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Abstract: Irritability is a common symptom associated with several pediatric mental health disorders including depression, anxiety, attention-deficit/hyperactivity disorder, and oppositional defiant disorder. Recommended treatments may be significantly different based on the target symptoms. Diagnostic clarification is achieved over time using screening tools, individual and family history, coordination with schools, and targeted observation.
Mental health disorders are defined and diagnosed using criteria established in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision(DSM-IV-TR). The DSM-IV-TR has defined irritable mood as "easily annoyed and provoked to anger."1
Irritability is a general symptom associated with several DSM-IV-TR diagnoses. This article will focus on irritability as a common denominator shared by four disorders commonly diagnosed and treated in primary care: depression, anxiety, attention-deficit hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD). Irritability is also associated with bipolar disorder, autism spectrum disorders, and many medical conditions; however, these will not be discussed. These conditions should be assumed to have been ruled out when reviewing symptomatology and treatment plans in this article.
It is not uncommon to hear parents say they are confused, especially when parenting an adolescent. Their adolescent is irritable and often unapproachable, yet the parents have been led to believe that this is developmentally normal. While many teens display mild irritability as part of their developmentally expected quest for independence, a departure from baseline mood and/or disruption in the ability to function is abnormal and may require intervention.
School-aged children and preteens may also display irritability that is more pervasive, hinders school performance, and impacts social and familial relationships. Parents concerned about their child's irritable mood often have to wait several months to see a pediatric mental health provider and longer for a child psychiatrist or psychiatric nurse practitioner. In some cases, these services may not even be available in the area.2 The burden of diagnosis and treatment then falls to the primary care provider.
Irritability is part of the diagnostic criteria for major depressive disorder (see Major depressive disorder DSM-IV-TR diagnostic criteria), generalized anxiety disorder (see Generalized anxiety disorder DSM-IV-TR diagnostic criteria), and is implied in the criteria for ODD (see ODD DSM-IV-TR diagnostic criteria).3 It is not listed as part of DSM-IV-TR criteria for ADHD (see ADHD DSM-IV-TR diagnostic criteria). Irritability, however, is a common symptom of ADHD and tends to improve with successful treatment.4
There is a lot of symptom overlap in addition to irritability between these four common pediatric disorders. Further complications include the high rate of comorbidity between all four diagnoses (with higher rates between depression and anxiety)5 as well ADHD and ODD.4 In addition to gathering a complete symptom history and family psychiatric history, formal screening tools can help determine the primary and more debilitating disorder. There are many free or easily accessible quality screening tools for each disorder that are easy to complete and evaluate (see Common screening tools).
As with many medical disorders, common mental health disorders tend to have a strong genetic component. ADHD has an estimated heritability of 76% based upon 20 twin studies.6 The heritability for pediatric depression is less clear and likely has moderate heritability with significant risk related to environmental stressors.7 While there are several different types of anxiety disorders, twin studies demonstrate a moderate heritability of 54% when examining negative cognition, negative affect, fear, and social anxiety.8 There is less evidence regarding the genetic loading for ODD, as the bulk of the evidence has focused on conduct disorder. In addition to genetic predisposition and environmental stressors, temperament likely plays an important role.9
In general, there are a few FDA-approved medications for use in pediatric patients. In regards to major depressive disorder, there are two selective serotonin reuptake inhibitors (SSRIs) approved for use: fluoxetine for ages 8 years and older and escitalopram for ages 12 years and older. When prescribing antidepressants to children and adolescents, the prescriber must inform patients and parents about the FDA black box warning regarding the increased risk of suicidal thoughts. Prescribers should also discuss a safety plan including determining an adult who the patient will alert if suicidal ideation occurs and that this adult will maintain close supervision and take the patient to the closest emergency department if safety remains a concern.
There are no FDA-approved medications for treatment of pediatric anxiety disorders (generalized anxiety disorder, social phobia, or separation anxiety). Fluoxetine, sertraline, fluvoxamine, and clomipramine are approved for treatment of pediatric obsessive-compulsive disorder. The evidence continues to demonstrate benefits of using SSRIs to reduce anxiety symptoms. Deciding which medication to use is based on the adverse reaction profile and duration of action.5
There are many FDA-approved medications for use in patients with ADHD, the bulk of which are the psychostimulants consisting of methylphenidate or amphetamine products. Evidence demonstrates methylphenidate and amphetamine products are equally efficacious.10 Reasons to choose one type of psychostimulant over another include duration of action (short versus long acting), timing of symptom severity, and medication preparation (pill, capsule, sprinkles, or transdermal patch). The FDA has also approved several nonstimulants as first-line treatment for ADHD: atomoxetine, a selective norepinephrine reuptake inhibitor, and long/centrally-acting alpha-2 agonist clonidine (as the brand, Kapvay) and guanfacine extended-release tablets (as the brand, Intuniv). These medications are often used when a psychostimulant is not tolerated due to adverse reactions, or there is comorbid aggression.4
There are no FDA-approved medications specific for ODD. Medications may be appropriate to treat comorbid disorders such as psychostimulants for comorbid ADHD.9 These medications should be prescribed with caution in this population as oppositional and defiant behaviors are inherent by definition. Medication nonadherence and possible diversion are significant possibilities.
Psychotherapy remains a priority recommendation with all four diagnoses. Those with mild depression without suicidality, agitation, or psychosis will likely benefit from education, support, and case management related to stressors. Those with moderate depression require more specific therapies with evidence supporting the use of cognitive behavioral therapy (CBT) or interpersonal psychotherapy (IPT). Lastly, those with severe depression including suicidality, agitation, or psychosis typically require the addition of an antidepressant. Patients presenting with suicidal ideation, intentions of self-harm, or harm to others must be referred to the emergency department for a psychiatric evaluation. Those who do not respond to monotherapy should undergo combination treatment consisting of psychotherapy and antidepressant therapy.11
CBT remains a first-line treatment for anxiety disorders, and medications tend to be added if the symptoms are so severe that therapy cannot be tolerated. CBT includes psychoeducation and teaching a skill set-which challenges negative thought patterns-and leads to a behavior change through planned, gradual exposures to the anxiety-provoking stimuli.12
Stimulant medication remains the first-line psychopharmacological treatment for ADHD.4 For those with mild symptoms or those who cannot tolerate a stimulant, behavior therapy has shown to be effective. Psychoeducation, along with a close working relationship with the school, improves outcomes.4
In the case of ODD, there is some evidence supporting the use of individual problem-solving skills training as well as family-based parent management training. Parent management training teaches parents how to consistently handle disruptive behaviors including reducing positive reinforcement for disruptive behavior, increased reinforcement of prosocial behavior, and the application of consequences.9
A 9-year-old White male, DS, presented with his parents to a metropolitan pediatric ED after threatening to hurt himself with a knife and becoming aggressive with his family at an outpatient psychotherapy appointment. At the psychotherapy appointment, DS became enraged with minimal provocation, yelled obscenities, and attempted to strangle and scratch his 6-year-old adopted brother. He was physically restrained by his mother in the waiting area, and once released, kicked over chairs, cursed, bit, and kicked his mother. The outpatient therapist called emergency services, and they transported the patient to the pediatric hospital ED. He was then admitted to an inpatient pediatric psychiatric unit for acute stabilization, safety, and assessment.
Prior to this incident and admission, DS had been in outpatient psychotherapy for 5 months. Review of psychiatric symptoms was positive for frequent sadness, suicidal ideation, hopelessness, irritability, poor self-care, rigidity in choosing clothes or toys, impulsivity, aggressiveness, argumentativeness, oppositional/defiant behaviors, and hyperactivity. He reported having no friends; however, his teachers told his parents that he got along well with his peers and appeared to have friends at school. He often made statements such as "my life stinks." DS had an insignificant birth and developmental history other than slight delays in reading. His symptom review was negative for auditory or visual hallucinations, delusions, mania, hypomania, and any history of physical, sexual, or emotional abuse.
DS's family history included diagnosed obsessive-compulsive disorder in his mother, and his father said he had been "an angry child" growing up. Recent significant psychosocial stressors include parental separation with a divorce planned within 1 month of this inpatient admission. He had voiced concerns to his mother that he caused the divorce and had refused to discuss his concerns with his father. DS had an Individualized Education Program for difficulties with reading. He had also experienced verbal bullying at school. Two years ago, his parents received custody of DS's younger paternal half-brothers. Prior to this, he had lived in the home as an only child. DS's father was diagnosed and successfully treated for leukemia 4 years ago, and, for much of DS's life, his mother had undergone extensive treatment for multiple sclerosis.
DS had previously been diagnosed with ADHD and prescribed long-acting methylphenidate. This medication was discontinued within 1 week of initiation, as DS experienced significant insomnia, anorexia, and aggression. His mother reported never agreeing with the ADHD diagnosis and did not recall completing any screening tools at home or sending any screening tools to school for teacher completion. Most recently, he was prescribed bupropion (the drug safety and effectiveness has not been established in pediatric patients) as an oral daily dose to target symptoms of depression and possible ADHD. His mother reported that while taking bupropion, DS demonstrated a decrease in aggression and irritability. Two weeks prior to admission, he consistently refused to take the medication for no apparent reason. He had not tried other psychotropic medications and had no significant medical or surgical history. Upon admission to the inpatient psychiatric unit, a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, and lipid panel were all essentially within normal limits.
DS's situation exemplifies the significant symptom overlap often present in pediatric mental health. His review of symptoms related to depression included frequent sadness, suicidal ideation, hopelessness, irritability, and poor self-care. Worthy of note, DS did have some symptom improvement on the antidepressant bupropion, although he did not experience complete symptom remission. He also expressed symptoms of anxiety including irritability, feeling on edge, separation anxiety related to leaving his mother, and frequent worries about the health of his parents (See Mnemonics). He reported symptoms of ADHD including hyperactivity, difficulty concentrating, impulsivity, and associated irritability. Lastly, he acknowledged ODD-type symptoms of oppositional, defiant, and argumentative behaviors, typically concentrated at home and focused toward his mother.
His family history was positive for obsessive-compulsive disorder with his mother and nonspecific anger with his father. He had a long history of significant environmental stressors including parental separation and looming divorce, legitimate fears of each parent's death, the addition of two half-brothers into his home and family, and school stress related to a learning delay in reading.
The priority symptoms included his suicidal ideation, aggression, and irritability. During his 7-day admission, his consistent presentation during group, individual, and family therapy was that of a healthy, well-nourished, and somewhat cooperative boy. His eye contact remained fair with normal psychomotor activity level, no concerns with speech or language usage, and an anxious/depressed mood and affect. He expressed passive wishes for death during his first 2 days. He consistently denied auditory/visual hallucinations and delusions. His sleep, appetite, and energy levels remained within normal limits with his insight, and judgment ranged between poor to fair. His attention span and concentration were fair. He became tearful and anxious when separating from his parents after visiting hours.
His total score on the Child Depression Inventory was a T score of 64 with clinical significance at a T score of 65 or greater. The subscale T scores included negative mood T = 70, interpersonal problems T = 71, ineffectiveness T = 64, anhedonia T = 64, and negative self-esteem T = 51. He also completed the Self-Report for Childhood Anxiety Related Disorders (SCARED) with a total score of 15 (a total score greater than 25 may indicate the presence of an anxiety disorder; scores higher than 30 are more specific).13 Significant subscale scores include (with the cutoff score in parenthesis) panic disorder/significant somatic symptoms 1 (7), generalized anxiety disorder 5 (9), separation anxiety disorder 4 (5), social anxiety disorder 4 (8), and significant school avoidance 1 (3). His working diagnoses included depressive disorder (not otherwise specified) and anxiety disorder (not otherwise specified). In regards to a previous ADHD diagnosis, his reported and observed symptoms of hyperactivity, restlessness, and poor concentration were associated with anxiety-provoking situations and not pervasive, thus, more consistent with an anxiety disorder instead of ADHD. He was not diagnosed with ODD, as he displayed few symptoms of the disorder other than blaming others for his mistakes and arguing with his mother.
Given the target symptoms of suicidal ideation, aggression, irritability, and his recent partial response to bupropion, the treatment team recommended adding sertraline 25 mg by mouth every morning to target the symptoms related to both depression and anxiety. While sertraline is not FDA-approved for use in pediatric depression or anxiety other than obsessive-compulsive disorder, it is prescribed and well tolerated in pediatric patients for multiple anxiety disorders14 and depression.15,16 DS tolerated the medication very well without signs of mood activation, increase in suicidal ideation, GI upset, or sleep disruption. He engaged in individual and group therapies related to identifying his physical cues to anxiety and anger, improved communication with his family, and demonstration of positive coping skills. His parents attended family therapy sessions twice per week to address the role of family dynamics in his situation. DS completed a viable safety plan as well as successful off-unit unsupervised visits with his family prior to discharge.
On the 7th day of admission, he transitioned to the psychiatric partial hospitalization program. The sertraline dose was increased to 50 mg by mouth 5 days after initiation, and it remained at that level for the duration of the partial hospitalization. At discharge, it was arranged for DS to return to his established outpatient individual therapist, engage in once-a-week family therapy, and outpatient medication management through a psychiatric prescriber. He was planning on returning to school and had consistently demonstrated increased frustration tolerance with his half-siblings and a mastery of positive coping skills to manage his emotions. He denied and demonstrated a lack of suicidal ideation, there was a significant decrease in irritability and oppositional behaviors with his mother, and many positive interactions with peers and adults were had.
Five or more of the following symptoms have been present during the same 2-week period and represent a change from the previous functioning. One is either depressed mood or loss of interest or pleasure.
1. Depressed mood (may be irritable mood in children and adolescents)
2. Loss of interest or pleasure in all or almost all activities
3. Weight loss or weight gain (change of more than 5% in a month)
4. Insomnia or hypersomnia nearly every day (often early morning awakening 2-4 a.m.)
5. Psychomotor agitation or retardation
7. Feelings of worthlessness or inappropriate guilt
8. Diminished concentration or indecisiveness
9. Suicidal ideation or recurrent thoughts of death
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, (Copyright (C)2000). American Psychiatric Association.
Excessive anxiety and worry that is difficult to control occurring more days than not (for at least 6 months).
Three or more of the following symptoms with some present for more days than not (for the past 6 months). For children, only one symptom is required.
1. Restlessness or feeling on edge
2. Being easily fatigued
3. Difficulty concentrating or mild going blank
5. Muscle tension
6. Sleep disturbance (difficulty falling or staying asleep, restless, or unsatisfying sleep)
A pattern of negativistic, hostile, and defiant behavior lasting at least 6 months during which four or more of the following symptoms are present with symptoms presenting by early adolescence:
1. often loses temper
2. often argues with adults
3. often actively defies or refuses to comply with adults' requests or rules
4. often deliberately annoys people
5. often blames others for his or her mistakes or misbehavior
6. is often touchy or easily annoyed by others
7. is often angry and resentful
8. is often spiteful or vindictive
(6 or more of the following symptoms persisted for at least 6 months to a degree that is maladaptive)
1. often fails to give close attention to details or makes careless mistakes
2. often has difficulty sustaining attention in tasks or play activities
3. often does not seem to listen when spoken to directly
4. often does not follow through on instructions or fails to finish schoolwork or chores
5. often has difficulty organizing tasks and activities
6. often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort
7. often loses necessary things
8. is often easily distracted by extraneous stimuli
9. is often forgetful in daily activities
Symptoms present before age 7, cause impairment, and are present in two or more settings (at home and at school)
1. often fidgets (with hands or feet) or squirms in seat
2. often leaves seat in classroom
3. often runs about or climbs excessively when it is inappropriate
4. often has difficulty playing or engaging in leisure activities quietly
5. is often "on the go" or acts as if "driven by a motor"
6. often talks excessivelyImpulsivity:
7. often blurts out answers before questions have been completed
8. often has difficulty awaiting turn
9. often interrupts or intrudes on others
Depression: Child Depression Inventory (CDI), derived from the Beck Depression Inventory, can be used with children and adolescents ages 7 to 17. Parent and teacher versions are available. In the self-report version, the child/adolescent reports on a variety of symptoms including negative mood, interpersonal problems, ineffectiveness, and negative self-esteem. Available for purchase.
Center for Epidemiological Studies Depression Scale Modified for Children (CES-DC) 20-time scale completed by children/adolescents (ages 6 to 17) takes 5 minutes to complete and is available free online at http://www.brightfutures.org/mentalhealth/pdf/professionals/bridges/ces_dc.pdf
Anxiety: SCARED-screens children and adolescents age 8 and older for anxiety disorders. Both SCARED versions (child and parent) contain 41 items that measure five factors: general anxiety, separation anxiety, social phobia, school phobia, and physical symptoms of anxiety, available for free online at http://www.psychiatry.pitt.edu/sites/default/files/Documents/assessments/SCARED%
ADHD/ODD: Vanderbilt ADHD Diagnostic Parent/Teacher Rating Scale-developed to assess for symptom presence and severity in home, classroom, and social settings in children ages 6 to 12, available for free online at http://www.brightfutures.org/mentalhealth/pdf/professionals/bridandhttp://dcf.ps
SNAP-IV Rating Scale-Revised (SNAP-IV-R)-used to assess children and adolescents ages 6 to 18, for symptoms of ADHD, oppositional defiant disorders (ODD), and aggression. Contains 90 items, and takes about 10 minutes to administer. Available online at http://www.adhd.net/
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