- 1 Introduction
- 2 Epidemiology and Comorbidity
- 3 Diagnosis according to DSM-IV-TR
- 4 Bipolar Disorder in Children and Adolescents
- 5 Diagnostic Pearls
- 6 Treatment of Children and Adolescents
- 7 Major Studies
- 8 High-Yield Facts
- 9 Further Reading
This article describes important considerations in assessment, diagnosis, and treatment of bipolar disorder (BD). Another article addresses properties of mood stabilizers.
Epidemiology and Comorbidity
- Lifetime prevalence of Bipolar I is between 0.4% and 1.6% (APA, 2000).
- National Comorbidity Survey found that approximately 1% of adolescents have strictly defined BD-I, that 6.2% have impairing symptoms of bipolar spectrum disorders,
- the prevalence of BD-I or BD-II doubles between ages 13 to 14 years and 17 to 18 years. (Merikangas JAACAP 2010)
- Equal gender distribution is characteristic (unlike MDD);
- however F:M ratio for rapid cycling BD is closer to 3:1.
- Women also have more depressive episodes than men do and are more likely to be misdiagnosed with MDD or be diagnosed later in the course of the illness.
- AA with BD are more likely to be misdiagnosed as having schizophrenia, than whites with BD.
The most common commorbidities of bipolar disrder are substance use disorders and anxiety disorders. Substance abuse and dependence are most disabling; over 60% of BD patients abuse some form of drug or substance. Rate of alcohol abuse/dependence in BD I patients can be as high as 30%, which constitutes a significant increase in risk over general population (rates of about 3-10%).
A child with one BD parent has 15-30% risk of having BD. If both parents have BD, the risk increases to 50-75% (NIMH).
Diagnosis according to DSM-IV-TR
Bipolar I disorder requires occurence of manic or mixed episode lasting 7+ days with impairment in functioning; a shorter episode that required hospitalization would also meet the criteria.
Bipolar II disorder requires occurence of hypomanic episodes lasting 4+ days and major depressive episodes without full or mixed manic state.
It is important to distingwish a manic episode of a bipoloar disorder from a mood disorder due to a genereal medical condition, for example, a situation when elevated mood is a direct physiological consequence of Cushing's syndrome. A substance-induced mood disorder is another important differential diagnosis.
Black belt DSM-IV-TR
- The definition of manic episode excludes mania-like mood changes due to general medical conditions, substance use, and antidepressant treatments, including SSRIs, light therapy, and ECT;
- so, not only is diagnosis of "bipolar disorder" inappropriate, but the manic presentation itself should not be called a manic episode. Therefore an adverse mood reaction to an SSRI in a patient with MDD, does not "flip" a depressed patient into a bipolar one. Axis I for that patient should say: Major Depressive Disorder, Recurrent; Sertraline-Induced Mood Disorder, With Mixed/Manic Features.
- there is evidence that a depressed patient who had experienced adverse mood reaction to an SSRI is at a higher risk for developing bipolar disrder in the future; however, an episode of manic features precipitated by SSRIs should not be called a "manic episode," and therefore, bipolar diagnosis is not appropriate.
- Mixed state (concurrent presence of manic and non-overlapping depressive symtpoms during an episode) was re-defined in DSM-5.
- patients experiencing mixed states have poorer prognosis: patients have more episodes, increased suicidality, higher rates of co-occurring conditions, and poorer response to monotherpay, including lithium.
Bipolar Disorder in Children and Adolescents
Prevalence of bipolar disorder (BD) in youth may be as high as 1%. The most common comorbidities are ADHD (>50%) and anxiety disorders. The rate of comorbid substance use increases in adolescence.
Approximately 20% of youth with MDD will be diagnosed with bipolar disorder later in life.
BD in children and adolescents is not the same as BD seen in adults
Adherence to the DSM-IV criteria for BD in establishing diagnosis in youth, will produce many false positives and false negatives. A few comments about specific symptoms:
- Elevated mood and grandiosity have been termed "cardinal" or "hallmark" features, but may still miss a number of cases of pediatric BD.
- Irritability, or having low threshold for experiencing distress in response to common triggers, is a very sensitive, but not at all specific characteristic of BD; almost all children with BD exhibit some form of irritability, but it can also be seen in DBDs, PTSD, MDD, personality disorders, and be a feature of family relational problems. Thus irritability should raise suspicion for BD, but be considered in the context of other symptoms.
- Decreased sleep is a common feature of pediatric BD; although not specific for BD, it can help distinguish it from the overlapping presentation of ADHD and DBDs.
- Pressured speech and racing thoughts are somewhat more specific for BD, but seen less frequently as distinct symptoms.
While most adult bipolar patients have distinct manic/hyponamic and depressive episodes, usually lasting days to weeks, the course of pediatric bipolar illness is more difficult to define. In children and adolescents it may resemble one or more of the following patterns:
- Classic BD presentation, resembling manic state and impairment described in the DSM-IV.
- Very brief somewhat less defined episodes of mood shifts and mania lasting hours to days. Common occurrence of this phenotype led to wide use of the following non-DSM-IV terms:
- ultrarapid cycling have been defined either in terms of episode duration or episode frequency. Such manic episodes that can last several hours to 4 days (longer episodes would be considered hypomania). Alternatively, having 5 to 364 cycles per year can be considered ultrarapid cycling.
- ultradian cycling are very brief manic states that last minutes to hours and occur daily.
- Chronic hypomanic/manic/mixed state with prominent irritability and hyperarrousal. Patient may be in a mixed state for months, switching between manic and depressed moods up to several times per day.
In addition to this variability in symptoms and course of illness, many presentations of pediatric BD may not be continuous with classic adult BD; a term Prepubertal and Early Adolescent Bipolar Disorder Phenotype (PEA-BP) is sometimes used in literature to emphasize this. A 4-year follow-up of a large PEA-BP study demonstrated stability of the diagnosis, chronicity of symptoms and very high relapse rate despite community treatment. (Geller, 2004)
Another way to conceptualize pediatric BD is to consider the age of onset:
- School-aged children often present with mixed manic-depressive mood, characterized by anger and dysphoria, which changes rapidly and erratically, rather than the protracted euphoria, seen in adults. There is high comorbidity with DBDs and anxiety disorders
- Adolescent bipolarity resembles that of adults somewhat more closely. Adolescents with BD may have psychotic symptoms and chronic irritability; features of borderline personality disorder and the comorbidities of DBDs, anxiety disorders, and substance use are common. The early course of BD in adolescents may be more chronic and refractory to treatment than adult-onset BD.
ACAAP Parameter on Assessment
- Screen all youth for BD; those in whom BD is suspected, thoroughly explore relevant history, characteristics of episodes, associated symptoms, comorbidities, medical problems, social factors, and safety.
- Documenting the diagnosis as Bipolar Disorder NOS is a good method of preserving clinical consistency and avoiding labeling youth with variable presentation of mood and behavioral difficulties who do not meet the diagnostic criteria for BD Type I or II.
- Validity of diagnosis of BD in children younger than 6 is even more uncretain. Particular caution when considering a BD diagnosis in pre-schoolers.
The variability outlined above presents significant diagnostic challenge.
Overlap of many symptoms seen in pediatric BD and those of ADHD/DBDs make it even more difficult. Since ADHD is in the differential diagnosis for bipolar disorder AND a common comorbidity of BD, the importance of good history is self-evident. "Atypical cases" that do not fit the DSM-IV template for bipolar disorder may be the rule rather than the exception in child psychiatry. Some children may present with very brief episodes of mood lability/iritability or mood swings, lasting only hours; other manic children may have chronically elevated mood or persistent baseline irritability.
- At least some symptoms of ADHD should be present before the age of 7. Sudden late onset of "ADHD symtoms" in a pre-adolescent is a red flag for BD
- Suspect BD in a child with ADHD who no longer responds to stimulants. Also suspect poor adherence, medication diversion, tolerance, and rebound effect.
- There is little evidence that use of stimulants predispose a child to the development of BD.
- Two grave pitfalls of not recognizing BD include:
- recognizing symptoms of BD as those of ADHD (which may comorbid!) and prescribing a stimulant before mood stabilizer :-(
- making the diagnosis of MDD without adequately exploring past history of mood changes and irritability and prescribing an antidepressant :-(
- Always screen for suicidality, common comorbidities, psychosocial stressors, and medical problems.
Treatment of Children and Adolescents
Pharmacological therapy is a first line treatment for pediatric BD; behavioral treatments and psychoeducation are necessary for improving global functioning and medication adherence. The current stage of BD must be considered before starting a medication; acute mania stabilization, relapse prevention, depressive episodes management, and long-term maintenance are important phases of BD treatment.
Start with a mood stabilizer (lithium, valproic acid) or an antipsychotic.
- Acute mania is best controlled with an antipsychotic. Only risperidone, aripiprazole (Abilify) and quetiapine (Seroquel) are approved down to the age of 10.
- Lithium is not recommended for children <12yo. Lithium may prevent relapse and decrease suicidal ideations.
- Anticonvulsants had not received FDA indication for treatment of pediatric BD. Valproic acid (Depakote) is an anticonvulsants that had been studied the most and had demonstrated effectiveness in acute stabilization of mania. Notably, most trials of anticonvulsants were characterized by high withdrawal rates. They are not considered effective at preventing relapse.
- According to AACAP Parameter a trial of a mood-stabilizer should continue for 6-8 weeks before adding or substituting. However, for severe illness, combination treatment from day 1 is indicated, particularly on inpatient unit. (expert panel AACAP 2016 Meeting WKSH 4)
Update Emerging evidence from meta-analyses suggests that SGAs are more efficacious (judging by YMRS scores) than traditional mood stabilizers; SGAs also have greater effect sizes in youth (but not in adults). SGA's caused more weight gain compared to other mood stabilizers; they also caused more weight gain in youth than in adults. (8)
Treatment of Early Age Mania (TEAM) study
A randomized controlled study of N=279 6-15-year-old manic/mixed BD type I youth. (Geller B. Arch.Gen Psychiatry 2011)
- risperidone vs lithium vs divalproex for 8 weeks
- Risperidone showed higher response rates (69%) than Li (36%) or Depakote (24%);
- ripserdone was also associated with greater weight gain at (3.3kg vs. 1.4-1.7kg) in just 8 weeks.
- effect was even greater in children with comorbid ADHD
Combining a mood stabilizer and an antipsychotic may be the most effective strategy in relapse prevention, particularly in severe BD and BD with psychotic features.
- As many as 58% of youth with BD fail monotherapy, 80-90% of those responded to a combination therapy;(6,7)
- Sustained remission may be harder to achieve (47-65%) in studies (9,10,11)
- While lamotrigine and SSRIs are used to treat pediatric BD with prominent depression, they should be titrated very slowly. SSRIs should not be used as monotherapy if BD is suspected. **Psychoeducation and monitoring for dermatological side effects of lamotrigine and suicidality and manic effects of SSRI is paramount.
Regiment for stabilization of acute mania should be continued for 12-24mo. Monotherapy, even with lithium, produces high relapse rate. Many adolescents will require lifelong maintanance therapy. Discontinuation of psychopharmocological treatment exposes the patient to high risk of recurrence of mania; if discontinuation is necessary, it should be done gradually. (AACAP)
Appropriate steps must be taken before starting a medication, and more detail can be found in the dedicated articles. Some highlights:
- Weight gain is a common and significant adverse effect of mood stabilizers and antipsychotics, observed in studies and in clinical practice. Record hight, weight, and calculate BMI for every child with BD.
- Lithium: Baseline assessment: H&P (including height and weight), calculate BMI, obtain UA, Upreg, TSH, free T4, CBC, CMP (electrolytes, BUN, creatinine, calcium, albumin). Repeat q3-6mo and with dose adjsutment; check lithium levels q3-6mo and after dose adjustment; lithium levels should be drawn 12 hr after last dose; therapeutic plasma level is between 0.8 and 1.2 mEq/L. Start at 300mg, (BID if older) titrate up q4-5d while checking levels 4+ days after dose increase.
- Valproic acid: Baseline assessment: H&P (including menstrual history and height and weight), calculate BMI, obtain Upreg, CBC with differential and platelet count, LFTs, lipase. Check levels 4 days after each dose increase and q3-6mo.
- Carbamazepine: Baseline assessment: H&P (including menstrual history and height and weight), calculate BMI, obtain Upreg, CBC with differential and platelet count, BMP, LFTs. Check levels 1 week after each dose increase, and q3-6mo.
- Antipsychotics: Baseline assessment: H&P (including measuring BP and waist circumference), calculate BMI, fasting glucose and lipid panel; repeat labs q3mo, then yearly.
Finally, psychoeducation and other behavioral and psychosocial interventions are integral components of comprehensive treatment of BD; they are important for relapse prevention as well as improving family, social, academic, and occupational functioning.
Course and Outcome of Bipolar Youth (COBY) study
4-year longitudinal study of youth (7-17yo) with BD revealed that 63% had some recurrence after the initial episode, mostly depression. 30% had more than one recurrence episode.
Treatment of Early Age mania (TEAM)
Randomized controlled 8-week trial of youth age 6-15, with diagnosis of bipolar I, n=279. Mean dose of risperidone was 2.7mg.
- Response in acute treatment of mania favored the antipsychotic: risperdone (68%), lithium - 35.6%, valproate (24%). (Geller 2012)
- Earlier onset signifies poorer prognosis
- DBDs is the most common commorbidity in children and adolescents; substance abuse is the most common commorbidity in adults.
- Always do a pregnancy test in adolescents of child-bearing age before starting a mood stabilizer (this includes lithium). Baseline test and regular levels are also very important.
 Martin A. Lewis's Child and Adolescent Psychiatry
 Practice Parameter for the Assessment and Treatment of Children and Adolescents with Bipolar Disorder JAACAP,46:1(2007)pp.107-124
 Geller, B. 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
 Birmaher B, et al. Four-year longitudinal course of children and adolescents with bipolar spectrum disorders: The course and outcome of bipolar youth (COBY) study. Am. J. Psych 166(7),795–802(2009).
 Kowatch R.A., Sethuraman G., Hume J.H., Kromelis M., Weinberg W.A.: Combination pharmacotherapy in children and adolescents with bipolar disorder. Biol Psychiatry 53. 978-984.2003;
 Findling R.L., McNamara N.K., Gracious B.L., et al: Combination lithium and divalproex sodium in pediatric bipolarity. J Am Acad Child Adolesc Psychiatry 42. 895-901.2003;
 Liu HY et al. Pharmacologic treatments for pediatric bipolar disorder: a review and meta-analysis. J Am Acad Child Adolesc Psychiatry AUG-2011; 50(8): 749-62.e39;
 Findling R.L., McNamara N.K., Gracious B.L., et al: Combination lithium and divalproex sodium in pediatric bipolarity. J Am Acad Child Adolesc Psychiatry 42. 895-901.2003;
 Pavuluri M.N., Henry D.B., Carbray J.A., Sampson G., Naylor M.W., Janicak P.G.: Open-label prospective trial of risperidone in combination with lithium or divalproex sodium in pediatric mania. J Affect Disord 82. (suppl 1): S103-S111.2004;
 Pavuluri M.N., Henry D.B., Carbray J.A., Sampson G.A., Naylor M.W., Janicak P.G.: A one-year open-label trial of risperidone augmentation in lithium nonresponder youth with preschool-onset bipolar disorder. J Child Adolesc Psychopharmacol 16. 336-350.2006
 Merikangas KR, He JP, Burstein M, et al. Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication–Adolescent Supplement. J Am Acad Child Adolesc Psychiatry. 2010;49(10):980-989
Copyright: 2010 E Grudnikoff
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