Soham Rej

A report on older‐age bipolar disorder from the International Society for Bipolar Disorders Task Force

In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older‐Age Bipolar Disorder (OABD).

The Effects of Lithium on Renal Function in Older Adults—A Systematic Review

Chronic renal failure (CRF) and nephrogenic diabetes insipidus (NDI) are potential consequences of chronic lithium use, while acute renal failure (ARF) has been described in lithium intoxication. We performed a systematic review of all studies pertaining to the effects of lithium on the kidney in older adults. The ARF incidence was 1.5% per person-year and concurrent loop diuretic and angiotensin-converting enzyme inhibitor use with lithium increased the risk. The CRF prevalence estimates varied from 1.2% to 34%, with risk factors including age, previous lithium intoxication, polyuria, previously impaired renal function, and decreased maximal urine osmolality. The prevalence of NDI varied widely from 1.8% to 85%. Risk factors included lithium duration, dose, level, slow-release formulation, and clinical nonresponse. Except for amiloride use in NDI, there is little evidence for treatment of other lithium-induced adverse renal effects. Currently, there is no compelling evidence to suggest that lithium should be avoided in elderly patients for fear of renal side effects.

Neuroimaging and neurocognitive abnormalities associated with bipolar disorder in old age.

Cognitive dysfunction is prevalent in older adults with bipolar disorder (BD). High white matter hyperintensity (WMH) burden, a marker of white matter disease, detected on T2/fluid‐attenuated inversion recovery brain magnetic resonance imaging (MRI) has been consistently reported in BD across all age ranges, including older adults. Yet, whether high WMH burden is related to the excess cognitive impairment present in older adults with BD is unknown. Therefore, we examine whether higher WMH burden is related to worse cognitive function in older adults with BD.

Chronic renal failure in lithium‐using geriatric patients: effects of lithium continuation versus discontinuation—a 60‐month retrospective study

Lithium remains an important treatment in bipolar disorder. Although lithium is often discontinued because of signs of renal failure, it is unclear if this alters the course of renal function in the majority of patients. We hypothesize that in geriatric patients with chronic renal failure (CRF), who have a high burden of medical illness, lithium continuation does not significantly impact renal function (glomerular filtration rate (eGFR)).

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

The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third‐ line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment‐emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second‐ line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence‐based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first‐line treatments for acute mania. First‐line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first‐line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.

Do current national and international guidelines have specific recommendations for older adults with bipolar disorder? A brief report

Older adults with bipolar disorder (OABD) are a growing segment of patients with bipolar disorder (BD) for which specific guidelines are warranted. Although, OABD are frequently excluded from randomized controlled trials due to their age or somatic comorbidity, more treatment data from a variety of sources have become available in recent years. It is expected that at least some of this emerging information on OABD would be incorporated into treatment guidelines available to clinicians around the world.

The McGill Geriatric Lithium-Induced Diabetes Insipidus Clinical Study (McGLIDICS)

Objective: Despite being a common and potentially serious condition, nephrogenic diabetes insipidus (NDI) remains poorly understood in older lithium users. Our main objective was to compare the prevalence of NDI symptoms and decreased urine osmolality ([UOsm] < 300 milli-Osmoles [mOsm/kg]) among geriatric and adult lithium users. We also assessed NDI symptoms, serum sodium (Na+), and urine specific gravity (USG) as possible surrogate measures of decreased UOsm, and ascertained whether potential etiologic factors independently correlated with decreased UOsm. Method: This was a cross-sectional study of 100 consecutive outpatients treated with lithium from 6 tertiary care clinics, of which 45 were geriatric (aged 65 years and older) and 55 adult (aged 18 to 64 years). Patients completed a symptom questionnaire and underwent laboratory tests, including UOsm, serum Na+, and USG. Results: Geriatric and adult lithium users had similar rates of decreased UOsm (12.5%, compared with 17.9%, P = 0.74), but geriatric patients reported less symptoms (P < 0.05). Although UOsm did not correlate with symptoms or current serum Na+, USG of less than 1.010 was suggestive of UOsm of less than 300 mOsm/kg. Age, lithium duration, and serum lithium level were independently associated with UOsm. Conclusions: The prevalence of decreased UOsm is similar in geriatric and adult lithium users, but older patients are less likely to report urinary and thirst symptoms. Although subjective symptoms do not correlate with UOsm, USG may be a cost-efficient clinical surrogate measure for UOsm. We suggest clinicians increase their vigilance for decreased UOsm, especially in lithium users with advanced age, longer duration of lithium exposure, and higher lithium levels. This may potentially prevent lithium intoxication, falls, hypernatremic events, and renal dysfunction.

Renal function in geriatric psychiatry patients compared to non-psychiatric older adults: effects of lithium use and other factors.

Objectives: Chronic renal failure is very common, affecting 30%–40% of community-dwelling elderly. We wished to verify whether geriatric psychiatry patients are at increased risk of renal dysfunction compared to elderly controls, as well as whether lithium exposure and other factors are important predictors of risk.Method: This is a four-year retrospective cohort and nested case-control study at a Canadian tertiary-care hospital using data from March 2007 to March 2011. We compared 82 geriatric psychiatry outpatients and 200 psychotropic-naïve family medicine controls aged ≥65. Our main continuous measure of renal outcome was change in estimated glomerular filtration rate (eGFR). Multivariate analyses were performed to determine potential risk factors for renal dysfunction in geriatric psychiatry patients, including age, hypertension, diabetes mellitus, diuretics, and lithium duration.Results: Clinically important decreases in eGFR (>8 mL/min/1.73 m2) were found in 40.2% of geriatric psychiatry patients compared to 29.5% of controls (p = 0.040). Multivariate analyses found that lithium duration was independently associated with adverse renal outcome in patients with eGFR < 60 mL/min/1.73 m2. In this sub-population, lithium users had clinically important decreases in eGFR when compared to non-lithium users: 10.3 vs. 0.40 mL/min/1.73 m2 (p = 0.017).Conclusion: Geriatric psychiatry patients are at a greater risk for clinically important decreases of renal function than similarly aged controls. Lithium appears to be an important risk factor for renal dysfunction when eGFR is <60 mL/min/1.73 m2. However, in the majority of older adults who have normal kidney function, lithium use appears to be safe.

Decreased Brain-Derived Neurotrophic Factor in Older Adults with Bipolar Disorder.

OBJECTIVES Decreased levels of brain derived neurotrophic factor (BDNF) have been found in adult patients with bipolar disorder (BD) compared with a comparison group, yet there are no data specifically examining this in geriatric patients. The objective of this study was to examine whether euthymic late-life BD patients have lower BDNF levels than healthy comparators. DESIGN Cross-sectional study. SETTING Clinics at the University of Pittsburgh and the Centre for Addiction and Mental Health (Toronto). PARTICIPANTS Older patients with BD (age ≥50 years, N = 118) and similarly aged healthy comparators (N = 76). There were both BD type I (N = 91) and type II (N = 27) patients. MEASUREMENTS Serum BDNF levels were assessed in BD patients and healthy comparators. RESULTS We found lower levels of BDNF in patients with BD than in healthy comparators (9.0 ± 6.2 versus 12.3 ± 8.9 pg/µg, t(192) = -3.01, p = 0.002), which remained even after controlling for age, sex, lithium use, and site (F(1,176) = 4.32, p = 0.039). This decrease was found specifically in patients with BD type I (8.0 ± 5.5 versus 12.3 ± 8.9 pg/µg, t(165) = 3.7, Bonferroni p < 0.001), but not type II (12.0 ± 7.5 versus 12.3 ± 8.9 pg/µg, t(101) = 0.14, Bonferroni p = 1.0). CONCLUSIONS Older patients with BD have lower serum levels of BDNF compared with similarly aged comparators. These effects appear to be specific to patients with BD type I. Future studies are needed to investigate the impact of reduced BDNF levels on cognition, mood, and other aspects of BD throughout the life course.

Asenapine for bipolar disorder

Asenapine (Saphris®) is an atypical antipsychotic drug which has been approved by the US Food and Drug Administration for the treatment of schizophrenia in adults, as well as the treatment of acute manic or mixed episodes of bipolar I in both adult and pediatric populations. Asenapine is a tetracyclic drug with antidopaminergic and antiserotonergic activity with a unique sublingual route of administration. In this review, we examine and summarize the available literature on the safety, efficacy, and tolerability of asenapine in the treatment of bipolar disorder (BD). Data from randomized, double-blind trials comparing asenapine to placebo or olanzapine in the treatment of acute manic or mixed episodes showed asenapine to be an effective monotherapy treatment in clinical settings; asenapine outperformed placebo and showed noninferior performance to olanzapine based on improvement in the Young Mania Rating Scale scores. There are limited data available on the use of asenapine in the treatment of depressive symptoms of BD, or in the maintenance phase of BD. The available data are inconclusive, suggesting the need for more robust data from prospective trials in these clinical domains. The most commonly reported adverse effect associated with use of asenapine is somnolence. However, the somnolence associated with asenapine use did not cause significant rates of discontinuation. While asenapine was associated with weight gain when compared to placebo, it appeared to be modest when compared to other atypical antipsychotics, and its propensity to cause increases in hemoglobin A1c or serum lipid levels appeared to be similarly modest. Asenapine does not appear to cause any clinically significant QTc prolongation. The most commonly reported extra-pyramidal symptom associated with asenapine was akathisia. Overall, asenapine appears to be a relatively well-tolerated atypical antipsychotic, effective in the treatment of acute manic and mixed episodes of BD.