Efficacy and Tolerability of a Standardized Herbal Product from Galphimia glauca on Generalized Anxiety Disorder. A Randomized, Double-Blind Clinical Trial Controlled with Lorazepam

Abstract

Galphimia glauca Cav. is a plant used in Mexican traditional medicine as a ”nerve tranquilizer”. Previous studies have demonstrated that the methanolic extract from this plant species possess an anxiolytic effect. Galphimine B (GB, a nor-seco-triterpene), is the active principle, with an innovative action mechanism. Against this background, a standardized herbal medicinal product was developed from the aqueous extract of G. glauca (GgHP). The present work compared the therapeutic effectiveness, safety, and tolerability of the new GgHP with lorazepam on patients with generalized anxiety disorder (GAD). By means of a controlled, randomized, double-blind clinical trial, outpatients of either sex who matched the DSM-IV diagnostic criteria with a score of ≥ 19 points on the Hamilton Anxiety Scale (HAM-A) were included. The experimental group was treated orally with GgHP in capsules twice a day for 4 weeks. The control group received lorazepam (1 mg) under the same conditions and presentation. A total of 152 patients were included in the trial (72 in the experimental group). From the first week of treatment, GgHP showed important anxiolytic effectiveness, very similar to that produced with lorazepam. Both treatments showed therapeutic safety (no alterations on biochemical analysis of hepatic and renal function). Nevertheless, concerning side effects, GgHP evidenced a considerably higher tolerability than lorazepam.

Abbreviations

ALP: alkaline phosphatase

ALT: alanine aminotransferase

AST: aspartate aminotransferase

GAD: generalized anxiety disorder

GB: galphimine B

GgHP: standardized herbal medicinal product from the aqueous extract of Galphimia glauca

HAM-A: Hamilton anxiety scale

SSRI: selective serotonin reuptake inhibitors

Galphimia glauca - Malpighiaceae - galphimine B - plant-derived medicine - anxiolytic, lorazepam - generalized anxiety disorder (GAD)

References

• 1 American Psychiatric Association. Diagnostic and statistical manual of mental disorders, fourth edition, text revision. Washington DC; American Psychiatric Association 2000: 472-6.
• 2 Kessler R C, Brandenburg N, Lane M, Roy-Byrne P, Stang P D, Stein D J. et al . Rethinking the duration requirement for generalized anxiety disorder: evidence from the National Comorbidity Survey Replication.  Psychol Med. 2005;  35 1073-82.
• 3 Kessler R C, McGonagle K A, Zhao S, Nelson C B, Hughes M, Eshleman S. et al . Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey.  Arch Gen Psychiatry. 1994;  51 8-19.
• 4 Couvee J E, Zitman F G. The benzodiazepine withdrawal symptom questionnaire: psychometric evaluation during a discontinuation program in depressed chronic benzodiazepine users in general practice.  Addiction. 2002;  97 337-45.
• 5 Rickels K, Schweizer E, DeMartinis N, Mandos L, Mercer C. Gepirone and diazepam in generalized anxiety disorder: a placebo-controlled trial.  J Clin Psychopharmacol. 1997;  17 272-7.
• 6 Llorca P M, Spadone C, Sol O, Danniau A, Bougerol T, Corruble E. et al . Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study.  J Clin Psychiatry. 2002;  63 1020-7.
• 7 Bielski R J, Bose A, Chang C C. A double-blind comparison of escitalopram and paroxetine in the long-term treatment of generalized anxiety disorder.  Ann Clin Psychiatry. 2005;  17 65-9.
• 8 Feltner D E, Crockatt J G, Dubovsky S J, Cohn C K, Shrivastava R K, Targum S D. et al . A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder.  J Clin Psychopharmacol. 2003;  23 240-9.
• 9 Martínez M. Las plantas medicinales de México, 5th edition.  Mexico: Andres. Botas;  1969 402-3.
• 10 Estrada E. Jardín botánico de plantas medicinales. Mexico; Universidad Autónoma de Chapingo. Departamento de Fitotécnia 1985: 15.
• 11 Tortoriello J, Lozoya X. Effect of Galphimia glauca methanolic extract on neuropharmacological tests.  Planta Med. 1992;  58 234-6.
• 12 Herrera-Ruiz M, Jimenez-Ferrer J E, De Lima T C, Aviles-Montes D, Perez-Garcia D, Gonzalez-Cortazar M. et al . Anxiolytic and antidepressant-like activity of a standardized extract from Galphimia glauca .  Phytomedicine. 2006;  13 23-8.
• 13 Herrera-Ruiz M, Gonzalez-Cortazar M, Jimenez-Ferrer E, Zamilpa A, Alvarez L, Tortoriello J. et al . Anxiolytic effect of natural galphimines from Galphimia glauca and their chemical derivatives.  J Nat Prod. 2006;  69 59-61.
• 14 Tortoriello J, Ortega A. Sedative effect of galphimine-B, a nor-seco-triterpenoid from Galphimia glauca .  Planta Med. 1993;  59 398-400.
• 15 Toscano R A, Ortega A, Maldonado E, Gaviño R, Lozoya X, Tortoriello J. Structure of galphimine B.  Acta Cryst C. 1993;  49 774-6.
• 16 Tortoriello J, Ortega A, Herrera-Ruíz M, Trujillo J, Reyes-Vázquez C. Galphimine-B modifies electrical activity of ventral tegemental area neurons in rats.  Planta Med. 1998;  64 309-13.
• 17 Prieto-Gomez B, Tortoriello J, Vazquez-Alvarez A, Reyes-Vazquez C. Galphimine B modulates synaptic transmission on dopaminergic ventral tegmental area neurons.  Planta Med. 2003;  69 38-43.
• 18 González-Cortazar M, Tortoriello J, Álvarez L. Norsecofriedelanos as spasmolytics. Advances of structure activity relationships.  Planta Med. 2005;  71 711-6.
• 19 Aguilar-Santamaría L, Ramírez G, Herrera-Arellano A, Zamilpa A, Jiménez J, Alonso-Cortes D. et al . Toxicological and cytotoxic evaluation of standardized extracts of Galphimia glauca .  J Ethnopharmacol. 2007;  109 35-40.
• 20 Rojas G, Aranda E, Navarro V, Zamilpa A, Tortoriello J. In vitro propagation of Galphimia glauca and content of the sedative compound galphimine-B in wild and micropropagated plants.  Planta Med. 2005;  71 076-8.
• 21 Organización Mundial de la Salud. Directrices de la OMS sobre buenas prácticas agrícolas y de recolección (BPAR) de plantas medicinales. Ginebra; Organización Mundial de la Salud 2003.
• 22 Comisión permanente de la farmacopea de los estados unidos mexicanos. Farmacopea de los Estados Unidos mexicanos, 8th edition. México; Secretaría de Salud 2004: 311-572.
• 23 Alpert J E, Franznick D A, Hollander S B, Fava M. Gepirone extended-release treatment of anxious depression: evidence from a retrospective subgroup analysis in patients with major depressive disorder.  . 2004;  65 1069-75.
• 24 Boerner R J, Sommer H, Berger W, Kuhn U, Schmidt U, Mannel M. Kava-Kava extract LI 150 is as effective as Opipramol and Buspirone in generalised anxiety disorder - an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patients.  Phytomedicine. 2003;  10 38-49.
• 25 Andreatini R, Sartori V A, Seabra M L, Leite J R. Effect of valepotriates (valerian extract) in generalized anxiety disorder: a randomized placebo-controlled pilot study.  Phytother Res. 2002;  16 650-4.
• 26 Schulze J, Raasch W, Siegers C P. Toxicity of kava pyrones, drug safety and precautions-a case study.  Phytomedicine. 2003;  10 68-73.
• 27 Hadley S, Petry J J. Valerian.  Am Fam Physician. 2003;  67 1755-8.
• 28 Rickels K, Pollack M H, Feltner D E, Lydiard R B, Zimbroff D L, Bielski R J. et al . Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam.  Arch Gen Psychiatry. 2005;  62 1022-30.
• 29 Goodman W K, Bose A, Wang Q. Treatment of generalized anxiety disorder with escitalopram: pooled results from double-blind, placebo-controlled trials.  J Affect Disord. 2005;  87 161-7.