As did the GSAD studies, this study compared extended-release fluvoxamine with placebo and not with the immediate-release formulation. Although no additional studies have examined the efficacy of extended-release fluvoxamine in treating OCD and the drug has not been evaluated in pediatric patients, the manufacturer notes that the immediate-release formulation has been evaluated in 2 studies with adult OCD patients and 1 pediatric OCD study, all of which had positive results.1
Table 2
Fluvoxamine extended-release: What the evidence says
| Study | Measures used | Results |
|---|---|---|
| Generalized social anxiety disorder | ||
| Westenberg et al (2004)3 | LSAS, CGI-S, CGI-I, SDS, PGI | Fluvoxamine was significantly more effective than placebo in decreasing LSAS total score (primary measure) starting at week 4 and in improving SDS, CGI-S, and CGI-I (secondary measures) |
| Stein et al (2003)4 | LSAS, CGI-S, CGI-I, SDS, PGI | Severity of illness on the CGI-S scale and disability on the SDS were significantly lower in the fluvoxamine group than in the placebo group; fluvoxamine-treated subjects had a numerically greater decrease in LSAS total scores than subjects treated with placebo |
| Davidson et al (2004)5 | LSAS, CGI-G, SDS, CGI-S, PGI | Fluvoxamine produced statistically and clinically significant improvements in symptoms starting at week 4 on the LSAS and CGI-I and at week 6 on the SDS, CGI-S, and PGI |
| Obsessive-compulsive disorder | ||
| Hollander et al (2003)6 | YBOCS, CGI-S, CGI-I | Fluvoxamine was significantly more effective than placebo in decreasing YBOCS total score beginning at week 2 and in improving CGI-S and CGI-I scores |
| LSAS: Liebowitz Social Anxiety Scale; SDS: Sheehan Disability Scale; CGI-S: Clinical Global Impression-Severity of illness; CGI-I: Clinical Global Impression-Improvement; PGI: Patient Global Impression of Improvement; YBOCS: Yale-Brown Obsessive Compulsive Scale | ||
Tolerability
In the 3 published trials of extended-release fluvoxamine, adverse event rates were similar and consistent with earlier studies of the immediate-release formulation. 1 The manufacturer considered adverse events likely to be drug-related if they had an incidence ≥5% and at least twice that of placebo (Table 3). 1, 3- 6
Adverse events caused 26% of patients in the GSAD studies and 19% in the OCD trial to discontinue treatment. No deaths, life-threatening adverse events, or suicide attempts were reported.3-6 No statistically significant differences in weight gain or loss, vital signs, laboratory findings, or ECG changes were found between patients treated with extended-release fluvoxamine and those receiving placebo.1
Table 3
Extended-release fluvoxamine: Adverse events*
| Study | Adverse events |
|---|---|
| Both GSAD and OCD studies | Abnormal ejaculation, anorexia, anorgasmia, asthenia, diarrhea, nausea, somnolence, sweating, tremor |
| GSAD studies only | Dyspepsia, dizziness, insomnia, yawning |
| OCD study only | Accidental injury, anxiety, decreased libido, myalgia, pharyngitis, emesis |
| * Includes events with an incidence ≥5% and at least twice that of placebo GSAD: generalized social anxiety disorder; OCD: obsessive-compulsive disorder | |
| Source: References 3-6 | |
Contraindications
Immediate- and extended-release fluvoxamine have the same active ingredient and therefore the same contraindications. Coadministration of alosetron, pimozide, thioridazine, or tizanidine, is contraindicated, as is using monoamine oxidase (MAO) inhibitors with extended-release fluvoxamine or within 14 days of discontinuing fluvoxamine treatment. Extended-release fluvoxamine has the same warnings that all SSRIs share regarding clinical worsening and suicide risk, administration to bipolar patients, neuroleptic malignant syndrome, serotonin syndrome, and possible increases in coagulation.1,2
The FDA classifies extended-release fluvoxamine as pregnancy category C.1 The drug is not contraindicated for lactating mothers, but because fluvoxamine is secreted in breast milk discuss with breast-feeding patients the benefits and risks of continuing fluvoxamine therapy.1 Infants exposed to immediate-release fluvoxamine in late pregnancy have developed serious adverse reactions, including respiratory distress, cyanosis, apnea, and seizures.1
Dosing
The recommended starting dose of extended-release fluvoxamine is 100 mg once daily, with or without food.1 The dose can be titrated in 50-mg/week increments as tolerated to achieve maximum therapeutic benefit, to the maximum recommended dose of 300 mg/d. Unlike immediate-release fluvoxamine, which is occasionally split into twice-daily doses, extended-release fluvoxamine must be administered only once daily, even at high doses.1,2
Related resource
- Luvox CR prescribing information. www.jazzpharmaceuticals.com/content/news/documents/LUVOX_CR.pdf.
Drug brand names
- Alosetron • Lotronex
- Fluvoxamine • Luvox
- Fluvoxamine extended-release • Luvox CR
- Pimozide • Orap
- Thioridazine • Mellaril
- Tizanidine • Zanaflex
Disclosures
Dr. Kuzma reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
Dr. Black receives research/grant support from Forest Laboratories and is a consultant to Jazz Pharmaceuticals.