Skip to main content

Advertisement

Log in

Managing fibromyalgia syndrome in pregnancy no bridges between USA and EU

  • Review Article
  • Published:
Archives of Women's Mental Health Aims and scope Submit manuscript

Abstract

The first aim of this article is to analyze the risk/benefit ratio of using psychotropic drugs approved in some countries for treating fibromyalgia syndrome (FMS) during pregnancy. Assessing the effectiveness of non-pharmacological interventions is the second scope of this article, in order to help clinicians to manage FMS in pregnancy in those countries were no drugs are approved for treating the disease. Following the PRISMA guidelines for systematic reviews, a literature search was conducted on PubMed and Google Scholar. Separate literature searches were performed for the three psychotropic drugs approved in the USA for treating FMS, psychotherapy, and transcranial magnetic stimulation (TMS). Perinatal duloxetine exposure is associated with increased risk of gestational and perinatal complications. With regards pregabalin, available information suggests that the drug is not devoid of structural teratogenicity potential. No data are available for milnacipran. Duloxetine and pregabalin should be only given to pregnant women diagnosed with severe forms of FMS after carefully weighing the benefits and risks for the mother-fetus dyad. On the other hand, we have to consider that the proportion of women who discontinue psychotropic drugs during pregnancy is as high as 85.4%. This figure raises further questions about adequate alternative treatment of FMS during the perinatal period. Moreover, neither duloxetine nor milnacipran or pregabalin have been approved by the EMEA for the treatment of FMS. Unfortunately, psychological treatment of FMS in perinatal women are not yet tested and data on TMS are conflicting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Abdy NA, Gerhart K (2013) Duloxetine withdrawal syndrome in a newborn. Clin Pediatr (Phila) 52:976–977

    Article  Google Scholar 

  • American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Arlington, VA, American Psychiatric Association

    Book  Google Scholar 

  • Atasever M, Namlı Kalem M, Sönmez Ç et al (2017) Lower serotonin level and higher rate of fibromyalgia syndrome with advancing pregnancy. J Matern Fetal Neonatal Med 30:2204–2211

    Article  CAS  PubMed  Google Scholar 

  • Bellantuono C, Marini A, Lucarelli C (2013) Infant health and neurodevelopmental outcomes following prenatal exposure to duloxetine. Clin Drug Investig 33:685–688

    Article  CAS  PubMed  Google Scholar 

  • Bérard A, Sheehy O, Zhao JP et al (2017) SSRI and SNRI use during pregnancy and the risk of persistent pulmonary hypertension of the newborn. Br J Clin Pharmacol 83:1126–1133

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bernardy K, Klose P, Welsch P et al (2018) Efficacy, acceptability and safety of cognitive behavioural therapies in fibromyalgia syndrome. A systematic review and meta-analysis of randomized controlled trials. Eur J Pain 22:242–260

    Article  CAS  PubMed  Google Scholar 

  • Bidonde J, Busch AJ, van der Spuy I et al (2017) Whole body vibration exercise training for fibromyalgia. Cochrane Database Syst Rev 9:CD011755

    PubMed  Google Scholar 

  • Bollettino di informazione sui farmaci. (2017) http://www.agenziafarmaco.gov.it/wscs_render_attachment_by_id/111.285018.115401469992960af.pdf?id=111.285023.1154014700132. Accessed: September, 15, 2017

  • Boyce PM, Hackett LP, Ilett KF (2011) Duloxetine transfer across the placenta during pregnancy and into milk during lactation. Arch Womens Ment Health 14:169–172

    Article  PubMed  Google Scholar 

  • Briggs GG, Ambrose PJ, Ilett KF et al (2009) Use of duloxetine in pregnancy and lactation. Ann Pharmacother 43:1898–1902

    Article  PubMed  Google Scholar 

  • Brown HK, Ray JG, Wilton AS, Lunsky Y, Gomes T, Vigod SN (2017) Association between serotonergic antidepressant use during pregnancy and autism spectrum disorder in children. JAMA 317:1544–1552

    Article  CAS  PubMed  Google Scholar 

  • De Ocampo MGP, Araneta MRG, Macera CA et al (2016) Risk of gestational hypertension and preeclampsia in women who discontinued or continued antidepressant medication use during pregnancy. Arch Womens Ment Health 19:1051–1061

    Article  PubMed  Google Scholar 

  • Dresser R, Frader J (2009) Off-label prescribing: a call for heightened professional and government oversight. J Law Med Ethics 37:476–486

    Article  PubMed  PubMed Central  Google Scholar 

  • Einarson A, Smart K, Vial T, Diav-Citrin O, Yates L, Stephens S, Pistelli A, Kennedy D, Taylor T, Panchaud A, Malm H, Koren G, Einarson TR (2012) Rates of major malformations in infants following exposure to duloxetine during pregnancy: a preliminary report. J Clin Psychiatry 73:1471

    Article  PubMed  Google Scholar 

  • EMEA. Refusal assessment report for Cymbalta (2008). http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000572/WC500076168.pdf. Accessed: February 16, 2018

  • EMEA. (2009) Milnacipran Pierre Fabre Medicament. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/001034/human_med_001311.jsp&murl=menus/medicines/medicines.jsp&mid=WC0b01ac058001d125. Accessed: February 16, 2018

  • Eyal R, Yaeger D (2008) Poor neonatal adaptation after in utero exposure to duloxetine. Am J Psychiatry 65:651

    Article  Google Scholar 

  • Furey K, Wilkins K (2016) Prescribing “off-label”: what should a physician disclose? AMA J Ethics 18:587–593

    Article  PubMed  Google Scholar 

  • Gentile S (2015) Early pregnancy exposure to selective serotonin reuptake inhibitors, risks of major structural malformations, and hypothesized teratogenic mechanisms. Expert Opin Drug Metab Toxicol 11:1585–1597

    Article  CAS  PubMed  Google Scholar 

  • Gentile S (2014) Anxiety and sleep disorders, psychopharmacology and pregnancy. In: psychopharmacology and pregnancy. Galbally, Snellen, and Lewis Edts. Springer Verlab, Berlin, pp 87–102

    Google Scholar 

  • Gentile S (2012) Bipolar disorder in pregnancy: to treat or not to treat? The real question is how to treat most effectively. Br Med J 345:e7367. https://doi.org/10.1136/bmj.e7367

    Article  Google Scholar 

  • Gentile S (2010) On categorizing gestational birth, and neonatal complications following late in utero exposure to antidepressants. The prenatal antidepressant exposure syndrome. CNS Spectr 15:167–185

    Article  PubMed  Google Scholar 

  • Guzman F. (2018) Pharmacology corner. Pregabalin (Lyrica) not approved for fibromyalgia by the EMEA. http://pharmacologycorner.com/pregabalin-lyrica-not-approved-fibromyalgia-emea/. Accessed: February 16, 201

  • Hedman E, Axelsson E, Andersson E, Lekander M, Ljótsson B (2016) Exposure-based cognitive-behavioural therapy via the internet and as bibliotherapy for somatic symptom disorder and illness anxiety disorder: randomised controlled trial. Br J Psychiatry 209:407–413

    Article  PubMed  Google Scholar 

  • Heider J, Köck K, Sehlbrede M, Schröder A (2017) Readiness to change as a moderator of therapy outcome in patients with somatoform disorders. Psychother Res 28:722–733. https://doi.org/10.1080/10503307.2016.1265686

    Article  PubMed  Google Scholar 

  • Henningsen P, Zipfel S, Sattel H et al (2018) Management of functional somatic syndromes and bodily distress. Psychother Psychosom 87:12–31

    Article  PubMed  Google Scholar 

  • Holland J, Brown R (2017) Neonatal venlafaxine discontinuation syndrome: a mini-review. Eur J Paediatr Neurol 21:264–268

    Article  PubMed  Google Scholar 

  • Hoog SL, Cheng Y, Elpers J, Dowsett SA (2013) Duloxetine and pregnancy outcomes: safety surveillance findings. Int J Med Sci 10:413–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hudson JI, Wohlreich MM, Daniel K, Kajdasz DK (2005) Safety and tolerability of duloxetine in the treatment of major depressive disorder: analysis of pooled data from eight placebo-controlled clinical trials. Hum Psychopharmacol Clin Exp 20:327–341

    Article  CAS  Google Scholar 

  • Källén B, Borg N, Reis M (2013) The use of central nervous system active drugs during pregnancy. Pharmaceuticals 6:1221–1286

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Khedr EM, Omran EAH, Ismail NM, el-Hammady DH, Goma SH, Kotb H, Galal H, Osman AM, Farghaly HSM, Karim AA, Ahmed GA (2017) Effects of transcranial direct current stimulation on pain, mood and serum endorphin level in the treatment of fibromyalgia: a double blinded, randomized clinical trial. Brain Stimul 10:893–901

    Article  PubMed  Google Scholar 

  • Kleinstäuber M, Witthöft M, Hiller W (2011) Efficacy of short-term psychotherapy for multiple medically unexplained physical symptoms: a meta-analysis. Clin Psychol Rev 31:146–160

    Article  PubMed  Google Scholar 

  • Knadler MP, Lobo E, Chappell J, Bergstrom R (2011) Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet 50:281–294

    Article  CAS  PubMed  Google Scholar 

  • Kjaersgaard MI, Parner ET, Vestergaard M et al (2013) Prenatal antidepressant exposure and risk of spontaneous abortion: a population-based study. PLoS One 8:e72095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kroenke K (2000) Somatoform disorders and recent diagnostic controversies. Psychiatr Clin North Am 30:593–619

    Article  Google Scholar 

  • Leo RJ, Brooks VL (2006) Clinical potential of milnacipran, a serotonin and norepinephrine reuptake inhibitor, in pain. Curr Opin Investig Drugs 7:637–642

    CAS  PubMed  Google Scholar 

  • Li F, Chin C, Wangsa J, Ho J (2012) Excretion and metabolism of milnacipran in humans after oral administration of milnacipran hydrochloride. Drug Metab Dispos 40:1723–1735

    Article  CAS  PubMed  Google Scholar 

  • Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151:W-65

    Article  Google Scholar 

  • Lupattelli A, Wood M, Lapane K, Spigset O, Nordeng H (2017) Risk of preeclampsia after gestational exposure to selective serotonin reuptake inhibitors and other antidepressants: a study from the Norwegian Mother and Child Cohort Study. Pharmacoepidemiol Drug Saf 26:1266–1276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Magtanong GG, Spence AR, Czuzoj-Shulman N, Abenhaim HA (2017) Maternal and neonatal outcomes among pregnant women with fibromyalgia: a population-based study of 12 million births. J Matern Fetal Neonatal Med Sep 27:1–7. https://doi.org/10.1080/14767058.2017.1381684

    Article  Google Scholar 

  • Medscape. News and perspectives. (2008) Cymbalta approved for fibromyalgia. https://www.medscape.org/viewarticle/576320. Accessed February 16, 2018

  • Medscape. News and perspectives. (2009) FDA approves milnacipran for fibromyalgia https://www.medscape.com/viewarticle/586898. Accessed: February 16

  • Mostacci B, Poluzzi E, D’Alessandro R, On behalf of the ESPEA Study Group et al (2018) Adverse pregnancy outcomes in women exposed to gabapentin and pregabalin: data from a population-based study. J Neurol Neurosurg Psychiatry 89:223–224

    Article  PubMed  Google Scholar 

  • Newport JD, Hostetter AL, Juul SH et al (2016) Prenatal psychostimulant and antidepressant exposure and risk of hypertensive disorders in pregnancy. J Clin Psychiatry 77:1538–1545

    Article  PubMed  Google Scholar 

  • Patorno E, Bateman BT, Huybrechts KF (2017) Pregabalin use early in pregnancy and the risk of major congenital malformations. Neurology 88:2020–2025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saa’d S, Many A, Jacob G et al (2013) High prevalence of fibromyalgia symptoms among healthy full-term pregnant women. Rheumatol Int 33:1555–1560

    Article  PubMed  Google Scholar 

  • Saltychev M, Laimi K (2017) Effectiveness of repetitive transcranial magnetic stimulation in patients with fibromyalgia: a meta-analysis. Int J Rehabil Res 40:11–18

    Article  PubMed  Google Scholar 

  • Savella Pregnancy Registry (2009) https://clinicaltrials.gov/ct2/show/NCT01026077. Last update: September 22, 2016. Accessed: February 17, 2018

  • Schaefer KM (2004) Breastfeeding in chronic illness: the voices of women with fibromyalgia. MCN Am J Matern Child Nurs 29:248–253

    Article  PubMed  Google Scholar 

  • Schröder A, Heider J, Zaby A et al (2013) Cognitive behavioral therapy versus progressive muscle relaxation training for multiple somatoform disorders: results of a randomized controlled trial. CognitTher Res 37:296–306

    Google Scholar 

  • Stahl SM, Grady MM, Moret C, et al (2005) SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. CNS Spectr 10:732–747

    Article  PubMed  Google Scholar 

  • Sujan AC, Rickert ME, Öberg SA et al (2017) Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring. JAMA 317:1553–1562

    Article  PubMed  PubMed Central  Google Scholar 

  • Sujan AC, Öberg AS, Quinn PD, D'Onofrio BM (2018) Annual Research Review: Maternal antidepressant use during pregnancy and offspring neurodevelopmental problems - a critical review and recommendations for future research. J Child Psychol Psychiatry. https://doi.org/10.1111/jcpp.13004

    Article  PubMed  Google Scholar 

  • Tassone DM, Boyce E, Guyer J, Nuzum D (2007) Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. Clin Ther 29:26–48

    Article  CAS  PubMed  Google Scholar 

  • Temple University (2006) Fibromyalgia increases pain and fatigue for pregnant women. ScienceDaily. ScienceDaily, 5. www.sciencedaily.com/releases/2006/07/060705184726.htm. Accessed: September 20, 2017

  • Trivedi MH, Desaiah D, Ossanna MJ et al (2008) Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. Int Clin Psychopharmacol 23:161–169

    Article  PubMed  Google Scholar 

  • Tulay KT, Emrullah T, Aydin A et al (2016) The effect of fibromyalgia syndrome to gravidity, parity and duration of breastfeeding; a prospective study from Turkey. Pak J Med Sci 32:545–549

    Article  PubMed  PubMed Central  Google Scholar 

  • van Dessel N, den Boeft M, van der Wouden JC et al (2014) On-pharmacological interventions for somatoform isorders and medically unexplained physical symptoms (MUPS) in adults. Cochr Database System Rev 11:CD011142

    Google Scholar 

  • van Ravesteyn LM, Lambregtse-van den Berg MP, Hoogendijk WJP et al (2017) Interventions to treat mental disorders during pregnancy: a systematic review and multiple treatment meta-analysis. PLoS One 12:e0173397

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Weiss N, Ivanova E (2008) Does the voltage-gated calcium channel alpha2delta-1 subunit play a dual function in skeletal muscle? J Physiol 586:2035–2037

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winterfeld U, Merlob P, Baud D, Rousson V, Panchaud A, Rothuizen LE, Bernard N, Vial T, Yates LM, Pistelli A, Ellfolk M, Eleftheriou G, de Vries LC, Jonville-Bera AP, Kadioglu M, Biollaz J, Buclin T (2016) Pregnancy outcome following maternal exposure to pregabalin may call for concern. Neurology 86(24):2251–2257. https://doi.org/10.1212/WNL.0000000000002767

    Article  CAS  PubMed  Google Scholar 

  • Wolfe F, Clauw DJ, Fitzcharles MA et al (2011) Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia. J Rheumatol 38:1113–1122

    Article  PubMed  Google Scholar 

  • Wolfe F, Wallitt BT, Katz RS et al (2014) Symptoms, the nature of fibromyalgia, and Diagnostic and Statistical Manual 5 (DSM-5) defined mental illness in patients with rheumatoid arthritis and fibromyalgia. PLoS One 9:e88740

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zioni T, Buskila D, Aricha-Tamir B, Wiznitzer A, Sheiner E (2011) Pregnancy outcome in patients with fibromyalgia syndrome. J Matern Fetal Neonatal Med 24:1325–1328

    Article  PubMed  Google Scholar 

  • Zoega H, Kieler H, Nørgaard M, Furu K, Valdimarsdottir U, Brandt L, Haglund B (2015) Use of SSRI and SNRI antidepressants during pregnancy: a population-based study from Denmark, Iceland, Norway and Sweden. PLoS One 10:e0144474

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Salvatore Gentile.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gentile, S., Fusco, M.L. Managing fibromyalgia syndrome in pregnancy no bridges between USA and EU. Arch Womens Ment Health 22, 711–721 (2019). https://doi.org/10.1007/s00737-018-0933-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00737-018-0933-z

Keywords

Navigation