Is fluvoxamine safe and effective for treating anxiety disorders in children?

BACKGROUND: Anxiety disorders are common psychiatric illnesses in children and may even precede the development of subsequent psychiatric illnesses in adulthood. Data are lacking to guide treatment decisions. Although commonly used for treating anxiety disorders in adults, selective serotonin reuptake inhibitors (SSRIs) are not well studied for anxiety in children, except for obsessive-compulsive disorder. Currently, only fluvoxamine and sertraline are approved by the US Food and Drug Administration for use in children (ages 6-8 years) with obsessive-compulsive disorder.

POPULATION STUDIED: Eligible subjects were aged 6 to 17 years, were recruited from 5 US university-based psychopharmacology department practices, and must have had either social phobia, separation anxiety, or generalized anxiety based on the criteria from the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. All patients had clinically important anxiety symptoms according to the Pediatric Anxiety Rating Scale (PARS) and impaired functioning (score <60) on the Children’s Global Assessment (CGA) scale. Each subject agreed to attend weekly visits with a parent. Children could not participate if they were treated with another psychoactive medication or had coexisting psychiatric disorders, conduct disorder, developmental delay, mental retardation, or attention-deficit/hyperactivity disorder. Most children were aged 6 to 12 years (74%) and had both parents at home (72%), but they had variable ethnic and socioeconomic backgrounds.

STUDY DESIGN AND VALIDITY: In this randomized double-blinded controlled trial, subjects received either fluvoxamine (n=63) or placebo (n=65) in conjunction with supportive psychotherapy (that did not include behavioral anxiety treatment) for 8 weeks. The authors did not state that allocation to treatment was concealed before entering patients into the study. The fluvoxamine dose was increased weekly in approximately 50-mg increments to a maximum daily dose of 300 mg in adolescents or 250 mg in children younger than 12 years unless the patient had resolution of symptoms or adverse effects. Intention-to-treat analysis was appropriately used, because the dropout rate approached 19% (24/128). To maintain inter-rater reliability, 16 subjects were rated by each clinician, and differences were resolved by discussion. The study was limited by its short duration (2 months), given that the anxiety disorders studied are commonly chronic. Also, long-term treatment would be necessary to evaluate possible drug-related adverse cognitive effects. This study included a heterogeneous group of patients and did not provide a subgroup analysis of response within the various anxiety disorders. The extensive exclusion criteria limit the external validity in the more complex patients likely encountered in clinical practice.

OUTCOMES MEASURED: The 2 primary outcomes focused on the anxiety symptoms and functional impairment as measured by changes in the weekly PARS and the Clinical Global Impressions-Improvement Scale (CGIS).

RESULTS: From baseline to study completion, the PARS decreased from 18.7+2.9 to 9.0+7.0 in the fluvoxamine group and from 19.0±3.0 to 15.9±5.3 in the placebo group (P <.001). Significant differences were detectable by week 3 and peaked at week 6. Adequate response, as defined as improvement scores less than 4 on the CGIS, was achieved in 48 of 63 children (76%) in the fluvoxamine group and 19 of 65 children (29%) in the placebo group (P <.001). Treatment discontinuation was attributable to adverse events in 5 children (8%) treated with fluvoxamine and 1 child (2%) in the placebo group. Five patients in the placebo group withdrew because of lack of efficacy. Abdominal discomfort was reported more often in the fluvoxamine group (49% vs 28%, P=.02). The greater likelihood of an increase in motor activity in the fluvoxamine group (27% vs 12%) did not quite reach statistical significance (P=.06).