PMID- 30944309 OWN - NLM STAT- MEDLINE DCOM- 20200109 LR - 20210109 IS - 2158-3188 (Electronic) IS - 2158-3188 (Linking) VI - 9 IP - 1 DP - 2019 Apr 3 TI - Prognosis and improved outcomes in major depression: a review. PG - 127 LID - 10.1038/s41398-019-0460-3 [doi] LID - 127 AB - Treatment outcomes for major depressive disorder (MDD) need to be improved. Presently, no clinically relevant tools have been established for stratifying subgroups or predicting outcomes. This literature review sought to investigate factors closely linked to outcome and summarize existing and novel strategies for improvement. The results show that early recognition and treatment are crucial, as duration of untreated depression correlates with worse outcomes. Early improvement is associated with response and remission, while comorbidities prolong course of illness. Potential biomarkers have been explored, including hippocampal volumes, neuronal activity of the anterior cingulate cortex, and levels of brain-derived neurotrophic factor (BDNF) and central and peripheral inflammatory markers (e.g., translocator protein (TSPO), interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor alpha (TNFalpha)). However, their integration into routine clinical care has not yet been fully elucidated, and more research is needed in this regard. Genetic findings suggest that testing for CYP450 isoenzyme activity may improve treatment outcomes. Strategies such as managing risk factors, improving clinical trial methodology, and designing structured step-by-step treatments are also beneficial. Finally, drawing on existing guidelines, we outline a sequential treatment optimization paradigm for selecting first-, second-, and third-line treatments for acute and chronically ill patients. Well-established treatments such as electroconvulsive therapy (ECT) are clinically relevant for treatment-resistant populations, and novel transcranial stimulation methods such as theta-burst stimulation (TBS) and magnetic seizure therapy (MST) have shown promising results. Novel rapid-acting antidepressants, such as ketamine, may also constitute a paradigm shift in treatment optimization for MDD. FAU - Kraus, Christoph AU - Kraus C AUID- ORCID: 0000-0002-7144-2282 AD - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. AD - Section on Neurobiology and Treatment of Mood Disorders, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. FAU - Kadriu, Bashkim AU - Kadriu B AUID- ORCID: 0000-0002-3809-9451 AD - Section on Neurobiology and Treatment of Mood Disorders, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. FAU - Lanzenberger, Rupert AU - Lanzenberger R AUID- ORCID: 0000-0003-4641-9539 AD - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. FAU - Zarate, Carlos A Jr AU - Zarate CA Jr AD - Section on Neurobiology and Treatment of Mood Disorders, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. FAU - Kasper, Siegfried AU - Kasper S AUID- ORCID: 0000-0001-8278-191X AD - Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. siegfried.kasper@meduniwien.ac.at. LA - eng GR - ZIA MH002927/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Review DEP - 20190403 PL - United States TA - Transl Psychiatry JT - Translational psychiatry JID - 101562664 RN - 0 (Antidepressive Agents) SB - IM MH - Antidepressive Agents/therapeutic use MH - Depressive Disorder, Major/diagnostic imaging/physiopathology/*therapy MH - Electroconvulsive Therapy/methods MH - Genome-Wide Association Study MH - Humans MH - Neuroimaging MH - Practice Guidelines as Topic MH - Psychotherapy MH - Randomized Controlled Trials as Topic MH - Treatment Outcome PMC - PMC6447556 COIS- Funding for this work was supported in part by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; ZIA MH002927). All support given to authors was not related to the design of the manuscript or the ideas stated in this review. Dr. Kasper received grants/research support, consulting fees, and/or honoraria within the last 3 years from Angelini, AOP Orphan Pharmaceuticals AG, AstraZeneca, Eli Lilly, Janssen, KRKA-Pharma, Lundbeck, Neuraxpharm, Pfizer, Pierre Fabre, Schwabe, and Servier. Dr. Lanzenberger received travel grants and/or conference speaker honoraria from AstraZeneca, Lundbeck A/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, and Roche Austria GmbH. Dr. Kraus has received travel grants from Roche Austria GmbH and AOP Orphan. Dr. Zarate is a full-time U.S government employee. He is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydro and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. EDAT- 2019/04/05 06:00 MHDA- 2020/01/10 06:00 PMCR- 2019/04/03 CRDT- 2019/04/05 06:00 PHST- 2018/11/07 00:00 [received] PHST- 2019/02/11 00:00 [accepted] PHST- 2019/01/10 00:00 [revised] PHST- 2019/04/05 06:00 [entrez] PHST- 2019/04/05 06:00 [pubmed] PHST- 2020/01/10 06:00 [medline] PHST- 2019/04/03 00:00 [pmc-release] AID - 10.1038/s41398-019-0460-3 [pii] AID - 460 [pii] AID - 10.1038/s41398-019-0460-3 [doi] PST - epublish SO - Transl Psychiatry. 2019 Apr 3;9(1):127. doi: 10.1038/s41398-019-0460-3.