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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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