A comprehensive new network meta-analysis on medications for generalized anxiety disorder has concluded that there are several effective treatment choices available across different classes of medication and that a failure of initial drug therapy might not be a reason to abandon a pharmacologic treatment strategy.
While treatment decisions may previously have been based on factors such as patient preference, clinician experience, comorbidities, and potential drug interactions, this meta-analysis allows an evidence-based prioritization of the many treatment options for GAD.
The meta-analysis found that duloxetine, venlafaxine, escitalopram, and pregabalin were effective and relatively well-tolerated. Mirtazapine, sertraline, fluoxetine, buspirone, and agomelatine, were also effective and well-tolerated but the supporting evidence base was smaller. Quetiapine, paroxetine, and benzodiazepines were effective but poorly tolerated.
The findings were based on 89 trials published between 1994 and 2017, and included more than 25,000 patients randomly assigned to 22 different active drugs or placebo. Outcomes were defined as mean difference in change in Hamilton Anxiety Scale score and acceptability (study discontinuations for any cause).
This topic has been updated to reflect these findings in the context of clinical experience with these drugs, and now recommends duloxetine, venlafaxine, and escitalopram as first-line options, with mirtazapine, sertraline, fluoxetine, paroxetine, and buspirone as alternatives. Quetiapine, benzodiazepines, and pregabalin are second-line options and should generally only be prescribed if first-line options have proved ineffective. Tricyclic antidepressants are not covered by the meta-analysis, but remain a second-line option.
Common condition defined as chronic, excessive worry for at least 6 months that causes distress or impairment.
At least 3 key symptoms out of a possible 6 are required to make a diagnosis: restlessness or nervousness, easy fatigability, poor concentration, irritability, muscle tension, or sleep disturbance.
It is in part a diagnosis of exclusion: medical conditions, medications or substances, and other mental disorders should be ruled out as a primary cause.
Physical examination and laboratory studies are generally normal if no coexisting medical problems or substance abuse issues exist.
Treatment is with either pharmacotherapy, psychotherapy, or a combination.
Generalized anxiety disorder (GAD) is defined as at least 6 months of excessive worry about everyday issues that is disproportionate to any inherent risk, causing distress, or impairment. The worry is not confined to features of another mental disorder, or as a result of substance abuse or a general medical condition. At least 3 of the following symptoms are present most of the time: restlessness or nervousness, being easily fatigued, poor concentration, irritability, muscle tension, or sleep disturbance.  Other common complaints are autonomic in nature, such as sweating, lightheadedness, palpitations, dizziness, and epigastric discomfort.  Anxiety may be "free-floating" (i.e., not restricted to, or even strongly predominating in, any particular environmental circumstances).  Examples of worries include fears that the patient or a relative will shortly become ill or have an accident.
Emeritus Professor Medical Director
Anxiety Treatment and Research Centre
McMaster University and St Joseph’s Hospital
RPS has personally received royalties for articles published in UpToDate (Wolters Kluwer) and the Compendium of Therapeutic Choices, 2nd edition (Canadian Pharmacists Association).
Southern District Health Board
Department of Psychological Medicine
Dunedin School of Medicine
CG is an author of the Royal Australian and New Zealand College of Psychiatrists clinical practice guideline on social phobia, panic disorder, and generalized anxiety disorder. He is a contributor to the Cochrane Common Mental Disorders group, writing on generalized anxiety disorder, and has authored papers relating to heterogeneity of the database separately to Cochrane work. Otago University has commercial and research relationships with multiple pharmaceutical companies.
Dr Richard P. Swinson and Dr Christopher Gale would like to gratefully acknowledge Dr Elizabeth Hoge and Dr Phebe Tucker, previous contributors to this topic.
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