The Natural History of Generalized Anxiety Disorder: A Review

Catherine L. Woodman, MD


Medscape Psychiatry & Mental Health eJournal. 1997;2(3) 

In This Article


Pure GAD appears to be relatively rare, and there is significant overlap with normal anxiety or other psychiatric disorders (Fig. 1). The most frequent complications of GAD are comorbid depression, alcohol abuse, and other anxiety disorders. Of particular note is that while only 8% of persons with GAD in this study met criteria only in the midst of another disorder, 90.4% of persons with GAD met criteria for another psychiatric disorder over the course of their lifetime. The most frequently noted concern raised about the validity of the diagnosis of GAD is the fact that it is associated with these high rates of comorbidity, as both a principal diagnosis and a secondary diagnosis.

The comorbidity of general anxiety disorder.

Several studies have shown that there is diagnostic overlap between GAD and other anxiety disorders.[10,44] Comorbidity with specific phobia occurs most frequently, but of all the anxiety disorders, panic disorder occurs at a much higher rate than its occurrence in the general population. Woodman and associates[43] followed up patients with panic disorder an average of 5 years after their initial evaluation and found that while 73% had panic disorder in remission, 25% of those in remission still met criteria for GAD.

Major depression has a high rate of comorbidity with anxiety disorders as a group and with GAD specifically. The National Comorbidity Survey found that both major depression and dysthymia occurred together at rates well above what would be expected in the general population. This comorbidity has led to questions of diagnostic validity for GAD, as opposed to a disorder that is a part of depression. Gray[45] and Paul[46] have both proposed specific biologic models to account for the high rates of overlap between chronic anxiety and depression, based largely on the learned-helplessness paradigm. Laboratory animals exposed to repeated noxious stimuli initially demonstrate an increase in arousal (ie, the equivalent of human anxiety), which is followed by behavioral immobility (ie, the equivalent of human depression). Kendler and colleagues[28,29] found that major depression and GAD traveled together in twins, and they postulated that the 2 disorders might be alternative expressions of the same gene. This is a controversial area, and more research is required to explore possible etiologies of the extensive overlap between the disorders.

Substance use disorders occur frequently in individuals with anxiety disorders, and GAD is no exception. As alcohol is the oldest anxiolytic known to humanity, there has been a long-standing distinction made between patients whose anxiety precedes the onset of alcohol abuse and those who develop an anxiety disorder secondary to alcohol abuse. The former can be seen as an out-of-control attempt to self-medicate the anxiety disorder, whereas the latter can be viewed as secondary to the physiologic consequences of alcohol dependence. In both situations, the initial treatment involves detoxification and psychosocial support,but subsequent treatment can be widely divergent for a primary anxiety disorder, compared with a secondary anxiety disorder.

The overlap between GAD and personality disorder has not been well studied. The early age of onset, modest response to treatment, and chronicity seen in GAD are features shared with personality disorders. The degree of comorbidity between these diagnoses needs further study.

Despite the frequent comorbidity of GAD and other psychiatric disorders, it does not appear to be associated with suicidality. Asnis and colleagues[47] found that in a psychiatric outpatient population, lifetime prevalence of suicidal ideation was 18% and suicide attempts 17% in patients with a diagnosis of GAD. This is significantly lower than the lifetime prevalence seen with MDD, substance use disorders, and even adjustment disorders.

GAD has extensive comorbidity with other psychiatric disorders, and while this has led to some question regarding diagnostic validity, the vast majority of subjects with comorbid disorders meet criteria for GAD in the absence of another diagnosis at some time during the course of their illness.


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