Duration of untreated illness and bipolar disorder: time for a new definition? Results from a cross-sectional study

Giovanna Fico; Gerard Anmella; Marta Gomez-Ramiro; Carlota de Miquel; Diego Hidalgo-Mazzei; Mirko Manchia; Martin Alda; Ana Gonzalez-Pinto; Andre F. Carvalho; Eduard Vieta; Andrea Murru

doi:10.1016/j.jad.2021.07.062

Duration of untreated illness and bipolar disorder: time for a new definition? Results from a cross-sectional study

Giovanna Fico, Gerard Anmella, Marta Gomez-Ramiro, Carlota de Miquel, Diego Hidalgo-Mazzei, Mirko Manchia, Martin Alda, Ana Gonzalez-Pinto, Andre F. Carvalho, Eduard Vieta, Andrea Murru

Medicine

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

Background: We primarily aimed to explore the associations between duration of untreated illness (DUI), treatment response, and functioning in a cohort of patients with bipolar disorder (BD). Methods: 261 participants with BD were recruited. DUI was defined as months from the first affective episode to the start of a mood-stabilizer. The functioning assessment short test (FAST) scores and treatment response scores for lithium, valproate, or lamotrigine according to the Alda Scale Total Score (TS) were compared between patients with short (<24 months) or long DUI. Differences in FAST scores among good (GR; TS≥7), poor (PR; TS=2-6), or non-responders (NR; TS<2) to each mood-stabilizer were analyzed. Linear regression was computed using the FAST global score as the dependent variable. Results: DUI and FAST scores showed no statistically significant correlation. Patients with a longer DUI showed poorer response to lithium (Z=-3.196; p<0.001), but not to valproate or lamotrigine. Response to lithium (β=-1.814; p<0.001), number of hospitalizations (β=0.237; p<0.001), and illness duration (β=0.160; p=0.028) were associated with FAST total scores. GR to lithium was associated with better global functioning compared to PR or NR [H=27.631; p<0.001]. Limitations: The retrospective design could expose our data to a recall bias. Also, only few patients were on valproate or lamotrigine treatment. Conclusions: Poor functioning in BD could be the result of multiple affective relapses, rather than a direct effect of DUI. A timely diagnosis with subsequent effective prophylactic treatment, such as lithium, may prevent poor functional outcomes in real-world patients with BD.

Original language	English
Pages (from-to)	513-520
Number of pages	8
Journal	Journal of Affective Disorders
Volume	294
DOIs	https://doi.org/10.1016/j.jad.2021.07.062
Publication status	Published - Nov 1 2021

Bibliographical note

Funding Information:
EV has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis and Takeda. GF has received CME-related honoraria, or consulting fees from Angelini, Janssen-Cilag and Lundbeck, unrelated to the present work. MM has received honoraria as CME speaker from Angelini. MA has no conflict of interest to declare. AGP has received grants and served as consultant, advisor or CME speaker for the following entities: Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Sanofi-Aventis, Alter, Angelini, Exeltis, Takeda, the Spanish Ministry of Science and Innovation (CIBERSAM), the Ministry of Science (Carlos III Institute), the Basque Government, and the European Framework Program of Research.

Funding Information:
GA's research is supported by a Pons Bartran 2020 grant (PI046549). EV thanks the support of the Spanish Ministry of Science and Innovation (PI15/00283, PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirecci?n General de Evaluaci?n and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357. Thanks the support of the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151). AM has received a grant (PI19/00672) from the Instituto de Salud Carlos III Subdirecci?n General de Evaluaci?n y Fomento de la investigaci?n, Plan Nacional 2019-2022. GA research is supported by a Pons Bartran 2020 grant (N? 249566). Dr Gonz?lez-Pinto is grateful to the University of the Basque Country 321218ELCY IT1232-19, and the Basque Government 2017111104.

Funding Information:
GA's research is supported by a Pons Bartran 2020 grant ( PI046549 ). EV thanks the support of the Spanish Ministry of Science and Innovation ( PI15/00283 , PI18/00805 ) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII - Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III ; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement ( 2017 SGR 1365 ), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357 . Thanks the support of the European Union Horizon 2020 research and innovation program ( EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3 . Treating and managing disease: Grant No 945151 ). AM has received a grant ( PI19/00672 ) from the Instituto de Salud Carlos III Subdirección General de Evaluación y Fomento de la investigación, Plan Nacional 2019-2022. GA research is supported by a Pons Bartran 2020 grant (N° 249566 ). Dr González-Pinto is grateful to the University of the Basque Country 321218ELCY IT1232-19 , and the Basque Government 2017111104 .

Publisher Copyright:
© 2021

ASJC Scopus Subject Areas

Clinical Psychology
Psychiatry and Mental health

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jad.2021.07.062

Cite this

Fico, G., Anmella, G., Gomez-Ramiro, M., de Miquel, C., Hidalgo-Mazzei, D., Manchia, M., Alda, M., Gonzalez-Pinto, A., Carvalho, A. F., Vieta, E., & Murru, A. (2021). Duration of untreated illness and bipolar disorder: time for a new definition? Results from a cross-sectional study. Journal of Affective Disorders, 294, 513-520. https://doi.org/10.1016/j.jad.2021.07.062

@article{6a58848441d443838dca577818b98832,

title = "Duration of untreated illness and bipolar disorder: time for a new definition? Results from a cross-sectional study",

abstract = "Background: We primarily aimed to explore the associations between duration of untreated illness (DUI), treatment response, and functioning in a cohort of patients with bipolar disorder (BD). Methods: 261 participants with BD were recruited. DUI was defined as months from the first affective episode to the start of a mood-stabilizer. The functioning assessment short test (FAST) scores and treatment response scores for lithium, valproate, or lamotrigine according to the Alda Scale Total Score (TS) were compared between patients with short (<24 months) or long DUI. Differences in FAST scores among good (GR; TS≥7), poor (PR; TS=2-6), or non-responders (NR; TS<2) to each mood-stabilizer were analyzed. Linear regression was computed using the FAST global score as the dependent variable. Results: DUI and FAST scores showed no statistically significant correlation. Patients with a longer DUI showed poorer response to lithium (Z=-3.196; p<0.001), but not to valproate or lamotrigine. Response to lithium (β=-1.814; p<0.001), number of hospitalizations (β=0.237; p<0.001), and illness duration (β=0.160; p=0.028) were associated with FAST total scores. GR to lithium was associated with better global functioning compared to PR or NR [H=27.631; p<0.001]. Limitations: The retrospective design could expose our data to a recall bias. Also, only few patients were on valproate or lamotrigine treatment. Conclusions: Poor functioning in BD could be the result of multiple affective relapses, rather than a direct effect of DUI. A timely diagnosis with subsequent effective prophylactic treatment, such as lithium, may prevent poor functional outcomes in real-world patients with BD.",

author = "Giovanna Fico and Gerard Anmella and Marta Gomez-Ramiro and {de Miquel}, Carlota and Diego Hidalgo-Mazzei and Mirko Manchia and Martin Alda and Ana Gonzalez-Pinto and Carvalho, {Andre F.} and Eduard Vieta and Andrea Murru",

note = "Funding Information: EV has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis and Takeda. GF has received CME-related honoraria, or consulting fees from Angelini, Janssen-Cilag and Lundbeck, unrelated to the present work. MM has received honoraria as CME speaker from Angelini. MA has no conflict of interest to declare. AGP has received grants and served as consultant, advisor or CME speaker for the following entities: Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Sanofi-Aventis, Alter, Angelini, Exeltis, Takeda, the Spanish Ministry of Science and Innovation (CIBERSAM), the Ministry of Science (Carlos III Institute), the Basque Government, and the European Framework Program of Research. Funding Information: GA's research is supported by a Pons Bartran 2020 grant (PI046549). EV thanks the support of the Spanish Ministry of Science and Innovation (PI15/00283, PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirecci?n General de Evaluaci?n and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357. Thanks the support of the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151). AM has received a grant (PI19/00672) from the Instituto de Salud Carlos III Subdirecci?n General de Evaluaci?n y Fomento de la investigaci?n, Plan Nacional 2019-2022. GA research is supported by a Pons Bartran 2020 grant (N? 249566). Dr Gonz?lez-Pinto is grateful to the University of the Basque Country 321218ELCY IT1232-19, and the Basque Government 2017111104. Funding Information: GA's research is supported by a Pons Bartran 2020 grant ( PI046549 ). EV thanks the support of the Spanish Ministry of Science and Innovation ( PI15/00283 , PI18/00805 ) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII - Subdirecci{\'o}n General de Evaluaci{\'o}n and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III ; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement ( 2017 SGR 1365 ), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357 . Thanks the support of the European Union Horizon 2020 research and innovation program ( EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3 . Treating and managing disease: Grant No 945151 ). AM has received a grant ( PI19/00672 ) from the Instituto de Salud Carlos III Subdirecci{\'o}n General de Evaluaci{\'o}n y Fomento de la investigaci{\'o}n, Plan Nacional 2019-2022. GA research is supported by a Pons Bartran 2020 grant (N° 249566 ). Dr Gonz{\'a}lez-Pinto is grateful to the University of the Basque Country 321218ELCY IT1232-19 , and the Basque Government 2017111104 . Publisher Copyright: {\textcopyright} 2021",

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doi = "10.1016/j.jad.2021.07.062",

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T1 - Duration of untreated illness and bipolar disorder

T2 - time for a new definition? Results from a cross-sectional study

AU - Fico, Giovanna

AU - Anmella, Gerard

AU - Gomez-Ramiro, Marta

AU - de Miquel, Carlota

AU - Hidalgo-Mazzei, Diego

AU - Manchia, Mirko

AU - Alda, Martin

AU - Gonzalez-Pinto, Ana

AU - Carvalho, Andre F.

AU - Vieta, Eduard

AU - Murru, Andrea

N1 - Funding Information: EV has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis and Takeda. GF has received CME-related honoraria, or consulting fees from Angelini, Janssen-Cilag and Lundbeck, unrelated to the present work. MM has received honoraria as CME speaker from Angelini. MA has no conflict of interest to declare. AGP has received grants and served as consultant, advisor or CME speaker for the following entities: Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Sanofi-Aventis, Alter, Angelini, Exeltis, Takeda, the Spanish Ministry of Science and Innovation (CIBERSAM), the Ministry of Science (Carlos III Institute), the Basque Government, and the European Framework Program of Research. Funding Information: GA's research is supported by a Pons Bartran 2020 grant (PI046549). EV thanks the support of the Spanish Ministry of Science and Innovation (PI15/00283, PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirecci?n General de Evaluaci?n and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2017 SGR 1365), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357. Thanks the support of the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3. Treating and managing disease: Grant No 945151). AM has received a grant (PI19/00672) from the Instituto de Salud Carlos III Subdirecci?n General de Evaluaci?n y Fomento de la investigaci?n, Plan Nacional 2019-2022. GA research is supported by a Pons Bartran 2020 grant (N? 249566). Dr Gonz?lez-Pinto is grateful to the University of the Basque Country 321218ELCY IT1232-19, and the Basque Government 2017111104. Funding Information: GA's research is supported by a Pons Bartran 2020 grant ( PI046549 ). EV thanks the support of the Spanish Ministry of Science and Innovation ( PI15/00283 , PI18/00805 ) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII - Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER); the Instituto de Salud Carlos III ; the CIBER of Mental Health (CIBERSAM); the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement ( 2017 SGR 1365 ), the CERCA Programme, and the Departament de Salut de la Generalitat de Catalunya for the PERIS grant SLT006/17/00357 . Thanks the support of the European Union Horizon 2020 research and innovation program ( EU.3.1.1. Understanding health, wellbeing and disease: Grant No 754907 and EU.3.1.3 . Treating and managing disease: Grant No 945151 ). AM has received a grant ( PI19/00672 ) from the Instituto de Salud Carlos III Subdirección General de Evaluación y Fomento de la investigación, Plan Nacional 2019-2022. GA research is supported by a Pons Bartran 2020 grant (N° 249566 ). Dr González-Pinto is grateful to the University of the Basque Country 321218ELCY IT1232-19 , and the Basque Government 2017111104 . Publisher Copyright: © 2021

PY - 2021/11/1

Y1 - 2021/11/1

N2 - Background: We primarily aimed to explore the associations between duration of untreated illness (DUI), treatment response, and functioning in a cohort of patients with bipolar disorder (BD). Methods: 261 participants with BD were recruited. DUI was defined as months from the first affective episode to the start of a mood-stabilizer. The functioning assessment short test (FAST) scores and treatment response scores for lithium, valproate, or lamotrigine according to the Alda Scale Total Score (TS) were compared between patients with short (<24 months) or long DUI. Differences in FAST scores among good (GR; TS≥7), poor (PR; TS=2-6), or non-responders (NR; TS<2) to each mood-stabilizer were analyzed. Linear regression was computed using the FAST global score as the dependent variable. Results: DUI and FAST scores showed no statistically significant correlation. Patients with a longer DUI showed poorer response to lithium (Z=-3.196; p<0.001), but not to valproate or lamotrigine. Response to lithium (β=-1.814; p<0.001), number of hospitalizations (β=0.237; p<0.001), and illness duration (β=0.160; p=0.028) were associated with FAST total scores. GR to lithium was associated with better global functioning compared to PR or NR [H=27.631; p<0.001]. Limitations: The retrospective design could expose our data to a recall bias. Also, only few patients were on valproate or lamotrigine treatment. Conclusions: Poor functioning in BD could be the result of multiple affective relapses, rather than a direct effect of DUI. A timely diagnosis with subsequent effective prophylactic treatment, such as lithium, may prevent poor functional outcomes in real-world patients with BD.

AB - Background: We primarily aimed to explore the associations between duration of untreated illness (DUI), treatment response, and functioning in a cohort of patients with bipolar disorder (BD). Methods: 261 participants with BD were recruited. DUI was defined as months from the first affective episode to the start of a mood-stabilizer. The functioning assessment short test (FAST) scores and treatment response scores for lithium, valproate, or lamotrigine according to the Alda Scale Total Score (TS) were compared between patients with short (<24 months) or long DUI. Differences in FAST scores among good (GR; TS≥7), poor (PR; TS=2-6), or non-responders (NR; TS<2) to each mood-stabilizer were analyzed. Linear regression was computed using the FAST global score as the dependent variable. Results: DUI and FAST scores showed no statistically significant correlation. Patients with a longer DUI showed poorer response to lithium (Z=-3.196; p<0.001), but not to valproate or lamotrigine. Response to lithium (β=-1.814; p<0.001), number of hospitalizations (β=0.237; p<0.001), and illness duration (β=0.160; p=0.028) were associated with FAST total scores. GR to lithium was associated with better global functioning compared to PR or NR [H=27.631; p<0.001]. Limitations: The retrospective design could expose our data to a recall bias. Also, only few patients were on valproate or lamotrigine treatment. Conclusions: Poor functioning in BD could be the result of multiple affective relapses, rather than a direct effect of DUI. A timely diagnosis with subsequent effective prophylactic treatment, such as lithium, may prevent poor functional outcomes in real-world patients with BD.

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Duration of untreated illness and bipolar disorder: time for a new definition? Results from a cross-sectional study

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

UN SDGs

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