fluvoxamine and Chronic-Disease

Cognitive impairments in schizophrenia are associated with suboptimal psychosocial performance. Several lines of evidence have suggested that endoplasmic reticulum protein sigma-1 receptors were involved in cognitive impairments in patients with schizophrenia and that the sigma-1 receptor agonist fluvoxamine was effective in treating cognitive impairments in animal models of schizophrenia and in some patients with schizophrenia. A randomized, double-blind, placebo-controlled, parallel trial of fluvoxamine adjunctive therapy in patients with schizophrenia was performed. A total of 48 patients with chronic schizophrenia were enrolled. Subjects were randomly assigned to an 8-week administration of add-on fluvoxamine (n = 24, titrated up to 150 mg/d) or placebo (n =24) in a total 12-week double-blind trial. The primary outcome measure was the Cambridge Neuropsychological Test Automated Battery (CANTAB), assessing visual memory, working memory, attention, and executive function. The secondary outcome measures were the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Quality of Life Scale, and the Montgomery-Åsberg Depression Rating Scale. Fluvoxamine was well tolerated. No significant time × group interaction effects were observed in the scores of the CANTAB, Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, or the Montgomery-Åsberg Depression Rating Scale. However, in secondary analyses, the change from baseline to end point on the Spatial Working Memory strategy score (executive function) of CANTAB improved in the fluvoxamine group. This study suggests no major benefit of fluvoxamine adjunctive therapy to improve cognitive impairments in patients with schizophrenia. Nevertheless, a further study using a large sample size will be needed to confirm the secondary analyses findings.

Topics: Adult; Chronic Disease; Cognition Disorders; Double-Blind Method; Drug Therapy, Combination; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Quality of Life; Receptors, sigma; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Sigma-1 Receptor; Time Factors; Treatment Outcome

Selective serotonin reuptake inhibitors (SSRIs) exert cardioprotective effects. We examined whether SSRIs a) modulate endothelial cell expression of vascular cell adhesion molecule (VCAM-1), intracellular adhesion molecule (ICAM-1) and adhesiveness to U937 monocytes, b) reduce the circulating levels of these adhesion molecules in vivo.. We assessed the effect of SSRIs, (citalopram, fluvoxamine and fluoxetine), on TNF-alpha-induced expression of VCAM-1 and ICAM-1 in human aorta endothelial cells and adhesiveness to U937 monocytes. Cells were incubated with TNF-alpha in the absence and in the presence of SSRIs concentrations from 10(-7) M to10(-4) M and the VCAM-1 and ICAM-1 expression was quantified by cell-ELISA. The TNF-alpha-stimulated adhesiveness to U937 monocytes was also assessed. Twenty five patients with chronic heart failure and depression were randomized to receive sertaline 50 mg, p.o., o.d. (n=13) or placebo. At baseline and 3-months after treatment, we measured VCAM-1 and ICAM-1 plasma levels.. SSRIs decreased the TNF-alpha-induced endothelial expression of VCAM-1 at concentration range 10(-7) M to 10(-4) M (p<0.05). ICAM-1 expression was decreased in the presence of fluvoxamine and fluoxetine at concentrations from 10(-7) M to 10(-4) M (p<0.05) and in the presence of citalopram at concentrations from 10(-7) M to 10(-5) M (p<0.05). All SSRIs inhibited the TNF-alpha-stimulated adhesiveness to U937 cells at 10(-5) M and 10(-4) M (p<0.05). Compared to baseline, there was a greater reduction in ICAM-1 and VCAM-1 levels post-sertaline than post placebo in heart failure patients (p<0.05).. SSRIs may exhibit an anti-inflammatory activity on endothelial cells and reduce circulating VCAM-1 and ICAM-1 in vivo, a mechanism which may partly mediate their cardioprotective effects.

Topics: Adult; Aged; Aorta; Cell Adhesion; Cell Survival; Chronic Disease; Citalopram; Depression; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Fluoxetine; Fluvoxamine; Heart Failure; Humans; Intercellular Adhesion Molecule-1; Middle Aged; Monocytes; Placebos; Selective Serotonin Reuptake Inhibitors; Sertraline; Tumor Necrosis Factor-alpha; U937 Cells; Vascular Cell Adhesion Molecule-1

To investigate the effects of age and chronic heart failure (CHF) on the oral disposition kinetics of fluvoxamine.. A single fluvoxamine dose (50 mg) was administered orally to 10 healthy young adults, 10 healthy elderly subjects and 10 elderly patients with CHF. Fluvoxamine concentration in plasma was measured for up to 96 h.. With the exception of apparent distribution volume, ageing modified all main pharmacokinetic parameters of fluvoxamine. Thus, peak concentration was about doubled {31 +/- 19 vs. 15 +/- 9 ng ml(-1); difference [95% confidence interval (CI)] 16 (3, 29), P < 0.05}, and area under the concentration-time curve was almost three times higher [885 +/- 560 vs. 304 +/- 84 ng h ml(-1); difference (95% CI) 581 (205, 957), P < 0.05]; half-life was prolonged by 63% [21.1 +/- 6.2 vs. 12.9 +/- 6.4 h; difference (95% CI) 8.2 (2.3, 14.1), P < 0.01], and oral clearance was halved (1.12 +/- 0.77 vs. 2.25 +/- 0.66 l h(-1) kg(-1); difference (95% CI) -1.13 (-1.80, -0.46), P < 0.001]. A significant inverse correlation was consistently observed between age and oral clearance (r=-0.67; P < 0.001). The coexistence of CHF had no significant effect on any pharmacokinetic parameters in elderly subjects.. Ageing results in considerable impairment of fluvoxamine disposition, whereas CHF causes no significant modifications. Therefore, adjustment of initial dose and subsequent dose titrations may be required in elderly subjects, whereas no further dose reduction is necessary in elderly patients with CHF.

Topics: Administration, Oral; Adult; Age Factors; Aged; Aged, 80 and over; Aging; Chronic Disease; Depression; Fluvoxamine; Heart Failure; Humans; Male; Metabolic Clearance Rate

Efficacy of antidepressants fluvoxamine, amitriptyline and transcranial electrostimulation of the brain in the treatment of chronic daily headache has been studied. Amitriptyline had the highest effect in dosage 50 mg daily but was not well tolerated by patients that resulted in that only 50% of them finished the study. Fluvoxamine had high efficacy and good tolerability in the treatment of chronic daily headache and medication overuse headache. Small dosages of amitriptyline and fluvoxamine potentiated the analgesic effect of transcranial electrostimulation of the brain. The combination of antidepressants with transcranial electrostimulation of the brain alleviated the negative effect of the withdrawal of overused analgesics and may be recommended for out-patient use.

Topics: Adrenergic Uptake Inhibitors; Adult; Amitriptyline; Chronic Disease; Electric Stimulation Therapy; Female; Fluvoxamine; Headache; Humans; Male; Middle Aged; Selective Serotonin Reuptake Inhibitors; Skull

A prospective, open-label clinical trial was conducted for two aims: first, to evaluate the role of fluvoxamine, one of selective serotonin reuptake inhibitors, in the treatment of dizziness for the first time and to investigate its effective mechanisms. Second, to test the hypothesis that dizziness in patients without abnormal neuro-otologic findings would be induced by psychiatric disorders rather than by unnoticed neuro-otologic diseases. Nineteen patients with neuro-otologic diseases (Group I) and 22 patients in whom standard vestibular tests revealed no abnormal findings (Group II) were treated by fluvoxamine (200 mg/day) for eight weeks. Subjective handicaps due to dizziness using a questionnaire, anxiety and depressive symptoms measured with the Hospital Anxiety and Depression Scale (HADS), and stress hormones (vasopressin and cortisol) were examined before and 8 weeks after treatment. Overall, fluvoxamine decreased subjective handicaps of both Groups I and II. Fluvoxamine decreased HADS of only patients whose subjective handicaps were reduced (=responders) in both groups, suggesting that fluvoxamine was effective for dizziness via psychiatric action rather than a recovery of vestibular function through serotonergic activation. In non-responders of Group II, pre-treatment HADS was higher than in Group I non-responders and it was not decreased by the treatment, suggesting that dizziness of Group II non-responders was due to severe psychiatric disorders rather than unnoticed neuro-otologic diseases. Anxiety and depression components of HADS showed a good correlation at both pre- and post-treatment periods. No post-therapeutic decrease was observed in either vasopressin or cortisol even in responders, suggesting that dizziness was not the sole cause of stress in chronic dizziness patients. In conclusion, patients with or without physical neuro-otologic deficits who report chronic dizziness accompanied by anxiety and depression (as measured by HADS) showed improvements across a full range of subjective handicaps and psychological distress, while patients with physical neuro-otologic defects and minimal anxiety or depression did not benefit. The main causes of dizziness in patients without physical neuro-otologic findings were psychiatric disorders.

Topics: Adult; Anxiety; Case-Control Studies; Chronic Disease; Cost of Illness; Depression; Disability Evaluation; Dizziness; Female; Fluvoxamine; Humans; Male; Meniere Disease; Middle Aged; Prospective Studies; Selective Serotonin Reuptake Inhibitors; Somatoform Disorders; Statistics, Nonparametric; Vestibular Diseases

Fluvoxamine CR has been reported effective in the short-term (12-wk) treatment of generalized social anxiety disorder (social phobia). Social anxiety disorder (SAD) is, however, a chronic disorder thought to require maintenance treatment. We report on data from the extension phase of a short-term study, in order to explore the efficacy and safety profile of fluvoxamine CR (100-300 mg/d) in the longer-term treatment of this disorder. Adult outpatients with generalized social anxiety disorder (GSAD) at 35 centres in Europe, South Africa, and USA were included in an acute phase study (12 wk). Subjects who demonstrated at least minimal improvement by endpoint (n=112), were offered participation in an extension phase, in which medication was continued for a further 12 wk under double-blind conditions. Efficacy was assessed using the Liebowitz Social Anxiety Disorder Scale (LSAS), the Clinical Global Impression Global Improvement score (CGI-I), the Clinical Global Impressions Severity of Illness score (CGI-S), and the Sheehan Disability Scale (SDS). Safety and tolerability assessments were also performed at regular intervals. Subjects treated with fluvoxamine CR had a numerically greater decrease in LSAS total scores than subjects treated with placebo at endpoint. Analysis of data from baseline (day 1) to endpoint (last observation carried forward) demonstrated that this difference tended towards significance, while severity of illness on the CGI-S and disability on the SDS were significantly lower in the fluvoxamine CR group than in the placebo group. The same trends were observed when only data from weeks 12-24 were included in the analysis; although the magnitude of changes was smaller in the extension phase than in the acute phase, fluvoxamine CR-treated subjects continued to show improvement compared to placebo-treated subjects. Most treatment-emergent signs and symptoms (TESS) were mild to moderate in severity. No unexpected abnormalities were reported on vital signs, electrocardiagrams, or laboratory investigations. These data support the long-term efficacy, safety, and tolerability of fluvoxamine CR in the treatment of GSAD. Given the prevalence, persistence, and disability associated with GSAD, and the relative paucity of long-term treatment studies of SAD, the current dataset provides empirical support for the current clinical consensus that pharmacotherapy of this disorder should be continued beyond the acute phase.

Topics: Adult; Anti-Anxiety Agents; Chronic Disease; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Personality Assessment; Phobic Disorders; Treatment Outcome

Olanzapine is a substrate of the cytochrome P450 enzyme (CYP) 1A2. In this study, pharmacokinetic interactions and clinical effects of adding the CYP1A2 inhibitor fluvoxamine to steady-state olanzapine was examined in patients suffering from schizophrenia. Eight patients had been treated for at least 3 months with 10 to 20 mg/day olanzapine. Fluvoxamine (100 mg/day) was added (week 0) to the olanzapine treatment and continued for 8 weeks. Concentrations of olanzapine and its metabolite N-desmethylolanzapine and of fluvoxamine were analyzed at weeks 0, 1, 4, and 8. Addition of fluvoxamine resulted in a 12% to 112% ( < 0.01) increase of olanzapine from 31 +/- SD 15 ng/mL (week 0) to 56 +/- 31 ng/mL (week 8) in all patients. N-desmethylolanzapine concentrations were not significantly changed ( > 0.05). Fluvoxamine concentrations were 48 +/- 26 ng/mL on week 1 and 83 +/- 47 ng/mL on week 8. It is concluded that fluvoxamine affects olanzapine degradation and thus increases olanzapine concentrations. Although the combination was well tolerated in this sample and the negative symptom response appeared to be favorable in at least five patients, the combination therapy of olanzapine and fluvoxamine should be used cautiously and should be controlled by therapeutic drug monitoring to avoid olanzapine-induced side effects or intoxications.

Topics: Adult; Benzodiazepines; Chemotherapy, Adjuvant; Chronic Disease; Drug Interactions; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Prospective Studies; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Time Factors

We investigated the efficacy and safety of augmenting risperidone with fluvoxamine for the treatment of residual positive and negative symptoms in patients with chronic schizophrenia who had shown an incomplete response to risperidone. A total of 30 patients completed the open trial over a 12-week period during which fluvoxamine was added to risperidone. The result from the positive and negative syndrome scale (PANSS) and Simpson-Angus extrapyramidal effects (S-A) scale were examined at baseline, 1, 2, 4, 8 and 12 weeks of treatment. There were no significant differences in PANSS positive, negative and general psychopathology scores, or in S-A scale scores at any point during the treatment. These results suggest that fluvoxamine appears to be ineffective in augmenting the risperidone treatment response in chronic schizophrenic patients. Further controlled trials will be needed to confirm this observation.

Topics: Antipsychotic Agents; Chronic Disease; Drug Interactions; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

Open-label addition of a low-dose typical (pimozide) neuroleptic was shown to be beneficial in some patients with serotonin reuptake inhibitor (SRI)-refractory trichotillomania (TTM). Risperidone's potentially more benign acute and long-term side effect profile makes it a candidate for investigation in the treatment of TTM. We report our experience with the systematic addition of open-label risperidone 0.5 to 3 mg/day in three patients with SRI-refractory TTM. All three patients had a robust decrease in hair pulling as measured by clinician-rated instruments. These results suggest that risperidone addition to ongoing treatment with SRIs may be an effective treatment strategy for patients with SRI-refractory TTM.

Topics: Adult; Chronic Disease; Drug Resistance; Female; Fluoxetine; Fluvoxamine; Humans; Male; Middle Aged; Risperidone; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Trichotillomania

Four patients with chronic schizophrenia were treated with a combination of fluvoxamine, haloperidol, and benztropine. The combination significantly impaired performance on tests of delayed recall memory and attentional function. Haloperidol concentrations in serum were monitored in three patients and were robustly elevated by fluvoxamine.

Topics: Adult; Benztropine; Chronic Disease; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Fluvoxamine; Haloperidol; Humans; Male; Middle Aged; Neurologic Examination; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Forty out-patients affected by chronic tension-type headache were selected according to the diagnostic criteria of International Headache Society (IHS) Headache Classification Committee. In a controlled trial patients received placebo for a four-week baseline period, then they were randomized in double-blind fashion to therapy with mianserine (30-60 mg/day) of fluvoxamine (50-100 mg/day) for another eight-week period. Frequency of headache, pain severity and analgesic consumption were evaluated using a self-monitoring system. Mood depression was evaluated at 0, 4 and 8 weeks by using Zung's Self-Rating Depression Scale and Hamilton Rating Scale for Depression. Both drugs were beneficial in the treatment of chronic tension-type headache. Non-depressed subjects with more severe headache responded best to fluvoxamine, whereas mianserine was more effective in the treatment of depressed patients with moderate headache. These results suggest that central serotoninergic neurotransmission can play a role in the pathophysiology of chronic tension-type headache also in non-depressed patients.

Topics: Adult; Chronic Disease; Depression; Double-Blind Method; Female; Fluvoxamine; Headache; Humans; Male; Mianserin; Middle Aged; Muscle Contraction; Placebos; Selective Serotonin Reuptake Inhibitors; Serotonin

Topics: Adolescent; Adult; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Fluvoxamine; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Psychiatric comorbidities are an important issue in the treatment of chronic dizziness patients.. To test the correlation between psychiatric status and subjective handicaps and to examine the effects of milnacipran on handicaps.. Hospital anxiety and depression scale (HADS) and handicaps were assessed by a questionnaire before and eight weeks after milnacipran treatment (50 mg/day) in 29 consecutive patients with chronic dizziness. Effects of milnaciplan were compared with fluvoxamine (200 mg/day).. A significant correlation was found between anxious and depressive scale scores and also between HADS and handicaps. Duration of symptoms was longer in the anxious/depressive group (HADS≧13) than in the non-anxious/depressive group. Handicaps and HADS were significantly decreased after treatment only in the anxious/depressive group. There were no overall differences in drug effects between milnaciplan and fluvoxamine. However, the rate of patients with a post/pre ratio of handicaps <80% was higher in milnaciplan group compared with the fluvoxamine group.. Not only anxiety disorders but also depression should be considered as comorbid psychiatric disorders in patients with chronic dizziness. Dizzy patients with psychiatric comorbidities have a longer duration of symptoms and more handicaps than those without psychiatric disorders. Milnacipran may be chosen as a treatment for patients with chronic dizziness with comorbid psychiatric disorders in case of and insufficient response to SSRIs.

Topics: Anxiety Disorders; Chronic Disease; Comorbidity; Cyclopropanes; Depressive Disorder; Dizziness; Female; Fluvoxamine; Humans; Male; Mental Disorders; Middle Aged; Milnacipran; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors

Emerging evidence from therapeutic trials in humans and animal models suggests that in the treatment of depression, antidepressants play a role by targeting the glutamatergic system. Fluvoxamine is one of the widely used SSRIs which has been considered to target monoamine neurotransmitter reuptake mechanisms. However, whether fluvoxamine has an effect on the glutamate release is still unclear. The present experiment studied the effect of fluvoxamine on presynaptic glutamate release in prelimbic cortex, both in control C57BL/6 mice and chronic restraint stress C57BL/6 mice, and further investigated the mechanism underlying this effect by using patch clamp, on-line fluorimetry, pharmacological approaches combined with other techniques. The results showed that fluvoxamine increased the glutamate release in the depression model mice but it had no effect on the glutamate release in the control mice. The mechanism underlying these effects in depression model mice was that, fluvoxamine firstly activated presynaptic 5-HT(3) receptors, which transiently increased the Ca(2+) concentration. The increase of Ca(2+) concentration via 5-HT(3) receptors caused the activation of sigma-1 receptors, which were activated by fluvoxamine. The activation of sigma-1 receptors increased the intrasynaptosomal Ca(2+) concentration significantly through the outflow of endoplasmic reticulum calcium and finally activated PKC. These results suggested that fluvoxamine may have a selective effect and different mechanism based on the condition of animal.

Topics: Animals; Benzophenanthridines; Calcium; Calcium Channel Blockers; Cerebral Cortex; Chronic Disease; Egtazic Acid; Endoplasmic Reticulum; Fluvoxamine; Glutamic Acid; Limbic System; Male; Mice; Mice, Inbred C57BL; Models, Biological; Protein Kinase C; Receptors, Serotonin, 5-HT3; Receptors, sigma; Restraint, Physical; Serotonin 5-HT3 Receptor Antagonists; Sigma-1 Receptor; Stress, Physiological; Synapses; Synaptosomes

Catatonia is a syndrome with protean manifestations and multiple aetiologies. In this report, the authors describe the case of a young woman who presented for care after a 13-year period of catatonia-like symptoms, including mutism, refusal to eat and persistent neck flexion. Medical management included placement of a percutaneous endoscopic gastric tube for nutritional support. A thorough medical investigation later revealed the presence of a cervical spine haemangioma that was treated surgically, with improvement in neck posturing. Psychopharmacological treatment included lorazepam, aripiprazole and memantine. Addition of fluvoxamine to target obsessive compulsive disorder (OCD)-like symptoms resulted in clinical improvement, suggesting OCD as a possible cause of this patient's chronic catatonic state.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Catatonia; Chronic Disease; Combined Modality Therapy; Dopamine Agents; Female; Fluvoxamine; GABA Modulators; Humans; Lorazepam; Memantine; Neurosurgical Procedures; Obsessive-Compulsive Disorder; Piperazines; Quinolones; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Amisulpride; Antipsychotic Agents; Chronic Disease; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Hyperpigmentation; Obsessive-Compulsive Disorder; Photosensitivity Disorders; Selective Serotonin Reuptake Inhibitors; Sertraline; Sulpiride

Chronic pruritus is difficult to treat and requires the evaluation of new therapeutic modalities. We initiated an open-labelled, two-arm prospective, proof-of-concept study applying two selective serotonin re-uptake inhibitors on a long-term basis. Paroxetine and fluvoxamine were tested in a total of 72 pruritic patients (27 men, 45 women, age range 28-88 years, mean age 59.2 years). The reduction in pruritus was evaluated by analysis of visual analogue scores and determination of the maximal antipruritic effect (maximal percentual reduction in pruritus). Forty-nine of 72 patients (68.0%) experienced a weak (n=9), good (n=16) or very good (n=24) antipruritic effect. Statistical analysis proved the efficacy of paroxetine and fluvoxamine with no significant difference. The best response was observed in patients with pruritus due to atopic dermatitis, systemic lymphoma and solid carcinoma. Chronic scratch lesions healed completely in 14/31 patients and partially in 17/31 patients. Adverse drug effects were observed in 70.8% of patients, resulting in discontinuation of treatment in 18 patients. These results support previous reports of high antipruritic potency of selective serotonin re-uptake inhibitors, which are a good alternative treatment modality in chronic pruritus. This should be confirmed in future double-blind studies.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma; Chronic Disease; Dermatitis, Atopic; Female; Fluvoxamine; Humans; Lymphoma; Male; Middle Aged; Paroxetine; Prospective Studies; Pruritus; Selective Serotonin Reuptake Inhibitors

A growing body of evidence suggests a disturbance of brain plasticity in major depression. In contrast to hippocampal neurogenesis, much less is known about the role of synaptic plasticity. Long-term potentiation (LTP) and long-term depression (LTD) regulate the strength of synaptic transmission and the formation of new synapses in many neural networks. Therefore, we examined the modulation of synaptic plasticity in the chronic mild stress animal model of depression.. Adult rats were exposed to mild and unpredictable stressors for 3 weeks. Thereafter, long-term synaptic plasticity was examined in the hippocampal CA1 region by whole-cell patch clamp measurements in brain slices. Neurogenesis was assessed by doublecortin immunostaining.. Exposure to chronic mild stress facilitated LTD and had no effect on LTP. Chronic application of the antidepressant fluvoxamine during the stress protocol prevented the facilitation of LTD and increased the extent of LTP induction. Neurogenesis in the dentate gyrus was impaired after chronic stress.. In addition to neurogenesis, long-term synaptic plasticity is an important and ubiquitous form of brain plasticity that is disturbed in an animal model of depression. Facilitated depression of synaptic transmission might impair function and structure of brain circuits involved in the pathophysiology of major depression. Antidepressants might counteract these alterations.

Topics: Animals; Chronic Disease; Dentate Gyrus; Depressive Disorder; Disease Models, Animal; Doublecortin Protein; Fluvoxamine; Hippocampus; Long-Term Potentiation; Long-Term Synaptic Depression; Neuronal Plasticity; Patch-Clamp Techniques; Rats; Rats, Wistar; Stress, Psychological; Synaptic Transmission

The dopamine D2/D3 receptor agonist and alpha2 adrenergic receptor antagonist, piribedil, is used clinically as monotherapy and as an adjunct to L-3,4-dihydroxyphenylalanine in the treatment of Parkinson's disease. As it appears to improve mood, we examined its actions in rodent models of antidepressant properties, in comparison with the prototypical anti-Parkinson agent, apomorphine, the D2/D3 receptor agonist, quinpirole, and the antidepressants, imipramine and fluvoxamine. In the mouse forced-swim test, acute administration of imipramine, fluvoxamine, apomorphine or quinpirole decreased immobility time, actions dose dependently mimicked by piribedil (2.5-10.0 mg/kg, subcutaneously). In rats, acute and subchronic administration of piribedil similarly reduced immobility (0.63-10.0 mg/kg, subcutaneously) and apomorphine, quinpirole and imipramine were also active in this test, whereas fluvoxamine was inactive. Both in mice and in rats, the D2/D3 receptor antagonist, raclopride, and the D2 receptor antagonist, L741,626, dose dependently blocked the antidepressant properties of piribedil, whereas the selective D3 receptor antagonists, S33084 and SB277,011, were ineffective. In a chronic mild stress model in rats, piribedil (2.5-40.0 mg/kg, subcutaneously) restored sucrose intake in stressed animals exerting its actions more rapidly (by week 1) than imipramine. Imipramine, fluvoxamine, apomorphine, quinpirole and piribedil dose dependently (0.63-10.0 mg/kg, subcutaneously) suppressed aggressive and marble-burying behaviour in mice. In the latter procedure, raclopride and L741,626, but not S33084, attenuated the actions of piribedil. Over a dose range (0.63-10.0 mg/kg, subcutaneously) equivalent to those active in models of antidepressant activity, piribedil did not stimulate locomotor behaviour. In conclusion, principally via recruitment of D2 receptors, piribedil exerts robust and specific antidepressant-like actions in diverse rodent models.

Topics: Aggression; Animals; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Antiparkinson Agents; Behavior, Animal; Chronic Disease; Dopamine Agonists; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Dose-Response Relationship, Drug; Fluvoxamine; Imipramine; Male; Mice; Motor Activity; Piribedil; Quinpirole; Raclopride; Rats; Rats, Wistar; Receptors, Dopamine D2; Receptors, Dopamine D3; Social Isolation; Stress, Psychological; Sucrose; Swimming

Locus coeruleus (LC) is the major component of noradrenergic neurons in the brain. corticotropine-releasing hormone (CRH) and norepinephrine (NE) are suggested to play significant roles in the pathophysiology of depression, although the involvement of the serotonergic system in the CRH-NE systems is not elucidated. Chronic inescapable and unpredictable stress can result in a sustained dysregulation of both of CRH and NE systems. In the present study we have investigated the TH immunoreactivity in the LC by immunohistochemical staining in rats treated with chronic variable stress (CVS) and concurrent administration with clomipramine or fluvoxamine. There was a significant decrease in TH levels 24 h after the last stressor of CVS, followed by a further decrease in that of 72 h later, whereas a marked increase was observed in TH levels immediately after the last stress of CVS 13 d. Concurrent clomipramine and fluvoxamine treatment prevented the sensitization of TH reactivity and the delayed decrease until 72 h later. These data suggest that an increase in serotonin availability would contribute to the normalization of both hypoactivity and sensitization of LC-NE neurons modified under "chronically stressful" situations.

Topics: Animals; Antidepressive Agents, Tricyclic; Chronic Disease; Clomipramine; Corticotropin-Releasing Hormone; Disease Models, Animal; Fluvoxamine; Immunohistochemistry; Locus Coeruleus; Male; Norepinephrine; Rats; Rats, Wistar; Selective Serotonin Reuptake Inhibitors; Serotonin; Stress, Psychological; Time Factors; Tyrosine 3-Monooxygenase

Case 1: female, age 76. Fluvoxamine (50 mg/day) initiated a reduction of pain on the 14th day of administration and completely ameliorated pain as well as depression. Case 2: female, age 76. Fluvoxamine (25 mg/day) was administered with tandospirone (15 mg/day) which augments the effect of an SSRI. This combination regimen induced a reduction of PHN-pain on the 10th day and as the analgesic effect attained nearly 50%, there occurred a reflaming of pain on the 35th day. Increasing fluvoxamine to 50 mg/day reameliorated pain on the 49th day, and a further increase to 75 mg/day finally eliminated pain and depression at the end of the 3rd month. The long latency of fluvoxamine action, its shortening by tandospirone and the parallel changes of PHN and depression are all indicative of that the same mechanism, namely renormalization of the dysfunctioned central serotonergic transmission would be underlying both the anti-PHN and antidepressant actions. It would be concluded that fluvoxamine alleviates PHN by restoration of the descending serotonergic inhibition of primary afferent activity that carries pain impulses.

Topics: Aged; Chronic Disease; Drug Therapy, Combination; Female; Fluvoxamine; Herpes Zoster; Humans; Isoindoles; Neuralgia; Piperazines; Pyrimidines; Selective Serotonin Reuptake Inhibitors; Serotonin Receptor Agonists; Treatment Outcome

Not enough is known about the propensity of individual negative symptoms to respond to treatment and the dynamics of this change. We have previously shown that adding the selective serotonin reuptake inhibitor fluvoxamine to antipsychotics can improve negative symptoms, and now provide data on the response of individual negative symptoms to such treatment. We examined items on the Schedule for the Assessment of Negative Symptoms for patients participating in two published controlled studies comparing the effect of add-on fluvoxamine and placebo on negative symptoms. Using a mixed regression model, we analysed item scores at each week of the study to identify the first signs of a treatment effect. Potential confounding effects of depressive extrapyramidal and positive symptoms were statistically controlled. Eleven of 16 items tested showed improvement, five within 2 weeks and a further four within 3 weeks of starting treatment. The most rapidly responding items included core negative symptoms such as alogia. The propensity for and rate of improvement with fluvoxamine treatment differs for the various negative symptoms. Many symptoms, including those generally agreed to be core features of the illness such as alogia, improved within 2-3 weeks of treatment initiation.

Topics: Antipsychotic Agents; Aphasia; Chronic Disease; Clinical Trials as Topic; Data Interpretation, Statistical; Drug Administration Schedule; Drug Therapy, Combination; Fluvoxamine; Humans; Regression Analysis; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Time Factors; Treatment Outcome

Topics: Adult; Antiemetics; Child; Chronic Disease; Disabled Persons; Feeding and Eating Disorders of Childhood; Fluvoxamine; Humans; Male; Mental Disorders; Selective Serotonin Reuptake Inhibitors; Vomiting

Although patients with trichotillomania typically present to dermatologists, the diagnosis and treatment lie in the field of psychiatry. We report an unusual case of a 33-year-old woman with severe trichotillomania. We review common clinical and pathologic findings of this often chronic and socially debilitating disorder. In addition, we discuss treatment options for dermatologists and how collaboration with psychiatrists is the most effective management for these difficult-to-treat patients.

Topics: Adult; Antidepressive Agents, Second-Generation; Chronic Disease; Female; Fluvoxamine; Humans; Psychotherapy; Trichotillomania

Establishing that treatment for negative symptoms improves primary features of schizophrenia rather than similar symptoms of other etiology is an important clinical issue. Primary negative symptoms may also differ among themselves in the propensity to respond to a given treatment. In this study, we examined the response of negative symptoms to add-on fluvoxamine by analyzing discrete symptoms independently and controlling for potential confounding variables. Data from two published controlled studies comparing fluvoxamine to placebo were pooled for the analysis. Eleven of sixteen Scale for the Assessment of Negative Symptoms items tested, including key negative symptoms such as affective flattening and alogia, improved. The improvement was not related to baseline levels of depressive, extrapyramidal, and positive symptoms or to changes in the symptom scores during the study. The findings support the view that fluvoxamine augmentation can improve primary negative symptoms in chronic schizophrenia patients.

Topics: Affect; Antipsychotic Agents; Chronic Disease; Diagnostic and Statistical Manual of Mental Disorders; Drug Synergism; Female; Fluvoxamine; Humans; Male; Schizophrenia; Selective Serotonin Reuptake Inhibitors

Concomitant fluvoxamine use can potentially reduce the dosage of clozapine needed in treatment-refractory patients with schizophrenia. Previous reports have shown that fluvoxamine can increase plasma clozapine concentrations by inhibition of cytochrome P450 (CYP) 1A2. We evaluated the safety and efficacy of fluvoxamine, 50 mg/day, coadministration with clozapine, 100 mg/day, in refractory schizophrenic patients.. In this prospective study, 18 treatment-refractory patients with DSM-IV schizophrenia (10 nonsmokers and 8 smokers) were treated with clozapine at a target dose of 100 mg h.s. After steady-state conditions of clozapine had been reached, 50 mg/day of fluvoxamine was then added. Plasma levels of clozapine, norclozapine, and clozapine N-oxide were measured prior to fluvoxamine addition and on days 14 and 28 during combined treatment. Side effects and efficacy were monitored with standardized rating instruments.. After 14 days of combined treatment, the mean +/- SD plasma clozapine level increased 2.3-fold to 432.4+/-190.9 ng/mL without further elevation on day 28. All patients completed the study without significant adverse side effects. Twelve of the 18 patients achieved plasma clozapine concentrations of at least 350 ng/mL. While plasma norclozapine levels also rose (but to a smaller extent), plasma clozapine N-oxide levels remained unchanged after the add-on therapy. Patients who smoked had 34% lower plasma clozapine concentrations than nonsmokers (NS). Three of the 4 patients who did not reach clozapine plasma levels of at least 300 ng/mL were smokers. Plasma norclozapine/clozapine ratios, especially in smokers, declined significantly with fluvoxamine addition.. The addition of fluvoxamine, 50 mg/day, to low-dose clozapine, 100 mg/day, can raise plasma clozapine levels to at least 300 ng/mL in most patients. Only slight dosage adjustments with clozapine may be needed after fluvoxamine coadministration in some patients who smoke. Plasma clozapine levels remained stable after 14 days of fluvoxamine addition. The combined treatment was well tolerated, and clinical improvement was observed in our patients. Further long-term studies with this drug combination are needed to determine its economic impact.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Clozapine; Comorbidity; Drug Administration Schedule; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Prospective Studies; Psychiatric Status Rating Scales; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Smoking; Treatment Outcome

Topics: Adult; Biomarkers; Chronic Disease; Dose-Response Relationship, Drug; Drug Tolerance; Female; Fluvoxamine; Humans; Male; Melatonin; Psychiatric Status Rating Scales; Schizophrenia; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Chronic Disease; Clozapine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Fluvoxamine; Humans; Male; Schizophrenia; Schizophrenic Psychology

Topics: Adult; Chromatography, High Pressure Liquid; Chronic Disease; Clozapine; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Metabolic Clearance Rate; Schizophrenia, Paranoid; Schizophrenic Psychology