Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

Articles   |    
Pharmacotherapy and Family-Focused Treatment for Adolescents With Bipolar I and II Disorders: A 2-Year Randomized Trial
David J. Miklowitz, Ph.D.; Christopher D. Schneck, M.D.; Elizabeth L. George, Ph.D.; Dawn O. Taylor, Ph.D.; Catherine A. Sugar, Ph.D.; Boris Birmaher, M.D.; Robert A. Kowatch, M.D.; Melissa P. DelBello, M.D.; David A. Axelson, M.D.
Am J Psychiatry 2014;171:658-667. doi:10.1176/appi.ajp.2014.13081130
View Author and Article Information

Dr. Miklowitz has received research funding from NIMH, NARSAD, the Attias Family Foundation, the Danny Alberts Foundation, the Carl and Roberta Deutsch Foundation, the Kayne Family Foundation, and the Knapp Foundation and book royalties from Guilford Press and John Wiley & Sons. Dr. Schneck has received research support from NIMH, the Crown Family Philanthropies, and the Ryan White HIV/AIDS Treatment Extension Act. Dr. Birmaher has received support from NIMH and has received royalties from Random House, Lippincott Williams & Wilkins, and UpToDate. Dr. Kowatch has served as a consultant for Forest Pharmaceuticals, AstraZeneca, Sunovion, and the REACH Foundation. Dr. DelBello has served as a consultant or speaker for Bristol-Myers Squibb, Dey, Lundbeck, Otsuka, Pfizer, and Sunovion. The other authors report no financial relationships with commercial interests.

Supported by NIMH grants R01 MH073871 and R34MH077856 to Dr. Miklowitz, grant R01MH073817 to Dr. Axelson, and grant R01MH074033 to Dr. Kowatch.

Clinicaltrials.gov identifier: NCT00332098.

From the Department of Psychiatry, University of California, Los Angeles (UCLA) School of Medicine, Los Angeles; the Department of Psychology, University of Colorado Boulder; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Biostatistics, UCLA, Los Angeles; the Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh; Cincinnati Children’s Hospital, Cincinnati; and the Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati.

Address correspondence to Dr. Miklowitz (dmiklowitz@mednet.ucla.edu).

Copyright © 2014 by the American Psychiatric Association

Received August 24, 2013; Revised January 01, 2014; Accepted January 29, 2014.


Objective  Previous studies have found that family-focused treatment is an effective adjunct to pharmacotherapy in stabilizing symptoms in adult bipolar disorder. The authors examined whether pharmacotherapy and family-focused treatment for adolescents with bipolar disorder was more effective than pharmacotherapy and brief psychoeducation (enhanced care) in decreasing time to recovery from a mood episode, increasing time to recurrence, and reducing symptom severity over 2 years.

Method  A total of 145 adolescents (mean age, 15.6 years) with bipolar I or II disorder and a DSM-IV-TR manic, hypomanic, depressive, or mixed episode in the previous 3 months were randomly assigned, with family members, either to pharmacotherapy and family-focused treatment, consisting of psychoeducation (i.e., recognition and early intervention with prodromal symptoms), communication enhancement training, and problem-solving skills training, delivered in 21 sessions over 9 months; or to pharmacotherapy and three weekly sessions of enhanced care (family psychoeducation). Independent evaluators assessed participants at baseline, every 3 months during year 1, and every 6 months during year 2, using weekly ratings of mood.

Results  Twenty-two participants (15.2%) withdrew shortly after randomization. Time to recovery or recurrence and proportion of weeks ill did not differ between the two treatment groups. Secondary analyses revealed that participants in family-focused treatment had less severe manic symptoms during year 2 than did those in enhanced care.

Conclusions  After an illness episode, intensive psychotherapy combined with best-practice pharmacotherapy does not appear to confer advantages over brief psychotherapy and pharmacotherapy in hastening recovery or delaying recurrence among adolescents with bipolar disorder.

Abstract Teaser
Figures in this Article

Your Session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 1. CONSORT Flow Diagram for a 2-Year Randomized Trial in Adolescents With Bipolar I or II Disorder Receiving Pharmacotherapy With Either Family-Focused Treatment or Enhanced Care

FIGURE 2. Mania/Hypomania Severity Scores Across Time in Adolescents With Bipolar I or II Disorder Receiving Pharmacotherapy With Either Family-Focused Treatment or Enhanced Carea

a Weekly Psychiatric Status Rating Scale mania scores were obtained from the Adolescent Longitudinal Interval Follow-Up Evaluation and averaged across 3-month intervals. Family-focused treatment for adolescents (N=72) was associated with lower mean mania/hypomania severity scores than enhanced care (N=73) during year 2 (treatment-by-time interaction, F=1.98, df=8, 742, p=0.046). Means are adjusted for prerandomization Mania Rating Scale scores from the Schedule for Affective Disorders and Schizophrenia for School-Age Children, for study site, and for living situation (with two biological parents or not).

Anchor for Jump
TABLE 1.Demographic and Clinical Characteristics of Adolescents With Bipolar I or II Disorder Receiving Pharmacotherapy With Either Family-Focused Treatment or Enhanced Care
Table Footer Note

a No significant difference on any variable between groups or sites, based on Mantel-Haenszel chi-square and two-way analysis of variance tests.

Table Footer Note

b Adolescents with subthreshold mood episodes had at least 1–2 weeks with Psychiatric Status Rating Scale scores of 3 or 4 for mania or depression in the past 3 months, as assessed with the Adolescent Longitudinal Interval Follow-up Evaluation.

Table Footer Note

c.Comorbid disorders that were present in less than 10% of participants are not listed.

Table Footer Note

d Higher values indicate higher education and occupation; a value of 3 indicates middle class.

Table Footer Note

e Depression and Mania Rating Scale scores were based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children interview at intake into the study, covering the worst 1–2 week period in the previous 3 months.

Anchor for Jump
TABLE 2.Percent of Weeks in Remission, in Subthreshold States, or in Episode During Study Years 1 and 2 for Adolescents With Bipolar Disorder Receiving Pharmacotherapy With Either Family-Focused Treatment or Enhanced Carea
Table Footer Note

a Treatment effects are based on mixed-effects regression models with time (year 1 or 2) as the within-subject factor, treatment group as the between-subject factor, a group-by-time interaction, and a subject-level random effect to account for correlations between the repeated measurements. Covariates included study site, baseline Mania or Depression Rating Scale scores from the Schedule for Affective Disorders and Schizophrenia for School-Age Children, living situation (with two biological parents or not), and number of weeks of follow-up. Means, standard deviations, and p values are adjusted for covariates. Analyses excluded participants who had less than 6 months of follow-up.

Anchor for Jump
TABLE 3.Medications Over Time in Adolescents With Bipolar Disorder Receiving Pharmacotherapy With Either Family-Focused Treatment or Enhanced Carea
Table Footer Note

a Antipsychotics included both first- and second-generation agents. Anticonvulsants included valproate, lamotrigine, carbamazepine, oxcarbazepine, and topiramate. There were no differences between the treatment groups or treatment-by-time interactions in the proportion of patients taking each medication or in the mean number of medications per patient.



Perlis  RH;  Miyahara  S;  Marangell  LB;  Wisniewski  SR;  Ostacher  M;  DelBello  MP;  Bowden  CL;  Sachs  GS;  Nierenberg  AA; STEP-BD Investigators:  Long-term implications of early onset in bipolar disorder: data from the first 1000 participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).  Biol Psychiatry 2004; 55:875–881
Merikangas  KR;  Jin  R;  He  JP;  Kessler  RC;  Lee  S;  Sampson  NA;  Viana  MC;  Andrade  LH;  Hu  C;  Karam  EG;  Ladea  M;  Medina-Mora  ME;  Ono  Y;  Posada-Villa  J;  Sagar  R;  Wells  JE;  Zarkov  Z:  Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative.  Arch Gen Psychiatry 2011; 68:241–251
Geller  B;  Tillman  R;  Bolhofner  K;  Zimerman  B:  Child bipolar I disorder: prospective continuity with adult bipolar I disorder; characteristics of second and third episodes; predictors of 8-year outcome.  Arch Gen Psychiatry 2008; 65:1125–1133
Birmaher  B;  Axelson  D;  Goldstein  B;  Strober  M;  Gill  MK;  Hunt  J;  Houck  P;  Ha  W;  Iyengar  S;  Kim  E;  Yen  S;  Hower  H;  Esposito-Smythers  C;  Goldstein  T;  Ryan  N;  Keller  M:  Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: the Course and Outcome of Bipolar Youth (COBY) study.  Am J Psychiatry 2009; 166:795–804
Goldstein  TR;  Ha  W;  Axelson  DA;  Goldstein  BI;  Liao  F;  Gill  MK;  Ryan  ND;  Yen  S;  Hunt  J;  Hower  H;  Keller  M;  Strober  M;  Birmaher  B:  Predictors of prospectively examined suicide attempts among youth with bipolar disorder.  Arch Gen Psychiatry 2012; 69:1113–1122
DelBello  MP;  Hanseman  D;  Adler  CM;  Fleck  DE;  Strakowski  SM:  Twelve-month outcome of adolescents with bipolar disorder following first hospitalization for a manic or mixed episode.  Am J Psychiatry 2007; 164:582–590
Geddes  JR;  Miklowitz  DJ:  Treatment of bipolar disorder.  Lancet 2013; 381:1672–1682
Miklowitz  DJ;  Otto  MW;  Frank  E;  Reilly-Harrington  NA;  Wisniewski  SR;  Kogan  JN;  Nierenberg  AA;  Calabrese  JR;  Marangell  LB;  Gyulai  L;  Araga  M;  Gonzalez  JM;  Shirley  ER;  Thase  ME;  Sachs  GS:  Psychosocial treatments for bipolar depression: a 1-year randomized trial from the Systematic Treatment Enhancement Program.  Arch Gen Psychiatry 2007; 64:419–426
Fristad  MA;  Verducci  JS;  Walters  K;  Young  ME:  Impact of multifamily psychoeducational psychotherapy in treating children aged 8 to 12 years with mood disorders.  Arch Gen Psychiatry 2009; 66:1013–1021
Miklowitz  DJ;  Schneck  CD;  Singh  MK;  Taylor  DO;  George  EL;  Cosgrove  VE;  Howe  ME;  Dickinson  LM;  Garber  J;  Chang  KD:  Early intervention for symptomatic youth at risk for bipolar disorder: a randomized trial of family-focused therapy.  J Am Acad Child Adolesc Psychiatry 2013; 52:121–131
Miklowitz  DJ;  Axelson  DA;  Birmaher  B;  George  EL;  Taylor  DO;  Schneck  CD;  Beresford  CA;  Dickinson  LM;  Craighead  WE;  Brent  DA:  Family-focused treatment for adolescents with bipolar disorder: results of a 2-year randomized trial.  Arch Gen Psychiatry 2008; 65:1053–1061
Miklowitz  DJ;  George  EL;  Richards  JA;  Simoneau  TL;  Suddath  RL:  A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder.  Arch Gen Psychiatry 2003; 60:904–912
Rea  MM;  Tompson  MC;  Miklowitz  DJ;  Goldstein  MJ;  Hwang  S;  Mintz  J:  Family-focused treatment versus individual treatment for bipolar disorder: results of a randomized clinical trial.  J Consult Clin Psychol 2003; 71:482–492
Chambers  WJ;  Puig-Antich  J;  Hirsch  M;  Paez  P;  Ambrosini  PJ;  Tabrizi  MA;  Davies  M:  The assessment of affective disorders in children and adolescents by semistructured interview: test-retest reliability of the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present Episode Version.  Arch Gen Psychiatry 1985; 42:696–702
Kaufman  J;  Birmaher  B;  Brent  D;  Rao  U;  Flynn  C;  Moreci  P;  Williamson  D;  Ryan  N:  Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version (K-SADS-PL): initial reliability and validity data.  J Am Acad Child Adolesc Psychiatry 1997; 36:980–988
Axelson  D;  Birmaher  BJ;  Brent  D;  Wassick  S;  Hoover  C;  Bridge  J;  Ryan  N;  Axelson  D;  Birmaher  BJ;  Brent  D;  Wassick  S;  Hoover  C;  Bridge  J;  Ryan  N:  A preliminary study of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Mania Rating Scale for children and adolescents.  J Child Adolesc Psychopharmacol 2003; 13:463–470
Begg  CB;  Iglewicz  B:  A treatment allocation procedure for sequential clinical trials.  Biometrics 1980; 36:81–90
Kowatch  RA;  Fristad  MA;  Findling  RL;  Post  R:  Clinical Manual for the Management of Bipolar Disorder in Children and Adolescents .  Washington, DC,  American Psychiatric Publishing, 2008
Pfeifer  JC;  Kowatch  RA;  DelBello  MP:  Pharmacotherapy of bipolar disorder in children and adolescents: recent progress.  CNS Drugs 2010; 24:575–593
Weisman  AG;  Okazaki  S;  Gregory  J;  Goldstien  MJ;  Tompson  MC;  Rea  M;  Miklowitz  DJ:  Evaluating therapist competency and adherence to behavioral family management with bipolar patients.  Fam Process 1998; 37:107–121
Keller  MB;  Lavori  PW;  Friedman  B;  Nielsen  E;  Endicott  J;  McDonald-Scott  P;  Andreasen  NC:  The Longitudinal Interval Follow-up Evaluation: a comprehensive method for assessing outcome in prospective longitudinal studies.  Arch Gen Psychiatry 1987; 44:540–548
Kaplan  EL;  Meier  P:  Nonparametric estimation from incomplete observations.  J Am Stat Assoc 1958; 53:457–481
Cox  DR:  Regression models and life tables.  J Res Stat Soc Behavior 1972; 34:187–220
Ger  D;  Everitt  BS:  Handbook of Statistical Analyses Using SAS , 2nd ed.  London,  CRC Press, 2001
Miklowitz  DJ;  Otto  MW;  Frank  E;  Reilly-Harrington  NA;  Kogan  JN;  Sachs  GS;  Thase  ME;  Calabrese  JR;  Marangell  LB;  Ostacher  MJ;  Patel  J;  Thomas  MR;  Araga  M;  Gonzalez  JM;  Wisniewski  SR:  Intensive psychosocial intervention enhances functioning in patients with bipolar depression: results from a 9-month randomized controlled trial.  Am J Psychiatry 2007; 164:1340–1347
Miklowitz  DJ;  Richards  JA;  George  EL;  Frank  E;  Suddath  RL;  Powell  KB;  Sacher  JA:  Integrated family and individual therapy for bipolar disorder: results of a treatment development study.  J Clin Psychiatry 2003; 64:182–191
Geller  B;  Tillman  R;  Craney  JL;  Bolhofner  K:  Four-year prospective outcome and natural history of mania in children with a prepubertal and early adolescent bipolar disorder phenotype.  Arch Gen Psychiatry 2004; 61:459–467
Kowatch  RA;  Fristad  M;  Birmaher  B;  Wagner  KD;  Findling  RL;  Hellander  M; Child Psychiatric Workgroup on Bipolar Disorder:  Treatment guidelines for children and adolescents with bipolar disorder.  J Am Acad Child Adolesc Psychiatry 2005; 44:213–235
Somerville  LH:  The teenage brain: sensitivity to social evaluation.  Curr Dir Psychol Sci 2013; 22:121–127
Kim  EY;  Miklowitz  DJ;  Biuckians  A;  Mullen  K:  Life stress and the course of early-onset bipolar disorder.  J Affect Disord 2007; 99:37–44
Tohen  M;  Strakowski  SM;  Zarate  CJ  Jr;  Hennen  J;  Stoll  AL;  Suppes  T;  Faedda  GL;  Cohen  BM;  Gebre-Medhin  P;  Baldessarini  RJ:  The McLean-Harvard first-episode project: 6-month symptomatic and functional outcome in affective and nonaffective psychosis.  Biol Psychiatry 2000; 48:467–476
Perlis  RH;  Delbello  MP;  Miyahara  S;  Wisniewski  SR;  Sachs  GS;  Nierenberg  AA;  Perlis  RH;  DelBello  MP;  Miyahara  S;  Wisniewski  SR;  Sachs  GS;  Nierenberg  AA; STEP-BD investigators:  Revisiting depressive-prone bipolar disorder: polarity of initial mood episode and disease course among bipolar I systematic treatment enhancement program for bipolar disorder participants.  Biol Psychiatry 2005; 58:549–553
Calabrese  JR;  Vieta  E;  El-Mallakh  R;  Findling  RL;  Youngstrom  EA;  Elhaj  O;  Gajwani  P;  Pies  R:  Mood state at study entry as predictor of the polarity of relapse in bipolar disorder.  Biol Psychiatry 2004; 56:957–963
Rosa  AR;  Andreazza  AC;  Kunz  M;  Gomes  F;  Santin  A;  Sanchez-Moreno  J;  Reinares  M;  Colom  F;  Vieta  E;  Kapczinski  F:  Predominant polarity in bipolar disorder: diagnostic implications.  J Affect Disord 2008; 107:45–51
Turvey  CL;  Coryell  WH;  Arndt  S;  Solomon  DA;  Leon  AC;  Endicott  J;  Mueller  T;  Keller  M;  Akiskal  H:  Polarity sequence, depression, and chronicity in bipolar I disorder.  J Nerv Ment Dis 1999; 187:181–187
Hlastala  SA;  Frank  E;  Mallinger  AG;  Thase  ME;  Ritenour  AM;  Kupfer  DJ:  Bipolar depression: an underestimated treatment challenge.  Depress Anxiety 1997; 5:73–83
Geller  B;  Craney  JL;  Bolhofner  K;  Nickelsburg  MJ;  Williams  M;  Zimerman  B:  Two-year prospective follow-up of children with a prepubertal and early adolescent bipolar disorder phenotype.  Am J Psychiatry 2002; 159:927–933
Post  RM;  Leverich  GS:  The role of psychosocial stress in the onset and progression of bipolar disorder and its comorbidities: the need for earlier and alternative modes of therapeutic intervention.  Dev Psychopathol 2006; 18:1181–1211
References Container

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe

Web of Science® Times Cited: 1

See Also...
Topic Collections