The response is either a clinically meaningful improvement in symptoms or a specific magnitude of change in a rating scale score from baseline.
Given the extensive use of health care resources, the residual subsyndromal symptoms, and the substantial relapse rate of anxious patients, the goal of therapy has evolved to that of achieving remission. Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorder.
While the 2- to 4-week delay in onset of therapeutic effect may be discouraging, significant reductions in “anxious mood” have been documented as early as 1 week into treatment.
Historically, benzodiazepines were the mainstay of GAD treatment, although the appropriateness of their use for long-term therapy is now under scrutiny.
Benzodiazepines indirectly affect the release and reuptake of monoamines via enhancement of the inhibitory effects of g-aminobutyric acid, thereby modulating fear, stress, and anxiety responses. Buspirone in depressed outpatients: a controlled study.
Aside from the obvious issue of potential dependence with prolonged use, benzodiazepines are not desirable as first-line therapy because of their potential for withdrawal syndromes and rebound effects on abrupt discontinuation.
The anxiolytic buspirone has been used with moderate success but has not consistently demonstrated utility in any of the potentially comorbid conditions that can accompany GAD, with the exception of MDD. Is the cutoff to define remission on the Hamilton Rating Scale for Depression too high?
A retrospective analysis demonstrated significant improvement in HAM-A and global improvement scores relative to baseline, and another study reported buspirone’s failure to differ from placebo on numerous outcome measures.
In addition, buspirone was shown to be superior to placebo in improving anxiety symptoms as well as coexisting depressive symptoms in patients with GAD. Remission is not static but rather should be sustainable over a considerable time—at least 8 consecutive weeks. Treatment options The treatment of GAD involves a sequential process of first resolving the acute, symptomatic anxiety and then maintaining a longer-term constant suppression of chronic anxiety. Remission is defined as a HAM-A score of 7 or less, with global recovery achieved at a CGI-I score of 1 (“not ill at all” or “borderline mentally ill”), and functional recovery at an SDS score of 5 or less. For this designation of remission to be clinically meaningful, it must incorporate a time component. Between 50% and 60% of patients respond clinically to therapy, but only one-third to one-half attain remission or realize full recovery during the acute phase of treatment.13 Some patients may achieve “durable remission” within the first 4 to 8 weeks of therapy, which may indicate an eventual sustained remission (lasting 4 to 9 months after acute treatment).