Pediatrics

Mood disorders

OVERVIEW: What every practitioner needs to know

Are you sure your patient has a mood disorder? What are the typical findings for this disease?

"Mood Disorders" refers to either depression (aka "unipolar depression"); two main types: (1) major depressive disorder [MDD] or (2) dysthymic disorder; OR bipolar disorder (aka "manic depressive disorder").

Shared features of mood disorders (both depression and bipolar disorder):

1. Change in mood (def. feeling state) from child's usual

2. Duration: mood change persists for specific amount of time (see below)

3. Associated symptoms: mood change is associated with other non-mood symptoms (referred to "neurovegetative" symptoms because they include changes in body function) - e.g., changes in sleep, attention/concentration, etc.

4. Functional impairment: mood change interferes with child's functioning at home/family, at school, and with peers.

Depression

Major depressive disorder (MDD):

A. Having at least 1 major depressive episode (MDE) consisting of 5 or more of the following symptoms during the same 2-week (or more) period [including either #1 or #2]:

  1. Depressed mood most of the day, nearly every day (Note: in children, DSM-5 allows this to be "irritable" mood, although as above in first paragraph, depressed or irritable mood needs to be a change from their usual mood. If they are chronically/always irritable, you need to consider another disorder - see below.).

  2. Decreased interest/pleasure in most activities most of the day, nearly every day.

  3. Significant weight loss (>5% of body weight/1 month) or decreased appetite.

  4. Insomnia OR hypersomnia.

  5. Psychomotor agitation OR retardation observable to others.

  6. Fatigue/loss of energy.

  7. Feelings of worthlessness or inappropriate guilt.

  8. Decreased ability to concentrate or to make decisions.

  9. Recurrent thoughts of death (not just fear of dying) or wanting to die/suicidal ideation.

B. Symptoms cause significant functional impairment at home, school, or peers.

C. Symptoms not directly due to substance use/abuse or medical condition.

D. Can never have had manic or hypomanic episode or psychotic disorder (e.g., schizophrenia).

Persistent depressive disorder (dysthymia):

A. Depressed mood, most of the day, more days than not, for >1 year (children) or >2 years (adults). (Note: children's mood can be irritable)

B. >2 of the following:

  1. Decreased or increased appetite.

  2. Insomnia or hyposomnia.

  3. Fatigue/low energy.

  4. Decreased self-esteem.

  5. Indecision/decreased concentration.

  6. Hopelessness.

C. No major depressive episode during first 2 years of dysthymic disorder (1 year in children).

D. No manic/hypomanic episode or psychotic disorder.

E. Not due to substance use/abuse or medical condition.

Disruptive mood dysregulation disorder:

Disruptive mood dysregulation disorder (DMDD) is a new diagnosis in DSM-5 based on more than 15 years of research designed to address key issues in pediatric bipolar disorder, namely are children with chronic, non-episodic irritability the same or different than children with distinct episodes of euphoric mania, including examination of longitudinal symptom trajectory from childhood to adulthood and neuroimaging findings.

Most importantly, DMDD is not meant to be a replacement for a “mood disorder not otherwise specified” that was eliminated in DSM-5. In particular, DMDD is meant to be among the most specific disorders in DSM-5 and is not a “catch all” for children with irritability. As below - criteria J - DMDD should not be used when children actually have bipolar disorder or autism spectrum disorder or other condition that better explains the chronic irritability.

DMDD is placed in the “depression” section of DSM-5 because those studies suggest that children with DMDD are at high risk of developing major depressive disorder when they are adults (rather than an elevated risk for bipolar disorder).

DMDD Criteria:

  • Severe recurrent out of proportion temper outbursts manifest verbally or physically (i.e., abnormally intense, long, or inconsistent with situation/trigger).

  • Temper outbursts are inconsistent with developmental level.

  • Temper outbursts occur on average >3 times/week.

  • Mood between temper outbursts is chronically irritable or angry most of the day, nearly every day, and observable to peers, parents, or teachers.

  • Criteria A-D are present >12 months without >3 consecutive months without A-D.

  • Criteria A and D are present in at least 2 of home, school, and peers, and are severe in at least 1.

  • Diagnosis should not be made before age 6 or after age 18.

  • Onset of A-E is before age 10.

  • Never >1 day of full symptom criteria (except duration) for mania or hypomania have occurred.

  • Does not occur during major depression, or better explained by other disorder (i.e., autism spectrum disorder, PTSD, dysthymia, substance use disorder, or neurological disorder.

Bipolar disorder

There are two major forms of bipolar disorder: type I (>1 manic episode lasting >7 days) or type II (>1 hypomanic episode lasting 4-7 days PLUS >1 major depressive episode lasting 2 weeks).

Important changes in the diagnostic criteria for bipolar disorder moving from DSM-IV to DSM-5 include:

(1) the euphoric or irritable mood change as part of bipolar disorder must be present most of the day, nearly every day (or any duration if hospitalization is necessary) mirroring language from a major depressive episode;

(2) either increased goal-directed activity or energy must also be present during the manic episode;

(3) the former “bipolar disorder not otherwise specified” has been split into two disorders:

  • “other specified bipolar disorder” (for patients with symptoms of bipolar disorder that cause distress/impairment, but do not meet full criteria for type I or II; e.g., someone with a 2-3 day full criteria except duration mania);

  • “unspecified bipolar disorder” (for patients whose symptoms of bipolar disorder cause impairment but do not meet full criteria).

Manic Episode:

A. Distinct period of abnormally elevated, expansive, or irritable mood, and abnormally and persistently increased goal directed activity or energy lasting at least 1 week (or any duration if hospitalization is necessary):

B. During mood disturbance, >3 of following if mood mostly elevated/expansive (aka "euphoric") OR >4 if mostly irritable:

  1. Grandiosity or inflated self-esteem.

  2. Pressured speech.

  3. Flight of ideas or racing thoughts.

  4. Decreased need for sleep (gets less sleep and not tired - different from major depression)

  5. Distractibility.

  6. Increased goal-directed activity or psychomotor agitation (e.g., excessive involvement in school, building things).

  7. Excessive involvement in pleasurable activities with high potential for painful consequences (spending/sex sprees, running away, gambling/risky financial decisions).

C. Symptoms cause significant functional impairment at home, school, or peers.

D. Not due to substance use/abuse or medical condition.

Hypomanic Episode:

Same as manic episode except: (1) 4-7 days (not >7 days), (2) less impairment (not severe, not hospitalized).

What other disease/condition shares some of these symptoms?

Mood disorders (both depression and bipolar disorder) can be mimicked by:

1. Hypo- or hyperthyroidism

2. Substance use/abuse

3. Anemia or malignancy

4. Other related psychiatric disorder (including anxiety disorders or eating disorders)

What caused this disease to develop at this time?

  • Epidemiology: By end of adolescence, depression prevalence ~20% (1-2% pre-pubertal children, 3-8% adolescents). Higher female/male ratio of depression starts in adolescence and continues through adulthood.

    • Of those with depression, 10-20% may develop bipolar disorder. Bipolar disorder prevalence ~3-5% of adult population (1/3 adults with bipolar disorder report onset of mania/hypomania prior to age 21 years).

  • Genetics: No single gene for depression or bipolar disorder. Increased risk among first-degree relatives; however, children with bipolar disorder more likely to have first-degree relative with major depression rather than bipolar disorder.

  • Sleep/circadian rhythm: Sleep deprivation is a known trigger for mania.

  • Family environment: Maternal depression strongly linked to onset of child depression and other psychiatric disorders. Family discord and elevated expressed emotion also linked to depression. Inter-personal conflict (i.e., fights with child peers or adolescent romantic relationships) also triggers for depression and/or suicide).

  • Stress: Stressful life events may be related to onset of depression and bipolar disorder.

  • Neuroendocrine: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction may be related to depression, though some data in children is mixed.

  • Neuroimaging: Brain imaging studies suggest frontal-amygdala (depression) or frontal-amygdala-striatal (bipolar disorder) structural and functional changes may be involved. Work is ongoing.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

  • Thorough review of symptoms is indicated to evaluate endocrine, hematological/oncological, neurological, substance use/abuse, and psychiatric differential diagnosis.

  • If indicated, it may be useful to evaluate TSH/free T4 (thyroid dysfunction), CBC+diff (heme), BMP (eating disorders), or toxicology screen (though many report adolescents fully disclose their use if asked non-judgementally).

  • Rating scales: Rating scales/questionnaires can be very helpful to clarify the diagnosis/severity of depression or co-occurring issues.

Would imaging studies be helpful? If so, which ones?

Not generally indicated unless strong suspicion of medical issues (e.g., early morning headaches/vomiting - suggestive of cerebral tumor rather than primary depression) or associated psychosis that is not mood-congruent (e.g., seems disconnected with psychiatric symptoms) or does not improve with treatment of underlying mood disorder.

Confirming the diagnosis

  • American Academy of Child/Adolescent Psychiatry (AACAP) practice parameters:

    • Psychiatric assessment of the child or adolescent patient.

    • Depression.

    • Bipolar disorder.

    • General website: www.aacap.org.

  • Rating forms/questionnaires that are often very useful:

    • Depression:

      • Beck Depression Inventory OR Children's Depression Inventory: Specific to depression; good for measuring severity of symptoms and illness progression.

    • Bipolar disorder:

      • Young Mania Rating Scale: Specific to mania; good for measuring symptom severity and illness progression.

      • Mood tracking sheets: Various freely available measures can chart daily mood fluctuations - e.g. "BEAM" mood chart (daily record of mood, anxiety, irritability, and sleep).

    • Co-occurring disorders:

      • Child Behavior Checklist (CBCL): Parent/teacher/child versions with age/sex norms to screen for co-occurring psychiatric issues such as depressed/anxious, withdrawn, social, thought, attention, delinquent, and aggressive problems.

If you are able to confirm that the patient has a mood disorder, what treatment should be initiated?

Depression:

  • Studies suggest that mild/moderate depression may be treated with therapy alone, whereas moderate/severe depression may benefit from the combination of psychotherapy plus medication.

  • Psychotherapy: the following types of psychotherapy can be used to treat depression in children/adolescents:

    • Psychoeducation: What is depression, identifying/minimizing triggers, increased knowledge of treatments and their side effects.

    • Cognitive behavioral therapy (CBT): Recognizing relationship between thoughts, feeling, and actions in continuing depression.

    • Interpersonal psychotherapy (IPT): Recognizing role of peers as triggers and supports for depression.

  • Medication treatment: Anti-depressant medication treatment typically starts with selective serotonin reuptake inhibitors (SSRIs).

    • Selection of which SSRI should be guided by first-degree relative positive or negative response and at present typically starts with any of these agents: fluoxetine (Prozac), sertraline (Zoloft), or citalopram (Celexa).

    • Use of SSRIs must also include a discussion of the FDA black box warning on anti-depressant/anti-anxiety serotonergic agents including SSRIs in any patient <25 years old (see www.fda.gov).

    • Medication treatment also requires close monitoring for treatment emergent side effects, including suicidality or mania, especially during the first 12 weeks. Many suggest this should include weekly check-ins (can be face-to-face or alternating with telephone contact) for the first 8-10 weeks, then gradually spaced out.

    • Use of dextromethorphan containing agents (i.e., cough suppressants) is contra-indicated with concomitant SSRI use due to increased risk for serotonin syndrome, including irritability and rage.

Bipolar Disorder (mania or hypomania):

  • Treatment involves a combination of medication and psychotherapy to address the following goals: (1) reducing or preventing mania, (2) reducing or preventing depression, (3) treating any co-morbid psychiatric disorders (e.g., ADHD, anxiety, drug use), (4) optimizing school, peer, and family function, (5) addressing any resulting side effects (e.g., metabolic syndrome [massive weight gain in short time period; i.e., >10 kg in <3 months] from atypical neuroleptic agents).

  • Medication treatment:

    • Anti-manic agents fall into 3 categories listed from strongest to weakest evidence in children with bipolar disorder at present: (1) atypical neuroleptics (e.g., risperidone, quetiapine, aripiprazole, etc.); (2) lithium; (3) anti-epileptic drugs (e.g., valproate).

    • All anti-manic agents require blood draws prior to initiation and 2-3 times/year to monitor effect/side effects (including metabolic [atypical neuroleptics; fasting lipid panel, haemoglobin A1c], hepatic [atypical neuroleptics and anti-epileptic drugs], renal [especially lithium], and thyroid [especially lithium]).

    • Term "mood stabilizer" should not be used as this is purely a marketing term coined by the pharmaceutical industry creating artificial expectations.

  • Psychotherapy:

    • Can involve psychoeducation or CBT (see above in “depression”) or:

      • Family-focussed therapy (FFT): Combines elements of psychoeducation and CBT administered to families and is highly effective for pediatric bipolar disorder.

      • Interpersonal social rhythm therapy (IPSRT): Focuses on maintaining regular sleep, exercise, diet, and social contact to avoid mania and depression and also, if those become irregular, to recognize that these may be warning signs of impending manic or depressive episode.

What are the adverse effects associated with each treatment option?

SSRIs: Common - stomach upset, irritability. Serious/possible - as in FDA black box warning risk for suicidality and mania.

Anti-manic medication: Vary by type including lithium, atypical neuroleptics (e.g., risperidone, aripiprazole, olanzapine, etc.), or anti-epileptic drugs (e.g., valproate, etc.). Too varied to list in this setting.

What are the possible outcomes of a mood disorder?

Untreated depression or bipolar disorder can be life-threatening, with high risk for suicide and functional impairment (school, peers, family).

Potential benefits of treatment: restored mood, functioning, and behavior.

Long-term: For depression, some (but not all) children/adolescents find after 1 year of treatment, it is possible to gradually taper to discontinuation their medications without recurrence/re-emergence of symptoms. For bipolar disorder, this is often a life-long condition, requiring careful adjustment of medication to meet a patient's symptoms as they grow/develop.

Other clinical manifestations that might help with diagnosis and management

Some say up to 20% of those initially presenting with depression may develop bipolar disorder. So, cautious monitoring for development of mania is warranted in anyone treated for depression.

What complications might you expect from the disease or treatment of the disease?

Depression: With time, some people who have responded to a certain anti-depressant may see their depression worse/re-emerge. The cause is unknown, but it may require dose adjustment, augmentation with another anti-depressant, or switch to another anti-depressant.

Bipolar disorder: As above, careful monitoring is required to meet the goals of minimizing/preventing mania or depression, while addressing co-occurring psychiatric disorders, and monitoring/treating any potential side effects of these medications (metabolic syndrome, thyroid dysfunction, etc.).

Are additional laboratory studies available; even some that are not widely available?

Despite many claims made on the internet, there is no gene or brain scan that can reliably diagnose either depression or bipolar disorder in children, adolescents, or adults.

How can mood disorders be prevented?

At this time, there is no primary prevention for either depression or bipolar disorder. Children of parents with either condition should be screened periodically, though it is not a 1:1 correspondence of parent with mood disorder = child with mood disorder.

What is the Evidence?

References and additional reading:

Practice Parameters:

Birmaher, B, Brent, D, Bernet, W, Bukstein, O, Walter, H, Benson, RS, Chrisman, A, Farchione, T. "Practice parameter for the assessment and treatment of children and adolescents with depressive disorders". J Am Acad Child Adolesc Psychiatry. vol. 46. 2007 Nov. pp. 1503-26.

McClellan, J, Kowatch, R, Findling, R.L.. "Practice parameter for the assessment and treatment of children and adolescents with bipolar disorder". J Am Acad of Child Adolesc Psychiatry. vol. 46. 2007. pp. 107-125.

Controversies in Pediatric Bipolar Disorder and Information about Disruptive Mood Dysregulation Disorder:

Leibenluft, E, Charney, DS, Towbin, KE, Bhangoo, RK, Pine, DS.. "Defining clinical phenotypes of juvenile mania". Am J Psychiatry.. vol. 160. 2003 Mar. pp. 430-7.

Dickstein, DP.. "The Diagnostic Dilemma: Why We Need to Change How We Diagnose Bipolar Disorder in Children". Cerebrum. November 2010.

Dickstein, DP, Leibenluft, E.. "Beyond dogma: from diagnostic controversies to data about pediatric bipolar disorder and children with chronic irritability and mood dysregulation". Isr J Psychiatry Relat Sci.. vol. 49. 2012. pp. 52-61.

Stringaris, A, Cohen, P, Pine, DS, Leibenluft, E.. "Adult outcomes of youth irritability: a 20-year prospective community-based study". Am J Psychiatry.. vol. 166. 2009 Sep. pp. 1048-54.

Treatment/phenomenology Studies of Depression and Bipolar Disorder:

March, J. "The Treatment for Adolescents With Depression Study (TADS): outcomes over 1 year of naturalistic follow-up". Am J Psychiatry. vol. 166. 2009 Oct. pp. 1141-9.

Curry, J, Rohde, P, Simons, A, Silva, S, Vitiello, B, Kratochvil, C. "Predictors and moderators of acute outcome in the Treatment for Adolescents with Depression Study (TADS)". J Am Acad Child Adolesc Psychiatry. vol. 45. 2006 Dec. pp. 1427-39.

Correll, CU, Kratochvil, CJ, March, JS.. "Developments in pediatric psychopharmacology: focus on stimulants, antidepressants, and antipsychotics". J Clin Psychiatry. vol. 72. 2011 May. pp. 655-70.

Findling, RL, Youngstrom, EA, Fristad, MA, Birmaher, B, Kowatch, RA, Arnold, LE. "Characteristics of children with elevated symptoms of mania: the Longitudinal Assessment of Manic Symptoms (LAMS) study". J Clin Psychiatry. vol. 71. 2010 Dec. pp. 1664-72.

Varigonda, AL, Jakubovski, E, Taylor, MJ, Freemantle, N. "Systematic Review and Meta-Analysis: Early Treatment Responses of Selective Serotonin Reuptake Inhibitors in Pediatric Major Depressive Disorder". J Am Acad Child Adolesc Psychiatry. vol. 54. 2015 Jul. pp. 557-64.

Walkup, JT, Wagner, KD, Miller, L, Yenokyan, G. "Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment". J Am Acad Child Adolesc Psychiatry. vol. 54. 2015 Dec. pp. 1008-19.

Ongoing controversies regarding etiology, diagnosis, treatment

Depression: Current research focused on: (a) bio-behavioral predictors of diagnosis and treatment response, (b) best practices for medication and therapy treatments, (c) improving access to currently available treatments, (d) identifying new treatments, especially novel medications.

Bipolar disorder: Controversial with regard to diagnosis - including how to establish the diagnosis (or rule it out) taking into account issues of development (i.e., distinguishing it from normal mood fluctuations or temper tantrums), and other psychiatric disorders (e.g., ADHD, anxiety, autism-spectrum disorders), and the new DSM-5 DMDD.

Current research focussed on increasing diagnostic specificity using both interviews, mood charting, questionnaires, and bio-behavioral markers. Using both cross-sectional and longitudinal data.

Also work akin to that in depression - i.e., (a) bio-behavioral predictors of diagnosis and treatment response, (b) best practices for medication and therapy treatments, (c) improving access to currently available treatments, (d) identifying new treatments, especially novel medications.

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