Functional recovery in generalised anxiety disorder: the utility of venlafaxine

Background

Generalized anxiety disorder (GAD) is highly prevalent worldwide and is associated with significant functional impairment. Severity of the disorder and high prevalence of comorbid illness markedly impair daily functioning. Crucially, symptoms of chronic excessive worry that are not infrequently accompanied by restlessness, muscle tension, irritability and difficulty with concentration can cause significant disability [1]. These symptoms may persist even when the patient is in apparent clinical remission and impede functional recovery. Addressing them effectively may aid with return to work, school and recreation. The efficacy of venlafaxine (a serotonin norepinephrine reuptake inhibitor) in GAD has been established in short- and long-term randomized studies. The objective of this study is to explore the effectiveness of venlafaxine in alleviating these symptoms [1,2].

Methods

We performed a targeted literature search to explore the effectiveness of venlafaxine in addressing excessive worry and specific associated symptoms in GAD. Individual items of the Hamilton anxiety rating scale (HAM-A) support the measurement of anxious mood, tension, symptoms of intellectual impairment and somatic (muscular) symptoms. These symptoms may also manifest as observable behaviors during the interview such as fidgeting, restlessness or pacing, and a strained facial expression. Our review identified those placebo-controlled studies that reported scores of individual HAM-A items, from which the findings presented here are derived.

Results

	Anxious Mood		Tension		Intellectual symptoms		Somatic (muscular) symptoms		Behavior at interview
Study	Venlafaxine	Placebo	Venlafaxine	Placebo	Venlafaxine	Placebo	Venlafaxine	Placebo	Venlafaxine	Placebo
Meoni et al. 2001 (Effect size at 8 weeks)	1.4	1	1.3	0.9	1	0.7	0.9	0.7	1.1	0.8
Meoni et al. 2001 (Effect size at 6 months)	1.5	0.9	1.4	0.9	1.1	0.7	1	0.8	1.2	0.8
Otsubo et al. 2025 (LS Mean change from baseline at 8 weeks)	1.3*	1	1.3*	1	0.9	0.8	0.8*	0.6	0.7	0.6

*P<0.05 compared to placebo

Venlafaxine demonstrated superiority over placebo in addressing symptoms of anxious mood, tension, intellectual impairment and somatic (muscular) symptoms in short- and long-term studies. Additionally, Otsubo et al reported statistically significant improvement (P=0.012) in the total scores of Sheehan’s Disability Scale (SDS) in 8 weeks of their study comparing venlafaxine treatment to placebo. The effect was seen across work, social and family life domains, denoting an improvement in functioning [2].

Conclusions

These findings point to superiority of venlafaxine over placebo to alleviate excessive worry and specific associated symptoms that may impede functional recovery. Symptoms of restlessness, muscle tension, irritability and difficulty with concentration may stay unrecognized in patients who appear to be in remission and prolong the course of illness. Clinicians may need to specifically look for them and an approach of measurement-based care with instruments such as HAM-A can support clinical practice. This will help optimize treatment with agents such as venlafaxine used for an adequate duration, and get the patient back to functional recovery. Our findings prompt the need for further research on factors impeding functional recovery in GAD and measures to overcome them.

References

Meoni P, Salinas E, Brault Y, Hackett D. Pattern of symptom improvement following treatment with venlafaxine XR in patients with generalized anxiety disorder. J Clin Psychiatry. 2001 Nov;62(11):888-93.
Otsubo T, Watanabe K, Inoue T, Inagaki A, Kikuchi T, Nomoto K, Higa S, Asami Y, Sun B, Marschall K. A randomized, double-blinded, placebo-controlled study to evaluate the efficacy and safety of venlafaxine extended release in Japanese patients with generalized anxiety disorder. Psychiatry Clin Neurosci. 2025 Dec;79(12):849-858.