Risk of cancer in bipolar disorder and the potential role of lithium: International collaborative systematic review and meta-analyses

Anmella, Gerard; Fico, Giovanna; Lotfaliany, Mojtaba; Hidalgo‐Mazzei, Diego; Soto-Angona, Óscar; Giménez‐Palomo, Anna; Amoretti, Sílvia; Murru, Andréa; Raduà, Joaquim; Solanes, Aleix; Pacchiarotti, Isabella; Verdolini, Norma; Cowdery, Stephanie; Dodd, Seetal; Williams, Lana J.; Mohebbi, Mohammadreza; Carvalho, André F.; Kessing, Lars Vedel; Vieta, Eduard; Berk, Michael

doi:10.1016/j.neubiorev.2021.03.034

Cited by 33 publications

(25 citation statements)

References 69 publications

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“…Based on its ability to stimulate the enzyme telomerase, lithium protects the length of telomeres, which are reduced in length by stress and depression [21]. This and other diverse mechanisms could account for the data suggesting that lithium could help prevent a variety of medical illnesses including cancer [22].…”

Section: The Case For Lithium Treatment Of Childrenmentioning

confidence: 99%

The Challenges of Children with Bipolar Disorder

Post

Grunze

2021

Medicina

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Childhood onset bipolar disorder (CO-BD) presents a panoply of difficulties associated with early recognition and treatment. CO-BD is associated with a variety of precursors and comorbidities that have been inadequately studied, so treatment remains obscure. The earlier the onset, the longer is the delay to first treatment, and both early onset and treatment delay are associated with more depressive episodes and a poor prognosis in adulthood. Ultra-rapid and ultradian cycling, consistent with a diagnosis of BP-NOS, are highly prevalent in the youngest children and take long periods of time and complex treatment regimens to achieve euthymia. Lithium and atypical antipsychotics are effective in mania, but treatment of depression remains obscure, with the exception of lurasidone, for children ages 10-17. Treatment of the common comorbid anxiety disorders, oppositional defiant disorders, pathological habits, and substance abuse are all poorly studied and are off-label. Cognitive dysfunction after a first manic hospitalization improves over the next year only on the condition that no further episodes occur. Yet comprehensive expert treatment after an initial manic hospitalization results in many fewer relapses than traditional treatment as usual, emphasizing the need for combined pharmacological, psychosocial, and psycho-educational approaches to this difficult and highly recurrent illness.

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Section: The Case For Lithium Treatment Of Childrenmentioning

confidence: 99%

The Challenges of Children with Bipolar Disorder

Post

Grunze

2021

Medicina

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“…[1][2][3][4] Increasing evidence suggests a biological link between severe mental disorder, including schizophrenia and bipolar disorder, and malignant cancers in these decades. [6][7][8][9][10] In early 2000, Lichtermann et al reported that patients with schizophrenia (n = 26 996) had increased overall cancer risk (standardized incidence ratio [SIR] = 1.17, 95% confidence interval [CI]: [1.09, 1.25]) and substantially greater risk of lung cancer (SIR = 2.17, 95% CI [1.78, 2.60]) compared to the general population. 11 BarChana et al demonstrated that patients with bipolar disorder (n = 2121), both men (SIR = 1.59, 95% CI [1.01, 2.17]) and women (SIR = 1.75, 95% CI [1.31, 2.18]), were more likely to develop cancer than were the general population 6 and discovered breast cancer risk to be higher in women with bipolar disorder than in the general female population (SIR = 1.70, 95% CI [0.99, 2.41]).…”

Section: Introductionmentioning

confidence: 99%

“…8 A recent meta-analysis study of 4 910 661 individuals from nine studies estimated an increased risk of all-cause cancer (relative risk [RR] = 1.24, 95% CI [1.05, 1.46]), especially breast cancer (RR = 1.33, 95% CI [1.15, 1.55]), in patients with bipolar disorder. 10 The chronic, systemic, low-grade inflammation and immune dysregulation in schizophrenia and bipolar disorder may be associated with the increased likelihood of cancer. [6][7][8][9]12 However, Kahan et al analyzed the Israel National Cancer Registry database, and demonstrated that patients with bipolar were no more likely than comparisons without bipolar disorder to be diagnosed with cancer during the follow-up period from 2000 to 2012 (SIR = 0.91, 95% CI [0.66, 1.22]).…”

Section: Introductionmentioning

confidence: 99%

Cancer risk in patients with bipolar disorder and unaffected siblings of such patients: A nationwide population‐based study

Chen

Tsai

et al. 2022

Intl Journal of Cancer

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Increasing evidence suggests that patients with bipolar disorder are more likely to develop malignant cancer than in the general population. However, the overall cancer risk in the unaffected siblings of such patients remains unknown. From the National Health Insurance Research Database of Taiwan, 25 356 patients with bipolar disorder, 25 356 agematched unaffected siblings of patients with bipolar disorder and 101 422 age-matched controls without severe mental disorders between 1996 and 2010 were enrolled in our study. Patients who developed cancer between the time of enrollment and the end of 2011 were identified. Cancers were divided into three subgroups based on the related layer of embryonic development: ectodermal, mesodermal and endodermal cancers. Patients with bipolar disorder (odds ratio [OR] = 1.22, 95% confidence interval [CI]: [1.06, 1.40]) and unaffected siblings of such patients (OR = 1.17, 95% CI [1.02, 1.34]) had greater risk of developing malignant cancer than did controls. Furthermore, only those aged <50 years, for both patients with bipolar disorder (OR = 1.90, 95% CI [1.38, 2.61]) and unaffected siblings (OR = 1.65, 95% CI [1.19, 2.28]), were more likely to develop the ectodermal cancer, especially breast cancer, than the control group. The associations of bipolar disorder and susceptibility to bipolar disorder with increased cancer risk in the younger population may imply a genetic overlap in neurodevelopment and malignancy pathogenesis. Our findings may encourage clinicians to monitor cancer risk factors and warning signs closely in patients with bipolar disorder and unaffected siblings of such patients.

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“…Lithium is well recognized as the first‐line maintenance treatment for bipolar disorder (BD) in most treatment guidelines 1–3 . Lithium can effectively reduce the risk of recurrence of mood episodes, 4 prevent suicide, 5 and might have a protective effect on certain types of cancers 6 . Although lithium has been proven to have a meaningful beneficial therapeutic effect, its narrow therapeutic index may limit its prescription despite being an archetypal mood stabilizer 7 .…”

Section: Introductionmentioning

confidence: 99%

“… 1 , 2 , 3 Lithium can effectively reduce the risk of recurrence of mood episodes, 4 prevent suicide, 5 and might have a protective effect on certain types of cancers. 6 Although lithium has been proven to have a meaningful beneficial therapeutic effect, its narrow therapeutic index may limit its prescription despite being an archetypal mood stabilizer. 7 However, there is uncertainty in the literature regarding which lithium serum levels would be more effective for the prevention of major mood episodes during the maintenance treatment of BD.…”

Section: Introductionmentioning

confidence: 99%

Lithium concentration and recurrence risk during maintenance treatment of bipolar disorder: Multicenter cohort and meta‐analysis

Hsu

Carvalho

Tsai

et al. 2021

Acta Psychiatr Scand

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Objective To compare differences in efficacy during maintenance treatment for bipolar disorder (BD) according to lithium serum levels. A multicenter retrospective cohort study and a dose‐response meta‐analysis were conducted. Methods The cohort study was conducted in Taiwan from 2001 to 2019 to identify patients with euthymic BD according to different serum levels (<0.4, 0.4–0.8, and 0.8–1.2 mmol/L). We adopted adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for time to the recurrence of mood episodes having the <0.4 mmol/L group as the reference group. Moreover, we systematically searched for related articles in major databases before January 31, 2021 (PROSPERO: CRD42021235812). We used random‐effects modeling to estimate the dose‐response relationships between lithium serum levels and recurrence of mood episodes, which were depicted as odds ratios (ORs) with 95% CIs. Results A total of 1406 participants (cohort: 466; meta‐analysis: 940) were included. In the cohort study, the 0.4–0.8 mmol/L group was associated with a significantly lower risk of recurrences (aHR: 0.75), while the 0.8–1.2 mmol/L group had a lower risk without statistical significance (aHR: 0.77). The dose‐response meta‐analysis showed that with the increase in lithium serum levels, the risk decreased (linear model OR: 0.85, for every 0.1 mmol/L increase; non‐linear model OR: 1.00 at 0.0 mmol/L, 0.42 at 0.4 mmol/L, and 0.27 at 0.8 mmol/L). Conclusion Although confounding by indication cannot be excluded, the combined results suggest a significant preventative effect on the recurrence of major affective episodes among those with serum levels of 0.4–0.8 mmol/L.

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Risk of cancer in bipolar disorder and the potential role of lithium: International collaborative systematic review and meta-analyses

Cited by 33 publications

References 69 publications

The Challenges of Children with Bipolar Disorder

The Challenges of Children with Bipolar Disorder

Cancer risk in patients with bipolar disorder and unaffected siblings of such patients: A nationwide population‐based study

Lithium concentration and recurrence risk during maintenance treatment of bipolar disorder: Multicenter cohort and meta‐analysis

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