The new antidepressants: Selective serotonin reuptake inhibitors

Since fluoxetine's (Prozac, Eli Lilly and Company, Indianapolis, IN) launch in 1988, similar new SSRIs have entered the United States market. The available SSRIs now include sertraline (Zoloft, Pfizer Inc., New York, NY, released in 1991), paroxetine (Paxil, Smith-Kline Beecham Pharmaceuticals, Philadelphia, PA, released in 1992), and fluvoxamine (Luvox, released in 1994, in addition to fluoxetine). Citalopram, an SSRI used extensively in Europe since 1989, is expected to be released in the United States in 1998. In clinical practice, many physicians use the SSRIs off-label in children and adolescents based on extrapolation from adult data and clinical lore suggesting benefit and tolerability in the pediatric population. After more than a decade, safety and efficacy data on SSRIs in children and adolescents are finally being generated. Currently, only two SSRIs have Food and Drug Administration (FDA) indication for use in children, and both indications were given in 1997, years after each medication entered the market: (1) fluvoxamine is indicated for use in children ages 8 to 17 years old with obsessive–compulsive disorder (OCD), and (2) sertraline is indicated for use in children ages 6 to 17 years old with OCD. Fluoxetine and paroxetine have new data on safety and efficacy in children and adolescents with major depressive disorder (MDD), and that data may eventually be used to apply for FDA indications. Each of the currently available SSRIs has at least one FDA approved adult indication, more likely reflecting marketing strategy rather than treatment specificity among agents in the SSRI class. Fluoxetine has FDA indications for adult use in MDD, OCD, and bulimia nervosa; both sertraline and paroxetine have FDA indications for adult use in MDD, OCD, and panic disorder; and fluvoxamine has an FDA indication for adult use in OCD. The initial FDA adult indication for citalopram is MDD. The SSRIs gained FDA approval in the adult population without definitive safety and efficacy data on children and adolescents. For patients of all ages, the SSRIs are revolutionary agents offering greater safety and easier monitoring than older agents such as the tricyclic antidepressants (TCAs) and the monoamine oxidase inhibitors (MAOIs). Venipuncture and serial EKGs are not required for safe monitoring of SSRIs. SSRIs do not have the cardiac risk potential widely discussed in the child and adolescent psychiatry literature on TCAs. SSRIs also lack the dangerous dietary interactions that require unrealistic dietary restriction in children and adolescents taking MAOIs. Until the appearance of SSRIs, the stimulants were the only psychotropic agents most pediatricians used frequently and with relative comfort. The SSRIs quickly became a welcome addition to the pediatric formulary, expanding treatment options for a number of psychiatric disorders: OCD, MDD, anxiety disorders, and bulimia nervosa. Pediatricians and child and adolescent psychiatrists are prescribing SSRIs with greater frequency because of the obvious advantages over older agents. In fact, fluoxetine and sertraline (along with methylphenidate) are now among the 10 medications most commonly used off-label in the pediatric population. 17 However, two caveats should govern the pediatrician prescribing SSRIs to children and adolescents: (1) a thorough psychiatric assessment is essential prior to starting any psychotropic agent, and (2) the treatment with SSRIs has potential complications that demand caution. This article describes SSRI treatment strategies for the pediatrician choosing among SSRIs based on several criteria, including: 1treatment efficacy data, 2untoward effects profile, 3pharmacokinetic characteristics, 4potential for drug–drug interactions, and 5cost. The article concludes with suggestions on SSRI dosing and pretreatment work-up.