Treatment of manic, hypomanic, or mixed episodes
|
Open-label |
Kafantaris, 20034040. Kafantaris V, Coletti D, Dicker R, Padula G, Kane JM. Lithium treatment of acute
mania in adolescents: a large open trial. J Am Acad Child Adolesc Psychiatry.
2003;42:1038-45.
|
Li |
0.6-1.2 mEq/L |
100 |
4 weeks |
63 of 100 subjects responded; 26 of 100 achieved remission |
Adjunctive antipsychotics were used in 46% of subjects |
Follow-up |
Pavuluri, 20054141. Pavuluri MN, Henry DB, Carbray JA, Naylor MW, Janicak PG. Divalproex sodium for
pediatric mixed mania: a 6-month prospective trial. Bipolar Disord. 2005;7:266-73.
|
DVP |
50-120 µg/mL |
34 |
6 months |
73.5% response rate52.9% remission rate |
Dropout rate: 6.4%, due to benign rash |
Open-label |
Wagner, 20024242. Wagner KD, Weller EB, Carlson GA, Sachs G, Biederman J, Frazier JA, et al. An
open label trial of divalproex in children and adolescents with bipolar disorder. J Am Acad Child
Adolesc Psychiatry. 2002;41:1224-30.
|
DVP |
45-125 µg/mL |
40 |
2-8 weeks |
61% response rate
|
10% used adjunctive therapy with Li and 53% used other drugs simultaneously |
Open-label |
Kowatch, 20005858. Kowatch RA, Suppes T, Carmody TJ, Bucci JP, Hume JH, Kromelis M, et al. Effect
size of lithium, divalproex sodium and carbamazepine in children and adolescent with bipolar
disorder. J Am Acad Child Adolesc Psychiatry. 2000;39:713-20.
|
Li, DVP, and CBZ |
Li: 0.8-1.2 mEq/LDVP: 85-110 µg/LCBZ: 7-10 µg/L |
42 |
6 weeks |
Response rates were as follows: DVP, 53%; Li, 38%; CBZ, 38%
|
All three mood stabilizers were well tolerated, with no serious adverse effects |
Open-label |
Joshi, 20105959. Joshi G, Wozniak J, Mick E, Doyle R, Hammerness P, Georgiopoulos A, et al. A
prospective open-label trial of extended-release carbamazepine monotherapy in children with bipolar
disorder. J Child Adolesc Psychopharmacol. 2010;20:7-14.
|
CBZ |
788±252 mg/day |
16 |
8 weeks |
Modest levels of improvement in YMRS scores |
Suggests lack of complete resolution of mania |
Open-label |
Pavuluri, 20094343. Pavuluri MN, Henry DB, Moss M, Mohammed T, Carbray JA, Sweeney JA. Effectiveness
of lamotrigine in maintaining symptom control in pediatric bipolar disorder. J Child Adolesc
Psychopharmacol. 2009;19:75-82.
|
Lamotrigine |
150-200 mg/day |
46 |
14 weeks |
Response rate: 72% for manic symptoms and 82% for depressive symptoms
|
Benign rash in 6.4% of subjects |
Open-label |
Biederman, 20104444. Biederman J, Joshi G, Mick E, Doyle R, Georgiopoulos A, Hammerness P, et al. A
prospective open-label trial of lamotrigine monotherapy in children and adolescents with bipolar
disorder. CNS Neurosci Ther. 2010;16:91-102.
|
Lamotrigine |
160.7±128.3 mg/day (subjects < 12 years);219.1±172.2 mg/day (subjects > 12
years) |
39 |
12 weeks |
Response rates: 66% (< 12 years) and 54% (> 12 years)
|
25% of subjects discontinued the trial due to adverse events, mostly dermatological |
Open-label |
Pavuluri, 20065151. Pavuluri MN, Henry DB, Carbray JA, Sampson GA, Naylor MW, Janicak PG. A one-year
open-label trial of risperidone augmentation in lithium nonresponder youth with preschool-onset
bipolar disorder. J Child Adolesc Psychopharmacol. 2006;16:336-50.
|
Li + Risp |
Li: 0.6-1.0 mEq/LRisp: 2 mg/day |
38 |
11 months |
Response rate: 85.7%
|
Weight gain, nausea/vomiting, increased appetite, stomach pain, sedation, polyuria, enuresis,
tremor, restlessness, muscle stiffness, fatigue, cognitive dulling, flu-like symptoms |
Open-label |
Pavuluri, 20045252. Pavuluri MN, Henry DB, Carbray JA, Sampson G, Naylor MW, Janicak PG. Open-label
prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric
mania. J Affect Disord. 2004;82:S103-11.
|
Risp + Li vs. Risp + DVP |
Risp: 3 mg/day;Li: 0.6-1.0 mEq/L;DVP: 50-120 µg/mL |
37 |
6 months |
Response rates (≥ 50% change from baseline YMRS score at the end of study): 80% for DVP
+ Risp and 82.4% for Li + Risp |
Combination therapy was well tolerated in both groups. Two subjects discontinued earlier in Risp
+ Li group due to enuresis and fatigue |
Open-label |
Wozniak, 20095454. Wozniak J, Mick E, Waxmonsky J, Kotarski M, Hantsoo L, Biederman J. Comparison
of open-label, 8-week trials of olanzapine monotherapy and topiramate augmentation of olanzapine for
the treatment of pediatric bipolar disorder. J Child Adolesc Psychopharmacol.
2009;19:539-45.
|
Olan vs. Olan + topiramate |
Monotherapy: Olan 8.6±3.4 mg/dayCombined: Olan 9.9±5.2 and topiramate 70.5-30.5
mg/day |
40 |
8 weeks |
Statistically significant reduction in YMRS scores with both treatments |
“Spacey”, tremor, akathisia, “dazed”, nystagmus, speech
deterioration |
Open-label |
Biederman, 20055353. Biederman J, Mick E, Hammernessa P, Harpold T, Aleardi M, Dougherty M, et al.
Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in
preschool-age children. Biol Psychiatry. 2005;58:589-94.
|
Olan vs. Risp |
Olan: 10 mg/dayRisp: 2 mg/day |
31 |
8 weeks |
Response rates: 69% for Risp and 53% for Olan
|
Preschoolers.Weight gain observed with both drugsHigher prolactin levels with Risp |
Open-label |
Biederman, 20054545. Biederman J, Mick E, Wozniak J, Aleardi M, Spencer T, Faraone SV. An open-label
trial of risperidone in children and adolescents with bipolar disorder. J Child Adolesc
Psychopharmacol. 2005;15:311-7.
|
Risp |
1.25±1.5 mg/day |
30 |
8 weeks |
Significant decrease in YMRS (average 14.4 points) |
Eight dropouts (seven due to lack of efficacy and one due to orthostatic hypotension) |
Open-label |
Frazier, 20014646. Frazier JA, Biederman J, Tohen M, Feldman PD, Jacobs TG, Toma V, et al. A
prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with
bipolar disorder. J Child Adolesc Psychopharmacol. 2001;11:239-50.
|
Olan |
2.5-20 mg/day |
23 |
8 weeks |
61% of response rate
|
Increase of body weight |
Retrospective |
Marchand, 20054747. Marchand WR, Wirth L, Simon C. Quetiapine adjunctive and monotherapy for
pediatric bipolar disorder: a retrospective chart review. J Child Adolesc Psychopharmacol.
2004;14:405-11.
|
Quetiapine |
397.4±221.4 mg/day |
32 |
6.1±5.9 months |
50% of subjects symptom improvement |
14 were on quetiapine monotherapy |
Open-label |
Biederman, 20074848. Biederman J, Mick E, Spencer T, Dougherty M, Aleardi M, Wozniak J. A prospective
open-label treatment trial of ziprasidone monotherapy in children and adolescents with bipolar
disorder. Bipolar Disord. 2007;9:888-94.
|
Ziprasidone |
57.3±33.9 mg/day |
21 |
8 weeks |
Improvement in mean YMRS and CGI-I scores |
Sedation, headache, and gastrointestinal problems |
Open-label |
Tramontina, 20074949. Tramontina S, Zeni CP, Pheula GF, de Souza CK, Rohde LA. Aripiprazole in
juvenile bipolar disorder comorbid with attention-deficit/hyperactivity disorder: an open clinical
trial. CNS Spectr. 2007;12:758-62.
|
Aripiprazole |
2-20 mg/day |
10 |
6 weeks |
Improvement in global functioning scores (p = 0.01), manic symptoms (p < 0.01), and ADHD
symptoms (p < 0.01) |
Sialorrhea, tiredness, sedation, confusion, depressive symptoms, increased appetite or decreased
appetite, sweating, tremors, nervousness, and anxiety |
Open-label |
Findling, 20115050. Findling RL, McNamara NK, Youngstrom EA, Stansbrey RJ, Frazier TW, Lingler J, et
al. An open-label study of aripiprazole in children with a bipolar disorder. J Child Adolesc
Psychopharmacol. 2011;21:345-51.
|
Aripiprazole |
15 mg/day |
69 |
16 weeks |
62.5% met response criteria
|
Stomachache, headache, and increased appetite |
Open-label |
Wozniak, 20065656. Wozniak J, Biederman J, Mick E, Waxmonsky J, Hantsoo L, Best C, et al. Omega-3
fatty acid monotherapy for pediatric bipolar disorder: a prospective open-label trial. Eur
Neuropsychopharmacol. 2007;17:440-7.
|
Omega-3 fatty acid |
1,290-4,300 mg/day |
20 |
8 weeks |
35% of subjects had improvement in symptoms (≥ 50% decrease in YMRS) |
Small but statistically significant weight gain |
Open-label |
Rucklidge, 20105757. Rucklidge JJ, Gately D, Kaplan BJ. Database analysis of children and adolescents
with bipolar disorder consuming a micronutrient formula. BMC Psychiatry.
2010;10:74.
|
Micronutrient formula (EMPowerplus) |
15 capsules of micronutrient formula
|
120 |
3-6 months |
43% decline in PBD symptoms and 40% in ADHD symptoms, evaluated by LOCF |
Data obtained from the formula manufacturer's database |
Depressive episode
|
Open-label |
Patel, 20066060. Patel NC, DelBello MP, Bryan HS, Adler CM, Kowatch RA, Stanford K, et al.
Open-label lithium for the treatment of adolescents with bipolar depression. J Am Acad Child Adolesc
Psychiatry. 2006;45:289-97.
|
Li |
1.0-1.2 mEq/L |
27 |
6 weeks |
48% response rate
|
Headache, nausea/vomiting, stomachache, abdominal cramps |
Open-label |
Chang, 20066161. Chang K, Saxena K, Howe M. An open-label study of lamotrigine adjunct or
monotherapy for the treatment of adolescents with bipolar depression. J Am Acad Child Adolesc
Psychiatry. 2006;45:298-304.
|
Lamotrigine |
100-200 mg/day |
20 |
8 weeks |
63% response rate
|
No significant adverse effects |
Review of medical records |
Biederman, 20006262. Biederman J, Mick E, Spencer TJ, Wilens TE, Faraone SV. Therapeutic dilemmas in
the pharmacotherapy of bipolar depression in the young. J Child Adolesc Psychopharmacol.
2000;10:185-92.
|
SSRIs and mood stabilizers |
|
59 |
|
Significant improvement of bipolar depression with SSRI.Improvement of manic symptoms with mood
stabilizers |
Recurrence of manic symptoms with SSRI.Mood stabilizers did not change course of bipolar
depression |
Maintenance treatment
|
Open-label |
Findling, 20056363. Findling RL, McNamara NK, Stansbrey R, Gracious BL, Whipkey RE, Demeter CA, et
al. Combination lithium and divalproex sodium in pediatric bipolar symptom restabilization. J Am
Acad Child Adolesc Psychiatry. 2006;45:142-8.
|
Li or DVP (monotherapy vs. combination) |
Li: 0.6-1.0 mmol/LDVP: 50-100 µg/L |
38 |
8 weeks |
Patients who became symptomatic with monotherapy had a 89.5% remission rate with combination
therapy |
Five patients discontinued study participation due to adverse events (alopecia in both groups;
increased thyrotropin blood level and thrombocytopenia in DVP group; enuresis in Li group) |
Open-label |
Tramontina, 20076464. Tramontina S, Zeni CP, Pheula G, Rohde LA. Topiramate in adolescents with
juvenile bipolar disorder presenting weight gain due to atypical antipsychotics or mood stabilizers:
an open clinical trial. J Child Adolesc Psychopharmacol. 2007;17:129-34.
|
Topiramate |
50-150 mg/day |
10 |
11 weeks |
Significant reduction in YMRS scores and in body weight |
Cognitive impairment |
Open-label |
Duffy, 20096565. Duffy A, Milin R, Grof P. Maintenance treatment of adolescent bipolar disorder:
open study of the effectiveness and tolerability of quetiapine. BMC Psychiatry.
2009;9:4.
|
Quetiapine |
50-800 mg/day |
18 |
48 weeks |
Effective and well tolerated |
Somnolence and flu-like symptoms |
Comorbidity with ADHD
|
Open-label |
Chang, 20096666. Chang K, Nayar D, Howe M, Rana M. Atomoxetine as an adjunct therapy in the
treatment of co-morbid attention-deficit/hyperactivity disorder in children and adolescents with
bipolar I or II disorder. J Child Adolesc Psychopharmacol. 2009;19:547-51.
|
Atomoxetine |
1.2 mg/kg |
12 |
8 weeks |
67% response rate;50% remission rate |
Two subjects discontinued due to worsening of mood symptoms |