fluvoxamine and Pain

To observe treatment effects and safety of fluvoxamine combined with oxycodone prolonged-release tablets in treating patients with moderate to severe cancer pain.. Patients confirmed pathologically with cancer and complicated with moderate to severe pain, were divided into control and experimental groups. Oxycodone prolonged-release tablets, with or without fluvoxamine, were administrated to all study patients until pain relief. Degree of pain relief, dose of oxycodone prolonged-release tablets, side effects and quality of life were compared before and after treatment.. In total, 120 patients were recruited. No statistically significant difference was detected regarding age, gender, types of cancer, KPS between two groups of patients (P> 0.05). Baseline pain score of patients with moderate pain in treatment and control group was 4.9±0.8 and 5.1±0.8, respectively; and decreased to 1.8±1.1 and 1.2±1.1 after treatment, respectively. Pain intensity was significantly reduced in the treatment group (P =0.028). Average daily consumption of oxycodone prolonged- release tablets was (54.0±19.6) mg and (44.7± 18.7) mg respectively, which is lower in treatment grpup than in control group, but the difference was not statistically significant (P=0.065). Baseline pain score of patients with severe pain in treatment and control groups were 8.3±1.1 and 8.3±1.1, respectively; and pain intensity after treatment decreased to 2.9±1.0 and 2.3±1.0. Pain intensity was significantly reduced in the treatment group, with statistical significance (P =0.026). Average daily consumption of oxycodone prolonged-release tablets was (132.0±42.2) mg and (110.7±33.9) mg, respectively, which is lower in treatment group than in control group, and the difference was statistically significant (P=0.035). In terms of quality of life, patients in treatment group had better performance status, daily activity, mood, and sleep than that in control group (P < 0.05). Patients in two groups had similar side effects, eg., constipation, nausea/vomiting, lethargy, dizziness, itchy skin, dysuria, and ataxia. Lower incidence of nausea/vomiting, lethargy, was obtained from patients in treatment than in control group, while significant low constipation was observed in treatment than in control group (35.0% vs 49.2%, P=0.026).. Fluvoxamine combined with oxycodone prolonged-release tablets could be more effective in treating patients with cancer pain, and could reduce the dosage of oxycodone prolonged-release tablets and thus be associated with lower side effects, and improved quality of life.

Topics: Analgesics, Opioid; Delayed-Action Preparations; Drug Therapy, Combination; Female; Fluvoxamine; Humans; Male; Neoplasms; Oxycodone; Pain; Pain Measurement; Quality of Life; Selective Serotonin Reuptake Inhibitors; Treatment Outcome

To better understand the antinociceptive effect of fluvoxamine, we measured regional cerebral blood flow during laser-evoked pain and hot sensations using H(2)15O positron emission tomography and also subjective pain and hot sensations before and after fluvoxamine or placebo administration for 7 days to 12 healthy volunteers. The subjectively rated pain score was significantly reduced by fluvoxamine administration. Painful stimuli activated multiple brain regions. After fluvoxamine administration the ipsilateral anterior cingulate cortex (ACC), contralateral insular cortex (IC), and contralateral secondary somatosensory cortex (SII) activations were reduced. The bilateral IC activation was also reduced in the placebo group. These results suggest that fluvoxamine specifically reduced activation of the ACC and SII, which are areas concerned with the affective and integrative components of pain.

Topics: Adult; Affect; Anti-Anxiety Agents; Brain; Brain Mapping; Cerebrovascular Circulation; Female; Fluvoxamine; Hot Temperature; Humans; Lasers; Male; Pain; Selective Serotonin Reuptake Inhibitors; Single-Blind Method; Tomography, Emission-Computed

Prostatodynia is a common and often disabling condition that affects males and has the characteristics of a somatoform pain disorder. It presents with urogenital pain and urinary symptoms. Failure of conventional treatment and a successful uncontrolled pilot study with fluvoxamine in this condition prompted this study.. In a randomized double-blind trial, 42 patients with prostatodynia were assigned to receive either fluvoxamine (N = 21) or placebo (N = 21) for up to 8 weeks. Doses were adjusted according to therapeutic need. The median dose of fluvoxamine was 150 mg (range, 50-300 mg). Self-rated pain scores, urinary flow rates, and depression and anxiety scores were measured at baseline and several times throughout the study period.. The groups were similar at baseline, and the results were examined by intent-to-treat analysis either using the last observation carried forward or, in the case of dichotomous measures, counting treatment dropouts as treatment failures. Fluvoxamine was significantly more likely to reduce pain intensity (p = .01) and normalize urinary flow rates (p = .03) with a clinically significant number needed to treat value of 1.5 (confidence interval = 1.12 to 5.50). This therapeutic effect could not be attributed to change in mood, as the 2 groups did not differ with respect to affective ratings at the end of the study. The fluvoxamine-treated group had significantly lower (p = .02) final scores on the General Health Questionnaire, indicating an overall benefit from pain relief.. Fluvoxamine is a viable treatment for prostatodynia. Dose-ranging studies and longer trials are needed to evaluate this agent further.

Topics: Adult; Diagnosis, Differential; Double-Blind Method; Fluvoxamine; Humans; Male; Pain; Pain Measurement; Placebos; Prostatic Diseases; Psychiatric Status Rating Scales; Selective Serotonin Reuptake Inhibitors; Sex Factors; Somatoform Disorders; Treatment Outcome; Urodynamics

To investigate the effect of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine on central poststroke pain (CPSP), fluvoxamine (25 to 125 mg daily) was given to 31 patients. Although 3 patients dropped out within 1 week, 28 patients who received fluvoxamine for 2 to 4 weeks showed a significant reduction in the visual analog scale (VAS) for pain from 7.7 +/- 2.2 to 6.0 +/- 3.4 (p < .01). This improvement in VAS was significant in patients within less than 1 year after stroke, but not in those with a duration of more than 1 year. Zung's Self-rating Depression Scale (SDS) was also significantly improved after treatment, but there was no significant correlation between the changes in VAS and SDS. Although this is not a double-blind, placebo-controlled trial, these results suggest that fluvoxarnine is useful for the control of CPSP regardless of depression when used relatively early after stroke.

Topics: Corpus Striatum; Double-Blind Method; Female; Fluvoxamine; Humans; Limbic System; Male; Middle Aged; Neural Pathways; Pain; Pain Measurement; Pain Threshold; Receptors, Serotonin; Selective Serotonin Reuptake Inhibitors; Stroke; Thalamus; Visual Perception

Analgesic properties of antidepressants are not yet well established. The aim of this study was to investigate the analgesic effect of three antidepressants after single oral dose administration to healthy volunteers. The late spinal R-III reflex threshold (objective pain threshold) and the subjective pain threshold (numerical categorical scale) were markers of analgesic effect. Desipramine induced significant increases in both thresholds. Fluvoxamine and moclobemide also exerted a significant analgesic effect, although displaying distinct patterns depending on the analgesic marker considered. Antidepressants exert a central analgesic effect independent of their antidepressive effect and, depending on their mode of action, already detectable at spinal level.

Topics: Analgesics; Antidepressive Agents; Benzamides; Desipramine; Double-Blind Method; Electric Stimulation; Fluvoxamine; Humans; Moclobemide; Monoamine Oxidase Inhibitors; Pain; Sural Nerve

The purpose of this work was to determine whether the intraperitoneal administration of glibenclamide as a K ATP channel blocker could have an effect on the antinociceptive effects of antidepressants with different mechanisms of action.. Three antidepressant drugs, amitriptyline as a dual-action, nonselective inhibitor of noradrenaline and a serotonin reuptake inhibitor, fluvoxamine as a selective serotonin reuptake inhibitor and maprotiline as a selective noradrenaline reuptake inhibitor, were selected, and the effect of glibenclamide on their antinociceptive activities was assessed in male Swiss mice (25-30 g) using a formalin test.. None of the drugs affected acute nociceptive responses during the first phase. Amitriptyline (5, 10 mg/ kg), maprotiline (10, 20 mg/kg) and fluvoxamine (20 and 30 mg/kg) effectively inhibited pain induction caused by the second phase of the formalin test. Glibenclamide (5 mg/kg) alone did not alter licking behaviors based on a comparison with the control group. However, the pretreatment of animals with glibenclamide (10 and 15 mg/kg) partially reversed the antinociceptive effects of fluvoxamine but not those of maprotiline. In addition, the highest dose of glibenclamide (15 mg/kg) partially prevented the analgesic effect of amitriptyline.. Therefore, it seems that adenosine triphosphate-dependent potassium channels have a major role in the analgesic activity of amitriptyline and fluvoxamine.

Topics: Amitriptyline; Analgesics; Analysis of Variance; Animals; Antidepressive Agents; Drug Interactions; Fluvoxamine; Glyburide; Male; Maprotiline; Mice; Models, Animal; Pain; Pain Measurement; Potassium Channel Blockers; Potassium Channels; Random Allocation

Anti-nociceptive effects of fluvoxamine, administered by intracerebroventricular (i.c.v.) injection, include inhibited pain behavior in both formalin-induced acute pain (p<0.05-0.01) and sciatic nerve ligation-allodynia (p<0.03). A 5-HT1 receptor antagonist (WAY-100635) and a 5-HT2 receptor antagonist (ketanserin), injected i.c.v., induced hyperalgesia and inhibited fluvoxamine's anti-nociceptive effects. We also investigated how fluvoxamine affects neural activities in brain areas involved in affectional pain using Fos-like protein immunohistochemistry. The acute pain and allodynia increased Fos-positive cells in the prefrontal cortex (PFC), basolateral nucleus (BL) and central nucleus of the amygdala (Ce), indicating that these areas are involved in pain processing. Fluvoxamine did not block the Fos expression, though it did produce anti-nociception. Moreover, fluvoxamine alone increased Fos in the BL and PFC. Ketanserin did not decrease the Fos expression induced by fluvoxamine. The results indicated that 5-HT2 receptor activities participate minimally in Fos induction by fluvoxamine in the PFC and BL. In contrast, WAY-100635 affected the Fos expression produced by fluvoxamine. In the portion of the brain with affectional pain pathways, 5-HT1 receptor activities induced anti-nociceptive effects and decreased Fos expression with fluvoxamine, while 5-HT2 receptor activation affected to anti-nociceptive effects but did not induce Fos expression.

Topics: Affect; Animals; Antidepressive Agents, Second-Generation; Behavior, Animal; Fluvoxamine; Formaldehyde; Gene Expression; Genes, fos; Injections, Intraventricular; Male; Mice; Neural Pathways; Pain; Pain Measurement; Receptors, Serotonin; Sciatic Neuropathy; Selective Serotonin Reuptake Inhibitors

Topics: Accidental Falls; Aged; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Delirium; Depressive Disorder, Major; Diclofenac; Drug Interactions; Female; Fluid Therapy; Fluvoxamine; Follow-Up Studies; Haloperidol; Humans; Lithium Carbonate; Pain

Neuropathic pain is characterized by pain hypersensitivity to innocuous stimuli (tactile allodynia) that is nearly always resistant to known treatments such as non-steroidal anti-inflammatory drugs or even opioids. It has been reported that some antidepressants are effective for treating neuropathic pain. However, the underlying molecular mechanisms are not well understood. We have recently demonstrated that blocking P2X4 receptors in the spinal cord reverses tactile allodynia after peripheral nerve injury in rats, implying that P2X4 receptors are a key molecule in neuropathic pain. We investigated a possible role of antidepressants as inhibitors of P2X4 receptors and analysed their analgesic mechanism using an animal model of neuropathic pain.. Antidepressants strongly inhibited ATP-mediated Ca2+ responses in P2X4 receptor-expressing 1321N1 cells, which are known to have no endogenous ATP receptors. Paroxetine exhibited the most powerful inhibition of calcium influx via rat and human P2X4 receptors, with IC50 values of 2.45 microM and 1.87 microM, respectively. Intrathecal administration of paroxetine produced a striking antiallodynic effect in an animal model of neuropathic pain. Co-administration of WAY100635, ketanserin or ondansetron with paroxetine induced no significant change in the antiallodynic effect of paroxetine. Furthermore, the antiallodynic effect of paroxetine was observed even in rats that had received intrathecal pretreatment with 5,7-dihydroxytryptamine, which dramatically depletes spinal 5-hydroxytryptamine.. These results suggest that paroxetine acts as a potent analgesic in the spinal cord via a mechanism independent of its inhibitory effect on serotonin transporters. Powerful inhibition on P2X4 receptors may underlie the analgesic effect of paroxetine, and it is possible that some antidepressants clinically used in patients with neuropathic pain show antiallodynic effects, at least in part via their inhibitory effects on P2X4 receptors.

Topics: Action Potentials; Animals; Antidepressive Agents; Cell Line, Tumor; Citalopram; Disease Models, Animal; Fluvoxamine; Humans; Injections, Spinal; Male; Pain; Pain Measurement; Paroxetine; Purinergic P2 Receptor Antagonists; Rats; Rats, Wistar; Receptors, Purinergic P2X4; Serotonin Antagonists; Spinal Cord

To report a case of severe serotonergic symptoms following the addition of oxycodone to fluvoxamine.. A 70-year-old woman developed severe serotonergic features, including confusion, nausea, fever, clonus, hyperreflexia, hypertonia, shivering, and tachycardia, following the addition of oxycodone 40 mg twice daily to fluvoxamine 200 mg/day, easily fulfilling diagnostic criteria for serotonin syndrome. Discontinuation of the offending drugs resulted in resolution of her symptoms over 48 hours, and no other cause of the syndrome was identified. Use of the Naranjo probability scale indicated a probable relationship between the serotonergic symptoms and the addition of oxycodone to fluvoxamine therapy.. Serotonin syndrome is a serious adverse reaction usually due to interactions with serotonergic drugs. There have been only 3 previous reports involving oxycodone. Most previous reports of serotonin syndrome involving analgesics have been associated with meperidine, dextromethorphan, and tramadol. Unlike these synthetic opioids, however, oxycodone does not inhibit the reuptake of serotonin. In addition, there are a number of other possible pharmacologic mechanisms for the interaction we observed.. Monitoring for serotonergic adverse events should be done when oxycodone is given to patients receiving serotonin-reuptake inhibitors.

Topics: Aged; Analgesics, Opioid; Depression; Drug Interactions; Female; Fluvoxamine; Humans; Oxycodone; Pain; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome

Some antidepressants, as well as antiepileptics, are effective for treating pain of varying etiology. The present study was designed to characterize the antinociceptive effects of imipramine, a tricyclic antidepressant, fluvoxamine, a selective serotonin reuptake inhibitor, milnacipran, a serotonin noradrenaline reuptake inhibitor, and carbamazepine, an antiepileptic drug, using the acetic acid-induced writhing test in mice. Imipramine (1.25-10 mg/kg, i.p.), fluvoxamine (5-40 mg/kg, i.p.) and milnacipran (2.5-20 mg/kg, i.p.) all dose-dependently and significantly reduced the number of writhes induced by the injection of acetic acid (0.8% (v/v)), although the maximal effect of milnacipran was weaker than those of imipramine and fluvoxamine. Similarly, carbamazepine (5-20 mg/kg, i.p.) also showed a dose-dependent and significant antinociceptive effect. In combination studies, the co-administration of a sub-effective dose of carbamazepine (5 mg/kg, i.p.) with imipramine (1.25 and 2.5 mg/kg, i.p.), fluvoxamine (10 mg/kg, i.p.) or milnacipran (1.25 and 2.5 mg/kg, i.p.) significantly reduced the number of writhes. Additionally, the hole-board test revealed that the medications with significant antinociceptive effects barely produced changes in motor activity that could possibly affect writhing behavior. Thus, the present study demonstrated that the antinociceptive effect of carbamazepine is enhanced by combination with imipramine, fluvoxamine and milnacipran. Therefore, the combined therapy using antidepressants and carbamazepine may be useful clinically for the control of pain.

Topics: Acetic Acid; Analgesics, Non-Narcotic; Animals; Antidepressive Agents; Antidepressive Agents, Second-Generation; Carbamazepine; Cyclopropanes; Fluvoxamine; Imipramine; Male; Mice; Mice, Inbred ICR; Milnacipran; Pain; Pain Measurement

There have been no systematic efforts to manage and treat patients with frontotemporal dementia (FTD), but Perry described pharmacologic interventions for some behavioral syndromes in 2001. In Perry's report, selective serotonin reuptake inhibitors (SSRI) were recommended as first choice drugs because they were well tolerated and might have an effect on some symptoms such as compulsive symptoms and eating abnormalities. Some reports were presented concerning Japanese FTD patients which showed the effect of SSRI on stereotyped behaviors and eating abnormalities by Nishikawa, et al. (2001), Ikeda, et al. (2004), and others. We describe two FTD patients with compulsive complaints of pain, one mainly on abdomen and the other on lumbar region. Fluvoxamine markedly improved their complaints of pain as well as stereotyped symptoms. Fluvoxamine might be effective for behavioral disturbances due to improvement of serotoninergic dysfunction in frontal medial and cingulated cortices, as previously described. Moreover, it has been reported that an altered response to pain stimuli, either via a loss of awareness of pain or exaggerated reaction to pain, is a specific feature of FTD, but there have been only a few reports on this feature. Fluvoxamine might be effective for compulsive complaints of pain due to improvements of compulsive symptoms and exaggerated reactions to pain in FTD, or due to the analgesic effect of SSRI. SSRI may improve compulsive complaints of pain in FTD patients.

Topics: Aged; Compulsive Behavior; Dementia; Female; Fluvoxamine; Frontal Lobe; Humans; Middle Aged; Pain; Selective Serotonin Reuptake Inhibitors; Stereotyped Behavior; Temporal Lobe; Treatment Outcome

Spinal cord injury (SCI) results in abnormal locomotor and pain syndromes in humans. In a rodent SCI model, T13 unilateral spinal hemisection results in bilateral mechanical allodynia and thermal hyperalgesia, partly by interruption of tonic descending serotonin (5-HT) inhibition. In the current study, we examined changes in density and distribution of 5-HT and 5-HT(T) in cervical (C8) and lumbar (L5) enlargements after T13 spinal hemisection and studied the effects of intrathecally delivered 5-HT (10, 21, and 63 microg), 5-HT antagonist methysergide (125 microg/kg), and 5-HT reuptake inhibitor fluvoxamine (75 microg/kg) on pain-related behaviors. Thirty-day-old male Sprague-Dawley rats were spinally hemisected and sacrificed at 3 (n = 20) and 28 (n = 20) days postsurgery for immunohistochemistry, Western blot, and ELISA analysis and compared against sham-operated animals (n = 10). At day 3, C8 5-HT levels were not significantly changed but at L5 there was a significant decrease in ipsilateral 5-HT in laminae I-II followed by incomplete recovery at 28 days postinjury. At both 3 and 28 days postinjury, C8 5-HT(T) levels were not significantly changed, but at L5 there was significant ipsilateral up-regulation of 5-HT(T) in laminae I-II. A second group of animals (n = 30) was hemisected and, starting at 28 days postinjury, behaviorally tested with intrathecal compounds. Increasing doses of 5-HT attenuated both fore- and hindlimb mechanical allodynia and thermal hyperalgesia, and effects of endogenous 5-HT were attenuated by methysergide and enhanced with fluvoxamine, all without locomotor alterations. Sham controls (n = 10) were unaffected. Thus, permanent changes occur in 5-HT and 5-HT(T) after SCI, denervation 5-HT supersensitivity develops, and modulation of 5-HT attenuates pain-related behaviors. Insight gained by these studies may aid in the understanding of dynamic 5-HT systems which will be useful in treating chronic central pain after SCI.

Topics: Animals; Blotting, Western; Carrier Proteins; Denervation; Enzyme-Linked Immunosorbent Assay; Fluvoxamine; Hot Temperature; Hyperalgesia; Immunohistochemistry; Injections, Spinal; Male; Membrane Glycoproteins; Membrane Transport Proteins; Methysergide; Motor Activity; Nerve Tissue Proteins; Pain; Physical Stimulation; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin Antagonists; Serotonin Plasma Membrane Transport Proteins; Spinal Cord; Spinal Cord Injuries

The acute effects of various doses of two selective serotonin reuptake inhibitors (fluoxetine and fluvoxamine) on thermal and electrical stimulation-induced pain were investigated in drug-naive Wistar rats. The hot-plate and the tail-flick test and the noxious-induced withdrawal test were used. The two drugs had no effects on heat-induced pain behavior. However, the two compounds enhanced the motor responses induced by noxious electrical stimulation. These data contrast to what is generally found for tricyclic antidepressants and suggest a modality specific pain system. Cardiac and blood pressure were also found to change, but these changes were not correlated to changes in nociception. Taken together, the data suggest that the acutely administered selective serotonin reuptake inhibitors may exacerbate an acute type of pain.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Electric Stimulation; Fluoxetine; Fluvoxamine; Heart Rate; Hot Temperature; Male; Pain; Pain Measurement; Rats; Rats, Wistar; Reaction Time; Selective Serotonin Reuptake Inhibitors

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.

Topics: Animals; Dose-Response Relationship, Drug; Fluvoxamine; Male; Mice; Mice, Inbred ICR; Pain; Sensory Thresholds

Topics: Adult; Depressive Disorder; Fluvoxamine; Genital Diseases, Male; Humans; Male; Middle Aged; Pain; Prospective Studies; Psychiatric Status Rating Scales; Serotonin