Selective serotonin reuptake inhibitors in children

Garland, E.J. and Baerg, E.A. (2001) Amotivational syndrome associated with selective serotonin reuptake inhibitors in children and adolescents. / Child Adolesc Psychopharmacol 11 181-186. 

Leonard, H.L., March, J., Rickler, K.C., and Allen, A.J. (1997) Review of the pharmacology of the selective serotonin reuptake inhibitors in children and adolescents. J Am Acad Child Adolesc Psychiatry 36 725—736. 

Although tricyclics continue to be used today to treat childhood depression (Zito et ah, 2000), the use in children with ADHD has decreased, most likely because of its association with the sudden deaths of five children (Biederman, 1991). Furthermore, the Physician s Desk Reference (PDR) warns that MPH may inhibit the metabolism of tricyclics, but no such warning exists for DEX or (AMP). Due to the concern that children on this combination of medications are prone to develop more side effects, it is not a recommended form of treatment. Instead, MPH combined with a selective serotonin reuptake inhibitor is preferable for treating a child with ADHD and comorbid depression. 

The selective serotonin reuptake inhibitors (SSRI) have been used in adults for a wide variety of disorders, including major depression, social anxiety (social phobia), generalized anxiety disorder (GAD), eating disorders, premenstrual dysphoric disorder (PMDD), post-traumatic stress disorder (PTSD), panic, obsessive-compulsive disorder (OCD), trichotillomania, and migraine headaches. Some of the specific SSRI agents have an approved indication in adults for some of these disorders, as reviewed later in this chapter. The SSRIs have also been tried in children and in adults for symptomatic treatment of pain syndromes, aggressive or irritable ( short fuse ) behavior, and for self-injurious and repetitive behaviors. This chapter will review general aspects of the SSRIs and discuss their approved indications in children and adolescents. 

The study of TCAs in children with OCD led directly from the use of these medications in adults with similar symptoms. Findings have shown significant advantage with both CMI and DMI over placebo in the treatment of this illness (Flament et al., 1985 deVaugh-Geiss et al., 1992). Clomipramine is the only TCA with a distinct indication from the FDA for the treatment of OCD. Use of TCAs has recently been supplanted by selective serotonin reuptake inhibitor (SSRI) medications that may have a more favorable side effect profile. 

Despite the diagnostic challenges that remain in trying to understand the nature of MDD in children and adolescents, advances in its treatment has progressed considerably since the last edition of this textbook. Over this interval, selective serotonin reuptake inhibitors (SSRIs) have superseded TCAs as the treatment of first choice based both on efficacy and safety considerations. As in adults, specific psychotherapies (cognitive therapy, cognitive-behavioral therapy, and interpersonal therapy) may be as effective as antidepressant medication, at least in mild to moderate depression in children and adolescents ( 111, 112). Also, evidence indicates that depression in children and adolescents may be more influenced than is depression in adults by psychosocial variables such as peers and family, as well as other environmental factors (113). 

Wilens, T., Biederman, J., Kwon, A., Chase R., Greenberg, L., Mick, E., et al. (2003). A systematic chart review of the nature of psychiatric adverse events in children and adolescents treated with selective serotonin reuptake inhibitors. Journal of Child and Adolescent Psychopharmacology, 13, 143-152. 

Committee on Safety of Medicines. Selective Serotonin Reuptake Inhibitors (SSRIs) overview of regulatory status and CSM advice relating to major depressive disorder (MDD) in children and adolescents including a summary of available safety and efficacy data. http /medicines.mh-ra.gov.uk/ourwork/monitorsafequalmed/safetymessages/ ssrioverview 101203.htm, updated 8.10.2004. 

Atomoxetine, bupropion, and TCAs are second-line alternatives to the stimulants for treatment of ADHD in children, teens, and adults. The potential benefits of these agents in comparison with stimulants include reduced risk of abuse and somewhat lower potential for sleep disturbance. TCAs are the most dangerous in overdose and pose the greatest risk for cardiovascular side effects. The monoamine oxidase inhibitor tranylcypromine is effective but used infrequently due to the potential for dangerous drug and dietary interactions. Selective serotonin reuptake inhibitors (SSRIs) are not effective for ADHD. ... 

Selective serotonin reuptake inhibitors (SSRIs) A relatively new group of medicines that have been used successfully to treat emotional and behavioral problems such as depression, panic disorder, obsessive-compulsive disorder ((XID), bulimia, and posttraumatic stress disorder in adults. These medications are now being used to treat the same types of behavior in children. Some examples of SSRIs include Prozac (fluoxetine), Zoloft (sertraline), Luvox (fluvoxamine), and Paxil (paroxetine). 

Metabolic and cardiovascular adverse events were further studied by the same authors in the same sample of children and adolescents [7 ]. Compared with the controls, the treated cohort had a higher prevalence of obesity (OR = 2.1), type 2 diabetes mellitus (OR = 3.2), cardiovascular conditions (OR = 2.7), and orthostatic hypotension (OR = 1.6). In the treated cohort, those who had been exposed to multiple antipsychotic drugs had a significantly higher risk of incident obesity/weight gain (OR = 2.3), type 2 diabetes mellitus (OR = 2.4), and dyslipidemia (OR = 5.3). Incident cardiovascular events were more likely with the use of conventional antipsychotic drugs (OR = 4.3) and mood stabilizers (OR = 1.3). Incident orthostatic hypotension h os more prevalent in those co-prescribed selective serotonin reuptake inhibitors (OR = 1.8) and mood stabilizers (OR = 1.3). 

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