May 1996

Pretreatment plasma free MHPG levels as predictors of fluoxetine response

Pretreatment plasma free MHPG levels as predictors of fluoxetine response

Mood, major depression, and fluoxetine response in cigarette smokers

Two smoking cessation studies provided venues to 1) look for differences in affective symptoms between cigarette smokers with and without a history of major depression or other psychiatric diagnoses who were not currently depressed and 2) evaluate the efficacy of fluoxetine in ameliorating affective symptoms in smokers with a history of major depression but not currently depressed. Part I: Three hundred sixty-eight smokers who enrolled in a smoking cessation treatment study completed baseline self-rating scales. The relationship between the scale scores and a history of major depression and other psychiatric diagnoses was examined. Part II: Thirty-nine smokers with a history of major depression were enrolled in a randomized, double-blind study that examined the utility of fluoxetine as an aid to smoking cessation. Self-rated scales were compared at baseline and after 3 weeks of medication treatment before the attempt to quit. A history of major depression had significant main effects across all scale scores; subjects with such a history rated themselves as more symptomatic. The effects of other psychiatric diagnoses were neither as pervasive nor as robust. There were no differences in baseline scores between the fluoxetine- and placebo-treated groups and no change within the placebo group after 3 weeks. There was significant improvement from baseline in several subscale scores for the group treated with fluoxetine. However, comparison of the score changes for the placebo and fluoxetine groups did not show a statistically significant difference, which limited the ability to conclude that active treatment was better than placebo. Subjects with a history of major depression, but without current affective illness, reported themselves to be more symptomatic than those without such-a history. Furthermore, in a group of smokers with a history of major depression, affective symptoms, without concurrent syndromal illness, may be ameliorated by treatment with fluoxetine.

Imipramine binding as a predictor of fluoxetine response in depressed patients.

We evaluated platelet 3H-imipramine (3H-IMI) binding parameters (Bmax and Kd) at baseline (t0) and 2 months after (t1) treatment with fluoxetine in a group of outpatients affected by a major depressive episode, according to DSM-IIIR criteria. The possible relationships between biological parameters and the Hamilton Rating Scale for Depression (HRSD) total score were examined. The results confirmed previous reports that depressed patients possessed a lower density (Bmax) of platelet 3H-IMI binding sites than healthy controls, but the Bmax tended to decrease with fluoxetine. In addition, we observed a negative correlation between Bmax values at t0 and the HRSD total scores at t1 indicating that the patients who responded better to fluoxetine were those with a lower Bmax at t0. Future studies will substantiate this preliminary observation on the possible usefulness of platelet 3H-IMI binding as a predictor of pharmacological response.

Latency to rapid eye movement sleep as a predictor of treatment response to fluoxetine and placebo in nonpsychotic depressed outpatients

Fluoxetine and placebo were compared in 89 outpatients with major depression with ( n = 45) or without ( n = 44) a reduced or shortened rapid eye movement latency (SREML) (≤65 minutes) to determine whether rapid eye movement latency (REML) predicted placebo and/or antidepressant response. Men and women were stratified based on polysomnographic recordings and then randomly assigned to receive double-blind fluoxetine (20 mg/day) or placebo for 8 weeks after a 2-week, single-blind, placebo lead-in period. Fluoxetine-treated patients demonstrated a significantly greater reduction in the Hamilton Rating Scale for Depression total score and a significantly greater response rate than placebo-treated patients in both the SREML and the combined strata. Treatment differences in the non-SREML stratum were not statistically significant. Results supported REML as a predictor of placebo nonresponse but did not predict a differential fluoxetine response in patients with SREML compared with patients without SREML.

Predictors of interepisode symptoms and relapse in affective disorder patients treated with lithium carbonate

For 98 affective disorder patients receiving lithium prophylaxis for a mean of 45 months, number of interepisode symptoms correlated with relapse rate. Response to prophylaxis appeared highly determined by prelithium frequency of episodes and duration of lithium treatment.