, Volume 46, Issue 5, pp 895–924


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

DOI: 10.2165/00003495-199346050-00008

Cite this article as:
Wilde, M.I., Plosker, G.L. & Benfield, P. Drugs (1993) 46: 895. doi:10.2165/00003495-199346050-00008



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.


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.

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

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