Prozac
Hypericum extract in patients with MDD and reversed vegetative signs: re-analysis from data of a double-blind, randomized trial of hypericum extract, fluoxetine, and placebo.

Murck H, Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, Zajecka J, Mannel M, Rosenbaum JF.

Lichtwer Pharma GmbH, Berlin, Germany.

Hypericum extract (HE) might be favourably active in depressed patients with reversed vegetative signs (RVS). Therefore, we performed an exploratory subgroup analysis of a three-armed study to compare HE, fluoxetine, and placebo in patients with major depressive disorder (MDD) in a 12 wk trial. A total of 135 patients were randomized to 12 wk treatment with HE LI 160 (900 mg/d), fluoxetine (20 mg/d), or placebo. Patients with RVS were defined in two steps, according to DSM-IV. First, patients with melancholy-related vegetative signs were excluded. Secondly, patients had to have at least one score of 2 for the items 22-26 of the HAMD-28 scale, which are related to hypersomnia and hyperphagia. Twenty-seven patients remained in the group. Analysis of covariance (ANCOVA) was applied using the HAMD-17 score. Secondly a chi2 test for response was performed, using the same and further an adapted criterium as in recently published studies. ANCOVA revealed a trend to a global difference. Post-hoc analysis showed a trend to superiority of HE compared to placebo and to fluoxetine, but a very large effect size for both differences. Fluoxetine was not different from placebo. The adapted response criterium showed a significant global difference as well as a significant superiority of HE over placebo and over fluoxetine. These data are based on a small sample size and must be considered tentative. A characterization of vegetative features of patients with depression could lead to an overall increased effect size in the treatment with HE.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15458612&dopt=Abstract fluoxetine Prozac



Prozac
Fluoxetine at anorectic doses does not have properties of a dopamine uptake inhibitor.

Fuller RW, Hemrick-Luecke SK, Snoddy HD.

Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN.

Although fluoxetine is a highly selective inhibitor of serotonin uptake in vitro and in vivo, some investigators have suggested that dopamine uptake inhibition may contribute to anorectic actions of fluoxetine. The present experiments were done to determine fluoxetine's effects in some animal protocols in which dopamine uptake inhibitors have characteristic actions. Mazindol prevented the depletion of striatal dopamine and its metabolites by amphetamine in iprindole-pretreated rats, but fluoxetine had no effect. Mazindol prevented the depletion of striatal dopamine and its metabolites by 6-hydroxydopamine injected intracerebroventricularly into rats, but fluoxetine had no effect. Mazindol enhanced the elevation of 3,4-dihydroxyphenylacetic acid concentration in rat brain after spiperone injection, but fluoxetine did not cause that effect. Fluoxetine did not mimic amfonelic acid in antagonizing the retention of alpha-methyl-m-tyramine invant striatum after the injection of alpha-methyl-m-tyrosine. These results show that fluoxetine, at doses that are effective in blocking the serotonin uptake carrier and causing anorexia, does not block the dopamine uptake carrier.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7826568&dopt=Abstract fluoxetine Prozac



Prozac
Facilitation of 5-hydroxytryptamine3 receptor desensitization by fluoxetine.

Fan P.

Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.

Effect of fluoxetine on the desensitization of the inward current mediated by 5-hydroxytryptamine3 receptors in rat nodose ganglion neurons was investigated with whole cell patch-clamp recording. 5-Hydroxytryptamine3 current desensitization was best fitted in most experiments by a single exponential function and showed little dependence on membrane potential. Fluoxetine greatly facilitated the rate of 5-hydroxytryptamine3 current desensitization in a dose-dependent manner. The effect of fluoxetine was gradual, long-lasting, voltage-independent and the recovery was incomplete. The IC50 value for the decrease of the desensitization time-constant by fluoxetine was 0.171 microM and the Hill coefficient was 1.1. Fluoxetine also inhibited the peak and steady-state 5-hydroxytryptamine3 current with the latter being more sensitive to fluoxetine. The IC50 value for the effect of fluoxetine on peak current was 1.27 microM and that on steady-state current was 0.172 microM. There is a highly significant correlation between the two effects of fluoxetine on current desensitization and on current amplitudes: r-values for the correlation between the decrease in time-constant and the reduction in peak and steady-state current amplitudes were 0.82 and 0.88, respectively (P < 0.001). This action of fluoxetine on 5-hydroxytryptamine3 receptors may be involved in the behavioral effects of fluoxetine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7830894&dopt=Abstract fluoxetine Prozac



Prozac
Personality disorder comorbidity with major depression and response to fluoxetine treatment.

Fava M, Bouffides E, Pava JA, McCarthy MK, Steingard RJ, Rosenbaum JF.

Clinical Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114.

The relationship between depression and comorbid personality disorders is still poorly understood. The aims of this study were to examine differences in depression severity between depressed outpatients with and without comorbid personality disorders, to determine the effect of a fixed dose of fluoxetine on personality disorders, and to assess the predictive value of personality disorder diagnoses at baseline with regard to response to fluoxetine. Eighty-three outpatients with major depressive disorder (MDD) were assessed with a self-rating scale, the Personality Diagnostic Questionnaire-Revised (PDQ-R), before and after 8 weeks of treatment with fluoxetine 20 mg/day. The presence of a cluster B diagnosis before treatment predicted positive outcome as measured by the change in score on the modified 17-item Hamilton Rating Scale for Depression (HAM-D-17*). Following treatment, we found significant reductions in the frequency of most individual personality disorder diagnoses and total PDQ-R score. While patients no longer meeting criteria for cluster B personality disorders after treatment had similar reductions in depressive symptoms compared to those maintaining the diagnoses, subjects no longer meeting criteria for cluster A and cluster C diagnoses after treatment exhibited significantly greater decreases in depression severity than those who maintained the diagnoses. Overall, these results suggest that fluoxetine may be beneficial in the treatment of certain personality disorder traits in patients with MDD.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7846259&dopt=Abstract fluoxetine Prozac



Prozac
Up-regulation of beta 1-adrenergic receptors in rat brain after chronic citalopram and fluoxetine treatments.

Palvimaki EP, Laakso A, Kuoppamaki M, Syvalahti E, Hietala J.

Department of Pharmacology, University of Turku, Finland.

Quantitative receptor autoradiography was used to study the effects of the selective serotonin reuptake inhibitors citalopram and fluoxetine and the tricyclic antidepressant imipramine on the regulation of beta 1-adrenergic receptors in the rat brain. Rats were treated with saline, citalopram (10 mg kg-1), fluoxetine (10 mg kg-1), or imipramine (15 mg kg-1) SC once daily for 14 days. [125I]Iodocyanopindolol binding to beta 1-adrenergic receptors was found to increase significantly in the caudate-putamen and the somatosensory areas of the frontal cortex after both citalopram and fluoxetine treatments. Imipramine treatment elicited a marked decrease in beta 1 binding in the outer laminae of the cingulate cortex, as well as in the motor and somatosensory areas of the frontal cortex. In a separate experiment, rats were treated with saline, citalopram (2.5, 10 and 20 mg kg-1) or fluoxetine (2.5, 10 and 20 mg kg-1) SC once daily for 14 days. The effects of citalopram and fluoxetine on beta 1 receptors in the somatosensory cortex and caudate-putamen were replicated. These results demonstrate that chronic administration of selective serotonin reuptake inhibitors, in contrast to imipramine, can cause a regional up-regulation of beta 1-adrenergic receptors in the rat brain.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7871100&dopt=Abstract fluoxetine Prozac



Prozac
In vivo biogenic amine efflux in medial prefrontal cortex with imipramine, fluoxetine, and fluvoxamine.

Jordan S, Kramer GL, Zukas PK, Moeller M, Petty F.

Veterans Affairs Medical Center, Dallas, Texas.

In vivo brain microdialysis was used to determine the effects of the standard tricyclic antidepressant imipramine and the two selective serotonin reuptake inhibitors (SSRIs) antidepressants, fluoxetine and fluvoxamine, on extracellular levels of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in rat medial prefrontal cortex. When given intraperitoneally (IP), imipramine increased NE in the microdialysis perfusate, and elevated DA and 5-HT to a lesser extent. Similar dose-dependent increases in DA and 5-HT were detected after IP fluoxetine, although NE was less affected. In contrast, IP fluvoxamine produced no change in basal NE nor DA, although a large increase in 5-HT occurred at an intermediate dose. When administered directly into cortex, all three antidepressants increased 5-HT by the same amount in a dose-dependent fashion. Intracortical imipramine and fluoxetine increased NE, and fluoxetine and fluvoxamine both increased DA, with fluoxetine doing so at a lower concentration. These data suggest that the SSRIs are not entirely selective for serotonin in vivo.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7886621&dopt=Abstract fluoxetine Prozac



Prozac
Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat.

Kodama M, Fujioka T, Duman RS.

Division of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508, USA.

BACKGROUND: There has been increasing evidence that atypical antipsychotics are effective in the treatment of mood disorders or for augmenting 5-hydroxytryptamine selective reuptake inhibitors for treatment-resistant depression. METHODS: Upregulation of neurogenesis in the adult hippocampus is a marker of antidepressant activity, and the present study investigated the influence of the atypical antipsychotic drug olanzapine on cell proliferation in the hippocampus of adult rat. The regulation of cell proliferation in the prelimbic cortex of adult rat was also examined. RESULTS: Chronic (21 days) olanzapine administration increased the number of newborn cells in the dentate gyrus of the hippocampus to the same extent as fluoxetine. Olanzapine or fluoxetine treatment also increased the number of proliferating cells in the prelimbic cortex. In contrast, there was no effect of either drug in the subventricular zone or primary motor cortex, and there was a trend for an increase in the striatum. Subchronic (7 days) administration of olanzapine had no effect on cell proliferation in hippocampus or prelimbic cortex, consistent with the time course for the effect of fluoxetine and the therapeutic actions of antidepressant treatment. The combination of olanzapine plus fluoxetine did not result in a greater induction of cell proliferation in either brain region. Analysis of the cell phenotype demonstrated that approximately 20% of the newborn cells in the prelimbic cortex differentiated into endothelial cells but not neurons, in contrast to the dentate gyrus, where most newborn cells differentiated into neurons. CONCLUSIONS: The results demonstrate that antidepressant or atypical antipsychotic medications can increase the proliferation of glia in limbic brain structures, an effect that could reverse the loss of glia that has been observed in depressed patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15476686&dopt=Abstract fluoxetine Prozac



Prozac
Efficacy of alprazolam in reducing fluoxetine-induced jitteriness in patients with major depression.

Amsterdam JD, Hornig-Rohan M, Maislin G.

Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia.

BACKGROUND: Serotonin selective reuptake inhibitors (SSRIs) have become the most widely prescribed antidepressants in the United States. The selective influence of SSRIs on serotonin neurotransmission has resulted in a specific constellation of adverse effects termed "jitteriness" syndrome, which occurs in at least 30% of patients taking SSRIs. Because there have been no systematic studies examining treatment of SSRI-induced jitteriness, we conducted a prospective study of the efficacy of adjunctive alprazolam therapy for fluoxetine-induced jitteriness symptoms. METHOD: Fifty-four subjects with major depression were treated with fluoxetine 20 mg/day. Subjects experiencing an increase in jitteriness symptoms within 2 weeks of starting fluoxetine were given adjunctive alprazolam 0.5 mg to 4.0 mg daily for 2 weeks followed by a 2-week taper period. RESULTS: Eighteen (33.3%) of 54 patients experienced jitteriness symptoms during fluoxetine treatment. We observed a statistically significant reduction in the severity and number of jitteriness symptoms with adjunctive alprazolam. Moreover, in most cases jitteriness symptoms did not reappear during the alprazolam taper period or after alprazolam was discontinued. CONCLUSION: These observations suggest that a brief course of adjunctive alprazolam treatment may be efficacious in reducing the duration and severity of jitteriness symptoms resulting from antidepressants that are selective for serotonin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7929020&dopt=Abstract fluoxetine Prozac