Evidence-based assessment/Rx4DxTx of bipolar in youths

=Resources for the Assessment and Treatment of Bipolar Disorders in Children and Adolescents= The diagnosis of bipolar disorder (BD) in youth has historically been controversial, with some clinicians and researchers debating its validity as a disorder that manifests in children. However, decades of research offer evidence that youth do experience bipolar disorder and benefit from the relevant evidence-based treatments. BD comprises a "spectrum" of disorders (i.e., BD-I, BD-II, cyclothymic disorder, and other specified bipolar and related disorders) and symptom presentations vary across individuals. Regardless of subtype, BD is associated with significant consequences for affected youth. Early diagnosis and intervention can help improve prognosis, but lack of knowledge and misperceptions about BD in youth may cause delays in seeking or receiving appropriate treatment. This paper will outline current evidence related to the prevalence, risk factors, assessment, comorbidity, and treatment of BD in youth.

Diagnostic Criteria



 * Bipolar Type I Disorder
 * Bipolar type I disorder is an episodic mood disorder defined by the occurrence of one or more manic or mixed episodes. A manic episode is an extreme mood state lasting at least one week unless shortened by a treatment intervention. It is characterized by euphoria, irritability, or expansiveness, and increased activity or a subjective experience of increased energy, accompanied by other characteristic symptoms such as rapid or pressured speech, flight of ideas, increased self-esteem or grandiosity, decreased need for sleep, distractibility, impulsive or reckless behavior, and rapid changes among different mood states (i.e., mood lability). A mixed episode is characterized by either a mixture or very rapid alternation between prominent manic and depressive symptoms on most days during a period of at least 2 weeks. Although the diagnosis can be made based on evidence of a single manic or mixed episode, typically manic or mixed episodes alternate with depressive episodes over the course of the disorder.
 * Note: The ICD-11 lists 18 additional subcategories of Bipolar type I disorder. They can be found here.
 * Bipolar Type II Disorder
 * Bipolar type II disorder is an episodic mood disorder defined by the occurrence of one or more hypomanic episodes and at least one depressive episode. A hypomanic episode is a persistent mood state characterized by euphoria, irritability, or expansiveness, and excessive psychomotor activation or increased energy, accompanied by other characteristic symptoms such as grandiosity, decreased need for sleep, pressured speech, flight of ideas, distractibility, and impulsive or reckless behavior lasting for at least four consecutive days and present most of the day. The symptoms represent a change from the individual’s typical behavior that is are observable to others and are not severe enough to cause marked impairment in functioning. A depressive episode is characterized by a period of almost daily depressed mood or diminished interest in activities lasting at least 2 weeks accompanied by other symptoms such as changes in appetite or sleep, psychomotor agitation or retardation, fatigue, feelings of worthless or excessive or inappropriate guilt, feelings or hopelessness, difficulty concentrating, and suicidality. Bipolar II does not have a history of manic or mixed episodes.
 * Note: The ICD-11 lists 13 additional subcategories of Bipolar type II disorder. They can be found here.
 * Cyclothymic Disorder
 * Cyclothymic disorder is characterized by a persistent instability of mood over a period of at least 2 years with symptoms present at least half of the time, involving numerous periods of hypomanic (e.g., euphoria, irritability, or expansiveness, psychomotor activation) and depressive (e.g., feeling down, diminished interest in activities, fatigue) symptoms that are present during more of the time than not. The hypomanic and depressive symptoms are not severe or prolonged enough to meet the full definitional requirements of a hypomanic or depressive episode (see Bipolar type II disorder). There is no history of manic or mixed episodes (see Bipolar type I disorder). The symptoms result in significant distress or significant impairment in personal, family, social, educational, occupational or other important areas of functioning.
 * Changes in DSM-5
 * The diagnostic criteria for Bipolar Disorder changed slightly from DSM-IV to DSM-5. This includes the removal of the not otherwise specified subtype. Summaries are available here and here.

The DSM-5 and ICD-11 provide diagnostic criteria for BD that are used by clinicians in the assessment of both adults and youth. The diagnostic criteria for PBD is similar to that used to assess BD in adults, with minor variations to address changes in development. For adults and children alike, there are four classifications of BD: bipolar I disorder, bipolar II disorder, cyclothymic disorder, and Other Specified Bipolar and Related Disorder. The table below describes the core features of bipolar disorder.

a Sensitivity estimates from Van Meter, Burke, Kowatch, et al. (2016) meta-analysis.

A bipolar I disorder diagnosis requires the patient to have at least one manic episode within their lifetime. Manic episodes are best described as a period of extreme elated mood/energy and irritability, and individuals must experience three or more of the symptoms provided ; among the most commonly experienced are grandiosity, racing thoughts, decreased/dysfunctional sleep, and being easily distracted. Major depressive episodes are common but not required for a diagnosis of bipolar disorder. Major depressive episodes are characterized by a period of either anhedonia or depressed mood in addition to having five or more of the classified symptoms within a period of 2 weeks such as lack of sleep, fatigue, worthlessness, or suicidal ideation. To be diagnosed with bipolar II disorder, a patient must demonstrate at least one hypomanic episode paired with at least one major depressive episode. The criteria are still the same for a depressive episode, but a hypomanic episode is a change in mood present for at least 4 consecutive days for a majority of the day. Three or more of the similar symptoms experienced for manic episodes are required. The DSM-5 specifies manic, hypomanic, and depressed as the three types of episodes of BD.

Adapted from DSM-5 ; ICD-11 ; ISBSD Child Diagnosis Task Force.

Cyclothymic disorder occurs when the patient experiences hypomanic episodes and depressive episodes (but not major depression) over a period of 2 years.

One of the symptoms most commonly experienced by children with pediatric bipolar disorder is irritability. This is observed during manic/hypomanic episodes. Although it is a distinct symptom of bipolar disorder, it is also a symptom of other psychological disorders such as ADHD or conduct disorder. If irritability is absent as a symptom for the patient and no other significant risk factors are present, bipolar disorder can be ruled out. . Grandiosity, or a heightened feeling of importance, is another major symptom for BD, but a large proportion of children with PBD do not experience this symptom.

Though the DSM-5 is typically used in the United States for diagnosing pediatric patients with bipolar disorder, the most recent edition of the ICD-11 can also be utilized. Like DSM-5, ICD-11 classifies bipolar disorders into bipolar I and bipolar II; however, the BD specifier of ‘mixed episode’ is still presented in ICD-11,. The DSM-5 changed the symptoms of ‘mixed episodes’ to be classified as a ‘mixed features’ specifier. The diagnosis of bipolar I disorder can also be validated by ICD-11, but it is questionable whether bipolar II disorder represents a subset of bipolar I disorder, but with more emphasis on depressive episodes.

Prevalence
A recent meta-analysis estimated the prevalence rate of PBD overall as 3.9% (when BD is defined as a spectrum diagnosis). Although this represents an increase in the rate as compared to an earlier meta-analysis's prevalence rate of 1.8%, this may be the result of a shift from the DSM-IV to the DSM-5 and subsequent changes to diagnostic specificity. It is also consistent with prevalence rates of other recent meta-analyses. Compared to the overall rate, Bipolar I has a prevalence rate of of 0.6%. These rates indicate that bipolar disorder in youth is more common than autism and schizophrenia but not more common than ADHD or unipolar depression.

Another study compared diagnostic rates of PBD in the United States to other countries and identified that U.S. children are just as likely to be diagnosed with PBD as children in any other country. This suggests that cultural and ethnic factors do not present risk factors for PBD or biases in the interpretation of bipolar symptoms. Older adolescents also have significantly higher prevalence rates compared to pre-pubertal youth.

Sex Differences
Studies of Bipolar I in adults have demonstrated that it occurs equally in men and women. No significant differences in PBD prevalence based on gender have been demonstrated after accounting for the fact that generally, more young males present to clinics for externalizing problems than females, although earlier studies have reported a higher percentage of females with bipolar II disorder than males.

Common Comorbidities
Many symptoms of PBD overlap with symptoms of other diagnoses that are common in childhood (e.g., ADHD, conduct disorder, oppositional defiant disorder), and bipolar disorder is often comorbid with other conditions. Comorbid psychopathology may also exacerbate bipolar symptoms in pediatric patients, complicating accurate diagnosis. A meta-analytic study investigating the phenomenology of mania in children, including the most common comorbidities, determined that ADHD is the most common comorbid diagnosis (62% of participants) in children with PBD, followed by Oppositional Defiant Disorder (ODD; 53%), psychosis (42%), and anxiety (27%).

In addition to being commonly comorbid, overlapping symptoms between PBD and ADHD include irritability, distractibility, and impulsivity. When pediatric patients are diagnosed with both ADHD and PBD, they may be more susceptible to an increased severity of shared symptoms. One study investigated the effect a comorbid diagnosis of both ADHD and bipolar spectrum disorder (BPSD) had on pediatric patients when compared to pediatric patients with only BD. When pediatric patients were diagnosed with both ADHD and BPSD, they were more likely to experience decreased overall functioning and increased severity of symptoms. Patients with both ADHD and BPSD also experienced higher rates of additional comorbidities when compared to patients with only BPSD or ADHD alone. Age of onset did not differ between the BPSD only group and the combination of ADHD and BPSD.

There have also been cases of patients with PBD and comorbid Autism Spectrum Disorder (ASD). Researchers have studied individuals diagnosed with ASD and experiencing bipolar symptoms to investigate neurocognitive and clinical impairment compared to individuals only with ASD, and discovered that the ASD + BD group experienced an increased rate of externalizing behaviors (e.g., aggression, delinquency) and behavioral inhibition. The ASD + BD group also experienced increased internalizing behaviors such as depression, suicidal ideation, and anxiety.

Prognosis or Developmental Course
Because the bipolar symptoms pediatric patients experience can be variable and unpredictable in nature (especially in terms of duration and frequency), it is difficult to determine if there is a concrete age of onset for PBD. According to a study by Leverich et al. (2007), when surveying 480 individuals with bipolar disorder, 14% reported their age of onset was between 0-12 years old, with the average age around 9.57. Patients with earlier onset of PBD were reported to have the highest incidence of parental history of depression and/or BD and greater environmental stressors. Earlier onset of bipolar disorder corresponded with longer time to treatment. Additionally, adult patients with earlier onset experienced a more convoluted developmental course of BD, including faster cycling periods, substance abuse, depressive episodes, and suicide attempts, demonstrating the importance of early intervention for PBD. The family environment of a child with PBD can also affect overall functioning and symptom severity. Pediatric patients that experience greater impairment in a variety of contexts (at home, in school, and other social settings) are more likely to have reduced overall functioning, a history of being admitted to a mental health institution, and/or a suicide attempt. Additionally, reduced functional and social impairment for children with PBD can ultimately lead to a reduced quality of life. Cotrena et al. (2020) measured the value of ‘quality of life’ (QoL) for patients with PBD based on how their personal QoL (how they view their lives) and social QoL (how they perceive the world) compared to how the patient managed their depression symptoms and their PBD diagnosis, and both were found to negatively affect outcomes. In particular, such factors (which factors?) influenced one’s personal QoL and cognitive performance. Because the presence of manic and depressive symptoms can impair function and, consequently, cognitive performance, children with PBD may experience lower self-esteem and reduced quality of life compared to healthy children.

Evidence-Based Assessment
PBD is considered a spectrum disorder, suggesting that children with PBD are likely to experience a range of symptoms. This can make PBD especially difficult to diagnose and, consequently, treat. Establishing a clear and well-defined assessment strategy for clinicians to use can provide a more accurate and reliable way to diagnose PBD and prevent misdiagnoses. Clinicians are recommended to use screening questions as an initial step in evidence-based assessment (EBA). Screening questions allow the clinician to gauge if the patient has had spontaneous changes in mood for defined periods of time and assess personal and family history of mood disorders. Symptom reports from family members, school, and peers are necessary to gauge the behavioral and emotional challenges a child is experiencing. Other potential medical conditions or comorbid disorders must be reported to determine the most appropriate treatment plan, especially if there is a presence of suicidal ideation and/or substance abuse. Following the screening, the use of a questionnaire and checklists are the next logical step in EBA.

Questionnaires like K-SADS, WASH-U-KSADS, and the Young Mania Rating Scale are pivotal for determining mania severity as well as feedback for treatment, but not for diagnosing a patient with PBD. One of the most effective assessment checklists for diagnosis is the Achenbach System of Empirically Based Assessment (also Child Behavior Checklist, CBCL). The CBCL represents a pediatric patient’s symptoms on a scale, conveying both externalizing and internalizing symptoms. The CBCL shows a higher sensitivity for externalizing scores for PBD, which is helpful in differentiating PBD from other disorders like ADHD. Such measures indicate what the appropriate approach for treatment is as well as the patient’s overall functioning level. However, in general, questionnaires are observed to be more effective when paired with a diagnostic structured interview.

Bayesian approaches, or nomograms, may also be used with checklists or questionnaires. Bayesian approaches identify the probability that a patient has a certain disorder using a patient's diagnostic likelihood and their test results on performance-based exams. The nomogram allows clinicians to create probabilities that are unbiased, efficient, and produce no variability, reducing the chance that PBD would be misdiagnosed.

Note. Bipolar Disorder is extremely rare before the age of 5; do not consider as a possible diagnosis except under highly extenuating circumstances.

Glossary: YSR = Youth Self Report ; BASC = Behavioral Assessment Scale for Children ; SDQ = Strengths and Difficulties Questionnaire ; ASI = Adolescent Symptom Inventory ; CSI = Child Symptom Inventory ; YASR = Young Adult Self-Report ; PPDS = Petersen Pubertal Developmental Screen ; FIRM = Family Index of Risk for Mood disorders ; GBI = General Behavior Inventory ; 7 Up = 7 Up ; PGBI-10M, 10Da, 10Db = 10 item forms of parent-reported GBI ; HCL = Hypomania Checklist ; BSDS = Bipolar Spectrum Diagnostic Scale ; MDQ = Mood Disorder Questionnaire ; ISS = Internal States Scale ; MINI = Mini International Neuropsychiatric Interview ; MINI-Kid = MINI for Children and Adolescents ; KMRS = KSADS Mania Rating Scale ; KDRS = KSADS Depression Rating Scale ; YMRS = Young Mania Rating Scale ; HDRS = Hamilton Depression Rating Scale ; CGAS = Children’s Global Assessment Scale ; GAF = Global Assessment of Functioning ; KINDL = quality of life scale (not an acronym) ; QoL.BSD = Quality of Life for Bipolar Disorder ; PGBI Sleep = sleep scale carved from parent GBI ; SMEQ = Student Morningness-Eveningness Questionnaire ; PSQI = Pittsburgh Sleep Quality Index.

Online Assessment Resources
There are a number of online assessment resources available for the general public (adolescents, parents, etc.) as well as clinicians. The Helping Give Away Psychological Science (HGAPS) Assessment Center offers a free, confidential platform to help you safely explore your mental health symptoms and determine if you should seek assistance from a mental health professional. Upon finishing an assessment, you will be given your results and offered recommended resources based on the symptoms you have endorsed.

The following links are to specific assessment batteries for adults, adolescents, and caregivers:

This survey contains self-report assessments used by mental health professionals to measure ADHD, depression, anxiety, PTSD, bipolar disorder, and substance use in adults. These questionnaires are designed to be taken by an adult about themselves.

This survey contains self-report assessments used by mental health professionals to measure depression, anxiety, PTSD, bipolar disorder, substance use, and oppositional defiant disorder/conduct disorder in youth. These questionnaires are designed to be taken by a child or adolescent about themselves.

This survey contains assessments used by mental health professionals to measure ADHD, depression, anxiety, PTSD, bipolar disorder, substance use, and oppositional defiant disorder/conduct disorder in youth. These questionnaires are designed to be taken by a caregiver about a child or adolescent.

The HGAPS Assessment Center also offers specific measures for clinician use.

Evidence-Based Treatment
After a child or adolescent has received a comprehensive, evidence-based assessment and is diagnosed with PBD, the clinician should devise the most appropriate evidence-based treatment plan specific to the patient. There are numerous treatment options for PBD, and research has demonstrated efficacy in pharmacotherapy, psychotherapy, and the combination of the two.

Medication
Medication is often the first line of treatment for children and adults with BD, though current recommendations suggest a combination of medication and therapy is most effective (Look at review by Kowatch; AACAP practice parameters- need EAY to send to JJ; Correll has meta-analyses about efficacy and side effects). Before medication is prescribed to pediatric patients, their medical history and the possibility of comorbidity must be considered. Lithium can only be prescribed to children who are 12 years of age or older. Lithium and Divalproex have been recommended as a first line for treatment, specifically for nonpsychotic manic episodes. A combination of medications such as lithium with Divalproex or lithium with an atypical antipsychotic can also be efficacious, but typically this treatment approach is only used if the use of a singular medication is unsuccessful. Overall, patients who are prescribed medication must be thoroughly monitored for adverse side effects (especially for lithium, which can be toxic if blood lithium levels are too high).

Lithium
Though there are variety of pharmacological treatment options for BD, lithium is a commonly used mood stabilizer. According to Harrison et al. (2016), lithium is the most effective treatment to prevent relapse of mood episodes. Lithium works by inhibiting inositol monophosphate and other enzymes signaling to calcium channels, inhibiting mitochondrial function, and G-protein activated potassium channels. Lithium use must be carefully monitored, because there is a delicate balance between a dosage that is helpful and one that is toxic or even deadly.

A meta-analysis completed by Nolen et al. (2019) found that optimal lithium dosages were around the lower end of 0.45-0.60 mmol/L and the higher end of 0.80-1.00 mmol/L. Individuals at the higher end of dosage (0.80-1.00 mmol/L) relapsed more often than those in the lower end of dosage. Patients who were given less than 0.45 mmol/L had a relapse rate of 61.5%, demonstrating that there is a minimum dosage in which lithium can be effective. Patients outside the two ranges did not see any benefit, especially if the individual was prescribed more than 1.00 mmol/L.

Lithium is a popular pharmacological treatment option because it can prevent mood episodes from reoccurring in patients with BD. Lithium may prevent manic episodes and decrease the risk of suicide (a notable benefit given that BD has one of the highest suicide rates in comparison to the general population). A study by Song et al. (2017) demonstrated a 14% decrease in suicide-related events (in patients with BD?) in comparison to a group with BD that was not receiving lithium (were they receiving anything else?). Because lithium may reduce manic episodes, it may subsequently reduce impulsivity. Decreased impulsivity can lead to decreased rates of self-harm in individuals with BD.

Though lithium's effectiveness makes it a frontline treatment for BD, it may also be a dangerous treatment option. The thyroid, kidneys, and the parathyroid glands are three large and important organ systems that may sustain damage from lithium intake. Most people experience mild side effects when actively taking lithium, all of which are related to organ damage over time. For example, lithium use can structurally damage kidney tubules, resulting in polyuria (increased urination). Symptoms of lithium toxicity must be closely monitored, and dosages of lithium must be adjusted based on a person’s sensitivity.

Lithium is widely used for BD treatment in adults, but its use in children is understudied. CoLT studies have found an optimal dosage in children of 0.3 and 1.3 mEq/L, which is much lower than the dosage for adults. In another research study in children with BD, some children who were taking lithium achieved remission. Those who were not considered "in remission" experienced stabilization of symptoms, a promising direction for future research.

Anticonvulsants (Antiepileptic Agents)
Antiepileptic agents are used for the treatment of BD in both youth and adults. The specific antiepileptic agents that have been studied in children and adolescents with BD are carbamazepine, divalproex sodium, lamotrigine, oxcarbazepine, and topiramate.

Antipsychotics
Antipsychotics (also known as neuroleptics) may be used in conjunction with lithium when someone is undergoing an acute, severe manic episode. However, there are concerns over neurotoxicity with a prolonged use of lithium and antipsychotics together. The FDA has approved antipsychotics for treatment of BD, mania and mixed states, and as maintenance to treat depressive, manic or mixed episodes. A common practice is also to use antipsychotics over a prolonged period. However, antipsychotics may cause several undesired side effects such as weight gain, late dyskinesia, sedation, sexual dysfunction and depression. Antipsychotics may be further classified into typical or atypical.

First Generation Antipsychotics (FGA; "Typical")
Typical antipsychotics, or first generation antipsychotics, are useful in treating manic symptoms even in the absence of psychotic symptoms. However, their use has drastically decreased in the treatment of BD due to the risk of extrapyramidal symptoms (drug-induced movement disorders).

Second Generation Antipsychotics (SGA; "Atypical")
Atypical antipsychotics, or second generation antipsychotics, are equally effective as typical antipsychotics in the treatment of manic symptoms, but they do not cause extrapyramidal symptoms. Since 2000, there have been several aytipcal psychotics that have been approved for treatment by the FDA. Olanzapine (generic form available) was approved in 2000, Risperidone was approved in 2003, Quetiapine, Aripiprazole, and Ziprasidone were approved in 2004, Olanzapine/fluoxetine combination was approved in 2012, Lurasidone was approved in 2013, and Cariprazine and Asenapine were approved in 2015.

Antidepressants
Depressive episodes within patients with BD are often difficult to treat pharmacologically, because elevating mood via antidepressants may lead to manic episodes.

Psychosocial Therapy
Another approach to treatment is psychosocial therapy. Cognitive-behavioral therapy (CBT) emphasizes the psychosocial factors of PBD and helps the pediatric patient change their thinking patterns and learn coping skills to manage their cognitions and emotions. An adaption of combined family-focused treatment and CBT called Child- and Family-Focused CBT (CFF-CBT), or the RAINBOW program, was established specifically for children with PBD between the ages of 8-12 and their families. This 12-session program focuses on teaching parents and children self-efficacy and behavioral management, engaging problem-solving skills, and increasing or maintaining social support. CBT and its many variations may be useful to help families and children learn to manage bipolar disorder as well as reduce the negative conflict and affect likely existent within a household.

Interpersonal Social Rhythms Therapy (IPSRT) has also been demonstrated as an effective treatment for adolescents with PBD, specifically to manage symptoms related to sleep dysfunction. IPSRT can help youth stabilize their moods, improve social functioning, and regulate their sleep patterns. It can also help clinicians establish the relationship between the beginning of mood episodes and sleep dysfunction patterns. When combined with medication, IPSRT has been shown to increase time between mood episodes.

Exercise as a Treatment Component
Exercise has been credited for its tremendous benefits in cardiovascular systems, the brain, sleep, and even mood. Although it is not a first-line treatment for PBD, there may be benefits to including an exercise regimen as an adjunctive treatment with medication and/or psychotherapy. There is limited research examining exercise's benefits in PBD, but studies in adults with BD demonstrate promising results. Consequently, adults with BD tend to have more sedentary lifestyles, which may lead to increased comorbidities and depressive symptoms.

One such promising study investigated the impact of exercise on adults with BD, examining improvements in quality of life and mood symptoms. 40% of participants reported not exercising at all, and the less participants exercised (of those who did), the more likely their quality of life and overall functioning was to be lower. Consequently, exercising more often corresponded to more frequent manic symptoms and mixed episodes.

Though the above studies observe adults with BD, it is likely that exercise is associated with the same effects on mood symptoms and quality of life in children, and additionally, one’s long-term trajectory of BD into adulthood. A study of adolescents demonstrated that when adolescents with BD participate in short-term, aerobic exercise, neural activity in the nucleus accumbens is different after exercising (measured by performing an executive task both before and after exercise). This suggests for adolescents, and possibly extending into younger children, exercise can increase concentration, an impairment that is often seen in youth with PBD.

Resources
Archived content from original draft (to be moved to talk page)

Pediatric bipolar disorder (PBD) has been acknowledged by clinicians and researchers alike for centuries, but the diagnosis of Bipolar Disorder in children has historically been controversial. There is a long-standing debate over whether or not bipolar disorder (BD) should be diagnosed in children at all, and if it should, at what age is it appropriate to begin to diagnose children with the disorder. According to meta-analytic evidence, the community prevalence of PBD is 3.9%, without a significant increase in prevalence over time. There is large variability demonstrated within the symptom presentation of children with PBD, partly due to the fact that BD is a "spectrum" of disorders with no clear qualitative boundaries separating the different types (i.e., BD-I, BD-II, cyclothymia, and Other Specified Bipolar and Related Disorder)identified by current classification systems. To combat this variability within symptoms and allow for a concrete diagnosis, it is important to evaluate the most appropriate plan for assessment, diagnosis, and treatment while also keeping in mind the risk factors and long-term prognosis for children with PBD.

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