Duloksetyna – profil farmakologiczny i kliniczny leku z grupy inhibitorów zwrotnego wychwytu serotoniny i noradrenaliny

• Authors: Marcin Wojtera , Tomasz Sobów

Title variants

EN

Duloxetine: the pharmacological and clinical profile of a drug from the group of serotonin and noradrenaline reuptake inhibitors

• Languages of publication: PL

Abstracts

PL

Duloksetyna, inhibitor zwrotnego wychwytu serotoniny i noradrenaliny, jest zarejestrowana w Polsce w leczeniu zaburzeń depresyjnych, zaburzenia lękowego uogólnionego i obwodowej neuropatii cukrzycowej. Badania potwierdziły też skuteczność leku w innych zaburzeniach związanych z obecnością bólu neuropatycznego, w fibromialgii, nietrzymaniu moczu oraz łagodzeniu objawów towarzyszących menopauzie. Duloksetyna podawana jest doustnie w formie kapsułek dojelitowych (30, 60, 90 i 120 mg). Stężenie leku w osoczu wykazuje dużą zmienność osobniczą. Bezwzględna dostępność biologiczna wynosi średnio 50%, może się jednak wahać od 32 do 80%. Duloksetyna wiąże się u ludzi z białkami osocza w 96%, jest intensywnie metabolizowana przez CYP1A2 i CYP2D6. Z uwagi na intensywny metabolizm przez CYP1A2 substancje hamujące ten enzym – fluwoksamina, ciprofloksacyna czy enoksacyna – zdecydowanie zwiększają stężenie duloksetyny i mogą spowodować wystąpienie objawów toksycznych. W zarejestrowanych wskazaniach duloksetyna wykazuje co najmniej taką samą skuteczność jak inne leki zalecane w terapii pierwszego rzutu. Jest dobrze tolerowana i bezpieczna – również pod względem wpływu na układ krążenia. Wśród najczęstszych działań niepożądanych należy wymienić nudności, suchość w ustach, zaparcia, bezsenność, zawroty głowy, uczucie zmęczenia i nadmiernej senności, wzmożone pocenie się i obniżony apetyt. U osób przyjmujących duloksetynę obserwuje się dysfunkcje seksualne podobne do tych związanych z przyjmowaniem leków serotoninowych. W razie nagłego przerwania leczenia duloksetyną, tak jak w przypadku wenlafaksyny czy paroksetyny, pojawiają się objawy dyskontynuacyjne. W artykule przedstawiono podstawowe właściwości farmakologiczne i profil kliniczny duloksetyny.

EN

Duloxetine, a serotonin and noradrenaline reuptake inhibitor, is registered in Poland for treatment of depressive disorders, generalized anxiety disorder and peripheral diabetic neuropathy. However, research has also confirmed its efficacy in other disorders associated with neuropathic pain, fibromyalgia, urinary incontinence and for relieving menopause symptoms. Duloxetine is an oral drug in the form of gastro-resistant capsules (30, 60, 90 and 120 mg). Its serum concentrations show high individual variability. Absolute bioavailability averages 50%, but may range from 32 to 80%. In humans, duloxetine binds with plasma proteins in 96%; it is intensively metabolised by CYP1A2 and CYP2D6. Due to the intensive metabolism by CYP1A2, substances that inhibit this enzyme (such as fluvoxamine, ciprofloxacin and enoxacin) increase duloxetine concentration significantly and may result in toxicity. In registered indications, duloxetine has at least equivalent efficacy to other drugs used in first-line therapy. It is both well-tolerated and safe, also in terms of cardiovascular effects. The most common adverse effects include: nausea, dry mouth, constipation, insomnia, dizziness, fatigue and drowsiness, excessive sweating and lower appetite. Patients treated with duloxetine develop sexual dysfunctions, similar to those associated with serotonin drugs. As with venlafaxine or paroxetine, withdrawal symptoms do develop after abrupt discontinuation of duloxetine therapy. This article presents basic pharmacological properties and the clinical profile of duloxetine.

Keywords

EN

ból neuropatyczny; depresja; duloksetyna; zaburzenie lękowe uogólnione

Discipline

• MEDICINE: MEDICINE

• Publisher: Medical Communications
• Journal: Psychiatria i Psychologia Kliniczna
• Year: 2018
• Volume: 18
• Issue: 1
• Pages: 74–80

Contributors

author

Marcin Wojtera

• Oddział Psychiatrii Wieku Podeszłego, Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi, Łódź, Polska

author

Tomasz Sobów

• Zakład Psychologii Lekarskiej, Uniwersytet Medyczny w Łodzi, Łódź, Polska

References

• Abbott CA, Malik RA, van Ross ER et al.: Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care 2011; 34: 2220–2224.
• Alaka KJ, Noble W, Montejo A et al.: Efficacy and safety of duloxetine in the treatment of older adult patients with generalized anxiety disorder: a randomized, double-blind, placebo-controlled trial. Int J Geriatr Psychiatry 2014; 29: 978–986.
• Alev L, Lenox-Smith A, Altin M et al.: A review of the serotonin-norepinephrine reuptake inhibitors: pharmacologic aspects and clinical implications for treatment of major depressive disorder and associated painful physical symptoms. Open Journal of Depression 2013; 2: 54–63.
• Allgulander C, Nutt D, Detke M et al.: A non-inferiority comparison of duloxetine and venlafaxine in the treatment of adult patients with generalized anxiety disorder. J Psychopharmacol 2008; 22: 417–425.
• Bair MJ, Robinson RL, Eckert GJ et al.: Impact of pain on depression treatment response in primary care. Psychosom Med 2004; 66: 17–22.
• Bair MJ, Robinson RL, Katon W et al.: Depression and pain comorbidity: a literature review. Arch Intern Med 2003; 163: 2433–2445.
• Bauer M, Bschor T, Pfennig A et al.; WFSBP Task Force on Unipolar Depressive Disorders: World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders in primary care. World J Biol Psychiatry 2007; 8: 67–104.
• Boyle J, Eriksson ME, Gribble L et al.: Randomized, placebo-controlled comparison of amitriptyline, duloxetine, and pregabalin in patients with chronic diabetic peripheral neuropathic pain: impact on pain, polysomnographic sleep, daytime functioning, and quality of life. Diabetes Care 2012; 35: 2451–2458.
• Brecht S, Courtecuisse C, Debieuvre C et al.: Efficacy and safety of duloxetine 60 mg once daily in the treatment of pain in patients with major depressive disorder and at least moderate pain of unknown etiology: a randomized controlled trial. J Clin Psychiatry 2007; 68: 1707–1716.
• Chang T, Fava M: The future of psychopharmacology of depression. J Clin Psychiatry 2010; 71: 971–975.
• Cipriani A, Koesters M, Furukawa TA et al.: Duloxetine versus other anti-depressive agents for depression. Cochrane Database Syst Rev 2012; 10: CD006533.
• Davidson JR, Wittchen HU, Llorca PM et al.: Duloxetine treatment for relapse prevention in adults with generalized anxiety disorder: a double-blind placebo-controlled trial. Eur Neuropsychopharmacol 2008; 18: 673–681.
• Doth AH, Hansson PT, Jensen MP et al.: The burden of neuropathic pain: a systematic review and meta-analysis of health utilities. Pain 2010; 149: 338–344.
• Dueñas H, Brnabic AJ, Lee A et al.: Treatment-emergent sexual dysfunction with SSRIs and duloxetine: effectiveness and functional outcomes over a 6-month observational period. Int J Psychiatry Clin Pract 2011; 15: 242–254.
• Fava M, Mallinckrodt CH, Detke MJ et al.: The effect of duloxetine on painful physical symptoms in depressed patients: do improvements in these symptoms result in higher remission rates? J Clin Psychiatry 2004; 65: 521–530.
• Finnerup NB, Attal N, Haroutounian S et al.: Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 162–173.
• Franklin GM, Shetterly SM, Cohen JA et al.: Risk factors for distal symmetric neuropathy in NIDDM. The San Luis Valley Diabetes Study. Diabetes Care 1994; 17: 1172–1177.
• Gao Y, Ning G, Jia WP et al.: Duloxetine versus placebo in the treatment of patients with diabetic neuropathic pain in China. Chin Med J (Engl) 2010; 123: 3184–3192.
• Girardi P, Pompili M, Innamorati M et al.: Duloxetine in acute major depression: review of comparisons to placebo and standard antidepressants using dissimilar methods. Hum Psychopharmacol 2009; 24: 177–190.
• Goldstein DJ, Lu Y, Detke MJ et al.: Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain 2005; 116: 109–118.
• Greco T, Eckert G, Kroenke K: The outcome of physical symptoms with treatment of depression. J Gen Intern Med 2004; 19: 813–818.
• Hamon M, Blier P: Monoamine neurocircuitry in depression and strategies for new treatments. Prog Neuropsychopharmacol Biol Psychiatry 2013; 45: 54–63.
• Hartford J, Kornstein S, Liebowitz M et al.: Duloxetine as an SNRI treatment for generalized anxiety disorder: results from a placebo and active-controlled trial. Int Clin Psychopharmacol 2007; 22: 167–174.
• Hefner J, Ashton AK, D’Mello DA et al.: Response to treatment: gaining and maintaining remission from depression. J Fam Pract 2003; Suppl: S61–S62.
• Hudson JI, Wohlreich MM, Kajdasz DK et al.: Safety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placebo-controlled clinical trials. Hum Psychopharmacol 2005; 20: 327–341.
• Kaur H, Hota D, Bhansali A et al.: A comparative evaluation of amitriptyline and duloxetine in painful diabetic neuropathy: a randomized, double-blind, cross-over clinical trial. Diabetes Care 2011; 34: 818–822.
• Knadler MP, Lobo E, Chappell J et al.: Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet 2011; 50: 281–294.
• Kremer M, Salvat E, Muller A et al.: Antidepressants and gabapentinoids in neuropathic pain: mechanistic insights. Neuroscience 2016; 338: 183–206.
• Leuchter AF, Husain MM, Cook IA et al.: Painful physical symptoms and treatment outcome in major depressive disorder: a STAR*D (Sequenced Treatment Alternatives to Relieve Depression) report. Psychol Med 2010; 40: 239–251.
• Martinez V, Attal N, Vanzo B et al.: Adherence of French GPs to chronic neuropathic pain clinical guidelines: results of a cross-sectional, randomized, “e” case-vignette survey. PLoS One 2014; 9: e93855.
• Nicolini H, Bakish D, Duenas H et al.: Improvement of psychic and somatic symptoms in adult patients with generalized anxiety disorder: examination from a duloxetine, venlafaxine extended-release and placebo-controlled trial. Psychol Med 2009; 39: 267–276.
• Papakostas GI, Thase ME, Fava M et al.: Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents. Biol Psychiatry 2007; 62: 1217–1227.
• Perahia DG, Gilaberte I, Wang F et al.: Duloxetine in the prevention of relapse of major depressive disorder: double-blind placebo-controlled study. Br J Psychiatry 2006; 188: 346–353.
• Perahia DG, Kajdasz DK, Desaiah D et al.: Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder. J Affect Disord 2005; 89: 207–212.
• Perahia DG, Quail D, Desaiah D et al.: Switching to duloxetine in selective serotonin reuptake inhibitor non- and partial-responders: effects on painful physical symptoms of depression. J Psychiatr Res 2009; 43: 512–518.
• Raskin J, Pritchett YL, Wang F et al.: A double-blind, randomized multicenter trial comparing duloxetine with placebo in the management of diabetic peripheral neuropathic pain. Pain Med 2005; 6: 346–356.
• Rowbotham MC, Arslanian A, Nothaft W et al.: Efficacy and safety of the α4β2 neuronal nicotinic receptor agonist ABT-894 in patients with diabetic peripheral neuropathic pain. Pain 2012; 153: 862–868.
• Schacht A, Gorwood P, Boyce P et al.: Depression symptom clusters and their predictive value for treatment outcomes: results from an individual patient data meta-analysis of duloxetine trials. J Psychiatr Res 2014; 53: 54–61.
• Stahl SM, Grady MM, Moret C et al.: SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. CNS Spectr 2005; 10: 732–747.
• Tanenberg RJ, Irving GA, Risser RC et al.: Duloxetine, pregabalin, and duloxetine plus gabapentin for diabetic peripheral neuropathic pain management in patients with inadequate pain response to gabapentin: an open-label, randomized, noninferiority comparison. Mayo Clin Proc 2011; 86: 615–626.
• Tesfaye S, Wilhelm S, Lledo A et al.: Duloxetine and pregabalin: highdose monotherapy or their combination? The “COMBO-DN study” – a multinational, randomized, double-blind, parallelgroup study in patients with diabetic peripheral neuropathic pain. Pain 2013; 154: 2616–2625.
• Thase ME, Tran PV, Wiltse C et al.: Cardiovascular profile of duloxetine, a dual reuptake inhibitor of serotonin and norepinephrine. J Clin Psychopharmacol 2005; 25: 132–140.
• Tokuoka H, Nishihara M, Fujikoshi S et al.: Predicting treatment outcomes of major depressive disorder by early improvement in painful physical symptoms: a pooled analysis of double-blind, placebocontrolled trials of duloxetine. Neuropsychiatr Dis Treat 2017; 13: 2457–2467.
• Treede RD, Jensen TS, Campbell JN et al.: Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008; 70: 1630–1635.
• Waldschmitt C, Vogel F, Pfuhlmann B et al.: Duloxetine serum concentrations and clinical effects. Data from a therapeutic drug monitoring (TDM) survey. Pharmacopsychiatry 2009; 42: 189–193.
• Wernicke JF, Pritchett YL, D’Souza DN et al.: A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology 2006; 67: 1411–1420.
• Westanmo AD, Gayken J, Haight R: Duloxetine: a balanced and selective norepinephrine- and serotonin-reuptake inhibitor. Am J Health Syst Pharm 2005; 62: 2481–2490.
• Wojtera M, Sobów T: Stosowanie pregabaliny w leczeniu uogólnionych zaburzeń lękowych. Czy należy bać się wysokich dawek? Psychiatr Psychol Klin 2016; 16: 91–98.
• Zhang Y, Huang G, Yang S et al.: Duloxetine in treating generalized anxiety disorder in adults: a meta-analysis of published randomized, double-blind, placebo-controlled trials. Asia Pac Psychiatry 2016; 8: 215–225.

• Document Type: article