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Anxiety in Children

Anxiety disorders are among the most common psychiatric conditions in children and adolescents with nearly two in ten being affected. These disorders increase the incidence of suicide attempts and are associated with significant morbidity and mortality. Anxiety disorders in youth predicts psychiatric disorders later in life to include not only anxiety, but also educational underachievement, substance abuse and depression. It is the earliest form of psychopathology, with phobias often presenting first, then agoraphobia, panic disorders, and obsessive compulsive disorder evident in adolescence (Skryabina, Taylor, & Stallard, 2016; Wehry, Beesdo-Baum, Hennelly, Connolly, & Strawn, 2015; Yalin Sapmaz et al., 2018).



Although prevalence is high, most children continue their course without diagnosis or treatment. Anxiety may at times be short-lived, but more often it is considered to be chronic-and-persistent. The overall course however, typically “waxes and wanes” and “syndrome shifts” to other syndromes. Early onset anxiety should be thought of as the onset of a cascade of psychopathology. The earlier the diagnosis the better the long term functioning throughout childhood. Suicidality is also diminished with early identification and treatment (Skryabina, Taylor, & Stallard, 2016; Wehry et al., 2015; Yalin Sapmaz et al., 2018).


Interestingly, this past decade has greatly improved the understanding of pediatric anxiety disorders. Prefontal-amygdala based circuits have been implicated, although so have abnormalities in default mode networks and posterior structures, including the posterior cingulate, precuneus, and cuneus. The amygdala is frequently “overactivated” in functional magnetic resonance imaging studies of youth with fear-based anxiety disorders. Intrinsic functional connectivity networks, including connectivity to the medial prefrontal cortex, anterior cingulate cortex, insula, and cerebellum have been described (Wehry et al., 2015).

The ventrolateral prefrontal cortex regulates the amygdala activity and plays a pivotal role in extinction in the context of fear conditioning and responds in tandem with the amygdala to emotional probes. It has been suggested as the lynchpin function in pediatric anxiety disorders. Research has been fairly consistent in indicating the ventrolateral prefrontal cortex as playing a compensatory role in youth with anxiety. Understanding this has directed treatment towards pharmaceuticals and therapy modalities that increase the activity of this structure, such as fluoxetine and cognitive-behavioral therapy. The cingulate cortex has also been found in a hyperactivated state in the youth with anxiety disorders, and glutamateric tone directly correlates with the severity of anxiety in adolescents with generalized anxiety. This “dose dependency” of sorts, is similar to the degree of hyperactivity with the VLPFC being inversely proportional to the severity of anxiety (Wehry et al., 2015).


Screening and Assessment


The American Academy of Child & Adolescent Psychiatry recommends screening for anxiety symptoms and specifically identifying the severity of those symptoms and their functional impairment. Co-morbid psychiatric conditions should be ruled out which may mimic anxiety symptoms, such as thyroid dysfunction. Developmentally appropriate worries should be differentiated from anxiety, as well as appropriate responses to situational stress. Finally, in discussion with parents, clinicians should be cognizant of identifying anxiety-provoking behaviors such as crying, irritability, and tantrums as indicative of anxiety, rather than oppositional or deviant. In these scenarios, parents can be educated that these behaviors may be the child’s attempt to avoid the anxiety-provoking stimulus and that they are in fact, in distress requiring environmental adjustment or a stricter routine (Wehry et al., 2015).


The Multidimentional Anxiety Scale for Children, the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Spence Children’s Anxiety Scale (SCAS) were developed to be sensitive and specific to assessing anxiety in youth eight-years and older, and are useful in clinical practice to monitor treatment progress. The preschool age group can be screened using a parent report adapted from the SCAS that was developed for children ages 2.5 to 6.5 years. The Pediatric Anxiety Rating Scale is used by the clinician to measure the severity of anxiety symptoms as they change over time, and the Social Anxiety Scale, the Social Worries Questionnaire, and the social phobia subscale of SCARED are brief screening measures for social phobia/social anxiety symptoms. Finally, anxiety scales have been developed to assist in clinical decision-making, with respect to the DSM, and to monitor treatment. These are specific to 11 years and older, are easily utilized, and span the array of disorders specific to anxiety (Wehry et al., 2015).


Psychological Treatments


Cognitive behavioral therapy includes psychoeducation of the child and caregivers regarding the nature of anxiety, techniques for managing somatic reactions including relaxation training and diaphragmatic breathing, cognitive restructuring by identifying and challenging anxiety-provoking thoughts, practicing problem-solving for coping with anticipated challenges, systematic exposure to feared situations or stimuli, desensitization to feared stimuli, and relapse prevention plans (Wehry et al, 2015, p 4). Cognitive behavioral therapy can improve not only the primary diagnosis of anxiety, but also work to improve functioning such as peer relationships, and training in anxiety reduction (Kilburn et al, 2018). Evidence has demonstrated that no matter the therapy, even when exceedingly successful, relapse is high suggesting that youth with anxiety disorders require intensive or extended treatment to maintain improvement (Wehrey et al, 2015).


Social Effectiveness Therapy for Children (SET-C) has demonstrated more effective than fluoxetine for treating social phobia in children ages seven to seventeen, and it has demonstrated significantly improved over placebo in children ages four to seven, with 59% of children free of all anxiety diagnosis following treatment (Wehrey et al., 2015). Therapeutic play has also demonstrated effectiveness for children suffering with anxiety, particularly when hospitalized (Anandhukrishnan, 2018).


Mindfulness has been utilized as the foundation for treatment of anxiety, and generalized anxiety, social anxiety, specific phobias, and panic disorders have all improved in adults. This modality has also sown to be as effective as cognitive behavioral therapy. However, there is limited evidence with regards to children and adolescents. One study found meditation-based relaxation more effective than trauma-focused cognitive behavioral therapy in treatment with post-traumatic stress and another found mindfulness intervention to be effective in decreasing symptoms of anxiety and depression in minority children. Generalized anxiety, social and separation anxiety disorders, and those at risk for bipolar might be best treated with group-based mindfulness-based cognitive-behavioral therapy (Wehrey et al., 2015, p 6).

Psychopharmacologic Interventions


Similar to the treatment for anxiety in the adult population, serotonergic antidepressants in youth has thus far been supported in the literature as effective at dampening fear responses in pre-clinical models. Fluoxetine has shown to reduce anxiety in youth with anxiety disorders. When started at 10mg a day, titrating up to 20mg a day by the end of the first week, significant improvement has been seen over a twelve week course of treatment with few side effects. Most concerns were nausea, abdominal pain, drowsiness, and headaches. Fluoxetine has also been used for social phobia, starting with the 10mg a day and increasing to 40mg a day, and this too was effective, with only nausea reported as a side effect (Wehrey et al., 2015).


Fluvoxamine has been examined for generalized anxiety disorders, social phobias and social anxiety disorders. In those ages six to seventeen years, a double-blind, placebo controlled study found fluvoxamine did improve PARS scores significantly and was well-tolerated. Paroxetine was evaluated in another study in children eight to seventeen years of age, and after initiating at a dose of 10mg/day, then titrating to 50 mg/day, social phobias were significantly improved. This regimen was well-tolerated although there was reports of decreased appetite, vomiting and insomnia and four of the sixty-two children experienced labile emotions with suicide ideation (Wehrey et al., 2015).


Sertraline was evaluated in five to seventeen year olds and was found to significantly improve generalized anxiety disorder. This study started the pharmaceutical at a dose of 25 mg/day and then increased it to 50 mg/day after the first week. At 8 weeks, anxiety was significantly improved and there were no significant differences in adverse events between the two groups. When combined with cognitive behavioral therapy, outcomes were even greater for sertraline. Half of these children successfully achieved remission as well (Wehrey et al., 2015).


Venlafaxine ER has been evaluated in randomized, double-blind studies and it too, demonstrated improved generalized anxiety disorders with the primary side effects being anorexia and somnolence. Children also demonstrated an increase in heart rate and blood pressure, with some weight loss. Two of the children reported suicidal ideation or suicide attempts. A second study initiated treatment of venlafaxine ER at 37.5 mg/day and titrated it according to body weight to a maximum of 225 mg/day and significant improvement was demonstrated, with side effects of weight loss, nausea and dizziness. Suicidal ideation was present in three, but no suicides or attempts of suicide (Wehrey et al., 2015).


Duloxetine is another pharmaceutical demonstrating an improvement in generalized anxiety disorder in children, and it has gained approval by the United States Food and Drug Administration for treatment of children seven through seventeen years of age. Side effects were nausea, vomiting, decreased appetite, dizziness, cough, and oropharyngeal pain, and palpitations. A large meta-analysis of all the SSRI/SSNRIs in the pediatric population was conducted and findings were reassuring, suggesting SSRIs are not associated with statistical significance with suicidality in those with anxiety (Wehrey et al., 2015).


Tricyclic antidepressants were once frequently utilized for pediatric anxiety disorders until the SSRIs and SSNRIs gained preference. The anticholinergic effects, need for cardiac monitoring, and the lethality in overdose limited their use in the pediatric population. The use of benzodiazepines in the pediatric population has not been widely studied, but the few publications available to date do not demonstrate significant improvement with alprazolam over placebo for generalized anxiety. Those in the treatment group however, did have complaints of fatigue, irritability, drowsiness, and dry mouth. Oppositional behavior was also common. Buspirone has been well-tolerated but not significantly helpful, and atomoxetine was helpful in children with ADHD who also had anxiety but did have higher rates of decreased appetite than the control group (Wehrey et al., 2015).


Demographic characteristics such as family structure and family history of anxiety play a large part in treatment success. Those with first-degree relatives with anxiety disorders often demonstrate poor outcomes, as well as those in which the family is already strained from caring for the challenged child. The older the child, the less likely they find remission. The more significant the symptoms upon initiation of treatment and the poorer the functional outcome, the less likely SSRIs will improve outcomes. When treating social anxiety disorder, cognitive therapy alone was unsuccessful. Success was achieved only when sertraline was provided in combination with therapy (Wehrey et al., 2015).


Studies have not evaluated the best dose or the length of pharmacologic treatment, nor have the new findings regarding the amygdala-prefrontal networks been correlated with best treatment or even the optimal number of therapy sessions. Next step interventions have not been identified either. There is still much to understand about the treatment of anxiety in children; however, there has been much gained to date (Wehrey et al., 2015).


Anxiety disorders in children present to the primary care clinic with some regularity. Significant morbidity is associated with anxiety, as well as suicidal attempts and self-harm. These disorders are now understood to be associated with dysfunction within the amygdala networks throughout the prefrontal cortex, and a plethora of screening tools have been developed to assist in identifying symptoms and accurately establishing diagnosis. Effective treatments have also been identified, and most are well tolerated; however, benzodiazepines or buspirone one are not recommended. Variables such as family dynamics, severity of symptoms, family history, and comorbidity are better appreciated as predictors for successful treatment outcomes (Wehrey, 2015).


References

Anandhukrishnan, T. G., Sivan A., Baiju, D., Raj, L., Sangeetha, S., Saritha, S., & Jayims, B. K. (2018). Effectiveness of play on anxiety among hospitalized children. Asian Journal of Nursing Education and Research, 8(2). Doi: 10.5958/2349-2996.2018.00046.0

Asselmann, E. & Beesdo-Baum, K. (2015). Predictors of the course of anxiety disorders in adolescents and young adults. Cure Psychiatry Rep,17(7), 155-164.

Kilburn, T. R., Sorensen, M. J., Thastum, M., Rapee, R. M., Rask, C. U., Arendt, K. B., & Thomsen, P. H. (2018). Rationale and design for cognitive behavioral therapy for anxiety disorders in children with autism spectrum disorder: a study protocol of a randomized controlled trial. Trials, 19(210). doi: 10.1186/s13063-018-2591-x

Skryabina, E., Taylor, G., & Stallard, P. (2016). Effect of a universal anxiety prevention programme (FRIENDS) on children’s academic performance: results from a randomized controlled trial. Journal of Child Psychology and Psychiatry, 57(11), 1297-1307. Doi: 10.1111/jcpp.12593

Wehry, A. M., Beesdo-Baum, K., Hennelly, M. M., Connolly, S. D., & Strawn, J. R. (2015). Assessment and treatment of anxiety disorders in children and adolescents. Cure Psychiatry Rep, 17(7). Doi:10.1007/s11920-015-0591-z

Yalin Sapmaz, S., Ozek Erkuran, H., Karaarslan, D., Ozturk, M., Yörük Ulker, G., Serim Demirgoren, B., Koroglu, E., & Aydemir, O. (2018). Validity and reliability of the Turkish version of DSM-5 level 2 anxiety scale (child form for 11-17 years and parent form for 6-17 years). Archives of Neuropsychiatry, 55, 152-156. Doi: 10.5152/npa.2017.15935

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