The use of thyroid hormones in the treatment of euthyroid patients with treatment-resistant depression. Data from a survey of 5695 European national endocrine professional organisation members

Stephen Ludgate^1,2*Anne McGowan^1,2Carla Moran^3,4,5Roberto Attanasio⁶Miloš Žarković⁷Endre V. Nagy⁸Roberto Negro⁹Enrico Papini¹⁰Chagit Adler Cohen¹¹Ersin Akarsu¹²Maria Alevizaki^13,14Göksun Ayvaz¹⁵Tomasz Bednarczuk¹⁶Biljana Nedeljković Beleslin¹⁷Eszter Berta¹⁸Miklós Bodor¹⁸Anna-Maria Borissova¹⁹Mihail Boyanov^20,21Camille Buffet²²Maria-Cristina Burlacu²³Jamina Ćirić⁷Juan Díez^24,25,26Harald Dobnig^27,28Valentin Fadeyev²⁹Benjamin CT Field³⁰Eric Fliers³¹Dagmar Führer-Sakel³²Juan Carlos Galofre^33,34Tommi Hakala³⁵Jan Jiskra³⁶Peter Kopp³⁷Michael Krebs³⁸Michal Kršek³⁶Martin Kužma³⁹Ivica Lazúrová⁴⁰Laurence Leenhardt⁴¹Vitaliy Luchytskiy⁴²Saara Metso⁴³Tatyana MORGUNOVA²⁹Dan Alexandru Niculescu⁴⁴Bozidar Peric⁴⁵Tereza Planck⁴⁶Catalina Poiana⁴⁴Francisca Marques Puga⁴⁷Eyal Robenshtok⁴⁸Patrick Rosselet⁴⁹Marek Ruchala⁵⁰Kamilla Ryom Riis⁵¹Alla Shepelkevich⁵²Mykola D Tronko⁵³Jacob Stampe Frølich⁵¹David Unuane⁵⁴Irfan Vardarli^55,56W Edward Visser⁵⁷Andromachi Vryonidou⁵⁸Younes R Younes⁵⁹Elena Yurenya⁶⁰Petros Perros⁶¹Laszlo Hegedüs⁵¹

• ¹School of Medicine, Trinity College Dublin, the University of Dublin, Dublin, Ireland
• ²Robert Graves Institute of Endocrinology, Tallaght University Hospital, Tallaght, Dublin, Ireland
• ³University College Dublin, Dublin, Ireland
• ⁴St Vincent's University Hospital, Dublin, Ireland
• ⁵Beacon Hospital, Sandyford, Ireland
• ⁶Scientific Committee Associazione Medici Endocrinologi, Udine, Italy
• ⁷Univerzitet u Beogradu, Belgrade, Serbia
• ⁸8Division of Endocrinology, Department of Medicine, Debreceni Egyetem, Debrecen, Hungary
• ⁹Universita del Salento, Lecce, Italy
• ¹⁰Ateneo Pontificio Regina Apostolorum, Rome, Italy
• ¹¹Rabin Medical Center, Petah Tikva, Israel
• ¹²Gaziantep Universitesi, Gaziantep, Türkiye
• ¹³Geniko Nosokomeio Athenon Alexandra, Athens, Greece
• ¹⁴Ethniko kai Kapodistriako Panepistemio Athenon, Athens, Greece
• ¹⁵Ozel Koru Sincan Hastanesi, Ankara, Türkiye
• ¹⁶15Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland
• ¹⁷Faculty of Medicine, Univerzitet u Beogradu, Belgrade, Serbia
• ¹⁸Debreceni Egyetem, Debrecen, Hungary
• ¹⁹Sofijski universitet Sv Kliment Ohridski Medicinski fakultet, Sofia, Bulgaria
• ²⁰17Clinic of Endocrinology and Metabolism, University Hospital “Alexandrovska”, Sofia, Bulgaria
• ²¹Department of Internal Medicine, Medical University Sofia, Sofia, Bulgaria
• ²²19Sorbonne Universitè, GRC n 16, GRC Thyroid Tumors, Thyroid Pathology and Endocrine Tumor Department, AP-HP, Hôpital Pitié-Salpêtriére, Paris, France
• ²³Cliniques universitaires Saint-Luc Service d'Endocrinologie et nutrition, Brussels, Belgium
• ²⁴Hospital Universitario Puerta de Hierro Majadahonda Servicio de Endocrinologia y Nutricion, Majadahonda, Spain
• ²⁵Instituto de Investigacion Sanitaria Puerta de Hierro - Segovia de Arana, Majadahonda, Spain
• ²⁶Universidad Autonoma de Madrid Facultad de Medicina, Madrid, Spain
• ²⁷Thyroid Practice for Radiofrequency Ablation, Vienna, Austria
• ²⁸Thyroid Endocrinology Osteoporosis Institute Dobnig, Graz, Austria
• ²⁹Department of Endocrinology No. 1, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russia
• ³⁰University of Surrey Faculty of Health and Medical Sciences, Guildford, United Kingdom
• ³¹Amsterdam UMC Endocrinologie en Metabolisme, Amsterdam, Netherlands
• ³²Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University-Duisburg-Essen, Essen, Germany
• ³³Clinica Universidad de Navarra, Pamplona, Spain
• ³⁴Instituto de Investigacion Sanitaria de Navarra, Pamplona, Spain
• ³⁵Department of Surgery, Tampere University Hospital, Tampere, Finland
• ³⁶3rd Department of Medicine, 1st Faculty of Medicine, Charles University, General University Hospital, Prague, Czechia
• ³⁷Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, Lausanne, Switzerland
• ³⁸Internal Medicine III, Division of Endocrinology, Medical University of Vienna, Vienna, Austria
• ³⁹5th Department of Internal Medicine, Medical Faculty of Comenius University and University Hospital, Bratislava, Slovakia
• ⁴⁰P.J. Šafárik University Košice, 1st Department of Internal Medicine of the Medical Faculty, Košice, Slovakia
• ⁴¹GRC Thyroid Tumors, Thyroid Pathology and Endocrine Tumor Department, AP-HP, Hôpital Pitié-Salpêtriére, Sorbonne Universite, Paris, France
• ⁴²Department of Reproductive Endocrinology, Institute of Endocrinology and Metabolism named after V.P. Komissarenko, Nacional'na akademia medicnih nauk Ukraini, Kyiv, Ukraine
• ⁴³Department of Endocrinology, Tampere University Hospital, Tampere, Finland
• ⁴⁴Department of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
• ⁴⁵Department of Endocrinology, Diabetes and Metabolic Diseases, University Hospital Centre Sisters of Mercy, Zagreb, Croatia
• ⁴⁶Department of Endocrinology, Skåne University Hospital, Malmo, Sweden
• ⁴⁷Serviço de Endocrinologia, Diabetes e Metabolismo, Unidade Local de Saude de Sao Joao, Porto, Portugal
• ⁴⁸Endocrinology Institute, Rabin Medical Center, Gray Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel
• ⁴⁹Cabinet Médical 2, Lausanne, Switzerland
• ⁵⁰Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland
• ⁵¹Department of Endocrinology, Odense Universitetshospital, Odense, Denmark
• ⁵²Department of Endocrinology, Belarusian State Medical University, Minsk, Belarus
• ⁵³V.P. Komissarenko Institute of Endocrinology and Metabolism, Nacional'na akademia medicnih nauk Ukraini, Kyiv, Ukraine
• ⁵⁴Department of Internal Medicine, Endocrine Unit, Vrije Universiteit Brussel, Brussels, Belgium
• ⁵⁵Department of Medicine I, Klinikum Vest GmbH Knappschaftskrankenhaus Recklinghausen, Ruhr-Universitat Bochum, Bochum, Germany
• ⁵⁶5th Medical Department, Division of Endocrinology and Diabetes, Medical Faculty Mannheim, Universitat Heidelberg, Heidelberg, Germany
• ⁵⁷Rotterdam Thyroid Center, Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands
• ⁵⁸Department of Endocrinology and Diabetes Centre, Hellenic Red Cross Hospital, Athens, Greece
• ⁵⁹Surrey & Sussex Healthcare NHS Trust, East Surrey Hospital, Redhill, United Kingdom
• ⁶⁰Minsk Endocrinology Medical Center, Minsk, Belarus
• ⁶¹Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom

Purpose: Treatment-resistant depression (TRD) is most commonly defined as depression that has not responded to two different pharmacological agents used for an adequate period of time. We explored the views of European specialists via survey, regarding the use of thyroid hormone (TH) in euthyroid patients with TRD as part of ‘Treatment of Hypothyroidism in Europe by Specialists: An International Survey’ (THESIS). Methods: The question “Thyroid hormones may be indicated in biochemically euthyroid patients with treatment resistant depression” was posed to specialists from 28 countries. Results: 5695 valid responses were received following 17,232 invitations (33.0% response rate; 65% female, 90% endocrinologists). 348 (6.1%) stated that TH may be indicated in biochemically euthyroid patients with TRD. This view was more common in males (p<0.01), respondents who saw ≥100 patients with hypothyroidism per year (p<0.01), respondents who worked in private practice (p=0.05) and respondents who were not members of international specialist associations (p=0.05). Geographical variation existed with respondents in Eastern Europe significantly more likely to use TH in TRD (p<0.01). Linear regression showed a statistically significant reduction in the use of TH for TRD with increasing gross national income (F-statistic=7.35, CI -0.15 - -0.02, p=0.01). TH in TRD was recommended in psychiatry guidelines but not endocrinology guidelines. Conclusion: While there is limited evidence for their use, over 6% of respondents stated that TH may be indicated in TRD. Due to the risk of iatrogenic thyrotoxicosis and increased morbidity the use of TH should be addressed in relevant endocrinology guidelines and consensus should be reached between specialities.