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Fluvoxamine is a selective serotonin reuptake inhibitor which was initially developed as an antidepressant. Additional clinical research has identified several other disorders of the central nervous system in whichfluvoxamine has potential benefits, and which are the focus of this review.
At present, the largest volume of data concerns the use of fluvoxamine in obsessive-compulsive disorder. Oral fluvoxamine at dosages of up to 300 mg/day is effective in alleviating, although not preventing, the symptoms of obsessivecompulsive disorder in 40 to 50% of patients, and limited data indicate that it is as effective as clomipramine. Encouraging initial data are also available regarding the efficacy of fluvoxamine in panic disorder. Further data are required to fully establish the efficacy of fluvoxamine in preventing panic attacks, and to investigate possible beneficial effects in the treatment of anxiety symptoms, bulimia nervosa, alcohol (ethanol )-induced amnesia, schizophrenia and several other psychiatric disorders, and pain states. Comparative and long term data in all disorders in which fluvoxamine shows potential are also required.
Fluvoxamine is well tolerated by the majority of patients. Nausea is the most frequent adverse effect and can lead to withdrawal from treatment. However, nausea and most other adverse effects are generally mild to moderate in nature. Fluvoxamine induces less anticholinergic and sedative effects than tricyclic antidepressants, and does not appear to have cardiotoxic effects. In addition, as with many other antidepressants there is no evidence thatfluvoxamine induces suicidal behaviour. Compared with tricyclic antidepressants,fluvoxamine is relatively safe in overdose.
Thus, studies available to date have demonstrated the efficacy offluvoxamine in obsessive-compulsive disorder. Efficacy in other central nervous system disorders has been indicated but further confirmatory data are required, as are comparative data in all disorders. The improved tolerability profile of fluvoxamine compared with many other agents used in these conditions will help to establish the agent as a useful alternative in obsessive-compulsive disorder, and in other conditions if preliminary efficacy findings are confirmed.
Fluvoxamine is a potent and selective inhibitor of serotonin reuptake. In addition to its lack of effects on other monoamine reuptake mechanisms, fluvoxamine has little or no effect on the neuronal function of other monoamines and has a low affinity for the receptors of a variety of neurotransmitters. While acute inhibition of serotonin reuptake by fluvoxamine is well documented, clinical response is slower and therefore is not readily explained by this acute effect.
Studies in animals and humans have shown that fluvoxamine, unlike the tricyclic antidepressants, has relatively few cardiovascular or anticholinergic effects. In addition, fluvoxamine does not appear to have pro-convulsive or sedative effects, and does not impair cognition. Fluvoxamine has anxiolytic and anti-nociceptive activity in some animal models, and reduces alcohol (ethanol) intake in alcohol-preferring rats. Pain thresholds in healthy volunteers are increased by fluvoxamine.
The pharmacokinetic properties of fluvoxamine are well established. The drug is almost completely absorbed following oral administration and the extent of absorption is not affected by the presence of food in the gastrointestinal tract. Maximum plasma concentrations are reached within 2 to 8 hours of administration and steady-state concentrations are achieved after 10 days. There is no drug accumulation after repeated administration. Fluvoxamine is extensively metabolised in the liver, with 11 pharmacologically inactive metabolites identified. Most of a dose offluvoxamineis excreted in the urine, with only about 3% as unchanged parent compound. Mean elimination half-life is 14 to 22 hours.
Limited data suggest that the pharmacokinetic parameters of fluvoxamine are not affected by increased age, renal impairment or genetic polymorphism. However, elimination half-life is increased in patients with hepatic disease.
Fluvoxamine at oral dosages of 50 to 300 mg/day has been investigated in a number of non-depressive disorders. Positive results in 6 placebo-controlled trials support the efficacy of fluvoxamine in obsessive-compulsive disorder. At present, comparative data are limited but promising, with 2 trials showing that fluvoxamine is as effective as clomipramine. As with clomipramine, fluvoxamine reduces but does not eliminate obsessions and compulsions, is effective in only 40 to 50% of patients and has a delay in onset of action of approximately 4 weeks.
Limited data indicate that fluvoxamine may also be effective in preventing panic attacks, although further placebo-controlled comparisons with standard agents are required. Encouraging preliminary results suggest that fluvoxamine may have potential in the treatment of anxiety symptoms, bulimia nervosa, alcohol- induced amnesia, schizophrenia and several other psychiatric disorders, and pain syndromes. Fluvoxamine does not appear to be effective in patients with dementia, post-traumatic stress disorder or menstrually related disorders, or in reducing body weight in obese patients.
Fluvoxamine is well tolerated in patients with depression or other central nervous system disorders at oral dosages of up to 300 mg/day for up to 12 weeks. Long term tolerability has not been fully established. A least 43% of patients experience at least 1 adverse effect, with the highest incidence of adverse effects being associated with the gastrointestinal tract (nausea, vomiting, abdominal pain) and central nervous system (somnolence, headache, insomnia). Asthenia is also a common adverse effect. The most common adverse effect is nausea, which can result in discontinuation of therapy. Most adverse effects are transient and of mild to moderate severity. No fluvoxamine-associated clinically significant changes in vital signs or laboratory parameters have been reported.
Fluvoxamine produces fewer anticholinergic effects than tricyclic antidepressants, and is thought to have less epileptogenic potential than these agents. In addition, fluvoxamine does not appear to have any cardiotoxic effects. The adverse effects profile of fluvoxamine appears to be similar to that of other selective serotonin reuptake inhibitors. Fluvoxamine treatment has not been associated with an increase in suicidal behaviour, and the agent is considered less harmful than tricyclic antidepressants in overdose.
Dosage and Administration
For the treatment of non-depressive disorders, fluvoxamine has been administered at oral dosages of 50 to 300 mg/day. Dosages over 100 mg/day were most commonly used. Titration of the dosage in 50mg increments is recommended for the treatment of depression and a similar procedure should probably be used for other disorders. A starting dosage of 50 mg/day may reduce nausea. Dosage should not exceed 100 mg/day in patients with hepatic or renal impairment. While it does not seem necessary to reduce the dosage in elderly patients, slow titration of the dosage should be employed in these patients.
Caution is recommended when administering fluvoxamine with agents with which it is known to interact, such as lithium, theophylline, tricyclic antidepressants or warfarin. In addition, cautious use is recommended when fluvoxamine is administered to patients with epilepsy or a medical condition that may be exacerbated by vomiting. Fluvoxamine should not be administered with or within 2 weeks of withdrawing a monoamine oxidase inhibitor, and a monoamine oxidase inhibitor should not be started within 1 week of stopping fluvoxamine.
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- 5.Hyttel J, Larsen J-J. Serotonin-selective antagonists. Acta Pharmacol Toxicol 1985; 56 Suppl. 1: 146–53Google Scholar
- 11.Dresse A, Scuvee-Moreau J. The effects of various antidepressants on the spontaneous firing rates of noradrenergic and serotonergic neurons. Clin Neuropharmacol 1984; 7 Suppl. 1: S312–9Google Scholar
- 20.Scherschlicht R, Pole P, Schneeberger J, et al. Selective suppression of rapid eye movement sleep (REMS) in cats by typical and atypical antidepressants. In: Costa, Ragcagni, editors. Advances in biochemical psychopharmacology, vol. 31. New York: Raven Press, 1982: 359–64PubMedCrossRefGoogle Scholar
- 29.Berger M, Emrich HM, Lund R, et al. Sleep-EEG variables as course criteria and predictors of antidepressant therapy with fluvoxamineloxaprotiline. Adv Pharamcother 1986; 2: 110–20Google Scholar
- 46.Kletzky OA, St-Michel P, Mashchak CA, et al. Lack of effect of fluvoxamine, a new serotonin reuptake inhibitor, on hypothalamic-pituitary function. Curr Ther Res 1983; 33: 394–400Google Scholar
- 48.Müller-Oerlinghausen B, Rao ML, Stieglitz RD, et al. Fluvoxamine challenge test, phototherapy, and successive fluvoxamine therapy in patients with non-seasonal depression. Pharmacopsychiatry 1989; 22: 209–10Google Scholar
- 49.Lister BS, Szabadi E, Bradshaw CM. Comparison of the effects of acute and chronic treatment with fluvoxamine on peripheral β-adrenoceptor-mediated responses in man. Br J Clin Pharmacol 1991; 31: 575P–6PGoogle Scholar
- 52.Benfield P, Heel RC, Lewis SP. Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 1986; 32: 482–508Google Scholar
- 63.File SE. The neurochemistry of anxiety. In: Burrows et al., editors. Anti-anxiety agents. Amsterdam: Elsevier Science Publications, 1984: 13–34Google Scholar
- 66.de Angelis L. ‘Newer’ versus ‘older’ antidepressant drugs in the treatment of chronic pain syndromes. Adv Ther 1992; 9: 91–7Google Scholar
- 76.Traskrnan L, Asberg M, Bertilsson L, et al. Plasma levels of chlorimiprarnine and its demethyl metabolite during treatment of depression. Clin Pharmacol Ther 1979; 26: 600–10Google Scholar
- 84.Raghoebar M, Roseboom H. Kinetics of fluvoxamine in special populations. Poster presented at Symposium on Variability in Pharmacokinetics and Drug Response; 1988 October 3-5; Gothenburg, SwedenGoogle Scholar
- 88.Kasper S, Dtitsch M, Vieira A. Plasma levels of fluvoxamine and maprotiline and clinical response in major depression [abstract]. Pharmacopsychiatry 1992; 25: 106Google Scholar
- 92.American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd rev., ed. Washington DC: American Psychiatric Association, 1987Google Scholar
- 93.Goodman WK, Kozak MJ, Liebowitz M, et al. Efficacy of fluvoxamine in obsessive-compulsive disorder; a second multicentre study. Poster presented at the 18th Collegium Internationale Neuro-Psychopharmacologicum; 1992 June 28- July I; Nice, FranceGoogle Scholar
- 94.Greist JH. Fluvoxarnine in OCD: a multicentre parallel design double-blind placebo-controlled trial. Poster presented at the 18th Collegium Internationale Neuro-Psychopharmacologicum; 1992 June 28-July1; Nice, FranceGoogle Scholar
- 98.George M, Moriarty J, Trimble MR, et al. Trial of fluvoxamine and sulpiride in the treatment of co-morbid obsessive-compulsive disorder and Gilles de la Tourette syndrome. Poster presented at the 18th Collegium Internationale Neuropsycho Pharmacologicum; 1992 June 28-July 1; Nice, FranceGoogle Scholar
- 102.Holland R, Vardy A, Block BA. Long-term use of fluvoxamine in obsessive compulsive disorder (OCD): sustained efficacy and good tolerability. Poster presented at the 18th Collegium Internationale Neuro-Psychopharmacologicum; 1992 June 28-July 1; Nice, FranceGoogle Scholar
- 107.Ananth J, Pecknold JC, Van Den Steen N, et al. Double-blind comparative study of clomipramine and amitriptyline in obsessive neurosis. Prog Neuropsychopharmacol BioI Psychiatry 1981; 5: 257–62Google Scholar
- 116.Asnis GM, Van Praag HM, Holland RL. Fluvoxamine in the treatment of panic disorder. Poster presented at 6th European Congress of the Association of European Psychiatrists, 1992 November 3-7Google Scholar
- 120.Gardiner HM, Freeman CPL, Jesinger DK, et al. Fluvoxamine: an open pilot study in moderately obese female patients suffering from atypical eating disorders and episodes of bingeing. Int Journal Obes 1993; 17: 301–5Google Scholar
- 121.Ayuso-Gutierrez JL, Casanueva MP, Ayuso-Mateos JL. An open trial of fluvoxamine in the treatment of bulimia nervosa. Int J Eating Disord. In pressGoogle Scholar
- 122.Fichter MM, Rief W, Diihne J, et al. Effects of fluvoxamine in bulimia nervosa: results of a controlled double-blind study. Proceedings of the 9th World Congress of Psychiatry; 1993 June 6-12: Rio de Janeiro, BrazilGoogle Scholar
- 123.Schmidt U for the British Bulimia Group. A one-year, prospective, double-blind, placebo-controlled multi-centre study of fluvoxamine in bulimia nervosa [abstract]. Proceedings of the 9th World Congress of Psychiatry; 1993 June 6-12: Rio de Janeiro, BrazilGoogle Scholar
- 124.Abell CA, Farquhar DL, Galloway SMCL, et al. Placebo controlled double-blind trial of fluvoxamine maleate in the obese [letter]. Pharmacopsychiatry 1986; 24: 180Google Scholar
- 125.de Zwaan M, Schönbeck G, Nutzinger D, et al. Fluvoxamine and behavior therapy in the treatment of depressed obese. Pharmacopsychiatry 1989; 22: 223Google Scholar
- 126.Meryn S, de Zwaan M, Schiinbeck G, et al. Effect of overweight and weight reduction with dietary therapy and/or fluvoxamine on liver function in obesity [abstract]. Gastroenterology 1990; 98: A607Google Scholar
- 127.Bagiella E, Cairella M, del Ben M, et al. Changes in attitude toward food by obese patients treated with placebo and serotoninergic agents. Curr Ther Res 1991; 50: 205–10Google Scholar
- 128.Gottfries CG. Disturbances of the 5-hydroxytryptamine metabolism in brains from patients with Alzheimer’s dementia. J Neural Trans 1990 Suppl.30: 33–43Google Scholar
- 134.Hendrickx B, van Moffaert M, Spiers R, et al. The treatment of psychocutaneous disorders: a new approach. Curr Ther Res 1991; 49: 111–9Google Scholar
- 141.Block BA, Holland RL. Recidivist alcoholics: a double-blind placebo-controlled study of fluvoxamine. Poster presented at 4th Congress of the European Society for Biomedical Research on Alcoholism; 1993 June 2-5; Genoa, Italy.Google Scholar
- 167.Ottevanger EA. Fluvoxamine activity profile with special emphasis on the effect on suicidal ideation. Eur J Clin Res 1991; 1: 47–54Google Scholar
- 168.Prager G, Cimander K, Wagner W, et al. The cardiotropic effect of antidepressants. Adv Pharmacother 1986; 2: 133–50Google Scholar
- 169.Prager G, Stollmaire W, Prager R, et al. Sicherheit ubd vertraglichkeit von fluvoxamin bei kardialen risikopatienten. TW Neurol Psychiatrie 1991; 5: 548–62Google Scholar
- 175.Fleishaker JC, Hulst LK. Effect of fluvoxamine on the pharmacokinetics and pharmacodynamics of alprazolam in healthy volunteers [abstract]. Pharm Res 1992; 9 Suppl.: S–295Google Scholar
- 177.Bonnet P, Vandel S, Nezelof S, et al. Carbamazepine, fluvoxamine. Is there a pharmacokinetic interaction? [letter] Therapie 1992; 47: 165Google Scholar
- 183.Thomson AH, McGovern EM, Bennie P, et al. Interaction between fluvoxarnine and theophylline. Pharm J 1992; 249: 137Google Scholar
- 189.Hendrickx B, Floris M. A controlled pilot study of the combination of fluvoxamine and lithium. Curr Ther Res 1991; 49: 106–10Google Scholar
- 193.van Harten J, Wesnes K, Raghoebar M. Negligible kinetic and dynamic interaction between fluvoxamine and alcohol [abstract. Clin Pharmacol Ther 1991; 49: 178Google Scholar
- 195.Committee on Safety of Medicines. Benzodiazepines, dependence and withdrawal symptoms. Current Probl 1988; 21: 1–2Google Scholar