Skip to main content

Fluvoxamine

An Updated Review of its Pharmacology, and Therapeutic Use in Depressive Illness

Drugs volume 46, pages 895–924 (1993)Cite this article

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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

49,54 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  • 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, 1984

  • 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, 1989

    Google Scholar 

  • Anon. Fluvoxamine prescribing information, The Netherlands, 1991

  • Ansseau M, Troisfontaines B, Papart P, von Frenckell R. Compulsive personality as predictor of response to serotoninergic antidepressants. British Medical Journal 303: 760–761, 1991

    PubMed  CAS  Google Scholar 

  • Baldessarini RJ. Overview of recent advances in antidepressant pharmacology: part II. McLean Hospital Journal 7 (1): 1–27, 1982

    Google Scholar 

  • Baldwin D, Fineberg N, Montgomery S. Fluoxetine, fluvoxamine and extrapyramidal tract disorders. International Clinical Psychopharmacology 6: 51–58, 1991

    PubMed  CAS  Google Scholar 

  • Bamrah JS, Benbow SM, McKenna J. Fluvoxamine and liver enzymes. Correspondence. British Journal of Psychiatry 156: 286–287,1990

    PubMed  CAS  Google Scholar 

  • Banerjee AK. Recovery from prolonged cerebral depression after fluvoxamine overdose. British Medical Journal 296: 1774, 1988

    PubMed  CAS  Google Scholar 

  • 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, 1991

    CAS  Google Scholar 

  • Bel N, Artigas F. Chronic treatment with fluvoxamine increases extracellular serotonin in frontal cortex but not in raphe nuclei. Synapse, in press, 1993

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • Benazzi F, Mazzoli M. Polydipsia induced by fluvoxamine. Correspondence. Pharmacopsychiatry 26: 63, 1993

    CAS  Google Scholar 

  • Benfield P, Ward A. Fluvoxamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 32: 313–334, 1986

    PubMed  CAS  Google Scholar 

  • Bertschy G, Vandel S, Vandel B, Allers G, Volmat R. Fluvoxaminetricyclic antidepressant interaction. European Journal of Clinical Pharmacology 40: 119–120, 1991

    PubMed  CAS  Google Scholar 

  • Bonnet P, Vandel S, Nezelof S, Sechter D, Bizouard P. Carbamazepine, fluvoxamine. Is there a pharmacokinetic interaction? Therapie 47: 165, 1992

    PubMed  CAS  Google Scholar 

  • 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, 1992

    Google Scholar 

  • Bradford LD. Preclinical pharmacology of fluvoxamine (Floxyfrol). Proceedings of the international symposium on fluvoxamine, Amsterdam, September 8–9, 1983, pp. 13–17, 1984

  • 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, 1986

    PubMed  CAS  Google Scholar 

  • Cassano G, Conti L. Preliminary results: placebo-controlled data on fluvoxamine maleate, a serotonergic antidepressant. Clinical Neuropharmacology 7 (Suppl. 1): S312–319, 1984

    Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • Cialdella E. Fluvoxamine in the management of depressive patients. Gazette Medicale 98: 43–47, 1991

    Google Scholar 

  • Claassen V. Review of the animal pharmacology and pharmacokinetics of fluvoxamine. British Journal of Clinical Pharmacology 15 (Suppl. 3): 349S–355S, 1983

    PubMed  Google Scholar 

  • Claassen V, Davies JE, Hertting G, Placheta P. Fluvoxamine, a specific 5-hydroxytryptamine uptake inhibitor. British Journal of Pharmacology 60: 505–516, 1977

    PubMed  CAS  Google Scholar 

  • 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, 1990

    PubMed  Google Scholar 

  • Coleman BS, Block A. Fluvoxamine maleate, a serotonergic antidepressant; a comparison with chlorimipramine. Progress in Neuro-Psychopharmacology and Biological Psychiatry 6: 475–478,1982

    PubMed  CAS  Google Scholar 

  • Constantinidis J, Dick P, Tissot R. Antidepressants and serotonin neurons of the raphe. Neuropsychobiology 7: 113–121, 1981

    PubMed  CAS  Google Scholar 

  • 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 43:468–480,1988

    Google Scholar 

  • Corrigan FM. Sodium valproate augmentation of fluoxetine or fluvoxamine effects. Correspondence. Biological Psychiatry 31: 1178–1179, 1992

    PubMed  CAS  Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • 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, 1986

    PubMed  CAS  Google Scholar 

  • 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, 1986

    PubMed  CAS  Google Scholar 

  • de Jonghe F, Swinkels J, Tuynman-Qua H. Randomized doubleblind study of fluvoxamine and maprotiline in treatment of depression. Pharmacopsychiatry 24: 21–27, 1991

    PubMed  Google Scholar 

  • de Jonghe F, Swinkels JA. The safety of antidepressants. Drugs 43 (Suppl. 2): 40–47, 1992

    PubMed  Google Scholar 

  • 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, 1990

    PubMed  CAS  Google Scholar 

  • 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, 1992

    PubMed  Google Scholar 

  • Deahl M, Trimble M. Serotonin reuptake inhibitors, epilepsy and myoclonus. British Journal of Psychiatry 159: 433–435, 1991

    PubMed  CAS  Google Scholar 

  • DeBree H, Van der Schoot JB, Post LC. Fluvoxamine maleate; disposition in man. European Journal of Drug Metabolism and Pharmacokinetics 8: 175–179, 1983

    CAS  Google Scholar 

  • 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, 1992

    Google Scholar 

  • 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: 411–418

  • Delgado PL, Price LH, Charney DS, Heninger GR. Efficacy of fluvoxamine in treatment-refractory depression. Journal of Affective Disorders 15: 55–60, 1988

    PubMed  CAS  Google Scholar 

  • 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, 1986

    CAS  Google Scholar 

  • Demisch L, Gerbaldo H, Demisch K. Fluvoxamine-melatonin-stimulation-tests (FMST) in patients with depressive disorders. Pharmacopsychiatry 21: 420–421, 1988

    PubMed  CAS  Google Scholar 

  • 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, 1983

    Google Scholar 

  • 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, 1983

    PubMed  Google Scholar 

  • Diot P, Jonville AP, Gerard F, Bonnelle M, Autret E, et al. Possible interaction entre théophylline et fluvoxamine. Therapie 46: 169–171. 1991

    Google Scholar 

  • 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, 1984

    Google Scholar 

  • Eckardt MJ, Stapleton JM, Rio D, et al. Interactions of fluvoxamine and ethanol in healthy volunteers. Clinical Neuropharmacology 9 (Suppl.) 4: 55–57, 1986

    Google Scholar 

  • Evans M, Marwick P. Fluvoxamine and lithium: an unusual interaction. Correspondence. British Journal of Psychiatry 156:286,1990

    PubMed  CAS  Google Scholar 

  • 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, 1992

  • Faverin Product Monograph. A review of pharmacological and clinical properties. Duphar Laboratories, Southampton, 1992

  • Feighner JP, Boyer WF, Meredith CH, Hendrickson GG. A placebocontrolled inpatient comparison of fluvoxamine maleate and imipramine in major depression 4: 239–244, 1989

    CAS  Google Scholar 

  • Feldmann HS, Denber HCB. Long-term study of fluvoxamine: a new rapid-acting antidepressant. International Pharmacopsychiatry 17: 114–122, 1982

    PubMed  CAS  Google Scholar 

  • Fleishaker JC, Hulst LK. Effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of alprazolam in healthy volunteers. Abstract. Pharmaceutical Research 9 (Suppl.): S292, 1992

    Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • Fritze J, Unsorg B, Lanczik M. Interaction between carbamazepine and fluvoxamine. Acta Psychiatrica Scandinavica 84: 583–584, 1991

    PubMed  CAS  Google Scholar 

  • Gaszner P. Fluvoxamine treatment of depressive disorders. Abstract. European Journal of Pharmacology 183: 1910, 1990

    Google Scholar 

  • George MS, Trimble MR. Dystonic reaction associated with fluvoxamine. Journal of Clinical Psychopharmacology 13: 220–221, 1993

    PubMed  CAS  Google Scholar 

  • Glassman AH, Preud’homme XA. Review of the cardiovascular effects of heterocyclic antidepressants. Journal of Clinical Psychiatry 54 (Suppl.): 16–22, 1993

    PubMed  Google Scholar 

  • Gonella G, Baignoli G, Ecari U. Fluvoxamine and imipramine in the treatment of depressive patients: a double-blind controlled study 12: 177–184, 1990

    CAS  Google Scholar 

  • Green BH. Fluvoxamine and hepatic function. British Journal of Psychiatry 153: 130–131, 1988

    PubMed  CAS  Google Scholar 

  • Grimsley SR, Jann MW. Paroxetine, sertraline, and fluvoxamine: new selective serotonin inhibitors. Clinical Pharmacy 11:930–957, 1992

    PubMed  CAS  Google Scholar 

  • Grinshpoon A, Berg Y, Mozes T, Mester R, Weizman A. Seizures induced by combined levomepromazine-fluvoxamine treatment. International Clinical Psychopharmacology 8: 61–62, 1993

    PubMed  CAS  Google Scholar 

  • Gruber AJ, Cole JO. Antidepressant effects of flupenthixol. Pharmacotherapy 11: 450–459, 1991

    PubMed  CAS  Google Scholar 

  • 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, 1984

    Google Scholar 

  • 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, 1987

    PubMed  CAS  Google Scholar 

  • Guelfi JD, Sutet P. Long-term study of fluvoxamine versus clomipramine. 18th C.I.N.P Congress, Nice, France, June 28-July 2, 1992

  • 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, 1989

    PubMed  CAS  Google Scholar 

  • Hansten PD, Horn JR (Eds). Drug Interactions and Updates, Lea & Febiger, Malvern, Pennsylvania, 1990

    Google Scholar 

  • Harmant J, van Rijckevorsel-Harmant K, de Barsy Th, Hendrickx B. Fluvoxamine: an antidepressant with low (or no) epileptogenic effect. Correspondence. Lancet 336: 386, 1990

    PubMed  CAS  Google Scholar 

  • Harris B, Ashford J. Maintenance antidepressants and weight gain: a comparison of fluvoxamine and amitriptyline. British Journal of Clinical Research 2: 81–88, 1991

    Google Scholar 

  • 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, 1991

    Google Scholar 

  • Härtter S, Wetzel H, Hammes E, Hiemke Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients. Psychopharmacology 110: 302–308, 1993

    PubMed  Google Scholar 

  • Hendrickx B, Floris M. A controlled pilot study of the combination of fluvoxamine and lithium. Current Therapeutic Research 49: 106–110, 1991

    Google Scholar 

  • Henry JA. Overdose and safety with fluvoxamine. International Clinical Psychopharmacology 6 (Suppl. 3): 41–47, 1991

    PubMed  Google Scholar 

  • 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, 1993

    PubMed  CAS  Google Scholar 

  • 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, 1983

    PubMed  Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • Kasper S, Fuger J, Möller H-J. Comparative efficacy of antidepressants. Drugs 43 (Suppl. 2): 11–23, 1992

    PubMed  Google Scholar 

  • 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, 1991

    Google Scholar 

  • 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, 1993

    PubMed  CAS  Google Scholar 

  • Kasper S, Dötsch M, Vieira A. Plasma levels of fluvoxamine and maprotiline and clinical response in major depression. Abstract. Pharmacopsychiatry 25: 106, 1992

    Google Scholar 

  • Kellett JM. Fluvoxamine: an antidepressant for the elderly? Journal of Psychiatry and Neuroscience 16 (Suppl. 1):26–29, 1991

    PubMed  CAS  Google Scholar 

  • 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, 1981

    PubMed  CAS  Google Scholar 

  • 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, 1984

    PubMed  CAS  Google Scholar 

  • 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, 1993

    PubMed  CAS  Google Scholar 

  • Lam KS, Blanchi A, Chavaillon JM. Hepatite probablement secondaire a la prise massive de fluvoxamine. Gastroenterologie Clinique et Biologique 12: 398–399, 1988

    PubMed  CAS  Google Scholar 

  • 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, 1987

    PubMed  CAS  Google Scholar 

  • Lapierre YD, Oyewumi LK, Coleman B. The efficacy of fluvoxamine as an antidepressant. Clinical Trials Journal 18: 313–320, 1981

    Google Scholar 

  • Leonard BE. Pharmacological differences of serotonin reuptake inhibitors and possible clinical relevance. Drugs 43 (Suppl. 2): 3–10, 1992

    PubMed  CAS  Google Scholar 

  • Linnoila M, Eckardt M, Durcan M, et al. Interactions of serotonin with ethanol: clinical and animal studies. Psychopharmacology Bulletin 23: 452–457, 1987

    PubMed  CAS  Google Scholar 

  • 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, 1993

    PubMed  CAS  Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • Mann JJ, Kapur S. The emergence of suicidal ideation and behavior during antidepressant pharmacotherapy. Archives of General Psychiatry 48: 1027–1033,1991

    PubMed  CAS  Google Scholar 

  • 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, 1990

    PubMed  CAS  Google Scholar 

  • Martin AJ, Tebbs VM, Ashford JJ. Affective disorders in general practice. Treatment of 6000 patients with fluvoxamine. Pharmatherapeutica 5: 40–49, 1987

    PubMed  CAS  Google Scholar 

  • 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, 1986

    PubMed  CAS  Google Scholar 

  • McHardy KSyndrome of inappropriate antidiuretic hormone secretion due to fluvoxamine therapy. British Journal of Clinical Pharmacology 47: 62–63, 1993

    Google Scholar 

  • Mendels J. Clinical experience with serotonin reuptake inhibiting antidepressants. Journal of Clinical Psychiatry 48 (Suppl. 3): 26–30, 1987

    PubMed  Google Scholar 

  • Montgomery SA. Depression in the elderly: pharmacokinetics of antidepressants and death from overdose. International Clinical Psychopharmacology 5(Suppl. 3): 67–76, 1990

    PubMed  Google Scholar 

  • Montgomery SA. Suicide and antidepressants. Drugs 43 (Suppl. 2): 24–31, 1992

    PubMed  Google Scholar 

  • 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, 1991

    PubMed  CAS  Google Scholar 

  • 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, 1991

    PubMed  Google Scholar 

  • 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, 1989

    Google Scholar 

  • Mullin JM, Pandita-Gunawardena VR, Whitehead AM. A doubleblind comparison of fluvoxamine and dothiepin in the treatment of major affective disorder 42: 51–55, 1988

    CAS  Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • 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, 1990

    PubMed  CAS  Google Scholar 

  • 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, 1990

    CAS  Google Scholar 

  • 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, 1988

    PubMed  CAS  Google Scholar 

  • 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, 1989

    PubMed  CAS  Google Scholar 

  • 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, 1993

    PubMed  Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • Ottevanger EA. Fluvoxamine activity profile with special emphasis on the effect on suicidal ideation. European Journal of Clinical Research 1:47–54, 1991b

    Google Scholar 

  • Ottevanger EA. The efficacy of fluvoxamine in patients with severe depression. British Journal of Clinical Research 2: 125–132,1991a

    Google Scholar 

  • Overmars H, Scherpenisse PM, Post LC. Fluvoxamine maleate: metabolism in man. European Journal of Drug Metabolism and Pharmacokinetics 8: 269–280, 1983

    PubMed  CAS  Google Scholar 

  • Paunovic VR, Jasovic-Gasic M, Timotijevic I. Serotonergic control of behaviour: fluvoxamine and suicidal syndrome. Iugoslavica Physiologica Pharmacologica Acta 25: 403–409, 1989

    Google Scholar 

  • 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, 1990

    PubMed  CAS  Google Scholar 

  • Phanjoo A. The elderly depressed and treatment with fluvoxamine. International Clinical Psychopharmacology 6 (Suppl.): 33–39

  • 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, 1991

    PubMed  CAS  Google Scholar 

  • 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, 1984

  • Prager G, Cimander K, Wagner W, Schnitker J, Koch H-F. The cardiotropic effect of antidepressants. Advances in Pharmacotherapy 2: 133–150, 1986

    Google Scholar 

  • 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, 1991

    Google Scholar 

  • 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, 1989

    PubMed  CAS  Google Scholar 

  • Racagni G, Bradford D. Biochemical and behavioural changes on chronic fluvoxamine administration. 14th CINP, Florence, Italy, 1984

  • Raghoebar M, Roseboom H. Kinetics of fluvoxamine in special populations. Poster. Symposium on variability in pharmacokinetics and drug response. Gothenburg, Oct 3–5, 1988

  • 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, 1991

    PubMed  CAS  Google Scholar 

  • 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, 1984

    PubMed  CAS  Google Scholar 

  • Rickeis K, Schweizer E. Clinical overview of serotonin reuptake inhibitors. Journal of Clinical Psychiatry 51 (Suppl): 9–12, 1990

    Google Scholar 

  • Robertson MM, Trimble MR. Depressive illness in patients with epilepsy: a review. Epilepsia 24 (Suppl 2): 109–116, 1983

    Google Scholar 

  • Roos JC. Cardiac effects of antidepressant drugs: a comparison of the tricyclic antidepressants and fluvoxamine. British Journal of Clinical Pharmacology 15 (Suppl.): 439S–445S, 1983

    PubMed  Google Scholar 

  • 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, 1984

    Google Scholar 

  • 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, 1990

    PubMed  CAS  Google Scholar 

  • 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, 1977

    PubMed  CAS  Google Scholar 

  • 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, 1985

    PubMed  CAS  Google Scholar 

  • Skjelbo E, Brøsen K. Inhibitors of imipramine metabolism by human liver microsomes. British Journal of Clinical Pharmacology 34: 256–261, 1992

    PubMed  CAS  Google Scholar 

  • Sperber AD. Toxic interaction between fluvoxamine and sustained release theophylline in an 11-year-old boy. Drug Safety 6: 460–462, 1991

    PubMed  CAS  Google Scholar 

  • 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, 1992

    Google Scholar 

  • 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, 1993

    PubMed  CAS  Google Scholar 

  • Spivey KM, Wait CM. Perioperative seizures and fluvoxamine. British Journal of Anaesthesia 71: 321–329, 1993

    PubMed  CAS  Google Scholar 

  • 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, 1989

    Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • Thomas DR, Nelson DR, Johnson AM. Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Psychopharmacology 93: 193–200, 1987

    PubMed  CAS  Google Scholar 

  • Thomson AH, McGovern EM, Bennie P, Caldwell G, Smith M. Interaction between fluvoxamine and theophylline. Correspondence. Pharmaceutical Journal 249: 137, 1992

    Google Scholar 

  • Van Harten. Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clinical Pharmacokinetics 24: 203–220, 1993a

    PubMed  Google Scholar 

  • 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, 1993b

    PubMed  Google Scholar 

  • 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, 1992b

    Google Scholar 

  • 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, 1992c

  • 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, 1992a

    PubMed  Google Scholar 

  • 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, 1991

    Google Scholar 

  • Vincenti GE. Fluvoxamine and epilepsy. Lancet 336: 947, 1990

    PubMed  CAS  Google Scholar 

  • 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, 1986

    Google Scholar 

  • Wagner W, Zaborny BA, Gray Fluvoxamine. A review of its safety profile in worldwide studies. Submitted for publication, 1993

  • Wakelin JS. Fluvoxamine in the treatment of the older depressed patient; double-blind, placebo-controlled data. International Clinical Psychopharmacology 1: 221–230, 1986

    PubMed  CAS  Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • 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, 1990

    PubMed  CAS  Google Scholar 

  • 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, 1992

    PubMed  CAS  Google Scholar 

  • Wils V. Extrapyramidal symptoms in a patient treated with fluvoxamine. Journal of Neurology, Neurosurgery and Psychiatry 55:330–331, 1992

    CAS  Google Scholar 

  • 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, 1983

    PubMed  Google Scholar 

  • Wolkenstein P, Revuz J, Diehl JL, Langeron O, Roupie E. Toxic epidermal necrolysis after fluvoxamine. Lancet 342: 304–305, 1993

    PubMed  CAS  Google Scholar 

  • Wright JH, Denber HCB. Clinical trial of fluvoxamine: a new serotonergic antidepressant. Current Therapeutic Research 23: 83–89,1978

    Google Scholar 

  • Wright S, Dawling S, Ashford JJ. Excretion of fluvoxamine in breast milk. British Journal of Clinical Pharmacology 31: 209, 1991

    PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Adis International Limited, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland 10, New Zealand

    Michelle I. Wilde, Greg L. Plosker & Paul Benfield

Authors
  1. Michelle I. Wilde
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Greg L. Plosker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul Benfield
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Various sections of the manuscript reviewed by: M. Amore, Institute of Psychiatry, University of Bologna, Bologna, Italy; F. Artigas, Department of Neurochemistry, Consejo Superior de investigaciones, Barcelona, Spain; F. de Jonghe, Department of Psychiatry, University of Amsterdam, Amsterdam, The Netherlands; L. Demisch, Departments of Psychiatry and Endocrinology, JW Goethe-Universität, Frankfurt, Federal Republic of Germany; K. Ghose, Centre for Adverse Reactions Monitoring, National Toxicology Group, University of Otago, Dunedin, New Zealand; B. Harris, Department of Psychological Medicine, University Hospital of Wales, Cardiff, Wales; M.H. Lader, Institute of Psychiatry, De Crespigny Park, London, England; S.A. Montgomery, Academic Department of Psychiatry, St Mary’s Hospital Medical School, London, England; S.H. Preskorn, Psychiatric Research Institute, St Francis Regional Medical Center, Wichita, Kansas, USA; S.C. Risch, Department of Psychiatry and Behavioural Sciences, Medical University of South Carolina, Charleston, South Carolina, USA; J.W.G. Tiller, Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Melbourne, Victoria, Australia

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wilde, M.I., Plosker, G.L. & Benfield, P. Fluvoxamine. Drugs 46, 895–924 (1993). https://doi.org/10.2165/00003495-199346050-00008

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199346050-00008

Keywords

  • Suicidal Ideation
  • Imipramine
  • Fluvoxamine
  • Desipramine
  • Clomipramine