SSRIs: Serotonin Syndrome, Hypomania, and Mania

When excessive serotonin stimulation occurs, a serotonin syndrome can develop, which includes confusion, diaphoresis, hyperreflexia, ataxia, and myoclonus, and it often occurs when SSRI agents are used together with monoamine oxidase inhibitors (MAOIs) (Lappin and Auchincloss 1994. The combined use of MAOIs and SSRIs can lead to fatal outcomes.

Although SSRIs often help with mood lability, on occasion hypomania or mania may develop with longer term use, particularly if there is a genetic predisposition to bipolar disorder (Sovner and Pary 1993). In patients with FXS, hypomania, mania, or severe agitation develops in 25% who are treated with SSRIs. Although the makers of citalopram have reported the lowest risk for mania in the initial study population, it is unclear whether this medication will have the lowest risk of all SSRIs for these symptoms in patients with FXS. If agitation or an increase in aggressive behavior occurs, then the SSRI dose should be lowered or discontinued (Hagerman 1999a, 1999b). If mood lability or aggression persists, then a mood stabilizer such as valproate, carbamazepine, lithium, or an atypical antipsychotic can be added.

SSRIs: Verbalization

In the report by Hagerman et al. (1994), four males with FXS experienced a significant increase in verbalizations and less social withdrawal on fluoxetine. This may be related to the activation effect of fluoxetine or to a decrease in anxiety, which facilitates social interaction. Such an effect has also been reported in autism (Cook et al. 1992; DeLong et al. 1998). There may also be a direct beneficial effect on language. For example, Kramer (1993) reported a case with improved language skills in an intellectually normal female who was treated for depression. Fluoxetine or fluvoxamine have also been used to treat selective mutism (Black and Uhde 1994; Lafferty and Constantino 1998). This disorder is related to anxiety, and the improvement in language on fluoxetine or fluvoxamine may be related to the antianxiety effects of SSRIs. Anxiety is a significant problem in FXS; we have seen seven cases of selective mutism in girls with FXS, and fluoxetine improved language in one girl in whom it was tried (Hagerman et al. 1999). A novel treatment for selective mutism which may have a synergistic effect with SSRIs is the audio feedforward treatment reported by Blum et al. (1998).

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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