Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: consensus definition

BackgroundMost people with bipolar disorder spend a significant percentage of their lifetime experiencing either subsyndromal depressive symptoms or major depressive episodes, which contribute greatly to the high levels of disability and mortality associated with the disorder. Despite the importance of bipolar depression, there are only a small number of recognised treatment options available. Consecutive treatment failures can quickly exhaust these options leading to treatment-resistant bipolar depression (TRBD). Remarkably few studies have evaluated TRBD and those available lack a comprehensive definition of multi-therapy-resistant bipolar depression (MTRBD).AimsTo reach consensus regarding threshold definitions criteria for TRBD and MTRBD.MethodBased on the evidence of standard treatments available in the latest bipolar disorder treatment guidelines, TRBD and MTRBD criteria were agreed by a representative panel of bipolar disorder experts using a modified Delphi method.ResultsTRBD criteria in bipolar depression was defined as failure to reach sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses, with at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. MTRBD included the same initial definition as TRBD, with the addition of failure of at least one trial with an antidepressant, a psychological treatment and a course of electroconvulsive therapy.ConclusionsThe proposed TRBD and MTRBD criteria may provide an important signpost to help clinicians, researchers and stakeholders in judging how and when to consider new non-standard treatments. However, some challenging diagnostic and therapeutic issues were identified in the consensus process that need further evaluation and research.Declaration of interestIn the past 3 years, M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Grunbiotics, Glaxo SmithKline, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka, Pfizer and Servier. A.J.C. has in the past 3 years received honoraria for speaking from Astra Zeneca and Lundbeck, honoraria for consulting from Allergan, Janssen, Lundbeck and LivaNova and research grant support from Lundbeck. G.M.G. holds shares in P1Vital and has served as consultant, advisor or CME speaker for Allergan, Angelini, Compass pathways, MSD, Lundbeck, Otsuka, Takeda, Medscape, Minervra, P1Vital, Pfizer, Servier, Shire and Sun Pharma. J.G. has received research funding from National Institute for Health Research, Medical Research Council, Stanley Medical Research Institute and Wellcome. H.G. received grants/research support, consulting fees or honoraria from Gedeon Richter, Genericon, Janssen Cilag, Lundbeck, Otsuka, Pfizer and Servier. R.H.M.-W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, Liva Nova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. R.M. has received research support from Big White Wall, Electromedical Products, Johnson and Johnson, Magstim and P1Vital. S.N. received honoraria from Lundbeck, Jensen and Otsuka. J.C.S. has received funds for research from Alkermes, Pfizer, Allergan, J&J, BMS and been a speaker or consultant for Astellas, Abbott, Sunovion, Sanofi. S.W has, within the past 3 years, attended advisory boards for Sunovion and LivaNova and has undertaken paid lectures for Lundbeck. D.J.S. has received honoraria from Lundbeck. T.S. has reported grants from Pathway Genomics, Stanley Medical Research Institute and Palo Alto Health Sciences; consulting fees from Sunovion Pharamaceuticals Inc.; honoraria from Medscape Education, Global Medical Education and CMEology; and royalties from Jones and Bartlett, UpToDate and Hogrefe Publishing. S.P. has served as a consultant or speaker for Janssen, and Sunovion. P.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. E.V. received grants/ research support, consulting fees or honoraria from Abbott, AB-Biotics, Allergan, Angelini, Dainippon Sumitomo, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka and Sunovion. L.N.Y. has received grants/research support, consulting fees or honoraria from Allergan, Alkermes, Dainippon Sumitomo, Janssen, Lundbeck, Otsuka, Sanofi, Servier, Sunovion, Teva and Valeant. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has also previously received funding for investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth. P.R.A.S. has received research funding support from Corcept Therapeutics Inc. Corcept Therapeutics Inc fully funded attendance at their internal conference in California USA and all related expenses. He has received grant funding from the Medical Research Council UK for a collaborative study with Janssen Research and Development LLC. Janssen Research and Development LLC are providing non-financial contributions to support this study. P.R.A.S. has received a presentation fee from Indivior and an advisory board fee from LivaNova.

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Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature

Mental Health Clinician ◽

10.9740/mhc.2017.01.016 ◽

2017 ◽

Vol 7 (1) ◽

pp. 16-23 ◽

Cited By ~ 19

Author(s):

Sarah E. Grady ◽

Travis A. Marsh ◽

Allison Tenhouse ◽

Kelsey Klein

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Bipolar Depression ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Major Depressive ◽

Randomized Controlled ◽

The Past ◽

Aspartate Receptor ◽

Resistant Depression

Abstract Introduction: Over the past decade, ketamine has been studied for major depressive disorder and bipolar depression. Ketamine is believed to exert its antidepressant properties through N-methyl-D-aspartate receptor antagonism. Methods: Study authors completed a literature review of seven randomized controlled trials of ketamine usage in major depressive disorder and bipolar depression. Results: Ketamine demonstrated a statistically significant improvement over placebo or midazolam in major depressive disorder. Ketamine also exhibited a statistically significant improvement over placebo in bipolar depression. Discussion: Ketamine has shown promise in quickly reducing symptoms in patients with treatment resistant depression and bipolar depression. Using ketamine may be helpful for patients that have exhausted other therapeutic options.

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Reassessing Carbamazepine in Bipolar Disorders

CNS Spectrums ◽

10.1017/s1092852900024512 ◽

2005 ◽

Vol 10 (S1) ◽

pp. 6-11 ◽

Cited By ~ 1

Author(s):

Terence A. Ketter

Keyword(s):

Bipolar Disorder ◽

Maintenance Treatment ◽

Atypical Antipsychotics ◽

Bipolar Depression ◽

Bipolar Disorders ◽

Clinical Implications ◽

Treatment Resistant ◽

Historical Trends ◽

Conventional Antipsychotics ◽

Important Progress

This discussion focuses on the historical trends of carbamazepine in the treatment of acute mania, acute bipolar depression, and as maintenance treatment for bipolar disorder. Clinical implications of efficacy, safety, tolerability, and drug interactions associated with carbamazepine are discussed as well.Important progress in bipolar disorders therapeutics began in the 1970s with lithium and the conventional antipsychotics, and continued in the 1980s with carbamazepine, in the 1990s with divalproex, and in the 2000s with lamotrigine and the introduction of the atypical antipsychotics. Electroconvulsive therapy (ECT) has been used throughout these periods and still has a place in bipolar disorder, especially for severe, treatment-resistant, and very acute cases.

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The CINP Guidelines on the Definition and Evidence-Based Interventions for Treatment-Resistant Bipolar Disorder

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyz064 ◽

2019 ◽

Vol 23 (4) ◽

pp. 230-256 ◽

Cited By ~ 1

Author(s):

Konstantinos N Fountoulakis ◽

Lakshmi N Yatham ◽

Heinz Grunze ◽

Eduard Vieta ◽

Allan H Young ◽

...

Keyword(s):

Bipolar Disorder ◽

Bipolar Depression ◽

Treatment Options ◽

Treatment Resistance ◽

Maintenance Phase ◽

Evidence Based ◽

Treatment Resistant ◽

Evidence Based Treatment ◽

Significant Disability ◽

Definition Of

Abstract Background Resistant bipolar disorder is a major mental health problem related to significant disability and overall cost. The aim of the current study was to perform a systematic review of the literature concerning (1) the definition of treatment resistance in bipolar disorder, (2) its clinical and (3) neurobiological correlates, and (4) the evidence-based treatment options for treatment-resistant bipolar disorder and for eventually developing guidelines for the treatment of this condition Materials and Methods The PRISMA method was used to identify all published papers relevant to the definition of treatment resistance in bipolar disorder and the associated evidence-based treatment options. The MEDLINE was searched to April 22, 2018. Results Criteria were developed for the identification of resistance in bipolar disorder concerning all phases. The search of the literature identified all published studies concerning treatment options. The data were classified according to strength, and separate guidelines regarding resistant acute mania, acute bipolar depression, and the maintenance phase were developed. Discussion The definition of resistance in bipolar disorder is by itself difficult due to the complexity of the clinical picture, course, and treatment options. The current guidelines are the first, to our knowledge, developed specifically for the treatment of resistant bipolar disorder patients, and they also include an operationalized definition of treatment resistance. They were based on a thorough and deep search of the literature and utilize as much as possible an evidence-based approach.

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Lurasidone Adjunctive to Lithium or Valproate for Prevention of Recurrence in Patients with Bipolar I Disorder

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2174 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S209-S209

Author(s):

J. Calabrese ◽

A. Pikalov ◽

J. Cucchiaro ◽

Y. Mao ◽

A. Loebel

Keyword(s):

Bipolar Disorder ◽

Bipolar Depression ◽

Hazard Ratio ◽

Open Label ◽

Recurrence Rates ◽

Double Blind ◽

Bipolar I Disorder ◽

Risk Of Recurrence ◽

Advisory Boards ◽

Time To Recurrence

IntroductionInformation is not available on the maintenance efficacy of lurasidone in bipolar disorder.Objectives/aimsTo evaluate the recurrence prevention efficacy of lurasidone plus lithium (Li) or valproate (VPA) for the maintenance treatment of bipolar disorder.MethodsPatients with bipolar I disorder received up to 20 weeks of open-label lurasidone (20–80 mg/d) plus Li or VPA. Patients who achieved consistent clinical stability were randomized to 28 weeks of double-blind treatment with lurasidone (20–80 mg/d) or placebo, plus Li or VPA.ResultsA total of 496 patients met stabilization criteria and were randomized to adjunctive lurasidone vs. placebo. Fewer patients in the lurasidone group had recurrence of any mood episode compared with the placebo group, with a hazard ratio of 0.71 (P = 0.078). In pre-planned secondary analyses, recurrence rates were significantly lower for the lurasidone group treated with a modal open-label dose of 80 mg/d (hazard ratio [HR], 0.35; P = 0.020); when patients presented with an index episode of depression (HR = 0.57; P = 0.039); and when outcome was time-to-all-cause discontinuation (HR = 0.72; P = 0.034), or time-to-recurrence based on symptom severity criteria (HR = 0.53; P = 0.025).ConclusionsIn patients stabilized on lurasidone plus Li or VPA, continued treatment was associated with non-significant reduction in risk of recurrence of any mood disorder (primary). Consistent with dose-response effects observed during acute treatment of bipolar depression, risk of recurrence on lurasidone was significantly reduced after open-label treatment with the 80 mg/d dose, and in the 20–80 mg/d dose in patients presenting with an index episode of depression.Clinicaltrials.gov: NCT01358357.Sponsored by Sunovion Pharmaceuticals Inc.Disclosure of interestDrs. Pikalov, Cucchiaro, Mao, and Loebel are employees of Sunovion Pharmaceuticals IncDr. Calabrese has received research support from Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Cleveland Foundation, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, NARSAD, Repligen, Stanley Medical Research Institute, Takeda, and Wyeth. Dr. Calabrese consulted to or served on advisory boards of Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Dainippon Sumitomo, Elan, EPI-Q, Inc., Forest, France Foundation, GlaxoSmithKline, Hoffman LaRoche, Janssen, Johnson and Johnson, Lundbeck, Merck, Neurosearch, OrthoMcNeil, Otsuka, Pfizer, Repligen, Servier, Solvay, Sunovion, Supernus, Synosia, Takeda, Teva, and Wyeth. Dr. Calabrese has provided CME lectures supported by AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen, Johnson and Johnson, Merck, Sanofi-Aventis, Schering-Plough, Pfizer, Solvay, Sunovion, and Wyeth.

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Multiple-therapy-resistant major depressive disorder: a clinically important concept

The British Journal of Psychiatry ◽

10.1192/bjp.2017.33 ◽

2018 ◽

Vol 212 (5) ◽

pp. 274-278 ◽

Cited By ~ 13

Author(s):

R. H. McAllister-Williams ◽

D. M. B. Christmas ◽

A. J. Cleare ◽

A. Currie ◽

J. Gledhill ◽

...

Keyword(s):

Advisory Board ◽

Pharmaceutical Companies ◽

Joint Research ◽

The Past ◽

Advisory Boards ◽

Specialist Services ◽

Grant Support ◽

White Wall ◽

Multiple Therapy ◽

Research Grant

SummaryMany novel therapeutic options for depression exist that are either not mentioned in clinical guidelines or recommended only for use in highly specialist services. The challenge faced by clinicians is when it might be appropriate to consider such ‘non-standard’ interventions. This analysis proposes a framework to aid this decision.Declaration of interestIn the past 3 years R.H.M.W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, LivaNova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. D.M.B.C. has received fees from LivaNova for attending an advisory board. In the past 3 years A.J.C. has received fees for lecturing from Astra Zeneca and Lundbeck; fees for consulting from LivaNova, Janssen and Allergan; and research grant support from Lundbeck.In the past 3 years A.C. has received fees for lecturing from pharmaceutical companies namely Lundbeck and Sunovion. In the past 3 years A.L.M. has received support for attending seminars and fees for consultancy work (including advisory board) from Medtronic Inc and LivaNova. R.M. holds joint research grants with a number of digital companies that investigate devices for depression including Alpha-stim, Big White Wall, P1vital, Intel, Johnson and Johnson and Lundbeck through his mindTech and CLAHRC EM roles. M.S. is an associate at Blueriver Consulting providing intelligence to NHS organisations, pharmaceutical and devices companies. He has received honoraria for presentations and advisory boards with Lundbeck, Eli Lilly, URGO, AstraZeneca, Phillips and Sanofi and holds shares in Johnson and Johnson. In the past 3 years P.R.A.S. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending an advisory board) from life sciences companies including Corcept Therapeutics, Indivior and LivaNova. In the past 3 years P.S.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has received funding for investigator initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth.

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Intranasal esketamine use in bipolar disorder: A case report

Mental Health Clinician ◽

10.9740/mhc.2021.07.259 ◽

2021 ◽

Vol 11 (4) ◽

pp. 259-262

Author(s):

Courtney Skriptshak ◽

Ashley Reich

Keyword(s):

Bipolar Disorder ◽

Case Report ◽

Mood Stabilizer ◽

Rapid Cycling ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

The Past ◽

Potential Safety ◽

History Of ◽

Resistant Depression

Abstract Over the past few years, intranasal esketamine has been FDA-approved for treatment-resistant depression as well as MDD with suicidal ideation. In the clinical trials leading to the recent FDA approvals, subjects with a diagnosis of bipolar disorder were excluded from participation in the trial. The manufacturer of intranasal esketamine states that it “has not been studied, and is not indicated, for patients with bipolar disorder.” Antidepressants are commonly associated with having the potential to induce rapid cycling in patients with bipolar disorder, though the mechanism is not fully understood. This case report demonstrates the potential safety of intranasal esketamine in combination with mood stabilizer therapy in a patient diagnosed with bipolar disorder without recent history of manic or hypomanic episodes.

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Deep brain stimulation for bipolar disorder—review and outlook

CNS Spectrums ◽

10.1017/s1092852915000577 ◽

2016 ◽

Vol 22 (3) ◽

pp. 254-257 ◽

Cited By ~ 10

Author(s):

Sabrina M. Gippert ◽

Christina Switala ◽

Bettina H. Bewernick ◽

Sarah Kayser ◽

Alena Bräuer ◽

...

Keyword(s):

Bipolar Disorder ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Depressive Symptomatology ◽

Bipolar Depression ◽

Single Case ◽

Treatment Resistant ◽

Stimulation Parameters ◽

Antidepressant Efficacy ◽

Deep Brain

Research on deep brain stimulation (DBS) for treatment-resistant psychiatric disorders has established preliminary efficacy signals for treatment-resistant depression. There are only few studies on DBS that included patients suffering from bipolar disorder. This article gives an overview of these studies concerning DBS targets, antidepressant efficacy, and the occurrence of manic/hypomanic symptoms under stimulation. First, promising results show that all patients experienced significant improvement in depressive symptomatology. In a single case, hypomanic symptoms occurred, but they could be resolved by adjusting stimulation parameters. Furthermore, this article highlights important clinical differences between unipolar and bipolar depression that have to be considered throughout the course of treatment.

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The consolidation of microscopy technology into a university research support facility: Reflections on the 1980's and projections for the 1990's at the university of iowa

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100148216 ◽

1993 ◽

Vol 51 ◽

pp. 476-477

Author(s):

Kenneth C. Moore

Keyword(s):

Laser Scanning ◽

Freeze Fracture ◽

Freeze Substitution ◽

Research Support ◽

University Of Iowa ◽

Staff Members ◽

The Past ◽

Research Grade ◽

The University ◽

Support Facility

The University of Iowa Central Electron Microscopy Research Facility(CEMRF) was established in 1981 to support all faculty, staff and students needing this technology. Initially the CEMRF was operated with one TEM, one SEM, three staff members and supported about 30 projects a year. During the past twelve years, the facility has replaced all instrumentation pre-dating 1981, and now includes 2 TEM's, 2 SEM's, 2 EDS systems, cryo-transfer specimen holders for both TEM and SEM, 2 parafin microtomes, 4 ultamicrotomes including cryoultramicrotomy, a Laser Scanning Confocal microscope, a research grade light microscope, an Ion Mill, film and print processing equipment, a rapid cryo-freezer, freeze substitution apparatus, a freeze-fracture/etching system, vacuum evaporators, sputter coaters, a plasma asher, and is currently evaluating scanning probe microscopes for acquisition. The facility presently consists of 10 staff members and supports over 150 projects annually from 44 departments in 5 Colleges and 10 industrial laboratories. One of the unique strengths of the CEMRF is that both Biomedical and Physical scientists use the facility.

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