SSRIs: Fluoxetine (Prozac)

The first SSRI, fluoxetine (Prozac), became available in the late 1980s. At the time of this writing, five SSRIs are available in the United States: fluoxetine (Prozac), sertraline (Zoloft), fluvoxamine (Luvox), paroxetine (Paxil), and citalopram (Celexa). In both adults and children with normal intellectual function, they effectively treat depression (Rey-Sanchez and Gutierrez-Casares 1997; DeVane and Sallee 1996; Mendels et al. 1999; Ambrosini et al. 1999), anxiety (Birmaher et al. 1994; March et al. 1998; Fairbanks et al. 1997; Lepola et al. 1994), obsessive-compulsive disorder (OCD) (Geller et al. 1995; Rosenberg et al. 1999, 2000; Thomsen 1997), panic disorder and school phobia (Lepola et al. 1996), ADHD (Barrickman et al. 1991), and irritable, difficult temperament (Garland and Weiss 1996). Because of their efficacy for a variety of problems and because of their relative safety compared to tricyclics, they are used by millions of patients worldwide (Kramer 1993).

In individuals with developmental disabilities, SSRIs have been helpful in decreasing obsessive-compulsive behavior (Dech and Budow 1991; Warnock and Kestenbaum 1992; Bodfish and Maddison 1993), self-injurious behavior (Markowitz 1992), autistic behavior (Cook et al. 1992; Hellings et al. 1996; Steingard et al. 1997), emotional lability (Sloan et al. 1992; Selinger et al. 1992), and aggression (Ghaziuddin and Tsai 1991).

In an open trial of fluoxetine in 37 children with autism between the ages of two and seven years, 22 (59%) had a positive response with improvements in behavior, cognition, and social abilities and marked increase in language acquisition (DeLong et al. 1998). The SSRIs block reuptake of serotonin, thereby enhancing levels in the synapse, particularly in the raphe nucleus and upper brain stem. The major ascending serotonin pathways go to the frontal cortex, cingulate cortex, and other limbic structures that are important for emotions.

The use of fluoxetine in FXS was surveyed by Hagerman et al. (1994). All males and females at our center who were affected by FXS and were prescribed fluoxetine for behavioral or emotional problems were surveyed with a questionnaire to evaluate the benefits and problems associated with the use of fluoxetine. The study of patients included 18 females (6 with the premutation and 10 with the full mutation) and 17 males with FXS (10 with the full mutation and 4 with a mosaic pattern). Overall fluoxetine was helpful in 83% of the females who were treated for depression, mood lability, anxiety, panic attacks, outburst behavior, or obsessive-compulsive symptoms. In the males fluoxetine was helpful in 71%, and it was usually prescribed for physical outbursts or severe verbal outbursts. Five males (29%) did not improve or had worse behavior on fluoxetine. Occasionally an increase in outburst behavior occurred in the males, probably related to the activation effect of fluoxetine. Other side effects included nausea in 12%, insomina 6%, increased hyperactivity 6%, weight gain 6%, and weight loss in 6% of the males. In the females similar side effects were noted, in addition to one woman who developed hypomania and another woman who experienced suicidal ideation, which was a problem before starting fluoxetine. In general fluoxetine was a very helpful medication for the majority of males and females who were treated. In women with the premutation, fluoxetine decreased obsessive worries, anxiety, and/or depression, and in women with the full mutation fluoxetine improved mood lability and the occasional problem with outburst behavior. In males fluoxetine usually improved physical or verbal outbursts, which are a common problem for the adolescent or adult male with FXS. This study was not a controlled and blinded assessment of the efficacy of fluoxetine in FXS. Instead, this report suggests efficacy and the need for controlled studies.

This article is not intended to give medical advice for individual cases.  Any change in medical treatment should be done in consultation with appropriate medical personnel. This article is written for medical professionals.  Some of the terms will be unfamiliar to those who are not trained in medical fields. *This article is from the chapter on treatment in the 3rd edition of Fragile X Syndrome: Diagnosis, Treatment, and Research edited by Randi Jenssen Hagerman, M.D. and Paul Hagerman, M.D., Ph.D., to be published May 2002.  It is included with permission from The Johns Hopkins University Press. References to other chapters refer to chapters in the book which are not included as part of this website. The complete 3rd edition of Fragile X Syndrome: Diagnosis, Treatment, and Research can be ordered from the National Fragile X Foundation by calling 1-800-688-8765 or from The Johns Hopkins University Press at 1-800-537-5487.

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