GAD has a lifetime prevalence of 5.7% with a higher prevalence in those over 65 years of age. This ailment may cause significant impairment in daily physical, psychological, and social functioning. The diagnosis of this disorder is often missed as the patient may not complain of specific symptoms. When treating individuals with a major psychiatric illness such as major depression and bipolar disorder we may miss the comorbid GAD resulting in a therapeutic impasse. This is one of the largest contemporary studies of GAD treatment. It included trials across a broad range of settings. Sixteen trials were published in Chinese and provided direct evidence for several comparisons that would not be available otherwise. This network meta-analysis assumes that the trials are similar. The exclusion of the Chinese trials did not make a difference in the findings.
A network meta-analysis is an extension of a pairwise meta-analysis which facilitates comparisons of multiple interventions that have not been studied in a head-to-head fashion.
Duloxetine, pregabalin, venlafaxine, and escitalopram were more efficacious than placebo based on a large sample size. Mirtazapine, sertraline, fluoxetine, buspirone, and agomelatine were also effective but the information was based on a smaller sample. This meta-analysis strengthens the case for using SSRIs and SNRIs for treating GAD. Benzodiazepines, due to their addiction potential and implications with alcohol and opiates should be avoided.
Quetiapine proved highly effective however, the side-effects such as sedation, tiredness, and the risk of tardive dyskinesia limit its use.
Please also consider the FDA indications while making a choice. Please note that pregabalin does not have any FDA indications for the treatment of psychiatric disorders.
This study strengthens the clinical basis for the use of duloxetine, venlafaxine, escitalopram, and pregabalin (not FDA approved in mental illness) as first-line choices for GAD treatment. Sertraline, fluoxetine, and buspirone are also first-line choices but the data was limited by small sample sizes. Vortioxetine and vilazodone are not effective for GAD. Mirtazapine has only been studied in China and has a risk of weight gain.
Speed: Buspirone and hydroxyzine are faster acting than most drugs in this analysis with reasonable effects.
Benzodiazepines get pushed to the back for the known reasons.
In my opinion, we should use the GAD-7 scale to screen for anxiety routinely especially at the initial evaluations. I would use the SSRIs first line followed by duloxetine. I would not give up on buspirone and would avoid hydroxyzine in older adults (anticholinergic effects). If patients have comorbid bipolar illness, I would try to avoid venlafaxine to avoid precipitating a manic episode. I would avoid the use of benzodiazepines except for emergencies. I always like to combine medication treatment with CBT or alternative treatments such as meditation or yoga.