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'''Anxiety''' is a physiological state marked by demonstrable changes in [[Cognition|cognitive]], [[Somatic|somatic]], [[Emotion|emotional]], and [[Behavior|behavioral]] components. <ref>Seligman, M.E.P., Walker, E.F. & Rosenhan, D.L. (2001). ''Abnormal psychology'', (4th ed.) New York: W.W. Norton & Company, Inc.</ref>  These changes combine to create the sensations typically recognized as [[fear]], [[apprehension (fear)|apprehension]], or [[worry]].  Anxiety is also often accompanied by physical sensations such as [[heart palpitations]], [[nausea]], [[chest pain]], [[shortness of breath]], [[stomach aches]], or [[headache|headache]].
'''Anxiety''' is a physiological state marked by demonstrable changes in [[Cognition|cognitive]], [[Somatic|somatic]], [[Emotion|emotional]], and [[Behavior|behavioral]] components. <ref>Seligman, M.E.P., Walker, E.F. & Rosenhan, D.L. (2001). ''Abnormal psychology'', (4th ed.) New York: W.W. Norton & Company, Inc.</ref>  These changes combine to create the sensations typically recognized as [[fear]], [[apprehension (fear)|apprehension]], or [[worry]].  Anxiety is also often accompanied by physical sensations such as [[heart palpitations]], [[nausea]], [[chest pain]], [[shortness of breath]], [[stomach aches]], or [[headache|headache]].


Cognitive changes point to an expectation of both present and diffuse danger.  Somatically, the body prepares the organism to deal with a perceived threat; [[blood pressure]] and [[heart rate]] increase, perspiration and bloodflow to the major muscle groups increases, while[[immune system|immune]] and [[Digestion|digestive]] functions are inhibited.  External somatic indicators may present as pale skin, sweating, trembling, and/or [[mydriasis|pupillary dilation]].  Emotionally, anxiety induces a sense of dread or panic, and behavior directed at escaping or avoiding the source of anxiety may arise, as the anxiety reaction is an important survival mechanism.  
Cognitive changes point to an expectation of both present and diffuse danger.  Somatically, the body prepares the organism to deal with a perceived threat; [[blood pressure]] and [[heart rate]] increase, perspiration and bloodflow to the major muscle groups increases, while [[immune system|immune]] and [[Digestion|digestive]] functions are inhibited.  External somatic indicators may present as pale skin, sweating, trembling, and/or [[mydriasis|pupillary dilation]].  Emotionally, anxiety induces a sense of dread or panic, and behavior directed at escaping or avoiding the source of anxiety may arise, as the anxiety reaction is an important survival mechanism.  


==Neurological considerations==
==Neurological considerations==
Neurological systems that underlie anxiety include the [[amygdala]] and [[hippocampus]].  <ref>Rosen, J.B. & Schulkin, J. (1998): "From normal fear to pathological anxiety". ''Psychological Review''. '''105'''(2); 325-350.</ref>. When confronted with unpleasant and potentially harmful stimuli, such as foul odors or tastes, [[Positron emission tomography|PET-scans]] show increased bloodflow through the amygdala, while participants reported moderate, but measurable, anxiety. This indicates that anxiety may be a protective mechanism designed to prevent the organism from engaging in potentially harmful behaviors. <ref>Zald, D.H. & Pardo, J.V. (1997). "Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation." ''Proc Nat'l Acad Sci'' USA. '''94'''(8), 4119-24.</ref> <ref>Zald, D.H., Hagen, M.C. & Pardo, J.V. (2002). "Neural correlates of tasting concentrated quinine and sugar solutions". ''J. Neurophysiol.'' '''87'''(2), 1068-75.</ref>
Neurological systems that underlie anxiety include the [[amygdala]] and [[hippocampus]].  <ref>Rosen, J.B. & Schulkin, J. (1998): "From normal fear to pathological anxiety". ''Psychological Review''. '''105'''(2); 325-350.</ref>. When confronted with unpleasant and potentially harmful stimuli, such as foul odors or tastes, [[Positron emission tomography|PET-scans]] show increased bloodflow through the amygdala, while participants reported moderate, but measurable, anxiety. This indicates that anxiety may be a protective mechanism designed to prevent the organism from engaging in potentially harmful behaviors. <ref>Zald, D.H. & Pardo, J.V. (1997). "Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation." ''Proc Nat'l Acad Sci'' USA. '''94'''(8), 4119-24.</ref> <ref>Zald, D.H., Hagen, M.C. & Pardo, J.V. (2002). "Neural correlates of tasting concentrated quinine and sugar solutions". ''J. Neurophysiol.'' '''87'''(2), 1068-75.</ref>
==Diagnosis==
The Generalized Anxiety Disorder - 2 (GAD-2) may screen patients.<ref name="pmid17339617">{{cite journal| author=Kroenke K, Spitzer RL, Williams JB, Monahan PO, Löwe B| title=Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. | journal=Ann Intern Med | year= 2007 | volume= 146 | issue= 5 | pages= 317-25 | pmid=17339617 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17339617 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17909240 Review in: Evid Based Med. 2007 Oct;12(5):149] </ref> The GAD-2 scale is the first two items of the [http://www.annals.org/content/146/5/317/F1.expansion.html GAD-7 scale]. Two or more points has:<ref name="pmid17339617"/>
* [[sensitivity and specificity|sensitivity]] 95%
* [[sensitivity and specificity|specificity]] 64%
The [http://www.annals.org/content/146/5/317/F1.expansion.html GAD-7 scale] may diagnose patients. A score of 10 or more has accuracy of:<ref name="pmid17339617"/>
* [[sensitivity and specificity|sensitivity]] 89%
* [[sensitivity and specificity|specificity]] 82%
The Overall Anxiety Severity and Impairment Scale (OASIS) has five items may help diagnose and monitor.<ref name="pmid18486238">{{cite journal| author=Campbell-Sills L, Norman SB, Craske MG, Sullivan G, Lang AJ, Chavira DA et al.| title=Validation of a brief measure of anxiety-related severity and impairment: the Overall Anxiety Severity and Impairment Scale (OASIS). | journal=J Affect Disord | year= 2009 | volume= 112 | issue= 1-3 | pages= 92-101 | pmid=18486238 | doi=10.1016/j.jad.2008.03.014 | pmc=PMC2629402 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18486238  }} </ref><ref name="pmid16688739">{{cite journal| author=Norman SB, Cissell SH, Means-Christensen AJ, Stein MB| title=Development and validation of an Overall Anxiety Severity And Impairment Scale (OASIS). | journal=Depress Anxiety | year= 2006 | volume= 23 | issue= 4 | pages= 245-9 | pmid=16688739 | doi=10.1002/da.20182 | pmc= | url= }} </ref><ref name="pmid19264941">{{cite journal| author=Roy-Byrne P, Veitengruber JP, Bystritsky A, Edlund MJ, Sullivan G, Craske MG et al.| title=Brief intervention for anxiety in primary care patients. | journal=J Am Board Fam Med | year= 2009 | volume= 22 | issue= 2 | pages= 175-86 | pmid=19264941 | doi=10.3122/jabfm.2009.02.080078 | pmc=PMC2896069 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19264941  }} </ref> Accuracy of a score of ≥ 8 is:<ref name="pmid18486238"/>
* Sensitivity 89%
* Specificity 71%
The [http://www.hcp.med.harvard.edu/ncs/k6_scales.php Kessler-6 scale] has been studied.<ref name="pmid12578436">{{cite journal| author=Kessler RC, Barker PR, Colpe LJ, Epstein JF, Gfroerer JC, Hiripi E et al.| title=Screening for serious mental illness in the general population. | journal=Arch Gen Psychiatry | year= 2003 | volume= 60 | issue= 2 | pages= 184-9 | pmid=12578436 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12578436 }} </ref> However, at a cutoff of 13 or more points, the accuracy is:
* Sensitivity 36%
* Specificity 96%
The Clinical Interview Schedule Revision (CIS-R) can help screen and diagnose.<ref>Singleton N, Bumpstead R, O'Brien M, Lee A, Meltzer H. [Singleton N, Bumpstead R, O'Brien M, Lee A, Meltzer H. National Statistics: Psychiatric Morbidity Among Adults Living in Private Households, 2000. London: The Stationery Office; 2000:154. National Statistics: Psychiatric Morbidity Among Adults Living in Private Households, 2000]. London: The Stationery Office; 2000:154.</ref>
==Treatment==
Treatment has been reviewed by the British [[National Institute for Health and Clinical Excellence]] (NICE).<ref name="pmid21270081">{{cite journal| author=Kendall T, Cape J, Chan M, Taylor C, On behalf of the Guideline Development Group| title=Management of generalised anxiety disorder in adults: summary of NICE guidance. | journal=BMJ | year= 2011 | volume= 342 | issue=  | pages= c7460 | pmid=21270081 | doi=10.1136/bmj.c7460 | pmc= | url= }} </ref><ref name="NICE-GAD_2011">National Institute for Health and Clinical Excellence (2011). [http://guidance.nice.org.uk/CG113 Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults]</ref>
===Non drug treatment===
[[Exercise]] may reduce anxiety.<ref name="pmid20177034">{{cite journal| author=Herring MP, O'Connor PJ, Dishman RK| title=The effect of exercise training on anxiety symptoms among patients: a systematic review. | journal=Arch Intern Med | year= 2010 | volume= 170 | issue= 4 | pages= 321-31 | pmid=20177034
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=20177034 | doi=10.1001/archinternmed.2009.530 }} </ref>
[[Cognitive behavioral therapy]] may help anxiety.<ref name="pmid20483968">{{cite journal| author=Roy-Byrne P, Craske MG, Sullivan G, Rose RD, Edlund MJ, Lang AJ et al.| title=Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial. | journal=JAMA | year= 2010 | volume= 303 | issue= 19 | pages= 1921-8 | pmid=20483968 | url=http://jama.ama-assn.org/cgi/content/full/303/19/1921 | doi=10.1001/jama.2010.608 }} </ref><ref name="pmid19351943">{{cite journal| author=Stanley MA, Wilson NL, Novy DM, Rhoades HM, Wagener PD, Greisinger AJ et al.| title=Cognitive behavior therapy for generalized anxiety disorder among older adults in primary care: a randomized clinical trial. | journal=JAMA | year= 2009 | volume= 301 | issue= 14 | pages= 1460-7 | pmid=19351943 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19351943 | doi=10.1001/jama.2009.458 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20164517 Review in: Evid Based Ment Health. 2010 Feb;13(1):20] </ref>
===Drug therapy===
{| class="wikitable" border="1" align="right"
|+ Evidence summary from [[National Institute for Health and Clinical Excellence|NICE]] of selected medications.<ref name="NICE-GAD_2011">National Institute for Health and Clinical Excellence (2011). [http://guidance.nice.org.uk/CG113 Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults]</ref>
! &nbsp;!!Evidence base!!Relative risk of <br/>non-response!!Relative risk of<br/>[[Drug toxicity]]
|-
| [[Sertraline]]|| Trials: 2<br/>(706 patients)|| style="background-color:lightgreen;"|0.70*|| 1.1<br/>Nausea<br/>Sexual
|-
| [[Venlafaxine]]|| Trials: 12<br/>(3470 patients)|| style="background-color:lightgreen;"|0.80*||style="background-color:coral"| 2.06*<br/>Nausea<br/>Sexual<br/>Insomnia
|-
| [[Citalopram]]|| Trials: 1<br/>(34 patients)|| style="background-color:lightgreen;"|0.46*|| 3.0
|-
| [[Escitalopram]]|| Trials: 6<br/>(2136 patients)|| 0.78||style="background-color:coral"|1.72*<br/>Nausea<br/>Sexual<br/>
|-
| [[Paroxetine]]|| Trials: 8<br/>(2748 patients)||0.91||style="background-color:coral"|2.5*<br/>Nausea<br/>Sexual<br/>Insomnia
|-
| [[Pregabalin]]|| Trials: 8<br/>(2079 patients)|| style="background-color:lightgreen;align:center"|0.79*||1.3<br/>Dizziness<br/>Fatigue
|-
| [[Buspirone]]|| Trials: 5<br/>(806 patients)|| 0.87||style="background-color:coral"|2.0*<br/>Nausea<br/>Dizziness
|-
| [[Hydroxyzine]]|| Trials: 3<br/>(482 patients)|| 0.81|| 1.48<br/>Little short term toxicity
|-
| [[Alprazolam]]|| Trials: 4<br/>(544 patients)|| 0.87|| 1.3<br/>Little short term toxicity
|-
| colspan="4"|*  P< 0.05
|}
According to NICE, the first medications to use are [[selective serotonin uptake inhibitor]]s or serotonin noradrenaline reuptake inhibitors (both are classes of [[second-generation antidepressant]]s).<ref name="pmid21398351">{{cite journal| author=Baldwin D, Woods R, Lawson R, Taylor D| title=Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis. | journal=BMJ | year= 2011 | volume= 342 | issue=  | pages= d1199 | pmid=21398351 | doi=10.1136/bmj.d1199 | pmc= | url= }} </ref><ref name="pmid21270081"></ref><ref name="NICE-GAD_2011">National Institute for Health and Clinical Excellence (2011). [http://guidance.nice.org.uk/CG113 Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults]</ref> SSRis are "likely to be beneficial" according to Clinical Evidence.<ref name="pmid19450347">{{cite journal| author=Gale CK, Millichamp J| title=Generalised anxiety disorder. | journal=Clin Evid (Online) | year= 2007 | volume= 2007 | issue=  | pages=  | pmid=19450347 | doi= | pmc=PMC2943796 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19450347  }} </ref> Escitalopram has uncertain benefit in patients aged 60 years or older according to a [[randomized controlled trial]].<ref name="pmid19155456">{{cite journal|  author=Lenze EJ, Rollman BL, Shear MK, Dew MA, Pollock BG, Ciliberti C  et al.| title=Escitalopram for older adults with generalized anxiety  disorder: a randomized controlled trial. | journal=JAMA | year= 2009 |  volume= 301 | issue= 3 | pages= 295-303 | pmid=19155456 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19155456  | doi=10.1001/jama.2008.977 | pmc=PMC2840403 }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19633255  Review in: Evid Based Ment Health. 2009 Aug;12(3):87] </ref>
[[Pregabalin]] is recommended by NICE after SSRIs.<ref name="NICE-GAD_2011"/> Pregabalin increases dizziness and fatigue.<ref name="NICE-GAD_2011"/> NICE performed meta-analysis of 8 [[randomized controlled trial]]s include the two largest by Phohl<ref name="pmid15738746">{{cite journal| author=Pohl RB, Feltner DE, Fieve RR, Pande AC| title=Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing. | journal=J Clin Psychopharmacol | year= 2005 | volume= 25 | issue= 2 | pages= 151-8 | pmid=15738746 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15738746  }} </ref> and Rickels<ref name="pmid16143734">{{cite journal| author=Rickels K, Pollack MH, Feltner DE, Lydiard RB, Zimbroff DL, Bielski RJ et al.| title=Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. | journal=Arch Gen Psychiatry | year= 2005 | volume= 62 | issue= 9 | pages= 1022-30 | pmid=16143734 | doi=10.1001/archpsyc.62.9.1022 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16143734  }} </ref>. One [[randomized controlled trial]] cited by NICE directly compared pregabalin with [[venlafaxine]].<ref>{{Cite journal | issn = 0268-1315 | volume = 24 | issue = 2 | last = Kasper | first = Siegfried | coauthors = Barry Herman, Giancarlo Nivoli, Michael Van Ameringen, Antonino Petralia, Francine S. Mandel, Francesca Baldinetti, Borwin Bandelow | title = Efficacy of pregabalin and venlafaxine-XR in generalized anxiety disorder: results of a double-blind, placebo-controlled 8-week trial | journal = International Clinical Psychopharmacology | date = 2009 }}</ref> Pregabilin is "likely to  be beneficial" according to Clinical Evidence.<ref  name="pmid19450347"></ref>
[[Azapirone]]s, such as [[buspirone]] may help, but have [[drug toxicity]]. Buspirone is "likely to  be beneficial" according to Clinical Evidence.<ref  name="pmid19450347"></ref> Buspirone may increase nausea and dizziness.<ref name="NICE-GAD_2011"/>
[[Benzodiazepine]]s have long been the core of short-term pharmacologic therapy, although some are habit forming and their usefulness may decrease  over time.
The [[antipsychotic agent]] [[quetiapine]] may reduce anxiety.<ref name="pmid21154392">{{cite journal| author=Depping AM, Komossa K, Kissling W, Leucht S| title=Second-generation antipsychotics for anxiety disorders. | journal=Cochrane Database Syst Rev | year= 2010 | volume= 12 | issue=  | pages= CD008120 | pmid=21154392 | doi=10.1002/14651858.CD008120.pub2 | pmc= | url= }} </ref>
The [[cholinergic antagonist]] hydroxyzine may help.<ref name="pmid21154375">{{cite journal| author=Guaiana G, Barbui C, Cipriani A| title=Hydroxyzine for generalised anxiety disorder. | journal=Cochrane Database Syst Rev | year= 2010 | volume= 12 | issue=  | pages= CD006815 | pmid=21154375 | doi=10.1002/14651858.CD006815.pub2 | pmc= | url= }} </ref>
===Monitoring the response to treatment===
The Daily Assessment of Symptoms - Anxiety (DAS-A) scale can help.<ref name="pmid18061206">{{cite journal| author=Morlock RJ, Williams VS, Cappelleri JC, Harness J, Fehnel SE, Endicott J et al.| title=Development and evaluation of the Daily Assessment of Symptoms - Anxiety (DAS-A) scale to evaluate onset of symptom relief in patients with generalized anxiety disorder. | journal=J Psychiatr Res | year= 2008 | volume= 42 | issue= 12 | pages= 1024-36 | pmid=18061206 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18061206 | doi=10.1016/j.jpsychires.2007.09.005 }} </ref>
The Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A) scale can help;<ref name="pmid16330721">{{cite journal| author=Rollman BL, Belnap BH, Mazumdar S, Houck PR, Zhu F, Gardner W et al.| title=A randomized trial to improve the quality of treatment for panic and generalized anxiety disorders in primary care. | journal=Arch Gen Psychiatry | year= 2005 | volume= 62 | issue= 12 | pages= 1332-41 | pmid=16330721 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16330721 | doi=10.1001/archpsyc.62.12.1332 }} </ref><ref name="pmid11413563">{{cite journal| author=Shear MK, Vander Bilt J, Rucci P, Endicott J, Lydiard B, Otto MW et al.| title=Reliability and validity of a structured interview guide for the Hamilton Anxiety Rating Scale (SIGH-A). | journal=Depress Anxiety | year= 2001 | volume= 13 | issue= 4 | pages= 166-78 | pmid=11413563 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11413563 }} </ref>; however, the SIGH-A may not well detect panic symptoms.<ref name="pmid16330721"/> A 40% decrease is considered a response.<ref name="pmid16330721"/>
The Brief Symptom Inventory (BIS) adapted from the longer SCL-90-R can help.<ref name="pmid6622612">{{cite journal| author=Derogatis LR, Melisaratos N| title=The Brief Symptom Inventory: an introductory report. | journal=Psychol Med | year= 1983 | volume= 13 | issue= 3 | pages= 595-605 | pmid=6622612 }} </ref><ref name="pmid20483968"/>
The  Overall Anxiety Severity and Impairment Scale (OASIS) can help.<ref name="pmid18486238"></ref><ref name="pmid20483968"/>
The Kessler 6 scale can help.<ref name="pmid12214795">{{cite journal| author=Kessler RC, Andrews G, Colpe LJ, Hiripi E, Mroczek DK, Normand SL et al.| title=Short screening scales to monitor population prevalences and trends in non-specific psychological distress. | journal=Psychol Med | year= 2002 | volume= 32 | issue= 6 | pages= 959-76 | pmid=12214795 | doi= | pmc= | url= }} </ref>


==References==
==References==
<references/>
{{reflist|2}}[[Category:Suggestion Bot Tag]]

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Anxiety is a physiological state marked by demonstrable changes in cognitive, somatic, emotional, and behavioral components. [1] These changes combine to create the sensations typically recognized as fear, apprehension, or worry. Anxiety is also often accompanied by physical sensations such as heart palpitations, nausea, chest pain, shortness of breath, stomach aches, or headache.

Cognitive changes point to an expectation of both present and diffuse danger. Somatically, the body prepares the organism to deal with a perceived threat; blood pressure and heart rate increase, perspiration and bloodflow to the major muscle groups increases, while immune and digestive functions are inhibited. External somatic indicators may present as pale skin, sweating, trembling, and/or pupillary dilation. Emotionally, anxiety induces a sense of dread or panic, and behavior directed at escaping or avoiding the source of anxiety may arise, as the anxiety reaction is an important survival mechanism.

Neurological considerations

Neurological systems that underlie anxiety include the amygdala and hippocampus. [2]. When confronted with unpleasant and potentially harmful stimuli, such as foul odors or tastes, PET-scans show increased bloodflow through the amygdala, while participants reported moderate, but measurable, anxiety. This indicates that anxiety may be a protective mechanism designed to prevent the organism from engaging in potentially harmful behaviors. [3] [4]

Diagnosis

The Generalized Anxiety Disorder - 2 (GAD-2) may screen patients.[5] The GAD-2 scale is the first two items of the GAD-7 scale. Two or more points has:[5]

The GAD-7 scale may diagnose patients. A score of 10 or more has accuracy of:[5]

The Overall Anxiety Severity and Impairment Scale (OASIS) has five items may help diagnose and monitor.[6][7][8] Accuracy of a score of ≥ 8 is:[6]

  • Sensitivity 89%
  • Specificity 71%

The Kessler-6 scale has been studied.[9] However, at a cutoff of 13 or more points, the accuracy is:

  • Sensitivity 36%
  • Specificity 96%

The Clinical Interview Schedule Revision (CIS-R) can help screen and diagnose.[10]

Treatment

Treatment has been reviewed by the British National Institute for Health and Clinical Excellence (NICE).[11][12]

Non drug treatment

Exercise may reduce anxiety.[13]

Cognitive behavioral therapy may help anxiety.[14][15]

Drug therapy

Evidence summary from NICE of selected medications.[12]
  Evidence base Relative risk of
non-response		 Relative risk of
Drug toxicity
Sertraline Trials: 2
(706 patients)		 0.70* 1.1
Nausea
Sexual
Venlafaxine Trials: 12
(3470 patients)		 0.80* 2.06*
Nausea
Sexual
Insomnia
Citalopram Trials: 1
(34 patients)		 0.46* 3.0
Escitalopram Trials: 6
(2136 patients)		 0.78 1.72*
Nausea
Sexual
Paroxetine Trials: 8
(2748 patients)		 0.91 2.5*
Nausea
Sexual
Insomnia
Pregabalin Trials: 8
(2079 patients)		 0.79* 1.3
Dizziness
Fatigue
Buspirone Trials: 5
(806 patients)		 0.87 2.0*
Nausea
Dizziness
Hydroxyzine Trials: 3
(482 patients)		 0.81 1.48
Little short term toxicity
Alprazolam Trials: 4
(544 patients)		 0.87 1.3
Little short term toxicity
* P< 0.05

According to NICE, the first medications to use are selective serotonin uptake inhibitors or serotonin noradrenaline reuptake inhibitors (both are classes of second-generation antidepressants).[16][11][12] SSRis are "likely to be beneficial" according to Clinical Evidence.[17] Escitalopram has uncertain benefit in patients aged 60 years or older according to a randomized controlled trial.[18]

Pregabalin is recommended by NICE after SSRIs.[12] Pregabalin increases dizziness and fatigue.[12] NICE performed meta-analysis of 8 randomized controlled trials include the two largest by Phohl[19] and Rickels[20]. One randomized controlled trial cited by NICE directly compared pregabalin with venlafaxine.[21] Pregabilin is "likely to be beneficial" according to Clinical Evidence.[17]

Azapirones, such as buspirone may help, but have drug toxicity. Buspirone is "likely to be beneficial" according to Clinical Evidence.[17] Buspirone may increase nausea and dizziness.[12]

Benzodiazepines have long been the core of short-term pharmacologic therapy, although some are habit forming and their usefulness may decrease over time.

The antipsychotic agent quetiapine may reduce anxiety.[22]

The cholinergic antagonist hydroxyzine may help.[23]

Monitoring the response to treatment

The Daily Assessment of Symptoms - Anxiety (DAS-A) scale can help.[24]

The Structured Interview Guide for the Hamilton Anxiety Scale (SIGH-A) scale can help;[25][26]; however, the SIGH-A may not well detect panic symptoms.[25] A 40% decrease is considered a response.[25]

The Brief Symptom Inventory (BIS) adapted from the longer SCL-90-R can help.[27][14]

The Overall Anxiety Severity and Impairment Scale (OASIS) can help.[6][14]

The Kessler 6 scale can help.[28]

References

  1. ↑ Seligman, M.E.P., Walker, E.F. & Rosenhan, D.L. (2001). Abnormal psychology, (4th ed.) New York: W.W. Norton & Company, Inc.
  2. ↑ Rosen, J.B. & Schulkin, J. (1998): "From normal fear to pathological anxiety". Psychological Review. 105(2); 325-350.
  3. ↑ Zald, D.H. & Pardo, J.V. (1997). "Emotion, olfaction, and the human amygdala: amygdala activation during aversive olfactory stimulation." Proc Nat'l Acad Sci USA. 94(8), 4119-24.
  4. ↑ Zald, D.H., Hagen, M.C. & Pardo, J.V. (2002). "Neural correlates of tasting concentrated quinine and sugar solutions". J. Neurophysiol. 87(2), 1068-75.
  5. ↑ 5.0 5.1 5.2 Kroenke K, Spitzer RL, Williams JB, Monahan PO, Löwe B (2007). "Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection.". Ann Intern Med 146 (5): 317-25. PMID 17339617. Review in: Evid Based Med. 2007 Oct;12(5):149
  6. ↑ 6.0 6.1 6.2 Campbell-Sills L, Norman SB, Craske MG, Sullivan G, Lang AJ, Chavira DA et al. (2009). "Validation of a brief measure of anxiety-related severity and impairment: the Overall Anxiety Severity and Impairment Scale (OASIS).". J Affect Disord 112 (1-3): 92-101. DOI:10.1016/j.jad.2008.03.014. PMID 18486238. PMC PMC2629402. Research Blogging.
  7. ↑ Norman SB, Cissell SH, Means-Christensen AJ, Stein MB (2006). "Development and validation of an Overall Anxiety Severity And Impairment Scale (OASIS).". Depress Anxiety 23 (4): 245-9. DOI:10.1002/da.20182. PMID 16688739. Research Blogging.
  8. ↑ Roy-Byrne P, Veitengruber JP, Bystritsky A, Edlund MJ, Sullivan G, Craske MG et al. (2009). "Brief intervention for anxiety in primary care patients.". J Am Board Fam Med 22 (2): 175-86. DOI:10.3122/jabfm.2009.02.080078. PMID 19264941. PMC PMC2896069. Research Blogging.
  9. ↑ Kessler RC, Barker PR, Colpe LJ, Epstein JF, Gfroerer JC, Hiripi E et al. (2003). "Screening for serious mental illness in the general population.". Arch Gen Psychiatry 60 (2): 184-9. PMID 12578436.
  10. ↑ Singleton N, Bumpstead R, O'Brien M, Lee A, Meltzer H. [Singleton N, Bumpstead R, O'Brien M, Lee A, Meltzer H. National Statistics: Psychiatric Morbidity Among Adults Living in Private Households, 2000. London: The Stationery Office; 2000:154. National Statistics: Psychiatric Morbidity Among Adults Living in Private Households, 2000]. London: The Stationery Office; 2000:154.
  11. ↑ 11.0 11.1 Kendall T, Cape J, Chan M, Taylor C, On behalf of the Guideline Development Group (2011). "Management of generalised anxiety disorder in adults: summary of NICE guidance.". BMJ 342: c7460. DOI:10.1136/bmj.c7460. PMID 21270081. Research Blogging.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 National Institute for Health and Clinical Excellence (2011). Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults
  13. ↑ Herring MP, O'Connor PJ, Dishman RK (2010). "The effect of exercise training on anxiety symptoms among patients: a systematic review.". Arch Intern Med 170 (4): 321-31. DOI:10.1001/archinternmed.2009.530. PMID 20177034. Research Blogging.
  14. ↑ 14.0 14.1 14.2 Roy-Byrne P, Craske MG, Sullivan G, Rose RD, Edlund MJ, Lang AJ et al. (2010). "Delivery of evidence-based treatment for multiple anxiety disorders in primary care: a randomized controlled trial.". JAMA 303 (19): 1921-8. DOI:10.1001/jama.2010.608. PMID 20483968. Research Blogging.
  15. ↑ Stanley MA, Wilson NL, Novy DM, Rhoades HM, Wagener PD, Greisinger AJ et al. (2009). "Cognitive behavior therapy for generalized anxiety disorder among older adults in primary care: a randomized clinical trial.". JAMA 301 (14): 1460-7. DOI:10.1001/jama.2009.458. PMID 19351943. Research Blogging. Review in: Evid Based Ment Health. 2010 Feb;13(1):20
  16. ↑ Baldwin D, Woods R, Lawson R, Taylor D (2011). "Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis.". BMJ 342: d1199. DOI:10.1136/bmj.d1199. PMID 21398351. Research Blogging.
  17. ↑ 17.0 17.1 17.2 Gale CK, Millichamp J (2007). "Generalised anxiety disorder.". Clin Evid (Online) 2007. PMID 19450347. PMC PMC2943796. [e]
  18. ↑ Lenze EJ, Rollman BL, Shear MK, Dew MA, Pollock BG, Ciliberti C et al. (2009). "Escitalopram for older adults with generalized anxiety disorder: a randomized controlled trial.". JAMA 301 (3): 295-303. DOI:10.1001/jama.2008.977. PMID 19155456. PMC PMC2840403. Research Blogging. Review in: Evid Based Ment Health. 2009 Aug;12(3):87
  19. ↑ Pohl RB, Feltner DE, Fieve RR, Pande AC (2005). "Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebo-controlled comparison of BID versus TID dosing.". J Clin Psychopharmacol 25 (2): 151-8. PMID 15738746. [e]
  20. ↑ Rickels K, Pollack MH, Feltner DE, Lydiard RB, Zimbroff DL, Bielski RJ et al. (2005). "Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam.". Arch Gen Psychiatry 62 (9): 1022-30. DOI:10.1001/archpsyc.62.9.1022. PMID 16143734. Research Blogging.
  21. ↑ Kasper, Siegfried; Barry Herman, Giancarlo Nivoli, Michael Van Ameringen, Antonino Petralia, Francine S. Mandel, Francesca Baldinetti, Borwin Bandelow (2009). "Efficacy of pregabalin and venlafaxine-XR in generalized anxiety disorder: results of a double-blind, placebo-controlled 8-week trial". International Clinical Psychopharmacology 24 (2). ISSN 0268-1315.
  22. ↑ Depping AM, Komossa K, Kissling W, Leucht S (2010). "Second-generation antipsychotics for anxiety disorders.". Cochrane Database Syst Rev 12: CD008120. DOI:10.1002/14651858.CD008120.pub2. PMID 21154392. Research Blogging.
  23. ↑ Guaiana G, Barbui C, Cipriani A (2010). "Hydroxyzine for generalised anxiety disorder.". Cochrane Database Syst Rev 12: CD006815. DOI:10.1002/14651858.CD006815.pub2. PMID 21154375. Research Blogging.
  24. ↑ Morlock RJ, Williams VS, Cappelleri JC, Harness J, Fehnel SE, Endicott J et al. (2008). "Development and evaluation of the Daily Assessment of Symptoms - Anxiety (DAS-A) scale to evaluate onset of symptom relief in patients with generalized anxiety disorder.". J Psychiatr Res 42 (12): 1024-36. DOI:10.1016/j.jpsychires.2007.09.005. PMID 18061206. Research Blogging.
  25. ↑ 25.0 25.1 25.2 Rollman BL, Belnap BH, Mazumdar S, Houck PR, Zhu F, Gardner W et al. (2005). "A randomized trial to improve the quality of treatment for panic and generalized anxiety disorders in primary care.". Arch Gen Psychiatry 62 (12): 1332-41. DOI:10.1001/archpsyc.62.12.1332. PMID 16330721. Research Blogging.
  26. ↑ Shear MK, Vander Bilt J, Rucci P, Endicott J, Lydiard B, Otto MW et al. (2001). "Reliability and validity of a structured interview guide for the Hamilton Anxiety Rating Scale (SIGH-A).". Depress Anxiety 13 (4): 166-78. PMID 11413563.
  27. ↑ Derogatis LR, Melisaratos N (1983). "The Brief Symptom Inventory: an introductory report.". Psychol Med 13 (3): 595-605. PMID 6622612.
  28. ↑ Kessler RC, Andrews G, Colpe LJ, Hiripi E, Mroczek DK, Normand SL et al. (2002). "Short screening scales to monitor population prevalences and trends in non-specific psychological distress.". Psychol Med 32 (6): 959-76. PMID 12214795. [e]
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