Fluvoxamine labeling

The results from an open-label, pilot study evaluating the efficacy of fluvoxamine for hypochondriasis were recently published (Fallon et al, 2003). The study sample included six Hispanics (subgroup unknown). Significant improvement (57.1%) was noted for the intent-to-treat group (eight out of fourteen) based on physicianrated and self-rated scales. The sample size was too small to identify differences in response or adverse effects by ethnicity. 

Since the introduction of the first approved SSRI, fluoxetine (1) in 1987 [9], a number of SSRIs have been developed for the treatment of depression [2], Currently, the five most commonly prescribed SSRIs are fluoxetine, escitalopram (2, S-enantiomer of citalopram), sertraline (3), paroxetine (4) and fluvoxamine (5). Recent effort in the clinical development of new SSRIs has focused on the treatment of premature ejaculation (PE) by taking advantage of the ejaculation-delaying side effects of SSRIs [10]. Although SSRIs have been prescribed off-label to treat this condition, an SSRI with rapid onset of action and rapid clearance could be preferred for on-demand treatment of PE [11,12]. Dapoxetine (LY210448, 6), an... 

Apter, A., Ratzoni, G., King, R., Weizman, A., lancu, I., Binder, M., and Riddle, M. (1994) Fluvoxamine open-label treatment of adolescent inpatients with obsessive-compulsive disorder or depression. J Am Acad Child Adolesc Psychiatry 33 342-348. 

Clomipramine, fluvoxamine, and sertraline labeling all describe positive results of trials of these drugs in pediatric patients with OCD, in effect, granting an indication for these drugs in pediatric OCD. 

As of the date of this chapter (circa March, 2002), labeling changes regarding pediatric use have resulted from only two programs—the study of buspirone in pediatric GAD and a pharmacokinetic study of fluvoxamine in pediatric OCD (fluvoxamine already had a controlled clinical trial in pediatric patients). Two placebo-controlled trials with buspirone in pediatric GAD did not reveal a treatment effect, and this negative outcome is reflected in Buspar labeling. A pharmacokinetic study of fluvoxamine dosed at 100 mg bid in pediatric... 

In a 10-week open-label study, fluvoxamine (10 to 250 mg per day) in 10 combat veterans with chronic PTSD was also shown to be effective and well tolerated ( 277). 

An open-label trial of fluvoxamine in 20 patients and a single case report with sertraline are also encouraging ( 537, 538). 

Oral 10, 20, 40 mg capsules 10, 20 mg tablets 20 mg/5 mL liquid Oral delayed-release (Prozac Weekly) 90 mg capsules Fluvoxamine (generic, labeled only for obsessive-compulsive disorder)... 

Fluvoxamine (Luvox, labeled only for obsessive- compulsive disorder)... 

According to the FDA-approved label for fluvoxamine (Luvox in the Physicians Desk Reference, 2001), the SSRI causes a 4% rate of mania in children under age 18, compared to no cases of mania produced in a similar group of children on placebo. The rate was at least 4 times greater than in adults (see Breggin, 2002a, for a more complete analysis of the Luvox label). Moore (2004) analyzed adverse event reports made to the FDA concerning children and adults in association with the six most commonly prescribed antidepressants Zoloft, Paxil, Prozac, Cel-exa, Wellbutrin, and Effexor. Fie reported the following ... 

Breggin, P. (2002a). Fluvoxamine as a cause of stimulation, mania, and aggression with a critical analysis of the FDA-approved label. International Journal of Risk and Safety in Medicine, 14, 71-86. 

SAD can present in children of preschool to elementary school age. If the disorder is not treated, it can persist into adulthood and increase the risk of depression and substance abuse. CBT and social skills training are effective nonpharmacological therapies in children. Pharmacological evidence is limited to case studies or open-label trials. SSRIs are considered first-line therapy because of tolerability and effectiveness. Fluoxetine, fluvoxamine, sertraline, and paroxetine were effective in children with SAD. Headache, nausea, drowsiness, insomnia, jitteriness, and stomach aches were reported in children receiving SSRIs. 

Although favorable reports for other SSRIs have been reported in open-label studies (reviewed by Posey et al., 2006), these are of doubtful value for the reasons discussed above. The fact that the largest, most comprehensive study to date failed to find a benefit of a SSRI for the specific indication for which these agents are most commonly prescribed in ASD casts doubt on the value of this class of medications in ASD. Indeed, aside from one study of fluvoxamine in adults (McDougle et al., 1996) and one of fluoxetine in children (Hollander et al., 2005) (discussed above), there is little to support the use of SSRIs in ASD. Moreover, even in the studies that have reported favorable results, improvement in core symptoms has been found to be variable and generally rather modest, providing little support for the hypothesis that abnormalities in serotonin systems play a central role in autism. 

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