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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]


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 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
Relative risk of
Drug toxicity
Sertraline Trials: 2
(706 patients)
0.70* 1.1
Venlafaxine Trials: 12
(3470 patients)
0.80* 2.06*
Citalopram Trials: 1
(34 patients)
0.46* 3.0
Escitalopram Trials: 6
(2136 patients)
0.78 1.72*
Paroxetine Trials: 8
(2748 patients)
0.91 2.5*
Pregabalin Trials: 8
(2079 patients)
0.79* 1.3
Buspirone Trials: 5
(806 patients)
0.87 2.0*
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]


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