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PubMed1990

Response to total sleep deprivation before and during treatment with fluvoxamine or maprotiline in patients with major depression--results of a double-blind study.

To test the hypothesis that the antidepressant effects of total sleep deprivation (TSD) are linked to the serotonergic and/or noradrenergic system the authors carried out a double-blind study (fluvoxamine versus maprotiline) in 42 inpatients with endogenous depression (ICD). Patients were randomized to a four-week treatment with either fluvoxamine (100-300 mg/day) or maprotiline (100-300 mg/day). In addition, patients underwent a TSD procedure before and after one week of antidepressant medication. There was a statistically significant reduction of depression ratings (HDRS) in both the fluvoxamine and maprotiline group. The day-1 response to TSD before antidepressive medication was not associated with a clear relationship to the outcome after four weeks of treatment with either fluvoxamine or maprotiline. On the other hand, the day-2 response to TSD was significantly correlated with a good outcome to subchronic treatment with maprotiline. Furthermore, the results of the authors' data suggest that a favorable short-term outcome of TSD may be connected to antidepressants enhancing the serotonergic neurotransmission. The global comparison between fluvoxamine and maprotiline revealed that the group of patients treated with fluvoxamine had a significantly higher efficiency index (CGI) than the maprotiline group; fluvoxamine was rated to be tolerated excellently in 70% of the patients whereas this percentage was only 43% in the maprotiline group. There was also significantly more vertigo and dry mouth in the maprotiline group whereas the fluvoxamine group was rated to have significantly more sleep disturbances during the trial.

Adult↗
PubMed2001

Fluvoxamine-theophylline interaction: gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2.

OBJECTIVE: Several reports indicate that fluvoxamine decreases the clearance of cytochrome P4501A2 (CYP1A2) substrates. This study compared in vitro and in vivo inhibition potencies of fluvoxamine toward CYP1A2 with an approach based on inhibition constants (K(i)) determined in vitro and in vivo. METHODS: In vitro inhibition constant values were determined with human liver microsomes and complementary deoxyribonucleic acid-expressed CYP1A2 (supersomes). Fluvoxamine in vivo inhibition constants (K(i)iv) for CYP1A2 were obtained from an investigation of single-dose theophylline (250 mg) disposition in 9 healthy volunteers receiving steady-state (9 days) fluvoxamine at 3 doses (0, 25, or 75 mg/d) in a randomized crossover design. RESULTS: In vitro K(i) values based on total inhibitor concentrations were 177 +/- 56 nmol/L, 121 +/- 21 nmol/L, and 52 +/- 13 nmol/L in human liver microsomes with 1 mg/ml protein and 0.5 mg/ml protein and in supersomes with 0.3 mg/ml protein, respectively. The corresponding in vitro K(i) values based on unbound fluvoxamine concentrations were 35 nmol/L, 36 nmol/L, and 36 nmol/L. The ratio of 1-methyluric acid formation clearances (control/inhibited) in 8 subjects was positively correlated with fluvoxamine concentration (r (2) = 0.87; P <.001) with an intercept near 1. Mean values for K(i)iv based on total and unbound plasma concentrations at steady state were 25.3 nmol/L (range, 14-39 nmol/L) and 3.6 nmol/L (range, 2.4-5.9 nmol/L), respectively. CONCLUSION: Comparison of in vitro and in vivo K(i) values based on unbound fluvoxamine concentrations suggests that fluvoxamine inhibition potency is approximately 10 times greater in vivo than in vitro.

Adult↗
PubMed2000

The effect of erythromycin, fluvoxamine, and their combination on the pharmacokinetics of ropivacaine.

UNLABELLED: We studied the effect of fluvoxamine and erythromycin on the pharmacokinetics of ropivacaine in a double-blinded, randomized, four-way cross-over study. Eight healthy volunteers ingested daily 1500 mg erythromycin for 6 days, 100 mg fluvoxamine for 5 days (Days 2-6), both erythromycin and fluvoxamine, or placebo. On Day 6, each subject received a single dose of 0.6 mg/kg ropivacaine IV over 30 min. Ropivacaine, 3-hydroxyropivacaine, and 2',6'-pipecoloxylidide in venous plasma and urine samples were measured for up to 12 h and 24 h, respectively. Fluvoxamine increased the area under the drug plasma concentration-time curve (AUC) of ropivacaine 3.7-fold (P: < 0.001), prolonged the elimination half-life (t(1/2)) from 2.3 to 7.4 h (P: < 0.01), and decreased the clearance by 77% (P: < 0.001). Erythromycin alone had only a minor effect on the pharmacokinetics of ropivacaine. However, when compared with fluvoxamine alone, the combination of fluvoxamine and erythromycin further increased the area under the drug plasma concentration-time curve and t(1/2) of ropivacaine by 50% (P: < 0.01). We conclude that inhibition of CYP1A2 by fluvoxamine considerably reduces elimination of ropivacaine. Concomitant use of fluvoxamine and CYP3A4 inhibitor erythromycin further increases plasma ropivacaine concentration by decreasing its clearance. IMPLICATIONS: Clinicians should be aware of the possibility of increased toxicity of ropivacaine when used together with inhibitors of CYP1A2. Concomitant use of CYP1A2 and CYP3A4 inhibitors further increases ropivacaine concentration.

Adult↗
PubMedDate not supplied

Fluvoxamine open-label treatment of adolescent inpatients with obsessive-compulsive disorder or depression.

OBJECTIVE: Fluvoxamine, a monocyclic, specific serotonin uptake inhibitor with demonstrated efficacy in obsessive-compulsive disorder (OCD) and depression in adults, is marketed in more than 30 countries worldwide, including Israel. In the United States, where fluvoxamine is available only on an investigational basis, marketing appears imminent. This study evaluates the safety and efficacy of fluvoxamine in adolescents. METHOD: In an 8-week, open-label trial of fluvoxamine, 20 adolescent inpatients, ages 13 to 18 years, were treated for OCD (n = 14) or major depressive disorder (MDD)(n = 6) with daily doses ranging from 100 to 300 mg. Target symptoms were rated at regular intervals with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS); Suicide Potential Scales (SPS); Beck Depression Inventory (BDI); the Overt Aggression Scale (OAS); and the Children's Global Adjustment Scale (CGAS). RESULTS: Fluvoxamine proved relatively safe and was especially effective in the patients with OCD; mean Y-BOCS scores decreased significantly (p < .0001) from 28.0 to 19.8 on medication. Although fluvoxamine also appeared effective in decreasing depression and bulimic symptoms, its impact on impulsive, suicidal, and anorectic symptoms was less clear. The commonest side effects (n > or = 3) were dermatitis, insomnia, hyperactivity, excitement, anxiety, tremor, and nausea. Fluvoxamine was discontinued in four patients because of side effects; the most serious side effect occurred in two debilitated anorexic patients, of whom one became delirious and the other developed hallucinations. CONCLUSION: Preliminary evidence suggests that short-term treatment of adolescents with fluvoxamine is relatively safe and may be effective for OCD and some affective spectrum symptoms.

Adolescent↗
PubMed2001

Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial.

OBJECTIVE: To determine the safety and efficacy of fluvoxamine for the treatment of children and adolescents with obsessive-compulsive disorder (OCD) with a double-blind, placebo-controlled, multicenter study. METHOD: Subjects, aged 8 to 17 years, meeting DSM-III-R criteria for OCD were recruited from July 1991 to August 1994. After a 7- to 14-day single-blind, placebo washout/screening period, subjects were randomly assigned to fluvoxamine 50 to 200 mg/day or placebo for 10 weeks. Subjects who had not responded after 6 weeks could discontinue the double-blind phase of the study and enter a long-term, open-label trial of fluvoxamine. Analyses used an intent-to-treat sample with a last-observation-carried-forward method. RESULTS: Mean Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores with fluvoxamine were significantly (p < .05) different from those with placebo at weeks 1, 2, 3, 4, 6, and 10. Significant (p < .05) differences between fluvoxamine and placebo were observed for all secondary outcome measures at all visits. Based on a 25% reduction of CY-BOCS scores, 42% of subjects taking fluvoxamine were responders compared with 26% taking placebo. Forty-six (19 fluvoxamine, 27 placebo) of 120 randomized subjects discontinued early. Adverse events with a placebo-adjusted rate greater than 10% were insomnia and asthenia. CONCLUSIONS: Fluvoxamine has a rapid onset of action and is well tolerated and efficacious for the short-term treatment of pediatric OCD.

Adolescent↗
PubMed1998

Faster onset of action of fluvoxamine in combination with pindolol in the treatment of delusional depression: a controlled study.

This double-blind, controlled study was undertaken to investigate whether the addition of pindolol could improve the therapeutic response to fluvoxamine of depressed patients with psychotic features. After a 1-week placebo run-in period, 72 patients received fluvoxamine 300 mg/day in combination with placebo or pindolol 7.5 mg/day. At study completion, 28 (80%) of 35 patients treated with fluvoxamine plus placebo and 29 (80.5%) of 36 patients treated with fluvoxamine plus pindolol were categorized as responders (reduction of their score on the 21-item Hamilton Rating Scale for Depression to 8 or less and on the Dimension for the Delusional Experience Rating Scale to 0). In the third and fourth weeks, the response rates were significantly superior in the fluvoxamine plus pindolol group (p = 0.0001, p = 0.023, respectively). Treatment response seemed to be unrelated to the demographic and the clinical characteristics recorded. No significant difference was found comparing plasma levels of fluvoxamine between groups, thus excluding a pharmacokinetic interaction. Other than mild nausea and sedation in a few patients, treatments were well tolerated. No medically significant adverse events occurred. Depressed patients with psychotic features who were administered pindolol experienced a more rapid improvement during fluvoxamine treatment. Thus, the combination of fluvoxamine with pindolol may be a useful pharmacologic strategy in the treatment of this disorder. A rapid clinical response in such patients is of relevance in clinical practice as well as in economic fields, given the direct and indirect costs of depression.

Adolescent↗
PubMed2000

Fluvoxamine-Clozapine drug interaction: inhibition in vitro of five cytochrome P450 isoforms involved in clozapine metabolism.

Administration of fluvoxamine to patients receiving clozapine therapy may increase the steady-state serum concentrations of clozapine by a factor of 5 to 10. The authors undertook in vitro studies to disclose the mechanism behind this clinically important interaction. In a human liver microsome preparation, fluvoxamine showed a concentration-dependent inhibition of clozapine N-demethylation. Fluvoxamine was much less effective as an inhibitor of clozapine N-oxidation. Fluvoxamine also inhibited in a concentration-dependent manner the activity of all five cytochrome P450 (CYP) isoforms previously determined to be capable of catalyzing the demethylation of clozapine. Fluvoxamine inhibited CYP1A2 and 2C19 with the highest affinities (Ki values of 0.041 and 0.087 microM, respectively). The Ki values for CYP2C9 and 2D6 were 2.2 and 4.9 microM, respectively, whereas the Ki for CY3A4 was 24 microM. Assuming a hepatic tissue concentration of fluvoxamine in the range of 4 to 7 microM under therapeutic conditions, a clinically significant inhibition of all but CYP3A4 is expected in relation to clozapine N-demethylation. No significant effect of fluvoxamine on clozapine N-oxidation is to be expected under therapeutic conditions. Because of the large interindividual variability of the quantity of the various CYP isoforms in liver tissue, it is not possible to predict the fluvoxamine-induced increase in the plasma concentration of clozapine of an individual patient.

Clozapine↗
PubMed1991

A review of fluvoxamine and its uses in depression.

Fluvoxamine is a potent and specific 5-HT reuptake inhibitor which has been available since 1983 and is estimated to have been given to two and a half million patients since it was first investigated in patients with depression in the late 1970s. The effectiveness of fluvoxamine in depression is therefore analysed in this review, on the basis of ten years experience. Results from 10 international double-blind placebo-controlled trials, the large majority of which included a positive control (usually imipramine), have shown that fluvoxamine is as effective as the older tricyclic antidepressants and significantly more effective than placebo. In the majority of twenty direct comparative studies against other antidepressants, fluvoxamine has been found to be as effective and well-tolerated as the reference drug. Effectiveness in the elderly depressed and support for the use of fluvoxamine in tricyclic-resistant depression is discussed. Clinical trials of fluvoxamine conducted in anxiety states and obsessive-compulsive disorder, both of which commonly co-occur with depression, are reviewed, and the efficacy of fluvoxamine in the depressed obese and patients with bulimia nervosa is examined. Reports of adverse experiences, both from clinical trials and clinical practice are discussed, and the overall risk-benefit for fluvoxamine treatment in depression is critically assessed.

Depressive Disorder↗
PubMed2004

A double-blind placebo-controlled study of controlled release fluvoxamine for the treatment of generalized social anxiety disorder.

This was a randomized double-blind placebo-controlled multicenter study to assess the efficacy, safety, and tolerability of fluvoxamine in a controlled release (CR) formulation for treatment of generalized social anxiety disorder (GSAD). A total of 300 subjects with GSAD were randomly assigned to receive either fluvoxamine CR (N = 149) or placebo (N = 151) for 12 weeks. Mean changes from baseline to end point in Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression Severity of Illness Scale (CGI-S), Sheehan Disability Scale (SDS), as well as the mean end point scores in Clinical Global Impression Improvement Scale (CGI-I) and Patient Global Impression of Improvement Scale (PGI) were compared between the fluvoxamine CR and placebo treatment groups. Arizona Sexual Experience Scale (ASEX), adverse event, and other safety parameters were also assessed. The results demonstrated that fluvoxamine CR was significantly superior to placebo in decreasing LSAS total score (primary measure) starting at week 4. At end point, there was a mean change from baseline of -36.1 +/- 2.7 (37% reduction) in the LSAS total score in the fluvoxamine CR group compared with -27.3 +/- 2.4 (28% reduction) in the placebo group (P = 0.020 for mean change). Fluvoxamine CR was also significantly superior to placebo in SDS, CGI-S, CGI-I at end point (secondary measures). When compared with placebo, fluvoxamine CR did not cause any significant weight gain or clinically significant sexual dysfunction as measured by ASEX. In summary, fluvoxamine CR is an efficacious, safe, and well-tolerated treatment of generalized social anxiety disorder.

Adolescent↗
PubMed2005

Fluvoxamine affects sildenafil kinetics and dynamics.

Sildenafil used as oral drug treatment for erectile dysfunction is predominantly metabolized by the cytochrome P450 isozyme 3A4. The antidepressant fluvoxamine is an inhibitor of cytochrome P450 3A4. In a randomized, double-blind, placebo-controlled, crossover study, we evaluated the effects of fluvoxamine dosed to steady state on the pharmacokinetics and pharmacodynamics of sildenafil. Twelve healthy men received oral fluvoxamine or placebo for 10 days (50 mg every day on days 1-3; 100 mg every day on days 4-10). On day 11, all participants received a single, oral, open-label dose of 50 mg sildenafil, and blood samples were collected for analysis of sildenafil plasma concentrations by liquid chromatography/mass spectrometry. Concurrently, the effect of sildenafil on venodilation induced by a constant dose of sodium nitroprusside was assessed using the dorsal hand vein compliance technique. Sildenafil was well tolerated in the presence of fluvoxamine. During fluvoxamine, sildenafil exposure (area under the curve) significantly increased by 40% (P < 0.001), and its half-life increased by 19% (P = 0.034). Concurrently, sodium nitroprusside-induced venodilation was significantly augmented by 59% during fluvoxamine compared to placebo (P = 0.012). In conclusion, sildenafil kinetics are mildly affected by fluvoxamine which translates into an increase in vascular sildenafil effects. Whereas the pharmacokinetic changes do not suggest a large clinically relevant interaction, it may be prudent to consider a starting dose of 25 mg in patients concurrently treated with fluvoxamine.

Adult↗
PubMed1983

Clinical trials of fluvoxamine vs chlorimipramine with single and three times daily dosing.

1 Two double-blind, randomised studies were performed to compare the efficacy of fluvoxamine and chlorimipramine in depressed patients. In the first study the effects of a single daily dosage of between 100 and 300 mg of fluvoxamine were compared with those of chlorimipramine at a dosage of 50-150 mg daily in 43 out-patients with endogenous depression. 2 In a second study using three times daily dosing with a daily dosage of 150-300 mg for both fluvoxamine and chlorimipramine, 30 in-patients with unipolar depression were assessed. 3 Four weeks of treatment with single daily dosing resulted in a mean improvement of 61.4% (+/- s.d. 31.7) on the Hamilton Rating Scale for Depression (HAMD) for fluvoxamine and of 65.3% (+/- s.d. 25.8) for chlorimipramine. In the study with three times daily dosing the mean results were 72.9% (+/- s.d. 22.3) improvement for fluvoxamine and 62.1% (+/- s.d. 28.5) for chlorimipramine. 4 At similar dosages, fluvoxamine had significantly less untoward effects on blood pressure than chlorimipramine. Anticholinergic effects were also fewer in the fluvoxamine group, as were nervous system symptoms, with the latter difference reaching statistical significance (P = 0.02). 5 We conclude that fluvoxamine, given in a single daily dose of 150-250 mg, provides antidepressant efficacy similar to chlorimipramine. At this dosage it may be expected to produce less anticholinergic effects and have less influence on blood pressure than chlorimipramine.

Adolescent↗
PubMed2004

Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes.

AIMS: Omeprazole is mainly metabolized by the polymorphic cytochrome P450 (CYP) 2C19. The inhibitory effect of fluvoxamine, an inhibitor of CYP2C19 as well as CYP1A2, on the metabolism of omeprazole was compared between different genotypes for CYP2C19. METHODS: Eighteen volunteers, of whom six were homozygous extensive metabolizers (EMs), six were heterozygous EMs and six were poor metabolizers (PMs) for CYP2C19, participated in the study. A randomized double-blind, placebo-controlled crossover study was performed. All subjects received two six-day courses of either daily 50 mg fluvoxamine or placebo in a randomized fashion with a single oral 40 mg dose of omeprazole on day six in both cases. Plasma concentrations of omeprazole and its metabolites, 5-hydroxyomeprazole, omeprazole sulphone, and fluvoxamine were monitored up to 8 h after the dosing. RESULTS: During placebo administration, geometric means of peak concentration (C(max)), under the plasma concentration-time curve from 0 to 8 h (AUC(0,8 h)) and elimination half-life (t(1/2)) of omeprazole were 900 ng ml(-1), 1481 ng ml(-1) h, and 0.6 h in homozygous EMs, 1648 ng ml(-1), 4225 ng ml(-1) h, and 1.1 h in heterozygous EMs, and 2991 ng ml(-1), 11537 ng ml(-1) h, and 2.8 h in PMs, respectively. Fluvoxamine treatment increased C(max) of omeprazole by 3.7-fold (95%CI, 2.4, 5.0-fold, P < 0.01) and 2.0-fold (1.4, 2.6-fold, P < 0.01), AUC(0,8 h) by 6.0-fold (3.3, 8.7-fold, P < 0.001) and 2.4-fold (1.7, 3.2-fold, P < 0.01), AUC(0, infinity ) by 6.2-fold (3.0, 9.3-fold, P < 0.01) and 2.5-fold (1.6, 3.4-fold, P < 0.001) and prolonged t((1/2)) by 2.6-fold (1.9, 3.4-fold, P < 0.001) and 1.4-fold (1.02, 1.7-fold, P < 0.05), respectively. However, no pharmacokinetic parameters were changed in PMs. The AUC(0,8 h) ratios of 5-hydroxyomeprazole to omeprazole were decreased with fluvoxamine in homozygous EMs (P < 0.05) and heterozygous EMs (P < 0.01). CONCLUSIONS: Even a low dose of fluvoxamine increased omeprazole exposure in EMs, but did not increase omeprazole exposure in PMs after a single oral dose of omeprazole. These findings confirm a potent inhibitory effect of fluvoxamine on CYP2C19 activity. The bioavailability of omeprazole might, to some extent, be increased through inhibition of P-glycoprotein during fluvoxamine treatment.

Adult↗
PubMed1999

Fluvoxamine treatment of social phobia (social anxiety disorder): a double-blind, placebo-controlled study.

OBJECTIVE: The purpose of this study was to determine the efficacy of fluvoxamine for the treatment of social phobia (social anxiety disorder). METHOD: In a 12-week multicenter, double-blind, randomized, placebo-controlled trial, 92 patients with social phobia were treated with the selective serotonin reuptake inhibitor fluvoxamine; 91.3% of the patients had the generalized subtype of the disorder. The primary criterion for response was a rating of "much improved" or "very much improved" on the Clinical Global Impression of Improvement scale. Secondary response criteria were changes on three specialized rating scales for social phobia symptoms: the Brief Social Phobia Scale, the Social Phobia Inventory, and the Liebowitz Social Anxiety Scale. Psychosocial impairment was assessed in three domains (disruption of work, social life, and home/family life) by using the Sheehan Disability Scale. RESULTS: The mean daily dose of fluvoxamine was 202 mg (SD = 86). At study end or with the last observation carried forward, within the evaluable subjects (N = 86) there was a significantly higher proportion of responders in the fluvoxamine group (42.9%, N = 18) than in the placebo group (22.7%, N = 10). Similarly, fluvoxamine was superior to placebo on all social phobia rating scales at week 8 and beyond. Fluvoxamine also resulted in significantly greater decreases in measures of psychosocial disability than did placebo. Overall, fluvoxamine was well tolerated and safe. CONCLUSIONS: These findings indicate that fluvoxamine is efficacious in the pharmacologic management of serious forms of social phobia.

Adolescent↗
PubMed2004

The differential effects of steady-state fluvoxamine on the pharmacokinetics of olanzapine and clozapine in healthy volunteers.

The combination of atypical antipsychotics and selective serotonin reuptake inhibitors is an effective strategy in the treatment of certain psychiatric disorders. However, pharmacokinetic interactions between the two classes of drugs remain to be explored. The present study was designed to determine whether there were different effects of steady-state fluvoxamine on the pharmacokinetics of a single dose of olanzapine and clozapine in healthy male volunteers. One single dose of 10 mg olanzapine (n = 12) or clozapine (n = 9) was administered orally. Following a drug washout of at least 4 weeks, all subjects received fluvoxamine (100 mg/day) for 9 days, and one single dose of 10 mg olanzapine or clozapine was added on day 4. Plasma concentrations of olanzapine, clozapine, and N-desmethylclozapine were assayed at serial time points after the antipsychotics were given alone and when added to fluvoxamine. No bioequivalence was found in olanzapine alone and cotreatment with fluvoxamine for the mean peak plasma concentration (C(max)), the area under the concentration-time curve from time 0 to last sampling time point (AUC(0-t)), and from time 0 to infinity (AUC(0- infinity )). Under the cotreatment, C(max) of olanzapine was significantly elevated by 49%, with a 32% reduced time (t(max)) to C(max), whereas the C(max) and t(max) of clozapine were unaltered. The cotreatment increased the AUC(0-t) and AUC(0- infinity ) of olanzapine by 68% and 76%, respectively, greater than those of clozapine (40% and 41%). The presence of fluvoxamine also prolonged the elimination half-life (t(1/2)) of olanzapine by 40% and, to a much greater extent, clozapine by 370% but reduced the total body clearance (CL/F) of clozapine (78%) more significantly than it did for olanzapine (42%). The apparent volume of distribution (V(d)) was suppressed by 31% in olanzapine combined with fluvoxamine but was unaltered in the clozapine regimen. A significant reduction in the N-desmethylclozapine to clozapine ratio was present in the clozapine with fluvoxamine regimen. The effects of fluvoxamine on different aspects of pharmacokinetics of the two antipsychotics may have implications for clinical therapeutics.

Adult↗
PubMed2004

Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia.

Olanzapine, an atypical antipsychotic agent, is a substrate of the cytochrome P4501A2 (CYP1A2) enzyme. Administration of a potent CYP1A2 inhibitor (eg, fluvoxamine) may alter the pharmacokinetics of olanzapine. This study investigated the pharmacokinetic interactions between olanzapine and fluvoxamine in patients with schizophrenia. Ten male smokers were administrated a single dose of olanzapine 10 mg at baseline, followed by 2 weeks of fluvoxamine 50 mg/day and another 2 weeks of fluvoxamine 100 mg/day. Olanzapine 10 mg was given at day 10 during each fluvoxamine treatment. After pretreatment with fluvoxamine, the area under the curve, maximal plasma concentration, and half-time of olanzapine were significantly increased by 30% to 55%, 12% to 64%, and 25% to 32%, respectively. Volume of distribution and apparent clearance were significantly reduced by 4% to 26% and 26% t O 38%, respectively, after administration of fluvoxamine. Increases in area under the plasma concentration-time curve from time 0 to infinity appear to be dose dependent. Presumably, altered olanzapine pharmacokinetics are attributed to the inhibition of CYP1A2. Patients treated with the combination of olanzapine and fluvoxamine should be monitored carefully.

Adult↗
PubMed2003

Possible involvement of peripheral serotonin 5-HT3 receptors in fluvoxamine-induced emesis in Suncus murinus.

Selective serotonin reuptake inhibitors fluvoxamine and fluoxetine, as well as serotonin (5-HT), induced vomiting in Suncus murinus (a house musk shrew). Fluvoxamine- and fluoxetine-induced vomiting gradually decreased with their repeated administration. Vomiting induced by serotonin also decreased with repeated treatment with serotonin. In these shrews, fluvoxamine-induced vomiting was partially inhibited. Fluvoxamine might induce vomiting, at least partially, by indirectly activating peripheral 5-HT(3) receptors, since serotonin has been reported to induce vomiting by activating peripheral 5-HT(3) receptors and granisetron, a 5-HT(3) antagonist, partially suppressed fluvoxamine-induced vomiting in our previous finding. In addition, fluvoxamine-induced vomiting was impaired more effectively using a step-wise dose-up schedule of fluvoxamine than a fixed high-dose schedule. Therefore, a careful dosing strategy starting with a low dose might be effective for avoiding emesis associated with the clinical use of fluvoxamine.

Animals↗
PubMed1995

Neither the 5-HT1A- nor the 5-HT2-receptor subtype mediates the effect of fluvoxamine, a selective serotonin reuptake inhibitor, on forced-swimming-induced immobility in mice.

The effect of fluvoxamine, a selective serotonin (5-HT) reuptake inhibitor, was studied in the forced-swimming test, a model of depression, in mice. Fluvoxamine at 60 mg/kg, p.o. significantly decreased the immobility time in the forced-swimming test. A similar effect was observed by the selective norepinephrine reuptake inhibitor desipramine at the same dose. Furthermore, the suppression of immobility time was slightly potentiated by repeated administration of fluvoxamine, and a significant effect was observed at 30 mg/kg, p.o. The effect of fluvoxamine on forced-swimming was unaffected by the 5-HT2 antagonist ritanserin. On the other hand, the 5-HT1A antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine) potentiated the effect of fluvoxamine on forced-swimming. It is expected, however, that a 5-HT1A antagonist should antagonize the effect of fluvoxamine when 5-HT1A mediates the suppressive effect of fluvoxamine on the immobility time in forced-swimming. From these results, neither the 5-HT1A- nor the 5-HT2-receptor subtype is involved in the suppressive effect of fluvoxamine on the immobility associated with forced-swimming.

Analysis of Variance↗
PubMed2003

High-performance liquid chromatographic determination of fluvoxamine and fluvoxamino acid in human plasma.

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of fluvoxamine and its major metabolite fluvoxamino acid in plasma. Fluvoxamine and fluvoxamino acid in plasma were extracted using a C18 bonded-solid phase cartridge, followed by C4 reversed-phase HPLC separation.Fluvoxamine, fluvoxamino acid and moperone as an internal standard were detected by ultraviolet absorbance at 254 nm. It was possible to determine both fluvoxamine and fluvoxamino acid in the concentration range of 25.0-200.0 ng/mL, respectively. The detection limits of both fluvoxamine and fluvoxamino acid were 10.0 ng/mL, respectively. The mean recoveries of fluvoxamine and fluvoxamino acid added to plasma were more than 94.0% and 96.5%, with a coefficient of variation of less than 7.6% and 8.2%, respectively. This method has been used for the simultaneous determination of steady-state plasma concentration (Css) of fluvoxamine and fluvoxamino acid in depressive patients treated with 200 mg of oral fluvoxamine dosed as 100 mg twice-daily. The Css values of fluvoxamine and fluvoxamino acid in twelve Japanese patients were showed individual variations, which were in the range of 48.3-532.9 ng/ml and 35.6-307.1 ng/ml, respectively.

Amino Acids↗