fluvoxamine and Body-Weight

Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity.

Topics: Antidepressive Agents, Second-Generation; Body Weight; Central Nervous System Diseases; Depressive Disorder; Fluvoxamine; Humans; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological; Sleep Wake Disorders

Numerous studies have demonstrated that fluvoxamine has considerable pharmacokinetic and pharmacodynamic interactions with clozapine. We conducted a 12-week, randomized, double-blind, placebo-controlled study to evaluate the effects of fluvoxamine on metabolic parameters and psychopathology in clozapine-treated patients with schizophrenia.. We recruited 85 patients who received a DSM-IV diagnosis of schizophrenia. Eligible patients were randomized to receive fluvoxamine 50mg/day plus clozapine 100mg/day or clozapine 300mg/day. We studied metabolic parameters, psychopathology, and drug levels at baseline and 4, 8, and 12weeks after the intervention. Plasma levels of clozapine, norclozapine, clozapine N-oxide, and fluvoxamine were determined using high-performance liquid chromatography with ultraviolet detection.. No significant difference was observed in baseline characteristics between the two groups. Clozapine-fluvoxamine combined treatment significantly attenuated the increments in body weight, insulin resistance, and levels of insulin, glucose, and triglycerides compared with clozapine monotherapy. Both groups exhibited significant improvements in their Positive and Negative Syndrome Scale (PANSS) total and negative scores. The combined treatment group showed significant reduction in the PANSS general psychopathology scores compared with the monotherapy group. No difference was observed in the plasma clozapine level between the two groups. The monotherapy group showed higher levels of norclozapine and clozapine N-oxide than the combined group.. Compared with clozapine monotherapy, treatment with adjunctive fluvoxamine with clozapine for 12weeks can alleviate body weight gain and metabolic abnormalities in patients with schizophrenia, without sacrificing the clinical effect. Clinicians should interpret these findings cautiously considering the short duration of this study. The study was registered at www.clinicaltrials.gov (NCT01401491).

Topics: Antipsychotic Agents; Antisocial Personality Disorder; Body Weight; Clozapine; Double-Blind Method; Drug Therapy, Combination; Female; Fluvoxamine; Follow-Up Studies; Humans; Leukocytes; Male; Metabolic Diseases; Psychiatric Status Rating Scales; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Time Factors; Treatment Outcome

Clozapine treatment is associated with side-effects such as blood cell dyscrasias and weight gain. Increased plasma levels of the cytokines and soluble cytokine receptors leptin, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors p55 and p75, as well as toxic metabolites of clozapine, have been suggested as the basis for these side-effects,. This study examined whether the coadministration of the selective serotonine reuptake inhibitor fluvoxamine, which interferes with clozapine's hepatic metabolism, affects the immunomodulation by clozapine and some of its side-effects.. The following parameters were measured: circulating levels of the cytokines and soluble receptors, plasma concentrations of clozapine and its metabolite N-desmethylclozapine, body weight and blood cell counts in 11 and 12 schizophrenic inpatients on combined and monotherapy, respectively, before and during the first 6 weeks of medication.. On the basis of comparable plasma levels of clozapine and N-desmethylclozapine, the coadministration of fluvoxamine 1) attenuated and delayed the clozapine-induced increase in TNF-alpha plasma levels, 2) enhanced and accelerated the clozapine-induced increase in leptin plasma levels without significant effect on clozapine-induced weight gain, and 3) decreased granulocyte counts.. As clozapine, its metabolite N-desmethylclozapine and fluvoxamine are unlikely to make these differences, other metabolites might be responsible. The coadministration of clozapine and fluvoxamine offers the opportunity to investigate further the putative associations between certain metabolites, immunomodulation and these side-effects.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Blood Cell Count; Body Weight; Clozapine; Cytokines; Drug Interactions; Drug Therapy, Combination; Female; Fluvoxamine; Granulocytes; Humans; Leptin; Male; Middle Aged; Schizophrenia; Selective Serotonin Reuptake Inhibitors

Fifteen women with bulimia nervosa were treated with a 4-month course of combined cognitive-behavioral, nutritional and antidepressant therapy (5 with amineptine and 10 with fluvoxamine). Patients were monitored before and after 1, 2 and 4 months of therapy for body mass index (BMI), for eating disorder symptoms by the Eating Disorder Inventory (EDI) and the Bulimic Investigation Test (BITE), and for depression and anxiety by the Hamilton Rating Scale for Depression and for Anxiety (HRS-D and -A). BITE symptoms and gravity improved significantly and equally in the two groups during the 4 months of therapy. Global EDI scores, depression and anxiety decreased but not significantly. BMI was normal before therapy and did not change during treatment.

Topics: Adolescent; Adult; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Behavior Therapy; Body Weight; Bulimia; Cognitive Behavioral Therapy; Combined Modality Therapy; Dibenzocycloheptenes; Female; Fluvoxamine; Humans; Nutritional Physiological Phenomena; Psychiatric Status Rating Scales; Recurrence; Time Factors

A series of double-blind hospital based studies comparing fluvoxamine with other antidepressants in depressed patients is reviewed. Overall there were no significant differences in terms of efficacy between fluvoxamine and the comparators (amitriptyline, dothiepin, lofepramine and mianserin). Fluvoxamine was shown to be associated with a low incidence of anticholinergic, cardiovascular or sedative effects. This profile of activity, together with low toxicity in overdosage, has established the place of fluvoxamine in the treatment of depressive illness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents, Tricyclic; Body Weight; Depressive Disorder; Double-Blind Method; Female; Fluvoxamine; Humans; Male; Middle Aged

The study of the relationship between 198 plasmatic fluvoxamine dosages and posology has been done on a sample of 80 inpatients. It shows that plasmatic levels increase proportionally with posology p.o. In contrast, plasmatic levels seem to be independent from weight and age of inpatients.

Topics: Aging; Body Weight; Depressive Disorder; Fluvoxamine; Hospitalization; Humans

Obesity and depression are common disorders which may co-exist. The management of the combination is complicated because some antidepressants cause weight gain fenfluramine, an effective antiobesity agent, may cause depression. Fluvoxamine is an antidepressant which, like fenfluramine, inhibits serotonin re-uptake within the brain. Forty obese female subjects with refractory obesity participated in a double-blind placebo controlled trial. During the twelve week study, those subjects receiving fluvoxamine achieved a mean weight loss greater than, but not significantly different from, that of the placebo group. The result suggests that fluvoxamine may be particularly useful in the management of obese patients requiring treatment with an antidepressant.

Topics: Adolescent; Adult; Antidepressive Agents; Body Weight; Dose-Response Relationship, Drug; Fluvoxamine; Humans; Middle Aged; Obesity; Oximes

Serotonin leads to reduced food intake and satiety. Disrupted circadian rhythms lead to hyperphagia and obesity. The serotonergic and circadian systems are intertwined, as the central brain clock receives direct serotonergic innervation and, in turn, makes polysynaptic output back to serotonergic nuclei. Our objective was to test the hypothesis that peripherally serotonin alters circadian rhythms leading to a shift towards fat synthesis and weight gain. We studied the effect of serotonin and fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), on the circadian clock and metabolic gene and protein expression in mouse liver, muscle and white adipose tissue (WAT) and cell culture. We found that serotonin and/or the SSRI fluvoxamine led to fat accumulation in mouse liver and hepatocytes by shifting metabolism towards fatty acid synthesis mainly through low average levels of phosphorylated acetyl CoA carboxylase (pACC) and phosphorylated protein phosphatase 2A (pPP2A). This shift towards fat synthesis was also observed in adipose tissue. Muscle cells were only slightly affected metabolically by serotonin or fluvoxamine. In conclusion, although centrally it leads to increased satiety, in peripheral tissues, such as the liver and WAT, serotonin induces fat accumulation.

Topics: Acetyl-CoA Carboxylase; Adipose Tissue; Animals; Body Weight; Cells, Cultured; Circadian Rhythm; Fluvoxamine; Gene Expression Regulation; Lipogenesis; Liver; Mice; Muscle, Skeletal; Phosphorylation; Protein Phosphatase 2; Selective Serotonin Reuptake Inhibitors; Serotonin

Oxidative stress is a critical route of damage in various psychological stress-induced disorders, such as depression. Antidepressants are widely prescribed to treat these conditions; however, few animal studies have investigated the effect of these drugs on endogenous antioxidant status in the brain. The present study employed a 21-day chronic regimen of random exposure to restraint stress to induce oxidative stress in brain, and behavioural aberrations, in rodents. The forced swimming (FST) and sucrose preference tests were used to identify depression-like phenotypes, and reversal in these indices indicated the effectiveness of treatment with fluoxetine (FLU; 20 mg/kg/day, p.o.; selective serotonin reuptake inhibitor), imipramine (IMI; 10 mg/kg/day, p.o.; tricyclic antidepressant) and venlafaxine (VEN; 10 mg/kg/day, p.o.; dual serotonin/norepinephrine reuptake inhibitor) following restraint stress. The antioxidant status was investigated in the brain of these animals. The results evidenced a significant recovery in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR) and glutathione (GSH) levels by antidepressant treatments following a restraint stress-induced decline of these parameters. The severely accumulated lipid peroxidation product malondialdehyde (MDA) and protein carbonyl contents in stressed animals were significantly normalized by antidepressant treatments. The altered oxidative status is implicated in various aspects of cellular function affecting the brain. Thus, it is possible that augmentation of in vivo antioxidant defenses could serve as a convergence point for multiple classes of antidepressants as an important mechanism underlying the neuroprotective pharmacological effects of these drugs observed clinically in the treatment of various stress disorders. Consequently, pharmacological modulation of stress-induced oxidative damage as a possible stress-management approach should be an important avenue of further research.

Topics: Animals; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Antioxidants; Body Weight; Cyclohexanols; Depressive Disorder; Fluvoxamine; Food Preferences; Imipramine; Lipid Peroxidation; Protein Carbonylation; Rats; Restraint, Physical; Stress, Psychological; Swimming; Taste; Venlafaxine Hydrochloride

The effects of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), were studied in normophagic and food-restriction-induced hyperphagic middle-aged Wistar rats. Normophagic intact Wistar rats were given fluvoxamine (100 mg/kg/d, per os (p.o.)) or vehicle for 10 d. Hyperphagic middle-aged Wistar rats were subjected to 10 d of food restriction; they were allowed to refeed for 10 d, with ad libitum food access and administered fluvoxamine (100 mg/kg/d, p.o.) or vehicle during the 10-d refeeding period. Fluvoxamine administration to normophagic middle-aged Wistar rats affected neither their weight nor food intake. However, administration to food-restricted rats showed inhibitory effects of weight gain and food intake during 10 d of refeeding. Fluvoxamine-treated rats showed significantly lower neuropeptide Y (NPY) immunostaining levels in the paraventricular nucleus (PVN) and dorsomedial hypothalamic nucleus (DMH) than untreated controls. Hypophagic and weight-inhibiting effects of fluvoxamine might be mediated via decreased NPY in PVN and DMH. These results suggest that the appetite-controlling effect of fluvoxamine might be responsive to the rats' appetite condition.

Topics: Animals; Antidepressive Agents, Second-Generation; Body Weight; Eating; Fluvoxamine; Hyperphagia; Hypothalamus; Male; Neuropeptide Y; Rats; Rats, Wistar; Weight Gain

Previous studies demonstrated that rats allowed access to running wheel with food restriction schedules run excessively. This hyperactivity consisted of a pre-feeding activity (an increase in running activity before the feeding time, also termed food-anticipatory activity: FAA) and a post-feeding activity (an increase in running activity after the feeding time, succeeding activity: SA). Here we evaluated the effect of fluvoxamine, a selective serotonin reuptake inhibitor, on food restriction-induced hyperactivity in rats. Furthermore, the effect of fluvoxamine on each of the FAA and the SA was also investigated. Rats were individually housed in a running-wheel cage under food restriction for 3 h per day, and running activity was measured for 7 consecutive days. This restricted feeding significantly increased the running activity and decreased body weight. Simultaneous administration of fluvoxamine (50 mg/kg/day, p.o.) for 7 days suppressed the increase in running activity (P<0.05) with no modification of the decrease in body weight or food intake. Analysis of each activity revealed that fluvoxamine's efficacy was observed only in the SA (p<0.01). These results suggest that repeated treatment with fluvoxamine attenuates the hyperactivity, which is exclusively dependent on the substantial reduction in the SA.

Topics: Animals; Body Weight; Caloric Restriction; Eating; Fluvoxamine; Hyperkinesis; Male; Motor Activity; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors

Treating primary 'negative symptoms' of schizophrenia with a combination of a typical antipsychotic and a selective serotonin reuptake inhibitor, is more effective than with antipsychotic alone and is similar to the effect of the atypical antipsychotic, clozapine. The mechanism of this treatment combination is unknown and may involve changes in dopaminergic and serotonin systems. We studied dopamine and serotonin metabolism in different rat brain areas at 1.5 and 24 h after the last dosage of chronic treatment (30 days), with haloperidol plus fluvoxamine, each drug alone, and clozapine. Haloperidol-fluvoxamine combination, haloperidol, and clozapine treatments increased striatal and frontal cortex dopamine turnover and reduced striatal tyrosine hydroxylase activity at 1.5 h. At 24 h both dopamine turnover and tyrosine hydroxylase activity were reduced. Thus, in chronically treated animals, release of striatal dopamine increases following a drug pulse and returns to baseline by 24 h. Serotonin and 5-hydroxyindoleacetic acid concentrations were decreased at 1.5 h in haloperidol-fluvoxamine and clozapine groups and returned to normal levels by 24 h. A limited behavioral assessment showed that treatment with haloperidol plus fluvoxamine reduced motor activity compared to haloperidol, and increased sniffing compared to haloperidol, fluvoxamine and clozapine. These findings indicate that combining antipsychotic with SSRI results in specific changes in dopaminergic and serotonergic systems and in behavior. The possibility that these may be relevant to the mechanism underlying the clinical effectiveness of augmentation treatment warrant further study.

Topics: Animals; Antipsychotic Agents; Behavior, Animal; Body Weight; Brain; Clozapine; Dopamine; Dopamine Antagonists; Drug Interactions; Fluvoxamine; Haloperidol; Immunohistochemistry; Male; Motor Activity; Neostriatum; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Serotonin; Tyrosine 3-Monooxygenase

Selective Serotonin Reuptake Inhibitors (SSRIs) are designed to treat adults, but are increasingly prescribed for adolescents. SSRIs might cause permanent changes in serotonin-related behavior in adolescents, since their serotonergic system is still developing. Male Wistar rats were treated with paroxetine (15 mg/kg p.o.) or fluvoxamine (30 mg/kg p.o.) throughout adolescence. After a washout period their behavior in the elevated plus-maze, prepulse inhibition test, Forced swimming test and elevated T-maze were studied. In addition, the effects of the 5-HT(1A) receptor agonist 8-OH-DPAT on sexual behavior and lower lip retraction were measured. Paroxetine mildly inhibited weight gain during treatment. Both SSRIs caused a reduction in ejaculation frequency and in time spent on the open arm of the elevated plus-maze in adult rats. Fluvoxamine slightly increased avoidance latency in the elevated T-maze compared to paroxetine. No differences between the groups were found in the other tests. Apparently, chronic treatment with SSRIs during adolescence may cause mild changes in adult behavior.

Topics: 8-Hydroxy-2-(di-n-propylamino)tetralin; Acoustic Stimulation; Analysis of Variance; Animals; Behavior, Animal; Body Weight; Dose-Response Relationship, Radiation; Drug Interactions; Fluvoxamine; Inhibition, Psychological; Male; Maze Learning; Paroxetine; Rats; Rats, Wistar; Reaction Time; Reflex, Startle; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Receptor Agonists; Sexual Behavior, Animal; Swimming

Bilateral removal of the olfactory bulbs (OBX) in rats results in a complex constellation of behavioral, neurochemical, neuroendocrine, and neuroimmune alterations, many of which are also reported in patients with major depressive disorder (MDD). Drawing on clinical findings, there has been considerable interest in the role of serotonin in the mechanism of action of OBX. However, to date, there has been no report of direct measurement of serotonergic functioning of bulbectomized animals using microdialysis. The present study describes the effects of olfactory bulbectomy on functioning of the serotonergic system.. In vivo microdialysis was performed in conscious rats that underwent OBX or sham surgery. Alterations in the functioning of the serotonergic system were assessed by administration of fluvoxamine, fenfluramine, and 3-hydroxybenzylhydrazine (NSD-1015). Animals were also repeatedly tested in an open field.. Bilateral removal of the olfactory bulbs decreased basal extracellular levels by decreasing the releasable pool of serotonin (5-HT) in the basolateral amygdala 2 weeks after surgery and in the dorsal hippocampus 2 weeks and 5 months after surgery. Olfactory bulbectomized animals showed a lower rate of 5-HT synthesis under basal conditions. However, the capacity of the system to synthesize 5-HT was not affected. Olfactory bulbectomized rats were hyperactive in the open field. This hyperactivity remained after successive testing, indicating permanent behavioral changes.. This microdialysis study shows that OBX has profound and long-lasting effects on serotonergic functioning and on activity levels and is therefore considered an intriguing and promising animal model for affective processes in the brain.

Topics: Animals; Area Under Curve; Behavior, Animal; Body Weight; Brain; Brain Chemistry; Chromatography, High Pressure Liquid; Dopamine; Electrochemistry; Enzyme Inhibitors; Exploratory Behavior; Fenfluramine; Fluvoxamine; Hydrazines; Hydroxyindoleacetic Acid; Male; Microdialysis; Multivariate Analysis; Olfaction Disorders; Olfactory Bulb; Olfactory Pathways; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Serotonin; Time Factors

We examined the effects of fluoxetine and fluvoxamine, selective serotonin reuptake inhibitors (SSRIs), and desipramine, a selective noradrenaline (NA) reuptake inhibitor, given alone or in combination with diazepam on immobility time in the tail suspension test in diabetic mice. Immobility time was significantly longer in diabetic than in nondiabetic mice. Diazepam (0.1 and 0.3 mg/kg s.c.) dose-dependently decreased immobility time in diabetic mice to the level observed in saline-treated nondiabetic mice. However, diazepam had no significant effect on immobility time in nondiabetic mice. Fluoxetine (3-56 mg/kg i.p.) and desipramine (1-30 mg/kg i.p.) produced marked, dose-dependent suppression of immobility time in both nondiabetic and diabetic mice. However, anti-immobility effects of fluoxetine and desipramine in diabetic mice were less than those in nondiabetic mice. Fluvoxamine (3-30 mg/kg i.p.) produced a dose-dependent suppression of immobility time in nondiabetic mice but not in diabetic mice. The anti-immobility effects of fluoxetine, fluvoxamine and desipramine in nondiabetic mice were antagonized by pretreatment with diazepam (0.3 mg/kg s.c.). Furthermore, fluoxetine, fluvoxamine and desipramine had no effect on the immobility time in diazepam (0.3 mg/kg s.c.)-treated diabetic mice. These results indicate that the anti-immobility effects of SSRIs and desipramine are less in diabetic mice than in nondiabetic mice in the tail suspension test. Furthermore, in diabetic mice, SSRIs and selective NA reuptake inhibitors did not affect immobility time even though the prolonged duration of immobility was suppressed by pretreatment with diazepam.

Topics: Adrenergic Uptake Inhibitors; Animals; Anti-Anxiety Agents; Blood Glucose; Body Weight; Desipramine; Diabetes Mellitus, Experimental; Diazepam; Dose-Response Relationship, Drug; Fluoxetine; Fluvoxamine; Hindlimb Suspension; Male; Mice; Mice, Inbred ICR; Motor Activity; Selective Serotonin Reuptake Inhibitors

Brain serotonin plays a crucial role in the regulation of food intake and body weight homeostasis. Previous data suggest an interaction with corticotropin-releasing hormone (CRH). To further examine the interaction between these neurotransmitters, the selective serotonin reuptake-inhibitor (SSRI) fluvoxamine was given intraperitoneally in fa/fa Zucker rats with and without the CRH-receptor-antagonist alpha-helical CRH administered intracerebroventricularly (i.c.v.). The saline treated animals gained weight. Fluvoxamine led to a significant weight loss while not affecting food intake. Furthermore, insulin levels in this animal model were reduced following fluvoxamine administration. These effects were antagonized by alpha-helical CRH and are thus most likely mediated via CRH or CRH-like peptides.

Topics: Animals; Body Weight; Corticotropin-Releasing Hormone; Eating; Fluvoxamine; Hormone Antagonists; Injections, Intraperitoneal; Male; Rats; Rats, Zucker; Selective Serotonin Reuptake Inhibitors; Weight Loss

Current literature suggests that the incidence of sexual dysfunction secondary to fluvoxamine therapy is 1% to 8%, while other selective serotonin reuptake inhibitors may have rates as high as 75%. The objective of this study was to determine the incidence of sexual dysfunction secondary to fluvoxamine in healthy volunteers.. 20 healthy volunteers (10 men, 10 premenopausal women) had adverse effects assessed at 6 visits while not receiving fluvoxamine, then twice while taking 150 mg fluvoxamine daily. Assessments occurred at 2-week intervals. Incidence rates for sexual dysfunction were calculated.. No sexual dysfunction was reported prior to fluvoxamine therapy. After 2 weeks and 4 weeks of therapy respectively, sexual dysfunction occurred in 20% (N = 4) and 35% (N = 7) of the healthy volunteers.. The incidence of sexual dysfunction during fluvoxamine therapy in healthy volunteers is 35%. This incidence is higher than previously reported and similar to that of other selective serotonin reuptake inhibitors.

Topics: Adult; Body Weight; Female; Fluvoxamine; Humans; Incidence; Male; Premenopause; Selective Serotonin Reuptake Inhibitors; Sex Factors; Sexual Dysfunctions, Psychological; Surveys and Questionnaires

Topics: Adult; Body Weight; Clozapine; Drug Interactions; Fluvoxamine; Humans