Fluvoxamine dosage

Lu, M. L. et al. (2000). Fluvoxamine reduces the clozapine dosage needed in refractory schizophrenic patients. /. Clin. Psychiatry, 61, 594—9. 

In general, the SSRIs have a more tolerable side effect profile than the tricyclic antidepressants with their anticholinergic effects. Review of the rate that subjects in the controlled studies discontinued a SSRI because of adverse effects provides some perspective on how well tolerated the medications are, although the specifics may vary according to dosage and design (e.g., forced titration) and are not directly comparable. The rate of discontinuation was reported to be 12% (4/48) for fluoxetine (Emslie et ah, 1997), 9.7% for paroxetine (Keller et ah, 2001), 13% (12/92) for sertraline (March et ah, 1998), and 33% (19/57) (Riddle et ah, 2001) and 7.9% (5/63) for fluvoxamine (Walkup et ah, 2001). 

Both fluvoxamine and sertraline are approved for the treatment of OCD in children and adolescents. Fluvoxamine was proven effective in a 10-week, double-blind, placebo-controlled trial in patients 8 to 17 years of age with OCD ( 149). Dosages in this study were adjusted to a total daily fluvoxamine dose of approximately 100 mg per day over the first 2 weeks using a balanced, twice-daily dosing schedule. After that, the dose was adjusted within a range of 50 to 200 mg per day based on clinical assessment of efficacy and tolerability. Fluvoxamine was superior to placebo on the Children s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) at weeks 1 to 6 and week 10. However, the effect was mainly in the 8- to 11-year-old versus the 12- to 17-year-old age group. The significance of this age difference is not known. 

A 27-year-old married woman with a borderline personality disorder was admitted to hospital with depression and suicidal ideation (65). Over 3 weeks she was given fluvoxamine in doses up to 150 mg/day, but because of lack of response the dosage was increased to 200 mg/day 3 days later she reported that her sex drive was greater than it had ever been before and that she felt she could not control it. There was no evidence of mania. Within a week of withdrawal of fluvoxamine her sexual desire had returned to its previous level. 

In a prospective study fluvoxamine, in a low dosage of 50 mg/day, produced a threefold increase in plasma clozapine concentrations (n = 16) (24). 

Fluvoxamine inhibits CYP1A2, and a low dosage (50 mg/ day) produced a 225% increase in plasma thioridazine concentrations in 10 patients with schizophrenia (31). This was not reflected in an increased incidence of clinical adverse events however, thioridazine prolongs the QTC interval, which was not measured. 

Since clozapine may be the gold standard and the last resort in the treatment of refractory schizophrenia, the authors of a review aimed to discover whether a trial with clozapine is adequate (15). The results favored the approach of increasing the clozapine plasma concentration in treatment-refractory schizophrenic patients who do not respond to an initial low-to-medium dose. Some patients, especially young male smokers, will need dosages over 900 mg/day, and the addition of low-dose fluvoxamine while closely monitoring clozapine concentrations can help to reduce the large number of tablets required, since fluvoxamine increases the clozapine plasma concentration 2- to 3-fold, maximally 5-fold, and reduces N-desmethylclozapine concentrations the combination can lead to non-linear kinetics of clozapine. 

Fluvoxamine under steady-state conditions increases the systemic availability of olanzapine and inhibits the metabolism of clozapine, as shown in 21 male non-smoking Chinese volunteers (mean age 27 years) (277). This could be related to the different metabolic pathways and secretion rates of the two drugs it would be advisable to reduce the dosage of olanzapine and to extend the dosing interval of clozapine when they are combined with fluvoxamine. 

A 23-year-old man had raised 9-hydroxyrisperidone concentrations in association with carbamazepine dosage reduction and concomitant fluvoxamine therapy (244). 

CYP450 3A4 inhibitors (e.g., nefazodone, fluvoxamine, fluoxetine) can raise clozapine levels, but dosage adjustment usually not necessary... 

Via CYP450 3A4 inhibition, fluvoxamine may reduce clearance of carbamazepine and benzodiazepines such as alprazolam and triazolam, and thus require dosage reduction... 

Dosing and Administration. Low initial doses of SSRIs are recommended (see Table 69-11) to avoid stimulatory side effects (e.g., insomnia or nervousness). The initial doses are much smaller than those used in depression and should be maintained for the first week of therapy. Paroxetine can be increased by 10 mg weekly the target dose is 40 mg. The starting dose of fluoxetine is 5 mg/day, with dosage increases every 2 or 3 days to a dosage range of 10 to 20 mg/day by the end of 2 weeks. Fluvoxamine can be increased to 150 mg/day in divided doses over 2 weeks. ... 

Dosing and Administration. SSRIs should be initiated at doses similar to those used for the treatment of depression and administered as a single daily dose with or without food (except for fluvoxamine). If the patient suffers from comorbid panic disorder, the SSRI dose should be started at one-fourth or one-half of the normal antidepressant dose. Patients should receive the starting dose for 2 to 4 weeks before it is increased slowly (i.e., paroxetine 10 mg/day and sertraline 50 mg/day) in weekly intervals as necessary to obtain a response. Safety for paroxetine in SAD was demonstrated in doses up to 60 mg/day, but additional therapeutic benefits above 20 mg/day were not shown. The maximum dosage of sertraline used in patients with SAD was 200 mg/day. ... 

The starting dose for fluvoxamine is 50 mg/day, which is then increased as tolerated and needed up to 300 mg/day divided into twice-daily doses. If citalopram is used, the initial dose is 20 mg/day, and it may be increased to 40 mg/day after 2 weeks. The starting dose for escitalopram is 10 mg/day, and it can be increased to a maximum of 20 mg/day. The dosage should be tapered slowly (i.e., decreasing sertraline by 50 mg/month or paroxetine by 10 mg/month) to decrease... 

Clomipramine, fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram are extensively metabolized in the Liver, and patients with significant liver disease should be prescribed these drugs cautiously and in lower doses than those used in healthy subjects. The pharmacokinetics of fluoxetine and fluvoxamine were similar in patients with renal faUme and in healthy subjects however, the manufacturer recommends starting with a lower dose in patients with renal impairment. The pharmacokinetics of sertraline are not altered in patients with significant renal dysfunction, and dosage adjustment is not necessary in these patients. Increased plasma concentrations of paroxetine occur in subjects with renal impairment. The initial dose of paroxetine should be reduced in patients with severe renal impairment, and upward titration should occm more slowly. No dosage adjustment is necessary for patients with mild to moderate renal impairment receiving citalopram. 

The multiple-dose elimination half-life of fluvoxamine was 17.4 and 25.9 hours in the elderly as compared to 13.6 and 15.6 hours in younger subjects at steady state for 50- and 100-mg doses, respectively. The safety of fluvoxamine has not been adequately studied in the elderly and patients with cardiovascular disease. Dosage should be titrated slowly during initiation of fluvoxamine therapy in elderly patients. 

Three additional agents in this group were introduced in 1993-1994 paroxetine, ven-lafloxine, and fluvoxamin. They differ from the earlier agents in duration of action, dosages, and metabolism rather than in mechanism or clinical indications. 

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