Irritability, as mentioned above, is also often mistaken as mania and not recognized as a symptom of depression. Finally, in younger children such depressive episodes are not as common as for adolescents with BD,but depressive symptoms may often intermingle with manic symptoms, and thus be underidentified. Clinicians may benefit from carefully eliciting depressive symptomatology in any child with BD, and recognizing any type of suicidal ideation, even passive, as a red flag for a serious depressive episode. Nonetheless, due to the morbidity and mortality of depression

in youth with BD, it is necessary to treat these children. One may look Inhibitors,research,lifescience,medical to the treatment of bipolar depression in adults for some guideposts, as this topic has been more studied in adults. There exist many treatment options

for patients with bipolar depression. While antidepressants have historically been the first line of treatment Inhibitors,research,lifescience,medical for bipolar depression, concern over the propensity for antidepressants to cause manic switching or cycle acceleration has led to questioning of this approach.18 It is becoming clear that overall, the addition of antidepressants to mood stabilizers for adult bipolar depression offers no greater benefit than placebo,19 and Inhibitors,research,lifescience,medical up to 44% of adults with BD have experienced a switch into mania or a mixed episode with an antidepressant trial.20 Thus, several expert consensuses have recommended nonanti depressant medications as first-line treatment for adults with bipolar depression, including lithium, Inhibitors,research,lifescience,medical lamotriginc, olanzapine-fluoxetine combination,21 and quetiapine.22 Other options showing some efficacy in controlled trials include divalproex, olanzapine, and pramipexole.23 Despite these adult data, it is still important to remember that children are distinct neurodevelopmentally, and so may not respond as adults do to psychotropic medications, both in positive and negative ways. Indeed, it appears that youth, particularly pcripubertal children, may be more Inhibitors,research,lifescience,medical susceptible to deleterious effects of selective serotonin reuptake PKC signaling pathway inhibitors inhibitors (SSRIs) than adults. In an analysis of an HMO database of 87 920

patients aged 5 to 29 years old, children 10 to 14 years old were at Rebamipide the highest risk of switching from a diagnosis of MOD to BD after being prescribed an SSRI.24 However, despite case reports of SSRI-induced mania in depressed children,25,26 one study found no evidence retrospectively that antidepressant exposure in depressed children led to higher rates of mania than children without such exposure.27 It is possible that bipolar youth are more susceptible to AIM. In a retrospective chart review, 42 children with BD who were prescribed SSRIs were seven times more likely to improve in depressive symptoms than children with BD who were not prescribed any other medication,28 but three times more likely to experience a subsequent manic episode.