Obsessive-Compulsive Disorder 
Fluvoxamine maleate is used in the treatment of obsessive-compulsive disorder in adults and pediatric patients 8 years of age and older when obsessions or compulsions cause marked distress, are time-consuming, or interfere substantially with social or occupational functioning.1,2,4,7,8,9,10,11,12,13,14,50,62,64
Efficacy of immediate-release fluvoxamine maleate tablets for the acute management of obsessive-compulsive disorder in adults has principally been established by 2 multicenter, placebo-controlled studies of 10 weeks' duration in outpatient settings.1,2,14,50 Patients enrolled in these studies had moderate to severe obsessive-compulsive disorder.50 Immediate-release fluvoxamine maleate was titrated to a total daily dosage of 150 mg daily over the first 2 weeks, and then the dosage was adjusted within the range of 100-300 mg daily (given in 2 divided doses) based on patient response and tolerability.50 In these and a limited number of other clinical studies in patients with obsessive-compulsive disorder, fluvoxamine was found to be more effective than placebo in reducing the severity of symptoms associated with this disorder.1,2,4,7,8,9,10,12,50 In the studies used to establish efficacy, a positive clinical response (much or very much improved on the Clinical Global Impressions scale) occurred in 43 or 12% of patients receiving fluvoxamine or placebo, respectively.1,2,14,50 No age- or gender-related differences in efficacy were noted in these studies.1,50
Efficacy of extended-release fluvoxamine maleate capsules for the acute treatment of obsessive-compulsive disorder was demonstrated in a multicenter, placebo-controlled study of 12 weeks' duration in adult outpatients with moderate to severe obsessive-compulsive disorder.62,64 Dosage was titrated in 50-mg increments over the first 6 weeks based on response and tolerability from an initial dosage of 100 mg daily to a dosage ranging from 100-300 mg daily.62,64 Patients receiving extended-release fluvoxamine demonstrated greater improvement on the Yale-Brown Obsessive-Compulsive Scale from baseline to week 12 compared with patients receiving placebo.62,64 The mean dosage of extended-release fluvoxamine maleate was 261 mg daily at the end of the study.62 No age- or gender-related differences in efficacy were observed in this study.62
Results from a limited number of comparative studies suggest that fluvoxamine immediate-release tablets are as effective as clomipramine in the management of obsessive-compulsive disorder.2,4,13 Like fluoxetine and clomipramine, fluvoxamine reduces but does not eliminate obsessions and compulsions.1,2,4,7,12,14,50,62 Therapeutic response to fluvoxamine in patients with obsessive-compulsive disorder generally is evident within 2-3 weeks, but may not be maximal until several months after beginning therapy with the drug.4,8,9,12,14
Efficacy of fluvoxamine for long-term use was established in a clinical trial in adults receiving immediate-release fluvoxamine tablets.50,62 In addition, the drug reportedly has been used in some patients for prolonged periods (i.e., for up to 8 years) without apparent loss of clinical effect.4,14 If fluvoxamine is used for extended periods, the need for continued therapy should be reassessed periodically.50,62
As with other antidepressants, the possibility that fluvoxamine may precipitate hypomanic or manic attacks in patients with bipolar or other major affective disorders should be considered.1,4,7,15,16
Bulimia Nervosa
Fluvoxamine has been used in the treatment of bulimia nervosa†.19,20 In one double-blind, placebo-controlled study in patients with bulimia nervosa, maintenance therapy with fluvoxamine following an inpatient treatment program resulted in an attenuated relapse rate compared with treatment with placebo.20 For further information on use of antidepressants in the treatment of bulimia nervosa, see Bulimia Nervosa under Uses: Eating Disorders, in Fluoxetine Hydrochloride 28:16.04.20.
Administration
Fluvoxamine maleate is administered orally either as immediate-release tablets or extended-release capsules.1,5,50,62 Since food does not appear to substantially affect GI absorption of fluvoxamine maleate from either formulation, the drug generally can be administered without regard to meals.1,17,50,62
Fluvoxamine maleate immediate-release tablets are administered orally once or twice daily.1,5,7,50 Dosages of 100 mg daily or less in adults or 50 mg daily or less in pediatric patients generally are given as a single daily dose at bedtime; higher dosages generally are given as 2 divided doses, either as equally divided doses or as unequal doses with the larger dose given at bedtime.1,5,50
Fluvoxamine maleate extended-release capsules are administered once daily at bedtime.62 The extended-release capsules should not be crushed or chewed.62
Because withdrawal effects may occur with discontinuance of selective serotonin-reuptake inhibitors (SSRIs), including fluvoxamine, and selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), abrupt discontinuance of these drugs should be avoided whenever possible.50,62 When fluvoxamine therapy is discontinued, the dosage should be reduced gradually and the patient monitored for possible withdrawal symptoms.50,62 If intolerable symptoms occur following a dosage reduction or upon discontinuance of therapy, the drug may be reinstituted at the previously prescribed dosage.50,62 Subsequently, the clinician may continue decreasing the dosage, but at a more gradual rate.50,62
Patients receiving fluvoxamine should be monitored for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment.23,24,25 (See Worsening of Depression and Suicidality Risk Precautions under Dosage and Administration: Dosage.)
Fluvoxamine should not be used concomitantly with thioridazine.1,22,26,50,62 In addition, fluvoxamine should not be used concurrently with alosetron, astemizole (no longer commercially available in the US), monoamine oxidase (MAO) inhibitors, pimozide, ramelteon, terfenadine (no longer commercially available in the US), or tizanidine.1,34,35,36,42,50,62 For additional information on potentially serious drug interactions that may occur between selective serotonin-reuptake inhibitors such as fluvoxamine and these agents, see Drug Interactions in Fluoxetine Hydrochloride 28:16.04.20.
Dosage
Obsessive-Compulsive Disorder
Adult Dosage
For the management of obsessive-compulsive disorder in adults, the recommended initial dosage of fluvoxamine maleate immediate-release tablets is 50 mg given as a single daily dose at bedtime.1,50 The dosage may be increased in increments of 50 mg daily at intervals of 4-7 days, as tolerated, to maximum therapeutic benefit up to a maximum dosage of 300 mg daily.1,50 Total daily doses exceeding 100 mg should be given in 2 divided doses.1,5,50 While a relationship between dosage and therapeutic effect in obsessive-compulsive disorder has not been established, efficacy of fluvoxamine maleate immediate-release tablets was demonstrated in clinical trials employing dosages of 100-300 mg daily.1
For the management of obsessive-compulsive disorder in adults, the recommended initial dosage of fluvoxamine maleate extended-release capsules is 100 mg given as a single daily dose at bedtime.62 The dosage may be increased in increments of 50 mg daily at weekly intervals, as tolerated, to maximum therapeutic benefit up to a maximum dosage of 300 mg daily.62 In the main clinical trial establishing efficacy of the extended-release capsules, the mean daily dosage was 261 mg at the end of the study.62
Because fluvoxamine clearance may be reduced in geriatric patients and/or such patients may have increased sensitivity to the adverse effects of CNS-active drugs, fluvoxamine maleate therapy may be initiated with a lower initial dosage of the immediate-release tablets (i.e., 25 mg daily)19 or an initial dosage of 100 mg daily of the extended-release capsules; subsequent slow dosage titration may be appropriate.1,50,62
Although the optimum duration of fluvoxamine therapy has not been established, obsessive-compulsive disorder requires several months or longer of sustained drug therapy.50,62 If therapy with the drug is prolonged, the lowest possible dosage should be employed and the need for continued therapy should be reassessed periodically.50,62
Pediatric Dosage
For the management of obsessive-compulsive disorder in pediatric patients 8-17 years of age, the recommended initial dosage of fluvoxamine maleate given as immediate-release tablets is 25 mg at bedtime.1,50 This dosage may be increased in increments of 25 mg every 4-7 days, as tolerated, until maximum therapeutic benefit is achieved.1,50 Total daily dosages exceeding 50 mg should be given in 2 divided doses.1,5,50 In one clinical study, immediate-release fluvoxamine maleate dosages for pediatric patients 8-17 years of age were titrated within a range of 50-200 mg daily.1,21,50 However, in a multiple-dose, pharmacokinetic study, steady-state plasma fluvoxamine concentrations were found to be twofold to threefold higher in children 6-11 years of age than in adolescents 12-17 years of age, and the area under the plasma concentration-time curve (AUC) and peak plasma concentrations were 1.5-2.7 times higher in children than in adolescents. 1,37 Both children and adolescents exhibited nonlinear pharmacokinetics, and female children exhibited higher AUC values and peak plasma concentrations compared with male children.1,37,50 Steady-state plasma concentrations were similar in adults and adolescents receiving 300 mg of fluvoxamine maleate daily, suggesting that fluvoxamine maleate exposure was similar in these two groups.1,37,50 Clinicians should consider both age and gender differences when selecting a fluvoxamine dosage in pediatric patients.1,37 The maximum dosage of fluvoxamine maleate in children up to 11 years of age should not exceed 200 mg daily, and therapeutic effects of the drug in female children may be achieved with a lower dosage than in male children.1,37,50 In adolescents, fluvoxamine maleate dosage adjustment up to the maximum daily dosage of 300 mg daily used in adults may be necessary to achieve optimal therapeutic benefit.1,37,50
Clinicians should consider that the lowest available dose (i.e., 100 mg) of fluvoxamine maleate extended-release capsules may not be appropriate for pediatric patients who have not previously received fluvoxamine.62
Although the optimum duration of fluvoxamine therapy has not been established, obsessive-compulsive disorder requires several months or longer of sustained drug therapy.50,62 If therapy with the drug is prolonged, the lowest possible dosage should be employed and the need for continued therapy should be reassessed periodically.50,62 (See Pediatric Precautions under Dosage and Administration: Dosage.)
Worsening of Depression and Suicidality Risk Precautions
Worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior may occur in both adult and pediatric (see Pediatric Precautions under Dosage and Administration: Dosage) patients with major depressive disorder or other psychiatric disorders, whether or not they are taking antidepressants.23,24,25,45 This risk may persist until clinically important remission occurs.23 Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.23,24,25 However, there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.23 Pooled analyses of short-term, placebo-controlled studies of antidepressants (i.e., selective serotonin-reuptake inhibitors and other antidepressants) have shown an increased risk of suicidality in children, adolescents, and young adults (18-24 years of age) with major depressive disorder and other psychiatric disorders.23,24 An increased suicidality risk was not demonstrated with antidepressants compared with placebo in adults older than 24 years of age, and a reduced risk was observed in adults 65 years of age or older.23,24
The US Food and Drug Administration (FDA) recommends that all patients being treated with antidepressants for any indication be appropriately monitored and closely observed for clinical worsening, suicidality, and unusual changes in behavior, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.23,24,25 Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be advised to monitor patients on a daily basis for the emergence of agitation, irritability, or unusual changes in behavior, as well as the emergence of suicidality, and to report such symptoms immediately to a health-care provider.23,25,47
Although a causal relationship between the emergence of symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.1,23,25 Consequently, consideration should be given to changing the therapeutic regimen or discontinuing therapy in patients whose depression is persistently worse or in patients experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if such manifestations are severe, abrupt in onset, or were not part of the patient's presenting symptoms.23 If a decision is made to discontinue therapy, fluvoxamine dosage should be tapered as rapidly as is feasible but with recognition of the risks of abrupt discontinuance.23 FDA also recommends that the drugs be prescribed in the smallest quantity consistent with good patient management, in order to reduce the risk of overdosage.23
Bipolar Disorder Precautions
It is generally believed (though not established in controlled trials) that treating a major depressive episode with an antidepressant alone may increase the likelihood of precipitating a mixed or manic episode in patients at risk for bipolar disorder.23 Therefore, patients should be adequately screened for bipolar disorder prior to initiating treatment with an antidepressant; such screening should include a detailed psychiatric history (e.g., family history of suicide, bipolar disorder, and depression).23 Fluvoxamine is not approved for use in treating bipolar depression.23
Pediatric Precautions
Safety and efficacy of fluvoxamine for the treatment of obsessive-compulsive disorder in children younger than 8 years of age have not been established.22,50,62 In addition, the safety and efficacy of fluvoxamine in the management of pediatric patients with conditions other than obsessive-compulsive disorder have not been established.1,50,62
The safety and efficacy of immediate-release fluvoxamine in pediatric patients with obsessive-compulsive disorder were established in a 10-week, placebo-controlled trial in children and adolescents 8-17 years of age.1,21,50,62 The majority of these patients continued receiving fluvoxamine therapy for up to 1-3 years longer in an open-label extension of the initial study.1,50,62 Adverse effects generally were similar to those reported in adults.1,21,50,62 Agitation, depression, dysmenorrhea, flatulence, hyperkinesia, and rash were reported in at least 5% of the pediatric patients and with an incidence at least twice that reported with placebo.1,50 In addition, increased cough, dysmenorrhea, ecchymosis, emotional lability, epistaxis, hyperkinesia, manic reaction, rash, sinusitis, and weight loss were reported in 2 or more of the 57 pediatric patients receiving fluvoxamine and more frequently than among the patients receiving placebo.50,62 Extended-release capsules of the drug have not been systematically evaluated in pediatric patients.62
The risks, if any, that may be associated with extended use of fluvoxamine in children and adolescents with obsessive-compulsive disorder have not been systematically evaluated.1,50,62 The evidence relied upon to conclude that fluvoxamine is safe for use in children and adolescents was derived from relatively short-term clinical studies and from extrapolation of experience gained with adult patients.1,50,62 In addition, the effects of long-term fluvoxamine use on the growth, cognitive behavioral development, and maturation of children and adolescents have not been established.1,50,62 Because decreased appetite and weight loss have been observed with the use of SSRIs, regular monitoring of weight and growth is recommended in children and adolescents receiving long-term fluvoxamine therapy.1,50,62
FDA has determined that antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder and other psychiatric disorders.23,24 However, FDA also states that depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.23,25,45 (See Cautions: Pediatric Precautions, in Fluoxetine Hydrochloride 28:16.04.20.) Anyone considering the use of fluvoxamine in a child or adolescent for any clinical use must therefore balance the potential risks with the clinical need.23,25 (See Worsening of Depression and Suicidality Risk Precautions under Dosage and Administration: Dosage.)
Risk of Serotonin Syndrome or Neuroleptic Malignant Syndrome-like Reactions
Potentially life-threatening serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions have been reported with SSRIs, including fluvoxamine, and selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs) alone, but particularly with concurrent use of other serotonergic drugs (including serotonin [5-hydroxytryptamine; 5-HT] type 1 receptor agonists [triptans]), drugs that impair the metabolism of serotonin (e.g., MAO inhibitors), or antipsychotics or other dopamine antagonists.43,49,50,62
Serious (sometimes fatal) adverse reactions, possibly related to serotonin syndrome or NMS, have been reported in patients who received an MAO inhibitor during or after serotonin-reuptake inhibitor therapy.50,62 Therefore, concomitant use of fluvoxamine and MAO inhibitors is contraindicated , and at least 2 weeks should elapse between discontinuance of an MAO inhibitor and initiation of fluvoxamine and vice versa.50,62
If concurrent therapy with fluvoxamine and a 5-HT1 receptor agonist (triptan) is clinically warranted, the patient should be observed carefully, particularly during initiation of therapy, when dosage is increased, or when another serotonergic agent is initiated.43,50,62 Concurrent use of fluvoxamine and serotonin precursors (e.g., tryptophan) is not recommended.50,62
If signs and symptoms of serotonin syndrome or NMS develop during fluvoxamine therapy, treatment with fluvoxamine and any concurrently administered serotonergic or antidopaminergic agents, including antipsychotic agents, should be discontinued immediately and supportive and symptomatic treatment should be initiated.49,50,62
For additional information on serotonin syndrome, see Drug Interactions: Serotonergic Drugs, in Fluoxetine Hydrochloride 28:16.04.20.
Other Considerations
Concomitant use of fluvoxamine is contraindicated in patients receiving astemizole (no longer commercially available in the US), pimozide, terfenadine (no longer commercially available in the US), thioridazine, and tizanidine, since fluvoxamine may inhibit metabolism of these drugs and increase the potential for serious adverse cardiac effects.1,50,62
Fluvoxamine inhibits cytochrome P-450 (CYP) isoenzymes 1A2, 2C9, 3A4, and 2C19; in vitro data suggest that the drug is a relatively weak inhibitor of CYP2D6.50 A clinically significant fluvoxamine interaction is possible with drugs having a narrow therapeutic ratio (e.g., pimozide, warfarin, theophylline, certain benzodiazepines, omeprazole, phenytoin).50
Since mean AUCs of alosetron were increased approximately sixfold and the elimination half-life was increased approximately threefold during concurrent fluvoxamine administration in one pharmacokinetic study, concurrent use of these drugs is contraindicated.1,34
In a limited number of male patients with schizophrenia, concomitant use of thioridazine and low-dosage fluvoxamine (25 mg twice daily for 1 week) resulted in a threefold increase in plasma concentrations of thioridazine and its two active metabolites (mesoridazine and sulforidazine).1,26 Thioridazine produces a dose-related prolongation of the QTc interval, which is associated with serious ventricular arrhythmias (e.g., torsades de pointes) and sudden death. 1 The possible effects of combining higher dosages of thioridazine and/or fluvoxamine are not yet known, but may be even more pronounced. 1 Therefore, concurrent administration of fluvoxamine and thioridazine is contraindicated.1
In a limited number of healthy individuals, concurrent administration of fluvoxamine (100 mg daily for 4 days) and tizanidine (single 4-mg dose) resulted in a 12-fold increase in peak plasma tizanidine concentrations, a threefold increase in elimination half-life of tizanidine, and a 33-fold increase in the AUC of tizanidine.1,35,42 The mean cardiovascular effects observed in this study were a decrease in systolic blood pressure of 35 mm Hg, a decrease in diastolic blood pressure of 20 mm Hg, and a decrease in heart rate of 4 beats/minute.1,35 In addition, drowsiness was substantially increased and psychomotor performance was substantially impaired during concurrent therapy.1,35 Since fluvoxamine has been shown to markedly affect the pharmacokinetics of tizanidine and to increase the risk of adverse cardiovascular (including substantial hypotension) and CNS (e.g., drowsiness, psychomotor impairment) effects associated with tizanidine use,1,35,42 concomitant use of tizanidine and fluvoxamine is contraindicated.1,35,36,42
Concomitant use of fluvoxamine (100 mg twice daily for 3 days) and ramelteon (single 16-mg dose) resulted in approximately a 190-fold increase in the ramelteon AUC and approximately a 70-fold increase in peak ramelteon concentrations compared with ramelteon administered alone.50,62,63 Concurrent use of fluvoxamine and ramelteon is contraindicated.62
Caution should be exercised if fluvoxamine is used concomitantly with benzodiazepines that are metabolized by hepatic oxidation (e.g., alprazolam, midazolam, triazolam).1 Concomitant use of diazepam and fluvoxamine generally should be avoided.1 The clearance of diazepam was reduced by 65% and that of its active metabolite N -desmethyldiazepam could not be determined during concomitant administration with fluvoxamine in one study.1 Concomitant use of fluvoxamine (100 mg daily) and alprazolam (1 mg 4 times daily) resulted in plasma alprazolam concentrations that were approximately twice those observed when alprazolam was administered alone.1 The initial dosage of alprazolam should be reduced by at least 50% if the drugs are administered concomitantly, with subsequent alprazolam dosages titrated to the lowest effective dosa modification of fluvoxamine maleate dosage is not necessary.1 The clearance of benzodiazepines that are metabolized by glucuronidation (e.g., lorazepam, oxazepam, temazepam) is unlikely to be affected by fluvoxamine.1
Fluvoxamine (50 mg twice daily for 7 days) reduced the clearance of mexiletine (administered as a single dose of 200 mg) by 38% in a limited number of healthy Japanese males in one pharmacokinetic study.1,38 Pending further accumulation of data, close patient monitoring and monitoring of serum mexiletine concentrations are recommended when fluvoxamine and mexiletine are given concurrently.1,38
Since fluvoxamine coadministration decreased theophylline clearance by approximately threefold, the theophylline dosage should be reduced to approximately one-third of the usual daily maintenance dosage and plasma theophylline concentrations should be monitored if the drugs are administered concomitantly.1
Epidemiologic case-control and cohort design studies that have demonstrated an association between selective serotonin-reuptake inhibitor therapy and an increased risk of upper GI bleeding also have shown that concurrent use of aspirin or other nonsteroidal anti-inflammatory agents substantially increases the risk of GI bleeding.1,39,41 Although these studies focused on upper GI bleeding, there is some evidence suggesting that bleeding at other sites may be similarly potentiated.1 The precise mechanism for this increased risk remains to be clearly established; however, serotonin release by platelets is known to play an important role in hemostasis, and SSRIs decrease serotonin uptake from the blood by platelets, thereby decreasing the amount of serotonin in platelets.1,40,41 Patients receiving fluvoxamine should be cautioned about the concomitant use of drugs that interfere with hemostasis, including aspirin and other nonsteroidal anti-inflammatory agents.1
Patients receiving fluvoxamine concomitantly with oral anticoagulants (e.g., warfarin) should have close monitoring of prothrombin times and adjustment of their anticoagulant dosage if indicated.1 Prothrombin times were prolonged and plasma warfarin concentrations were increased when the drug was administered concomitantly with fluvoxamine.1
Dosage in Renal and Hepatic Impairment
Because patients with hepatic impairment have reduced fluvoxamine clearance, reduction of the initial dosage of the immediate-release tablets and modification of subsequent dosage titration may be appropriate; subsequent dosage adjustments generally should be made in smaller increments and at longer intervals in such patients.1,19,50 In patients with hepatic impairment receiving the extended-release capsules, an initial dosage of 100 mg daily and subsequent slow dosage titration may be appropriate.62
Limited evidence indicates that dosage modification is not necessary in patients with renal impairment.1,18,19,50,62
Treatment of Pregnant Women during the Third Trimester
Some neonates exposed to fluvoxamine and other SSRIs or SNRIs late in the third trimester of pregnancy have developed complications, which have sometimes been severe and required prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care in special-care nurseries.1,27,28,29,30,31,32,33,50,62 Therefore, the clinician should carefully consider the potential risks and benefits of treating a pregnant woman with fluvoxamine during the third trimester of pregnancy.1,28,29,30,33,50,62 In addition, consideration may be given to cautiously tapering fluvoxamine therapy in the third trimester prior to delivery if the drug is administered during pregnancy.1,30 For additional information on use of SSRIs during pregnancy, see Pregnancy, under Cautions: Pregnancy, Fertility, and Lactation, in Fluoxetine Hydrochloride 28:16.04.20.
1. Barr Laboratories, Inc. Fluvoxamine maleate tablets prescribing information. Pomona, NY; 2005 Jan.
2. Anon. Fluvoxamine for obsessive-compulsive disorder. Med Lett Drug Ther . 1905; 37:13-6.
3. Wilde MI, Plosker GL, Benfield P. Fluvoxamine: an updated review of its pharmacology, and therapeutic use in depressive illness. Drugs . 1993; 45:895-24. [PubMed 7691497]
4. Palmer KJ, Benfield P. Fluvoxamine: an overview of its pharmacological properties and review of its therapeutic potential in non-depressive disorders. CNS Drugs . 1994; 1: 57-87.
5. Solvay Pharmaceuticals. Luvox® (fluvoxamine maleate) tablets product monograph. Marietta, GA; 1993 Dec.
6. Richelson E. Pharmacology of antidepressants-characteristics of the ideal drug. Mayo Clin Proc . 1994; 69:1069-81. [PubMed 7967761]
7. Perse TL, Greist JH, Jefferson JW et al. Fluvoxamine treatment of obsessive-compulsive disorder. Am J Psych . 1987; 144:1543-8.
8. Montgomery SA, Manceaux A. Fluvoxamine in the treatment of obsessive compulsive disorder. Int Clin Psychopharmacol . 1992; 7:5-9. [PubMed 1355499]
9. Jenike JA, Hyman S, Baer L et al. A controlled trial of fluvoxamine in obsessive-compulsive disorder: implications for a serotonergic theory. Am J Psych . 1990; 147:1209-15.
10. Price LH, Goodman WK, Charney DS et al. Treatment of severe obsessive-compulsive disorder with fluvoxamine. Am J Psych . 1987; 144:1059-61.
11. Goodman WK, Price LH, Delgado PL et al. Specificity of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder. Arch Gen Psych . 1990; 47:577-85.
12. Goodman WK, Price LH, Rasmussen SA et al. Efficacy of fluvoxamine in obsessive-compulsive disorder. Arch Gen Psych . 1989; 48:36-44.
13. Freeman CPL, Trimble MR, Deakin JFW et al. Fluvoxamine versus clomipramine in the treatment of obsessive compulsive disorder: a multicenter, randomized, double-blind, parallel group comparison. J Clin Psych . 1994; 55:301-5.
14. Greist JH, Jefferson JW, Kobalt KA et al. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. Arch Gen Psych . 1995; 52:53-60.
15. Edwards JG, Inman WHW, Wilton L et al. Prescription-event monitoring of 10401 patients treated with fluvoxamine. Br J Psych . 1994; 164:387-95.
16. Jefferson JW, Greist JH, Perse TL et al. Fluvoxamine-associated mania/hypomania in patients with obsessive-compulsive disorder. J Clin Psychopharmacol . 1991; 11:391. [PubMed 1770160]
17. Van Den Brekel A, Harrington L. Toxic effects of theophylline caused by fluvoxamine. CMAJ . 1994; 151:1289-90. [PubMedCentral][PubMed 7954177]
18. Van Harten J. Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clin Pharmacokinet . 1993; 24:203-20. [PubMed 8384945]
19. American Psychiatric Association. Practice guideline for the treatment of patients with eating disorders (revision). Am J Psychiatry . 2000; 157(Suppl 1):1-39.
20. Fichter MM, Kruger R, Rief W et al. Fluvoxamine in prevention of relapse in bulimia nervosa: effects on eating-specific psychopathology. J Clin Psychopharmacol . 1996; 16:9-18. [PubMed 8834413]
21. Riddle MA, Reeve EA, Yaryura JA et al. Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial. J Am Acad Child Adolesc Psychiatry . 2001; 40:222-9. [PubMed 11211371]
22. Apotex Corporation. Fluvoxamine maleate tablets prescribing information. Weston, FL; 2001 Jan.
23. Food and Drug Administration. Antidepressant use in children, adolescents, and adults: class revisions to product labeling. Rockville, MD; 2007 May 2. From the FDA web site. [Web]
24. Food and Drug Administration. FDA news: FDA proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications. Rockville, MD; 2007 May 2. From the FDA web site. [Web]
25. Food and Drug Administration. Revisions to medication guide: antidepressant medicines, depression and other serious mental illnesses and suicidal thoughts or actions. Rockville, MD; 2007 May 2. From the FDA web site. [Web]
26. Carrillo JA, Ramos SI, Herraiz AG et al. Pharmacokinetic interaction of fluvoxamine and thioridazine in schizophrenic patients. J Clin Psychopharmacol . 1999; 19:494-9. [PubMed 10587283]
27. Morag I, Batash D, Keidar R et al. Paroxetine use throughout pregnancy: does it pose any risk to the neonate? J Toxicol Clin Toxicol . 2004; 42:97-100.
28. Haddad PM, Pal BR, Clarke P et al. Neonatal symptoms following maternal paroxetine treatment: serotonin toxicity or paroxetine discontinuation syndrome? J Psychopharmacol . 2005; 19:554-7.
29. Moses-Kolko EL, Bogen D, Perel J et al. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA . 2005; 293:2372-85. [PubMed 15900008]
30. Sanz EJ, De-Las-Cuevas C, Kiuru A et al. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet . 2005; 365:482-7. [PubMed 15705457]
31. Nordeng H, Lindemann R, Perminov KV et al. Neonatal withdrawal syndrome after in utero exposure to selective serotonin-reuptake inhibitors. Acta Paediatr . 2001; 90:288-91. [PubMed 11332169]
32. Dahl ML, Olhager E, Ahlner J. Paroxetine withdrawal syndrome in a neonate. Br J Psychiatr . 1997; 171:391-2.
33. Anon. Neonatal complications after intrauterine exposure to SSRI antidepressants. Prescrire Int . 2004;13:103-4.
34. GlaxoSmithKline. Lotronex® (alosetron hydrochloride) tablets prescribing information. Research Triangle Park, NC; 2005 Feb.
35. Granfors MT, Backman JT, Neuvonen M et al. Fluvoxamine drastically increases concentrations and effects of tizanidine: a potentially hazardous interaction. Clin Pharmacol Ther . 2004; 75:331-41. [PubMed 15060511]
36. Momo K, Doki K, Hosono H et al. Drug interaction of tizanidine and fluvoxamine. Clin Pharmacol Ther . 2004; 76:509-10. [PubMed 15536467]
37. Labellarte M, Biederman J, Emslie G et al. Multiple-dose pharmacokinetics of fluvoxamine in children and adolescents. J Am Acad Child Adolesc Psychiatry . 2004; 43:1497-505. [PubMed 15564819]
38. Kusumoto M, Ueno K, Oda A et al. Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men. Clin Pharmacol Ther . 2001; 69:104-7. [PubMed 11240973]
39. Dalton SO, Johansen C, Mellemkjaer L et al. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med . 2003; 163:59-64. [PubMed 12523917]
40. van Walraven C, Mamdani MM, Wells PS et al. Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ . 2001; 323:655-8. [PubMedCentral][PubMed 11566827]
41. de Abajo FJ, Rodriguez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ . 1999; 319:1106-9. [PubMedCentral][PubMed 10531103]
42. Acorda Therapeutics, Inc. Zanaflex® (tizanidine hydrochloride) tablets and capsules prescribing information. Hawthorne, NY; 2005 Apr 2.
43. Food and Drug Administration. Public health advisory: combined use of 5-hydroxytryptamine receptor agonists (triptans), selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs) may result in life-threatening serotonin syndrome. Rockville, MD; 2006 Jul 19. From the FDA website. [Web]
44. Eli Lilly and Company. Prozac® (fluoxetine capsules, USP and fluoxetine oral solution USP) prescribing information. Indianapolis, IN: 2006 Aug 9.
45. Bridge JA, Iyengar S, Salary CB. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA . 2007; 297:1683-96. [PubMed 17440145]
46. Forest Pharmaceuticals, Inc. Lexapro® (escitalopram oxalate) tablets/oral solution prescribing information. St. Louis, MO; 2007 May.
47. Pfizer Roerig. Zoloft® (sertraline hydrochloride) tablets and oral concentrate prescribing information. New York; 2007 Jul.
48. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med . 2005; 352:1112-20. [PubMed 15784664]
49. Kaufman KR, Levitt MJ, Schlitz JF et al. Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis. Ann Clin Psychiatry . 2006 Jul-Sep; 18:201-4.
50. ANI Pharmaceuticals, Inc. Fluvoxamine maleate tablets prescribing information. Baudette, MN; 2011 Mar.
51. US Food and Drug Administration. Drug Safety Communication: Serious CNS reactions possible when methylene blue is given to patients taking certain psychiatric medications. 2011 Jul 26. From FDA website. [Web]
52. US Food and Drug Administration. Drug Safety Communication: Updated information about the drug interaction between methylene blue (methylthioninium chloride) and serotonergic psychiatric medications. 2011 Oct 20. From FDA website. [Web]
53. US Food and Drug Administration. Drug Safety Communication: Serious CNS reactions possible when linezolid (Zyvox) is given to patients taking certain psychiatric medications. 2011 Jul 26. From FDA website. [Web]
54. US Food and Drug Administration. Drug Safety Communication: Updated information about the drug interaction between linezolid (Zyvox®) and serotonergic psychiatric medications. 2011 Oct 20. From FDA website. [Web]
55. Clark DB, Andrus MR, Byrd DC. Drug interactions between linezolid and selective serotonin reuptake inhibitors: case report involving sertraline and review of the literature. Pharmacotherapy . 2006; 26:269-76. [PubMed 16466332]
56. Pfizer. Zyvox® (linezolid) injection, tablets, and for oral suspension prescribing information. New York, NY: 2008 Jul.
57. Steinberg M, Morin AK. Mild serotonin syndrome associated with concurrent linezolid and fluoxetine. Am J Health-Syst Pharm . 2007; 264:59-62.
58. Taylor JJ, Wilson JW, Estes LL et al. Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis . 2006; 43:180-7. [PubMed 16779744]
59. Sola CL, Bostwick JM, Hart DA et al. Anticipating linezolid-SSRI interactions in the general hospital setting: an MAOI in disguise. Mayo Clin Proc . 2006; 81:330-4. [PubMed 16529136]
60. Hachem RY, Hicks K, Huen A et al. Myelosuppression and serotonin syndrome associated with concurrent use of linezolid and selective serotonin reuptake inhibitors in bone marrow transplant recipients. Clin Infect Dis . 2003; 37:e8-11. [PubMedCentral][PubMed 12830431]
61. Gabriel A. Serotonin reuptake inhibitor and fluvoxamine-induced severe hyponatremia in a 49-year-old man. Case Report Med . 2009; 2009:585193.
62. Jazz Pharmaceuticals, Inc. Luvox CR® (fluvoxamine maleate) extended-release capsules prescribing information. Palo Alto, CA; 2011 Jun.
63. Obach RS, Ryder TF. Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. Drug Metab Dispos . 2010; 38:1381-91. [PubMed 20478852]
64. Hollander E, Koran LM, Goodman WK et al. A double-blind, placebo-controlled study of the efficacy and safety of controlled-release fluvoxamine in patients with obsessive-compulsive disorder. J Clin Psychiatry . 2003; 64:640-7. [PubMed 12823077]
65. Hägg S, Granberg K, Carleborg L. Excretion of fluvoxamine into breast milk. Br J Clin Pharmacol . 2000; 49:286-8. [PubMedCentral][PubMed 10718788]
600. US Food and Drug Administration. FDA drug safety communication: Selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and reports of a rare heart and lung condition in newborn babies. 2011 Dec 14. From the FDA website. [Web]
602. Chambers CD, Hernandez-Diaz S, Van Marter LJ et al. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New Engl J Med . 2006; 354:579-87. [PubMed 16467545]
603. Källén B, Olausson PO. Maternal use of selective serotonin re-uptake inhibitors and persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf . 2008; 17:801-6. [PubMed 18314924]
604. Wichman CL, Moore KM, Lang TR et al. Congenital heart disease associated with selective serotonin reuptake inhibitor use during pregnancy. Mayo Clin Proc . 2009; 84:23-7. [PubMedCentral][PubMed 19121250]
605. Andrade SE, McPhillips H, Loren D et al. Antidepressant medication use and risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf . 2009; 18:246-52. [PubMed 19148882]
606. Wilson KL, Zelig CM, Harvey JP et al. Persistent pulmonary hypertension of the newborn is associated with mode of delivery and not with maternal use of selective serotonin reuptake inhibitors. Am J Perinatol . 2011; 28:19-24. [PubMed 20607643]
607. US Food and Drug Administration. Public health advisory: treatment challenges of depression in pregnancy and the possibility of persistent pulmonary hypertension in newborns. Rockville, MD; 2006 Jul 19. From the FDA website. [Web]
608. Yonkers KA, Wisner KL, Stewart DE et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol . 2009; 114:703-13. [Web][PubMedCentral][PubMed 19701065]
609. Cohen LS, Altshuler LL, Harlow BL et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA . 2006; 295:499-507. [PubMed 16449615]
610. Kieler H, Artama M, Engeland A et al. Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries. Br Med J . 2012; 344:d8012.