Prozac
Efficacy of cognitive behavioral therapy and fluoxetine for the treatment of binge eating disorder: a randomized double-blind placebo-controlled comparison.

Grilo CM, Masheb RM, Wilson GT.

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06520, USA. carlos.grilo yale.edu

BACKGROUND: Cognitive behavioral therapy (CBT) and certain medications have been shown to be effective for binge eating disorder (BED), but no controlled studies have compared psychological and pharmacological therapies. We conducted a randomized, placebo-controlled study to test the efficacy of CBT and fluoxetine alone and in combination for BED. METHODS: 108 patients were randomized to one of four 16-week individual treatments: fluoxetine (60 mg/day), placebo, CBT plus fluoxetine (60 mg/day) or CBT plus placebo. Medications were provided in double-blind fashion. RESULTS: Of the 108 patients, 86 (80%) completed treatments. Remission rates (zero binges for 28 days) for completers were: 29% (fluoxetine), 30% (placebo), 55% (CBT+fluoxetine), and 73% (CBT+placebo). Intent-to-treat (ITT) remission rates were: 22% (fluoxetine), 26% (placebo), 50% (CBT+fluoxetine), and 61% (CBT+placebo). Completer and ITT analyses on remission and dimensional measures of binge eating, cognitive features, and psychological distress produced consistent findings. Fluoxetine was not superior to placebo, CBT+fluoxetine and CBT+placebo did not differ, and both CBT conditions were superior to fluoxetine and to placebo. Weight loss was modest, did not differ across treatments, but was associated with binge eating remission. CONCLUSIONS: CBT, but not fluoxetine, demonstrated efficacy for the behavioral and psychological features of BED, but not obesity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15691532&dopt=Abstract fluoxetine Prozac



Prozac
Comparison of the effects of mirtazapine and fluoxetine in severely depressed patients.

Versiani M, Moreno R, Ramakers-van Moorsel CJ, Schutte AJ, Antidepressants Study Group CE.

Institute of Psychiatry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

INTRODUCTION: Depression is a major global problem associated with large medical, sociological and economic burdens. Mirtazapine (Remeron((R)), Organon NV, The Netherlands) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression. However, this agent has not yet been tested in patients with severe depression alone.OBJECTIVE: To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression (>/=25 points on the first 17 items of the Hamilton Depression Rating Scale [HDRS-17]).METHODS: In this double-blind study, 297 severely depressed patients were randomised to receive mirtazapine 15-60 mg/day (n = 147) or fluoxetine 20-40 mg/day (n = 152) for 8 weeks. 294 subjects were actually treated and 292 included in the intent-to-treat population. Symptom severity was measured by the HDRS-17, Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) rating scale. Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Questionnaire and the Quality of Life, Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study.RESULTS: No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point; both treatments were associated with large (~15 points) decreases by study end. However, more mirtazapine-treated patients tended to exhibit a >/=50% decrease in HDRS score (significant at day 7; 9.0% vs 0.7%, p = 0.002). Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores (-10.9 vs -8.5, p = 0.006) and the proportion of patients with >/=50% decrease in MADRS score (21.4% vs 10.9%, p = 0.031). On the CGI, the proportion of 'much/very much improved' patients tended to be greater with mirtazapine (significant at day 7; 9.7% vs 3.4%, p = 0.032). No significant between-group differences were observed for the majority of quality-of-life measures. However, mirtazapine produced significantly better improvements on 'sleeping assessment 1' (14.9 +/- 5.2 vs 13.7 +/- 5.4, p = 0.028) and 'sleeping assessment 2' (p = 0.013) than fluoxetine. Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 +/- 2.7kg compared with a mean decrease in weight of 0.4 +/- 2.1kg for fluoxetine-treated patients (p < 0.001).CONCLUSIONS: Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15697327&dopt=Abstract fluoxetine Prozac



Prozac
Control of urine marking by use of long-term treatment with fluoxetine or clomipramine in cats.

Hart BL, Cliff KD, Tynes VV, Bergman L.

Behavior Service, Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.

OBJECTIVES: To determine whether clomipramine differs from fluoxetine in reducing feline urine marking; whether reduction of marking continues in cats treated >8 weeks; whether recurrence of marking, after abrupt drug withdrawal, is less in cats treated >8 weeks; and whether cats that are successfully treated but resume marking after drug withdrawal can be successfully treated again with the same drug regimen. DESIGN: Positive-controlled, double-masked clinical trial. ANIMALS: 22 neutered cats (2 females, 20 males) > or =1 year old with objectionable urine marking. PROCEDURE: Cats that marked vertically > or =3 times/wk were treated with fluoxetine (1 mg/kg [0.45 mg/lb], q 24 h, PO) or clomipramine (0.5 mg/kg [0.23 mg/lb], q 24 h, PO) for 16 weeks, and efficacy was compared. Recurrence of marking was determined after abrupt withdrawal of fluoxetine at 16 or 32 weeks. Reduction in marking in cats treated with fluoxetine for 8 weeks after returning to marking following drug withdrawal was compared with the initial 8 weeks of successful treatment. RESULTS: Efficacy of fluoxetine and clomipramine was similar. Treatment >8 weeks revealed increasing efficacy in reduction of marking. Return of marking after termination of fluoxetine administration occurred in most cats. Cats successfully treated initially with fluoxetine responded similarly to repeated treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Clomipramine and fluoxetine were equivalent in treating urine marking. Longer treatment increased efficacy. Most cats return to marking after abrupt drug withdrawal. A second course of treatment can be expected to be as effective as the first.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15702686&dopt=Abstract fluoxetine Prozac



Prozac
The ethics and science of medicating children.

Sparks JA, Duncan BL.

The University of Rhode Island, Kingston, RI, USA.

Prescriptions for psychiatric drugs to children and adolescents have skyrocketed in the past 10 years. This article presents evidence that the superior effectiveness of stimulants and antidepressants is largely a presumption based on an empirical house of cards, driven by an industry that has no conscience about the implications of its ever growing, and disturbingly younger, list of consumers. Recognizing that most mental health professionals do not have the time, and sometimes feel ill-equipped to explore the controversy regarding pharmacological treatment of children, this article discusses the four fatal flaws of drug studies to enable critical examination of research addressing the drugging of children. The four flaws are illustrated by the Emslie studies of Prozac and children, which offer not only a strident example of marketing masquerading as science, but also, given the recent FDA approval of Prozac for children, a brutal reminder of the danger inherent in not knowing how to distinguish science from science fiction. The authors argue that an ethical path requires the challenge of the automatic medical response to medicate children, with an accompanying demand for untainted science and balanced information to inform critical decisions by child caretakers.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15706694&dopt=Abstract fluoxetine Prozac



Prozac
Fluoxetine - do the benefits outweigh the risks in adolescent major depression?

Doggrell SA.

Doggrell Biomedical Communications, 47 Caronia Crescent, Lynfield, Auckland, New Zealand. s_doggrell yahoo.com.

Major depressive disorder probably occurs in approximately 5% of adolescents. In these adolescents, selective serotonin re-uptake inhibitors (SSRIs), other than fluoxetine, have shown limited benefit and may increase the risk of suicide. In the Treatment for Adolescents with Depression Study, treatment with fluoxetine of adolescents diagnosed with major depressive disorder, or with the combination of fluoxetine and cognitive behavioural therapy, was superior to placebo. Cognitive behavioural therapy alone was not shown to be superior to placebo. Of the patients in the study, 27% had at least minimal suicidal ideation at baseline, and this reduced to 9% at the end of the treatment period, with the reduction being similar in each of the treatment groups. There were more suicide-related adverse events in the patients treated with fluoxetine (15 of 216) than in patients not treated with fluoxetine (9 of 223). There were no actual suicides. Although further investigation of any association between fluoxetine and suicidal tendencies is clearly required, at present, fluoxetine is the only SSRI for which benefit has been clearly shown, and the benefits seem to outweigh the risks. Thus, fluoxetine should generally be the first choice drug of clinicians if they decide that antidepressant drug treatment is indicated in adolescents with major depressive disorder.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15709892&dopt=Abstract fluoxetine Prozac



Prozac
Chronic coadministration of olanzapine and fluoxetine activates locus coeruleus neurons in rats: implications for bipolar disorder.

Seager MA, Barth VN, Phebus LA, Rasmussen K.

Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA, rasmussen_kurt lilly.com.

RATIONALE: The depressive phase of bipolar disorder (bipolar depression) is a difficult-to-treat form of depression. The olanzapine/fluoxetine combination (Symbyax) is the only medication approved to treat this disorder. The precise neural mechanisms responsible for its efficacy are not clearly understood. OBJECTIVES: In order to further elucidate the neurobiological mechanisms responsible for the beneficial clinical effects of the olanzapine/fluoxetine combination, the current experiment was designed to investigate the effects of chronic coadministration of olanzapine and fluoxetine on electrophysiological activity in the locus coeruleus (LC). METHODS: Rats received olanzapine for 3 weeks via subcutaneous osmotic pumps while simultaneously receiving daily intraperitoneal injections of fluoxetine. These chronically treated rats were anesthetized, and single-unit recordings of LC neurons were made. RESULTS: Chronic administration of olanzapine alone significantly increased firing of LC neurons, while, as reported previously, chronic administration of fluoxetine alone significantly reduced firing of LC neurons. However, in the combination condition, olanzapine was able to block the fluoxetine-induced suppression of the LC, and a significant increase in LC activity was observed. CONCLUSIONS: The observed increase in firing of LC neurons could lead to enhanced levels of norepinephrine release in projection areas and amelioration of the clinical symptoms of bipolar depression.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15719213&dopt=Abstract fluoxetine Prozac



Prozac
Treatment effect of sibutramine compared to fluoxetine on leptin levels in polycystic ovary disease.

Karabacak IY, Karabacak O, Toruner FB, Akdemir O, Arslan M.

Department of Nuclear Medicine, Gazi University Medical Faculty, Ankara, Turkey. iyetkin tr.net

Weight reduction on its own is observed to cause improvement in some of the abnormalities seen in patients with polycystic ovary syndrome (PCOS). With respect to this observation, we studied the possible effects of different serotonin reuptake inhibitors (fluoxetine and sibutramine) on serum leptin levels that might play a role in the obesity component seen in patients with PCOS. In a random design, sixteen patients were assigned to fluoxetine and sibutramine for a period of 10 days. In both treatment groups, no significant differences were observed between pre-treatment and post-treatment values in insulin levels (p > 0.05). There was no significant difference between pretreatment and post-treatment serum leptin levels in the fluoxetine treatment group (p > 0.05). However, a significant reduction was observed in the serum leptin levels at the end of treatment in the sibutramine group (p < 0.05). The observed difference in the serum leptin response to the treatment effect of sibutramine compared to fluoxetine seems to be due to a mechanism independent of serotonin reuptake inhibition, possibly to the thermogenic effect of the sibutramine itself. Further studies with larger groups are warranted, to examine the mechanism of the weight-reducing effect of sibutramine. Detailed analyses of basal metabolic activity and change in serum leptin levels should be carried out.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15724802&dopt=Abstract fluoxetine Prozac



Prozac
Antidepressant-like actions of intra-accumbens infusions of allopregnanolone in ovariectomized Wistar rats.

Molina-Hernandez M, Tellez-Alcantara NP, Perez Garcia J, Olivera Lopez JI, Teresa Jaramillo M.

Laboratorio de Conducta, Instituto de Investigaciones Psicologicas, Universidad Veracruzana, Jalapa, POB 361, Veracruz, 91000, Mexico.

This study was aimed to verify the role of the nucleus accumbens (NAcc) in the antidepressant-like effects of allopregnanolone in ovariectomized rats forced to swim. The interaction between infusions of allopregnanolone (intra-NAcc) with systemic administrations of allopregnanolone, muscimol, fluoxetine and GABA-A antagonists was assessed. Results showed that allopregnanolone (intra-NAcc; 1.5 mug, p<0.05; 2.0 mug, p<0.05) or systemic injections of allopregnanolone (1.5 mg/kg, p<0.05; 2.0 mg/kg, p<0.05; s.c.) or muscimol (0.3 mg/kg, p<0.05; 0.6 mg/kg, p<0.05; i.p.) reduced immobility by increasing climbing in the forced swimming task (FST), whereas fluoxetine (1.0 mg/kg, p<0.05; 2.0 mg/kg, p<0.05; i.p.) reduced immobility by increasing swimming. Allopregnanolone (intra-NAcc; 0.5 mug/side) synergized with systemic doses of allopregnanolone (0.5 mg/kg; p<0.05), muscimol (0.1 mg/kg; p<0.05) or fluoxetine (0.5 mg/kg; p<0.05) and reduced immobility by increasing climbing. Picrotoxin (0.125 mg/kg; i.p.) attenuated the synergism of the combination allopregnanolone (intra-NAcc; 0.5 mug/side) plus fluoxetine (i.p.) or allopregnanolone (s.c.) and the effects of allopregnanolone (intra-NAcc; 1.5 mug/side). Bicuculline (2.0 mg/kg; i.p.) attenuated the synergism between the combination allopregnanolone (intra-NAcc; 0.5 mug/side) plus muscimol (i.p.), but not the synergism of the combination allopregnanolone (intra-NAcc; 0.5 mug/side) plus allopregnanolone (s.c.). In conclusion, allopregnanolone (systemic injections or intra-NAcc), fluoxetine or muscimol produced antidepressant-like effects in the FST. Subthreshold doses of allopregnanolone (intra-NAcc) synergized with systemic subthreshold doses of fluoxetine, muscimol or allopregnanolone. Antagonists of the GABA-A receptor canceled the synergism.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15740782&dopt=Abstract fluoxetine Prozac