The complexity of delayed diagnosis in bipolar disorder. a systematic review of associated precursors, outcomes, and suggested avenues for improvement

The complexity of delayed diagnosis in bipolar disorder. a systematic review of associated precursors, outcomes, and suggested avenues for improvement | medRxiv /* */ /* */ <!-- <!-- /*! * yepnope1.5.4 * (c) WTFPL, GPLv2 */ (function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-P4HH5NV'); Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search The complexity of delayed diagnosis in bipolar disorder. a systematic review of associated precursors, outcomes, and suggested avenues for improvement View ORCID Profile Gergel Tania , Al-Janabi Mariam , View ORCID Profile Talwar Shivangi , Ahmed Haleemah , View ORCID Profile Wright Talen doi: https://doi.org/10.1101/2025.10.13.25337871 Gergel Tania 1 Division of Psychiatry, University College London , 149 Tottenham Court Road, London, W1T 7NF 2 Bipolar UK , 32 Cubitt Street, London, WC1X 0LS, UK 3 Division of Psychological Medicine and Clinical Neurosciences, Cardiff University , UK 4 Department of English, King’s College London , UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Gergel Tania For correspondence: tania.gergel{at}ucl.ac.uk Al-Janabi Mariam 1 Division of Psychiatry, University College London , 149 Tottenham Court Road, London, W1T 7NF Find this author on Google Scholar Find this author on PubMed Search for this author on this site Talwar Shivangi 1 Division of Psychiatry, University College London , 149 Tottenham Court Road, London, W1T 7NF Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Talwar Shivangi Ahmed Haleemah 1 Division of Psychiatry, University College London , 149 Tottenham Court Road, London, W1T 7NF Find this author on Google Scholar Find this author on PubMed Search for this author on this site Wright Talen 2 Bipolar UK , 32 Cubitt Street, London, WC1X 0LS, UK Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Wright Talen Abstract Full Text Info/History Metrics Supplementary material Data/Code Preview PDF Summary There are widespread stakeholder concerns about adverse consequences of persistent long delays in diagnosing and treating bipolar disorder. Average five-to-ten-year delays are substantiated by previous evidence synthesis, which has focused primarily on quantifying scale. Nevertheless, we lack a complex and broad understanding of diagnostic delay. This review incorporates a complex intervention framework, using co-produced narrative synthesis of quantitative and qualitative studies to identify associated precursors, outcomes, and suggested avenues for improvement. We searched four databases and included 49 generally high-quality studies from high or middle-income countries. This review reinforces some findings from previous reviews regarding scale of delayed diagnosis and key associated precursors, including: history of depression, suicide attempts, earlier onset, female sex, BD-II presentation. However, we also identify a wider range of associated factors and proposed strategies for improvement, which lead us to conclude that future research and interventions should examine delayed diagnosis in terms of its breadth and complex interrelationships with other aspects of bipolar disorder which remain insufficiently understood. These include: mixed, hypomanic, ‘atypical’, and rapid cycling presentations; suicidality in bipolar and its interrelationship with diagnosis, acknowledging the persistence of suicide risk following diagnosis; interrelationship with diverse mental and physical health conditions; attitudes and management of bipolar; the diagnostic process in lower-and-middle income countries; clinical pathways associated with diagnosis and the complex interplay of socio-economic, cultural, and demographic factors and diagnosis. Our review also highlights the need for deeper insight into stakeholder experiences and attitudes toward bipolar management and diagnosis, particularly through qualitative, mixed-methods, and co-produced research. Introduction Bipolar disorder (BD) is a severe and chronic episodic mood disorder, estimated to affect 2-4% of the global population, with a high disease burden including premature mortality, high rates of suicide deaths and attempts, and poor general health and socio-economic outcomes. 1 – 6 Delayed diagnosis (DD) and concomitant delays accessing appropriate treatment are consistently identified by all stakeholders as key challenges for people living with BD. 1 , 5 , 7 – 16 Delays are widely acknowledged to average approximately five to ten years, with depression a common prior diagnosis and high rates of unrecognised BD amongst people diagnosed with depressive disorders. 1 , 14 , 15 , 17 This is supported by evidence from five recent meta-analyses which provide reasonable consensus, although they identify significant between-sample heterogeneity as a limitation 7 , 8 , 16 , 18 , 19 . Nevertheless, despite increasing research examining the scale of delays and some associated factors, the absence of evidence that suggests any substantial reduction in delays suggests that our understanding of the causes, consequences, and pathways to improving BD diagnosis remains limited 8 , 17 , 20 . Within medicine, it is increasingly recognised that both diagnosis and interventions designed to reduce diagnostic delays should be viewed as complex and multifactorial interventions. The diagnostic process should be understood as a “complex, patient-centred, collaborative activity”, 21 and research should use diverse approaches including qualitative work to capture complexity, interpersonal, and socio-cultural dimensions. 22 – 26 The value of stakeholder involvement in improving diagnostic processes and acceptability is also emphasised both in general medicine and psychiatry, 22 , 27 as are the particular complexities, challenges, and limitations associated with diagnosing mental disorder. 28 , 29 Nevertheless, a complex intervention framework has not yet been applied to research on DD and closely related phenomena, such as unrecognised BD amongst people diagnosed with depressive disorders. To date, DD research and systematic synthesis has focused on synthesising epidemiological evidence to establish average duration of delayed diagnosis and treatment or rates of unrecognised BD and diagnostic conversion amongst those diagnosed with depression. One short 2012 narrative review describes some putative adverse clinical, functional, and economic consequences of DD in BD, 17 while Ratheesh et al. 2017 includes an informal summary of qualitative date relating to predictors of diagnostic conversion, 18 and Scott et al. 2022 and Keramatian et al. 2025 include informal supplementary narrative reviews of putative predictors of duration of DD, and associated lifetime outcomes and clinical characteristics respectively. 8 , 16 . A few qualitative studies also identify themes relating to DD. To our knowledge, there has been no systematic narrative synthesis of DD and no inclusion of relevant qualitative literature in any systematic synthesis. Moreover, despite DD being a priority area for people living with BD, there has been, to our knowledge, no co-produced research specifically targeting DD. Our aim, therefore, is to shift the focus of DD evidence synthesis from quantitative analysis of average duration or rates to a model of evidence synthesis suited to complex intervention frameworks, designed to capture breadth and complexity. We seek to identify a wider range of factors relating to DD than previously identified, increasing understanding while highlighting key gaps and potential novel directions for progressing future research or clinical interventions. We use systematic narrative synthesis to integrate diverse study types into a review of DD research, to identify a broad range of themes and subthemes stratified into associated precursors, outcomes, and avenues for improvement. 30 Furthermore, a core priority is incorporation of stakeholder perspectives to reflect the interpersonal and collaborative aspects of diagnosis, through inclusion of qualitative studies and through co-production in design and execution of this systematic review. This review was conceived and supervised by a researcher with lived experience of DD in BD and includes other authors with lived experience of mood disorder. It was conducted within a partnership between Bipolar UK and University College London, established to address stakeholder priorities identified within co-produced initiatives such as the user-led Bipolar UK Bipolar Commission, which reported average DD of 9.5 years, 31 and the James Lind Alliance Priority Setting Partnership, which identified questions relating to DD as a top-ten priority for research into BD. 10 Methods Our review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and is registered on PROSPERO, CRD42024537132 (further information about protocol development can be found in Supplementary Materials). Search strategy, inclusion and exclusion criteria We searched MEDLINE, PsycINFO, Embase, and Web of Science from database inception until July 2024, supplemented by reference searches of included articles and relevant reviews. Key search terms included the main constructs and their derivatives, designed to capture core concepts of delay (including failure to recognise BD and instances where diagnostic conversion from depression to BD is indicated), diagnosis and/or treatment, and BD (for full search strategy see Supplementary Materials). Eligible studies comprised quantitative, qualitative, or mixed-methods studies published in English in peer-reviewed journals with adults diagnosed and/or treated for BD as a primary population, and with delayed diagnosis and/or treatment of BD identified as primary or secondary exposure or a theme/subtheme. With evidence indicating depression as the most common precursor diagnosis to BD diagnosis, we included studies with diagnostic conversion from depression to BD or unrecognised BD amongst people with a depression diagnosis as a primary exposure, viewing such studies as highly relevant to the issue of DD. We did not assess grey literature sources and, given our primary focus on adult-pattern BD, We did not assess grey literature sources and study samples with mean age ≤18 years or studies focused on Bipolar At-Risk (BAR) criteria, which typically target early identification in youth populations, Study selection Titles and abstracts were extracted into endnote for deduplication. TG and MA independently screened titles, abstracts, and full texts. At each stage, disagreements were resolved by discussion between the two raters, with input from TW, HA, and ST in complex cases. Case studies or studies with ≤5 participants, along with studies failing to meet a moderate standard of quality assessment, including relevance, reliability, validity, and applicability, were excluded. Data extraction A data extraction table was created in Excel to include study location; methods (including evidence of incorporation of co- production); sample size and characteristics; primary diagnostic delay exposure and/or focus of study; average length of delay; and main study findings relating to delays in diagnosing and treating BD. Quantitative data for duration was classified following latencies outlined in previous meta-analysis (see Table 2 ), with supplementary descriptions of any variance. Data for all studies was extracted independently by MA and TG, with any disagreements resolved by discussion between the two reviewers, with all authors helping to resolve any uncertainties or ongoing disagreements and carrying out final checks. Quality assessment The quality of included studies was assessed using the KMET scale of standard quality assessment criteria for evaluating primary research papers from a variety of fields 32 . The KMET was selected as having been validated and used in previous systematic reviews including both quantitative and qualitative designs. Quality of included studies was assessed by one reviewer (MA), with a second reviewer (TG) independently conducting quality assessment of a randomly generated sample of 25% of studies. There were high levels of agreement between reviewers and any conflicts in quality appraisal were discussed with the wider review team until consensus was reached. All studies were attributed equal value in terms of contributing to the summary findings. Data synthesis Given our emphasis on breadth and complexity, and the substantial variability in focus, methodology, variables, measurements, and study populations, we analysed findings through qualitative narrative synthesis. 30 At all stages, we followed an integrated approach in which data extraction, analysis, and presentation of findings are executed within a unified framework, regardless of study type. The approach was qualitising, insofar as identification of associated precursors, consequences and outcomes was not based purely statistical significance or frequency of findings, and analysis was thematic, allowing for a small degree of quantification through indicating the frequency of appearance of themes. 30 We used extracted data to identify themes and subthemes for associated precursors, outcomes, and putative avenues for improvement using an iterative deductive methodology combining guidelines for narrative synthesis in systematic reviews and thematic analysis. 33 , 34 TG and MA coded all articles independently using Microsoft Excel, returning to the full text of articles when clarification and expansion of findings was needed. An inductive approach was then used to refine and expand initial coding and themes through an iterative process until all articles were analysed, with codes and themes reviewed regularly by TW and ST, until reaching consensus. Results Our search identified 8334 studies after deduplication and screening by article type, with 7843 excluded by title. 362 articles were excluded after screening abstracts. Of 129 full-text records screened, 40 met inclusion criteria. Nine further studies were added After reference searches and full text screening of 14, nice further studies were added. This totalled 49 studies included in the systematic review (see Figure 1 ). Download figure Open in new tab Figure 1: Study flow diagram Study characteristics Study characteristics are presented in Table 2 . Studies were conducted in 27 countries, with 22 in Europe, four in North America, three in Australasia, nine in Asia, five in South America, and two in Africa. All studies took place in high or middle-income countries, with two middle-income based studies exploring the interrelationship of socio-economic factors and DUB in developing nations. 35 , 36 39 studies were observational epidemiological studies, with delayed diagnosis, duration of untreated bipolar disorder, or unrecognised BD and diagnostic conversion from depression to BD as primary or secondary exposures. The primary exposure was delayed diagnosis or treatment in 13 studies, associated precursors or outcomes in 14 studies, and rates of diagnostic conversion to BD or unrecognised BD amongst people diagnosed with depressive disorders in 12 studies. We also included ten qualitative studies which DD identified as a theme/subtheme. Involvement of people with lived experience of BD in design, implementation, or dissemination of research was reported in three qualitative studies, 37 – 39 but in no epidemiological studies. There was substantial variation in the primary focus of included studies. 12 epidemiological studies focused broadly on clinical and/or socio-demographic associated precursors or outcomes. Other studies focused on specific associations or populations: anti-depressant use; 40 – 42 clinical cost of DUB; 43 relapse frequency; 44 manic or depressive polarities; 35 , 45 increased suicidality; 46 – 48 psychotic symptoms; 49 cannabis use; 50 general medical comorbidities. 51 Some comparative studies examined whether DD duration is reducing; 52 , 53 variation between BD-I and BD-II; 48 , 54 duration in LMICs; 36 variation between early onset and later onset BD. 55 , 56 Nine qualitative studies focused on lived experience of BD examining challenges; 37 , 57 healthcare; 58 , 59 diagnosis; 38 , 59 – 62 ; suicide; 39 research priorities. 63 One qualitative study explored clinical BD research priorities and correlation with service user priorities. 11 Quality assessment We judged 28 of the studies to be of high methodological quality (with 22 studies judged high and 16 very high), with the remaining studies medium (N=9) and low (N=2) [See Quality Assessment Table in Supplementary Materials]. Qualitative synthesis of scale of delay and unrecognised BD All studies measuring delay duration reported long delays in diagnosing and treating BD and high rates of unrecognised BD, despite heterogeneity of study methods, measurements, latencies, and populations. The majority of studies (17/25) presenting average delays in diagnosis or treatment found averages ranging between 5.16 and 10.4 years. Nine of 12 (75%) studies presenting unrecognised BD rates found averages ranging between 18.21% and 39.84%. Further details about these findings, including population-based factors for studies with unusually high or low averages can be found in Supplementary Materials. Narrative synthesis of precursors, consequences, and avenues for improving delays in diagnosing and treating BD We identified five themes amongst delay precursors, with four involving clinical factors, including illness presentation, course, and management. A positive association with increased delay was identified for BD subtypes associated with mixed, hypomanic, or depressive presentations, and with prior depression diagnosis. Studies examining associations with history of anxiety disorders, ADHD, PTSD, personality disorders, multiple misdiagnoses, and general medical conditions also found positive associations with increased delay duration. However, results were more mixed for substance abuse and psychosis. For substance abuse, findings were a mixture of positive, negative, or no association. While history of psychosis was generally associated with shorter delays, some studies identified psychotic disorder diagnosis as a common precursor to BD diagnosis, and one qualitative study linked this phenomenon to predominantly hypo/manic presentations. For illness course, multiple epidemiological studies found earlier age of onset positively associated with increased delay duration, while 12 of 15 studies examining associations with suicide attempt history showed positive associations, and one study showed positive associations with reduced interepisodic recovery. Findings relating to family history of BD were varied and inconclusive. Multiple studies showed diverse positive associations between elements of clinical pathways and longer delay duration. These included particular diagnostic frameworks, poor clinical knowledge, primary care, shorter treatment periods, and increased frequency of medication changes. However, findings relating to history and pattern of hospitalisations were mixed. Three clinical pathway subthemes were identified in qualitative studies as factors potentially associated with increased DD, with three studies highlighting restricted knowledge and treatment options within primary care, 37 , 58 , 59 one identifying clinical non-disclosure of diagnosis, 61 and four studies suggesting that particular mood states may not be witnessed by a clinician. 37 , 38 , 59 , 60 Finally, positive or putative associations with various demographic, socioeconomic and cultural factors, and increased duration of DD/DUB were presented. These included poor psychoeducation, stigma, and concerns surrounding BD, lower socio-economic status, and female sex, although one DC study found associations with male sex and one study found higher functioning in BD-I associated with longer DD. 64 Findings were inconclusive in relation to social isolation and duration of DD/DUB. Additional factors and complexities reported in qualitative studies included clinical reluctance to diagnose BD due to stigma, high-functioning presentations, or concerns about overdiagnosis; how clinical failure to diagnose BD may result in inaccurate suicide risk assessment; clinical prioritisation of physical healthcare issues in primary care; service user/family failure to recognise certain mood states as needing medical attention and reluctance to report hypomanic/manic symptoms or accept diagnosis, although non-acceptance of diagnosis did not necessarily cause rejection of BD-specific treatment. Outcomes associated with delays in diagnosing and treating BD We identified three themes amongst outcomes associated with delays, all pointing to association of longer delays with poorer outcomes post-diagnosis and treatment. Poorer illness course outcomes were: worsened overall illness course, increased incidence of suicide attempts, poorer outcomes following anti-depressant monotherapy, worsened physical health, and increased incidence of comorbidity with anxiety disorder and substance abuse. Poorer clinical outcomes related to increased frequency of hospitalisations, cost of care, and delays accessing treatment. Qualitative studies also suggested associations with decreased service user faith in the healthcare system and insufficient information at diagnosis resulting in longer delays in accessing treatment. Finally, increased delay duration was positively associated with multiple poorer socio-environmental outcomes. Suggested avenues for improving BD diagnosis We identified four themes amongst avenues for improving the diagnostic process amongst included studies, with three themes relating to potential interventions and one relating to research. Two themes related to aspects of clinical care, the need to implement some form of routine and improved screening process and the need for improved services and clinical education. Screening for BD was a very common suggestion, particularly amongst service users presenting with depression or suicide attempts. There was a broad variety of subthemes, focusing on looking for particular BD subtypes amongst particular cohorts or family history. Suggestions for improving services and clinical education included changing clinical pathways and education, improving resources, and introducing BD early intervention services. Our third theme was identified within multiple studies, suggesting that community and stakeholder psychoeducation could improve diagnosis and reduce stigma. Suggestions for improving research ranged from general suggestions about DD research to targeting specific areas, such as differentiating BD subtypes or BD depression from major depressive disorder and research on diagnostic processes and assessment. Stakeholders in qualitative studies highlighted the potential usefulness of collaborative measures and interpersonal exploration, including team-based assessment with family involvement; symptom tracking; expanded psychoeducation, involvement, and co-management; increased clinical disclosure; collaborative exploration of diagnostic experience and implications to facilitate stakeholder acceptance; qualitative work exploring clinical assumptions surrounding high-functioning presentations. Discussion How our findings build on prior research Our narrative synthesis identified diverse and multifactorial associated precursors, outcomes, and suggested avenues for improving diagnosis, which supports stakeholder recognition of widespread five-to-ten-year averages for DD, associated negative outcomes, and urgent calls for provision of timely BD diagnosis and access to appropriate treatment. 1 , 5 , 10 , 11 , 14 , 31 , 63 , 65 – 70 Consistent with prior systematic reviews, we found long and widespread delays in diagnosing and treating BD, with no evidence of substantive delay reduction despite longstanding recognition of this issue and extensive epidemiological research. Our review was broadly consistent with previous reviews in identifying some widely reported precursors of longer DD, such as history of depressive states, predominance of depressive polarity or BD-II sub-type, earlier age of onset, female sex, and history of suicide attempts (see Table 1 ). This underscores the importance of prioritising improved detection amongst individuals meeting these criteria. However, our use of narrative synthesis and stratification of results into associated precursors, outcomes, and avenues for improvement, together with inclusion of DC and qualitative research, facilitated identification of a broader range of associated factors than previous systematic reviews, which expand upon and sometimes challenging previous findings. View this table: View inline View popup Table 1 Summary of results from previous systematic reviews and meta-analyses Abbreviations: DD = Duration of delay between onset of illness and diagnosis. DUB = Duration of untreated bipolar disorder (delay between onset or seeking professional help and clinical management with appropriate treatment). DC = Rates of diagnostic conversion in sample from major depressive disorder / unipolar depression diagnosis to BD diagnosis. UB = Unrecognised bipolar disorder amongst those with a diagnosis of depression. DHS = Duration of delay between onset of illness and seeking clinical help. DUDB = Duration of delay between onset of illness and clinical management with appropriate treatment or BD diagnosis. View this table: View inline View popup Table 2 Study characteristic Abbreviations: DD = delayed diagnosis. DUB = duration of untreated bipolar disorder. DC = diagnostic conversion. BD = bipolar disorder. MDD = major depressive disorder View this table: View inline View popup Table 3: Themes relating to associated precursors, outcomes, and suggested avenues for improvement. For example, multiple included studies identified higher frequency of hypomanic, mixed, rapid-cycling and atypical depressive presentations as associated precursors. One illustrative example is Abhari et al. 2013, which found that broader diagnostic frameworks incorporating mixed and anti-depressant-induced manic/hypomanic features increased BD diagnosis amongst participants with depression from 18.21% to 53.9%. 71 It seems that an over-reliance on classic binary diagnostic distinctions between manic and depressive states, with insufficient attention to prevalent but often neglected mixed, hypomanic, or rapidly shifting presentations may be exacerbating diagnostic delays. 15 , 72 With the exception of one short qualitative synthesis identifying ‘subthreshold manic symptoms’ as a precursor to delayed diagnosis, 18 previous research synthesis is dominated by these classificatory polarities. The need to expand our understanding of depressive, mixed, hypomanic, and rapid-cycling mood states is also supported by extensive research showing limitations in current understanding and consensus on classification and treatment of bipolar depressive states, despite well-documented prevalence and poor outcomes. 73 – 76 1 , 6 , 14 , 16 , 70 , 72 , 77 – 89 Our mixed findings about association of diagnostic delays with substance abuse and family history were consistent with systematic reviews by Scott at al. 2022 and Keramatian et al. 2025, but diverged from Ratheesh et al. 2017. However, we also identified multiple conditions associated with increased diagnostic delays which were not highlighted in previous reviews. These included intellectual disabilities, PTSD, personality disorders, and general health conditions. Our finding that delays were generally shorter in BD with a history of psychotic features is consistent with the identification of psychosis as associated with shorter DD in previous reviews. Nevertheless, we also found that psychotic features, particularly associated with hypomanic/manic presentations, can lead to an initial psychotic disorder diagnosis and, thereby, to diagnostic delay, even if eventual delays may average shorter duration than without psychotic features. We identified themes and subthemes relating to clinical pathways and care, together with socio-economic, environmental, and demographic factors which augment and sometimes challenge findings from previous systematic reviews. Our review was consistent with previous reviews in identifying potential association between female-sex and increased delays, 17 , 90 – 93 although one included study found that early onset and delayed DC association was stronger for males than females. 94 Unlike Scott et al. 2022, our exclusion of studies with a paediatric majority or non-BD-specific focus meant that we did not identify the association of diagnostic delays with history of involuntary detention or childhood neglect, 8 and our findings for associations with prior hospitalisation were also mixed. Other themes not identified in previous reviews included mixed and complex associations with socio-economic status. While we found that lower socio-economic status was generally associated with increased delay duration, we also found some evidence of higher social functioning in BD-I presentations being associated with increased delays, while we identified similar complexities relating to social isolation. The inclusion of qualitative studies added numerous insights, including associations between diagnostic delay and poor psychoeducation and stigma, or concerns relating to BD and diagnosis, as documented in other qualitative literature on BD. 95 – 99 Qualitative evidence presented complex pictures of stakeholder reluctance to diagnose and accept BD, which did not necessarily correlate with treatment acceptance, as well as clinical reluctance to diagnose BD in service users with high-functioning presentations. 37 , 60 In general, our review provided evidence to corroborate many suggestions made in Scott and Leboyer’s 2011 narrative review of the consequences of diagnostic delay, including increased use of anti-depressant monotherapy, suicide attempts, hospitalisations, illness episodes, poorer socio-economic outcomes and quality of life, and higher costs of care. 17 However, we identified many additional associated outcomes, including poorer physical health outcomes, longer delays in accessing appropriate treatment even post-diagnosis, longer episode duration, poorer risk assessment and self-management. Interestingly, qualitative studies also included findings relating to the effect of diagnostic delays on service users, including reduced faith in healthcare systems and feeling insufficiently informed, which might well affect outcomes. Suggestions and challenges for future research and clinical practice The most widely suggested avenue for improvement was, understandably, routine screening for BD amongst service users treated for varied presentations of depression or suicidality. However, the need for breadth in future approaches was also evidenced by wide-ranging suggestions about the need for improved clinical care, including clinical education, provision of early intervention services, continuity of care and community psychoeducation. Qualitative studies highlighted collaborative elements of the diagnostic process, including working with service users and their families on team-based assessment, mood tracking, community psychoeducation, diagnostic disclosure and information, and exploring the experience and implications of diagnosis in order to improve BD diagnosis acceptance and reduce stigma. The most common suggestion relating to research was increased research on diagnostic delays and, once again, the breadth of suggestions was notable, including more research on comorbidities, socio-environmental and cultural associations, improved tools and markers for BD assessment and diagnosis, including specific BD-subtypes and symptoms. Qualitative studies again highlighted the collaborative and interpersonal elements of the clinical process, suggesting, for example, further qualitative research exploring weakness in clinical risk assessment, managing suicidality, and identification of BD amongst high-functioning presentations. The urgent need for increased and improved interventions and research relating to DD seems undeniable, with many useful suggestions identified. Before presenting some recommendations for improving the diagnostic process, we must emphasise the need for caution and recognition of related complexities and uncertainties. For example, the current over-reliance on classic binary classificatory distinctions between mania and depression does not reflect the complex range of bipolar presentations and thereby presents potential limitations to implementation of successful BD screening. In general, we lack both consensus about classification and assessment of BD and subtypes, and reliable biomarkers. 15 , 100 – 102 For example, some question the phenomenological validity of the BD-II classification and favour dimensional models, 103 while recent research suggests distinct ‘genetic architectures’ differentiating BD-I and BD-II. 104 Recent developments in genetic, neuroscientific, epidemiological, computational, and multidisciplinary research on differentiating BD from major depression may be useful, 15 , 105 – 112 although applicability remains limited by uncertainties relating to both environmental factors and biomarkers, and considerable overlap of potential predictors with other severe mental illness. 113 Similar challenges face early BD intervention, a common suggestion in included studies and wider research, which seems particularly important given the association of early age of onset and diagnostic delays. 5 , 6 , 16 , 18 , 114 – 116 However, the heterogeneity and absence of distinct patterns in prodromal BD increases the difficulties of identifying and differentiating early-onset BD from other mood fluctuations associated with adolescence and early adulthood. 117 Early BD presentation often resembles unipolar depression with mixed, fluctuating, or less extreme affective presentations. 1 , 118 – 120 16 , 100 Moreover, while earlier detection could potentially reduce prescription of antidepressant monotherapy, the common depressive presentation of early BD may actually mean that anti-depressant induced polarity switches often constitute the first detectable BD symptom. Potential applicability of evidence-based interventions for early intervention in psychosis 8 , 121 – 123 may also be limited by factors including the more episodic and heterogenous presentation of BD. 124 We must be cautious about inferring causation from association with particular precursors and framing outcomes as straightforward consequences of DD itself. 16 , 17 Our stratification of findings into associated precursors and outcomes indicates complex interrelationships and suggests that earlier diagnosis alone may be insufficient to improve outcomes significantly. 7 For example, while mixed, suicidal, atypical depressive and BD-II presentations were all identified as associated precursors, response rates to available treatment options and general outcomes for these presentations, even when recognised, remain comparatively poor. 6 , 125 Additionally, increased incidence of suicide attempts persists even post-diagnosis in those experiencing longer diagnostic delays. Future research should avoid over-simplification or exaggeration of the standalone benefits of diagnosis. While accurate diagnosis may facilitate timely access to appropriate treatment, reduced antidepressant monotherapy, psychoeducation, guidance for self-management, and other tailored interventions, multiple challenges persist. These include limited understanding of non-classically manic presentations, inadequate resources, education, and suboptimal treatment options for BD management for many individuals and presentations, with high side effect burden and treatment resistance. Conventional clinical guidelines for preventative maintenance treatment with mood-stabilisers have been questioned, due to weak evidence for effectiveness and user desirability. 126 Furthermore, qualitative studies included here highlight reasons for negative views of diagnosis, including stigma, rejection by loved ones, 60 poor BD outcomes, perceiving diagnosis as indeterminate and unscientific, 60 , 127 lack of specialist care and insufficient information post-diagnosis. 37 , 61 Finally, estimated delay duration may have limitations concerning reliability and significance. BD diagnosis is not always feasible based on early symptoms, 7 , 16 and calculations of diagnostic delay may overlook potentially large numbers of suicide deaths prior to diagnosis, despite associations between suicide attempts and diagnostic delay, general high incidence of suicide attempts in early BD and lethality of BD suicide attempts. 6 , 128 Regarding research on “duration of untreated bipolar” (DUB), caution is needed in defining appropriate BD treatments and examining the interrelationship of treatment and diagnosis, given diverse BD presentations, treatment options, and high treatment resistance. While DUB figures are generally based on prescription of mood stabilisers and antipsychotics, the management of bipolar symptoms, regardless of correct diagnosis, may involve a wider range of interventions. These include ECT, 129 benzodiazepines, 130 while less severe symptoms may respond to self-management, or psychosocial interventions. Study limitations Our study has several limitations. Key findings are contingent on variables selected in included studies and important issues may therefore have been overlooked. Heterogeneity and potential bias are increased through including small qualitative studies, with limited broad representativeness, while suggested improvements we identified, though interesting, remain subjective. As all studies were conducted in high or middle-income countries, findings may not generalise to low or lower-middle income countries, where stigma surrounding severe mental illness and limited specialist healthcare may have distinct effects on diagnosis. Finally, given our broad inclusion criteria, despite rigorous methods, certain article inclusion or exclusion may be questioned and English-language inclusion restrictions may exclude relevant research. However, our use of narrative synthesis, rather than meta-analysis, and relatively consistent findings suggest that these limitations are unlikely substantially to impact key conclusions. Conclusion While prior reviews have suggested that refining DD-related measures to overcome methodological heterogeneity is a priority for future research, 7 , 8 , 16 , 18 , 19 our findings suggest that achieving swifter BD diagnosis and more targeted and effective management requires new approaches with increased breadth, granularity, and complexity. Most importantly perhaps, the range and diversity of precursors, outcomes, and suggested interventions identified here demonstrate the breadth, complexity, and interrelationship of BD diagnosis with other phenomena pertaining to BD where our current limitations in understanding, clinical consensus, and appropriate management are most profound. This suggests that improving BD diagnosis depends upon departing from models of examining diagnostic delay in isolation from these broader BD challenges. It also highlights the substantial limitations surrounding the current classification, understanding, and management of BD, compared to other health conditions. Despite all our caveats and limitations, the need to improve BD diagnosis seems incontrovertible, with several key areas identified for future work. These include the need to increase understanding of: mixed, hypomanic, ‘atypical’, and rapid cycling presentations; the interrelationship of suicidality and diagnosis, given persistence of suicide risk following diagnosis; complex interrelationships between BD and diverse mental and physical health conditions; 131 – 133 diagnostic processes in lower-and-middle income countries; influence of clinical, socio-economic, cultural, and demographic factors; stakeholder perspectives, including building trust in healthcare systems following diagnostic delays. 16 Importantly, the identification of many distinct themes in qualitative research, particularly relating to collaborative components of diagnostic processes, highlights the need for further qualitative, mixed-methods, and co-produced research. Finally, if we are to progress beyond the current impasse in BD diagnosis towards swifter and more targeted identification and management, it seems critical that the design of future related research and interventions must reflect the complexity of the diagnostic process and its interrelationship with multiple broader challenges associated with the management of this condition. Supplementary material The supplementary material for this article can be found at: Author contributions TG, MA, ST, and TW contributed to the conception and design of this project. TG and MA devised and refined the review and led, both jointly and independently, on all areas of searches, analysis, and data extraction. TW and ST assisted in reviewing the study at all stages, and HA assisted in reviewing initial screening and analysis. Financial support This research was part-funded by a donation from the Macdonald Buchanan Charitable Trust to Bipolar UK. 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Share The complexity of delayed diagnosis in bipolar disorder. a systematic review of associated precursors, outcomes, and suggested avenues for improvement Gergel Tania , Al-Janabi Mariam , Talwar Shivangi , Ahmed Haleemah , Wright Talen medRxiv 2025.10.13.25337871; doi: https://doi.org/10.1101/2025.10.13.25337871 Share This Article: Copy Citation Tools The complexity of delayed diagnosis in bipolar disorder. a systematic review of associated precursors, outcomes, and suggested avenues for improvement Gergel Tania , Al-Janabi Mariam , Talwar Shivangi , Ahmed Haleemah , Wright Talen medRxiv 2025.10.13.25337871; doi: https://doi.org/10.1101/2025.10.13.25337871 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Psychiatry and Clinical Psychology Subject Areas All Articles Addiction Medicine (568) Allergy and Immunology (863) Anesthesia (299) Cardiovascular Medicine (4425) Dentistry and Oral Medicine (443) Dermatology (382) Emergency Medicine (607) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1507) Epidemiology (15221) Forensic Medicine (30) Gastroenterology (1123) Genetic and Genomic Medicine (6588) Geriatric Medicine (667) Health Economics (997) Health Informatics (4524) Health Policy (1368) Health Systems and Quality Improvement (1612) Hematology (540) HIV/AIDS (1264) Infectious Diseases (except HIV/AIDS) (15910) Intensive Care and Critical Care Medicine (1103) Medical Education (623) Medical Ethics (145) Nephrology (667) Neurology (6588) Nursing (346) Nutrition (998) Obstetrics and Gynecology (1143) Occupational and Environmental Health (956) Oncology (3331) Ophthalmology (970) Orthopedics (369) Otolaryngology (420) Pain Medicine (435) Palliative Medicine (129) Pathology (663) Pediatrics (1690) Pharmacology and Therapeutics (691) Primary Care Research (710) Psychiatry and Clinical Psychology (5440) Public and Global Health (9219) Radiology and Imaging (2195) Rehabilitation Medicine and Physical Therapy (1369) Respiratory Medicine (1196) Rheumatology (593) Sexual and Reproductive Health (710) Sports Medicine (529) Surgery (710) Toxicology (99) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'9ffabc7b4da4aa64',t:'MTc3OTQ0MTUzNQ=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();