Prof. Michael Bauer

Ponencia	Ciclación rápida en pacientes bipolares con resistencia al tratamiento
Fecha	Viernes, 26 de Abril, 2019
Hora	17:15 a 18:00
Mesa redonda	Resistencia al tratamiento en trastornos afectivos

Michael Bauer, MD, PhD, is Professor of Psychiatry and Chair of the Department of Psychiatry and Psychotherapy at the University Hospital Carl Gustav Carus, Technische Universität Dresden, in Germany, where he is also Physician-in-Chief at the Psychiatric Hospital and Outpatient Clinics. For his research in the field of mood disorders, he received several international and national awards/prices, e.g., the NARSAD Independent Investigator Award, the ARETÄUS Price for "Exeptional dedication in the field of bipolar disorder" by the German Society for Bipolar Disorders, the AGNP-Prize for Research in Psychopharmacology, Achievements in the Field of Treatment of Mood Disorders with Thyroid Hormones, and the Anna Monika Prize for research in neurobiology and treatment of depressive disorders (2017). He is President of the International Group for the Study of Lithium-Treated Patients (IGSLi), and chairs the World Federation of Societies of Biological Psychiatry's Task Force on Treatment Guidelines for Unipolar Depressive Disorders. Dr. Bauer is Editor-in-Chief of the International Journal of Bipolar Disorders, and of Pharmacopsychiatry, and has (co-)authored more than 400 articles published in peer-reviewed journals or books in the field of mood disorders.

The term "rapid cycling" was introduced in 1974 by Dunner and Fieve to denote a course of illness in which four or more mood episodes occurred in the year preceding their study of lithium prophylaxis. The number four was chosen arbitrarily to obtain a population of sufficient size to study. In most of the patients with rapid cycling (RC), lithium failed to prevent recurrences, although it did attenuate the further course of illness. Four decades later, it is clear that this relative resistance is found to all standard pharmacological treatments and not just lithium. Rapid cycling can be conceptualized as either a high frequency of episodes of any polarity or as a temporal sequence of episodes of opposite polarity. The DSM 5 defines rapid cycling as a course specifier, signifying at least four episodes of major depression, mania, mixed mania, or hypomania in the past year, occurring in any combination or order. It is estimated that RC is present in about 12-24% of patients at specialized mood disorder clinics. However, apart from episode frequency, studies over the past 40 years have been unable to determine clinical characteristics that define patients with RC as a specific subgroup. There is a longstanding controversy as to whether antidepressants, particularly tricyclic antidepressants (TCA), and other drugs that affect monoaminergic neurotransmitter systems, can trigger and prolong rapid cycling. Some longitudinal, observational studies have implicated both brief and prolonged antidepressant drug use and some report that women have an increased risk of antidepressant-induced RC. Mood stabilizers, including lithium, used alone or in double or triple combination, provide benefit to many patients with rapid cycling by reducing the severity and duration of episodes, even if complete remission and prevention of subsequent episodes is rare.

There is a longstanding debate as to whether thyroid axis abnormalities contribute to the development of rapid cycling. Several studies have found an association among indices of low thyroid function or clinical hypothyroidism and RC, while other studies refute this association. It was postulated that patients with RC may manifest no thyroid abnormalities until physiologically challenged by "antithyroid" stressors. Such stressors may include spontaneously occurring thyroid disease or goiterogenic drugs such as lithium. In a controlled study, when previously un-medicated patients with rapid cycling were challenged with therapeutic doses of lithium, a significantly higher delta TSH after thyrotropin-releasing-hormone (TRH) stimulation was found than in age-and gender-matched healthy controls who also received lithium. This result suggests that some patients with bipolar disorder have a dysfunction in the hypothalamic-pituitary-thyroid (HPT) axis that remains latent until the axis is challenged by the thyroprivic effect of lithium, and that changes in the thyroid economy may play a modulating role in the development of the rapid cycling pattern.

A recent report describes the first comparative double-blind, placebo controlled trial of levothyroxine (L-T4) and triiodothyronine (T3) as adjunctive treatments in rapid cycling bipolar disorder. Within groups, post-treatment the L-T4 group spent significantly less time depressed or in a mixed state and greater time euthymic. T3 and placebo groups did not differ significantly pre- and post-treatment in any mood state although the pattern of effects was the same for the T3 group as the L-T4 group. Between-groups, the L-T4 group had a significantly greater increase in time euthymic and decrease in time in the mixed state than the placebo group. Other group differences were not significant, although they were in the expected direction. Findings provide evidence for the benefit of adjunctive L-T4 but not T3 in alleviating resistant depression, reducing time in mixed states and increasing time euthymic.

[PDF] Walshaw PD, Gyulai L, Bauer M et al (2018). Adjunctive thyroid hormone treatment in rapid cycling bipolar disorder: A double-blind placebo-controlled trial of levothyroxine (L-T4 ) and triiodothyronine (T3 ).. Bipolar Disord. 2018 Nov;20(7):594-603. doi: 10.1111/bdi.12657. Epub 2018 Jun 4.

[PDF] Bauer M et al (2008). Rapid cycling bipolar disorder – diagnostic concepts. Bipolar Disord. 2008 Feb;10(1 Pt 2):153-62. doi: 10.1111/j.1399-5618.2007.00560.x.

[PDF] Gyulai L1, Bauer M et al (2003). Thyroid Hypofunction in Patients with Rapid-Cycling Bipolar Disorder after Lithium Challenge. Biol Psychiatry. 2003 May 15;53(10):899-905.

[book] Muzina DJ, Bauer M, Calabrese JR (2006). Lithium in rapid cycling bipolar disorder. Bauer M, Grof P, Müller-Oerlinghausen (Eds.) Lithium in Neuropsychiatry – The Comprehensive Guide. Informa Healthcare, Abingdon, pp.145-156