Anxiety Disorders: Rule-Outs And Comorbid Disorders

Anxiety disorders commonly co-occur with other disorders, and some disorders not classified as anxiety disorders may include features of anxiety, complicating the diagnosis. It is imperative for mental health professionals to carefully examine all symptoms in order to perform a comprehensive differential diagnosis. In order to select an appropriate therapeutic compound, the diagnosis must be parsimonious, but at the same time it must account for all symptoms that are evident. To assist clinicians, this section reviews the disorders commonly associated with anxiety that need to be examined when rule-outs and comorbidities are considered.

Mood Disorders

Depression and anxiety frequently co-occur. In one study, 10-15 percent of children and adolescents with anxiety disorders also had clinical depression, and about 25-50 percent of youths with depression also had an anxiety disorder. Anxiety disorders and depression are both considered ‘internalizing’ disorders where stress is experienced through internal discomfort (rather than behavioral disturbances commonly associated with ‘externalizing’ disorder, like ADHD). Hyperarousal is characteristic of anxiety disorders, but may also be a feature of depression, as well as mania. In addition, those who experience chronic discomfort secondary to long-standing symptoms of anxiety may also develop depression. Consequently, when a patient presents with symptoms of anxiety, it is usually necessary to rule out the presence of a mood disorder.


A child or adolescent with an anxiety disorder may exhibit withdrawal, apathy, and limited motivation when facing anxiety-provoking situations. For example, a child with separation anxiety disorder may dread detachment from the parent and display symptoms of depression when away from home, but will usually exhibit relief when reunited with the attachment figure. Adolescents with social phobia will exhibit flatness and social withdrawal when among peers, but these symptoms usually resolve at home. However, because symptoms of anxiety disorders often cause unpleasant outcomes in the youngsters’ familial, social, and academic life, children and adolescents who live with chronic symptoms of anxiety may gradually develop symptoms of depression, fatigue, poor concentration, and sleep disturbance. In addition, some research findings suggest that youth who experience comorbid anxiety and depression exhibit higher levels of anxiety as compared to those without depression. Thus, if symptoms of anxiety and depression are present, a compound should be selected that may address both groups of symptoms, or an addition of another supplement may become necessary.

Mania or Agitation

Anxiety may precipitate agitation, and even more commonly, agitation and mania may include features of anxiety. For example, Harpold et al. (2005) reported that 51 percent of youth with bipolar disorder had at least one comorbid anxiety disorder. Because the overlap is so common, clinicians must determine whether comorbid presentation of mania and/ or agitation with symptoms of anxiety require multiple diagnosis and treatment strategies to address both sets of symptoms.

This distinction may be especially difficult when symptoms of a mixed episode are present. These commonly include agitation and may also involve a discomfort that may sometimes present as anxiety. However, the subjective experience usually is not one of fear, but more of apathy, anger, and restlessness. If such symptoms are also accompanied by significant anxiety, then both groups of symptoms must be captured with appropriate diagnosis. In such situations, it is likely that both disorders will need to be treated with specific compounds, although in some cases one supplement may have beneficial effects on both groups of symptoms. Clinicians should compare the discussion of compounds in this chapter with the compounds discussed in site. Since some compounds are discussed in both chapters, these may be a good place to start when treating comorbid mania/agitation and anxiety.

Disruptive Disorders

Although symptoms of anxiety are not commonly mistaken for disruptive behaviors, and anxiety and disruptive behaviors may represent opposite ends of a conceptual spectrum of internalizing/externalizing disorders, anxiety symptoms can coexist with symptoms of some disruptive disorders.


As discussed in Chapter 5, attention deficit hyperactivity disorder is an externalizing disorder in which children and adolescents exhibit persistent patterns of inattention/disorganization and/or hyperactivity/impulsivity. Although very different from the internalizing symptoms of anxiety disorders, attention deficit hyperactivity disorder and anxiety disorders are sometimes comorbid, and studies report that 25-35 percent of individuals with attention deficit hyperactivity disorder also present symptoms of at least one anxiety disorder. Symptoms of anxiety can usually be differentiated from symptoms of attention deficit hyperactivity disorder with little difficulty, but sometimes poor concentration, nervousness, and not following instructions may be mistaken for symptoms of attention deficit hyperactivity disorder while these may be secondary to anxiety disorders. However, when symptoms of both disorders co-occur, each may change the expression of the other. For example, individuals with attention deficit hyperactivity disorder and anxiety tend to exhibit less impulsivity, and comorbid attention deficit hyperactivity disorder and anxiety may result in more aggression. In addition, when symptoms of obsessive compulsive disorder and attention deficit hyperactivity disorder are simultaneously present, the combination often results in significant impairment and high levels of aggression.

When symptoms of attention deficit hyperactivity disorder and anxiety disorders coexist, the selection of effective compounds may become more difficult. Generally, supplements that increase catecholaminergic activity, such as stimulants, are effective in reducing symptoms of attention deficit hyperactivity disorder (ADHD), but the same compounds are also associated with increasing anxiety in those susceptible to these symptoms. Thus, stimulants and related compounds often are not a good choice for individuals with comorbid attention deficit hyperactivity disorder and anxiety. Instead, some compounds have been shown to be effective in management of both anxiety and attention deficit hyperactivity disorder (ADHD), and readers should review this chapter and Chapter 5 to see which compounds seem supported for the management of both sets of symptoms (for example, inositol). When monotherapy is not sufficient, the use of compounds to separately manage symptoms of attention deficit hyperactivity disorder and anxiety may be necessary.

Tic Disorders

Of the three specific tic disorders recognized in the DSM system Tourette’s disorder (TD) is the least common, but it is most likely to co-occur with an anxiety disorder ― obsessive compulsive disorder. Normally, compulsions and tics can easily be differentiated ― compulsions are accompanied, and preceded by, anxiety, and are performed to relieve it. The tics, however, are not associated with any fears and are performed impulsively, usually without much thought accompanying or preceding them. However, the compulsions and tics may coexist, and therefore all unusual behaviors performed by a patient should carefully be examined, especially when anxiety is also evident. In addition, DSM requires the presence of obsessions or compulsions for the diagnosis of obsessive compulsive disorder (obsessive compulsive disorder), and so it is possible that someone can be diagnosed with obsessive compulsive disorder based on obsessions only, and in such a case, compulsions will not be evident. Thus, comorbid TD and obsessive compulsive disorder may exist when tics (motor and vocal) and anxiety-driven obsessions (but not compulsions) are evident. As always, when a patient presents symptoms of two or more disorders simultaneously, all must be treated, although it is probably best to address the disorders one at a time, starting with the one that presents the most debilitating symptoms. As with other cases where symptoms of two or more disorders are simultaneously apparent, readers should check the compounds discussed in each relevant chapter to determine whether any one supplement is known to simultaneously address symptoms of both disorders. If so, administering that compound is the most logical place to start, but if sufficient response is not evident, use of multiple supplements may be necessary.

Adjustment and Trauma

As children and adolescents grow, they encounter many stressors that require adaptation, and may also experience traumatic events. In response, children and adolescents may develop symptoms of anxiety, including fears, nervousness, worry, or separation anxiety. These symptoms resemble the symptoms of many anxiety disorders, and so it is important to rule out an adjustment to stress or trauma before an anxiety disorder is diagnosed.

Adjustment Disorders

Children and adolescents who have been exposed to family conflicts, moves, or parental separation, or similarly stressful events may experience various symptoms of anxiety. Within the DSM system, these may meet the criteria for various forms of adjustment disorder (APA, 2000), and some specific subtypes of adjustment disorder include symptoms of anxiety. Youngsters who experience such emotional reactions commonly benefit from counseling and psychotherapy in order to help them cope with the stressors. If anxiety is apparent, adjunct use of an anxiolytic supplement may be beneficial. However, clinicians should administer treatment that comprehensively focuses on helping the child or adolescent cope with the stressful events.

Post-Traumatic Disorders

Children and adolescents who have been exposed to severe trauma, such as abuse, loss of a parent, severe injury, or exposure to a major catastrophe, may exhibit symptoms of acute stress disorder (ASD) or post-traumatic stress disorder (PTSD). Although these are classified within the DSM system as anxiety disorders, they are differentiated from the other disorders discussed in this chapter by the significant severity and wide range of symptoms. Children with ASD or PTSD usually exhibit substantial disturbance of overall functioning, including severe anxiety and hypervigilance, sleep disturbance and nightmares (which do not necessarily need to contain trauma-related content), reliving the event through play (or other forms of flashbacks), and avoidance of (and/or detachment from) trauma-related stimuli. Often, significant depression and behavioral disturbances also accompany these symptoms.

When clinicians encounter children or adolescents with ASD or PTSD, all symptom groups must be managed. Intensive psychotherapy and/or psychiatric treatment is likely to be necessary, and anxiety should not be treated in isolation. While using an anxiolytic supplement may be helpful, it is not likely to be effective unless the other symptoms are also being addressed. Unfortunately, this will usually mean that multiple supplements will need to be used, and such cases should be approached with extreme caution, since the use of multiple supplements has rarely been researched, especially in the pediatric population.

Medical Disorders

Many medical conditions may be accompanied by anxiety. Endocrine problems, in particular, are often associated with anxiety. Hyperthyroidism usually results in restlessness, irritability, and nervousness. Hyperglycemia and adrenal tumors (for example, pheochromocytoma) may also produce similar symptoms. These disorders should be ruled out, especially if the onset of symptoms is sudden and pronounced. Because such disorders need to be treated medically, it is necessary to carefully perform a differential diagnosis, including a medical check-up. Immunological problems are also associated with anxiety, particularly when obsessions and compulsions are also evident. When symptoms begin, or are notably exacerbated, after a bacterial infection, such as strep throat or scarlet fever, it is possible that symptoms of anxiety are secondary to PANDAS.