In cases of psychosis, atypical antipsychotics must be added after working down the list of agents that worked previously in a particular patient.26,33 If mild aggression is present, switching to atypical antipsychotic monotherapy may be helpful. For moderate to severe aggression, the combination of a mood stabilizer and an atypical antipsychotic may be beneficial. Clonidine(Drug information on clonidine) can be used to subdue uncontrolled rage attacks.34,35 However, in our experience, children can become disinhibited or become more aroused after persistent use of clonidine, although this particular observation needs to be further examined.
If sleeping difficulties arise, the clinician can increase the evening dose of a sedating mood stabilizer. Beyond that, 1 to 3 mg of melatonin(Drug information on melatonin) or 25 to 50 mg of trazodone can be administered to establish a sleep routine, which is critical in managing PBD.36-38 While these compounds are not empirically supported by specific research on sleep in PBD, they are known to be sedating and safe in pediatric populations. Also, they interfere minimally with rapid eye movement sleep. Because of abuse potential, benzodiazepines are not recommended.39
Since the start of our algorithm project and the subsequent publication of our feasibility study, we have continued to update our strategies and tactics on the basis of new information.26 Aripiprazole(Drug information on aripiprazole) has been added to the list of atypical antipsychotics. Lamotrigine(Drug information on lamotrigine) has been elevated as a first-line agent for depression. Atomoxetine(Drug information on atomoxetine) was added as a second-line medication after trying stimulants for comorbid ADHD.
In our experience, clonidine has been shown to exacerbate symptoms in a subgroup of patients with PBD despite excellent short-term response for autonomic arousal. We are closely monitoring this phenomenon. Consequently, we are currently choosing guanfacine(Drug information on guanfacine) (given the longer half-life than that of clonidine) or propranolol(Drug information on propranolol) as an alternative for extreme hyperarousal that does not respond to mood stabilization. Given the recent review presenting equivocal evidence of trazodone’s efficacy as sleep medication, this agent was placed lower on the list after medications such as melatonin that had better safety and efficacy data in idiopathic insomnia, even though trazodone was not tested for sleep problems directly in patients with PBD.36,40 Chronic unremitting symptoms must be treated by using:
• Alternative monotherapy
• At least 2 trials of combination mood stabilizers plus an atypical antipsychotic
• Moving on to triple therapy and addressing comorbidities (eg, an additional stimulant for comorbid ADHD)
While ADHD is a distinct disorder separate from PBD, it is not understood whether the ADHD-like symptoms in children with PBD warrant additional treatment beyond mood stabilization. In our study, several participants continued to show symptoms of inattention after mood stabilization that warranted stimulant medication.26 Cognitive difficulties, such as shifting attention and executive dysfunction, seen in both ADHD and PBD, potentially can be addressed with stimulants. Stimulants are almost always given in long-acting formulations unless an additional after-school dose is required to sustain the benefits.
Among psychostimulants, long-acting methylphenidate(Drug information on methylphenidate) and mixed amphetamine salts are equally effective.41 Atomoxetine is an alternative treatment if stimulants have been ineffective or have not been tolerated. No data establish the safety or efficacy of atomoxetine in treating youth with comorbid ADHD and PBD. Atomoxetine is a selective norepinephrine(Drug information on norepinephrine) reuptake inhibitor with potential antidepressant effects and could theoretically trigger or exacerbate symptoms of mania in patients with PBD. Atomoxetine should be used with great care in youth with PBD.
Anxiety disorders, including generalized anxiety disorder and separation anxiety disorder, are relatively common, especially in those with bipolar I disorder. Psychotherapeutic interventions, such as cognitive-behavioral therapy (CBT), remain the first choice of treatment in children and adolescents with comorbid PBD and anxiety disorder. Small doses of SSRIs—such as escitalopram(Drug information on escitalopram) XR as adjuvant medication—may be effective if mania is stabilized, although there are no controlled trials for anxiety comorbid with bipolar disorder. SSRIs are the only medications consistently shown to be effective in controlled trials for childhood anxiety disorders.42,43
SSRI treatment intervention requires educating the family about the risk of a manic switch, and close monitoring of the treatment response is necessary. Guanfacine may be considered if vigilance and autonomic hyperarousal are prominent.44 Benzodiazepines and buspirone(Drug information on buspirone) are alternative choices.26 The risk of developing dependence needs to be considered for long-term use of benzodiazepines in adolescents. Buspirone may not be effective in all cases. Propranolol may be considered in cases of performance anxiety. Medication is often used in small doses to reduce risks of exacerbating bipolar disorder and to enable patients to benefit from psychotherapeutic interventions.