Based on the TMAP algorithm, recent clinical trial evidence, and our experience in treating pediatric BPD, we offer an approach for treating mania/hypomania in patients age 10 to 17 (see Proposed Algorithm). For dosing and precautions when using atypical antipsychotics in children and adolescents with BPD, see Table 2.15-17
Comorbid psychiatric illnesses (such as anxiety disorders) are prevalent in adolescents with BPD. Evidence in adults and adolescents suggests that some atypical antipsychotics may provide additional benefit for these conditions as well. Thus, consider comorbid conditions and symptoms when choosing antimanic agents.
Attention-deficit/hyperactivity disorder (ADHD) is a common comorbidity in children with BPD, and stimulant medications are most often prescribed to treat inattentiveness and hyperactivity. Caution is imperative when treating bipolar youth with stimulants, which can exacerbate manic symptoms. Treat the patient’s mania before adding or reintroducing stimulant medication. Research and clinical experience suggest that if you first stabilize these patients on a mood stabilizer or atypical antipsychotic, adding a stimulant can be very helpful in treating comorbid ADHD symptoms. Start with low stimulant doses, and increase slowly.
Table 1
RCTs of atypical antipsychotics in patients age 10 to 17
with bipolar I disorder*
| Antipsychotic and source | Bipolar I episode (# of subjects) | Trial duration (days) | Dosage (mg/d) | Response rate or YMRS score change | NNT | Mean weight gain (kg) |
|---|---|---|---|---|---|---|
| Risperidone Pandina et al3 AACAP 2007 | Manic, mixed (169) | 21 | 0.5 to 2.5 3 to 6 | 59% 63% | 3.3 3.5 | 1.9 1.4 |
| Olanzapine Tohen et al4 | Manic, mixed (161) | 21 | 10.4 ± 4.5 | 49% | 4.1 | 3.7 ± 2.2 |
| Quetiapine DelBello et al5 AACAP 2007 | Manic (284) | 21 | 400 600 | 64% 58% | 4.4 4.2 | 1.7 1.7 |
| Aripiprazole Wagner et al6 ACNP 2007 | Manic, mixed (296) | 28 | 10 30 | 45% 64% | 4.1 2.4 | 0.9 0.54 |
| Ziprasidone DelBello et al7 APA 2008 | Manic, mixed (238) | 28 | 80 to 160 | –13.83 with ziprasidone, –8.61 with placebo | 3.7 | None |
| *Each trial included a 6-month open extension phase; results are pending | ||||||
| AACAP: American Academy of Child and Adolescent Psychiatry; ACNP: American College of Neuropsychopharmacology; APA: American Psychiatric Association; NNT: number needed to treat; RCT: randomized controlled trial; YMRS: Young Mania Rating Scale | ||||||
Table 2
Recommended antipsychotic use in pediatric bipolar disorder
| Drug | Starting dosage (mg) | Target dosage (mg/d) | Precautions |
|---|---|---|---|
| Aripiprazole | 2.5 to 5 at bedtime | 10 to 30 | Monitor for CYP 3A4 and 2D6 interactions, weight, BMI, cholesterol, lipids, and glucose |
| Olanzapine | 2.5 bid | 10 to 20 | Monitor for CYP 2D6 interactions, weight, BMI, cholesterol, lipids, glucose, and prolactin levels |
| Quetiapine | 50 bid | 400 to 1,200 | Monitor for weight, BMI, cholesterol, lipids, and glucose |
| Risperidone | 0.25 bid | 1 to 2.5 | Monitor for EPS, hyperprolactinemia (and associated sexual side effects, including galactorrhea), weight, BMI, cholesterol, lipids, glucose, and prolactin levels |
| Ziprasidone | 20 bid | 80 to 160 | Check baseline ECG and as dose increases or with reason for high level of concern; monitor prolactin levels |
| BMI: body mass index; CYP: cytochrome P450; ECG: electrocardiography; EPS: extrapyramidal symptoms | |||
| Source: References 15-17 | |||
Proposed Algorithm: Treating a bipolar mixed/manic episode in patients age 10 to 17
Stage 1. Consider patient’s experience with antipsychotics, body weight, and family history when choosing first-line monotherapy (1A). Quetiapine poses low risk for extrapyramidal symptoms and tardive dyskinesia. Aripiprazole and ziprasidone pose relatively low risk of weight gain. Risperidone is potent at low doses but increases prolactin levels (long-term effect unknown).
Second-line choices (1B) are mood stabilizers lithium and valproate (because of lower potency than atypical antipsychotics), and olanzapine (which—although potent—causes substantial weight gain). In case of lack of response or intolerable side effects with initial agent, select an alternate from 1A or 1B. If this is not effective, move to Stage 2.
Stage 2. Consider augmentation for patients who show partial response to monotherapy (in your clinical judgment “mild to moderately improved” but not “much or very much improved”).
Stage 3. Combination therapy could include 2 mood stabilizers (such as lithium and valproate) plus an atypical antipsychotic; 2 atypical antipsychotics; or other combinations based on patient’s past responses. No research has shown these combinations to be efficacious in bipolar children and adolescents, but we find they sometimes help those with treatment-resistant symptoms.
Duration. Maintain psychotropics 12 to 18 months. When patient is euthymic, slowly taper 1 medication across several months. If symptoms recur, reintroduce the mood-stabilizing agent(s).
Source: Adapted and reprinted with permission from Kowatch RA, Fristad MA, Findling R, et al. Clinical manual for the management of bipolar disorder in children and adolescents. Arlington, VA: American Psychiatric Publishing, Inc.; 2008
Managing adverse effects
Although clinically effective, atypical antipsychotics may cause serious side effects that must be recognized and managed. These include extrapyramidal symptoms (EPS), tardive dyskinesia (TD), weight gain and obesity, hyperlipidemia, increased prolactin levels, and QTc changes. Counsel patients and families about the risks and benefits of antipsychotics when you consider them for children and adolescents with BPD (Table 3).
EPS. Drug-induced parkinsonism and akathisia are the most common EPS in children and adolescents with BPD treated with atypical antipsychotics.18