In a prospective study, Takano et al 15 performed positron emission tomography scans before and 5 hours, 26 hours, and 53 hours after the administration of 50 mg of fluvoxamine to 6 healthy male volunteers. Mean serotonin transporter occupancies were It is likely that different SRIs including fluvoxamine and dopaminergic antagonists have similar effects on certain neurobiological systems. In a pharmacological fMRI study conducted by Takahashi et al 16 both fluvoxamine and sulto-pride, a D2 receptor antagonist, attenuated the activity in the amygdala of healthy volunteers during exposure to unpleasant pictures, although the two treatments had slightly different modulatory effects on other components of the neural circuit of emotional processing.
Unlike suto-pride, fluvoxamine reduced activation in the orbito-frontal cortex OFC , basal ganglia, and insula and induced greater activation in the temporal and parietal cortex.
Indeed, some authors have debated whether fluvoxamine and other SRIs exert their antiobsessional effects solely through an increase in the levels of serotonin or by an ultimate regulation of dopaminergic receptors. Of note, after a week treatment, responders had mean binding potential values closer to those of normal volunteers, while the non-responder patients did not show increases in binding potential values in the dorsal part of the basal ganglia.
Therefore, there is some evidence suggesting that fluvoxamine is able to modify the dopaminergic system, in general, and the availability of striatal dopamine D2 receptors, in particular, in patients with OCD. In light of these results, the increase in the availability of receptors may be consequent to the reduction of dopamine concentration induced by fluvoxamine and other SRIs.
In this experimental paradigm, burying begins as an appropriate, investigative activity but, after frustrated investigation of a non-reactive stimulus object ie, the marble , it persists as a compulsive stereotypy.
Fluvoxamine exhibits significant particularities in its pharmacokinetics, including the lack of pharmacological activity of its metabolites, a low degree of binding to plasma proteins, and a high affinity for various cytochrome P CYP enzymes.
After oral administration, fluvoxamine is nearly completely absorbed from the gastrointestinal tract, and the extent of the absorption is unaffected by the presence of food.
Steady-state plasma concentrations were achieved within a week. Fluvoxamine undergoes extensive oxidative metabolism, most probably in the liver. However, its elimination is prolonged in patients with hepatic cirrhosis. Comparison between the pharmacokinetic parameters of IR and CR formulations of fluvoxamine.
Abbreviations: IR, immediate release; CR, extended release; T max , time to maximum plasma concentration; C max , maximum plasma concentration; AUC 0—inf , area under the curve.
In a study using fluorine magnetic resonance spectroscopy 19F MRS , the elimination half-lives of fluvoxamine in brain and plasma were determined to assess their interdependence. Depending on the ability of the prescriber, these interactions may lead to either an increased efficacy or to toxicity. The efficacy of fluvoxamine in the management of OCD has been confirmed by a number of randomized, double-blind, controlled studies, making it the first selective SRI to be registered for this clinical indication.
The majority of double-blind, active treatment-controlled studies of fluvoxamine have been conducted with clomipramine, another SRI. Although meta-analytic studies suggest that there is a small advantage for clomipramine over fluvoxamine and other selective SRI, they generally confirmed that its lower tolerability, as will be discussed below, makes clomipramine a second-line medication.
Fluvoxamine is the only selective SRI that has been tested so far against a noradrenaline reuptake inhibitor, desipramine, in the acute treatment of OCD. Long-term maintenance treatment with fluvoxamine seems to reduce the risk of relapse, and there is some indication that lower dosages may also be effective, although only small scale studies have been conducted to date. Few neuroimaging studies have investigated the presence of predictors of response to fluvoxamine among patients with OCD.
Rauch et al 49 found that lower regional cerebral blood flow rCBF values in OFC and higher rCBF values in posterior cingulate cortex predicted better treatment response to fluvoxamine among patients with contamination-related OCD. This same pattern of associations was present regardless of whether the imaging data were acquired during a provoked or neutral state.
Conversely, Ho Pian et al 50 reported that levels of rCBF decreased significantly in the left caudate nucleus and in the left and right putamen in both responders and non-responders to treatment with fluvoxamine. However, only in responders a significant decrease in rCBF was found in the right thalamus. Taken together, these findings suggest that the pattern of activity of structures from the cortico-striato-thalamo-cortical circuit may help predict individuals who will respond to treatment with fluvoxamine, a finding that is consistent with the results obtained in prediction studies with other SRIs.
Patients with OCD often require long-term treatment. However, discontinuation of drug treatment remains a significant hurdle in the management of patients with OCD, leading to relapse in the majority of cases, even when treatment has been administered for more than 2 years.
Controlled-release formulations of newer antidepressants, including fluvoxamine, could lead to less short-term side effects and facilitate a more rapid titration regimen, an approach that could hasten treatment response in OCD. The starting dose was twice the dose usually employed in earlier comparable studies of fluvoxamine IR in OCD. Unfortunately, this study did not report any attempt to establish the therapeutic plasma concentration range of fluvoxamine.
Of interest, while the differences between fluvoxamine IR and placebo emerged from the 4th to the 10th week of treatment in early studies of patients with primary OCD, 35 — 38 the differences between fluvoxamine CR and placebo in Hollander et al 37 study achieved statistical significance at the second week of treatment both in the primary efficacy variable ie, the Y-BOCS total score and in the secondary efficacy variables ie, CGI-score and responder rate.
In other words, fluvoxamine CR showed a consistent earlier onset of therapeutic effects across different efficacy parameters when compared with the findings of previous studies involving other selective SRI. Therefore, no information regarding the percentage and speed of relapse is available. Hollander et al 53 proposed several possible explanations for the earlier onset of action of fluvoxamine CR. First, because fluvoxamine CR exhibits less circadian fluctuation in plasma levels peak to trough concentration , patients may benefit from having drug concentrations that are above the minimally therapeutically effective one during most of the day.
Second, because fluvoxamine CR has a lower maximal concentration compared with fluvoxamine after the same dosing, subjects could be started at a higher dosage of fluvoxamine CR but still enjoyed a similar tolerability profile, akin to a pulse loading strategy with clomipramine. For example, in the study by Westenberg et al 60 who investigated the effectiveness of this formulation in patients with SAD, fluvoxamine CR was titrated in a similar fashion to that adopted in the OCD study 53 but differed from placebo only after the fourth week of treatment.
In fact, since both disorders were previously found to exhibit similar patterns of response to selective SRIs, we can only speculate about the reasons underlying this apparently inconsistent finding. Finally, there may be some unidentified differences other than the diagnoses between the samples recruited for these studies. One way or another, further controlled studies are needed to elucidate whether the earlier onset of action of fluvoxamine CR in OCD patients is also found in patients with other anxiety or mood disorders.
Fluvoxamine IR exhibits antiobsessional properties similar to those of other selective SRIs and clomipramine, but has a somewhat superior tolerability profile than clomipramine, particularly with respect to a lower incidence of anticholinergic effects and reduced cardiotoxic potential. Only a minority of patients who survive trauma go on to develop PTSD, thus suggesting that it is not just a normal reaction. Fluvoxamine has shown efficacy in both civilians and war veterans with PTSD, although only small open, noncomparative studies have been conducted to date.
Improvements were seen in intrusion, avoidance, and hyperarousal symptoms in all four studies, together with a reduction in anxiety. In one study that focused particularly on sleep disturbance, fluvoxamine improved all domains of subjective sleep quality, the greatest effect being seen for reduction of dreams linked to the traumatic experience Neylan et al Sleep maintenance insomnia and troubled sleep also showed a large treatment response.
A substantial improvement in sleep quality was also noted in the study involving World War II veterans de Boer et al Two studies have assessed fluvoxamine in civilians with PTSD. Significant improvements were also seen in PTSD symptom clusters and depression. In common with other SSRIs, nausea is the most frequent adverse event.
A very low level of suicidality was reported in these studies Edwards et al ; Wagner et al and this was confirmed in global postmarketing surveillance data obtained over 17 years in an estimated 28 million patients exposed to fluvoxamine Buchberger and Wagner et al Switch to mania, serotonin syndrome, and convulsions are rarely reported and, although some patients may experience withdrawal symptoms, they are generally mild and resolve spontaneously.
Fluvoxamine is relatively safe in overdose, an important consideration in patients with psychiatric disorders. Adapted from Wagner et al Studies have shown negligible sedation or impairment in cognitive or psychomotor function Saletu et al ; Hindmarch A meta-analysis of 73 double-blind, crossover, placebo- or verum-controlled studies assessing the effects of drugs used in the treatment of SAD on objective parameters of cognitive and psychomotor performance in healthy volunteers showed that only fluvoxamine and bupropion were entirely free of impairment in any test Hindmarch and Trick in press.
Fluvoxamine does not appear to disrupt sleep Silvestri et al and has indeed shown beneficial effects on sleep in patients with PTSD Neylan et al In contrast to many antidepressants, fluvoxamine has a low incidence of sexual dysfunction.
Prescription event monitoring and postmarketing studies rarely report sexual problems. However, in studies designed to specifically assess sexual side effects, fluvoxamine appears to have less effect than the other SSRIs on sexual function Nemeroff et al ; Montejo et al , A 6-week, double-blind study in healthy men with premature ejaculation showed that placebo and fluvoxamine had no effect on ejaculation time whilst paroxetine, fluoxetine, and sertraline all significantly increased ejaculation latency, the greatest effect being seen with paroxetine Figure 3 Waldinger et al Increase in intravaginal ejaculation latency time IELT after 6 weeks in patients with premature ejaculation.
Data adapted from Waldinger et al Anxiety disorders are extremely common, highly disabling, and associated with considerable comorbidity with depression, substance abuse disorders, and other serious psychiatric illnesses. This category of illness therefore represents an important area of medical need.
The well known disadvantages of the benzodiazepines, tricyclic antidepressants, and neuroleptics have resulted in the SSRIs, with their relatively benign adverse event profile, becoming first-line treatment for many anxiety disorders. Importantly, fluvoxamine has also been fully studied in children and adolescents, since some anxiety disorders OCD and SAD in particular have their onset in childhood.
The efficacy of fluvoxamine has been demonstrated by double-blind, randomized, controlled studies in OCD, SAD, and panic disorder. It lacks the common treatment-limiting anticholinergic and cognitive side effects and cardiotoxicity of the tricyclic antidepressants heretofore clomipramine was the mainstay of OCD treatment , and the cognitive impairment and dependence susceptibility of the benzo-diazepines that are used in a variety of other anxiety disorders.
It is also safe in overdose and is associated with a low incidence of suicidality. Compared with the other SSRIs, fluvoxamine has a generally similar tolerability profile, dominated by usually mild and self-limiting gastrointestinal complaints, but appears to cause less sexual side effects and less cognitive disturbance.
Unlike paroxetine, it does not induce a significant withdrawal syndrome. Fluvoxamine can therefore be considered a first-line treatment for adults and children with a range of anxiety disorders. As well as clinical trials, the safety and tolerability of fluvoxamine has been established in extensive, published postmarketing studies, prescription event monitoring, and specific studies in patients with concomitant medical problems such as cardiovascular disease and multi-medicated elderly patients.
The safety and tolerability of fluvoxamine in real-world use has thus been widely studied. Whilst the efficacy of fluvoxamine in a variety of anxiety disorders is well established from randomized, clinical studies, there is a relative lack of published large naturalistic efficacy studies. However, there is now considerable clinical experience with fluvoxamine and no reason to believe that the efficacy of fluvoxamine under routine clinical conditions would differ in any significant way from that observed in clinical studies.
Its tolerability profile is better than traditional treatments and may offer some advantages over other SSRIs. National Center for Biotechnology Information , U. Journal List Neuropsychiatr Dis Treat v. Neuropsychiatr Dis Treat. Jane Irons. Author information Copyright and License information Disclaimer. All rights reserved. This article has been cited by other articles in PMC. Abstract Fluvoxamine is a selective-serotonin reuptake inhibitor SSRI that has proved effective in large double-blind, randomized, controlled trials involving patients with social anxiety disorder SAD , obsessive-compulsive disorder OCD , and panic disorder.
Keywords: fluvoxamine, anxiety disorders, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder. Introduction Fluvoxamine was the first of the selective serotonin reuptake inhibitors SSRIs that remains in clinical use. Pharmacokinetics The key pharmacokinetic properties of fluvoxamine are summarized in Table 1.
Table 1 Pharmacokinetic properties of fluvoxamine. Open in a separate window. Table 2 Summary of randomized, double-blind, placebo controlled trials with fluvoxamine in social anxiety disorder. Figure 1. Obsessive-compulsive disorder OCD is characterized by recurrent or persistent obsessions thoughts and compulsions behaviors that cause marked distress and significantly interfere with everyday functioning.
Table 3 Summary of randomized, double-blind, active controlled trials with fluvoxamine in obsessive-compulsive disorder. Figure 2. Obsessive-compulsive spectrum disorders Obsessive-compulsive spectrum disorders consist of a group of conditions, each of which has distinct diagnostic criteria, which share certain features with OCD eg, demographics, symptoms, neurobiology, and effective treatments Hollander and Wong et al Binge eating disorder Binge eating is one of the common eating disorders and is characterized by recurrent episodes of uncontrolled overeating.
Bulimia nervosa Patients with bulimia nervosa also experience compulsive eating binges, but their fear of loss of control and consequent weight gain leads them to use measures such as vomiting and taking laxatives. Pathological gambling Pathological gambling is a chronic and progressive condition that results in significant impairment in everyday living and a high rate of suicide attempts.
Body dysmorphic disorder Although no double-blind studies have been reported to date, there are considerable data from noncomparative trials to indicate that fluvoxamine is beneficial in patients with body dysmorphic disorder Hollander et al ; Perugi et al ; Phillips et al , Other disorders Other disorders in which fluvoxamine has shown beneficial effects include pervasive developmental disorders Martin et al , trichotillomania Stanley et al , and hypochondriasis Fallon et al Panic disorder Patients with panic disorder suffer from recurrent panic attacks characterized by a range of somatic and cognitive symptoms including sweating, trembling, shortness of breath, palpitations, and fear of dying or losing control.
Post-traumatic stress disorder Patients with post-traumatic stress disorder PTSD re-experience previous extreme trauma eg, rape or combat in the form of persistent dreams and flashbacks and suffer from hyperarousal and numbing symptoms. Figure 3. Conclusions Anxiety disorders are extremely common, highly disabling, and associated with considerable comorbidity with depression, substance abuse disorders, and other serious psychiatric illnesses.
An open clinical trial of fluvoxamine treatment of psychogenic excoriation. J Clin Psychopharmacol. Fluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled study in outpatients. Psychiatry Res. Open trial of fluvoxamine in the treatment of bulimia nervosa. Int J Eating Disord. A double-blind, placebo-controlled trial comparing fluvoxamine and imipramine in the treatment of panic disorder with or without agoraphobia. Psychopharmacol Bull.
Many patients drink alcohol while on these medications and handle it well, but be sure to ask your doctor or pharmacist if it is safe. It is important to keep in mind that alcohol may have a greater effect on individuals who are taking these medications; one drink could affect an individual as if it were two drinks.
Drug companies give doctors free samples of some medications. Doctors give these samples to patients who cannot afford the cost of the medications. Most drug companies also have programs that help patients get these and other medications free or at a reduced cost. For more information, visit: www. Please check with your physician. Overview Medication is an effective treatment for OCD. For medications to work, they must be taken regularly and as directed by their doctor. About half of OCD patients stop taking their medication due to side effects or for other reasons.
If you experience side effects, you should bring this up with your doctor so they can help you address them.
They may be able to change your dose or find a different type of SRI that your system better tolerates. What kinds of medications may help OCD? Do all antidepressants help OCD symptoms? How Do These Medications Work? Are There Side Effects? Most patients will experience one or more side effects from all of the medications listed above. The patient and doctor must weigh the benefits of the drug against the side effects. It is important for the patient to be open about problems that may be caused by the medication.
Sometimes an adjustment in dose or a switch in the time of day it is taken is all that is needed. Fluvoxamine may increase the levels and effects of:. Fluvoxamine may increase the effects of other medications that can cause bleeding e. Sleep, energy, or appetite may show some improvement within the first weeks.
Improvement in these physical symptoms can be an important early signal that the medication is working. Depressed mood and lack of interest in activities may need up to weeks to fully improve. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. This risk may persist until significant remission occurs. In short-term studies, antidepressants increased the risk of suicidality in children, adolescents, and young adults when compared to placebo.
Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age Adults age 65 and older taking antidepressants have a decreased risk of suicidality. Patients, their families, and caregivers should be alert to the emergence of anxiety, restlessness, irritability, aggressiveness and insomnia.
All patients being treated with antidepressants for any indication should watch for and notify their health care provider for worsening symptoms, suicidality and unusual changes in behavior, especially during the first few months of treatment.
Last Updated: January This information is being provided as a community outreach effort of the College of Psychiatric and Neurologic Pharmacists. This information is for educational and informational purposes only and is not medical advice. This information contains a summary of important points and is not an exhaustive review of information about the medication.
Always seek the advice of a physician or other qualified medical professional with any questions you may have regarding medications or medical conditions. Never delay seeking professional medical advice or disregard medical professional advice as a result of any information provided herein. The College of Psychiatric and Neurologic Pharmacists disclaims any and all liability alleged as a result of the information provided herein.
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