SeminarVolume 406, Issue 10506p963-978August 30, 2025

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Bipolar disorder

Balwinder Singh, MD MS 0000-0001-7062-8192
Correspondence
Correspondence to: Dr Balwinder Singh, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, USA
Affiliations
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
a singh.balwinder@mayo.edu
Prof Holly A Swartz, MD
Affiliations
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
b
Prof Alfredo B Cuellar-Barboza, MD
Affiliations
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
Department of Psychiatry, Autonomous University of Nuevo Leon, San Nicolas de los Garza, Mexico
a,c
Prof Ayal Schaffer, MD
Affiliations
Department of Psychiatry, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
d
Prof Tadafumi Kato, MD PhD
Affiliations
Department of Psychiatry and Behavioral Science, Juntendo University Graduate School of Medicine, Tokyo, Japan
e
Prof Annemieke Dols, MD PhD
Affiliations
Department of Psychiatry, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands
f
Sarah H Sperry, PhD
Affiliations
Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA
g
Andrea B Vassilev, PsyD
Affiliations
Los Angeles, CA, USA
h
Prof Katherine E Burdick, PhD
Affiliations
Department of Psychiatry, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA
i
Prof Mark A Frye, MD
Affiliations
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
a
∙ et al. Show more

Summary

The hallmark of bipolar disorder is hypomania or mania, and the predominant phase of illness is depression. Affecting approximately 40 million individuals worldwide, bipolar disorder is associated with a substantial psychosocial, medical, and financial burden and increased mortality from suicide and other causes. Diagnosis can be challenging due to symptom overlap with attention-deficit hyperactivity disorder, major depressive disorder, psychotic spectrum disorders, and personality disorders, which often leads to a delay in diagnosis. Recent advancements in understanding disease risk and pathophysiology have identified multigene risk and possible infectious and mitochondrial causes. Treatment approaches include pharmacotherapy, psychotherapy, and lifestyle modifications, which should always be patient-centred and aligned with individual goals and priorities. Future directions for bipolar disorder care include increasing the availability of psychosocial interventions aimed at self-management, addressing treatment-resistant bipolar depression, deepening the understanding of pathophysiology, and exploring novel interventions, such as ketamine, esketamine, other rapid-acting antidepressants, and various neuromodulation approaches.

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References

1.
McIntyre, RS ∙ Berk, M ∙ Brietzke, E ∙ et al.
Bipolar disorders
Lancet. 2020; 396:1841-1856
2.
Oliva, V ∙ Fico, G ∙ De Prisco, M ∙ et al.
Bipolar disorders: an update on critical aspects
Lancet Reg Health Eur. 2024; 48, 101135
3.
Singh, B ∙ Yocum, AK ∙ Strawbridge, R ∙ et al.
Patterns of pharmacotherapy for bipolar disorder: a GBC survey
Bipolar Disord. 2024; 26:22-32
4.
Goetzel, RZ ∙ Hawkins, K ∙ Ozminkowski, RJ ∙ et al.
The health and productivity cost burden of the “top 10” physical and mental health conditions affecting six large U.S. employers in 1999
J Occup Environ Med. 2003; 45:5-14
5.
Mavranezouli, I ∙ Lokkerbol, J
A systematic review and critical appraisal of economic evaluations of pharmacological interventions for people with bipolar disorder
PharmacoEconomics. 2017; 35:271-296
6.
Bessonova, L ∙ Ogden, K ∙ Doane, MJ ∙ et al.
The economic burden of bipolar disorder in the United States: a systematic literature review
Clinicoecon Outcomes Res. 2020; 12:481-497
7.
Simon, J ∙ Pari, AAA ∙ Wolstenholme, J ∙ et al.
The costs of bipolar disorder in the United Kingdom
Brain Behav. 2021; 11, e2351
8.
Dembek, C ∙ Mackie, D ∙ Modi, K ∙ et al.
The economic and humanistic burden of bipolar disorder in adults in the United States
Ann Gen Psychiatry. 2023; 22:13
9.
Merikangas, KR ∙ Jin, R ∙ He, JP ∙ et al.
Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative
Arch Gen Psychiatry. 2011; 68:241-251
10.
Nierenberg, AA ∙ Agustini, B ∙ Köhler-Forsberg, O ∙ et al.
Diagnosis and treatment of bipolar disorder: a review
JAMA. 2023; 330:1370-1380
11.
He, H ∙ Hu, C ∙ Ren, Z ∙ et al.
Trends in the incidence and DALYs of bipolar disorder at global, regional, and national levels: results from the Global Burden of Disease Study 2017
J Psychiatr Res. 2020; 125:96-105
12.
Post, RM ∙ Altshuler, LL ∙ Kupka, R ∙ et al.
More childhood onset bipolar disorder in the United States than Canada or Europe: implications for treatment and prevention
Neurosci Biobehav Rev. 2017; 74:204-213
13.
Semahegn, A ∙ Torpey, K ∙ Manu, A ∙ et al.
Psychotropic medication non-adherence and its associated factors among patients with major psychiatric disorders: a systematic review and meta-analysis
Syst Rev. 2020; 9:17
14.
Chan, JKN ∙ Tong, CHY ∙ Wong, CSM ∙ et al.
Life expectancy and years of potential life lost in bipolar disorder: systematic review and meta-analysis
Br J Psychiatry. 2022; 221:567-576
15.
Kessing, LV ∙ Vradi, E ∙ McIntyre, RS ∙ et al.
Causes of decreased life expectancy over the life span in bipolar disorder
J Affect Disord. 2015; 180:142-147
16.
Foroughi, M ∙ Medina Inojosa, JR ∙ Lopez-Jimenez, F ∙ et al.
Association of bipolar disorder with major adverse cardiovascular events: a population-based historical cohort study
Psychosom Med. 2022; 84:97-103
17.
Miller, JN ∙ Black, DW
Bipolar disorder and suicide: a review
Curr Psychiatry Rep. 2020; 22:6
18.
Dev, DA ∙ Le, GH ∙ Kwan, ATH ∙ et al.
Comparing suicide completion rates in bipolar I versus bipolar II disorder: a systematic review and meta-analysis
J Affect Disord. 2024; 361:480-488
19.
Khoso, AB ∙ Noureen, A ∙ Un Nisa, Z ∙ et al.
Prevalence of suicidal ideation and suicide attempts in individuals with psychosis and bipolar disorder in South Asia: systematic review and meta-analysis
BJPsych Open. 2023; 9:e179
20.
Plans, L ∙ Barrot, C ∙ Nieto, E ∙ et al.
Association between completed suicide and bipolar disorder: a systematic review of the literature
J Affect Disord. 2019; 242:111-122
21.
Schaffer, A ∙ Isometsä, ET ∙ Azorin, JM ∙ et al.
A review of factors associated with greater likelihood of suicide attempts and suicide deaths in bipolar disorder: part II of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder
Aust N Z J Psychiatry. 2015; 49:1006-1020
22.
Paljärvi, T ∙ Herttua, K ∙ Taipale, H ∙ et al.
Cause-specific excess mortality after first diagnosis of bipolar disorder: population-based cohort study
BMJ Ment Health. 2023; 26, e300700
23.
Bartoli, F ∙ Bassetti, C ∙ Gazzola, M ∙ et al.
Prevalence and correlates of manic/hypomanic and depressive predominant polarity in bipolar disorder: systematic review and meta-analysis
BJPsych Open. 2024; 10:e100
24.
Manchia, M ∙ Miola, A ∙ Tondo, L ∙ et al.
Unipolar mania: prevalence and patient characteristics
Acta Psychiatr Scand. 2025; 151:680-688
25.
Alloy, LB ∙ Urošević, S ∙ Abramson, LY ∙ et al.
Progression along the bipolar spectrum: a longitudinal study of predictors of conversion from bipolar spectrum conditions to bipolar I and II disorders
J Abnorm Psychol. 2012; 121:16-27
26.
Yatham, LN ∙ Chakrabarty, T ∙ Bond, DJ ∙ et al.
Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) recommendations for the management of patients with bipolar disorder with mixed presentations
Bipolar Disord. 2021; 23:767-788
27.
Miola, A ∙ Fountoulakis, KN ∙ Baldessarini, RJ ∙ et al.
Prevalence and outcomes of rapid cycling bipolar disorder: mixed method systematic meta-review
J Psychiatr Res. 2023; 164:404-415
28.
Ratheesh, A ∙ Davey, C ∙ Hetrick, S ∙ et al.
A systematic review and meta-analysis of prospective transition from major depression to bipolar disorder
Acta Psychiatr Scand. 2017; 135:273-284
29.
Scott, J ∙ Graham, A ∙ Yung, A ∙ et al.
A systematic review and meta-analysis of delayed help-seeking, delayed diagnosis and duration of untreated illness in bipolar disorders
Acta Psychiatr Scand. 2022; 146:389-405
30.
Dunayevich, E ∙ Keck, Jr, PE
Prevalence and description of psychotic features in bipolar mania
Curr Psychiatry Rep. 2000; 2:286-290
31.
Nusslock, R ∙ Frank, E
Subthreshold bipolarity: diagnostic issues and challenges
Bipolar Disord. 2011; 13:587-603
32.
Torales, J ∙ González, I ∙ Barrios, I ∙ et al.
Manic episodes due to medical illnesses: a literature review
J Nerv Ment Dis. 2018; 206:733-738
33.
Lichtenstein, P ∙ Yip, BH ∙ Björk, C ∙ et al.
Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study
Lancet. 2009; 373:234-239
34.
O'Connell, KS ∙ Koromina, M ∙ van der Veen, T ∙ et al.
Genomics yields biological and phenotypic insights into bipolar disorder
Nature. 2025; 639:968-975
35.
Aas, M ∙ Bellivier, F ∙ Bettella, F ∙ et al.
Childhood maltreatment and polygenic risk in bipolar disorders
Bipolar Disord. 2020; 22:174-181
36.
Fürtjes, AE ∙ Coleman, JRI ∙ Tyrrell, J ∙ et al.
Associations and limited shared genetic aetiology between bipolar disorder and cardiometabolic traits in the UK Biobank
Psychol Med. 2021; 52:1-10
37.
Meijsen, J ∙ Hu, K ∙ Krebs, MD ∙ et al.
Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians
Nat Commun. 2024; 15, 5064
38.
O'Connell, KS ∙ Coombes, BJ
Genetic contributions to bipolar disorder: current status and future directions
Psychol Med. 2021; 51:2156-2167
39.
Kato, T
Bipolar disorder: from pathophysiology to treatment
Juntendo Iji Zasshi. 2021; 68:17-24
40.
Rowland, T ∙ Perry, BI ∙ Upthegrove, R ∙ et al.
Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar disorder: systematic review and meta-analyses
Br J Psychiatry. 2018; 213:514-525
41.
Scaini, G ∙ Andrews, T ∙ Lima, CNC ∙ et al.
Mitochondrial dysfunction as a critical event in the pathophysiology of bipolar disorder
Mitochondrion. 2021; 57:23-36
42.
Bodenstein, DF ∙ Kim, HK ∙ Brown, NC ∙ et al.
Mitochondrial DNA content and oxidation in bipolar disorder and its role across brain regions
NPJ Schizophr. 2019; 5:21
43.
Meloni, A ∙ Paribello, P ∙ Pinna, M ∙ et al.
Mitochondrial DNA copy number is significantly increased in bipolar disorder patients and is correlated with long-term lithium treatment
Eur Neuropsychopharmacol. 2025; 91:37-44
44.
Nishioka, M ∙ Takayama, J ∙ Sakai, N ∙ et al.
Deep exome sequencing identifies enrichment of deleterious mosaic variants in neurodevelopmental disorder genes and mitochondrial tRNA regions in bipolar disorder
Mol Psychiatry. 2023; 28:4294-4306
45.
Giménez-Palomo, A ∙ Andreu, H ∙ de Juan, O ∙ et al.
Mitochondrial dysfunction as a biomarker of illness state in bipolar disorder: a critical review
Brain Sci. 2024; 14, 1199
46.
McCarthy, MJ ∙ Gottlieb, JF ∙ Gonzalez, R ∙ et al.
Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: a critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology
Bipolar Disord. 2022; 24:232-263
47.
Frye, MA ∙ Coombes, BJ ∙ McElroy, SL ∙ et al.
Association of cytomegalovirus and toxoplasma gondii antibody titers with bipolar disorder
JAMA Psychiatry. 2019; 76:1285-1293
48.
Tanaka, T ∙ Matsuda, T ∙ Hayes, LN ∙ et al.
Infection and inflammation in schizophrenia and bipolar disorder
Neurosci Res. 2017; 115:59-63
49.
Munkholm, K ∙ Jacoby, AS ∙ Lenskjold, T ∙ et al.
Leukocytes in peripheral blood in patients with bipolar disorder - trait and state alterations and association with levels of cytokines and C-reactive protein
Psychiatry Res. 2018; 261:383-390
50.
Chen, Z ∙ Huang, Y ∙ Wang, B ∙ et al.
T cells: an emerging cast of roles in bipolar disorder
Transl Psychiatry. 2023; 13:153
51.
Pereira, AC ∙ Oliveira, J ∙ Silva, S ∙ et al.
Inflammation in bipolar disorder (BD): identification of new therapeutic targets
Pharmacol Res. 2021; 163, 105325
52.
Cuellar-Barboza, AB ∙ Cabello-Arreola, A ∙ Winham, SJ ∙ et al.
Body mass index and blood pressure in bipolar patients: target cardiometabolic markers for clinical practice
J Affect Disord. 2021; 282:637-643
53.
Barbosa, IG ∙ Rocha, NP ∙ Vieira, EL ∙ et al.
Decreased percentage of CD4+ lymphocytes expressing chemokine receptors in bipolar disorder
Acta Neuropsychiatr. 2019; 31:246-251
54.
Hibar, DP ∙ Westlye, LT ∙ Doan, NT ∙ et al.
Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
Mol Psychiatry. 2018; 23:932-942
55.
Sun, YR ∙ Herrmann, N ∙ Scott, CJM ∙ et al.
Global grey matter volume in adult bipolar patients with and without lithium treatment: a meta-analysis
J Affect Disord. 2018; 225:599-606
56.
Favre, P ∙ Pauling, M ∙ Stout, J ∙ et al., the ENIGMA Bipolar Disorder Working Group
Widespread white matter microstructural abnormalities in bipolar disorder: evidence from mega- and meta-analyses across 3033 individuals
Neuropsychopharmacology. 2019; 44:2285-2293
57.
Damgaard, V ∙ Fortea, L ∙ Schandorff, JM ∙ et al.
Multivariate patterns among multimodal neuroimaging and clinical, cognitive, and daily functioning characteristics in bipolar disorder
Neuropsychopharmacology. 2025; 50:976-982
58.
Kjærstad, HL ∙ de Siqueira Rotenberg, L ∙ Macoveanu, J ∙ et al.
Stable neural underpinnings of emotional cognition subgroups in patients newly diagnosed with bipolar disorder: a prospective fMRI study
Bipolar Disord. 2024; 26:556-569
59.
Mesbah, R ∙ Koenders, MA ∙ van der Wee, NJA ∙ et al.
Association between the fronto-limbic network and cognitive and emotional functioning in individuals with bipolar disorder: a systematic review and meta-analysis
JAMA Psychiatry. 2023; 80:432-440
60.
Krystal, S ∙ Gracia, L ∙ Piguet, C ∙ et al.
Functional connectivity of the amygdala subnuclei in various mood states of bipolar disorder
Mol Psychiatry. 2024; 29:3344-3355
61.
Schumer, MC ∙ Bertocci, MA ∙ Aslam, HA ∙ et al.
Patterns of neural network functional connectivity associated with mania/hypomania and depression risk in 3 independent young adult samples
JAMA Psychiatry. 2024; 81:167-177
62.
Jauhar, S ∙ Nour, MM ∙ Veronese, M ∙ et al.
A test of the transdiagnostic dopamine hypothesis of psychosis using positron emission tomographic imaging in bipolar affective disorder and schizophrenia
JAMA Psychiatry. 2017; 74:1206-1213
63.
Bi, B ∙ Che, D ∙ Bai, Y
Neural network of bipolar disorder: toward integration of neuroimaging and neurocircuit-based treatment strategies
Transl Psychiatry. 2022; 12:143
64.
Amanollahi, M ∙ Jameie, M ∙ Looha, MA ∙ et al.
Machine learning applied to the prediction of relapse, hospitalization, and suicide in bipolar disorder using neuroimaging and clinical data: a systematic review
J Affect Disord. 2024; 361:778-797
65.
Claude, LA ∙ Houenou, J ∙ Duchesnay, E ∙ et al.
Will machine learning applied to neuroimaging in bipolar disorder help the clinician? A critical review and methodological suggestions
Bipolar Disord. 2020; 22:334-355
66.
Keramatian, K ∙ Chithra, NK ∙ Yatham, LN
The CANMAT and ISBD guidelines for the treatment of bipolar disorder: summary and a 2023 update of evidence
Focus Am Psychiatr Publ. 2023; 21:344-353
67.
Lin, SK ∙ Yang, SY ∙ Park, SC ∙ et al.
Prescription patterns for bipolar disorder in Asian countries: findings from research on Asian prescription pattern-bipolar disorder
Clin Psychopharmacol Neurosci. 2022; 20:61-69
68.
Tajika, A ∙ Hori, H ∙ Iga, JI ∙ et al.
Mood stabilizers and antipsychotics for acute mania: systematic review and meta-analysis of augmentation therapy vs monotherapy from the perspective of time to the onset of treatment effects
Int J Neuropsychopharmacol. 2022; 25:839-852
69.
Torres, R ∙ Czeisler, EL ∙ Chadwick, SR ∙ et al.
Efficacy and safety of iloperidone in bipolar mania: a double-blind, placebo-controlled study
J Clin Psychiatry. 2024; 85, 23m14966
70.
Monahan, C ∙ McCoy, L ∙ Powell, J ∙ et al.
Olanzapine/samidorphan: new drug approved for treating bipolar I disorder and schizophrenia
Ann Pharmacother. 2022; 56:1049-1057
71.
Yildiz, A ∙ Siafis, S ∙ Mavridis, D ∙ et al.
Comparative efficacy and tolerability of pharmacological interventions for acute bipolar depression in adults: a systematic review and network meta-analysis
Lancet Psychiatry. 2023; 10:693-705
72.
Singh, B
Lithium for depression-related hospitalisation in bipolar disorder
Lancet Psychiatry. 2025; 12:165-166
73.
Park, JH ∙ Nuñez, NA ∙ Gardea-Resendez, M ∙ et al.
Short term second-generation antidepressant monotherapy in acute depressive episodes of bipolar ii disorder: a systematic review and meta-analysis
Psychopharmacol Bull. 2022; 52:45-72
74.
Chen, YB ∙ Liang, CS ∙ Wang, LJ ∙ et al.
Comparative effectiveness of valproic acid in different serum concentrations for maintenance treatment of bipolar disorder: a retrospective cohort study using target trial emulation framework
EClinicalMedicine. 2022; 54, 101678
75.
Medicines and Healthcare products Regulatory Agency
Valproate: review of safety data and expert advice on management of risks
76.
Kong, L ∙ Wang, H ∙ Yan, N ∙ et al.
Effect of antipsychotics and mood stabilisers on metabolism in bipolar disorder: a network meta-analysis of randomised-controlled trials
EClinicalMedicine. 2024; 71, 102581
77.
Li, S ∙ Xu, C ∙ Hu, S ∙ et al.
Efficacy and tolerability of FDA-approved atypical antipsychotics for the treatment of bipolar depression: a systematic review and network meta-analysis
Eur Psychiatry. 2024; 67:e29
78.
Kendall, T ∙ Morriss, R ∙ Mayo-Wilson, E ∙ et al., the Guideline Development Group of the National Institute for Health and Care Excellence
Assessment and management of bipolar disorder: summary of updated NICE guidance
BMJ. 2014; 349, g5673
79.
Yatham, LN ∙ Kennedy, SH ∙ Parikh, SV ∙ et al.
Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder
Bipolar Disord. 2018; 20:97-170
80.
Oud, M ∙ Mayo-Wilson, E ∙ Braidwood, R ∙ et al.
Psychological interventions for adults with bipolar disorder: systematic review and meta-analysis
Br J Psychiatry. 2016; 208:213-222
81.
Miklowitz, DJ ∙ Efthimiou, O ∙ Furukawa, TA ∙ et al.
Adjunctive psychotherapy for bipolar disorder: a systematic review and component network meta-analysis
JAMA Psychiatry. 2021; 78:141-150
82.
Novick, DM ∙ Swartz, HA
Evidence-based psychotherapies for bipolar disorder
Focus Am Psychiatr Publ. 2019; 17:238-248
83.
Kato, T ∙ Ogasawara, K ∙ Motomura, K ∙ et al.
Practice guidelines for bipolar disorder by the JSMD (Japanese Society of Mood Disorders)
Psychiatry Clin Neurosci. 2024; 78:633-645
84.
Eisner, E ∙ Faulkner, S ∙ Allan, S ∙ et al.
Barriers and facilitators of user engagement with digital mental health interventions for people with psychosis or bipolar disorder: systematic review and best-fit framework synthesis
JMIR Ment Health. 2025; 12, e65246
85.
Morton, E ∙ Nicholas, J ∙ Yang, L ∙ et al.
Evaluating the quality, safety, and functionality of commonly used smartphone apps for bipolar disorder mood and sleep self-management
Int J Bipolar Disord. 2022; 10:10
86.
Gliddon, E ∙ Barnes, SJ ∙ Murray, G ∙ et al.
Online and mobile technologies for self-management in bipolar disorder: a systematic review
Psychiatr Rehabil J. 2017; 40:309-319
87.
Hirakawa, H ∙ Terao, T ∙ Muronaga, M ∙ et al.
Adjunctive bright light therapy for treating bipolar depression: a systematic review and meta-analysis of randomized controlled trials
Brain Behav. 2020; 10, e01876
88.
Sit, DK ∙ McGowan, J ∙ Wiltrout, C ∙ et al.
Adjunctive bright light therapy for bipolar depression: a randomized double-blind placebo-controlled trial
Am J Psychiatry. 2018; 175:131-139
89.
Fregna, L ∙ Attanasio, F ∙ Colombo, C
The effect of bright light therapy on irritability in bipolar depression: a single-blind randomised control trial
Int J Psychiatry Clin Pract. 2023; 27:416-418
90.
Singh, B ∙ Kung, S ∙ Poppe, KA ∙ et al.
Partial wake therapy and luminotherapy as an adjunct to usual care in hospitalized patients with depression - a pilot study
Psychiatry Res. 2024; 337, 115921
91.
Hester, L ∙ Dang, D ∙ Barker, CJ ∙ et al.
Evening wear of blue-blocking glasses for sleep and mood disorders: a systematic review
Chronobiol Int. 2021; 38:1375-1383
92.
Simjanoski, M ∙ Patel, S ∙ Boni, R ∙ et al.
Lifestyle interventions for bipolar disorders: a systematic review and meta-analysis
Neurosci Biobehav Rev. 2023; 152, 105257
93.
Kim, JA ∙ Sankar, A ∙ Marks, R ∙ et al.
Chronotherapeutic intervention targeting emotion regulation brain circuitry, symptoms, and suicide risk in adolescents and young adults with bipolar disorder: a pilot randomised trial
BMJ Ment Health. 2025; 28, e301338
94.
Swartz, HA
The social rhythm therapy workbook for bipolar disorder: stabilize your circadian rhythms to reduce stress, manage moods, and prevent future episodes
New Harbinger Publications, 2024
95.
Elsayed, OH ∙ Ercis, M ∙ Pahwa, M ∙ et al.
Treatment-resistant bipolar depression: therapeutic trends, challenges and future directions
Neuropsychiatr Dis Treat. 2022; 18:2927-2943
96.
Schoeyen, HK ∙ Kessler, U ∙ Andreassen, OA ∙ et al.
Treatment-resistant bipolar depression: a randomized controlled trial of electroconvulsive therapy versus algorithm-based pharmacological treatment
Am J Psychiatry. 2015; 172:41-51
97.
Zhang, J ∙ Wang, G ∙ Yang, X ∙ et al.
Efficacy and safety of electroconvulsive therapy plus medication versus medication alone in acute mania: a meta-analysis of randomized controlled trials
Psychiatry Res. 2021; 302, 114019
98.
Popiolek, K ∙ Bejerot, S ∙ Brus, O ∙ et al.
Electroconvulsive therapy in bipolar depression - effectiveness and prognostic factors
Acta Psychiatr Scand. 2019; 140:196-204
99.
Popiolek, K ∙ Bejerot, S ∙ Landén, M ∙ et al.
Association of clinical and demographic characteristics with response to electroconvulsive therapy in mania
JAMA Netw Open. 2022; 5, e2218330
100.
Loef, D ∙ Hoogendoorn, AW ∙ Somers, M ∙ et al.
A prediction model for electroconvulsive therapy effectiveness in patients with major depressive disorder from the Dutch ECT Consortium (DEC)
Mol Psychiatry. 2025; 30:1915-1924
101.
Kishi, T ∙ Sakuma, K ∙ Matsuda, Y ∙ et al.
Repetitive transcranial magnetic stimulation for mania: a systematic review and meta-analysis
Bipolar Disord. 2023; 25:160-161
102.
Konstantinou, G ∙ Hui, J ∙ Ortiz, A ∙ et al.
Repetitive transcranial magnetic stimulation (rTMS) in bipolar disorder: a systematic review
Bipolar Disord. 2022; 24:10-26
103.
McGirr, A ∙ Karmani, S ∙ Arsappa, R ∙ et al.
Clinical efficacy and safety of repetitive transcranial magnetic stimulation in acute bipolar depression
World Psychiatry. 2016; 15:85-86
104.
Biazus, TB ∙ Beraldi, GH ∙ Tokeshi, L ∙ et al.
All-cause and cause-specific mortality among people with bipolar disorder: a large-scale systematic review and meta-analysis
Mol Psychiatry. 2023; 28:2508-2524
105.
O'Connor, RC ∙ Worthman, CM ∙ Abanga, M ∙ et al.
Gone too soon: priorities for action to prevent premature mortality associated with mental illness and mental distress
Lancet Psychiatry. 2023; 10:452-464
106.
Belsher, BE ∙ Smolenski, DJ ∙ Pruitt, LD ∙ et al.
Prediction models for suicide attempts and deaths: a systematic review and simulation
JAMA Psychiatry. 2019; 76:642-651
107.
Clements, C ∙ Morriss, R ∙ Jones, S ∙ et al.
Suicide in bipolar disorder in a national English sample, 1996-2009: frequency, trends and characteristics
Psychol Med. 2013; 43:2593-2602
108.
Schaffer, A ∙ Malhi, GS
A new model for the prevention of suicide in bipolar disorder: every patient, every setting, every provider
Bipolar Disord. 2024; 26:309-312
109.
Del Matto, L ∙ Muscas, M ∙ Murru, A ∙ et al.
Lithium and suicide prevention in mood disorders and in the general population: a systematic review
Neurosci Biobehav Rev. 2020; 116:142-153
110.
Izadi, N ∙ Mitchell, RHB ∙ Giacobbe, P ∙ et al.
Suicide assessment and prevention in bipolar disorder: how current evidence can inform clinical practice
Focus Am Psychiatr Publ. 2023; 21:380-388
111.
Chung, TH ∙ Hanley, K ∙ Le, YC ∙ et al.
A validation study of PHQ-9 suicide item with the Columbia Suicide Severity Rating Scale in outpatients with mood disorders at National Network of Depression Centers
J Affect Disord. 2023; 320:590-594
112.
Stanley, B ∙ Brown, GK ∙ Brenner, LA ∙ et al.
Comparison of the safety planning intervention with follow-up vs usual care of suicidal patients treated in the emergency department
JAMA Psychiatry. 2018; 75:894-900
113.
Skopp, NA ∙ Smolenski, DJ ∙ Bush, NE ∙ et al.
Caring contacts for suicide prevention: a systematic review and meta-analysis
Psychol Serv. 2023; 20:74-83
114.
Chaudhary, AMD ∙ Memon, RI ∙ Dar, SK ∙ et al.
Suicide during transition of care: a review of targeted interventions
Psychiatr Q. 2020; 91:417-450
115.
WHO
LIVE LIFE: an implementation guide for suicide prevention in countries
World Health Organization, Geneva, 2021
116.
Shitomi-Jones, LM ∙ Dolman, C ∙ Jones, I ∙ et al.
Exploration of first onsets of mania, schizophrenia spectrum disorders and major depressive disorder in perimenopause
Nat Ment Health. 2024; 2:1161-1168
117.
Truong, D ∙ Marsh, W
Bipolar disorder in the menopausal transition
Curr Psychiatry Rep. 2019; 21:130
118.
Sharma, V ∙ Wood, KN ∙ Weaver, B ∙ et al.
Occurrence of postpartum manic or mixed episodes in women with bipolar I disorder: a systematic review and meta-analysis
Bipolar Disord. 2024; 26:240-248
119.
Vigod, SN ∙ Frey, BN ∙ Clark, CT ∙ et al.
Canadian Network for Mood and Anxiety Treatments 2024 clinical practice guideline for the management of perinatal mood, anxiety, and related disorders: guide de pratique 2024 du Canadian Network for Mood and Anxiety Treatments pour le traitement des troubles de l'humeur, des troubles anxieux et des troubles connexes périnatals
Can J Psychiatry. 2025;
120.
Nicoloro-SantaBarbara, J ∙ Majd, M ∙ Miskowiak, K ∙ et al.
Cognition in bipolar disorder: an update for clinicians
Focus Am Psychiatr Publ. 2023; 21:363-369
121.
Miskowiak, KW ∙ Seeberg, I ∙ Jensen, MB ∙ et al.
Randomised controlled cognition trials in remitted patients with mood disorders published between 2015 and 2021: a systematic review by the International Society for Bipolar Disorders Targeting Cognition Task Force
Bipolar Disord. 2022; 24:354-374
122.
Bora, E
A meta-analysis of data-driven cognitive subgroups in bipolar disorder
Eur Neuropsychopharmacol. 2025; 90:48-57
123.
Green, MJ ∙ Girshkin, L ∙ Kremerskothen, K ∙ et al.
A systematic review of studies reporting data-driven cognitive subtypes across the psychosis spectrum
Neuropsychol Rev. 2020; 30:446-460
124.
Miskowiak, KW ∙ Seeberg, I ∙ Kjaerstad, HL ∙ et al.
Affective cognition in bipolar disorder: a systematic review by the ISBD targeting cognition task force
Bipolar Disord. 2019; 21:686-719
125.
Kanady, JC ∙ Soehner, AM ∙ Klein, AB ∙ et al.
The association between insomnia-related sleep disruptions and cognitive dysfunction during the inter-episode phase of bipolar disorder
J Psychiatr Res. 2017; 88:80-88
126.
Gogia, M ∙ Shah, AQ ∙ Kapczinski, F ∙ et al.
The impact of substance use disorder comorbidity on cognition of individuals with bipolar disorder: a systematic review
Psychiatry Res. 2022; 311, 114525
127.
Mario, A ∙ Ivana, L ∙ Anita, M ∙ et al.
Inflammatory biomarkers, cognitive functioning, and brain imaging abnormalities in bipolar disorder: a systematic review
Clin Neuropsychiatry. 2024; 21:32-62
128.
Millett, CE ∙ Perez-Rodriguez, M ∙ Shanahan, M ∙ et al.
C-reactive protein is associated with cognitive performance in a large cohort of euthymic patients with bipolar disorder
Mol Psychiatry. 2021; 26:4096-4105
129.
Van Rheenen, TE ∙ Lewandowski, KE ∙ Bauer, IE ∙ et al.
Current understandings of the trajectory and emerging correlates of cognitive impairment in bipolar disorder: an overview of evidence
Bipolar Disord. 2020; 22:13-27
130.
Samamé, C ∙ Durante, P ∙ Cattaneo, B ∙ et al.
Efficacy of cognitive remediation in bipolar disorder: systematic review and meta-analysis of randomized controlled trials
Psychol Med. 2023; 53:5361-5373
131.
Camprodon-Boadas, P ∙ De Prisco, M ∙ Rabelo-da-Ponte, FD ∙ et al.
Cognitive reserve and cognition in mood disorders: a systematic review and meta-analysis
Psychiatry Res. 2024; 339, 116083
132.
Dols, A ∙ Kessing, LV ∙ Strejilevich, SA ∙ et al.
Do current national and international guidelines have specific recommendations for older adults with bipolar disorder? A brief report
Int J Geriatr Psychiatry. 2016; 31:1295-1300
133.
Schouws, SN ∙ Comijs, HC ∙ Dols, A ∙ et al.
Five-year follow-up of cognitive impairment in older adults with bipolar disorder
Bipolar Disord. 2016; 18:148-154
134.
Diniz, BS ∙ Teixeira, AL ∙ Cao, F ∙ et al.
History of bipolar disorder and the risk of dementia: a systematic review and meta-analysis
Am J Geriatr Psychiatry. 2017; 25:357-362
135.
van Liempt, S ∙ Dols, A ∙ Schouws, S ∙ et al.
Comparison of social functioning in community-living older individuals with schizophrenia and bipolar disorder: a catchment area-based study
Int J Geriatr Psychiatry. 2017; 32:532-538
136.
Sinha, A ∙ Shariq, A ∙ Said, K ∙ et al.
Medical comorbidities in bipolar disorder
Curr Psychiatry Rep. 2018; 20:36
137.
Lala, SV ∙ Sajatovic, M
Medical and psychiatric comorbidities among elderly individuals with bipolar disorder: a literature review
J Geriatr Psychiatry Neurol. 2012; 25:20-25
138.
Lambert, AM ∙ Parretti, HM ∙ Pearce, E ∙ et al.
Temporal trends in associations between severe mental illness and risk of cardiovascular disease: a systematic review and meta-analysis
PLoS Med. 2022; 19, e1003960
139.
Hayes, JF ∙ Miles, J ∙ Walters, K ∙ et al.
A systematic review and meta-analysis of premature mortality in bipolar affective disorder
Acta Psychiatr Scand. 2015; 131:417-425
140.
Teixeira, AL ∙ Almeida, OP ∙ Lavin, P ∙ et al.
Physical comorbidities of older age bipolar disorder (OABD) patients: a global replication analysis of prevalence and sex differences
Gen Hosp Psychiatry. 2024; 90:6-11
141.
Almeida, OP ∙ Dols, A ∙ Blanken, MAJT ∙ et al.
Physical health burden among older men and women with bipolar disorder: results from the GAGE-BD collaboration
Am J Geriatr Psychiatry. 2022; 30:727-732
142.
Blanken, MAJT ∙ Oudega, ML ∙ Almeida, OP ∙ et al.
Sex differences among older adults with bipolar disorder: results from the Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) project
Am J Geriatr Psychiatry. 2024; 32:326-338
143.
Sajatovic, M ∙ Rej, S ∙ Almeida, OP ∙ et al.
Bipolar symptoms, somatic burden and functioning in older-age bipolar disorder: a replication study from the Global Aging & Geriatric Experiments in Bipolar Disorder database (GAGE-BD) project
Int J Geriatr Psychiatry. 2024; 39, e6057
144.
Montejo, L ∙ Torrent, C ∙ Jiménez, E ∙ et al.
Cognition in older adults with bipolar disorder: an ISBD task force systematic review and meta-analysis based on a comprehensive neuropsychological assessment
Bipolar Disord. 2022; 24:115-136
145.
Orhan, M ∙ Schouws, S ∙ van Oppen, P ∙ et al.
Cognitive functioning in late life affective disorders: comparing older adults with bipolar disorder, late life depression and healthy controls
J Affect Disord. 2023; 320:468-473
146.
Beunders, AJM ∙ Kemp, T ∙ Korten, NCM ∙ et al.
Cognitive performance in older-age bipolar disorder: investigating psychiatric characteristics, cardiovascular burden and psychotropic medication
Acta Psychiatr Scand. 2021; 144:392-406
147.
Ehrlich, TJ ∙ Ryan, KA ∙ Burdick, KE ∙ et al.
Cognitive subgroups and their longitudinal trajectories in bipolar disorder
Acta Psychiatr Scand. 2022; 146:240-250
148.
Burdick, KE ∙ Russo, M ∙ Frangou, S ∙ et al.
Empirical evidence for discrete neurocognitive subgroups in bipolar disorder: clinical implications
Psychol Med. 2014; 44:3083-3096
149.
Regier, DA ∙ Farmer, ME ∙ Rae, DS ∙ et al.
Comorbidity of mental disorders with alcohol and other drug abuse. results from the Epidemiologic Catchment Area (ECA) study
JAMA. 1990; 264:2511-2518
150.
Hunt, GE ∙ Malhi, GS ∙ Cleary, M ∙ et al.
Prevalence of comorbid bipolar and substance use disorders in clinical settings, 1990-2015: systematic review and meta-analysis
J Affect Disord. 2016; 206:331-349
151.
Bahji, A ∙ Danilewitz, M ∙ Vazquez, G ∙ et al.
The prevalence of cannabis use disorder comorbidity in individuals with bipolar disorder: a systematic review and meta-analysis
Can J Addict. 2021; 12:22-38
152.
Lasagna, CA ∙ Pleskac, TJ ∙ Burton, CZ ∙ et al.
Mathematical modeling of risk-taking in bipolar disorder: evidence of reduced behavioral consistency, with altered loss aversion specific to those with history of substance use disorder
Comput Psychiatr. 2022; 6:96-116
153.
Swann, AC
The strong relationship between bipolar and substance-use disorder
Ann N Y Acad Sci. 2010; 1187:276-293
154.
Bart, CP ∙ Titone, MK ∙ Ng, TH ∙ et al.
Neural reward circuit dysfunction as a risk factor for bipolar spectrum disorders and substance use disorders: a review and integration
Clin Psychol Rev. 2021; 87, 102035
155.
Sperry, SH ∙ Stromberg, AR ∙ Murphy, VA ∙ et al.
Longitudinal interplay between alcohol use, mood, and functioning in bipolar spectrum disorders
JAMA Netw Open. 2024; 7, e2415295
156.
Mueser, KT ∙ Glynn, SM ∙ Cather, C ∙ et al.
A randomized controlled trial of family intervention for co-occurring substance use and severe psychiatric disorders
Schizophr Bull. 2013; 39:658-672
157.
Gordon-Smith, K ∙ Lewis, KJS ∙ Vallejo Auñón, FM ∙ et al.
Patterns and clinical correlates of lifetime alcohol consumption in women and men with bipolar disorder: findings from the UK Bipolar Disorder Research Network
Bipolar Disord. 2020; 22:731-738
158.
Beaulieu, S ∙ Saury, S ∙ Sareen, J ∙ et al.
The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid substance use disorders
Ann Clin Psychiatry. 2012; 24:38-55
159.
Salloum, IM ∙ Cornelius, JR ∙ Daley, DC ∙ et al.
Efficacy of valproate maintenance in patients with bipolar disorder and alcoholism: a double-blind placebo-controlled study
Arch Gen Psychiatry. 2005; 62:37-45
160.
Morton, E ∙ Foxworth, P ∙ Dardess, P ∙ et al.
“Supporting Wellness”: a depression and bipolar support alliance mixed-methods investigation of lived experience perspectives and priorities for mood disorder treatment
J Affect Disord. 2022; 299:575-584
161.
Jagfeld, G ∙ Lobban, F ∙ Marshall, P ∙ et al.
Personal recovery in bipolar disorder: systematic review and “best fit” framework synthesis of qualitative evidence—a POETIC adaptation of CHIME
J Affect Disord. 2021; 292:375-385
162.
Kelly, JF ∙ Hoffman, L ∙ Vilsaint, C ∙ et al.
Peer support for mood disorder: characteristics and benefits from attending the Depression and Bipolar Support Alliance mutual-help organization
J Affect Disord. 2019; 255:127-135
163.
Murray, G ∙ Suto, M ∙ Hole, R ∙ et al.
Self-management strategies used by ‘high functioning’ individuals with bipolar disorder: from research to clinical practice
Clin Psychol Psychother. 2011; 18:95-109
164.
Perich, T ∙ Mitchell, PB ∙ Vilus, B
Stigma in bipolar disorder: a current review of the literature
Aust N Z J Psychiatry. 2022; 56:1060-1064
165.
Ellouze, S ∙ Jenhani, R ∙ Bougacha, D ∙ et al.
[Self-stigma and functioning in patients with bipolar disorder]
Encephale. 2023; 49:34-40
166.
Gilkes, MJ ∙ Perich, T ∙ Meade, T
Predictors of self-stigma in bipolar disorder: depression, mania, and perceived cognitive function
Stigma Health. 2019; 4:330-336
167.
Post, F ∙ Pardeller, S ∙ Frajo-Apor, B ∙ et al.
Quality of life in stabilized outpatients with bipolar I disorder: associations with resilience, internalized stigma, and residual symptoms
J Affect Disord. 2018; 238:399-404
168.
Hidalgo-Mazzei, D ∙ Berk, M ∙ Cipriani, A ∙ et al.
Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: consensus definition
Br J Psychiatry. 2019; 214:27-35
169.
Zengin, G ∙ Topak, OZ ∙ Atesci, O ∙ et al.
The efficacy and safety of transcranial magnetic stimulation in treatment-resistant bipolar depression
Psychiatr Danub. 2022; 34:236-244
170.
Hsu, CW ∙ Chou, PH ∙ Brunoni, AR ∙ et al.
Comparing different non-invasive brain stimulation interventions for bipolar depression treatment: a network meta-analysis of randomized controlled trials
Neurosci Biobehav Rev. 2024; 156, 105483
171.
Raj, KS ∙ Geoly, AD ∙ Veerapal, C ∙ et al.
Pilot study of stanford neuromodulation therapy (SNT) for bipolar depression
Brain Stimul. 2024; 17:321-323
172.
Li, K ∙ Bichlmeier, A ∙ DuPont, C ∙ et al.
Fast depressive symptoms improvement in bipolar I disorder after Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT): a two-site feasibility and safety open-label trial
J Affect Disord. 2024; 365:359-363
173.
Nunez, NA ∙ Joseph, B ∙ Kumar, R ∙ et al.
An update on the efficacy of single and serial intravenous ketamine infusions and esketamine for bipolar depression: a systematic review and meta-analysis
Brain Sci. 2023; 13, 1672
174.
Singh, B ∙ Vande Voort, JL ∙ Frye, MA ∙ et al.
Can ketamine be a safe option for treatment-resistant bipolar depression?
Expert Opin Drug Saf. 2022; 21:717-720
175.
Aaronson, ST ∙ van der Vaart, A ∙ Miller, T ∙ et al.
Single-dose synthetic psilocybin with psychotherapy for treatment-resistant bipolar type II major depressive episodes: a nonrandomized open-label trial
JAMA Psychiatry. 2024; 81:555-562
176.
Fried, EI ∙ Cristea, IA ∙ Naudet, F
Treating bipolar depression using psilocybin-validity threats regarding efficacy and safety
JAMA Psychiatry. 2024; 81:633-634

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