While severity of manic episodes can be successfully reduced, repeated recurrences are common with ~40% of patients meeting criteria for rapid cycling after aggressive treatment. Manic episodes present much earlier in children of bipolars and due to unique presentation physicians often mistakenly diagnose such children with attention-deficit/hyperactivity disorder. Differential symptoms include suicidal thoughts, grandiosity, hallucinations, and depressive withdrawal. Such children may require the usual combination treatment with a mood stabilizer and an antipsychotic, with the addition of a stimulant as well. Treatment of adults and children often includes second-generation antipsychotics, which have increasingly shown efficacy both as monotherapy and adjunctive treatments of acute mania. Most recently, some anticonvulsants have demonstrated acute antimanic properties as well and more studies of their role in bipolar disorder are underway.

Antipsychotics have been utilized in thetreatment of bipolar disorder for many decades and were the mainstay oftreatment before lithium was reintroduced in the late 1960s.Today, many bipolar patients who present with psychotic features aremisdiagnosed and prescribed an antipsychotic for another disorder.Estimates of psychotic symptoms in bipolar disorder, particularly duringa manic episode, are ≥50% by clinical assessment and even higher byindividual reports. Thus, antipsychotics are frequently used: as firsttreatment for psychosis not recognized as bipolar disorder, and as anadjunct to a mood-stabilizing agent in bipolars with psychotic symptoms.

Most recently, antipsychotics have beenexamined for their mood-stabilizing properties as well (Slide 9). Onemay conceptualize using a selective serotonin reuptake inhibitor (SSRI)antidepressant for disorders such as panic disorder orobsessive-compulsive disorder, and using an antiepileptic as amood-stabilizing agent; however, it is more difficult to accept that anagent approved for treatment of psychosis can be a primary therapy forbipolar disorder. Data from the monotherapy trials suggest thatsecond-generation antipsychotics (SGAs) are at least as effective aslithium and valproic acid for acute mania. There is a very largedatabase indicating that SGAs can be utilized as monotherapy for acutemania. However, there is limited data on the role of theseagents in prevention of relapse and recurrence and in their efficacy fordepression in the context of bipolar disorder. More studies will beneeded to clarify whether SGAs should be used as monotherapy or whetherthey would be best used as augmenting agents in severe and psychoticallymanic or depressed patients.

Bipolar disorder is presenting at a younger ageof onset. In the past, many children with bipolar disorder wereundiagnosed and ended up in juvenile detention centers. These childrenwere also often misdiagnosed with severe attention-deficit/hyperactivitydisorder (ADHD) or conduct disorder. In addition, an increasedprevalence rate of substance use disorders and possibly stimulantprescriptions may be responsible for the shift in age of onset ofbipolar disorder. The most compelling epidemiological observations havecome out of the Netherlands, where they typically treat ADHDbehaviorally rather than with stimulants. Childhood bipolar disorderremains unidentified in the Netherlands despite aggressive searching,whereas adolescent and adult bipolar disorder has been found in numberssimilar to those in the United States. This providescross-sectional epidemiological evidence that stimulants may be shiftingthe age of onset in patients who are presenting with potentiallyprodromal bipolar symptoms. Lastly, several researchers speculate thattrinucleotide repeats in the DNA (deoxyribonucleic acid) may beresponsible for so-called genetic anticipation phenomenon, by whichexpansion of trinucleotide repeats in successive generations may beshifting the age of onset to an earlier age. These are just some of themechanistic possibilities for why we are seeing a shift in the age ofonset of bipolar disorder.

Lewinsohn and colleagues found thatthe lifetime prevalence of adolescent bipolar I and II disorder is ~1%,with a 5% lifetime prevalence rate of subsyndromal bipolar disorder.Many symptomatic children and adolescents do not meet full durationcriteria for a hypomanic or manic episode, or they may be one symptomshort of meeting criteria for the disorder.