Stosowanie pregabaliny w leczeniu uogólnionych zaburzeń lękowych. Czy należy bać się wysokich dawek?

• Authors: Marcin Wojtera , Tomasz Sobów

Title variants

EN

The application of pregabalin in general anxiety disorders treatment. Should one be afraid of high doses?

• Languages of publication: EN PL

Abstracts

EN

General anxiety disorder is a chronic mental disorder with intensification and improvement stages alternately. Emotional, cognitive and physiological symptoms are present in its course (somatic anxiety symptoms), disturbing daily functioning of the patients in personal and professional life. The nuclear symptom is “free-floating anxiety” intensifying in various situations related to insecurity. The basic goal of treatment is remission. Both non-pharmacological methods (e.g. behavioural-cognitive psychotherapy) and pharmacotherapy are applied. Medicines of best, proven effectiveness as regards general anxiety disorder, recommended to be used as the first ones, are selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors and pregabalin. In Poland, pregabalin – though registered – has been absent for many years from the psychiatric formulary – owing to high price and lack of refund with the indication “general anxiety disorder.” Currently, the situation has changed. Pregabalin is a derivative of gamma-aminobutyric acid, which shows no action similar to that acid. The substance is a ligand of the aiding subunit (α2-δ protein) opened through the change in the membrane tone of the calcium channel, which is present at the presynaptic neuron terminals localised in the brain and spinal cord. The combination of pregabalin with subtype 1 of subunit α2-δ (α2-δ-1) is responsible for anxiolytic operation, modulating pain impulse and anti-epileptic operation. Certainly, there is a possibility that the medicine operates in another, so far unknown mechanism, but up till now, there are no available data indicating that. The study covers and discusses the data available in bibliography concerning the application of pregabalin in clinical practice, its wide indications, safety profile and recommendations concerning dosage.

PL

Zaburzenie lękowe uogólnione jest przewlekłym zaburzeniem psychicznym, przebiegającym z okrasami zaostrzeń i popraw. W jego przebiegu pojawiają się objawy emocjonalne, poznawcze i fizjologiczne (somatyczne objawy lęku), zaburzające codzienne funkcjonowanie chorych w życiu osobistym i zawodowym. Osiowym objawem jest „lęk wolnopłynący”, który znacząco nasila się w różnych sytuacjach związanych z niepewnością. Podstawowy cel leczenia stanowi uzyskanie remisji. Wykorzystuje się zarówno metody niefarmakologiczne (np. psychoterapię behawioralno-poznawczą), jak i farmakoterapię. Lekami o najlepiej udowodnionej skuteczności w zaburzeniu lękowym uogólnionym, zalecanymi do stosowania w pierwszym rzucie, są inhibitory zwrotnego wychwytu serotoniny, inhibitory zwrotnego wychwytu serotoniny i noradrenaliny oraz pregabalina. W Polsce pregabalina, choć zarejestrowana, przez wiele lat była praktycznie nieobecna w receptariuszu psychiatrycznym – ze względu na wysoką cenę i brak refundacji we wskazaniu „zaburzenie lękowe uogólnione”. Obecnie ta sytuacja się zmieniła. Pregabalina to pochodna kwasu gamma-aminomasłowego, która nie wykazuje działania podobnego do tego kwasu. Substancja ta jest ligandem pomocniczej podjednostki (białko α2-δ) otwieranego przez zmianę napięcia błonowego kanału wapniowego, który występuje na zakończeniach presynaptycznych neuronów zlokalizowanych w mózgu i rdzeniu kręgowym. Łączenie się pregabaliny z podtypem 1 podjednostki α2-δ (α2-δ-1) odpowiada za działanie przeciwlękowe, modulujące impulsację bólową i działanie przeciwpadaczkowe. Istnieje oczywiście możliwość, że lek działa jeszcze w innym, nieznanym dotychczas mechanizmie, lecz na razie jednak żadne dostępne dane na to nie wskazują. W pracy zebrano i omówiono dostępne w piśmiennictwie dane dotyczące zastosowania pregabaliny w praktyce klinicznej, jej szerokie wskazania, profil bezpieczeństwa i zalecenia dotyczące dawkowania.

Keywords

EN

GAD; general anxiety disorder; pregabalin; pregabalina; zaburzenie lękowe uogólnione

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Psychiatria i Psychologia Kliniczna
• Year: 2016
• Volume: 16
• Issue: 2
• Pages: 91–98

Contributors

author

Marcin Wojtera

• Oddział Psychogeriatrii, Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi, Łódź, Polska

author

Tomasz Sobów

• Oddział Psychogeriatrii, Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi, Łódź, Polska. Zakład Psychologii Lekarskiej, Wydział Nauk o Zdrowiu, Uniwersytet Medyczny w Łodzi, Łódź, Polska

References

• Alyahri A, Goodman R: The prevalence of DSM-IV psychiatric disorders among 7–10 year old Yemeni schoolchildren. Soc Psychiatry Psychiatr Epidemiol 2008; 43: 224–230.
• Aupperle RL, Ravindran L, Tankersley D et al.: Pregabalin influences insula and amygdala activation during anticipation of emotional images. Neuropsychopharmacology 2011; 36: 1466–1477.
• Baldwin DS, Ajel K, Masdrakis VG et al.: Pregabalin for the treatment of generalized anxiety disorder: an update. Neuropsychiatr Dis Treat 2013; 9: 883–892.
• Baldwin DS, Schweizer E, Xu Y et al.: Does early improvement predict endpoint response in patients with generalized anxiety disorder (GAD) treated with pregabalin or venlafaxine XR? Eur Neuropsychopharmacol 2012; 22: 137–142.
• Bazil CW, Dave J, Cole J et al.: Pregabalin increases slow-wave sleep and may improve attention in patients with partial epilepsy and insomnia. Epilepsy Behav 2012; 23: 422–425.
• Bech P: Dose-response relationship of pregabalin in patients with generalized anxiety disorder. A pooled analysis of four placebo-controlled trials. Pharmacopsychiatry 2007; 40: 163–168.
• Bollu V, Bushmakin AG, Cappelleri JC et al.: Pregabalin reduces sleep disturbance in patients with generalized anxiety disorder via both direct and indirect mechanisms. Eur J Psychiatry 2010; 24: 18–27.
• Brown T: 100 best-selling, most prescribed branded drugs through March. Medscape Medical News 2015. Available from: http://www.medscape.com/viewarticle/844317.
• Combs H, Markman J: Anxiety disorders in primary care. Med Clin North Am 2014; 98: 1007–1023
• Dell’Osso B, Camuri G, Benatti B et al.: Differences in latency to first pharmacological treatment (duration of untreated illness) in anxiety disorders: a study on patients with panic disorder, generalized anxiety disorder and obsessive-compulsive disorder. Early Interv Psychiatry 2013; 7: 374–380.
• Feltner DE, Crockatt JG, Dubovsky SJ et al.: A randomized, doubleblind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder. J Clin Psychopharmacol 2003; 23: 240–249.
• Feltner D, Wittchen HU, Kavoussi R et al.: Long-term efficacy of pregabalin in generalized anxiety disorder. Int Clin Psychopharmacol 2008; 23: 18–28.
• Gahr M, Freudenmann RW, Hiemke C et al.: Pregabalin abuse and dependence in Germany: results from a database query. Eur J Clin Pharmacol 2013; 69: 1335–1342.
• Garcia-Borreguero D, Larrosa O, Williams AM et al.: Treatment of restless legs syndrome with pregabalin: a double-blind, placebocontrolled study. Neurology 2010; 74: 1897–1904.
• Gonano C, Latzke D, Sabeti-Aschraf M et al.: The anxiolytic effect of pregabalin in outpatients undergoing minor orthopaedic surgery. J Psychopharmacol 2011; 25: 249–253.
• Grant BF, Hasin DS, Stinson FS et al.: Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychol Med 2005; 35: 1747–1759.
• Holsboer-Trachsler E, Prieto R: Effects of pregabalin on sleep in generalized anxiety disorder. Int J Neuropsychopharmacol 2013; 16: 925–936.
• Kasper S, Herman B, Nivoli G et al.: Efficacy of pregabalin and venlafaxine-XR in generalized anxiety disorder: results of a doubleblind, placebo-controlled 8-week trial. Int Clin Psychopharmacol 2009; 24: 87–96.
• Kasper S, Iglesias-García C, Schweizer E et al.: Pregabalin long-term treatment and assessment of discontinuation in patients with generalized anxiety disorder. Int J Neuropsychopharmacol 2014; 17: 685–695.
• Kessler RC, Brandenburg N, Lane M et al.: Rethinking the duration requirement for generalized anxiety disorder: evidence from the National Comorbidity Survey Replication. Psychol Med 2005; 35: 1073–1082.
• Kessler RC, Frank RG, Edlund M et al.: Differences in the use of psychiatric outpatient services between the United States and Ontario. N Engl J Med 1997; 336: 551–557.
• Kim JS, Bashford G, Murphy TK et al.: Safety and efficacy of pregabalin in patients with central post-stroke pain. Pain 2011; 152: 1018–1023.
• Lieb R, Becker E, Altamura C: The epidemiology of generalized anxiety disorder in Europe. Eur Neuropsychopharmacol 2005; 15: 445–452.
• Lydiard RB, Rickels K, Herman B et al.: Comparative efficacy of pregabalin and benzodiazepines in treating the psychic and somatic symptoms of generalized anxiety disorder. Int J Neuropsychopharmacol 2010; 13: 229–241.
• LYRICA. Available from: http://labeling.pfizer.com/ShowLabeling.aspx?id=561.
• Lyrica. Available from: http://www.ema.europa.eu/docs/pl_PL/document_library/EPAR_-_Summary_for_the_public/human/000546/WC500046603.pdf.
• Maier W, Linden M, Sartorius N: Psychische Erkrankungen in der Allgemeinpraxis: Ergebnisse und Schlußfolgerungen einer WHO-Studie. Dtsch Arztebl 1996; 93: A-1202–A-1206.
• Mandos LA, Reinhold JA, Rickels K: Achieving remission in generalized anxiety disorder: what are the treatment options? Psychiatr Times 2009; 26: 38–41.
• Marencak J, Cossons NH, Darekar A et al.: Investigation of the clinical efficacy and safety of pregabalin alone or combined with tolterodine in female subjects with idiopathic overactive bladder. Neurourol Urodyn 2011; 30: 75–82.
• Montgomery SA, Tobias K, Zornberg GL et al.: Efficacy and safety of pregabalin in the treatment of generalized anxiety disorder: a 6-week, multicenter, randomized, double-blind, placebo-controlled comparison of pregabalin and venlafaxine. J Clin Psychiatry 2006; 67: 771–782.
• Montgomery S, Chatamra K, Pauer L et al.: Efficacy and safety of pregabalin in elderly people with generalised anxiety disorder. Br J Psychiatry 2008; 193: 389–394.
• Nutt D, Mandel F, Baldinetti F: Early onset anxiolytic efficacy after a single dose of pregabalin: double-blind, placebo- and activecomparator controlled evaluation using a dental anxiety model. J Psychopharmacol 2009; 23: 867–873.
• Ogawa S, Satoh J, Arakawa A et al.: Pregabalin treatment for peripheral neuropathic pain: a review of safety data from randomized controlled trials conducted in Japan and in the west. Drug Saf 2012; 35: 793–806.
• Pande AC, Crockatt JG, Feltner DE et al.: Pregabalin in generalized anxiety disorder: a placebo-controlled trial. Am J Psychiatry 2003; 160: 533–540.
• Pohl RB, Feltner DE, Fieve RR et al.: Efficacy of pregabalin in the treatment of generalized anxiety disorder: double-blind, placebocontrolled comparison of BID versus TID dosing. J Clin Psychopharmacol 2005; 25: 151–158.
• Pużyński S, Wciórka J (eds.): Klasyfikacja zaburzeń psychicznych i zaburzeń zachowania w ICD-10. Badawcze kryteria diagnostyczne. Uniwersyteckie Wydawnictwo Medyczne „Vesalius”, Kraków – Warszawa 2000.
• Reinhold JA, Rickels K: Pharmacological treatment for generalized anxiety disorder in adults: an update. Expert Opin Pharmacother 2015; 16: 1669–1681.
• Rickels K, Pollack MH, Feltner DE et al.: Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, doubleblind, placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry 2005; 62: 1022–1030.
• Rickels K, Rynn M, Iyengar M et al.: Remission of generalized anxiety disorder: a review of the paroxetine clinical trials database. J Clin Psychiatry 2006; 67: 41–47.
• Rickels K, Shiovitz TM, Ramey TS et al.: Adjunctive therapy with pregabalin in generalized anxiety disorder patients with partial response to SSRI or SNRI treatment. Int Clin Psychopharmacol 2012; 27: 142–150.
• Roth T, van Seventer R, Murphy TK et al.: The effect of pregabalin on pain-related sleep interference in diabetic peripheral neuropathy or postherpetic neuralgia: a review of nine clinical trials. Curr Med Res Opin 2010; 26: 2411–2419.
• Schifano F: Misuse and abuse of pregabalin and gabapentin: cause for concern? CNS Drugs 2014; 28: 491–496.
• Sjoberg G, Feychting K: Pregabalin overdose in adults and adolescents – experience in Sweden. Clin Toxicol 2010; 48: 282.
• Stahl SM, Porreca F, Taylor CP et al.: The diverse therapeutic actions of pregabalin: is a single mechanism responsible for several pharmacological activities? Trends Pharmacol Sci 2013; 34: 332–339.
• Taylor CP, Angelotti T, Fauman E: Pharmacology and mechanism of action of pregabalin: the calcium channel α2–δ (alpha2–delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res 2007; 73: 137–150.
• Valente MM, Bortolotto V, Cuccurazzu B et al.: α2δ ligands act as positive modulators of adult hippocampal neurogenesis and prevent depression-like behavior induced by chronic restraint stress. Mol Pharmacol 2012; 82: 271–280.
• Wittchen HU, Jacobi F: Size and burden of mental disorders in Europe – a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 2005; 15: 357–376.
• Wittchen HU, Jacobi F, Rehm J et al.: The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 2011; 21: 655–679.
• Wittchen HU, Zhao S, Kessler RC et al.: DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51: 355–364.
• Wood DM, Berry DJ, Glover G et al.: Significant pregabalin toxicity managed with supportive care alone. J Med Toxicol 2010; 6: 435–437.
• Zaccara G, Perucca P, Gangemi PF: The adverse event profile of pregabalin across different disorders: a meta-analysis. Eur J Clin Pharmacol 2012; 68: 903–912.

• Document Type: review