Drugs

, Volume 46, Issue 5, pp 895–924

Fluvoxamine

An Updated Review of its Pharmacology, and Therapeutic Use in Depressive Illness
  • Michelle I. Wilde
  • Greg L. Plosker
  • Paul Benfield
Drug Evaluation

Abstract

Synopsis

Fluvoxamine facilitates serotoninergic neurotransmission via potent and selective inhibition of serotonin (5-hydroxytryptamine; 5-HT) reuptake into presynaptic neurones.

The overall antidepressant efficacy of fluvoxamine 100 to 300 mg/day for 4 to 6 weeks in once daily or divided dosage regimens appears to be at least comparable to that of imipramine and similar to that of clomipramine, dothiepin, desipramine, amitriptyline, lofepramine, maprotiline, mianserin and moclobemide. The efficacy of fluvoxamine has been maintained for up to 1 year, but long term data are limited, and there are no comparative studies of fluvoxamine with other selective serotonin reuptake inhibitors. In some studies, fluvoxamine appeared to have an earlier beneficial effect on suicidal ideation and/or anxiety or somatic complaints compared with imipramine, dothiepin and maprotiline.

Gastrointestinal adverse effects, especially nausea, are commonly reported with fluvoxamine but are generally mild to moderate in severity. The tolerability profile of fluvoxamine appears to be more favourable than that of tricyclic antidepressants in terms of cardiotoxic and anticholinergic adverse effects, sedation, weight gain and death from overdosage.

Thus, fluvoxamine is an effective and well tolerated antidepressant agent that is becoming established as an alternative to older agents in patients with mild, moderate or severe depression. Fluvoxamine may be particularly beneficial in potentially suicidal patients with severe depression, in those with an underlying compulsive personality or cardiovascular disorder, in patients with coexistent anxiety or agitation, and in the elderly.

Pharmacodynamic Properties

In vitro and in vivo studies in animals and humans have demonstrated that fluvoxamine facilitates serotoninergic neurotransmission by potent and specific inhibition of presynaptic neuronal reuptake of serotonin (5-hydroxytryptamine; 5-HT). Single-dose administration of fluvoxamine significantly reduced serotonin turnover in rat brain, and histochemical studies demonstrated that fluvoxamine increases extraneuronal concentrations of serotonin in the raphé nucleus and frontal cortex, and decreases intraneuronal concentrations of serotonin in the raphé nucleus. In contrast, fluvoxamine generally has no effect on noradrenergic and dopaminergic mechanisms. In vitro radioligand binding studies have demonstrated that fluvoxamine, like other selective serotonin reuptake inhibitors, has little or no affinity for α1, α2, β, dopamine D2, histamine H1, 5-HT1, 5-HT2 or muscarinic receptors. Fluvoxamine does not appear to inhibit monoamine oxidase.

Studies in animals and humans have shown relatively few cardiovascular effects with fluvoxamine, and suggest that it is less likely to produce adverse cardiovascular effects than tricyclic antidepressants. Trials in healthy human volunteers have confirmed the results of in vitro and in vivo studies in animals which suggested that fluvoxamine is unlikely to cause anticholinergic effects. In contrast with other antidepressant agents such as tricyclic antidepressants, mianserin and maprotiline, fluvoxamine did not exhibit pro-convulsive effects in animal models of epilepsy, except at very high doses (⩾ 100 mg/kg intraperitoneally). Electroencephalographic and psychometric tests in healthy humans suggest that fluvoxamine is less sedating than imipramine or mianserin.

Pharmacokinetic Properties

Fluvoxamine is well absorbed following oral administration to healthy volunteers, and peak plasma concentrations are achieved within approximately 2 to 8 hours. Food does not significantly affect the rate or extent of absorption. Mean elimination half-life (t½) is approximately 19 and 22 hours after single and multiple doses, respectively, and is not significantly increased in the elderly. Fluvoxamine undergoes extensive hepatic metabolism to at least 11 metabolites; however, none of these is likely to possess psychotropic activity. More than 90% of a dose is eliminated in the urine as metabolites, with ⩽ 4% of a dose eliminated in the urine as unchanged drug. Increases in mean area under the plasma concentration-time curve and t½ values (by up to 64%) were noted in patients with biopsy-proven liver cirrhosis compared with healthy volunteers receiving singledose fluvoxamine, suggesting the need for dosage adjustment in patients with hepatic impairment. Pharmacokinetic parameters of fluvoxamine in the elderly appear similar to those in younger volunteers, although data are limited.

Therapeutic Efficacy

Results from several double-blind comparative trials indicate that fluvoxamine 100 to 300 mg/day is at least as effective as imipramine in patients with mainly moderate to severe major depression. Hamilton Depression Rating Scale (HDRS) scores were reduced by 28 to 75% (mean 37.6%) with fluvoxamine, by 28 to 55% (mean 39%) with imipramine and by 6 to 37% (mean 27%) with placebo after 4 to 6 weeks’ treatment. Corresponding reductions in Clinical Global Impression (CGI) scores were 29 to 68%, 23 to 52% and 21 to 28.5%. The therapeutic efficacy of fluvoxamine appears to be similar to that of clomipramine, dothiepin, desipramine, lofepramine, amitriptyline, maprotiline, mianserin and moclobemide. Although improvements in HDRS, CGI and Montgomery-Åsberg Depression Rating Scale scores with fluvoxamine have been maintained in the long term (up to 1 year), such data are limited. Results from individual studies should be interpreted with caution because of significant placebo effects (as is common with all antidepressant trials), small numbers of patients and inconsistencies in the demonstration of the known superior efficacy of fluvoxamine and other antidepressant agents over placebo in some studies.

The onset of antidepressant effect with fluvoxamine appears to be similar to that of standard antidepressant agents. However, results from some studies suggest that fluvoxamine may have an earlier beneficial effect on suicidal ideation and/or anxiety or somatic complaints compared with imipramine, dothiepin and maprotiline.

Limited data suggest that fluvoxamine may be more effective in patients with severe rather than mild or moderate depression, and results from 1 study suggest that fluvoxamine may be particularly effective in patients with an underlying compulsive personality. Evidence suggests that the efficacy of fluvoxamine in elderly patients with depressive illness is similar to that in younger patients. Responses to fluvoxamine in patients refractory to standard antidepressants have been reported.

Tolerability

Fluvoxamine in dosages of 50 to 300 mg/day has been generally well tolerated by patients with depressive illness in short (4 to 6 weeks) and long (up to 48 weeks) term clinical trials.

Gastrointestinal disturbances are the most common adverse effects associated with fluvoxamine, with the incidence of nausea ranging from ≈ 16 to 37%. These adverse effects appear to be mild to moderate in severity; the effect of meal times on the incidence of these adverse effects has not been reported. Pooled data from postmarketing surveillance studies involving more than 34 000 patients (most of whom had depression) showed nausea to be the most common adverse effect associated with fluvoxamine therapy (15.7%), followed by somnolence (6.4%) and asthenia (5.1%).

The overall tolerability profile of fluvoxamine appears to be more favourable than that of tricyclic antidepressants, being devoid of clinically significant anticholinergic or cardiotoxic adverse effects, sedation or weight gain.

Overall incidence rates of fluvoxamine-associated adverse effects in the elderly are similar to those in younger patients. However, more elderly than younger patients withdrew from fluvoxamine treatment because of adverse effects.

Although fluvoxamine is thought to have less epileptogenic potential than tricyclic antidepressants, possible fluvoxamine-induced seizures have been reported. There have been no reports of fluvoxamine-associated increases in suicidal ideation or aggressive behaviour. Increases in liver enzyme levels during fluvoxamine treatment have been reported although no other clinically significant changes in laboratory parameters have been observed. Fluvoxamine is relatively safe in overdosage; in over 300 reports of fluvoxamine overdosage (up to 10g), there has been only 1 reported death attributable to fluvoxamine alone.

Dosage and Administration

The effective dosage of fluvoxamine in patients with depression usually varies between 100 and 200 mg/day. The dosage should be adjusted according to individual response, and some patients may require up to 300 mg/day. The minimum effective starting dosage is 100 mg/day administered at night; dosages > 100 mg/day should be given in divided doses. An initial dosage of 50 mg/day for 1 week may minimise nausea.

Reduced dosages are recommended in patients with hepatic or renal insufficiency, and careful laboratory monitoring, particularly during the first month of treatment, is advised. Dosage adjustments appear to be unnecessary in the elderly although fluvoxamine should be titrated slowly during the initial stages of therapy.

Fluvoxamine inhibits cytochrome P450IICg/IA2-mediated N-demethylation of various tricyclic antidepressants but, in contrast with fluoxetine, paroxetine and sertraline, has minimal inhibitory effects on cytochrome P-450IID6-catalysed hydroxylation of these agents. Fluvoxamine should be avoided in patients with a history of epilepsy. Caution is also recommended with the concomitant administration of fluvoxamine and lithium, theophylline or warfarin. Fluvoxamine should not be administered with, or within 2 weeks of, treatment with a monoamine oxidase inhibitor, and a monoamine oxidase inhibitor should not be initiated within 1 week after stopping fluvoxamine therapy.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amin MM, Ananth JV, Coleman BS, Darcourt G, Farkas T, et al. Fluvoxamine: antidepressant effects confirmed in a placebo-controlled international study. Clinical Neuropharmacology & (Suppl. 1): 312–319, 1984Google Scholar
  2. Amore M, Bellini M, Berardi D, Berlinzani L, Cervino G, et al. Double-blind comparison of fluvoxamine and imipramine in depressed patients. Current Therapeutic Research 46: 815–820, 1989Google Scholar
  3. Anon. Fluvoxamine prescribing information, The Netherlands, 1991Google Scholar
  4. Ansseau M, Troisfontaines B, Papart P, von Frenckell R. Compulsive personality as predictor of response to serotoninergic antidepressants. British Medical Journal 303: 760–761, 1991PubMedGoogle Scholar
  5. Baldessarini RJ. Overview of recent advances in antidepressant pharmacology: part II. McLean Hospital Journal 7 (1): 1–27, 1982Google Scholar
  6. Baldwin D, Fineberg N, Montgomery S. Fluoxetine, fluvoxamine and extrapyramidal tract disorders. International Clinical Psychopharmacology 6: 51–58, 1991PubMedGoogle Scholar
  7. Bamrah JS, Benbow SM, McKenna J. Fluvoxamine and liver enzymes. Correspondence. British Journal of Psychiatry 156: 286–287,1990PubMedGoogle Scholar
  8. Banerjee AK. Recovery from prolonged cerebral depression after fluvoxamine overdose. British Medical Journal 296: 1774, 1988PubMedGoogle Scholar
  9. Barrelet L, Blajev B, Bolzani L, de Saussure Ch, Kasas A, et al. Multicenter study comparing efficacy and tolerance of moclobemide and fluvoxamine in in- and outpatients with a severe depressive episode. Schweizerische Rundschau fur Medizin/Praxis 80: 524–528, 1991Google Scholar
  10. Bel N, Artigas F. Chronic treatment with fluvoxamine increases extracellular serotonin in frontal cortex but not in raphe nuclei. Synapse, in press, 1993Google Scholar
  11. Bel N, Artigas F. Fluvoxamine preferentially increases extracellular 5-hydroxytryptamine in the raphe nuclei: an in vivo microdialysis study. European Journal of Pharmacology 229: 101–103, 1992PubMedGoogle Scholar
  12. Benazzi F, Mazzoli M. Polydipsia induced by fluvoxamine. Correspondence. Pharmacopsychiatry 26: 63, 1993Google Scholar
  13. Benfield P, Ward A. Fluvoxamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 32: 313–334, 1986PubMedGoogle Scholar
  14. Bertschy G, Vandel S, Vandel B, Allers G, Volmat R. Fluvoxaminetricyclic antidepressant interaction. European Journal of Clinical Pharmacology 40: 119–120, 1991PubMedGoogle Scholar
  15. Bonnet P, Vandel S, Nezelof S, Sechter D, Bizouard P. Carbamazepine, fluvoxamine. Is there a pharmacokinetic interaction? Therapie 47: 165, 1992PubMedGoogle Scholar
  16. Bougerol T, Uchida C, Gachoud J-P, Köhler M, Mikkelsen H. Efficacy and tolerability of moclobemide compared with fluvoxamine in depressive disorder (DSM-III). Psychopharmacology 106 (Suppl.): 102–108, 1992Google Scholar
  17. Bradford LD. Preclinical pharmacology of fluvoxamine (Floxyfrol). Proceedings of the international symposium on fluvoxamine, Amsterdam, September 8–9, 1983, pp. 13–17, 1984Google Scholar
  18. Brown WA, Arato M, Shrivastava R. Pituitary-adrenocortical hyperfunction and intolerance to fluvoxamine, a selective serotonin uptake inhibitor. American Journal of Psychiatry 143(1): 88–90, 1986PubMedGoogle Scholar
  19. Cassano G, Conti L. Preliminary results: placebo-controlled data on fluvoxamine maleate, a serotonergic antidepressant. Clinical Neuropharmacology 7 (Suppl. 1): S312–319, 1984Google Scholar
  20. Celada P, Dolera M, Alvarez E, Artigas F. Effects of acute and chronic treatment with fluvoxamine on extracellular and platelet serotonin in the blood of major depressive patients. Relationship to clinical improvement. Journal of Affective Disorders 25: 243–250, 1992PubMedGoogle Scholar
  21. Cialdella E. Fluvoxamine in the management of depressive patients. Gazette Medicale 98: 43–47, 1991Google Scholar
  22. Claassen V. Review of the animal pharmacology and pharmacokinetics of fluvoxamine. British Journal of Clinical Pharmacology 15 (Suppl. 3): 349S–355S, 1983PubMedGoogle Scholar
  23. Claassen V, Davies JE, Hertting G, Placheta P. Fluvoxamine, a specific 5-hydroxytryptamine uptake inhibitor. British Journal of Pharmacology 60: 505–516, 1977PubMedGoogle Scholar
  24. Cohn CK, Shrivastava R, Mendels J, Cohn JB, Fabre LF, et al. Double-blind, multicenter comparison of sertraline and amitriptyline in elderly depressed patients. Journal of Clinical Psychiatry 51 (Suppl. B): 28–33, 1990PubMedGoogle Scholar
  25. Coleman BS, Block A. Fluvoxamine maleate, a serotonergic antidepressant; a comparison with chlorimipramine. Progress in Neuro-Psychopharmacology and Biological Psychiatry 6: 475–478,1982PubMedGoogle Scholar
  26. Constantinidis J, Dick P, Tissot R. Antidepressants and serotonin neurons of the raphe. Neuropsychobiology 7: 113–121, 1981PubMedGoogle Scholar
  27. Conti L, Dell’osso L, Re F, Musetti L, Cassano GB. Fluvoxamine maleate: double-blind clinical trial vs placebo in hospitalised depressed patients. Current Therapeutic Research 43:468–480,1988Google Scholar
  28. Corrigan FM. Sodium valproate augmentation of fluoxetine or fluvoxamine effects. Correspondence. Biological Psychiatry 31: 1178–1179, 1992PubMedGoogle Scholar
  29. Crewe HK, Lennard MS, Tucker GT, Woods FR, Haddock RE. The effect of selective serotonin re-uptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. British Journal of Clinical Pharmacology 34: 262–265, 1992PubMedGoogle Scholar
  30. Curran HV, Lader M. The psychopharmacological effects of repeated doses of fluvoxamine, mianserin and placebo in healthy human subjects. European Journal of Clinical Pharmacology 29: 601–607, 1986PubMedGoogle Scholar
  31. Curran HV, Shine P, Lader M. Effects of repeated doses of fluvoxamine, mianserin and placebo on memory and measures of sedation. Psychopharmacology 89: 360–363, 1986PubMedGoogle Scholar
  32. de Jonghe F, Swinkels J, Tuynman-Qua H. Randomized doubleblind study of fluvoxamine and maprotiline in treatment of depression. Pharmacopsychiatry 24: 21–27, 1991PubMedGoogle Scholar
  33. de Jonghe F, Swinkels JA. The safety of antidepressants. Drugs 43 (Suppl. 2): 40–47, 1992PubMedGoogle Scholar
  34. Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, et al. Serotonin function and the mechanism of antidepressant action. Archives of General Psychiatry 47: 411–419, 1990PubMedGoogle Scholar
  35. de Vries MH, Raghoebar M, Mathlener IS, Van Harten J. Single and multiple oral dose fluvoxamine kinetics in young and elderly subjects. Therapeutic Drug Monitoring 14: 493–498, 1992PubMedGoogle Scholar
  36. Deahl M, Trimble M. Serotonin reuptake inhibitors, epilepsy and myoclonus. British Journal of Psychiatry 159: 433–435, 1991PubMedGoogle Scholar
  37. DeBree H, Van der Schoot JB, Post LC. Fluvoxamine maleate; disposition in man. European Journal of Drug Metabolism and Pharmacokinetics 8: 175–179, 1983Google Scholar
  38. Deerling R, Rees-Jones DI, Simmons R, Ashford J. Rising-dose fluvoxamine therapy in depression; an overview of two clinical studies. European Neuropsychopharmacology 2(3): 302, 1992Google Scholar
  39. Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, et al. Serotonin function and the mechanism of antidepressant action. Archives of General Psychiatry 47: 411–418Google Scholar
  40. Delgado PL, Price LH, Charney DS, Heninger GR. Efficacy of fluvoxamine in treatment-refractory depression. Journal of Affective Disorders 15: 55–60, 1988PubMedGoogle Scholar
  41. Demisch K, Demisch L, Bochnik HJ, Nickelsen T, Althoff PH, et al. Melatonin and cortisol increase after fluvoxamine. Correspondence. British Journal of Clinical Pharmacology 22: 620–622, 1986Google Scholar
  42. Demisch L, Gerbaldo H, Demisch K. Fluvoxamine-melatonin-stimulation-tests (FMST) in patients with depressive disorders. Pharmacopsychiatry 21: 420–421, 1988PubMedGoogle Scholar
  43. De Wilde JE, Mertens C, Wakelin JS. Clinical trials of fluvoxamine vs chlorimipramine with single and three times daily dosing. British Journal of Clinical Pharmacology 15 (Suppl): 427–431, 1983Google Scholar
  44. Dick P, Ferrero E. A double-blind comparative study of the clinical efficacy of fluvoxamine and chlorimipramine. British Journal of Clinical Pharmacology 15 (Suppl, 3): 419S–425S, 1983PubMedGoogle Scholar
  45. Diot P, Jonville AP, Gerard F, Bonnelle M, Autret E, et al. Possible interaction entre théophylline et fluvoxamine. Therapie 46: 169–171. 1991Google Scholar
  46. Dresse A, Scuvee-Moreau J. The effects of various antidepressants on the spontaneous firing rates of noradrenergic and serotonergic neurons. Clinical Neuropharmacology 7 (Suppl. 1): S312–319, 1984Google Scholar
  47. Eckardt MJ, Stapleton JM, Rio D, et al. Interactions of fluvoxamine and ethanol in healthy volunteers. Clinical Neuropharmacology 9 (Suppl.) 4: 55–57, 1986Google Scholar
  48. Evans M, Marwick P. Fluvoxamine and lithium: an unusual interaction. Correspondence. British Journal of Psychiatry 156:286,1990PubMedGoogle Scholar
  49. Fabre L, Vettraine J, Birkhimer L, Houser V. Fluvoxamine in the treatment of depression: a double-blind comparison with imipramine and placebo in outpatients with major depression. CINP Meeting, Nice, France, 1992Google Scholar
  50. Faverin Product Monograph. A review of pharmacological and clinical properties. Duphar Laboratories, Southampton, 1992Google Scholar
  51. Feighner JP, Boyer WF, Meredith CH, Hendrickson GG. A placebocontrolled inpatient comparison of fluvoxamine maleate and imipramine in major depression 4: 239–244, 1989Google Scholar
  52. Feldmann HS, Denber HCB. Long-term study of fluvoxamine: a new rapid-acting antidepressant. International Pharmacopsychiatry 17: 114–122, 1982PubMedGoogle Scholar
  53. Fleishaker JC, Hulst LK. Effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of alprazolam in healthy volunteers. Abstract. Pharmaceutical Research 9 (Suppl.): S292, 1992Google Scholar
  54. Flett SR, Szabadi E, Bradshaw CM. A comparison of the effects of fluvoxamine and amitriptyline on autonomic functions in healthy volunteers. European Journal of Clinical Pharmacology 42: 529–533, 1992PubMedGoogle Scholar
  55. Fritze J, Unsorg B, Lanczik M. Interaction between carbamazepine and fluvoxamine. Acta Psychiatrica Scandinavica 84: 583–584, 1991PubMedGoogle Scholar
  56. Gaszner P. Fluvoxamine treatment of depressive disorders. Abstract. European Journal of Pharmacology 183: 1910, 1990Google Scholar
  57. George MS, Trimble MR. Dystonic reaction associated with fluvoxamine. Journal of Clinical Psychopharmacology 13: 220–221, 1993PubMedGoogle Scholar
  58. Glassman AH, Preud’homme XA. Review of the cardiovascular effects of heterocyclic antidepressants. Journal of Clinical Psychiatry 54 (Suppl.): 16–22, 1993PubMedGoogle Scholar
  59. Gonella G, Baignoli G, Ecari U. Fluvoxamine and imipramine in the treatment of depressive patients: a double-blind controlled study 12: 177–184, 1990Google Scholar
  60. Green BH. Fluvoxamine and hepatic function. British Journal of Psychiatry 153: 130–131, 1988PubMedGoogle Scholar
  61. Grimsley SR, Jann MW. Paroxetine, sertraline, and fluvoxamine: new selective serotonin inhibitors. Clinical Pharmacy 11:930–957, 1992PubMedGoogle Scholar
  62. Grinshpoon A, Berg Y, Mozes T, Mester R, Weizman A. Seizures induced by combined levomepromazine-fluvoxamine treatment. International Clinical Psychopharmacology 8: 61–62, 1993PubMedGoogle Scholar
  63. Gruber AJ, Cole JO. Antidepressant effects of flupenthixol. Pharmacotherapy 11: 450–459, 1991PubMedGoogle Scholar
  64. Guelfi JD, Dreyfus JF, G.E.P.E.C.E.P. Fluvoxamine: efficacy and tolerance of a new antidepressant in a large multicentre study. Clinical Neuropharmacology 7 (Suppl. 1): S312–319, 1984Google Scholar
  65. Guelfi JD, Dreyfus JF, Pichot P, G.E.P.E.C.E.P. Fluvoxamine and imipramine: results of a long-term controlled trial. International Clinical Psychopharmacology 2: 103–109, 1987PubMedGoogle Scholar
  66. Guelfi JD, Sutet P. Long-term study of fluvoxamine versus clomipramine. 18th C.I.N.P Congress, Nice, France, June 28-July 2, 1992Google Scholar
  67. Hamilton BA, Jones PG, Hoda AN, Keane PM, Maiid I, et al. Flupenthixol and fluvoxamine in mild to moderate depression: a comparison in general practice. Pharmatherapeutica 5: 292–297, 1989PubMedGoogle Scholar
  68. Hansten PD, Horn JR (Eds). Drug Interactions and Updates, Lea & Febiger, Malvern, Pennsylvania, 1990Google Scholar
  69. Harmant J, van Rijckevorsel-Harmant K, de Barsy Th, Hendrickx B. Fluvoxamine: an antidepressant with low (or no) epileptogenic effect. Correspondence. Lancet 336: 386, 1990PubMedGoogle Scholar
  70. Harris B, Ashford J. Maintenance antidepressants and weight gain: a comparison of fluvoxamine and amitriptyline. British Journal of Clinical Research 2: 81–88, 1991Google Scholar
  71. Harris B, Szulecka TK, Anstee JA. Fluvoxamine versus amitriptyline in depressed hospital out-patients: a multicentre double-blind comparative trial. British Journal of Clinical Research 2: 89–99, 1991Google Scholar
  72. Härtter S, Wetzel H, Hammes E, Hiemke Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients. Psychopharmacology 110: 302–308, 1993PubMedGoogle Scholar
  73. Hendrickx B, Floris M. A controlled pilot study of the combination of fluvoxamine and lithium. Current Therapeutic Research 49: 106–110, 1991Google Scholar
  74. Henry JA. Overdose and safety with fluvoxamine. International Clinical Psychopharmacology 6 (Suppl. 3): 41–47, 1991PubMedGoogle Scholar
  75. Hoeksema T, Goekoop JG, van Kempen GMJ. Effects of fluvoxamine on whole-blood serotonin and platelet number. Correspondence. Journal of Clinical Psychopharmacology 13: 75–76, 1993PubMedGoogle Scholar
  76. Itil TM, Shrivastava RK, Mukherjee S, Coleman BS, Michael ST. A double-blind placebo-controlled study of fluvoxamine and imipramine in out-patients with primary depression. British Journal of Clinical Pharmacology 15 (Suppl. 3): 433S–438S, 1983PubMedGoogle Scholar
  77. Jeffries J, Bezchlibnyk-Butler K, Remington G. Amenorrhea and galactorrhea associated with fluvoxamine in a loxapine-treated patient. Journal of Clinical Psychopharmacology 12: 296–297, 1992PubMedGoogle Scholar
  78. Kapur S, Mieczkowski T, Mann JJ. Antidepressant medications and the relative risk of suicide attempt and suicide. Journal of the American Medical Association 268: 3441–3445, 1992PubMedGoogle Scholar
  79. Kasper S, Fuger J, Möller H-J. Comparative efficacy of antidepressants. Drugs 43 (Suppl. 2): 11–23, 1992PubMedGoogle Scholar
  80. Karege F, Bovier Ph, Gaillard J-M, Tissot R. Plasma MHPG and AMDP depression relations, evolution and drug effect in a followup study of depressed patients. Human Psychopharmacology 6: 11–17, 1991Google Scholar
  81. Kasper S, Dötsch M, Kick H, Vieira A, MH-J Möller. Plasma concentrations of fluvoxamine and maprotiline in major depression: implications on therapeutic efficacy and side effects. European Neuropsychopharmacology 3: 13–21, 1993PubMedGoogle Scholar
  82. Kasper S, Dötsch M, Vieira A. Plasma levels of fluvoxamine and maprotiline and clinical response in major depression. Abstract. Pharmacopsychiatry 25: 106, 1992Google Scholar
  83. Kellett JM. Fluvoxamine: an antidepressant for the elderly? Journal of Psychiatry and Neuroscience 16 (Suppl. 1):26–29, 1991PubMedGoogle Scholar
  84. Klok CJ, Brouwer GJ, van Praag HM, Doogan D. Fluvoxamine and clomipramine in depressed patients: a double-blind clinical study. Acta Psychiatrica Scandinavica 64: 1–11, 1981PubMedGoogle Scholar
  85. Krijzer F, Snelder M, Bradford D. Comparison of the (pro)convulsive properties of fluvoxamine and clovoxamine with eight other antidepressants in an animal model. Neuropsychobiology 12: 249–254, 1984PubMedGoogle Scholar
  86. Laird LK, Lydiard RB, Morton WA, Steele Kellner et al. Cardiovascular effects of imipramine, fluvoxamine, and placebo in depressed outpatients. Journal of Clinical Psychiatry 54: 224–228, 1993PubMedGoogle Scholar
  87. Lam KS, Blanchi A, Chavaillon JM. Hepatite probablement secondaire a la prise massive de fluvoxamine. Gastroenterologie Clinique et Biologique 12: 398–399, 1988PubMedGoogle Scholar
  88. Lapierre YD, Browne M, Horn E, Oyewumi LK, Sarantidis D, et al. Treatment of major affective disorder with fluvoxamine. Journal of Clinical Psychiatry 48(2): 65–68, 1987PubMedGoogle Scholar
  89. Lapierre YD, Oyewumi LK, Coleman B. The efficacy of fluvoxamine as an antidepressant. Clinical Trials Journal 18: 313–320, 1981Google Scholar
  90. Leonard BE. Pharmacological differences of serotonin reuptake inhibitors and possible clinical relevance. Drugs 43 (Suppl. 2): 3–10, 1992PubMedGoogle Scholar
  91. Linnoila M, Eckardt M, Durcan M, et al. Interactions of serotonin with ethanol: clinical and animal studies. Psychopharmacology Bulletin 23: 452–457, 1987PubMedGoogle Scholar
  92. Linnoila M, Stapleton JM, George DT, Lane E, Eckardt MJ. Effects of fluvoxamine, alone and in combination with ethanol, on psychomotor and cognitive performance and on autonomic nervous system reactivity in healthy volunteers. Journal of Clinical Psychopharmacology 13: 175–180, 1993PubMedGoogle Scholar
  93. Lupp A, Bär KI, Lücking CH, Feuerstein TJ. Different effects of serotonin (5-HT) uptake blockers in caudate nucleus and hippocampus of the rabbit: role of monoamine oxidase in dopaminergic terminals. Psychopharmacology 106: 118–126, 1992PubMedGoogle Scholar
  94. Mann JJ, Kapur S. The emergence of suicidal ideation and behavior during antidepressant pharmacotherapy. Archives of General Psychiatry 48: 1027–1033,1991PubMedGoogle Scholar
  95. March JS, Kobak KA, Jefferson JW, Mazza J, Greist JH. A doubleblind, placebo-controlled trial of fluvoxamine versus imipramine in outpatients with major depression. Journal of Clinical Psychiatry 51(5): 200–202, 1990PubMedGoogle Scholar
  96. Martin AJ, Tebbs VM, Ashford JJ. Affective disorders in general practice. Treatment of 6000 patients with fluvoxamine. Pharmatherapeutica 5: 40–49, 1987PubMedGoogle Scholar
  97. Martin AJ, Wakelin J. Fluvoxamine. A baseline study of clinical response, long term tolerance and safety in a general practice population. British Journal of Clinical Practice 40: 95–99, 1986PubMedGoogle Scholar
  98. McHardy KSyndrome of inappropriate antidiuretic hormone secretion due to fluvoxamine therapy. British Journal of Clinical Pharmacology 47: 62–63, 1993Google Scholar
  99. Mendels J. Clinical experience with serotonin reuptake inhibiting antidepressants. Journal of Clinical Psychiatry 48 (Suppl. 3): 26–30, 1987PubMedGoogle Scholar
  100. Montgomery SA. Depression in the elderly: pharmacokinetics of antidepressants and death from overdose. International Clinical Psychopharmacology 5(Suppl. 3): 67–76, 1990PubMedGoogle Scholar
  101. Montgomery SA. Suicide and antidepressants. Drugs 43 (Suppl. 2): 24–31, 1992PubMedGoogle Scholar
  102. Moon CAL, Jesinger DK. The effects of psychomotor performance of fluvoxamine versus mianserin in depressed patients in general practice. British Journal of Clinical Practice 45: 259–262, 1991PubMedGoogle Scholar
  103. Mück-Seler D, Jakovljevic M, Deanovic Z. Effect of antidepressant treatment on platelet 5-HT content and relation to therapeutic outcomes in unipolar depressive patients. Journal of Affective Disorders 23: 157–164, 1991PubMedGoogle Scholar
  104. Müller-Oerlinghausen B, Rao ML, Stieglitz RD, Volz HP. Fluvoxamine challenge test, phototherapy, and successive fluvoxamine treatment in patients with non-seasonal depression. Pharmacopsychiatry 22: 209–210, 1989Google Scholar
  105. Mullin JM, Pandita-Gunawardena VR, Whitehead AM. A doubleblind comparison of fluvoxamine and dothiepin in the treatment of major affective disorder 42: 51–55, 1988Google Scholar
  106. Murdoch D, McTavish D. Sertraline. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder. Drugs 44(4): 604–624, 1992PubMedGoogle Scholar
  107. Nathan RS, Perel JM, Pollock BG, Kupfer DJ. The role of neuropharmacologic selectivity in antidepressant action: fluvoxamine versus desipramine. Journal of Clinical Psychiatry 51: 367–372, 1990PubMedGoogle Scholar
  108. Nestler EJ, McMahon A, Sabban EL, Tallman JF, Duman RS. Chronic antidepressant administration decreases the expression of tyrosine hydroxylase in the rat locus coeruleus. Proceedings of the National Academy of Science 87: 7522–7526, 1990Google Scholar
  109. Nolen WA, van de Putte JJ, Dijken WA, Kamp JS, Blansjaar BA, et al. Treatment strategy in depression. I. Non-tricyclic and selective reuptake inhibitors in resistant depression: a double-blind partial crossover study on the effects of oxaprotiline and fluvoxamine. Acta Psychiatrica Scandinavica 78: 668–675, 1988PubMedGoogle Scholar
  110. Ochs HR, Greenblatt DJ, Verburg-Ochs B, Labedski L. Chronic treatment with fluvoxamine, clovoxamine, and placebo: interaction with digoxin and effects on sleep and alertness. Journal of Clinical Pharmacology 29: 91–95, 1989PubMedGoogle Scholar
  111. Olivier B, Bosch L, Van Hest A, van der Heyden, Mos J, et al. Preclinical evidence on the psychotropic profile of fluvoxamine. Pharmacopsychiatry 26 (Suppl. 1): 2-9, 1993PubMedGoogle Scholar
  112. Ortiz J, Artigas F. Effects of monoamine uptake inhibitors on extracellular and platelet 5-hydroxytryptamine in rat blood; different effects of clomipramine and fluoxetine. British Journal of Pharmacology 105: 941–946, 1992PubMedGoogle Scholar
  113. Ottevanger EA. Fluvoxamine activity profile with special emphasis on the effect on suicidal ideation. European Journal of Clinical Research 1:47–54, 1991bGoogle Scholar
  114. Ottevanger EA. The efficacy of fluvoxamine in patients with severe depression. British Journal of Clinical Research 2: 125–132,1991aGoogle Scholar
  115. Overmars H, Scherpenisse PM, Post LC. Fluvoxamine maleate: metabolism in man. European Journal of Drug Metabolism and Pharmacokinetics 8: 269–280, 1983PubMedGoogle Scholar
  116. Paunovic VR, Jasovic-Gasic M, Timotijevic I. Serotonergic control of behaviour: fluvoxamine and suicidal syndrome. Iugoslavica Physiologica Pharmacologica Acta 25: 403–409, 1989Google Scholar
  117. Perez A, Ashford JJ. A double-blind, randomized comparison of fluvoxamine with mianserin in depressive illness. Current Medical Research and Opinion 12(4): 234–241, 1990PubMedGoogle Scholar
  118. Phanjoo A. The elderly depressed and treatment with fluvoxamine. International Clinical Psychopharmacology 6 (Suppl.): 33–39Google Scholar
  119. Phanjoo AL, Wonnacott S, Hodgson A. Double-blind comparative multicentre study of fluvoxamine and mianserin in the treatment of major depressive episode in elderly people. Acta Psychiatrica Scandinavica 83: 476–479, 1991PubMedGoogle Scholar
  120. Poeldinger W, Bures E. Fluvoxamine in patients with depressive disorder. Proceedings of the International Symposium on Fluvoxamine, Amsterdam, September 8–9, 1983, p 13–17, 1984Google Scholar
  121. Prager G, Cimander K, Wagner W, Schnitker J, Koch H-F. The cardiotropic effect of antidepressants. Advances in Pharmacotherapy 2: 133–150, 1986Google Scholar
  122. Prager G, Stollmaier W, Prager R, Koch H-F, Wagner W, et al. Sicherheit ubd Verträglichkeit von fluvoxamin bei kardialen risikopatienten. In German. TW Neurologie Psychiatrie 5: 548–562, 1991Google Scholar
  123. Price LH, Charney DS, Delgado PL, Anderson GM, Heninger GR. Effects of desipramine and fluvoxamine treatment on the prolactin response to tryptophan. Archives of General Psychiatry 46: 625–631, 1989PubMedGoogle Scholar
  124. Racagni G, Bradford D. Biochemical and behavioural changes on chronic fluvoxamine administration. 14th CINP, Florence, Italy, 1984Google Scholar
  125. Raghoebar M, Roseboom H. Kinetics of fluvoxamine in special populations. Poster. Symposium on variability in pharmacokinetics and drug response. Gothenburg, Oct 3–5, 1988Google Scholar
  126. Rahman MK, Akhtar MJ, Savla NC, Sharma RR, Kellett JM, et al. A double-blind, randomised comparison of fluvoxamine with dothiepin in the treatment of depression in elderly patients. British Journal of Clinical Practice 45(4): 255–258, 1991PubMedGoogle Scholar
  127. Richelson E, Nelson A. Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. Journal of Pharmacology and Experimental Therapeutics 230: 94–102, 1984PubMedGoogle Scholar
  128. Rickeis K, Schweizer E. Clinical overview of serotonin reuptake inhibitors. Journal of Clinical Psychiatry 51 (Suppl): 9–12, 1990Google Scholar
  129. Robertson MM, Trimble MR. Depressive illness in patients with epilepsy: a review. Epilepsia 24 (Suppl 2): 109–116, 1983Google Scholar
  130. Roos JC. Cardiac effects of antidepressant drugs: a comparison of the tricyclic antidepressants and fluvoxamine. British Journal of Clinical Pharmacology 15 (Suppl.): 439S–445S, 1983PubMedGoogle Scholar
  131. Roos JC, Sharp DJ. Antidepressant drugs and cardiovascular side effects. A comparison of fluvoxamine and the tricyclic antidepressant drugs. In Burrows et al. (Eds) Biological psychiatry: recent studies, John Libbey, London & Paris, 1984Google Scholar
  132. Roth D, Mattes J, Sheehan KH, Sheehan DV. A double-blind comparison of fluvoxamine, desipramine and placebo in outpatients with depression. Progress in Neuro-Psychopharmacology and Biological Psychiatry 14: 929–939, 1990PubMedGoogle Scholar
  133. Saletu B, Schjerve M, Grimberger J, Schanda H, Arnold OH. Fluvoxamine — a new serotonin re-uptake inhibitor: first clinical and psychometric experiences in depressed patients. Journal of Neural Transmission 41: 17–36, 1977PubMedGoogle Scholar
  134. Siddiqui UA, Chakravarti SK, Jesinger DK. The tolerance and antidepressive activity of fluvoxamine as a single dose compared to a twice daily dose. Current Medical Research and Opinion 9: 681–690, 1985PubMedGoogle Scholar
  135. Skjelbo E, Brøsen K. Inhibitors of imipramine metabolism by human liver microsomes. British Journal of Clinical Pharmacology 34: 256–261, 1992PubMedGoogle Scholar
  136. Sperber AD. Toxic interaction between fluvoxamine and sustained release theophylline in an 11-year-old boy. Drug Safety 6: 460–462, 1991PubMedGoogle Scholar
  137. Spina E, Avenoso A, Pollicano AM, Fazio A, Pisani F, et al. No effect of fluvoxamine or fluoxetine on plasma concentrations of carbamazepine in epileptic patients. Pharmacological Research 25 (Suppl. 2)214–215, 1992Google Scholar
  138. Spina E, Pollicano AM, Avenoso A, Campo GM, Perucca E, et al. Effect of fluvoxamine on the pharmacokinetics of imipramine and desipramine in healthy subjects. Therapeutic Drug Monitoring 15: 243–246, 1993PubMedGoogle Scholar
  139. Spivey KM, Wait CM. Perioperative seizures and fluvoxamine. British Journal of Anaesthesia 71: 321–329, 1993PubMedGoogle Scholar
  140. Stollmaier W, Cimander KF, Wagner W. Efficacy and tolerance of fluvoxamine (Fevarin®) in depressive syndromes in the practice. The results of a multicentred study on 2296 patients [Translated into English from German]. Nervenheilkunde 8: 247–252, 1989Google Scholar
  141. Szabo B, Karsch V, Starke K. Effects of inhibitors of neuronal uptake of 5-HT on sympathetic cardiovascular regulation. Journal of Cardiovascular Pharmacology 20: 99–107, 1992PubMedGoogle Scholar
  142. Thomas DR, Nelson DR, Johnson AM. Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Psychopharmacology 93: 193–200, 1987PubMedGoogle Scholar
  143. Thomson AH, McGovern EM, Bennie P, Caldwell G, Smith M. Interaction between fluvoxamine and theophylline. Correspondence. Pharmaceutical Journal 249: 137, 1992Google Scholar
  144. Van Harten. Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clinical Pharmacokinetics 24: 203–220, 1993aPubMedGoogle Scholar
  145. Van Harten J, Duchier J, Devissaguet J-P, van Bemmel P, de Vries MH, et al. Pharmacokinetics of fluvoxamine maleate in patients with liver cirrhosis after single-dose oral administration. Clinical Pharmacokinetics 24: 177–182, 1993bPubMedGoogle Scholar
  146. Van Harten J, Holland RL, Wesnes K. Influence of multiple-dose administration of fluvoxamine on the pharmacokinetics of the benzodiazepines bromazepam and lorazepam: a randomised, cross-over study. Abstract. European Neuropsychopharmacology 2: 381, 1992bGoogle Scholar
  147. Van Harten J, Holland RL, Wesnes K, Raghoebar M. Kinetic and dynamic interaction study between fluvoxamine and benzodiazepines. Poster presented at the Second Jerusalem Conference on Pharmaceutical Sciences and Clinical Pharmacology, Jerusalem, May 24–29, 1992cGoogle Scholar
  148. Van Harten J, Stevens LA, Raghoebar M, Holland RL, Wesnes K, et al. Fluvoxamine does not interact with alcohol or potentiate alcohol-related impairment of cognitive function. Clinical Pharmacology and Therapeutics 52: 427–435, 1992aPubMedGoogle Scholar
  149. Van Harten J, Van Bemmel P, Dobrinska MR, Ferguson RK, Raghoebar M. Bioavailability of fluvoxamine given with and without food. Biopharmaceutics and Drug Disposition 12: 571–576, 1991Google Scholar
  150. Vincenti GE. Fluvoxamine and epilepsy. Lancet 336: 947, 1990PubMedGoogle Scholar
  151. Wagner W, Cimander K, Schnitker J, Koch H-F. Influence of concomitant psychotropic medication on the efficacy and tolerance of fluvoxamine. Advances in Pharmacotherapy 2: 34–56, 1986Google Scholar
  152. Wagner W, Zaborny BA, Gray Fluvoxamine. A review of its safety profile in worldwide studies. Submitted for publication, 1993Google Scholar
  153. Wakelin JS. Fluvoxamine in the treatment of the older depressed patient; double-blind, placebo-controlled data. International Clinical Psychopharmacology 1: 221–230, 1986PubMedGoogle Scholar
  154. White K, Kando J, Park T, Waternaux C, Brown WA. Side effects and the “blindability” of clinical drug trials. American Journal of Psychiatry 149: 1730–1731, 1992PubMedGoogle Scholar
  155. White K, Wykoff W, Tynes LL, Schneider L, Zemansky M. Fluvoxamine in the treatment of tricyclic-resistant depression. Psychiatric Journal of the University of Ottawa 15:156–158, 1990PubMedGoogle Scholar
  156. Whitehead AM, Ashford JJ. Fluvoxamine in the treatment of depressive illness. A series of double-blind hospital based comparative studies carried out in the UK. British Journal of Clinical Practice 46: 21–23, 1992PubMedGoogle Scholar
  157. Wils V. Extrapyramidal symptoms in a patient treated with fluvoxamine. Journal of Neurology, Neurosurgery and Psychiatry 55:330–331, 1992Google Scholar
  158. Wood K, Swade C, Alou-Saleh M, Millu P, Coppen A. Drug plasma levels and platelet 5-HT uptake inhibition during long-term treatment with fluvoxamine or lithium in patients with affective disorders. British Journal of Clinical Pharmacology 15 (Suppl. 3): 365S–368S, 1983PubMedGoogle Scholar
  159. Wolkenstein P, Revuz J, Diehl JL, Langeron O, Roupie E. Toxic epidermal necrolysis after fluvoxamine. Lancet 342: 304–305, 1993PubMedGoogle Scholar
  160. Wright JH, Denber HCB. Clinical trial of fluvoxamine: a new serotonergic antidepressant. Current Therapeutic Research 23: 83–89,1978Google Scholar
  161. Wright S, Dawling S, Ashford JJ. Excretion of fluvoxamine in breast milk. British Journal of Clinical Pharmacology 31: 209, 1991PubMedGoogle Scholar

Copyright information

© Adis International Limited 1993

Authors and Affiliations

  • Michelle I. Wilde
    • 1
  • Greg L. Plosker
    • 1
  • Paul Benfield
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

Personalised recommendations