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PubMed2001

Serum fluvoxamine levels in breastfed infants.

BACKGROUND: Between 10% and 15% of new mothers will experience an episode of postpartum depression. Although antidepressants are effective agents for the treatment of postpartum depression, minimal data are available to support their safety in infants of breastfeeding mothers. METHOD: In this article, we present 2 cases of nursing mother-infant pairs in which the mother was treated with fluvoxamine and in which infant serum fluvoxamine levels were obtained. Both mothers began the fluvoxamine treatment postpartum, and serum levels were obtained from mothers and infants after a minimum of 7 days on a stable maternal dose. One level was obtained from the infant in case 1, and 2 levels were obtained from the infant in case 2. RESULTS: Each of the infant serum fluvoxamine levels obtained was too low to quantify (at a limit of detection of 2.5 ng/mL). Neither of the infants experienced adverse events related to the mother's treatment with fluvoxamine. Each of the infants is reportedly healthy 2 to 3 years after the exposure. CONCLUSION: While these results are encouraging, they are limited and cannot be generalized to all cases of infants exposed to fluvoxamine. Additional mother-infant serum fluvoxamine levels and infant behavioral observations will facilitate the risk-benefit decision-making process for women who choose to breast-feed while taking fluvoxamine.

Breast Feeding↗
PubMed2003

[Serotonin 2A receptor gene polymorphism and clinical efficacy of fluvoxamine in children with autistic disorder].

Fluvoxamine, a selective serotonin reuptake inhibitor which modulates serotoninergic activities, is a useful drug for patients with an autistic disorder. Genetic variation of the serotonin receptor may influence the efficacy of fluvoxamine treatment. We studied the correlation between clinical responses to fluvoxamine and serotonin receptor gene polymorphism (5-HT2AR) in children with an autistic disorder. Eighteen patients completed a 12-week double-blind, placebo-controlled, randomized crossover study. Clinical global impression (CGI) by child neurologists and interviews for parents were assessed after 12 weeks of fluvoxamine treatment. Behavioral assessments consisting of 20 items by newly created Behavioral Assessment Scale (BAS) were obtained before as well as 6 and 12 weeks after treatment. For genotyping of 5-HT2AR, 102 T/C polymorphism was analyzed by the PCR method. Seven cases of T/T, 6 of T/C and 5 of C/C were identified. The patients with the genotype T/C responded more favorably when estimated by CGI and parents' report at 12 weeks of treatment. Although not significant statistically (p = 0.0578), the number of improved BAS items in these patients were larger after fluvoxamine than placebo treatment. On analyses of individual BAS items, the patients with the genotype C/C showed improvement of unnatural facial expression, which was significant at 6 weeks, but not at 12 weeks, of fluvoxamine treatment. In the patients with the genotype T/C, eye movements and emotional changes were significantly improved at 12 weeks of treatment. Our results suggested that genetic polymorphism of 102 T/C in the 5-HT2AR gene may have influence on the response to fluvoxamine treatment for patients with an autistic disorder. Because of the small numbers of subject studied here, further studies are needed. The methods of fluvoxamine treatment, such as appropriate dosage and treatment duration, should also be clarified.

Child↗
PubMed2000

The effect of fluvoxamine and behavior therapy on children and adolescents with obsessive-compulsive disorder.

OBJECTIVE: The efficacy of medications, consisting of serotonin partial and specific reuptake blockers, and behavior therapy, consisting of exposure and response prevention in addition to social skills training, cognitive therapy, and habit reversal, in the treatment of obsessive-compulsive disorder are well documented. The purpose of the study was to explore if adding behavior therapy to medication would enhance treatment efficacy. METHODS: Ten children/adolescents who had not previously responded to behavior therapy were randomly assigned to two groups: fluvoxamine alone or fluvoxamine with behavior therapy. All 10 patients received fluvoxamine for 10 weeks-five continued solely on fluvoxamine for one year and five engaged in behavior therapy for 20 sessions along with fluvoxamine and then continued solely on medication until the end of the year. RESULTS: Eight of 10 patients improved significantly on fluvoxamine at week 10 on the primary outcome variable, the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS). According to the other measurements-National Institute of Mental Health-Global Obses-sive-Compulsive Scale, Clinical Global Impression-Improvement (assessing level of im-provement from week to week), and Clinical Global Impression-Severity of Illness Scale (as-sessing how ill the patient is from week to week)-improvement was not as evident. According to the CY-BOCS, those who received a combination of fluvoxamine and exposure with response prevention showed significantly more improvement than those who only took medication. At two-year follow-up, all patients continued to improve, with those in the combined approach improving more than those in the medication-alone group. CONCLUSIONS: Future studies should determine the specific effect of each treatment group, combined and singularly. Reasons for discrepancy in improvement ratings as noted by the different instruments are discussed. The addition of behavior therapy to fluvoxamine seems to enhance treatment efficacy, according to the CY-BOCS.

Adolescent↗
PubMed1977

Fluvoxamine, a specific 5-hydroxytryptamine uptake inhibitor.

1. On the basis of both in vitro and in vivo experiments fluvoxamine has been characterized as a potential anti-depressant drug with almost exclusively 5-hydroxytryptamine (5-HT) uptake inhibiting properties. 2. Fluvoxamine is effective in inhibiting 5-ht uptake by blood platelets and brain synaptosomes. Due to inhibition of the membrane pump the compound prevents 5-HT depletion by the tyramine-derivatives H 75/12 and H 77/77. As a result of the interference with the neuronal re-uptake mechanism for 5-HT, fluvoxamine produces a decreased 5-HT turnover in the brain. Effects of 5-hydroxytryptophan (5-HTP) are potentiated in mice and in combination with pargyline, fluvoxamine induces 5-HT-like behavioural effects. 3. In contrast to tricyclic antidepressants, noradrenaline uptake processes are either unaffected or only slightly inhibited by fluvoxamine. The noradrenaline depleting effects of tyramine derivates are not influenced by fluvoxamine. Reserpine effects, such as ptosis are affected only at very high doses of the test compound. The antagonism by fluvoxamine of the reserpine-induced lowering of the pentamethylenetetrazole convulsive threshold can be regarded as due to an effect upon 5-HT uptake. In contrast to the effects of desmethylimipramine and imipramine, no stimulatory effects are found in rats when rapidly acting reserpine-like compounds are given following a dose of fluvoxamine.

5-Hydroxytryptophan↗
PubMed1993

A comparison of fluvoxamine, cognitive therapy, and placebo in the treatment of panic disorder.

Seventy-five outpatients with moderate to severe panic disorder were randomly assigned to receive 8 weeks of fluvoxamine, cognitive therapy, or placebo. Fifty-five patients completed the treatment protocol. Fluvoxamine was found to be an effective and well-tolerated treatment for panic using clinician- and patient-rated variables. Subjects receiving cognitive therapy also showed improvement, but this improvement did not significantly differ from the experience of the placebo-treated group for most comparisons. Fluvoxamine was superior to cognitive therapy for many ratings, but cognitive therapy was not superior to fluvoxamine on any rating. Fluvoxamine also produced improvement earlier than cognitive therapy. At the main comparison point (week 4), 57% (13/23) of patients receiving fluvoxamine were rated moderately improved or better vs 40% (8/20) of the group given cognitive therapy and 22% (5/23) of the placebo-treated group. At that point, 43% (10/23) of the fluvoxamine recipients vs 25% (5/20) of cognitive therapy and 4% (1/23) of placebo recipients were free of panic attacks.

Adolescent↗
PubMed1994

Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics.

BACKGROUND: To determine the efficacy of adding haloperidol to the treatment of patients with obsessive-compulsive disorder (OCD), with or without a comorbid chronic tic disorder, who were refractory to adequate treatment with the serotonin-uptake inhibitor fluvoxamine alone. It was hypothesized that OCD patients with a concurrent chronic tic disorder would preferentially respond to this treatment. METHODS: Sixty-two patients with a primary DSM-III-R diagnosis of OCD received placebo fluvoxamine for 1 week, followed by 8 weeks of active fluvoxamine. Thirty-four of these patients were refractory to fluvoxamine and were randomized in a double-blind fashion to 4 weeks of treatment with either haloperidol (n = 17) or placebo (n = 17) added to ongoing fluvoxamine treatment. The placebo-treated group included five women and 12 men, six inpatients and 11 outpatients, and eight patients with a comorbid chronic tic disorder. The haloperidol-treated group consisted of two women and 15 men, three inpatients and 14 outpatients, and seven patients with a comorbid chronic tic disorder. All 34 patients completed the entire study. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression scale were the principal measures of treatment outcome. RESULTS: Haloperidol addition was significantly better than placebo in reducing the severity of obsessive-compulsive symptoms as measured by the Y-BOCS. Eleven of 17 patients responded to the haloperidol, compared with none of 17 patients given placebo. Eight of eight patients with comorbid chronic tic disorders, such as Tourette's disorder, responded to double-blind haloperidol addition to ongoing fluvoxamine treatment. Haloperidol addition was of little benefit in treating OCD patients without tics. Fluvoxamine blood levels were not related to treatment response. CONCLUSIONS: The results of this study suggest that OCD patients with a comorbid chronic tic disorder constitute a clinically meaningful subtype of OCD that might require conjoint serotonin-uptake inhibitor/neuroleptic therapy for effective symptom reduction.

Adolescent↗
PubMed2003

Possible predictors of response to fluvoxamine for depression.

INTRODUCTION: An investigation of the characteristics of patients being treated with antidepressants would seem to be useful in determining which patients would be most likely benefit from antidepressant medication. AIMS: The purpose of this preliminary study was to examine the possible predictors of response to fluvoxamine for depression. METHOD: A retrospective cohort analysis was carried out among depression patients treated in the Department of Psychiatry, Kawasaki Medical School Hospital, Kurashiki, Japan, in 2000. Seventy two patients were identified who were receiving fluvoxamine to treat depression. RESULTS: A variety of clinical factors including age, gender, type of depression, frequency of episodes, family history and daily dose of fluvoxamine were examined as possible predictors of the response to fluvoxamine. A Weibull regression analysis showed age, frequency of episodes and daily dose to be the independent predictive factors of improvement in fluvoxamine treatment. The most influential factor was age (ecoef = 2.109), followed by daily dose (ecoef = 0.648) and frequency of episode (ecoef = 0.512). An age of 49 years or younger (chi(2) = 6.767, df = 1, p = 0.0093), a first episode (chi(2) = 9.079, df = 1, p = 0.0026) and a daily dose of 100-150 mg (chi(2) = 5.353, df = 1, p = 0.02) were significantly better predictors of improvement. CONCLUSIONS: Age, the frequency of episodes and the daily dose of fluvoxamine may be considered as predictors of the response to fluvoxamine treatment for depression. This result should be examined in future prospective study.

Adolescent↗
PubMed1995

Chronic treatment with fluvoxamine by osmotic minipumps fails to induce persistent functional changes in central 5-HT1A and 5-HT1B receptors, as measured by in vivo microdialysis in dorsal hippocampus of conscious rats.

This study investigated the alterations of the 5-HT1A and 5-HT1B autoreceptor function following chronic treatment with fluvoxamine using osmotic minipumps. The 5-HT1A and 5-HT1B autoreceptor function were studied using microdialysis in the dorsal hippocampus. The effect of the 5-HT1A receptor agonist 8-OH-DPAT (0.3 mg/kg, SC) and the 5-HT1B receptor agonist RU-24969 (100 nM through the dialysis probe for 30 min) on 5-HT release was compared with rats chronically treated with saline. 8-OH-DPAT decreased 5-HT release to 55% and 60% of baseline, while RU-24969 decreased 5-HT release to 66% and 70% of baseline value in the saline and fluvoxamine group, respectively. In both cases, differences between the saline and fluvoxamine groups were not statistically significant. Plasma levels of fluvoxamine after 21 days of treatment ranged from 3 to 5 ng/ml. Fluvoxamine concentration in rat brain during treatment was estimated between 100 and 200 nM, which approximates to the IC50 value of fluvoxamine on the 5-HT transporter in synaptosomes and is 50 times higher than the Kd value for the 5-HT reuptake site. In conclusion, no evidence was found for changes in 5-HT1A,B receptor function using 8-OH-DPAT and RU-24969 as probes after continuous treatment with fluvoxamine by means of osmotic minipumps.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients.

Bidirectional drug interactions between fluvoxamine and classical antidepressants were studied in depressed patients. A column switching technique combined with high performance liquid chromatography (HPLC) enabled automated analyses of plasma for simultaneous determination of fluvoxamine, tricyclic and tetracyclic antidepressants and demethylated and major hydroxylated metabolites in a single HPLC run. The measurements revealed that fluvoxamine inhibited N-demethylation of imipramine, clomipramine, amitriptyline and maprotiline whereas interferences with hydroxylation reactions were restricted to aromatic 8-hydroxylation of clomipramine. In patients under fluvoxamine monotherapy before comedication, plasma concentrations of fluvoxamine increased after administration of a tricyclic antidepressant, thus indicating bidirectional drug interactions. The inhibitory effects of fluvoxamine on the metabolism of classical antidepressants disappeared after discontinuation of concomitant fluvoxamine treatment within at least 1-2 weeks. The reported alterations in drug metabolism observed in depressed patients who were under fluvoxamine/tricyclic antidepressant comedication suggested that careful supervision and regular drug monitoring are necessary in such patients.

Adult↗
PubMed1996

Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine.

OBJECTIVE: The purpose of this pharmacokinetic study was to investigate the dose-dependent inhibition of model substrates for CYP2D6, CYP2C19 and CYP1A2 by four marketed selective serotonin reuptake inhibitors (SSRIs): citalopram, fluoxetine, fluvoxamine and paroxetine. METHODS: The study was carried out as an in vivo single-dose study including 24 young, healthy men. All volunteers had been identified as sparteine- and mephenytoin-extensive metabolisers. The volunteers received in randomised order, at weekly intervals, increasing single oral doses of one of the four SSRIs, followed 3 h later by sparteine (CYP2D6), mephenytoin (CYP2C19) and caffeine (CYP1A2) tests. Fluoxetine was given at 3-week intervals because of the long half-life of fluoxetine and its metabolite norfluoxetine. Citalopram, fluoxetine and paroxetine were given in doses of 10, 20, 40 and 80 mg and fluvoxamine was given in doses of 25, 50, 100 and 200 mg. RESULTS: With increasing doses, there was a statistically significant increase in the sparteine metabolic ratio (MR) (P < 0.01, Page's test for trend) for all four SSRIs. The increase was modest after intake of citalopram and fluvoxamine, while the increase was more pronounced after fluoxetine intake, although no volunteers changed phenotype from extensive metabolisers to poor metabolisers. Three of the six volunteers changed phenotype from extensive metabolisers to poor metabolisers after intake of 40 or 80 mg paroxetine. There was a statistically significant increase in the mephenytoin S/R ratio (P < 0.01, Page's test for trend) with increasing doses of fluoxetine and fluvoxamine, but not after citalopram and paroxetine. However, no volunteers changed phenotype from extensive to poor metabolisers of S-mephenytoin. After intake of fluvoxamine, the urinary excretion of the metabolites related to N3 demethylation of caffeine were below the limit of quantification, whereas there were no significant changes in the urinary caffeine metabolic ratios after intake of the other three SSRIs. CONCLUSION: This investigation confirms that paroxetine and fluoxetine are potent inhibitors of CYP2D6, that fluvoxamine and fluoxetine are moderate inhibitors of CYP2C19 and that fluvoxamine is a potent inhibitor of CYP1A2 in humans in vivo. The clinical prediction of interaction from single-dose experiments may have to take the degree of accumulation during steady-state after multiple doses into account.

Adult↗
PubMed1999

Lack of correlation between fluvoxamine clearance and CYP1A2 activity as measured by systemic caffeine clearance.

OBJECTIVE: Evidence exists to suggest that fluvoxamine is metabolized by CYP1A2. The present study was undertaken in order to further elucidate the role of CYPIA2 in fluvoxamine disposition. METHODS: Twelve healthy non-smoking male volunteers participated in this cross-over study. Six subjects received first fluvoxamine 50 mg as a single oral dose and, some weeks later, caffeine 200 mg as a single oral dose. The other six subjects received the drugs in reverse order. Serum concentrations of fluvoxamine, caffeine and paraxanthine were measured and standard pharmacokinetic parameters were calculated. RESULTS: There were no significant correlations between caffeine clearance and fluvoxamine oral clearance (rs = -0.30; P = 0.43) or between the paraxanthine/caffeine ratio in serum 6 h after caffeine intake and fluvoxamine oral clearance (rs = -0.18; P = 0.58). CONCLUSION: CYP1A2 does not appear to be of major importance in the metabolism of fluvoxamine.

Caffeine↗
PubMed1982

Fluvoxamine and chlorimipramine in endogenous depression.

Thirty patients were treated in a randomised double-blind efficacy study of fluvoxamine and chlorimipramine. The dose range for both drugs was 50-300 mg in divided daily doses. Mean daily doses were higher for fluvoxamine than chlorimipramine. Generally the baseline recordings were comparable for both drug groups. Fluvoxamine was superior to chlorimipramine in all the rating scales used without achieving statistical significance. Chlorimipramine, but not fluvoxamine, caused a significant decrease in blood pressure. There were no significant effects on ECG or laboratory variables. There was no significant relationship between plasma levels of either compound or metabolite and clinical response. Chlorimipramine exerted more unwanted effects than fluvoxamine. Autonomic effects of fluvoxamine were minimal in comparison with chlorimipramine. Chlorimipramine patients required more concurrent anxiolytic medication than fluvoxamine. Both drug groups required a significant amount of concurrent hypnotic medication.

Adolescent↗
PubMed2006

Liver dysfunction markedly decreases the inhibition of cytochrome P450 1A2-mediated theophylline metabolism by fluvoxamine.

BACKGROUND AND OBJECTIVES: In vivo inhibition of cytochrome P450 (CYP) 1A2 by fluvoxamine causes a reduction in the clearance of the high-extraction drug lidocaine, which decreases in proportion to the degree of liver dysfunction. The objectives of this study were (1) to evaluate the effect of liver cirrhosis on the inhibition by fluvoxamine of the metabolic disposition of theophylline, a CYP1A2 substrate with a low-extraction ratio, to assess whether decreased sensitivity to CYP1A2 inhibition in liver disease is a general characteristic of CYP1A2 substrates, regardless of their pharmacokinetic properties, and (2) to investigate the mechanism(s) underlying the effect of liver dysfunction on CYP1A2 inhibition. METHODS: The study was carried out in 10 healthy volunteers and 20 patients with cirrhosis, 10 with mild liver dysfunction (Child class A) and 10 with severe liver dysfunction (Child class C), according to a randomized, double-blind, 2-phase, crossover design. In one phase all participants received placebo for 7 days; in the other phase they received one 50-mg fluvoxamine dose for 2 days and two 50-mg fluvoxamine doses, 12 hours apart, in the next 5 days. On day 6, 4 mg/kg of theophylline was administered orally 1 hour after the morning fluvoxamine dose. Concentrations of theophylline and its metabolites, 3-methylxanthine, 1-methyluric acid, and 1,3-dimethyluric acid, were then measured in plasma and urine up to 48 hours. RESULTS: Fluvoxamine-induced inhibition of theophylline clearance decreased from 62% in healthy subjects to 52% and 12% in patients with mild cirrhosis and those with severe cirrhosis, respectively. CYP1A2-mediated formations of 3-methylxanthine and 1-methyluric acid were almost totally inhibited in control subjects, whereas they were only reduced by one third in patients with Child class C cirrhosis. Inhibition of 1,3-dimethyluric acid formation, which is catalyzed by CYP1A2 and CYP2E1, progressively decreased from 58% in healthy subjects to 43% and 7% in patients with mild cirrhosis and those with severe cirrhosis, respectively. CONCLUSIONS: The effect of liver dysfunction on the inhibition of CYP1A2-mediated drug elimination is a general phenomenon, independent of the pharmacokinetic characteristics of the CYP1A2 substrate. Therefore, for any drug metabolized by CYP1A2, the clinical consequences of enzyme inhibition are expected to become less and less important as liver function worsens. Two mechanisms, as follows in order of importance, are responsible for the effect of liver dysfunction: (1) decreased sensitivity to fluvoxamine of CYP1A2-mediated biotransformations in the cirrhotic liver, probably resulting from reduced uptake of the inhibitory drug, and (2) reduced hepatic expression of CYP1A2, which makes its contribution to overall drug elimination less important.

Adult↗
PubMed2004

Chronic treatment with fluvoxamine desensitizes 5-HT2C receptor-mediated hypolocomotion in rats.

The effectiveness of fluvoxamine, a selective serotonin re-uptake inhibitor (SSRI), in the treatment of anxiety disorders, such as obsessive-compulsive, panic and social anxiety disorders, has been confirmed in clinical studies. The hypersensitivity of 5-HT2C receptors has been reported in subjects with these disorders, and SSRIs have been suggested to have therapeutic effects in such cases through the desensitization of the 5-HT2C receptor function. In the present study, we investigated whether chronic administration of fluvoxamine desensitizes 5-HT2C receptors using a putative in vivo rat model of 5-HT2C receptor function. Acute treatment with fluvoxamine or another SSRI, paroxetine, reduced spontaneous locomotion, as observed with the administration of m-chlorophenylpiperazine (mCPP). This effect of fluvoxamine was reversed by treatment with a selective 5-HT2C receptor antagonist, SB 242084. On the other hand, chronic treatment with fluvoxamine or paroxetine inhibited mCPP-induced hypolocomotion, while they had no effects in control rats. In addition, chronic treatment with these drugs had no effects on the mCPP concentration in the rat brain. These results suggest that 5-HT2C receptors are desensitized by chronic treatment with fluvoxamine, as well as paroxetine. Thus, the clinical efficacy of fluvoxamine on anxiety disorders might involve the normalization of the 5-HT2C receptor function.

Animals↗
PubMed2002

Changes in synaptic plasticity in the rat hippocampo-medial prefrontal cortex pathway induced by repeated treatments with fluvoxamine.

The present studies were conducted to examine the effects of single and repeated treatments with fluvoxamine, which is a selective serotonin reuptake inhibitor (SSRI), on the synaptic efficacy and synaptic plasticity in the rat hippocampo-medial prefrontal cortex (mPFC) pathway in vivo. It has been reported that the projections arising from the hippocampal structures to the mPFC are involved in the execution of higher cognitive functions in rats. The evoked potentials were recorded in the mPFC by stimulation of the CA1/subicular region of the ventral hippocampus in halothane-anesthetized rats. Single administration of fluvoxamine (10 and 30 mg/kg, i.p.) enhanced synaptic efficacy in the hippocampo-mPFC pathway in a dose-dependent manner. Although repeated treatments with fluvoxamine (30 mg/kg, i.p. after 30 mg/kg/dayx21 days, p.o.) caused an enhancement of synaptic efficacy, there was no significant difference between single and repeated treatments. The input/output characteristics showed hypersensitivity to stimulation intensity in the group with repeated fluvoxamine treatments. The establishment of long-term potentiation (LTP) in the hippocampo-mPFC pathway after a single administration of fluvoxamine was not different from that in the saline-injected group. On the other hand, the hippocampo-mPFC LTP was significantly augmented by repeated treatments with fluvoxamine when compared to a single treatment. These findings suggest that the serotonergic system could modulate the synaptic plasticity at hippocampal-mPFC synapses. The present study, furthermore, suggests that the enhancement of LTP in the hippocampo-mPFC pathway produced by repeated treatments with fluvoxamine may be implicated in the SSRI-induced therapeutic effect on psychiatric disorders.

Afferent Pathways↗
PubMed1997

Fluvoxamine inhibits the CYP2C19-catalyzed bioactivation of chloroguanide.

OBJECTIVE: To investigate the interaction between fluvoxamine and chloroguanide (INN, proguanil) to confirm that fluvoxamine inhibits CYP2C19. METHODS: The study was carried out with a randomized, in vivo, crossover design. Six volunteers were extensive metabolizers of the S-mephenytoin oxidation polymorphism, and six volunteers were poor metabolizers. In period A of the study, each subject took 200 mg chloroguanide orally. In period B, each subject took 100 mg/day fluvoxamine for 8 days and on day 6 ingested 200 mg chloroguanide. In both periods, blood and urine were sampled at regular intervals. Chloroguanide and its two metabolites cycloguanil and 4-chlorphenylbiguanide in plasma and in urine were assayed by means of HPLC. RESULTS: During fluvoxamine use, the median of the total clearance of chloroguanide decreased in a statistically significant way from 1282 ml/min to 782 ml/min among the extensive metabolizers, whereas there was no change among the poor metabolizers. The partial clearance of chloroguanide by means of cydoguanil and 4-chlorphenylbiguanide formation among the extensive metabolizers decreased from 222 ml/min and 97 ml/min before to 33 ml/min and 11 ml/min during fluvoxamine intake, respectively. Among poor metabolizers the corresponding values were 35 ml/min and 7.6 ml/min before and 38 ml/min and 6.9 ml/min during fluvoxamine intake. For each metabolite clearance the change was statistically significant among the extensive metabolizers but not among the poor metabolizers. Both cycloguanil and 4-chlorphenylbiguanide formation clearances were statistically significantly higher among the extensive metabolizers than the poor metabolizers in period A but not in period B (phenocopy). CONCLUSION: Fluvoxamine is an effective inhibitor of CYP2C19.

Administration, Oral↗
PubMed1997

Serotonin and human information processing: fluvoxamine can improve reaction time performance.

Fluvoxamine is a specific serotonin reuptake inhibitor. Recent evidence suggests that this antidepressive drug shortens the reaction time (RT) of healthy volunteers. The first objective of the present study was to decipher whether this effect is due to an improvement in information processing per se or to the adoption of an error-prone strategy. The second objective was to locate the effect of fluvoxamine within the series of information processing stages by means of Sternberg's additive factor method. After administration of a single oral dose of fluvoxamine (100 mg) or a placebo (randomized double-blind, cross-over design), eight healthy volunteers performed a choice RT task in which stimulus intensity, stimulus-response compatibility and response repertoire were manipulated. Fluvoxamine shortened RT without decreasing the accuracy of the responses. This demonstrates that fluvoxamine improves information processing per se. The effect of fluvoxamine was additive on RT with the respective effects of stimulus intensity and stimulus-response compatibility. This result suggests that fluvoxamine spares the processing stages of stimulus preprocessing and response selection.

Adult↗
PubMed1996

The antinociceptive effect of fluvoxamine.

The authors conducted a study in order to evaluate the antinociceptive effects of the serotonin-selective reuptake inhibitor (SSRI) antidepressant fluvoxamine and its interaction with various opioid receptor subtypes. Male ICR mice were tested with a hotplate analgesia meter. Fluvoxamine elicited antinociceptive effect in a dose-dependent manner following i.p., i.t. and i.c.v. injection. Naloxone 10 mg/kg s.c. did not abolish the fluvoxamine antinociceptive effect. At the next stage fluvoxamine was administered together with various agonists of opioid receptors. When administered together with opiates, fluvoxamine significantly potentiated analgesia at the kappa(3)-opioid receptor subtype (P < .005) and to a lesser extent, at the mu-, delta-, and kappa(1)-opioid receptors. We conclude that fluvoxamine alone induces an antinociceptive effect. This effect is mediated by non-opioid mechanism of action. These results suggest a potential role for fluvoxamine in the management of pain when co-administered with opioids at low doses.

Animals↗