Anxiety disorders are characterized by persistent and excessive fear and anxiety and the dysfunctional behavioral changes a patient may use to mitigate these feelings. Anxiety disorders are differentiated from one another based on the specific objects or situations that induce the fear, anxiety, and associated behavioral changes.
Everyone periodically experiences fear and anxiety.
Fear is an emotional, physical, and behavioral response to an immediately recognizable external threat (eg, an intruder, a car spinning on ice).
Anxiety is a distressing, unpleasant emotional state of nervousness and uneasiness; its causes are less clear. Anxiety is less tied to the exact timing of a threat; it can be anticipatory before a threat, persist after a threat has passed, or occur without an identifiable threat.
People often experience both fear and anxiety as changes in their body (eg, sweating, nausea) and their behaviors (eg, avoidance, anger). Often, people are aware of these physical and behavioral changes without clearly identifying that they are anxious or fearful.
Adaptive anxiety can help motivate people to prepare, practice, and rehearse; it can also encourage appropriate caution in potentially dangerous situations. When anxiety causes dysfunction and undue distress, however, it is considered maladaptive and, thus, a psychiatric disorder.
Anxiety disorders are more common than any other class of psychiatric disorder, with about one third of people meeting criteria for an anxiety disorder at some point in their lifetime (1, 2). Anxiety disorders tend to be underdiagnosed, however, and can be associated with suicidal thoughts and suicide attempts.
The Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) lists the various anxiety disorders in order of the typical age of onset (3):
Selective mutism
Specific phobia (animal, natural environment, blood-injection injury, situational)
Substance-induced/medication-induced anxiety disorder
Anxiety due to another medical condition
Other specified anxiety disorder (applies when patient has significant symptoms but does not meet criteria for any specific anxiety disorder)
Separation anxiety and selective mutism tend to arise during childhood, whereas the other disorders listed above generally develop in adulthood.
Substance-induced/medication-induced anxiety disorder and anxiety due to another medical condition should always be considered when people present with significant anxiety.
Other disorders that often present with prominent anxiety include acute stress disorder, adjustment disorders, and posttraumatic stress disorder (PTSD). Because they are deemed to arise out of traumatic or stressful experiences, they are grouped separately in the DSM-5-TR.
Anxiety disorders tend to be highly comorbid with other medical and psychiatric conditions. Depression, substance use disorders, personality disorders, and other anxiety disorders are particularly common comorbidities, as are cardiovascular disease, asthma, migraines, and arthritis. Because anxiety disorders often precede other psychiatric comorbidities, early and effective treatment of the anxiety disorder can prevent or mitigate their development.
General references
1. Bandelow B, Michaelis S: Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci 17(3):327-335, 2015. doi: 10.31887/DCNS.2015.17.3/bbandelow
2. Penninx BW, Pine DS, Holmes EA, et al: Anxiety disorders. Lancet 97(10277):914-927, 2021. doi: 10.1016/S0140-6736(21)00359-7
3. Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR). American Psychiatric Association Publishing, Washington, DC, pp 215-262.
Etiology of Anxiety Disorders
There is no single gene or psychological cause for anxiety disorders, but they do seem to develop in the context of typical biopsychosocial factors. Anxiety disorders tend to run in families, and they do so through at least 2 mechanisms (1):
A childhood trait of "behavioral inhibition" appears to be somewhat inherited, and that trait is associated with an increased risk of anxiety disorders in adolescence.
Social fears and avoidance can be transmitted to children through parental modeling and/or early traumatic experiences that might include childhood maltreatment or medical illnesses (eg, asthma). It has been hypothesized that these experiences and genetic vulnerabilities prime some children to be unusually attentive to their own physical and emotional reactions to stress, which can then lead to panic disorder and social anxiety disorder.
Many people develop an anxiety disorder, however, without an identifiable antecedent trigger. For example, most people with a snake phobia have never been bitten by a snake and do not report a characteristic traumatic experience. Anxiety can also be a response to environmental and social stressors during adulthood, such as the ending of a significant relationship or exposure to a life-threatening disaster, though most people who experience such stressors do not go on to develop an anxiety disorder.
Some medical disorders can directly cause anxiety. These include asthma, cardiac arrhythmias, chronic obstructive pulmonary disease (COPD), heart failure, hyperthyroidism, Cushing syndrome, and pheochromocytoma.
The medications used to treat some medical disorders can also induce anxiety as a symptom. These include
Attention deficit/hyperactivity disorder (amphetamines and other stimulants)
Seasonal allergies (antihistamines and decongestants)
, and MDMA (ecstasy). Some drugs that are generally used to induce relaxation can also cause anxiety. Cannabis (marijuana) induces anxiety in some people, either directly or through an adulterant such as phencyclidine (PCP). Withdrawal from alcohol, sedatives, and some other drugs can also cause anxiety.
COVID-19–related anxiety
The COVID-19 pandemic was associated with surges in rates of depression and anxiety in people who had not been infected (2). Such psychological reactions may have been exacerbations of underlying issues, but the symptoms are often intensified by media exposure, economic hardship, uncertainty regarding the future, fears of infection (for themselves and loved ones), loss of familiar supports (eg, friends, employment), and behavioral restrictions (eg, masks, social distancing).
Symptomatic COVID-19 infection is also associated with increased anxiety (3). The triggers for this increased anxiety can be physiologic (eg, shortness of breath); psychological (eg, immediate fears of death); social (eg, isolation from loved ones); and pharmacologic (eg, corticosteroids are often used in treatment of COVID-19). In addition, it has been hypothesized that COVID-19 induces a host immune response that directly leads to neuropsychiatric symptoms (eg, anxiety, mood changes, neuromuscular dysfunction); these neuropsychiatric reactions may be acute or part of a syndrome known as long COVID. (See also COVID-Related Neuropsychiatric Manifestations.)
Etiology references
1. Juruena MF, Eror F, Cleare AJ, et al: The role of early life stress in HPA axis and anxiety. Adv Exp Med Biol 1191:141-153, 2020. doi: 10.1007/978-981-32-9705-0_9
2. Shafran R, Rachman S, Whittal M, et al: Fear and anxiety in COVID-19: Preexisting anxiety disorders. Cogn Behav Pract 28(4):459-467, 2021. doi:10.1016/j.cbpra.2021.03.003
3. Troyer EA, Kohn JN, Hong S: Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms. Brain Behav Immun 87:34-39, 2020. doi: 10.1016/j.bbi.2020.04.027
Symptoms and Signs of Anxiety Disorders
Anxiety disorders tend to differ from usual and normal anxiety by being persistent (> 6 months), excessive, debilitating, and uncomfortable.
Anxiety disorders can induce a broad range of physical symptoms, including (1):
Gastrointestinal: Nausea, vomiting, diarrhea
Pulmonary: Shortness of breath, choking
Autonomic: Dizziness, faintness, sweats, hot and cold flashes
Cardiac: Palpitations, accelerated heart rate
Musculoskeletal: Muscle tension, chest pain or tightness
A panic or worry diary can be a useful tool for recording symptoms, both because retrospective anxiety reports can be vague and because treatment strategies often depend on details.
Signs and symptoms reference
1. Craske MG, Stein MB: Anxiety. Lancet 388:3048-3059, 2016. doi: 10.1016/S0140-6736(16)30381-6
Diagnosis of Anxiety Disorders
Diagnostic and Statistical Manual of Mental Disorders, 5th edition, Text Revision (DSM-5-TR) criteria
Diagnosis of a specific anxiety disorder is based on its characteristic symptoms and signs according to DSM-5-TR. In general, an anxiety disorder may be suspected when the following apply (1):
Anxiety is very distressing.
Anxiety interferes with functioning.
Anxiety does not stop spontaneously within a few days.
Other causes are not identified.
When diagnosing an anxiety disorder, it is important to rule out anxiety attributable to certain medical conditions (eg, asthma, hyperthyroidism), and/or substances or medications (2). Furthermore, if present, the clinician needs to assess the extent to which the medical disorder and/or substance is actually implicated in the anxiety. As is true in all psychiatric assessments, a careful history is crucial to accurate diagnosis.
If patients meet criteria for an anxiety disorder, and the clinician concludes that the symptoms are best explained by the direct physiologic effects of a medication or illicit drug/substance, the patient is deemed to have a substance-/medication-induced anxiety disorder. Similarly, if the significant anxiety is deemed to be the direct physiologic result of another medical condition, the patient may be diagnosed with anxiety disorder due to another medical condition.
As is true for almost all psychiatric conditions, there are no laboratory tests for anxiety disorders, though laboratory tests may help identify medical conditions associated with the anxiety. Clinical judgment is required before making the diagnosis. In addition to eliciting characteristic symptoms and time course, the clinician must also evaluate whether the clinical situation meets the threshold for causing clinically significant distress and/or dysfunction.
The different anxiety disorders can often be distinguished from one another based on the answers to 3 key questions:
What situations induce the fear and anxiety?
What thoughts are associated with the anxiety?
What avoidance strategies are used?
Cultural factors
Culture influences the expression, conceptualization, and treatment of all psychiatric conditions, including anxiety disorders (3, 4). During the psychiatric assessment, it is important to look for ways in which the anxiety symptoms might be affected by the surrounding political, economic, and legal systems, as well as by specific issues related to migrant status, sexual orientation, socioeconomic status, religion, spirituality, and family structures.
Patients may feel intimidated, embarrassed, or reluctant to discuss anxiety with anyone, much less physicians, who may appear to belong to a different and potentially more privileged socioeconomic group. Similarly, people who want to be "good patients" might not be upfront about psychiatric issues if they suspect that their clinicians are too busy to address anything other than their most prominent nonpsychiatric medical issue.
It is useful for the clinician to consider that different individuals or groups use different words to describe distress. For example, people in many countries use the phrase "thinking too much" rather than describing symptoms that match specific psychiatric criteria for disorders such as major depression, posttraumatic stress disorder (PTSD), or generalized anxiety disorder (5).
It can also be useful to ask patients what they think is causing their problems. Not all patients believe completely in the medical model, and, if tactfully asked, many patients might reluctantly mention that they (or their relatives) believe their symptoms were induced by a religious or other mystical source (eg, an "evil eye").
Eliciting such information improves the patient-clinician alliance, deepens the understanding of both the patient and the presenting complaints, and improves the likelihood that the patient will be more transparent and adherent going forward.
Diagnosis references
1. Diagnostic and Statistical Manual of Mental Disorders, 5th edition,Text Revision (DSM-5-TR). American Psychiatric Association Publishing, Washington, DC, pp 215-221.
2. Craske MG, Stein MB: Anxiety. Lancet 388:3048-3059, 2016. doi: 10.1016/S0140-6736(16)30381-6
3. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-5-TR), Cultural Concepts of Distress. American Psychiatric Association Publishing, Washington, DC, pp 872-880.
4. Lewis-Fernández R, Aggarwal NK, Lam PC, et al: Feasibility, acceptability and clinical utility of the Cultural Formulation Interview: Mixed-methods results from the DSM-5 international field trial. Br J Psychiatry 210(4):290-297, 2017. doi: 10.1192/bjp.bp.116.193862
5. Kaiser BN , Haroz EE, Kohrt BA, et al: "Thinking too much": A systematic review of a common idiom of distress. Soc Sci Med 147:170-183, 2015. doi: 10.1016/j.socscimed.2015.10.044
Treatment of Anxiety Disorders
Psychoeducation
Relaxation techniques
Psychotherapies, such as cognitive-behavioral psychotherapy (CBT)
Pharmacotherapy (benzodiazepines, selective serotonin reuptake inhibitors [SSRIs])
The following general principles are important to take into consideration when treating anxiety disorders:
A variety of interventions are effective for managing anxiety disorders.
Most patients can be managed successfully in primary care settings.
Accurate identification of the anxiety disorder and pertinent comorbidities is crucial.
Treatment of comorbid medical conditions that can contribute to anxiety (eg, asthma).
Co-occurring substance use disorders should generally be treated concomitantly with the anxiety disorder. It should be recognized that the substance is often partly being used to reduce anxiety, and withdrawal can induce additional anxiety.
Lifestyle modifications such as obtaining adequate exercise and sleep (1
Treatment recommendations are influenced by patient preferences and access to mental health care professionals.
Psychotherapy and medications are effective for most anxiety disorders, particularly when used together (2, 3).
Psychoeducation and relaxation techniques
Psychoeducation is typically fundamental to the treatment of anxiety disorders. It can feel liberating for the patient to understand how a sometimes bewildering array of symptoms and behaviors can be conceptualized into a diagnosis. Education also provides a cognitive structure to help patients pursue a treatment that may feel uncomfortable.
Relaxation techniques should be taught early in the treatment. These techniques are useful both because fear and anxiety are fundamental to anxiety disorders and because the treatment can transiently intensify the disabling thoughts and feelings. Without a tool for controlling anxiety, many patients will not adhere to treatment. Relaxation techniques may include muscle relaxation, breathing management, yoga, hypnosis, and/or meditation, but patient preference is important in determining the specific approach. Relaxation techniques can be briefly described and then "prescribed" as homework. Adherence and effectiveness are more likely to be optimized if the clinician periodically demonstrates the techniques (eg, slow, steady breathing) with enthusiasm.
Psychotherapies
Various psychotherapies are equally efficacious for most psychiatric disorders. This equivalency appears to be related to so-called nonspecific factors, which include the personal characteristics of the therapist and a positive therapeutic climate that allows the patient to effectively engage in the talk therapy and remain adherent with agreed-upon practices and medications.
Cognitive-behavioral therapy (CBT) has the most robust evidence as a psychosocial treatment for anxiety disorders (4). Psychoeducation and relaxation techniques should be introduced early in CBT.
CBT involves both cognitive restructuring and exposure therapy. Cognitive restructuring begins with the idea that patients with anxiety disorders overestimate the danger (catastrophize) and underestimate their ability to deal with the danger. These inaccurate thoughts and antecedent triggers are clarified during treatment. Often, the pattern of anxiety can be neatly laid into a characteristic cycle of triggers, behaviors, and anxiety. As this cycle is clarified, patients are taught to recognize and confront their inaccurate thoughts (ie, cognitive restructuring).
CBT also focuses on the behavioral elements of the anxiety disorder. Typically, patients with anxiety disorders respond to perceived danger with a "fight-or-flight" response. Some patients with prominent anxiety are able to "fight" their anxiety, often with a counter-phobic response (eg, an actor with prominent social anxiety), but most respond with avoidance. Exposure therapy aims to identify the avoidance behavior and then present the patient with gradually intensifying opportunities to be safely exposed to the fearful trigger, gradually desensitizing the patient.
Other psychotherapies used for treatment of anxiety disorders combine aspects of CBT, relaxation, and mindfulness along with other strategies that appear to be helpful. These treatments include mindfulness-based stress reduction, hypnosis, panic-focused psychodynamic psychotherapy, interpersonal therapy, and supportive psychotherapy:
Mindfulness-based stress reduction is a standardized program in which groups meet for 8 consecutive weeks; sessions feature sitting and walking meditation, yoga, and mindful relaxation techniques. There is also a daily home practice to reinforce the principles practiced during the 2.5-hour sessions (5). Mindfulness-based cognitive therapy combines these mindfulness elements with CBT methods such as psychoeducation and cognitive restructuring.
Hypnosis is used to teach management of the interaction between mental anxiety and physical stress such as muscle tension, increase in respiratory and heart rate, and sweating. Mental anxiety and physical stress tend to reinforce each other, while hypnotic suggestions to imagine being in a safe and comfortable place coupled with visualization of means of successful stress management can reduce anxiety symptoms rapidly while teaching a coping skill (6).
Panic-focused psychodynamic psychotherapy is a structured, time-limited psychotherapy that shares features with other interventions, though the sessions tend to focus on the stressors, feelings, and emotional meanings of panic attacks (7).
Interpersonal psychotherapy (IPT) is a structured, time-limited psychotherapy that addresses current problems and relationships. IPT focuses on 1 or more of 4 areas: relationship conflicts, life changes, grief or loss, and problems with relationships. Most often used to treat depression, IPT appears to be well-tolerated and effective for several anxiety disorders (8). While CBT focuses on cognitions and behaviors, IPT focuses on feelings that develop in the context of interpersonal situations.
Supportive psychotherapy aims to support the patient's healthy defenses and healthy behaviors through empathy, validation, and nonjudgmental listening. Supportive techniques tend to improve the therapeutic alliance and reduce treatment nonadherence. Supportive psychotherapy can be therapeutic by itself and can also be a fundamental part of other psychotherapies.
Pharmacotherapy
9).
Selective serotonin reuptake inhibitors (SSRIs) are generally considered first-line based on their efficacy and safety profiles. These "antidepressant" medications address the symptoms of the anxiety disorders regardless of whether there is a comorbid depressive disorder.
SSRI antidepressants are generally started at the lowest available dose to minimize adverse effects. Patients with anxiety may be sensitive to bodily changes and may discontinue treatment if they experience adverse effects early on. Once the patient has tolerated the initial dose, the antidepressant can be gradually increased until a therapeutic dose or therapeutic effect is reached. A positive clinical effect may occur at any time but often takes 6 or more weeks to achieve.
Benzodiazepines may be used for acute relief of anxiety but can create dependence and a desire for increasing levels that limit their benefit/risk ratio for chronic use (10). They are often used in conjunction with an antidepressant and psychotherapy. The benzodiazepine can often be tapered once the anxiety symptoms have improved.
Treatment of comorbidities
When present, comorbid substance use disorders and other psychiatric conditions must also be appropriately managed.
Comorbid substance use disorders are often not spontaneously reported (11). Substances such as alcohol, marijuana, and benzodiazepines are often used to self-medicate by those with anxiety disorders. Patients may be reluctant to give up these substances until they trust that the clinician has a viable alternative treatment. Self-medication often leads to a vicious cycle. For example, the alcohol use that quickly reduces anxiety may be followed by rebound anxiety, followed by an increased urgency to self-medicate.
Comorbid bipolar disorder can cause specific management difficulties. Many people with bipolar disorder are initially misdiagnosed, particularly because they often have far more periods of depression than mania. Treatment with an antidepressant medication may be an appropriate first-line treatment for an anxiety disorder with comorbid major depression. However, for an individual with both anxiety and a bipolar disorder, that same medication choice can trigger a manic episode consisting of intensified anxiety and irritability. A missed bipolar disorder can result in decades of inappropriate treatments.
Comorbid medical disorders can also be challenging to manage. For example, asthma can physiologically cause anxiety, but so can some of the medications used to treat asthma. Anxiety can contribute to an asthma exacerbation, and fears of an asthma exacerbation can lead to avoidance behaviors (eg, diminished activity, medication nonadherence) that in turn can exacerbate asthma and lead to a diminished quality of life.
Treatment references
1. Chellappa SL, Aeschbach D: Sleep and anxiety: From mechanisms to interventions. Sleep Med Rev61:101583, 2022. doi: 10.1016/j.smrv.2021.101583
2. Bandelow B, Michaelis S, Wedekind D: Treatment of anxiety disorders. Dialogues Clin Neurosci 19(2):93-107, 2017. doi: 10.31887/DCNS.2017.19.2/bbandelow
3. Cuijpers P, Sijbrandij M, Koole SL, et al: Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta-analysis. World Psychiatry, 13(1), 56-67, 2014.doi: 10.1002/wps.20089
4. Szuhany KL, Simon NM: Anxiety disorders: A review. JAMA 328(24):2431-2445, 2022. doi: 10.1001/jama.2022.22744
5. Haller H, Breilmann P, Schröter, M. et al: A systematic review and meta-analysis of acceptance- and mindfulness-based interventions for DSM-5 anxiety disorders. Sci Rep 11(1):20385, 2021. doi: 10.1038/s41598-021-99882-w
6. Valentine KE, Milling LS, Clark LJ, et al: The efficacy of hypnosis as a treatment for anxiety: A meta-analysis. Int J Clin Exp Hyposis 67(3)336-363, 2019. doi: 10.1080/00207144.2019.1613863
7. Barber JP, Milrod B, Gallop R, et al: Processes of therapeutic change: Results from the Cornell-Penn Study of Psychotherapies for Panic Disorder. J Couns Psychol 67(2):222-231, 2020. doi: 10.1037/cou0000417
8. Markowitz JC, Milrod B, Luyten P, et al: Mentalizing in interpersonal psychotherapy. Am J Psychother 72(4):95-100. 2019. doi: 10.1176/appi.psychotherapy.20190021
9. Slee A, Nazareth I, Bondaronek P, et al: Pharmacological treatments for generalised anxiety disorder: A systematic review and network meta-analysis. Lancet 2019393(10173):768-777. doi: 10.1016/S0140-6736(18)31793-8
10. Balon R, Starcevic V: Role of benzodiazepines in anxiety disorders. Adv Exp Med Biol 1191:367-388, 2020. doi: 10.1007/978-981-32-9705-0_20
11. Anker JJ, Kushner MG: Co-occurring alcohol use disorder and anxiety: Bridging psychiatric, psychological, and neurobiological perspectives. Alcohol Res 40(1):arcr.v40.1.03, 2019. doi: 10.35946/arcr.v40.1.03
