Generalized anxiety disorder is a diagnosable psychiatric condition encompassing hallmark signs of excessive, uncontrollable worry and anxiety about everyday, routine life circumstances (APA, 2013, p. 222).
Anxiety disorders are the most prevalent psychiatric disorder with up to one third of the population suffering from an anxiety disorder at some point in their lifetime (Bandelow & Michaelis, 2015). The median age of onset for anxiety disorders is 11 years old; however, the median age of onset in GAD ranges from late adolescence to early adulthood (Tusaie & Fitzpatrick, 2017). In the United States, the 12-month prevalence of GAD is 0.9% and 2.9% among adolescents and adults respectively, with women twice as likely as men to suffer from the disorder (APA, 2013). Prevalence increases until middle age where it peaks and declines over later years; however, a prevalence rate of up to 11% may also be present in the geriatric population (APA, 2013; Tusaie & Fitzpatrick, 2017). Differences in prevalence rates between the United States and other countries have been recognized and may be the result of methodological as opposed to culture-specific factors; however, it has been noted that somatic symptoms predominate in certain cultures while cognitive symptoms predominate on initial presentation among other cultures (APA, 2013; Bandelow & Michaelis, 2015). Individuals who suffer with GAD carry a lifetime morbidity rate of 9.0%, contributing to high health care utilization, increased economic burden and elevated degree of impairment due to the disorder (APA, 2013; Bandelow & Michaelis, 2015).
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Pathophysiology. Generalized anxiety disorder encompasses two core features of fear and worry thought to originate in the amygdala and cortico-striato-thalamo-cortical (CSTC) circuits. The amygdala is responsible for regulating the fear response while the cortico-striato-CSTC circuits mediate the symptoms of worry (Stahl, 2013). It has been proposed that numerous neurotransmitters are involved in the regulation of circuits responsible for anxiety such as y-aminobutyric acid (GABA), serotonin, norepinephrine and a2 delta ligands. GABA is an inhibitory neurotransmitter thought to play a key role in reducing activity in the amygdala and CSTC loop; serotonin innervates the amygdala and CSTC circuits and is thought to modulate fear and worry; norepinephrine provides important regulatory functions in the amygdala and CSTC loop and, when present in excess, increases anxiety (Stahl, 2013). It is hypothesized that malfunctioning of the amygdala, CSTC circuits, and neurotransmitters results in maladaptive symptoms of fear and worry giving way to anxiety (Stahl, 2013).
In addition to the neurobiological pathophysiology of generalized anxiety, there are psychological theories thought to contribute to the development of the disorder such as cognitive, behavioral, and psychodynamic factors. Negative biases are hypothesized to lead to the negative misinterpretation of stimuli in the cognitive domain, while the behavioral view highlights the impact of classical conditioning and social learning on the development of anxiety; finally, the psychodynamic perspective focuses on unresolved conflicts and discord between the ego, id and superego to describe the etiology of generalized anxiety (Tusaie & Fitzpatrick, 2016).
Risk factors. Generalized anxiety disorder has a broad range of risk factors including temperamental, environmental, genetic, and physiological factors. It is thought that one-third of the risk of experiencing GAD is genetic in nature while the remaining risk is realized through temperamental factors such as neuroticism, harm avoidance, behavior inhibition, and environmental factors such as childhood adversities, over protective parenting, low socioeconomic status and female sex (APA, 2013; Lock et al., 2015).
Screening tools. Anxiety disorders often go undetected and untreated for multiple reasons to include patients failing to disclose their symptoms and/or focusing more on physical or somatic symptoms unknowingly misleading the provider (Kehoe, n.d). Consequently, two-thirds of patients do not receive adequate or appropriate therapeutic interventions to address their anxiety. This highlights the importance of screening tools in the detection of GAD to include the Hamilton Anxiety Scale, Generalized Anxiety Disorder 7-Item Scale, Penn State Worry Questionnaire, PRO-MIS Emotional Distress-Anxiety-Short Form and the Severity Measure for Generalized Anxiety Disorder—Adult among others (Kehoe, n.d; Lock et al., 2015; Tusaie & Fitzpatrick, 2013).
Diagnostic criteria. The DSM-5 provides comprehensive diagnostic criteria for GAD if screening tools and/or history and physical indicate an anxiety disorder is present. According to the DSM-5, an individual meets the diagnosed criteria for GAD if they have experienced excessive, uncontrollable worry and anxiety more days than not for at least six months surrounding a number of events or activities and experience three or more associated symptoms such as restlessness, fatigue, difficulty concentrating or mind going blank, irritability, muscle tension or sleep disturbances. Additionally, anxiety, worry and physical symptoms cause clinically significant distress and are not attributable to the effects of substance, medical condition or better explained by another mental disorder (APA, 2013, p.222).
Treatment. Medication, psychotherapy and education are the cornerstone in the management of GAD once all other possible etiologies have been ruled out including medical conditions and medications/substances that can mimic the symptoms of GAD (Kehoe, n.d.). Education focusing on the nature of the disorder along with empathetic listening helps establish a trusting therapeutic relationship improving patient outcomes and increasing patient participation in the treatment plan and recovery (Lock et al., 2015; NICE, 2018).
The NICE (2018) guidelines utilize a stepwise approach when treating GAD. Step one includes identification, education and active monitoring. Step two includes self-help and group therapy modalities. Step three introduces high-intensity psychological intervention (CBT) or drug treatment while step four focuses on highly specialized treatment with complex drug and/or psychological treatment regimens to include crisis services and hospitalization. Bandelow et al. (2017) and Lock et al. (2015) indicate that step two may be marginally effective in the United States as self-help and group therapies are relatively less available and of minimal effectiveness, therefore they recommend starting treatment with psychotherapy, medication or a combination.
If initiating treatment with psychotherapy, the modality of choice is CBT when treating GAD, as it has proven effective in multiple studies (Lock et al., 2015; NICE, 2018). If initiating treatment with medication, selective serotonin reuptake inhibitors (SSRIs) such as sertraline, serotonin-norepinephrine reuptake inhibitors (SNRIs), and buspirone are all considered first line agents (Lock el al., 2015; NICE, 2018). Second line agents include tricyclic antidepressants, antiepileptics (Pregabalin), antipsychotics (Seroquel) and hydroxyzine while third line and augmenting agents include monoamine oxidase inhibitors and benzodiazepines, respectively (Lock et al., 2015). Lock et al. (2015), NICE (2018) and Bandelow el al. (2017) indicate that combined treatment with medication has proven superior to either alone and has been found to prevent relapse up to two years, therefore combined therapy should be considered when initiating treatment for GAD. Psychotherapy with CBT should consist of 12-15 one hour weekly sessions regardless if utilized as monotherapy or utilized in conjunction with pharmacotherapy; likewise, medications should be continued for at least 12 months or longer until symptoms have remitted before tapering to reduce the likelihood of relapse (Lock et al., 2015; NICE 2018).
Finally, additional treatment modalities to consider include complementary and alternative medicine therapies such as music therapy, aromatherapy, acupuncture, and homeopathic medications such as Kava, St. Johns wort, tryptophan, 5-Hydroxytryptophan, etc. If these treatments are recommended or desired by the patient, providers should inform their patient of the lack of studies evaluating their effectiveness as well as the potential risk involved in utilizing botanicals and supplements as they have been found to cause hepatotoxicity and increase the risk for serotonin syndrome when used concomitantly with SSRIs (Lock et al., 2015).
Health Promotion. Health promotion is an integral part of managing generalized anxiety and usually focuses on common lifestyle recommendations such as stress management, dietary modifications, physical activity and the importance of obtaining quality sleep (Lock et al., 2015). Murphy and Mercer (2013) report that diets high in healthy fats tend to be anxiolytic while diets high in sugar have more anxiogenic qualities. Furthermore, exercise and relaxation therapy have demonstrated effectiveness at reducing anxiety symptoms (Bandelow et al., 2017). Finally, Staner (2003) indicates that obtaining quality sleep and alleviating sleep disturbances can greatly reduce the symptoms of anxiety.
Migraine is a primary headache disorder characterized by a variety of neurological manifestations and recurrent painful and non-painful episodic phenomena and consists of two major subtypes: migraine without aura and migraine with aura (Antonaci et al., 2011).
Lifelong prevalence of all headaches to include primary and secondary headaches is 96% worldwide (Rizzoli & Mullaly, 2018). The global prevalence rate for migraines is 10% with most migraines occurring between the ages of 25 to 55 years among women; in fact, migraines are three times more likely to occur in women than men (Rizzoli & Mullally, 2018). Migraine disorder is associated with significant disability due to severe pain, suffering and neurological symptoms and is estimated to contribute $6-7 billion per year of economic burden in the United States due to lost manpower and medical treatment (Hansrivijlt, Nimnuan, Srikiatkhachorn, & Wang, 2017). Despite the crippling impact on the economy and the individual livelihood of those who suffer from the disorder, migraine headaches continue to be under diagnosed and treated, likely the consequence of clinical and sociological barriers given that most migraines are episodic, nonfatal and noncontagious (Rizzoli & Mullally, 2018). For example, only three to 13% of the million who suffer migraines are currently undergoing preventative treatment while it is estimated roughly 38% would benefit from preventative treatment (Estemalik & Tepper, 2013).
Review of Literature
Pathophysiology. Migraine pathophysiology is poorly understood but is thought to occur when neuronal activation is initiated through either cortical spreading depression (CSD) or a brainstem generator (Estemalik & Teppers, 2013). Cortical spreading consists of slow activation of neurons and glia followed by postictal depression of neuronal firing and is hypothesized to be the basis of migraine with aura. Cortical spreading alters the blood brain barrier allowing brain matric metalloproteinases to alter the blood-brain barrier, which triggers meningeal pains through inflammation, vasodilation and plasma protein extravasation (Estemalik & Teppers, 2013). The neuronal activation and subsequent depression impacts various areas of the brain such as the cerebellum, cortex and hippocampus resulting in the physical, sensory and psychological effects such as depression, cognitive dysfunction, irritability, euphoria, neck stiffness/pain and fatigue, which are known to substantially impact an individual’s daily functioning (Estemalik ; Teppers, 2103; Heba Al-kotb, 2016; Rizzoli ; Mullally, 2018).
Risk factors. While the pathophysiology of migraines is poorly understood it is thought certain predisposing factors along with a genetic vulnerability contribute to the development of the headache disorder (May ; Schulte, 2016). The most common risk factors consist of obesity, mood and anxiety disorders, stressful life events, ineffective acute treatment or overtreatment, female sex, poor nutritional status and low-level education (Heba Al-kotb ; Ibrahim, 2016; May ; Schulte, 2016). The threshold theory of migraine asserts that internal and external factors combined with a genetic predisposition triggers changes in brain chemistry causing the migraine attack (MacGregor, 2016). For example, an individual with a genetic vulnerability (lower headache threshold) stays out late drinking, starts her menstrual cycle and is stressed with excess work resulting in a migraine (crossing the threshold).
Screening tools. Identifying and correctly diagnosing migraine disorder is a challenging endeavor. Aside from obtaining a detailed history and physical and imagining when red flags are present such as headache in older patients, abnormal neurological exam, changing headache patters, first or worst headache, etc. MacGregor (2016) promotes the use of two valid and reliable screening tools to aid in the identification and diagnosis of migraine with or without an aura: ID-Migraine and visual rating scale (VARS) (Rizzoli ; Mullally, 2018). ID-Migraine focuses on the most common predications for a migraine without aura to include photophobia, disability, and nausea, while he the VARS screening is based on the diagnostic criteria for migraine with aura such as onset, duration scotoma, fortification spectra, etc. (MacGregor, 2016).
Diagnostic criteria. The International Classification Committee of the International Headache Society (IHS, 2013) provides comprehensive diagnostic criteria for migraines with and without aura if screening tools and/or history and physical indicate a migraine disorder is present. In order to fulfill a diagnosis of migraine without aura a client must have at least five attacks lasting four to 72 hours with two of the following characteristics such as unilateral location, pulsating, moderate to severe pain aggravate by routine physical activity with nausea and/or vomiting or photophobia and/or photophobia (HIS, 2013). Likewise, in order to fulfill diagnostic criteria for a migraine with aura an individual must have two one more attacks with fully reversible aura symptoms such as visual, sensory, speech and/or language, motor, brainstem or retinal (HIS, 2013). Additionally at least two of the following characteristics must occur: one aura symptoms increasing over greater than five minutes and/or two or more symptoms occur in succession; each aura symptoms lasts five to 60 minutes; one aura symptom is unilateral; and the aura is accompanied or followed by a headache within 60 minutes following the aura (IHS, 2013). In both cases, the migraine symptoms cannot be attributed to other medical or psychiatric conditions.
Treatment. Migraine treatment aims to prevent or reverse the underlying chemical and electrical malfunction thought to contribute to a migraine attack and can be divided preventative lifestyle modification such as trigger identification and avoidance and pharmacological commonly identified as either abortive and preventative treatment (Rizzoli ; Mullally, 2018). Abortive medications such as nonsteroidal anti-inflammatory agents, analgesics, antiemetic, triptans and corticosteroids are prescribed to treat an acute migraine attack while preventative medications including propranolol, divalproex sodium, topiramate, amitriptyline, venlafaxine and cyproheptadine are prescribed to reduce the frequency and severity of a migraine attack in order to reduce overall association disability (Rizzoli ; Mullally, 2018). Preventative medication should be considered when an individual suffers from headaches great than six days, impaired for at least four days, or is completely unable to function for three days each month with abortive treatment (Rizzoli ; Mullally, 2018). Additionally, there is strong evidence for the use of riboflavin, magnesium, butterbur root, CoQ10 and onabotulinumtoxinA (Estemalik ; Tepper, 2013). Finally, effective non-pharmacological management options consists of physical therapy, local injections, CBT, relaxation techniques and biofeedback (Rizzoli ; Mullally, 2018). Migraine management will vary patient to patient and should consider level of efficacy for a given treatment, adverse side effects, and patient comorbidities in order to address multiple disorders with a single treatment to improve patient adherence (Estemalik ; Tepper, 2013).
Health Promotion. Genetics heavily influence the development of migraine headache; however, combined internal and external factors such as environmental (bright lights, odors), dietary (wine, chocolate) and physiologic (stress, fatigue) factors are postulated to propel an individual across the attack threshold resulting in a migraine attack (MacGregor, 2016). The mainstay of treatment for migraine headaches is trigger identification and avoidance confirming the extraordinary role of lifestyle modifications in reducing disease. Modifiable lifestyle factors include, “dieting and fasting, exercising and physical activities, stress level and sleeping and resting habits, smoking and medications and drugs” (Al-kotb ; Ibrahim, 2016, p. 281). In quasi-experimental study consisting of 70 subjects who were admitted for inpatient care with an acute migraine attack, Al-kotb and Ibrahim (2016) found significant improvements over the course of the study in the subject’s migraine frequency and severity following changes in diet, physical activity, sleep and stress management. Additionally, a review conducted by Martin and Vij (2016) concluded certain beverage and foods increase migraine in susceptible individuals such as caffeine, monosodium glutamate, aspartame, gluten and histamine containing foods and alcohol. Unfortunately, triggers vary for each migraine suffer and require trial and error in the identification process.