Generalized anxiety disorder

1. Generalized anxiety disorder Mukesh Bhimani

2. Objectives • Historical perspective • Epidemiology • Clinical features • Diagnosis • Comorbidity • Course and prognosis • Management

3. Introduction • Generalized anxiety disorder (GAD) is a chronic disturbance characterized by excessive worry and apprehension accompanied by psychic and somatic symptoms of stress and anxiety Medscape Psychiatry & Mental Health eJournal 2(3), 1997

4. Historical perspective • Anxiety was first recognized as a medical diagnostic entity in the late 1800s. Before that, anxiety was considered a feature of many medical conditions. • In 1871, Jacob DaCosta described a chronic cardiac syndrome with no apparent organic cause . • In the early 1900s, Sigmund Freud recognized anxiety as a central component of mental diseases, and coined term "anxiety neurosis". J Am Pharm Assoc 39(6):811-821, 1999.

5. Historical perspective • With the publication of the Diagnostic and Statistical Manual, Third Edition (DSM-III) in 1980, generalized anxiety disorder (GAD) was first identified as a diagnostic entity. In the current version of this manual (DSM-IV), GAD was changed from a residual category describing individuals who do not fit other anxiety categories to a well-defined condition with sound diagnostic criteria J Am Pharm Assoc 39(6):811-821, 1999.

6. Epidemiology • Estimates for one year rates are around 3% and life time rates around 4-5%, with women effected more often than men • In the US Epidemiological Catchment Area Study, the one year prevalence of GAD, using DSM-III criteria was 3.8%(Blazer et al., 1991) • In the US National Comrbidity Survey, the one year prevalence rates was 2.8% when clinical significance criterion was applied (Narrowet al., 2002 • A survey in Africa using DSM-IV criteria found a weighted prevalence of 3.7% (Bhagwanjee et al,. 1998) Shorter Oxford textbook of psychiatry

7. Clinical features • The essential characteristics of GAD are sustained and excessive anxiety and worry accompanied by a number of physiological symptoms, including motor tension, autonomic hyperactivity, and cognitive vigilance • The symptoms of GAD are persistent and are not restricted to, or markedly increase in any particular set of circumstances (in contrast to phobic anxiety disorder) • Typically GAD patients suffer symptoms for 5 to 10 years before diagnosis and treatment. • NICE: Clinical Guidelines for the Management of Anxiety. Management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care • Kaplan and Sadock’s synopsis of Psychiatry, Tenth Edition

8. Symptoms of GAD • Worry and apprehension • Muscle tension • Autonomic overactivity • Psychological arousal • Sleep disturbance Other features • Depression • Obsessions • depersonalization

9. Clinical signs • Face appears strained, the brow is furrowed, and posture is tense • Person is restless and may tremble • The skin is pale and sweating is common • Readiness to tears which reflects the generally apprehensive state

10. Diagnosis • This disorder is more common in women, and often related to chronic environmental stress • In ICD-10 GAD is not diagnosed when the symptoms fulfill the diagnostic criteria for phobic anxiety disorder, panic disorder or OCD. • In DSM-IV the emphasis placed on the worrying thoughts in GAD makes it possible to diagnose GAD when these are present even in the presence of symptoms of one of the other three anxiety disorder ICD-10 classification of Mental and BehaviouralmDisorder Shorter Oxford textbook of psychiatry

11. DSM-IV criteria of GAD • Excessive anxiety and worry, occurring for at least 6 months, about a number of events or activities (such as work or school performance). • Difficulty controlling the worry. • The anxiety and worry are associated with 3 (or more) of the following 6 symptoms (with at least some symptoms for more days than not for the past 6 months). Only 1 item is required in children. • Restlessness or feeling keyed up or on edge • Being easily fatigued • Difficulty concentrating or mind going blank • Irritability • Muscle tension • Sleep disturbance (difficulty falling or staying asleep, or restless, unsatisfying sleep) • The focus of anxiety and worry is not confined to features of an Axis I disorder

12. DSM-IV criteria of GADCont: • The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. • The disturbance is not due to the direct physiological effects of a substance (eg, a drug of abuse, a medication) or a general medical condition (eg, hyperthyroidism) and does not occur exclusively during a mood disorder, a psychotic disorder, or a pervasive developmental disorder.

13. ICD-10 criteria Generalized anxiety disorder • A period of at least six months with prominent tension, worry and feelings of apprehension, about every-day events and problems. B. At least four symptoms out of the following list of items must be present, of which at least one from items (1) to (4). Autonomic arousal symptoms (1) Palpitations or pounding heart, or accelerated heart rate. (2) Sweating. (3) Trembling or shaking. (4) Dry mouth (not due to medication or dehydration). Symptoms concerning chest and abdomen (5) Difficulty breathing. (6) Feeling of choking. (7) Chest pain or discomfort. (8) Nausea or abdominal distress (e.g. churning in stomach).

14. ICD-10 criteria Generalized anxiety disorder Cont: Symptoms concerning brain and mind (9) Feeling dizzy, unsteady, faint or light-headed. (10) Feelings that objects are unreal (derealization), or that one's self is distant or "not really here" (depersonalization). (11) Fear of losing control, going crazy, or passing out. (12) Fear of dying. General symptoms (13) Hot flushes or cold chills. (14) Numbness or tingling sensations. Symptoms of tension (15) Muscle tension or aches and pains. (16) Restlessness and inability to relax. (17) Feeling keyed up, or on edge, or of mental tension. (18) A sensation of a lump in the throat, or difficulty with swallowing.

15. ICD-10 criteria Generalized anxiety disorder Cont: Other non-specific symptoms (19) Exaggerated response to minor surprises or being startled. (20) Difficulty in concentrating, or mind going blank, because of worrying or anxiety. (21) Persistent irritability. (22) Difficulty getting to sleep because of worrying. C. The disorder does not meet the criteria for panic disorder (F41.0), phobic anxiety disorders , obsessive-compulsive disorder or hypochondriacal disorder D. Most commonly used exclusion criteria: not sustained by a physical disorder, such as hyperthyroidism, an organic mental disorder (F0) or psychoactive substance-related disorder (F1), such as excess consumption of amphetamine-like substances, or withdrawal from benzodiazepines

16. Differential diagnosis • GAD has to be distinguished not only from other psychiatric disorders but also from certain physical conditions • Anxiety symptoms can occur in nearly all the psychiatric disorders, but there are some in which particular diagnostic difficulties arise. • Depressive disorder • the diagnosis is usually decided on the basis of severity of two kinds of symptoms and the • Schizophrenia • dementia • Substance misuse • Physical illness Thyrotoxicosis Pheochromocytoma hypoglycemia

17. Comorbidity • 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. • Depression Approximately 25% to 30% of patients with GAD present with comorbid depression, and 20% to 30% of patients with depression meet the diagnostic criteria for GAD • substance use disorder Up to 60% of patients treated for alcohol-related disorders report clinically significant anxiety, including GAD. • Kaplan HI, Sadock BJ, eds. Comprehensive Textbook of Psychiatry. 6th ed. Baltimore, Md: Williams and Wilkins; 1995:1236-49. • Craig KJ, Brown KJ, Baum A. Environmental factors in the etiology of anxiety. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology:

18. Comorbidity cont: • Suicide Asnis and colleagues . • lifetime prevalence of suicidal ideation was 18% • lifetime prevalence of suicide attempts 17% • Personality disorders • Up to 50% of the patients with GAD have coexisting personality disorders

19. Course and prognosis • Approximately 50 percent of cases begin in childhood or adolescence • It occurs more commonly in women than men.. • Only 1/3 of patients who have GAD seeks psychiatric treatment • The disorder typically runs a chronic and fluctuating course, with periods of increased symptoms usually associated with life stress or impending difficulties Yonkers KA, Warshaw MG, Massion AO, Keller MB. Phenomenology and course of generalised anxiety disorder. Br J Psychiatry. 1996;168:308-313. Wittchen HU, Zhao S, Kessler RC, Eaton WW. DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1994;51:355-364

20. Etiology • In general terms, GAD appears to be caused by stressors acting on a personality predisposed by a combination of genetic factors and environmental influences in childhood The etiology of GAD can be addressed from four perspectives: • Psychoanalytic theory. • Cognitive behavior theory. • Biological theory. • Genetic theory.

21. Psychoanalytic theory • Freud propose that anxiety arises when ego is overwhelmed by excitation from any of three sources: • The out side world (realistic anxiety) • The instinctual level of the id including love, anger and sex (neurotic anxiety) • The superego (moral anxiety) • According to this theory, in GAD, anxiety is experienced directly unmodified by the defense mechanisms that are thought to be the basis of phobias and obsessions • The theory proposes that in GAD, the ego is readily overwhelmed because it has been weakened by a developmental failure in childhood. Separation and loss are thought to be particularly important causes of this failure (Bowlby, 1969) • Normally, children overcome anxiety through secure relationships with loving parents. If they do not achieve this security, they will be liable, as adult, to anxiety when experiencing separation

22. Cognitive behavior theory • It proposes that GAD arises from a tendency to worry unproductively about problems and to focus attention on potentially threatening circumstances. • This theory is supported directly by studies of thinking in anxious patients and controls, and indirectly by the efficacy of CBT.

23. Neurobiological theory • As GAD symptoms responds to benzodiazepines, antidepressants and azaspirones (e.g. buspirone) so it is hypothesized that there must be abnormality GABA and serotonergic system. • Other neurotransmitter system that have been the subject of research in GAD includes norepinephrine, glutamate, cholecystokinin systems. • Brain areas hypothesized to be involved in GAD are limbic system, basal ganglia and frontal cortex

24. Genetic theory • Family studies:- GAD are more frequent among first degree relative of probands with GAD than among first degree relatives of control. • Some Twin studies reports a concordance rate of 50% in monozygotic twins and 15% in dizygotic twins

25. Important messages to share with people with generalised anxiety disorder • Anxiety disorders are • common • chronic • the cause of considerable distress and disability • often unrecognised and untreated • If left untreated they are costly to both the individual and society. • A range of effective interventions is available to treat anxiety disorders, including medication, psychological therapies and self-help. NICE: Clinical Guidelines for the Management of Anxiety. Management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care

26. Treatment • The most effective treatment of GAD is probably one that combine psychotherapeutic, pharmacotherapeutic, and supportive approaches. Psychotherapy • The major approaches to GAD are CBT, supportive therapy and insight oriented therapy

27. CBT • This treatment combines relaxation with cognitive procedures designed to help patient to control worrying thoughts. • CBT in the optimal range of duration (16–20 hours in total) should be offered. • It has following stages: • Ask patient to keep a diary record of: • The frequency and severity of symptoms • The situations in which they occur • Avoidance behavior

28. CBT cont: • Provide information about the physiology of anxiety and other matters that correct misconceptions • Explanation of the various vicious circles of anxiety • Relaxation training as a means of controlling of anxiety • Graded exposure to situations that provoke anxiety 6. Distraction to reduce the impact of anxiety provoking thoughts

29. Psychotherapy cont: • Supportive therapy offers patients reassurance and comfort, although its long term efficacy is doubtful. • Insight-orientated psychotherapy focuses on uncovering unconscious conflicts and identify ego strengths

30. Pharmacotherapy • Placebo response rate with GAD is about 40% (Fossey and Lydiard, 1990). • Because of the long term nature of the disorder, a treatment plan must be carefully thought out • Drug treatment of GAD is sometimes seen as a 6 to 12 months treatment, some evidence indicates that treatment should be long term, perhaps life long • About 25% of patients relapse in the first month after the discontinuation of therapy and 60 to 80% relapse over the course of next year

31. Pharmacotherapy cont: • Three major drug groups to be considered for the treatment of GAD • Benzodiazepines • Antidepressants • Buspirone • Others e.g. beta blockers

32. Benzodiazepines • This group is appropriate for short term treatment • Before starting treatment with BNZ the patient’s diagnosis, the specific target symptoms, and the duration of treatment should all be defined and the information should be shared with the patient. • start with lowest of its therapeutic range and to increase the dose to achieve a therapeutic response. Shorter Oxford textbook of psychiatry

33. Antidepressants • As patients with GAD often require lengthy treatment, for which BNZ are unsuitable and because depressive disorders often develop during follow up so long term treatment is usually with one of the antidepressant be effective. • Both SSRI and TCA can be used for this purpose. • The available evidence suggests that imipramine, venlafaxine and paroxetine are superior to placebo in treating GAD in adults. • The dose of venlafaxine should be no higher than 75 mg per day. • NICE: Clinical Guidelines for the Management of Anxiety. Management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care • Antidepressants for generalized anxiety disorder (Cochrane Review)Kapczinski F, Lima MS, Souza JS, Cunha A, Schmitt R

34. Antidepressants Cont: • Sertraline has been shown to be superior to placebo in treating GAD in children and adolescents. • There is evidence from one trial suggesting that paroxetine and imipramine are similar in terms of efficacy and tolerability. • It is reasonable to begin with one of the SSRI plus BNZ, then to taper BNZ use after 2 to 3 weeks. • Antidepressants for generalized anxiety disorder (Cochrane Review)Kapczinski F, Lima MS, Souza JS, Cunha A, Schmitt R • Kaplan and Sadock’s synopsis of Psychiatry, Tenth Edition

35. Buspirone • It is 5-HT1A receptor partial agonist • Advantages • Effective in 60-80% of patients with GAD • Effective in reducing cognitive symptoms of GAD • No potential for addiction • It is non-sedating • Disadvantages • Its effect take 2-3 weeks to become evident • Less effective in reducing somatic symptoms • Patients who had previously treated with BNZ are not likely to respond to Buspirone