Generalized anxiety disorder

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The relationship between genetics and anxiety disorders is an ongoing area of research.{{Cite journal|last1=Craske|first1=Michelle G.|last2=Stein|first2=Murray B.|date=December 17, 2016|title=Anxiety|journal=Lancet|volume=388|issue=10063|pages=3048–3059|doi=10.1016/S0140-6736(16)30381-6|issn=1474-547X|pmid=27349358|s2cid=208789585}} It is broadly understood that there exists a hereditary basis for GAD, but the exact nature of this hereditary basis is not fully understood.  While investigators have identified several genetic loci that are regions of interest for further study, there is no singular gene or set of genes that have been identified as causing GAD.  Nevertheless, genetic factors may play a role in determining whether an individual is at greater risk for developing GAD,{{Cite book|url=http://link.springer.com/10.1007/978-3-030-30687-8|title=Clinical Handbook of Anxiety Disorders: From Theory to Practice|date=2020|publisher=Springer International Publishing|isbn=978-3-030-30686-1|editor-last=Bui|editor-first=Eric|series=Current Clinical Psychiatry|location=Cham|language=en|doi=10.1007/978-3-030-30687-8|s2cid=209509839|editor-last2=Charney|editor-first2=Meredith E.|editor-last3=Baker|editor-first3=Amanda W.}} structural changes in the brain related to GAD, or whether an individual is more or less likely to respond to a particular treatment modality.  Genetic factors that may play a role in development of GAD are usually discussed in view of environmental factors (e.g., life experience or ongoing stress) that might also play a role in development of GAD.{{Cite journal|last1=Hettema|first1=J. M.|last2=Neale|first2=M. C.|last3=Kendler|first3=K. S.|date=October 2001|title=A review and meta-analysis of the genetic epidemiology of anxiety disorders|journal=The American Journal of Psychiatry|volume=158|issue=10|pages=1568–1578|doi=10.1176/appi.ajp.158.10.1568|issn=0002-953X|pmid=11578982}} The traditional methods of investigating the possible hereditary basis of GAD include using family studies and twin studies (there are no known adoption studies of individuals who have anxiety disorders, including GAD). Meta-analysis of family and twin studies suggests that there is strong evidence of a hereditary basis for GAD in that GAD is more likely to occur in first-degree relatives of individuals who have GAD than in non-related individuals in the same population. Twin studies also suggest that there may be a genetic linkage between GAD and major depressive disorder (MDD), which may explain the common occurrence of MDD in individuals who have GAD (e.g., comorbidity of MDD in individuals with GAD has been estimated at 60%{{Cite journal|last1=Hall|first1=Jo|last2=Kellett|first2=Stephen|last3=Berrios|first3=Raul|last4=Bains|first4=Manreesh Kaur|last5=Scott|first5=Shonagh|date=November 2016|title=Efficacy of Cognitive Behavioral Therapy for Generalized Anxiety Disorder in Older Adults: Systematic Review, Meta-Analysis, and Meta-Regression|journal=The American Journal of Geriatric Psychiatry|volume=24|issue=11|pages=1063–1073|doi=10.1016/j.jagp.2016.06.006|issn=1545-7214|pmid=27687212|url=http://eprints.whiterose.ac.uk/102819/5/GAD-OA-META.pdf }}).{{Cite journal|last1=Kessler|first1=R. C.|last2=DuPont|first2=R. L.|last3=Berglund|first3=P.|last4=Wittchen|first4=H. U.|date=December 1999|title=Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys|journal=The American Journal of Psychiatry|volume=156|issue=12|pages=1915–1923|doi=10.1176/ajp.156.12.1915|issn=0002-953X|pmid=10588405|s2cid=6527201 }} When GAD is considered among all anxiety disorders (e.g., panic disorder, social anxiety disorder), genetic studies suggest that hereditary contribution to the development of anxiety disorders amounts to only approximately 30–40%, which suggests that environmental factors are likely more important to determining whether an individual may develop GAD. In regard to environmental influences in the development of GAD, it has been suggested that parenting behaviour may be an important influence since parents potentially model anxiety-related behaviours. It has also been suggested that individuals with GAD have experienced a greater number of minor stress-related events in life and that the number of stress-related events may be important in development of GAD (irrespective of other individual characteristics). Further research on the life context and social factors of individuals with GAD has provided greater insight into the influence of interpersonal relationships, with one study noting strong associations between partner abuse in women with the anxiety apparent in GAD.{{Cite journal |last1=Tait |first1=Lynda |last2=Berrisford |first2=Giles |date=2011-06-01 |title=Generalised anxiety disorder: the importance of life context and social factors |url=https://bjgp.org/content/61/587/378 |journal=British Journal of General Practice |language=en |volume=61 |issue=587 |pages=378–379 |doi=10.3399/bjgp11X572625 |issn=0960-1643 |pmid=21801521|pmc=3103673 }} Thus, strained or stressful social relationships, as evidenced by abusive partners, display some association with the emergence of anxiety as a symptom of GAD.

Studies of possible genetic contributions to the development of GAD have examined relationships between genes implicated in brain structures involved in identifying potential threats (e.g., in the amygdala) and also implicated in neurotransmitters and neurotransmitter receptors known to be involved in anxiety disorders.{{Cite journal|last1=Perna|first1=Giampaolo|last2=Alciati|first2=Alessandra|last3=Riva|first3=Alice|last4=Micieli|first4=Wilma|last5=Caldirola|first5=Daniela|date=March 2016|title=Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review|journal=Current Psychiatry Reports|volume=18|issue=3|page=23|doi=10.1007/s11920-016-0668-3|issn=1535-1645|pmid=26830881|s2cid=24141971}} More specifically, genes studied for their relationship to development of GAD or demonstrated to have had a relationship to treatment response include:

• PACAP (A54G polymorphism): remission after 6-month treatment with Venlafaxine suggested to have a significant relationship with the A54G polymorphism (Cooper et al. (2013))
• HTR2A gene (rs7997012 SNP G allele): HTR2A allele suggested to be implicated in a significant decrease in anxiety symptoms associated with response to six months of Venlafaxine treatment (Lohoff et al. (2013))
• SLC6A4 promoter region (5-HTTLPR): Serotonin transporter gene suggested to be implicated in significant reduction in anxiety symptoms in response to six months of Venlafaxine treatment (Lohoff et al. (2013))

{{See also|Screen time|Binge-watching|Fear of missing out|Internet addiction disorder|Nomophobia|Problematic smartphone use|Problematic social media use|Television addiction|Video game addiction}}

{{Excerpt|Digital media use and mental health|Anxiety}}

File:Amygdala_small.gif

The pathophysiology of GAD is an active and ongoing area of research often involving the intersection of genetics and neurological structures. GAD has been linked to changes in functional connectivity of the amygdala and its processing of fear and anxiety.{{cite journal|last1=Etkin|first1=Amit|last2=Prater|first2=Katherine E.|last3=Schatzberg|first3=Alan F.|last4=Menon|first4=Vinod|last5=Greicius|first5=Michael D.|year=2009|title=Disrupted Amygdalar Subregion Functional Connectivity and Evidence of a Compensatory Network in Generalized Anxiety Disorder|journal=Archives of General Psychiatry|volume=66|issue=12|pages=1361–72|doi=10.1001/archgenpsychiatry.2009.104|pmid=19996041|doi-access=free}} Sensory information enters the amygdala through the nuclei of the basolateral complex (consisting of lateral, basal and accessory basal nuclei). The basolateral complex processes the sensory-related fear memories and communicates information regarding threat importance to memory and sensory processing elsewhere in the brain, such as the medial prefrontal cortex and sensory cortices. Neurological structures traditionally appreciated for their roles in anxiety include the amygdala, insula and orbitofrontal cortex (OFC). It is broadly postulated that changes in one or more of these neurological structures are believed to allow greater amygdala response to emotional stimuli in individuals who have GAD as compared to individuals who do not have GAD.

Individuals with GAD have been suggested to have greater amygdala and medial prefrontal cortex (mPFC) activation in response to stimuli than individuals who do not have GAD. However, the exact relationship between the amygdala and the frontal cortex (e.g., prefrontal cortex or the orbitofrontal cortex [OFC]) is not fully understood because there are studies that suggest increased or decreased activity in the frontal cortex in individuals who have GAD. Consequently, because of the tenuous understanding of the frontal cortex as it relates to the amygdala in individuals who have GAD, it's an open question as to whether individuals who have GAD bear an amygdala that is more sensitive than an amygdala in an individual without GAD or whether frontal cortex hyperactivity is responsible for changes in amygdala responsiveness to various stimuli. Recent studies have attempted to identify specific regions of the frontal cortex (e.g., dorsomedial prefrontal cortex [dmPFC]) that may be more or less reactive in individuals who have GAD or specific networks that may be differentially implicated in individuals who have GAD. Other lines of study investigate whether activation patterns vary in individuals who have GAD at different ages with respect to individuals who do not have GAD at the same age (e.g., amygdala activation in adolescents with GAD).

From an evolutionary perspective, generalized anxiety can be viewed as an overextension of the protective mechanisms that help organisms avoid danger. Cost–benefit analyses, sometimes referred to as the “smoke detector principle,”{{Cite journal |last=Nesse |first=Randolph M |date=2019-01-01 |title=The smoke detector principle |url=https://academic.oup.com/emph/article/2019/1/1/5229271 |journal=Evolution, Medicine, and Public Health |language=en |volume=2019 |issue=1 |pages=1 |doi=10.1093/emph/eoy034 |pmid=30697424 |pmc=6343816 |issn=2050-6201|hdl=2027.42/75092 |hdl-access=free }} propose that false alarms (unnecessary worry) are less costly than failing to detect real threats. As a result, having a relatively low threshold for perceiving danger may have historically conferred survival benefits. In individuals with GAD, however, this adaptive threshold appears to be set too low or activated too often, generating pervasive worry about routine events and relatively minor stressors.{{Cite book |last=Nesse |first=Randolph M. |title=Good reasons for bad feelings: insights from the frontier of evolutionary psychiatry |date=2020 |publisher=Penguin Books |isbn=978-0-14-198491-9 |location=London}}

Empirical work supports the idea that GAD involves heightened reactivity in brain regions associated with threat detection, including the amygdala. Researchers have also found links between GAD and elevated inflammation markers, suggesting a possible physiological correlate for the chronic anxiety seen in the disorder. Although anxiety's defensive functions may have been advantageous in unpredictable environments, modern contexts can render this vigilance maladaptive when it persists as near-constant worry and avoidance. This view places GAD at the extreme end of a continuum, where otherwise beneficial anxiety responses overshoot, leading to significant distress and functional impairment.{{Cite book |last=Del Giudice |first=Marco |title=Evolutionary psychopathology: a unified approach |date=2018 |publisher=Oxford University Press |isbn=978-0-19-024684-6 |location=New York, NY}}

The diagnostic criteria for GAD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), published by the American Psychiatric Association, are paraphrased as follows:{{ordered list|"Excessive anxiety or worry" experienced most days over at least six months and which involve a plurality of concerns.|Inability to manage worry.|At least three of the following occur:

{{ordered list

|1=Restlessness

|2=Fatigability

|3=Problems concentrating

|4=Irritability

|5=Muscle tension

|6=Difficulty with sleep

}}

Note that in children, only one of the above items is required.|One experiences significant distress in functioning (e.g., work, school, social life).|Symptoms are not due to a substance use disorder, prescription medication, or other medical condition(s).|Symptoms do not fit better with another psychiatric condition such as panic disorder.

| list_style_type = upper-alpha

}}No major changes to GAD have occurred since publication of the Diagnostic and Statistical Manual of Mental Disorders (2004); minor changes include wording of diagnostic criteria.{{cite journal |last1=Möller |first1=Hans-Jürgen |last2=Bandelow |first2=Borwin |last3=Bauer |first3=Michael |last4=Hampel |first4=Harald |last5=Herpertz |first5=Sabine C. |last6=Soyka |first6=Michael |last7=Barnikol |first7=Utako B. |last8=Lista |first8=Simone |last9=Severus |first9=Emanuel |last10=Maier |first10=Wolfgang |date=26 August 2014 |title=DSM-5 reviewed from different angles: goal attainment, rationality, use of evidence, consequences—part 2: bipolar disorders, schizophrenia-spectrum disorders, anxiety disorders, obsessive–compulsive disorders, trauma- and stressor-related disorders, personality disorders, substance-related and addictive disorders, neurocognitive disorders |journal=European Archives of Psychiatry and Clinical Neuroscience |volume=265 |issue=2 |pages=87–106 |doi=10.1007/s00406-014-0521-9 |pmid=25155875 |s2cid=24165894}}

The 10th revision of the International Statistical Classification of Disease (ICD-10) provides a different set of diagnostic criteria for GAD than the DSM-5 criteria described above. In particular, ICD-10 allows diagnosis of GAD as follows:

{{ordered list

| list_style_type = upper-alpha

| 1 = A period of at least six months with prominent tension, worry, and feelings of apprehension, about everyday events and problems.

| 2 = 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 the stomach).

;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 flashes 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.

;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.

| 3 = The disorder does not meet the criteria for panic disorder (F41.0), phobic anxiety disorders (F40.-), obsessive-compulsive disorder (F42.-) or hypochondriacal disorder (F45.2).

| 4 = 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.International Classification of Diseases) ICD-10

}}[http://apps.who.int/classifications/icd10/browse/2010/en#/F41.1 See ICD-10 F41.1]{{cite web |title=The ICD-10 Classification of Mental and Behavioural Disorders |url=https://www.who.int/classifications/icd/en/bluebook.pdf |publisher=WHO}} Note: For children different ICD-10 criteria may be applied for diagnosing GAD (see F93.80).

Traditional treatment modalities broadly fall into two categories, i.e., psychotherapeutic and pharmacological intervention. In addition to these two conventional therapeutic approaches, areas of active investigation include complementary and alternative medications (CAMs), brain stimulation, exercise, therapeutic massage, balneotherapy and other interventions that have been proposed for further study.{{Cite journal|last1=Barić|first1=Hrvoje|last2=Đorđević|first2=Veljko|last3=Cerovečki|first3=Ivan|last4=Trkulja|first4=Vladimir|date=2018-03-01|title=Complementary and Alternative Medicine Treatments for Generalized Anxiety Disorder: Systematic Review and Meta-analysis of Randomized Controlled Trials|journal=Advances in Therapy|language=en|volume=35|issue=3|pages=261–288|doi=10.1007/s12325-018-0680-6|pmid=29508154|s2cid=3939726|issn=1865-8652}} MindMed’s MM120 (a form of lysergic acid diethylamide; LSD) is also being investigated in clinical settings after it showed strong, lasting anxiety relief after one dose in a Phase 2b trial, earning FDA breakthrough status and advancing to Phase 3 in 2024.{{Cite web |date=2024-03-07 |title=MindMed Receives FDA Breakthrough Therapy Designation and Announces Positive 12-Week Durability Data From Phase 2B Study of MM120 for Generalized Anxiety Disorder |url=https://ir.mindmed.co/news-events/press-releases/detail/137/mindmed-receives-fda-breakthrough-therapy-designation-and-announces-positive-12-week-durability-data-from-phase-2b-study-of-mm120-for-generalized-anxiety-disorder?utm_ |access-date=2025-05-22 |website=Mind Medicine (MindMed) Inc. |language=en}} Treatment modalities can, and often are, utilized concurrently so that an individual may pursue psychological therapy (i.e., psychotherapy) and pharmacological therapy.{{Cite journal|last1=Hunot|first1=V.|last2=Churchill|first2=R.|last3=Silva de Lima|first3=M.|last4=Teixeira|first4=V.|date=2007-01-24|title=Psychological therapies for generalised anxiety disorder|journal=The Cochrane Database of Systematic Reviews|volume=2007 |issue=1|pages=CD001848|doi=10.1002/14651858.CD001848.pub4|issn=1469-493X|pmc=7025441|pmid=17253466}} Both cognitive behavioral therapy (CBT) and medications (such as SSRIs) have been shown to be effective in reducing anxiety.{{Cite journal |title=Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options |url=https://vitaliboost.com/journal/pharmacotherapy-of-anxiety-disorders-current-and-emerging-treatment-options/ |journal=Journal of Health & Wellness|date=13 July 2023 }} A combination of both CBT and medication is generally seen as the most desirable approach to treatment.{{cite journal|last1=Bandelow|first1=Borwin|last2=Sher|first2=Leo|last3=Bunevicius|first3=Robertas|last4=Hollander|first4=Eric|last5=Kasper|first5=Siegfried|last6=Zohar|first6=Joseph|last7=Möller|first7=Hans-Jürgen|date=June 2012|title=Guidelines for the pharmacological treatment of anxiety disorders, obsessive–compulsive disorder and posttraumatic stress disorder in primary care|url=http://www.wfsbp.org/fileadmin/user_upload/Treatment_Guidelines/Bandelow_et_al_01.pdf|journal=International Journal of Psychiatry in Clinical Practice|volume=16|issue=2|pages=77–84|doi=10.3109/13651501.2012.667114|pmid=22540422|access-date=24 November 2015|s2cid=16253034|archive-date=3 April 2018|archive-url=https://web.archive.org/web/20180403134713/http://www.wfsbp.org/fileadmin/user_upload/Treatment_Guidelines/Bandelow_et_al_01.pdf|url-status=dead}} Use of medication to lower extreme anxiety levels can be important in enabling patients to engage effectively in CBT.{{cn|date=February 2024}}

Psychotherapeutic interventions{{Cite journal|last1=Strawn|first1=Jeffrey R.|last2=Geracioti|first2=Laura|last3=Rajdev|first3=Neil|last4=Clemenza|first4=Kelly|last5=Levine|first5=Amir|date=July 2018|title=Pharmacotherapy for generalized anxiety disorder in adult and pediatric patients: an evidence-based treatment review|journal=Expert Opinion on Pharmacotherapy|volume=19|issue=10|pages=1057–1070|doi=10.1080/14656566.2018.1491966|issn=1744-7666|pmc=6340395|pmid=30056792}} include a plurality of therapy types that vary based upon their specific methodologies for enabling individuals to gain insight into the working of the conscious and subconscious mind and which sometimes focus on the relationship between cognition and behavior.{{Cite book|title=Clinical handbook of anxiety disorders: from theory to practice|date=2020|publisher=Humana Press|vauthors=Bui E, Charney, Meredith E, Baker, Amanda W|isbn=978-3-030-30687-8|location=Cham|oclc=1134852696}} Cognitive behavioral therapy (CBT) is widely regarded as the first-line psychological therapy for treating GAD. Additionally, many of these psychological interventions may be delivered in an individual or group therapy setting. While individual and group settings are broadly both considered effective for treating GAD, individual therapy tends to promote longer-lasting engagement in therapy (i.e., lower attrition over time).

For children, the role of the parent is important. They serve as co-therapists who make sure the tasks set by the therapists are implemented and for giving children positive reinforcement throughout the tasks. The "transfer of control" model highlights the growing responsibility of the parents as the role of the therapist fades away. {{Cite journal |last1=King |first1=Neville J. |last2=Heyne |first2=David |last3=Ollendick |first3=Thomas H. |date=2005 |title=Cognitive-Behavioral Treatments for Anxiety and Phobic Disorders in Children and Adolescents: A Review |url=https://www.jstor.org/stable/43153784 |journal=Behavioral Disorders |volume=30 |issue=3 |pages=241–257 |doi=10.1177/019874290503000304 |jstor=43153784 |issn=0198-7429|url-access=subscription }}

Psychodynamic therapy is a type of therapy premised upon Freudian psychology in which a psychologist enables an individual explore various elements in their subconscious mind to resolve conflicts that may exist between the conscious and subconscious elements of the mind.{{Cite journal|last1=Wehry|first1=Anna M.|last2=Beesdo-Baum|first2=Katja|last3=Hennelly|first3=Meghann M.|last4=Connolly|first4=Sucheta D.|last5=Strawn|first5=Jeffrey R.|date=July 2015|title=Assessment and treatment of anxiety disorders in children and adolescents|journal=Current Psychiatry Reports|volume=17|issue=7|page=52|doi=10.1007/s11920-015-0591-z|issn=1535-1645|pmc=4480225|pmid=25980507}} In the context of GAD, the psychodynamic theory of anxiety suggests that the unconscious mind engages in worry as a defense mechanism to avoid feelings of anger or hostility because such feelings might cause social isolation or other negative attribution toward oneself. Accordingly, the various psychodynamic therapies attempt to explore the nature of worry as it functions in GAD in order to enable individuals to alter the subconscious practice of using worry as a defense mechanism and to thereby diminish GAD symptoms. Variations of psychotherapy include a near-term version of therapy, "short-term anxiety-provoking psychotherapy (STAPP).

Behavioral therapy is therapeutic intervention premised upon the concept that anxiety is learned through classical conditioning (e.g., in view of one or more negative experiences) and maintained through operant conditioning (e.g., one finds that by avoiding a feared experience that one avoids anxiety). Thus, behavioral therapy enables an individual to re-learn conditioned responses (behaviors) and to thereby challenge behaviors that have become conditioned responses to fear and anxiety, and which have previously given rise to further maladaptive behaviors.

Cognitive therapy (CT) is premised upon the idea that anxiety is the result of maladaptive beliefs and methods of thinking. Thus, CT involves assisting individuals to identify more rational ways of thinking and to replace maladaptive thinking patterns (i.e., cognitive distortions) with healthier thinking patterns (e.g., replacing the cognitive distortion of catastrophizing with a more productive pattern of thinking). Individuals in CT learn how to identify objective evidence, test hypotheses, and ultimately identify maladaptive thinking patterns so that these patterns can be challenged and replaced.

Acceptance and commitment therapy (ACT) is a behavioral treatment based on acceptance-based models. ACT is designed with the purpose to target three therapeutic goals: (1) reduce the use of avoiding strategies intended to avoid feelings, thoughts, memories, and sensations; (2) decreasing a person's literal response to their thoughts (e.g., understanding that thinking "I'm hopeless" does not mean that the person's life is truly hopeless), and (3) increasing the person's ability to keep commitments to changing their behaviors. These goals are attained by switching the person's attempt to control events to working towards changing their behavior and focusing on valued directions and goals in their lives as well as committing to behaviors that help the individual accomplish those personal goals.{{cite journal|last1=Roemer|first1=Lizabeth|last2=Orsillo|first2=Susan M.|year=2006|title=Expanding Our Conceptualization of and Treatment for Generalized Anxiety Disorder: Integrating Mindfulness/Acceptance-Based Approaches with Existing Cognitive-Behavioral Models|journal=Clinical Psychology: Science and Practice|volume=9|pages=54–68|doi=10.1093/clipsy.9.1.54|s2cid=33507029}} This psychological therapy teaches mindfulness (paying attention on purpose, in the present, and in a nonjudgmental manner) and acceptance (openness and willingness to sustain contact) skills for responding to uncontrollable events and therefore manifesting behaviors that enact personal values.{{cite journal|last1=Smout|first1=M|year=2012|title=Acceptance and commitment therapy - pathways for general practitioners|journal=Australian Family Physician|volume=41|issue=9|pages=672–6|pmid=22962641}}

Intolerance of uncertainty (IU) refers to a consistent negative reaction to uncertain and ambiguous events regardless of their likelihood of occurrence. Intolerance of uncertainty therapy (IUT) is used as a stand-alone treatment for GAD patients. Thus, IUT focuses on helping patients in developing the ability to tolerate, cope with and accept uncertainty in their life in order to reduce anxiety. IUT is based on the psychological components of psychoeducation, awareness of worry, problem-solving training, re-evaluation of the usefulness of worry, imagining virtual exposure, recognition of uncertainty, and behavioral exposure. Studies have shown support for the efficacy of this therapy with GAD patients with continued improvements in follow-up periods.{{cite journal|last1=Hoyer|first1=Jürgen|last2=van der Heiden|first2=Colin|last3=Portman|first3=Michael E.|date=February 2011|title=Psychotherapy for Generalized Anxiety Disorder|journal=Psychiatric Annals|volume=41|issue=2|pages=87–94|doi=10.3928/00485713-20110203-07}}

A promising innovative approach to improving recovery rates for the treatment of GAD is to combine CBT with motivational interviewing (MI). Motivational interviewing is a strategy centered on the patient that aims to increase intrinsic motivation and decrease ambivalence about change due to the treatment. MI contains four key elements: (1) express empathy, (2) heighten dissonance between behaviors that are not desired and values that are not consistent with those behaviors, (3) move with resistance rather than direct confrontation, and (4) encourage self-efficacy. It is based on asking open-ended questions and listening carefully and reflectively to patients' answers, eliciting "change talk", and talking with patients about the pros and cons of change. Some studies have shown the combination of CBT with MI to be more effective than CBT alone.

Cognitive behavioral therapy (CBT) is an evidence-based type of psychotherapy that demonstrates efficacy in treating GAD and which integrates the cognitive and behavioral therapeutic approaches. The objective of CBT is to enable individuals to identify irrational thoughts that cause anxiety and to challenge dysfunctional thinking patterns by engaging in awareness techniques such as hypothesis testing and journaling. Because CBT involves the practice of worry and anxiety management, CBT includes a plurality of intervention techniques that enable individuals to explore worry, anxiety and automatic negative thinking patterns. These interventions include anxiety management training, cognitive restructuring,{{Cite journal|last1=Gould|first1=Robert A.|last2=Otto|first2=Michael W.|last3=Pollack|first3=Mark H.|last4=Yap|first4=Liang|date=1997|title=Cognitive behavioral and pharmacological treatment of generalized anxiety disorder: A preliminary meta-analysis|journal=Behavior Therapy|language=en|volume=28|issue=2|pages=285–305|doi=10.1016/S0005-7894(97)80048-2}} progressive relaxation, situational exposure and self-controlled desensitization. Several modes of delivery are effective in treating GAD, including internet-delivered CBT, or iCBT.{{Cite journal |title=Internet-Delivered Cognitive Behavioral Therapy for Generalized Anxiety Disorder in Nationwide Routine Care: Effectiveness Study |journal=Journal of Medical Internet Research |year=2022 |language=en |doi=10.2196/29384|last1=Ritola |first1=Ville |last2=Lipsanen |first2=Jari Olavi |last3=Pihlaja |first3=Satu |last4=Gummerus |first4=Eero-Matti |last5=Stenberg |first5=Jan-Henry |last6=Saarni |first6=Suoma |last7=Joffe |first7=Grigori |volume=24 |issue=3 |pages=e29384 |pmid=35323119 |pmc=8990365 |doi-access=free }}

Emotion-focused therapy (EFT) is a short-term psychotherapy that is focused on humanistic needs of emotions when treating individuals with GAD. EFT can incorporate numerous practices such as experimental therapy, systemic therapy, and elements of CBT to allow individuals to work through difficult emotional states.{{Cite journal |last1=Timulak |first1=Ladislav |last2=Keogh |first2=Daragh |last3=Chigwedere |first3=Craig |last4=Wilson |first4=Charlotte |last5=Ward |first5=Fiona |last6=Hevey |first6=David |last7=Griffin |first7=Patrick |last8=Jacobs |first8=Louise |last9=Hughes |first9=Suzanne |last10=Vaughan |first10=Christina |last11=Beckham |first11=Kea |date=March 2022 |title=A comparison of emotion-focused therapy and cognitive-behavioral therapy in the treatment of generalized anxiety disorder: Results of a feasibility randomized controlled trial. |url=http://doi.apa.org/getdoi.cfm?doi=10.1037/pst0000427 |journal=Psychotherapy |language=en |volume=59 |issue=1 |pages=84–95 |doi=10.1037/pst0000427 |pmid=35113639 |hdl=2262/98065 |s2cid=246530249 |issn=1939-1536|hdl-access=free }} The primary goal of EFT is assisting individuals in living with their vulnerable emotions and overcoming avoidance so that adaptive experiences such as compassion and protective anger can be generated in response to the emotional needs that are embedded in core emotional vulnerability.

Sandplay therapy (SPT) is an intervention based on nonverbal therapeutic practices. The main objective of SPT is to allow the individual the ability to work through their emotional problems from childhood traumas (CT) through play using sand and toy figures.{{Cite journal |last1=Foo |first1=Mariana |last2=Freedle |first2=Lorraine R. |last3=Sani |first3=Riryn |last4=Fonda |first4=Grace |date=October 2020 |title=The effect of sandplay therapy on the thalamus in the treatment of generalized anxiety disorder: A case report. |url=http://doi.apa.org/getdoi.cfm?doi=10.1037/pla0000137 |journal=International Journal of Play Therapy |language=en |volume=29 |issue=4 |pages=191–200 |doi=10.1037/pla0000137 |s2cid=224903536 |issn=1939-0629|url-access=subscription }} Although the therapy is mainly focused on nonverbal cues, verbal cues are also observed and documented during the rehabilitation process of the individual.{{Cite journal |last1=Foo |first1=Mariana |last2=Pratiwi |first2=Anggun |date=July 2021|title=The effectiveness of sandplay therapy in treating generalized anxiety disorder patients with childhood trauma using magnetic resonance spectroscopy to examine choline level in the dorsolateral prefrontal cortex and centrum semiovale. |url=http://doi.apa.org/getdoi.cfm?doi=10.1037/pla0000162 |journal=International Journal of Play Therapy |language=en |volume=30 |issue=3 |pages=177–186 |doi=10.1037/pla0000162 |s2cid=236233712 |issn=1939-0629|url-access=subscription }} SPT allows a multi-sensory experience through a safe and protected space allowing the individual the opportunity to regulate their mind and emotions. This therapeutic practice is offered in both adults and children.

There is empirical evidence that exposure therapy can be an effective treatment for people with GAD, citing specifically in vivo exposure therapy (exposure through a real-life situation),{{Cite journal | vauthors = Kaplan JS, Tolin DF |title=Exposure Therapy for Anxiety Disorders|url=https://www.psychiatrictimes.com/view/exposure-therapy-anxiety-disorders|access-date=2021-09-22|journal=Psychiatric Times |date=6 September 2011 |volume=28 |issue=9 }} which has greater effectiveness than imaginal exposure in regards to generalized anxiety disorder. The aim of in vivo exposure treatment is to promote emotional regulation using systematic and controlled therapeutic exposure to traumatic stimuli.{{cite journal | vauthors = Parsons TD, Rizzo AA | title = Affective outcomes of virtual reality exposure therapy for anxiety and specific phobias: a meta-analysis | journal = Journal of Behavior Therapy and Experimental Psychiatry | volume = 39 | issue = 3 | pages = 250–261 | date = September 2008 | pmid = 17720136 | doi = 10.1016/j.jbtep.2007.07.007 | s2cid = 6688068 }} Exposure is used to promote fear tolerance."Instead of teaching patients to resist, control or "fix" their fear or anxiety, exposure is used to promote 'fear tolerance' given that fear and anxiety are universal, inevitable and safe." Exposure Therapy for Anxiety, Second Edition (2019), p18, Abramowitz, Deacon and Whiteside

Exposure therapy is also a preferred method for children who struggle with anxiety.{{cite journal | vauthors = Whiteside SP, Deacon BJ, Benito K, Stewart E | title = Factors associated with practitioners' use of exposure therapy for childhood anxiety disorders | journal = Journal of Anxiety Disorders | volume = 40 | pages = 29–36 | date = May 2016 | pmid = 27085463 | pmc = 4868775 | doi = 10.1016/j.janxdis.2016.04.001 }} Children also typically prefer using a group format for exposure therapy treatment. This allows for peer learning and the opportunity to develop social skills. {{Cite journal |last1=King |first1=Neville J. |last2=Heyne |first2=David |last3=Ollendick |first3=Thomas H. |date=2005 |title=Cognitive-Behavioral Treatments for Anxiety and Phobic Disorders in Children and Adolescents: A Review |url=https://www.jstor.org/stable/43153784 |journal=Behavioral Disorders |volume=30 |issue=3 |pages=241–257 |doi=10.1177/019874290503000304 |jstor=43153784 |issn=0198-7429|url-access=subscription }}

• Relaxation techniques (e.g., relaxing imagery, meditational relaxation)
• Metacognitive therapy (MCT): The objective of MCT is to alter thinking patterns regarding worry so that worry is no longer used as a coping strategy. It has promising results in treatment of GAD as well as other mental issues.{{Cite journal|last1=Behar|first1=Evelyn|last2=DiMarco|first2=Ilyse Dobrow|last3=Hekler|first3=Eric B.|last4=Mohlman|first4=Jan|last5=Staples|first5=Alison M.|date=December 2009|title=Current theoretical models of generalized anxiety disorder (GAD): conceptual review and treatment implications|journal=Journal of Anxiety Disorders|volume=23|issue=8|pages=1011–1023|doi=10.1016/j.janxdis.2009.07.006|issn=1873-7897|pmid=19700258|s2cid=10962212 }}
• Mindfulness based stress reduction (MBSR)
• Mindfulness based cognitive therapy (MBCT): The goal of MBCT is to be used as an alternative or adjunctive to Cognitive Behavior Therapy (CBT).{{cite book |last1=Evans |first1=Susan |title=Mindfulness-Based Cognitive Therapy |chapter=Mindfulness-Based Cognitive Therapy for Generalized Anxiety Disorder |date=2016 |pages=145–154 |publisher=Springer |location=Cham |doi=10.1007/978-3-319-29866-5_13 |isbn=978-3-319-29864-1}}
• Supportive therapy: This is a Rogerian method of therapy in which subjects experience empathy and acceptance from their therapist to facilitate increasing awareness. Variations of active supportive therapy include Gestalt therapy, Transactional analysis and Counseling.
• Internet-delivered interpretation training: The focus of this training is to reduce worry and anxiety while promoting positive outcomes and positive interpretations.{{Cite journal |last1=Hirsch |first1=Colette R. |last2=Krahé |first2=Charlotte |last3=Whyte |first3=Jessica |last4=Krzyzanowski |first4=Hannah |last5=Meeten |first5=Frances |last6=Norton |first6=Sam |last7=Mathews |first7=Andrew |date=July 2021 |title=Internet-delivered interpretation training reduces worry and anxiety in individuals with generalized anxiety disorder: A randomized controlled experiment. |url=http://doi.apa.org/getdoi.cfm?doi=10.1037/ccp0000660 |journal=Journal of Consulting and Clinical Psychology |language=en |volume=89 |issue=7 |pages=575–589 |doi=10.1037/ccp0000660 |pmid=34383532 |s2cid=236998717 |issn=1939-2117}}

Medications that have been studied were reviewed in a recent network meta-analysis that compared all studied medications with placebo and also with each other {{cite journal | vauthors = Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N | title = Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis | journal = Lancet | volume = 393 | issue = 10173 | pages = 768–777 | year = 2019| pmid = 30712879| doi = 10.1016/S0140-6736(18)31793-8 | s2cid = 72332967 | url = https://discovery.ucl.ac.uk/id/eprint/10070219/ }} and another compared the rates of remission between different medications.{{cite journal | vauthors = Kong W, Deng H, Wan J, Zhou Y, Zhou Y, Song B, Wang X | title = Comparative Remission Rates and Tolerability of Drugs for Generalised Anxiety Disorder: A Systematic Review and Network Meta-analysis of Double-Blind Randomized Controlled Trials | journal = Front Pharmacol | volume = 11 | issue = 11| page = 580858 | year = 2019| pmid = 33343351 | doi = 10.3389/fphar.2020.580858 | pmc = 7741609 | doi-access = free }} Benzodiazepines (BZs) have been used to treat anxiety starting in the 1960s.{{Cite news|url=https://www.wsj.com/articles/an-anxious-history-of-valium-1384547451|title = An Anxious History of Valium|newspaper = Wall Street Journal|date = 16 November 2013|last1 = Cooper|first1 = Arnie}} There is a risk of dependence and tolerance to benzodiazepines.{{Cite journal|last=Ashton|first=Heather|date=May 2005|title=The diagnosis and management of benzodiazepine dependence|journal=Current Opinion in Psychiatry|volume=18|issue=3|pages=249–255|doi=10.1097/01.yco.0000165594.60434.84|issn=0951-7367|pmid=16639148|s2cid=1709063}} BZs have a number of effects that make them a good option for treating anxiety including anxiolytic, hypnotic (induce sleep), myorelaxant (relax muscles), anticonvulsant, and amnestic (impair short-term memory) properties. While BZs work well to alleviate anxiety shortly after administration, they are also known for their ability to promote dependence and are frequently used recreationally or non-medically. Antidepressants (e.g., SSRIs / SNRIs) have become a mainstay in treating GAD in adults. First-line medications from any drug category often include those that have been approved by the Food and Drug Administration (FDA) or other similar regulatory body such as the EMA or TGA for treating GAD because these drugs have been shown to be safe and effective.

FDA-approved medications for treating GAD include:Escitalopram Oxalate: Mechanism of Action. (2020). In Micromedex for iOS (Version No. 1.81.0b3005) [electronic version]. Retrieved 8 November 2020.Venlafaxine Hydrochloride: Mechanism of Action. (2020). In Micromedex for iOS (Version No. 1.81.0b3005) [electronic version]. Retrieved 8 November 2020.{{Cite journal|last1=Hidalgo|first1=Rosario B.|last2=Tupler|first2=Larry A.|last3=Davidson|first3=Jonathan R. T.|date=November 2007|title=An effect-size analysis of pharmacologic treatments for generalized anxiety disorder|journal=Journal of Psychopharmacology|volume=21|issue=8|pages=864–872|doi=10.1177/0269881107076996|issn=0269-8811|pmid=17984162|s2cid=27127585}}{{Excessive citations inline|date=September 2021}} {{ordered list|SSRIs

{{ordered list

|1=Paroxetine

|2=Escitalopram

}}|SNRIs

{{ordered list

|1=Venlafaxine

|2=Duloxetine

}}|Benzodiazepines

{{ordered list

|1=Alprazolam

}}|Azapirones

{{ordered list

|1=Buspirone

}}

|||list_style_type=upper-alpha}}

While certain medications are not specifically FDA approved for treatment of GAD, there are a number of medications that historically have been used or studied for treating GAD. Other medications that have been used or evaluated for treating GAD include:

• SSRIs
• Citalopram
• Fluoxetine
• Sertraline
• Fluvoxamine
• Benzodiazepines
• Clonazepam
• Lorazepam
• Diazepam
• GABA analogs
• Pregabalin{{Cite journal|last1=Strawn|first1=Jeffrey R.|last2=Geracioti|first2=Thomas D.|date=April 2007|title=The treatment of generalized anxiety disorder with pregabalin, an atypical anxiolytic|journal=Neuropsychiatric Disease and Treatment|volume=3|issue=2|pages=237–243|doi=10.2147/nedt.2007.3.2.237|issn=1176-6328|pmc=2654629|pmid=19300556 |doi-access=free }}{{Cite journal|last1=Generoso|first1=Marcelo B.|last2=Trevizol|first2=Alisson P.|last3=Kasper|first3=Siegfried|last4=Cho|first4=Hyong J.|last5=Cordeiro|first5=Quirino|last6=Shiozawa|first6=Pedro|date=January 2017|title=Pregabalin for generalized anxiety disorder: an updated systematic review and meta-analysis%2FYIC.0000000000000147|journal=International Clinical Psychopharmacology|language=en|volume=32|issue=1|pages=49–55|doi=10.1097/YIC.0000000000000147|pmid=27643884|s2cid=29623356|issn=0268-1315}}{{Excessive citations inline|date=September 2021}}
• Tiagabine
• Second-generation antipsychotics
• Olanzapine (evidence of effectiveness is merely a trend)
• Ziprasidone
• Risperidone
• Aripiprazole (studied as an adjunctive measure in concert with other treatment)
• Quetiapine (atypical antipsychotic studied as an adjunctive measure in adults and geriatric patients)
• Antihistamines
• Hydroxyzine (H₁ receptor antagonist)
• Mirtazapine (atypical antidepressant having 5-HT_2A and 5-HT_2C receptor affinity)
• Tricyclic antidepressants
• Amitriptyline
• Clomipramine
• Doxepin
• Imipramine
• Trimipramine
• Desipramine
• Nortriptyline
• Protriptyline
• Opipramol (atypical TCA)
• Trazodone
• Monoamine oxidase inhibitors (MAOIs)
• Tranylcypromine
• Phenelzine

Pharmaceutical treatments for GAD include selective serotonin reuptake inhibitors (SSRIs).[http://www.mayoclinic.com/health/generalized-anxiety-disorder/DS00502/DSECTION=8 "Generalized anxiety disorder"], Mayo Clinic. Accessed 29 May 2007. SSRIs increase serotonin levels through inhibition of serotonin reuptake receptors.{{Cite journal|last1=Carrasco|first1=J. L.|last2=Sandner|first2=C.|date=December 2005|title=Clinical effects of pharmacological variations in selective serotonin reuptake inhibitors: an overview|journal=International Journal of Clinical Practice|volume=59|issue=12|pages=1428–1434|doi=10.1111/j.1368-5031.2005.00681.x|issn=1368-5031|pmid=16351675|s2cid=13336009}}

FDA approved SSRIs used for this purpose include escitalopram{{cite journal|vauthors=Bech P, Lönn SL, Overø KF|year=2010|title=Relapse prevention and residual symptoms: a closer analysis of placebo-controlled continuation studies with escitalopram in major depressive disorder, generalized anxiety disorder, social anxiety disorder, and obsessive-compulsive disorder|journal=Journal of Clinical Psychiatry|volume=71|issue=2|pages=121–9|doi=10.4088/JCP.08m04749blu|pmid=19961809}} and paroxetine.{{Cite journal|last1=Wagstaff|first1=Antona J.|last2=Cheer|first2=Susan M.|last3=Matheson|first3=Anna J.|last4=Ormrod|first4=Douglas|last5=Goa|first5=Karen L.|date=2002-01-01|title=Paroxetine: an update of its use in psychiatric disorders in adults|journal=Drugs|volume=62|issue=4|pages=655–703|doi=10.2165/00003495-200262040-00010|issn=0012-6667|pmid=11893234|s2cid=195692589}} However, guidelines suggest using sertraline first due to its cost-effectiveness compared to other SSRIs used for generalized anxiety disorder and a lower risk of withdrawal compared to SNRIs. If sertraline is found to be ineffective, then it is recommended to try another SSRI or SNRI.{{Cite web|title=Generalised anxiety disorder and panic disorder in adults: management {{!}} Guidance and guidelines {{!}} NICE|url=https://www.nice.org.uk/guidance/cg113/chapter/1-Guidance#stepped-care-for-people-with-gad|access-date=2018-11-02|website=www.nice.org.uk|date=26 January 2011 }}

Common side effects include nausea, sexual dysfunction, headache, diarrhea, constipation, restlessness, increased risk of suicide in young adults and adolescents,{{cite web|title=Antidepressant Medications for Children and Adolescents: Information for Parents and Caregivers|url=http://www.nimh.nih.gov/health/topics/child-and-adolescent-mental-health/antidepressant-medications-for-children-and-adolescents-information-for-parents-and-caregivers.shtml|archive-url=https://web.archive.org/web/20100301063959/http://www.nimh.nih.gov/health/topics/child-and-adolescent-mental-health/antidepressant-medications-for-children-and-adolescents-information-for-parents-and-caregivers.shtml|archive-date=1 March 2010|access-date=1 September 2015|publisher=National Institute of Mental Health}} among others. Sexual side effects, weight gain, and higher risk of withdrawal are more common in paroxetine than escitalopram and sertraline.{{Cite journal|last=Ferguson|first=James M.|date=February 2001|title=SSRI Antidepressant Medications: Adverse Effects and Tolerability|journal=Primary Care Companion to the Journal of Clinical Psychiatry|volume=3|issue=1|pages=22–27|doi=10.4088/PCC.v03n0105|issn=1523-5998|pmc=181155|pmid=15014625}} In older populations or those taking concomitant medications that increase risk of bleeding, SSRIs may further increase the risk of bleeding. Overdose of an SSRI or concomitant use with another agent that causes increased levels of serotonin can result in serotonin syndrome, which can be life-threatening.

First line pharmaceutical treatments for GAD also include serotonin-norepinephrine reuptake inhibitors (SNRIs).{{cite journal|vauthors=Baldwin DS, Anderson IM, Nutt DJ, Allgulander C, Bandelow B, den Boer JA, Christmas DM, Davies S, Fineberg N, Lidbetter N, Malizia A, McCrone P, Nabarro D, O'Neill C, Scott J, van der Wee N, Wittchen HU|date=May 2014|title=Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology|url=http://tud.qucosa.de/api/qucosa%3A35384/attachment/ATT-0/|journal=Journal of Psychopharmacology|volume=28|issue=5|pages=403–39|doi=10.1177/0269881114525674|pmid=24713617|s2cid=28893331|access-date=2019-12-02|archive-date=2020-06-09|archive-url=https://web.archive.org/web/20200609181444/https://tud.qucosa.de/api/qucosa%3A35384/attachment/ATT-0/|url-status=dead}} These inhibit the reuptake of serotonin and noradrenaline to increase their levels in the CNS.{{cite journal|vauthors=Sansone RA, Sansone LA|date=March 2014|title=Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison|journal=Innovations in Clinical Neuroscience|volume=11|issue=3–4|pages=37–42|pmc=4008300|pmid=24800132}}

FDA approved SNRIs used for this purpose include duloxetine (Cymbalta) and venlafaxine (Effexor).{{Cite journal|last1=Baldwin|first1=David S|last2=Anderson|first2=Ian M|last3=Nutt|first3=David J|last4=Allgulander|first4=Christer|last5=Bandelow|first5=Borwin|last6=den Boer|first6=Johan A|last7=Christmas|first7=David M|last8=Davies|first8=Simon|last9=Fineberg|first9=Naomi|date=2014-04-08|title=Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology|url=https://eprints.soton.ac.uk/367917/1/AnxietyGuidelines2014%255B1%255D.pdf|journal=Journal of Psychopharmacology|volume=28|issue=5|pages=403–439|doi=10.1177/0269881114525674|issn=0269-8811|pmid=24713617|s2cid=28893331}} While SNRIs have similar efficacy as SSRIs,{{Cite journal|last1=Baldwin|first1=David|last2=Woods|first2=Robert|last3=Lawson|first3=Richard|last4=Taylor|first4=David|date=2011-03-11|title=Efficacy of drug treatments for generalised anxiety disorder: systematic review and meta-analysis|url=https://www.bmj.com/content/342/bmj.d1199|journal=BMJ|volume=342|pages=d1199|doi=10.1136/bmj.d1199|issn=0959-8138|pmid=21398351|doi-access=free}} many psychiatrists prefer to use SSRIs first in the treatment of Generalized Anxiety Disorder.{{Cite journal|last1=Baldwin|first1=David S.|last2=Allgulander|first2=Christer|last3=Bandelow|first3=Borwin|last4=Ferre|first4=Francisco|last5=Pallanti|first5=Stefano|date=October 2012|title=An international survey of reported prescribing practice in the treatment of patients with generalised anxiety disorder|journal=The World Journal of Biological Psychiatry|volume=13|issue=7|pages=510–516|doi=10.3109/15622975.2011.624548|issn=1814-1412|pmid=22059936|s2cid=35359537}}{{Cite journal|last1=Baldwin|first1=David S|last2=Anderson|first2=Ian M|last3=Nutt|first3=David J|last4=Allgulander|first4=Christer|last5=Bandelow|first5=Borwin|last6=den Boer|first6=Johan A|last7=Christmas|first7=David M|last8=Davies|first8=Simon|last9=Fineberg|first9=Naomi|date=2014-04-08|title=Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology|url=https://eprints.soton.ac.uk/367917/1/AnxietyGuidelines2014%255B1%255D.pdf|journal=Journal of Psychopharmacology|volume=28|issue=5|pages=403–439|doi=10.1177/0269881114525674|issn=0269-8811|pmid=24713617|s2cid=28893331}}{{Cite journal|last1=Katzman|first1=Martin A.|last2=Bleau|first2=Pierre|last3=Blier|first3=Pierre|last4=Chokka|first4=Pratap|last5=Kjernisted|first5=Kevin|last6=Van Ameringen|first6=Michael|last7=Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles anxieux and McGill University|last8=Antony|first8=Martin M.|last9=Bouchard|first9=Stéphane|date=2014|title=Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders|journal=BMC Psychiatry|volume=14|issue=Suppl 1 |pages=S1|doi=10.1186/1471-244X-14-S1-S1|issn=1471-244X|pmc=4120194|pmid=25081580 |doi-access=free }} The slightly higher preference for SSRIs over SNRIs as a first choice for treatment of anxiety disorders may have been influenced by the observation of poorer tolerability of the SNRIs in comparison to SSRIs in systematic reviews of studies of depressed patients.{{Cite journal|last1=Baldwin|first1=David S|last2=Anderson|first2=Ian M|last3=Nutt|first3=David J|last4=Allgulander|first4=Christer|last5=Bandelow|first5=Borwin|last6=den Boer|first6=Johan A|last7=Christmas|first7=David M|last8=Davies|first8=Simon|last9=Fineberg|first9=Naomi|date=2014-04-08|title=Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology|url=https://eprints.soton.ac.uk/367917/1/AnxietyGuidelines2014%255B1%255D.pdf|journal=Journal of Psychopharmacology|volume=28|issue=5|pages=403–439|doi=10.1177/0269881114525674|issn=0269-8811|pmid=24713617|s2cid=28893331}}{{Cite journal|last1=Schueler|first1=Y.-B.|last2=Koesters|first2=M.|last3=Wieseler|first3=B.|last4=Grouven|first4=U.|last5=Kromp|first5=M.|last6=Kerekes|first6=M. F.|last7=Kreis|first7=J.|last8=Kaiser|first8=T.|last9=Becker|first9=T.|date=April 2011|title=A systematic review of duloxetine and venlafaxine in major depression, including unpublished data|journal=Acta Psychiatrica Scandinavica|volume=123|issue=4|pages=247–265|doi=10.1111/j.1600-0447.2010.01599.x|issn=1600-0447|pmid=20831742|s2cid=2262158|doi-access=free}}{{Cite journal|last1=Cipriani|first1=Andrea|last2=Purgato|first2=Marianna|last3=Furukawa|first3=Toshi A.|last4=Trespidi|first4=Carlotta|last5=Imperadore|first5=Giuseppe|last6=Signoretti|first6=Alessandra|last7=Churchill|first7=Rachel|last8=Watanabe|first8=Norio|last9=Barbui|first9=Corrado|date=2012-07-11|title=Citalopram versus other anti-depressive agents for depression|journal=The Cochrane Database of Systematic Reviews|volume=2012 |issue=7|pages=CD006534|doi=10.1002/14651858.CD006534.pub2|issn=1469-493X|pmc=4204633|pmid=22786497}}

Side effects common to both SNRIs include anxiety, restlessness, nausea, weight loss, insomnia, dizziness, drowsiness, sweating, dry mouth, sexual dysfunction and weakness.{{Cite journal|last1=Santarsieri|first1=Daniel|last2=Schwartz|first2=Thomas L.|date=2015|title=Antidepressant efficacy and side-effect burden: a quick guide for clinicians|journal=Drugs in Context|volume=4|page=212290|doi=10.7573/dic.212290|issn=1745-1981|pmc=4630974|pmid=26576188}} In comparison to SSRIs, the SNRIs have a higher prevalence of the side effects of insomnia, dry mouth, nausea and high blood pressure.{{Cite journal|last1=Baldwin|first1=David S.|last2=Anderson|first2=Ian M.|last3=Nutt|first3=David J.|last4=Allgulander|first4=Christer|last5=Bandelow|first5=Borwin|last6=den Boer|first6=Johan A.|last7=Christmas|first7=David M.|last8=Davies|first8=Simon|last9=Fineberg|first9=Naomi|date=May 2014|title=Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology|url=https://eprints.soton.ac.uk/367917/1/AnxietyGuidelines2014%255B1%255D.pdf|journal=Journal of Psychopharmacology|volume=28|issue=5|pages=403–439|doi=10.1177/0269881114525674|issn=1461-7285|pmid=24713617|s2cid=28893331}} Both SNRIs have the potential for discontinuation syndrome after abrupt cessation, which can precipitate symptoms including motor disturbances and anxiety and may require tapering.{{Citation|last1=Chow|first1=Robert M.|title=Serotonin-Norepinephrine Reuptake Inhibitors|date=2017|work=Pain Medicine|pages=169–170|publisher=Springer International Publishing|doi=10.1007/978-3-319-43133-8_44|isbn=978-3-319-43131-4|last2=Issa|first2=Mohammed|doi-access=free}}{{Cite journal|last1=Baldwin|first1=David S|last2=Anderson|first2=Ian M|last3=Nutt|first3=David J|last4=Allgulander|first4=Christer|last5=Bandelow|first5=Borwin|last6=den Boer|first6=Johan A|last7=Christmas|first7=David M|last8=Davies|first8=Simon|last9=Fineberg|first9=Naomi|date=2014-04-08|title=Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology|url=https://eprints.soton.ac.uk/367917/1/AnxietyGuidelines2014%255B1%255D.pdf|journal=Journal of Psychopharmacology|volume=28|issue=5|pages=403–439|doi=10.1177/0269881114525674|issn=0269-8811|pmid=24713617|s2cid=28893331}} Like other serotonergic agents, SNRIs have the potential to cause serotonin syndrome, a potentially fatal systemic response to serotonergic excess that causes symptoms including agitation, restlessness, confusion, tachycardia, hypertension, mydriasis, ataxia, myoclonus, muscle rigidity, diaphoresis, diarrhea, headache, shivering, goose bumps, high fever, seizures, arrhythmia and unconsciousness.{{Cite journal|last1=Jurek|first1=L.|last2=Nourredine|first2=M.|last3=Megarbane|first3=B.|last4=d'Amato|first4=T.|last5=Dorey|first5=J.-M.|last6=Rolland|first6=B.|date=2018-09-19|title=[The serotonin syndrome: An updated literature review]|journal=La Revue de Médecine Interne|volume=40|issue=2|pages=98–104|doi=10.1016/j.revmed.2018.08.010|issn=1768-3122|pmid=30243558|s2cid=196505807}} SNRIs like SSRIs carry a black box warning for suicidal ideation, but it is generally considered that the risk of suicide in untreated depression is far higher than the risk of suicide when depression is properly treated.{{Cite journal|last1=Bitter|first1=Istvan|last2=Filipovits|first2=Dora|last3=Czobor|first3=Pal|date=November 2011|title=Adverse reactions to duloxetine in depression|journal=Expert Opinion on Drug Safety|volume=10|issue=6|pages=839–850|doi=10.1517/14740338.2011.582037|issn=1744-764X|pmid=21545241|s2cid=207487375}}

Pregabalin (Lyrica) is effective for treating GAD.{{Cite journal |date=2022-10-17 |title=Review finds little evidence to support gabapentinoid use in bipolar disorder or insomnia |url=https://evidence.nihr.ac.uk/alert/review-finds-little-evidence-support-gabapentinoid-use-bipolar-disorder-or-insomnia/ |journal=NIHR Evidence |type=Plain English summary |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_54173 |s2cid=252983016|url-access=subscription }}{{cite journal |vauthors=Hong JS, Atkinson LZ, Al-Juffali N, Awad A, Geddes JR, Tunbridge EM, Harrison PJ, Cipriani A |date=March 2022 |title=Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale |journal=Molecular Psychiatry |volume=27 |issue=3 |pages=1339–1349 |doi=10.1038/s41380-021-01386-6 |pmc=9095464 |pmid=34819636}} It acts on the voltage-dependent calcium channel to decrease the release of neurotransmitters such as glutamate, norepinephrine and substance P. Its therapeutic effect appears after one week of use and is similar in effectiveness to lorazepam, alprazolam and venlafaxine but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance and additionally, unlike benzodiazepines, it does not disrupt sleep architecture and produces less severe cognitive and psychomotor impairment. It also has a low potential for misuse and dependency and may be preferred over the benzodiazepines for these reasons.{{cite journal|last1=Bandelow|first1=Borwin|last2=Wedekind|first2=Dirk|last3=Leon|first3=Teresa|year=2007|title=Pregabalin for the treatment of generalized anxiety disorder: A novel pharmacologic intervention|journal=Expert Review of Neurotherapeutics|volume=7|issue=7|pages=769–81|doi=10.1586/14737175.7.7.769|pmid=17610384|s2cid=6229344}}{{cite journal|last1=Owen|first1=R. T.|year=2007|title=Pregabalin: Its efficacy, safety and tolerability profile in generalized anxiety|journal=Drugs of Today|volume=43|issue=9|pages=601–10|doi=10.1358/dot.2007.43.9.1133188|pmid=17940637}} The anxiolytic effects of pregabalin appear to persist for at least six months continuous use, suggesting tolerance is less of a concern; this gives pregabalin an advantage over certain anxiolytic medications such as benzodiazepines.{{cite journal|last1=Wensel|first1=T. M.|last2=Powe|first2=K. W.|last3=Cates|first3=M. E.|year=2012|title=Pregabalin for the Treatment of Generalized Anxiety Disorder|journal=Annals of Pharmacotherapy|volume=46|issue=3|pages=424–9|doi=10.1345/aph.1Q405|pmid=22395254|s2cid=26320851}}

Gabapentin (Neurontin), a closely related medication to pregabalin with the same mechanism of action, has also demonstrated effectiveness in the treatment of GAD,{{cite book|author1=Rif S. El-Mallakh|url=https://books.google.com/books?id=fFKgiZU2KscC&pg=PA158|title=Bipolar Depression: A Comprehensive Guide|author2=S. Nassir Ghaemi|date=2 April 2007|publisher=American Psychiatric Pub|isbn=978-1-58562-651-9|page=158}} though unlike pregabalin, it has not been approved specifically for this indication. Nonetheless, it is likely to be of similar usefulness in the management of this condition, and by virtue of being off-patent, it has the advantage of being significantly less expensive in comparison.{{cite book|author1=Stephen M. Stahl|url=https://books.google.com/books?id=ssls1CRstw4C&pg=PT65|title=Anxiety Disorders: A Guide for Integrating Psychopharmacology and Psychotherapy|author2=Bret A. Moore|date=13 February 2013|publisher=Routledge|isbn=978-1-136-44588-0|page=65}} In accordance, gabapentin is frequently prescribed off-label to treat GAD.{{cite book|author1=D. John Reynolds|url=https://books.google.com/books?id=82oiYYHGNTQC&pg=PA765|title=Oxford Handbook of Practical Drug Therapy|author2=Jamie Coleman|author3=Jeffrey Aronson|date=10 November 2011|publisher=Oxford University Press|isbn=978-0-19-956285-5|page=765}}

Complementary and alternative medicines (CAMs) are widely used by individuals with GAD despite having no evidence or varied evidence regarding efficacy. Efficacy trials for CAM medications often have various types of bias and low quality reporting in regard to safety. In regard to efficacy, critics point out that CAM trials sometimes predicate claims of efficacy based on a comparison of a CAM against a known drug after which no difference in subjects is found by investigators and which is used to suggest an equivalence between a CAM and a drug. Because this equates a lack of evidence with the positive assertion of efficacy, a "lack of difference" assertion is not a proper claim for efficacy. Moreover, an absence of strict definitions and standards for CAM compounds further burdens the literature regarding CAM efficacy in treating GAD. CAMs academically studied for their potential in treating GAD or GAD symptoms along with a summary of academic findings are given below. What follows is a summary of academic findings. Accordingly, none of the following should be taken as offering medical guidance or an opinion as to the safety or efficacy of any of the following CAMs.

1. Kava (Piper methysticum) extracts: Meta-analysis does not suggest efficacy of kava extracts due to few data available yielding inconclusive results or non-statistically significant results. Nearly a quarter (25.8%) of subjects experienced adverse effects (AEs) from Kava Kava extracts during six trials. Traditional kava is low-risk; solvent-based extracts or poor-quality forms may harm the liver.{{cite report

|title=Kava: A Review of the Safety of Traditional and Recreational Beverage Consumption

|author=Food and Agriculture Organization of the United Nations

|publisher=Food and Agriculture Organization of the United Nations

|date=2016

|url=https://openknowledge.fao.org/server/api/core/bitstreams/f97fbe5f-244e-4301-be2a-03ac39ef630b/content

|access-date=2025-05-22

|series=FAO Food and Nutrition Paper

|number=103

|location=Rome

|isbn=978-92-5-109270-5

}}

1. Lavender (Lavandula angustifolia) extracts: Small and varied studies may suggest some level of efficacy as compared to placebo or other medication; claims of efficacy are regarded as needing further evaluation. Silexan is an oil derivative of Lavender studied in pediatric patients with GAD. Concern exists regarding the question as to whether Silexan may cause unopposed estrogen exposure in boys due to disruption of steroid signaling.
2. Galphimia glauca extracts: While Galphima glauca extracts have been the subject of two randomised controlled trials (RCTs) comparing Galphima glauca extracts to lorazepam, efficacy claims are regarded as "highly uncertain."
3. Chamomile (Matricaria chamomilla) extracts: Poor quality trials have trends that may suggest efficacy but further study is needed to establish any claim of efficacy.
4. Crataegus oxycantha and Eschscholtzia californica extracts combined with magnesium: A single 12-week trial of Crataegus oxycantha and Eschscholtzia californica compared to placebo has been used to suggest efficacy. However, efficacy claims require confirmation studies. For the minority of subjects who experienced AEs from extracts, most AEs implicated gastrointestinal tract (GIT) intolerance.
5. Echium amoneum extract: A single, small trial used this extract as a supplement to fluoxetine (vs using a placebo to supplement fluoxetine); larger studies are needed to substantiate efficacy claims.
6. Gamisoyo-San: Small trials of this herbal mixture compared to placebo have suggested no efficacy of the herbal mixture over placebo but further study is necessary to allow definitive conclusion of a lack of efficacy.
7. Passiflora incarnata extract: Claims of efficacy or benzodiazepine equivalence are regarded as "highly uncertain."
8. Valeriana extract: A single 4-week trial suggests no effect of Valeriana extract on GAD but is regarded as "uninformative" on the topic of efficacy in view of its finding that the benzodiazepine diazepam also had no effect. Further study may be warranted.

A 2022 meta-analysis found that some herbs—particularly lavender (Silexan), kava, Ginkgo biloba, and Withania somnifera—show promise for treating anxiety, though overall evidence remains preliminary due to small sample sizes and possible placebo effects.{{Cite journal |last=Zhang |first=Wenting |last2=Yan |first2=Yonghuang |last3=Wu |first3=Yujie |last4=Yang |first4=Han |last5=Zhu |first5=Peixuan |last6=Yan |first6=Fang |last7=Zhao |first7=Ruixue |last8=Tian |first8=Peng |last9=Wang |first9=Ting |last10=Fan |first10=Qiongyin |last11=Su |first11=Zeqi |date=2022 |title=Medicinal herbs for the treatment of anxiety: A systematic review and network meta-analysis |url=https://pubmed.ncbi.nlm.nih.gov/35378276 |journal=Pharmacological Research |volume=179 |pages=106204 |doi=10.1016/j.phrs.2022.106204 |issn=1096-1186 |pmid=35378276}}

Lifestyle factors including: stress management, stress reduction, relaxation, sleep hygiene, and caffeine and alcohol reduction can influence anxiety levels. Physical activity has shown to have a positive impact whereas low physical activity may be a risk factor for anxiety disorders.{{cite journal |last1=Boschloo |first1=L |title=The impact of lifestyle factors on the 2-year course of depressive and/or anxiety disorders. |journal=Journal of Affective Disorders |volume=159 |pages=73–9 |pmid=24679393 |year=2014 |doi=10.1016/j.jad.2014.01.019 }}

Engaging in physical activity appears to significantly reduce the risk of developing anxiety symptoms and disorders, though limitations in study quality and consistency highlight the need for further research.{{Cite journal |last=McDowell |first=Cillian P. |last2=Dishman |first2=Rodney K. |last3=Gordon |first3=Brett R. |last4=Herring |first4=Matthew P. |date=2019 |title=Physical Activity and Anxiety: A Systematic Review and Meta-analysis of Prospective Cohort Studies |url=https://pubmed.ncbi.nlm.nih.gov/31542132 |journal=American Journal of Preventive Medicine |volume=57 |issue=4 |pages=545–556 |doi=10.1016/j.amepre.2019.05.012 |issn=1873-2607 |pmid=31542132}}

Certain substances or the withdrawal from certain substances have been implicated in promoting the experience of anxiety. For example, even while benzodiazepines may afford individuals with GAD relief from anxiety, withdrawal from benzodiazepines is associated with the experience of anxiety among other adverse events like sweating and tremor.

Nicotine withdrawal symptoms may provoke anxiety in tobacco smokers{{cite journal|vauthors=Morissette SB, Tull MT, Gulliver SB, Kamholz BW, Zimering RT|date=March 2007|title=Anxiety, anxiety disorders, tobacco use, and nicotine: a critical review of interrelationships|journal=Psychological Bulletin|volume=133|issue=2|pages=245–72|doi=10.1037/0033-2909.133.2.245|pmid=17338599}} and excessive caffeine use has been linked to aggravating and maintaining anxiety.{{cite journal|author=Bruce M. S., Lader M.|last2=Lader|year=2009|title=Caffeine abstention in the management of anxiety disorders|journal=Psychological Medicine|volume=19|issue=1|pages=211–4|doi=10.1017/S003329170001117X|pmid=2727208|s2cid=45368729 }}

A longitudinal cohort study found 12% of 972 participants had GAD comorbid with major depressive disorder.{{cite journal |doi=10.1001/archpsyc.64.6.651 |title=Depression and Generalized Anxiety Disorder |year=2007 |last1=Moffitt |first1=Terrie E. |journal=Archives of General Psychiatry |volume=64 |issue=6 |pages=651–60 |pmid=17548747 |last2=Harrington |first2=H |last3=Caspi |first3=A |last4=Kim-Cohen |first4=J |last5=Goldberg |first5=D |last6=Gregory |first6=AM |last7=Poulton |first7=R|doi-access=free }} Accumulating evidence indicates that patients with comorbid depression and anxiety tend to have greater illness severity and a lower treatment response than those with either disorder alone.{{cite journal |doi=10.1002/da.20653 |title=Anxiety disorders in older adults: A comprehensive review |year=2010 |last1=Wolitzky-Taylor |first1=Kate B. |last2=Castriotta |first2=Natalie |last3=Lenze |first3=Eric J. |last4=Stanley |first4=Melinda A. |last5=Craske |first5=Michelle G. |s2cid=12981577 |journal=Depression and Anxiety |volume=27 |issue=2 |pages=190–211 |pmid=20099273|doi-access=free }} In addition, social function and quality of life are more greatly impaired.

For many, the symptoms of both depression and anxiety are not severe enough (i.e., are subsyndromal) to justify a primary diagnosis of either major depressive disorder (MDD) or an anxiety disorder. However, dysthymia is the most prevalent comorbid diagnosis of GAD clients. Patients can also be categorized as having mixed anxiety-depressive disorder, though this is an unstable diagnosis that typically either goes away or shifts to a different diagnosis later on.{{Cite journal |last1=Barkow |first1=Katrin |last2=Heun |first2=Reinhard |last3=Wittchen |first3=Hans-Ulrich |last4=Üstün |first4=T Bedirhan |last5=Gänsicke |first5=Michael |last6=Maier |first6=Wolfgang |date=April 2004 |title=Mixed anxiety–depression in a 1 year follow-up study: shift to other diagnoses or remission? |journal=Journal of Affective Disorders |volume=79 |issue=1–3 |pages=235–239 |doi=10.1016/S0165-0327(02)00343-9 |pmid=15023500 |url=https://tud.qucosa.de/api/qucosa%3A26807/attachment/ATT-0/ }}

Various explanations for the high comorbidity between GAD and depressive disorders have been suggested, ranging from genetic pleiotropy (i.e., GAD and nonbipolar depression might represent different phenotypic expressions of a common etiology {{cite journal |last1=Crocq |first1=Marc-Antoine |date=June 1, 2017 |title=The History of Generalized Anxiety Disorder as a Diagnostic Category |journal=Dialogues in Clinical Neuroscience |volume=19 |issue=2 |pages=107–116 |doi=10.31887/DCNS.2017.19.2/macrocq |pmc=5573555 |pmid=28867935}}) to impaired executive control {{cite journal|last1=Coussement|first1=C.|last2=De Longueville|first2=X.| last3=Heeren|first3=A.|year=2022|title=Attentional networks in co-occurring generalized anxiety disorder and major depression disorder: Towards a staging approach to the executive control deficits|journal=Comprehensive Psychiatry|volume=113|page=152294|doi=10.1016/j.comppsych.2021.152294|pmid=34942482|doi-access=free|hdl=2078.1/255311|hdl-access=free}} or sleep problems and fatigue as potential bridging mechanisms between the two disorders.{{cite journal|last1=Coussement|first1=C.|last2=Heeren|first2=A.|year=2022|title=Sleep problems as a transdiagnostic hub bridging impaired attention control, generalized anxiety, and depression|journal=Journal of Affective Disorders|volume=296|pages=305–308|doi=10.1016/j.jad.2021.09.092|pmid=34606807|s2cid=238357084|hdl=2078.1/251649|hdl-access=free}}

Both disorders are found to be precede each other, or help the other develop. In 32% of anxiety cases, depression was seen to begin before or concurrently, while in 37% of depression cases, anxiety was seen to begin before or concurrently. Within 72% of anxiety cases, a history of depression was found.

Therapy has been shown to have equal efficacy in patients with GAD and patients with GAD and comorbid disorders. Patients with comorbid disorders have more severe symptoms when starting therapy, but demonstrated a greater improvement than patients with GAD alone.{{Citation needed|date=February 2025}}

Pharmacological approaches (i.e., the use of antidepressants) must be adapted for different comorbidities. For example, selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are used for depression and anxiety. However, for patients with anxiety and a substance use disorder, benzodiazepines should be avoided due to their addictive properties.{{cite journal | vauthors = Back SE, Brady KT | title = Anxiety Disorders with Comorbid Substance Use Disorders: Diagnostic and Treatment Considerations | journal = Psychiatric Annals | volume = 38 | issue = 11 | pages = 724–729 | date = November 2008 | pmid = 20717489 | pmc = 2921723 | doi = 10.3928/00485713-20081101-01 }} CBT has been found an effective treatment since it improves symptoms of GAD and substance use.

Compared to the general population, patients with internalizing disorders such as depression, generalized anxiety disorder, and post-traumatic stress disorder (PTSD) have higher mortality rates, but die of the same age-related diseases as the population, such as heart disease, cerebrovascular disease and cancer.{{cite journal|last1=Shalev|first1=I|last2=Moffitt|first2=Terrie Edith|author-link2=Terrie Moffitt|last3=Braithwaite|first3=A W|last4=Danese|first4=A|last5=Fleming|first5=N I|last6=Goldman-Mellor|first6=S|last7=Harrington|first7=H L|last8=Houts|first8=R M|last9=Israel|first9=S|date=2014-01-14|title=Internalizing disorders and leukocyte telomere erosion: a prospective study of depression, generalized anxiety disorder and post-traumatic stress disorder|url=http://www.moffittcaspi.com/sites/moffittcaspi.com/files/field/publication_uploads/Shalev_MP2014.pdf.pdf|journal=Molecular Psychiatry|volume=19|issue=11|pages=1163–1170|doi=10.1038/mp.2013.183|pmc=4098012|pmid=24419039|access-date=21 April 2014|last10=Poulton|first10=R|last11=Robertson|first11=S P|last12=Sugden|first12=K|last13=Williams|first13=B|last14=Caspi|first14=A|archive-date=2014-04-23|archive-url=https://web.archive.org/web/20140423060546/http://www.moffittcaspi.com/sites/moffittcaspi.com/files/field/publication_uploads/Shalev_MP2014.pdf.pdf|url-status=dead}}

Patients with GAD can sometimes present with symptoms such as insomnia or headaches.{{citation needed|date=January 2022}}

There is also observed comorbidity between GAD and attention deficit hyperactivity disorder (ADHD). Anxiety disorders and major depressive disorder occur in a minority of individuals with ADHD, but more often than in the general population.{{Cite book |title=Diagnostic and Statistical Manual of Mental Disorders |date=2013-05-22 |publisher=American Psychiatric Association |isbn=978-0-89042-555-8 |edition=Fifth |language=en |doi=10.1176/appi.books.9780890425596 | author1 = American Psychiatric Association }} Further research suggests that about 20 to 40 percent of individuals with ADHD have comorbid anxiety disorders, with GAD being the most prevalent.{{cite web|title=Access|url=http://www.medscape.org/viewarticle/555748_5|access-date=2013-01-15|website=Medscape}}

Those with GAD have a lifetime comorbidity prevalence of 30% to 35% with alcohol use disorder and 25% to 30% for another substance use disorder.Scott, E. L. (2011, September 6). Anxiety Disorders With Comorbid Substance Abuse. Psychiatric Times. Retrieved July 1, 2013, from http://www.psychiatrictimes.com/anxiety/anxiety-disorders-comorbid-substance-abuse {{Webarchive|url=https://web.archive.org/web/20191212075645/https://www.psychiatrictimes.com/anxiety/anxiety-disorders-comorbid-substance-abuse |date=2019-12-12 }} People with both GAD and a substance use disorder also have a higher lifetime prevalence for other comorbidities. A study found that GAD was the primary disorder in slightly more than half of the 18 participants that were comorbid with alcohol use disorder.{{cite journal|last1=Smith|first1=Joshua P.|last2=Book|first2=Sarah W.|year=2010|title=Comorbidity of generalized anxiety disorder and alcohol use disorders among individuals seeking outpatient substance abuse treatment|journal=Addictive Behaviors|volume=35|issue=1|pages=42–5|doi=10.1016/j.addbeh.2009.07.002|pmc=2763929|pmid=19733441}}

GAD is often estimated to affect approximately 3–6% of adults and 5% of children and adolescents. Although estimates have varied to suggest a GAD prevalence of 3% in children and 10.8% in adolescents.{{cite book|last1=Albano|first1=Anne Marie|title=Child Psychopathology|last2=Chorpita|first2=Bruce F.|last3=Barlow|first3=David H.|publisher=Guilford Press|year=2003|isbn=978-1-57230-609-7|editor1-last=Mash|editor1-first=Eric J.|edition=2nd|location=New York|pages=279–329|chapter=Childhood Anxiety Disorders|editor2-last=Barkley|editor2-first=Russell A.|chapter-url=https://books.google.com/books?id=T3zarJqFDbwC&pg=PA279}} When GAD manifests in children and adolescents, it typically begins around 8 to 9 years of age.{{cite journal|last=Keeton|first=CP|author2=Kolos, AC|author3=Walkup, JT|year=2009|title=Pediatric generalized anxiety disorder: epidemiology, diagnosis, and management|journal=Paediatric Drugs|volume=11|issue=3|pages=171–83|doi=10.2165/00148581-200911030-00003|pmid=19445546|s2cid=39870253}}

Estimates regarding prevalence of GAD or lifetime risk (i.e., lifetime morbid risk [LMR]){{Cite journal |last1=Kessler |first1=Ronald C. |last2=Petukhova |first2=Maria |last3=Sampson |first3=Nancy A. |last4=Zaslavsky |first4=Alan M. |last5=Wittchen |first5=Hans-Ullrich |date=September 2012 |title=Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States |journal=International Journal of Methods in Psychiatric Research |volume=21 |issue=3 |pages=169–184 |doi=10.1002/mpr.1359 |issn=1557-0657 |pmc=4005415 |pmid=22865617}} for GAD vary depending upon which criteria are used for diagnosing GAD (e.g., DSM-5 vs ICD-10) although estimates do not vary widely between diagnostic criteria. In general, ICD-10 is more inclusive than DSM-5, so estimates regarding prevalence and lifetime risk tend to be greater using ICD-10. In regard to prevalence, in a given year, about two (2%) percent of adults in the United States and Europe have been suggested to have GAD.[http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disorders-in-america/index.shtml "The Numbers Count"] {{Webarchive|url=https://web.archive.org/web/20140728102548/http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disorders-in-america/index.shtml|date=2014-07-28}}, National Institute of Mental Health. Accessed 28 May 2007.{{cite journal |last1=Lieb |first1=Roselind |last2=Becker |first2=Eni |last3=Altamura |first3=Carlo |year=2005 |title=The epidemiology of generalized anxiety disorder in Europe |journal=European Neuropsychopharmacology |volume=15 |issue=4 |pages=445–52 |doi=10.1016/j.euroneuro.2005.04.010 |pmid=15951160 |s2cid=19888900 |hdl-access=free |hdl=2066/54596}} However, the risk of developing GAD at any point in life has been estimated at 9.0%. Although it is possible to experience a single episode of GAD during one's life, most people who experience GAD experience it repeatedly over the course of their lives as a chronic or ongoing condition. GAD is diagnosed twice as frequently in women as in men{{cite book |last1=Geddes |first1=John |title=Psychiatry |last2=Price |first2=Jonathan |last3=Gelder |first3=Rebecca McKnight |last4=Mayou |first4=Richard |date=2012 |publisher=Oxford University Press |isbn=978-0-19-923396-0 |edition=4th |location=Oxford |page=287}} and is more often diagnosed in those who are separated, divorced, unemployed, widowed or have low levels of education,{{Cite journal|last1=Ansseau|first1=Marc|last2=Fischler|first2=Benjamin|last3=Dierick|first3=Michel|last4=Albert|first4=Adelin|last5=Leyman|first5=Sophie|last6=Mignon|first6=Annick|date=26 June 2007|title=Socioeconomic correlates of generalized anxiety disorder and major depression in primary care: The GADIS II study (Generalized Anxiety and Depression Impact Survey II)|journal=Depression and Anxiety|volume=25|issue=6|pages=506–513|doi=10.1002/da.20306|pmid=17595015|s2cid=38539957|doi-access=free}} and among those with low socioeconomic status. African Americans have higher odds of having GAD and the disorder often manifests itself in different patterns.{{Cite journal|last1=Soto|first1=José A.|last2=Dawson-Andoh|first2=Nana A.|last3=Belue|first3=Rhonda|date=March 2011|title=The relationship between perceived discrimination and Generalized Anxiety Disorder among African Americans, Afro Caribbeans, and non-Hispanic Whites|journal=Journal of Anxiety Disorders|volume=25|issue=2|pages=258–265|doi=10.1016/j.janxdis.2010.09.011|pmc=3053120|pmid=21041059}}{{Cite journal|last1=Neal|first1=Angela M.|last2=Turner|first2=Samuel M.|date=May 1991|title=Anxiety disorders research with African Americans: Current status|journal=Psychological Bulletin|volume=109|issue=3|pages=400–410|doi=10.1037/0033-2909.109.3.400|pmid=2062979}} It has been suggested that greater prevalence of GAD in women may be because women are more likely than men to live in poverty, are more frequently the subject of discrimination, and be sexually and physically abused more often than men.{{cite book|last1=Schacter|first1=Daniel L.|title=Psychology|last2=Gilbert|first2=Daniel T.|last3=Wegner|first3=Daniel M.|date=2011|publisher=Worth, Incorporated|edition=2nd|location=New York|pages=559–560|chapter=Generalized Anxiety Disorders}} In regard to the first incidence of GAD in an individual's life course, a first manifestation of GAD usually occurs between the late teenage years and the early twenties with the median age of onset being approximately 31{{cite journal|last1=Kessler|first1=Ronald C.|last2=Chiu|first2=WT|last3=Demler|first3=O|last4=Merikangas|first4=KR|author-link4=Kathleen Merikangas|last5=Walters|first5=EE|year=2005|title=Prevalence, Severity, and Comorbidity of 12-Month DSM-IV Disorders in the National Comorbidity Survey Replication|journal=Archives of General Psychiatry|volume=62|issue=6|pages=617–27|doi=10.1001/archpsyc.62.6.617|pmc=2847357|pmid=15939839}} and mean age of onset being 32.7.{{cite journal|last1=Grant|first1=Bridget F.|last2=Hasin|first2=Deborah S.|last3=Stinson|first3=Frederick S.|last4=Dawson|first4=Deborah A.|last5=June Ruan|first5=W.|last6=Goldstein|first6=Risë B.|last7=Smith|first7=Sharon M.|last8=Saha|first8=Tulshi D.|last9=Huang|first9=Boji|year=2005|title=Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: Results from the National Epidemiologic Survey on Alcohol and Related Conditions|url=https://zenodo.org/record/1235807|journal=Psychological Medicine|volume=35|issue=12|pages=1747–59|doi=10.1017/S0033291705006069|pmid=16202187|s2cid=28490763}} However, GAD can begin or reoccur at any point in life. Indeed, GAD is common in the elderly population.{{cite book|last=Cameron|first=Alasdair|title=Crash Course Psychiatry|publisher=Elsevier Ltd|year=2004|isbn=978-0-7234-3340-8}}

United States: Approximately 3.1 percent of people age 18 and over in a given year (9.5 million).

5.9 percent of adults were affected by GAD in 2019.{{Cite web|url=https://www.mentalhealth.org.uk/statistics|title=Statistics|website=Mental Health Foundation|access-date=2018-12-19}}

• Australia: 3 percent of adults[https://www.who.int/bulletin/pdf/2000/issue4/bu00-0485.pdf "Relating the burden of anxiety and depression to effectiveness of treatment"], World Health Organization.
• Canada: 2.5 percent{{Cite web|url=https://www.canada.ca/en/public-health/services/reports-publications/health-promotion-chronic-disease-prevention-canada-research-policy-practice/vol-37-no-2-2017/burden-generalized-anxiety-disorder-canada.html|title=The burden of generalized anxiety disorder in Canada - HPCDP: Volume 37-2, February 2017|last1=Canada|first1=Public Health Agency of|date=2017-01-31|website=aem|access-date=2018-12-19}}
• Italy: 2.9 percent{{cite journal |date=1 December 2016|title=Anxiety Disorders: Background, Anatomy, Pathophysiology|url=http://emedicine.medscape.com/article/286227-overview|website=Medscape}}
• Taiwan: 0.4 percent

The American Psychiatric Association introduced GAD as a diagnosis in the DSM-III in 1980, when anxiety neurosis was split into GAD and panic disorder. The definition in the DSM-III required uncontrollable and diffuse anxiety or worry that is excessive and unrealistic and persists for one month or longer. High rates in comorbidity of GAD and major depression led many commentators to suggest that GAD would be better conceptualized as an aspect of major depression instead of an independent disorder.{{Cite journal |last1=Kessler |first1=Ronald C. |last2=Keller |first2=Martin B. |last3=Wittchen |first3=Hans-Ulrich |date=1 March 2001 |title=The Epidemiology of Generalized Anxiety Disorder |journal=Psychiatric Clinics of North America |volume=24 |issue=1 |pages=19–39 |doi=10.1016/S0193-953X(05)70204-5 |pmid=11225507}} Many critics stated that the diagnostic features of this disorder were not well established until the DSM-III-R.{{Cite book |last=Craighead |first=W. Edward |title=Psychopathology: History, Diagnosis, and Empirical Foundations |publisher=John Wiley & Sons, Inc. |year=2013}} Since comorbidity of GAD and other disorders decreased with time, the DSM-III-R changed the time requirement for a GAD diagnosis to six months or longer.{{Cite journal |last1=Breslau |first1=Naomi |author-link=Naomi Breslau |last2=Davis |first2=Glenn C. |date=July 1985 |title=DSM-III generalized anxiety disorder: An empirical investigation of more stringent criteria |journal=Psychiatry Research |volume=15 |issue=3 |pages=231–238 |doi=10.1016/0165-1781(85)90080-0 |pmid=3875873 |s2cid=23120081 |doi-access=free}} The DSM-IV changed the definition of excessive worry and the number of associated psychophysiological symptoms required for a diagnosis. Another aspect of the diagnosis the DSM-IV clarified was what constitutes a symptom as occurring "often".{{Cite journal |last1=Wittchen |first1=Hans-Ulrich |last2=Kessler |first2=Ronald C. |last3=Zhao |first3=Shanyang |last4=Abelson |first4=Jamie |date=March–April 1995 |title=Reliability and clinical validity of UM-CIDI DSM-III-R generalized anxiety disorder |journal=Journal of Psychiatric Research |volume=29 |issue=2 |pages=95–110 |doi=10.1016/0022-3956(94)00044-R |pmid=7666382}} The DSM-IV also required difficulty controlling the worry to be diagnosed with GAD. The DSM-5 emphasized that excessive worrying had to occur more days than not and on a number of different topics. It has been stated that the constant changes in the diagnostic features of the disorder have made assessing epidemiological statistics such as prevalence and incidence difficult, as well as increasing the difficulty for researchers in identifying the biological and psychological underpinnings of the disorder. Consequently, making specialized medications for the disorder is more difficult as well. This has led to the continuation of GAD being medicated heavily with SSRIs.

• Daily Assessment of Symptoms – Anxiety
• Mental health
• Mental health professional
• Psychotherapy
• Psychiatry

{{reflist}}

• {{Cite journal |last1=McLean |first1=Carmen P. |last2=Asnaani |first2=Anu |last3=Litz |first3=Brett T. |last4=Hofmann |first4=Stefan G. |date=August 2011 |title=Gender differences in anxiety disorders: Prevalence, course of illness, comorbidity and burden of illness |journal=Journal of Psychiatric Research |language=en |volume=45 |issue=8 |pages=1027–1035 |doi=10.1016/j.jpsychires.2011.03.006 |pmc=3135672 |pmid=21439576}}

• Brown, T. A., O'Leary, T. A., & Barlow, D. H. (2001). "Generalised anxiety disorder". In D. H. Barlow (ed.), Clinical handbook of psychological disorders: A step-by-step treatment manual (3rd ed.). New York: Guilford Press.
• Barlow, D. H., & Durand, V. M. (2005). Abnormal psychology: An integrative approach. Australia; Belmont, Calif.: Wadsworth.
• {{cite journal |doi=10.1016/S0140-6736(06)69865-6 |title=Generalised anxiety disorder |year=2006 |last1=Tyrer |first1=Peter |last2=Baldwin |first2=David |journal=The Lancet |volume=368 |issue=9553 |pages=2156–66 |pmid=17174708|s2cid=18959359 }}

{{Medical resources

| ICD10 = {{ICD10|F|41|1|t|66}}

| ICD9 = {{ICD9|300.02}}

| MedlinePlus = 000917

| eMedicineSubj=article

| eMedicineTopic=916933

|ICD10CM={{ICD10CM|F41.1}}|ICD11={{ICD11|6B00}}}}

• [http://www.mayoclinic.com/health/generalized-anxiety-disorder/DS00502 Mayo Clinic] – Information on diagnosis and treatment for GAD
• [http://www.webmd.com/anxiety-panic/guide/general-anxiety-disorder WebMD] – Information on symptoms and causes of GAD
• [http://www.adaa.org Anxiety Disorders Association of America] – Information for families, clinicians, and researchers
• [https://www.nimh.nih.gov/health/publications/generalized-anxiety-disorder-gad/index.shtml National Institute of Mental Health, Generalized Anxiety Disorder: When Worry Gets Out of Control]
• [https://nccih.nih.gov/health/providers/digest/anxiety National Center for Complementary and Integrative Health, Anxiety and Complementary Health Approaches]

{{Mental and behavioural disorders|selected=neurotic}}

{{Digital media use and mental health}}

Category:Anxiety disorders

Category:Anxiety or fear-related disorders

Category:Anxiety