Clinical and economic outcomes of adjunctive therapy with pregabalin or usual care in generalized anxiety disorder patients with partial response to selective serotonin reuptake inhibitors

Abstract

BackgroundThis study is done to compare the effect of adjunctive therapy with pregabalin versus usual care (UC) on health-care costs and clinical and patients consequences in generalized anxiety disorder (GAD) subjects with partial response (PR) to a previous selective serotonin reuptake inhibitor (SSRI) course in medical practice in Spain.MethodsPost hoc analysis of patients with PR to SSRI monotherapy enrolled in a prospective 6-month naturalistic study was done. PR was defined as a Clinical Global Impression (CGI) scale score ≥3 and insufficient response with persistence of anxiety symptoms ≥16 in the Hamilton Anxiety Rating Scale (HAM-A). Two groups were analyzed: 1) adjunctive therapy (AT) with pregabalin (150–600 mg/day) to existing therapy and 2) UC (switching to a different SSRI or adding another anxiolytic different than pregabalin). Costs included GAD-related health-care resources utilization. Consequences were a combination of psychiatrist-based measurements [HAM-A, CGI, and Montgomery-Asberg Depression Rating Scale (MADRS)] and patient-reported outcomes [Medical Outcomes Study Sleep (MOS-sleep) scale, disability (World Health Organization Disability Assessment Schedule II (WHO-DAS II) and quality-of-life (Euro Qol-5D (EQ-5D)]. Changes in both health-care costs and scale scores were compared separately at end-of-trial visit by a general linear model with covariates.ResultsFour hundred eighty-six newly prescribed pregabalin and 239 UC GAD patients [mean (SD) HAM-A 26.7 (6.9) and CGI 4.1 (0.5)] were analyzed. Adding pregabalin was associated with significantly higher mean (95% CI) score reductions vs. UC in HAM-A [−14.9 (−15.6; −14.2) vs. −11.2 (−12.2; −10.2), p < 0.001] and MADRS [−11.6 (−12.2; −10.9) vs. −7.8 (−8.7; −6.8), p < 0.001]. Changes in all patient-reported outcomes favored significantly patients receiving pregabalin, including quality-of-life gain; 26.4 (24.7; 28.1) vs. 19.4 (17.1; 21.6) in the EQ-VAS, p < 0.001. Health-care costs were significantly reduced in both cohorts yielding similar 6-month costs; €1,565 (1,426; 1,703) pregabalin and €1,406 (1,200; 1,611) UC, p = 0.777. The effect of sex on costs and consequences were negligible.ConclusionIn medical practice, GAD patients with PR to SSRI experienced greater consequence improvements with adjunctive therapy with pregabalin versus UC, without increasing health-care cost. The effect of pregabalin was independent of patient gender.

Management of treatment-resistant generalized anxiety disorder

“…8,18 The efficacy of pregabalin as an adjunctive treatment in TR-GAD has been studied in randomized, double-blind, placebo-controlled trials. 19,20 Studies were 8 weeks in length and used the HAM-A as the primary endpoint for measuring anxiety refractory to treatment with antidepressants. Results from these trials show clinical response compared to placebo 19 or usual care 20 by week 1 and the addition of pregabalin as an augmenting agent was associated with significantly higher benefit in anxiety outcomes.…”

“…19,20 Studies were 8 weeks in length and used the HAM-A as the primary endpoint for measuring anxiety refractory to treatment with antidepressants. Results from these trials show clinical response compared to placebo 19 or usual care 20 by week 1 and the addition of pregabalin as an augmenting agent was associated with significantly higher benefit in anxiety outcomes. A potential benefit of using pregabalin may be this quick time to effect as demonstrated in these studies, compared to the delayed effect of trialing another antidepressant medication.…”

Die generalisierte Angststörung – ein Update

“…Lassen sich jedoch keine diesbezüglichen Gründe eruieren, kann man entweder auf eine Substanz der gleichen Gruppe oder in eine andere Wirkstoffklasse wechseln und den beschriebenen Behandlungsablauf erneut beginnen 63 . Sind entsprechende Therapieversuche wiederholt nicht mit einer zufriedenstellenden Besserung der GAS-Symptomatik verbunden, können Substanzen der weiteren Wahl eingesetzt werden.…”

“…Insbesondere vor dem Hintergrund der substanzspezifisch unterschiedlich ausgeprägten metabolischen und endokrinologischen Nebenwirkungsprofile sowie Hinweisen auf substanzinduzierte strukturelle Hirnveränderungen als möglicher Klasseneffekt kann der Einsatz dieser Substanzen bei der GAS deshalb unserer Ansicht nach gegenwärtig nicht empfohlen werden. Lassen sich jedoch keine diesbezüglichen Gründe eruieren, kann man entweder auf eine Substanz der gleichen Gruppe oder in eine andere Wirkstoffklasse wechseln und den beschriebenen Behandlungsablauf erneut beginnen [63]. Sind entsprechende Therapieversuche wiederholt nicht mit einer zufriedenstellenden Besserung der GAS-Symptomatik verbunden, können Substanzen der weiteren Wahl eingesetzt werden.…”

“…B. [63]). Entsprechend kann diesbezüglich eine duale Behandlung neben einem "Switch" eine eine weitere Option darstellen.…”