Use of adjunctive endoxifen in older adults with mania: A clinical case audit

Since the initial scientific statement on Secondary Prevention of Coronary Heart Disease (CHD) in the Elderly was published in 2002,1 several trends have continued that make an update highly appropriate. First, the graying of the US population and those of other industrialized countries has progressed unabated because more adults are surviving into their senior years. The number of Americans aged ≥75 years was estimated at 18.6 million in 2010, representing ≈6% of the population,2 and it is expected to double by 2050. The population aged ≥85 years is growing the most rapidly, with numbers expected to reach 19.5 million by 2040. In 2008, 67% of the 811 940 cardiovascular deaths in the United States occurred in people aged ≥75 years.3 In parallel to this increase in the older adult demographic, the number of Americans with CHD has increased to an estimated 16.3 million, more than half of whom are >65 years of age.3 Similarly, 7 million have had a stroke, the incidence of which approximately doubles with successive age decades after 45 to 54 years.3 Peripheral artery disease (PAD) affects 8 to 10 million Americans, the majority of whom are >65 years of age. Between 2015 and 2030, annual US costs related to atherosclerotic cardiovascular disease (ASCVD) are projected to increase from $84.8 billion to $202 billion.3 Moreover, given that ASCVD often undermines functional capacity and independence and increases reliance on long-term care, indirect expenses related to ASCVD are also expected to increase. Thus, the need for effective secondary prevention measures in the older adult population with known ASCVD has never been greater. Notably, the 2011 American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) updated guidelines for secondary prevention of CHD broadened …

Acute mania requires hospitalization and prompt control of symptoms. The aim of this study was to compare the efficacy of sodium valproate and olanzapine administered alone or in combination in patients suffering from acute mania. Patients (N = 30) suffering from acute mania were divided into two equal groups. Group 1 patients were treated with sodium valproate 250 mg 3 times a day and Group 2 patients received olanzapine 5 mg twice daily. In both groups sodium valproate or olanzapine was given as add-on therapy at 3 weeks. The primary method of assessment was 50% or more improvement on the Young Mania Rating Scale (YMRS). The serum levels of valproic acid were also measured. Sodium valproate and olanzapine were effective in the treatment of acute mania with all patients demonstrating a 50% or more improvement on the YMRS. Sodium valproate-treated patients receiving olanzapine in the third week had a 15.3% decrease in the YMRS score and patients on olanzapine receiving sodium valproate had a 23.7% decrease. Patients who attained serum valproic acid levels of 100 μg/mL showed improvement on the YMRS. The present study supports combination therapy in the management of acute mania and suggests that serum valproic acid levels of 100 microg/mL are necessary for clinical response.

Although mania is commonly associated with bipolar disorder, it can have many etiologies (1). Thus, “primary mania” results from bipolar disorder, whereas “secondary mania” results from pharmacological, metabolic, or neurologic causes (1, 2). Older adults are at risk for secondary mania because of increased medical comorbidities and neurological changes. In one retrospective study of 50 patients with mania who were older than 65 years, it was the first manic episode for 28% of the patients and 71% had a comorbid neurological disorder (3). The etiology of mania is important because although acute symptomatic treatment of both primary and secondary mania may be similar, appropriate treatment of secondary mania includes addressing the cause (1). We present here two case histories of secondary mania in older adults, discuss their presentations and differential diagnosis in turn, and discuss treatment.

Background Bipolar affective disorder (BPAD) and major depressive disorder (MDD) are two mood disorders whose pathophysiology may involve the purinergic system. Elevated uric acid levels, associated with this system, can impact various behaviors in individuals affected by these conditions. In addition to genetic predisposition, blood uric acid levels can be impacted by various factors, including metabolic syndrome, the consumption of psychoactive medications, and other underlying kidney conditions such as gout. Objective The study aims to investigate the relationship between blood uric acid levels and mental health conditions, specifically BPAD subtypes (manic and depressive) and MDD. The study also examines changes in blood uric acid levels following treatment and evaluates the effectiveness of different treatment approaches in reducing uric acid levels. Methodology To be eligible to participate, individuals must have a confirmed diagnosis of BPAD (manic or depressive type) or MDD, according to the International Classification of Diseases (ICD-10). Blood uric acid levels were measured at both baseline and follow-up assessments. Symptoms were assessed weekly using standardized rating scales (Young Mania Rating Scale (YMRS) and Hamilton Rating Scale for Depression (HAM-D)) until treatment response was achieved, which was defined as a 50% reduction in initial scores on both scales. We used ANOVA to examine the differences among the three patient groups and paired sample t-tests to examine the changes in means before and after treatment conditions. Results A significant positive correlation was found between the severity of illness and serum uric acid levels across all three patient groups: those with BPAD-mania, BPAD-depression, and MDD. Notably, patients with BPAD-mania patients had significantly higher serum uric acid levels (5.2±0.9 mg/dL) compared to those with BPAD-depression (4.8±1.0 mg/dL) and MDD (4.0±1.1 mg/dL). After treatment, all patient groups exhibited a decrease in serum uric acid levels. The reduction in serum uric acid levels was pronounced in all patient groups, with decreases of 3.1±0.8 mg/dL in patients with BPAD-mania, 3.1±0.9 mg/dL in those with BPAD-depression, and 3.5±1.1 mg/dL in those with MDD. The study showed that the reduction in serum uric acid levels was significantly correlated with the severity of illness in patients with BPAD-mania, but not in those with BPAD-depression or MDD. Furthermore, the study found that treatment with lithium carbonate, sodium valproate, or carbamazepine was equally effective in reducing serum uric acid levels, regardless of the mood stabilizer used. Conclusion The study supports that dysfunction in the purine system might play a significant role in the development and progression of BPAD, suggesting that this phenomenon is not solely due to chronicity or medication exposure. This study also introduces a fresh perspective on the underlying biological processes that contribute to the development of BPAD and also sheds light on new treatment regimens targeting uric acid reduction in treating patients with bipolar disorder.

This study was carried out to compare the efficacy of intravenous sodium valproate with intramuscular haloperidol in patients with acute mania. A total of 30 patients meeting DSM-IV criteria for acute manic episodes were enrolled. They were randomly assigned to 2 groups of 15 patients each. Both groups were treated twice daily with haloperidol (10 mg, intramuscular) and sodium valproate (500 mg, intravenous). The patients were assessed on days 1, 5, 9, and 13. Improvement in symptoms was assessed by reduction in the Young Mania Rating Scale (YMRS). Outcome criterions for analysis were latency of response and remission; additional drugs were required for sedation. At the end of the 2-week study period, overall response rate in both the groups was similar (P > .1). In comparison to haloperidol group, patients treated with sodium valproate showed faster response, and on day 5, significant reduction in YMRS score was observed in the group treated with sodium valproate (P < .05). Total amount of lorazepam was less in patients treated with sodium valproate. Extrapyramidal symptom episodes were observed in 60% of patients treated with haloperidol. Sodium valproate in the treatment of acute mania is as efficacious as haloperidol but provides a faster response. It is safer compared to haloperidol.

To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder. In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of > or =1 previous manic or mixed episodes, and > or =20 Young Mania Rating Scale (YMRS) score were randomized to double-blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9-week double-blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study. Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, -5.1 to -8.4). Mean YMRS reductions in lithium-treated groups were significantly greater (p < or = 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo. These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression. Lithium was confirmed as an effective therapy in this population.

A post hoc analysis of pooled data from two quetiapine monotherapy clinical trials was conducted to evaluate the efficacy and tolerability of quetiapine therapy (twice daily, 400-800 mg/day) among bipolar manic adults aged 55 years and older. The primary efficacy endpoint was the change from baseline in Young Mania Rating Scale (YMRS) total score at Day 21. A secondary endpoint was change from baseline in YMRS score at Day 84. A total of 407 patients made up the safety population, consisting of 59 older adults (aged >or=55 years) and 348 younger adults. A total of 403 patients made up the efficacy population, consisting of 59 older adults and 344 younger adults. Efficacy outcomes were analyzed using covariance models (ANCOVA); descriptive statistics are presented for safety outcomes. Both older and younger individuals treated with quetiapine had significant improvement from baseline on YMRS scores compared with placebo-treated patients. The older adult group demonstrated a sustained reduction in YMRS score compared with placebo that was apparent by Day 4 of treatment. For the quetiapine treatment groups, the most common adverse effects (at a frequency >or=10%) were dry mouth, somnolence, postural hypotension, insomnia, weight gain, and dizziness in older adults, and dry mouth, somnolence, and insomnia in younger adults. For the placebo treatment groups, insomnia was the most common adverse event in both older and younger adults. This secondary analysis suggests that quetiapine represents a potentially useful treatment option among older adults with bipolar I mania. Studies with a primary focus of geriatric bipolar mania, and including larger patient numbers, are needed to confirm these findings.

Approach to acute psychosis in older adults.

Background: Acute mania causes many problems for the patient and others. Therefore, it is very important to eliminate the symptoms quickly. Objectives: The present study made the individual comparison of the therapeutic effects of sodium valproate combined with quetiapine or haloperidol as an add-on among patients with bipolar I disorder experiencing an episode of mania or mixed feature admitted to a Psychiatric Center in Tehran. Methods: The present study was a double-blind clinical randomized trial conducted on 36 patients. All patients were investigated by the Young Mania Rating Scale (YMRS). The study lasted six weeks in total (after raising drug dosage to the maximum level). We prescribed sodium valproate 15 mg/kg plus quetiapine 500 mg daily in one group and sodium valproate 15 mg/kg plus haloperidol 10 mg daily in the other group. In addition, an equivalent dosage of quetiapine and haloperidol was prescribed. This study used different data analysis methods such as Paired t test, ANOVA, and chi-square test. Results: The YMRS scores did not show any statistically significant difference between quetiapine and haloperidol receiving groups (P &gt; 0.05). Conclusions: This paper argued that a combination of sodium valproate with either quetiapine or haloperidol could be effective in the management of acute mania or mixed bipolar I disorder to reduce the severity and duration of symptoms, although there was no statistically significant difference between the efficacy of these two pharmacological therapies.

Subclinical manic symptoms predict social cognitive impairment mediated by deficits in executive functioning in older adults with mood disorders

Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: A pilot study

Speechreading and Aging

SUBJECTIVELY AND OBJECTIVELY RATED MIXED AFFECTIVE STATES IN A MIXED-AGE SAMPLE OF ADULTS WITH BIPOLAR DISORDER: ASSOCIATIONS WITH AGE, SUICIDALITY, SYMPTOM SEVERITY, COGNITION AND INFLAMMATION

A systematic review of measures of mania and depression in older people with bipolar disorder.

Electroconvulsive therapy (ECT) is an effective treatment for major affective disorders. The combined use of ECT and anticonvulsant mood stabilizers is a common clinical scenario. There is dearth of systematic studies on the use of this combination with regard to clinical or cognitive outcomes. We aimed to compare clinical improvement and cognitive adverse effects between patients who received only ECT versus those who received ECT and anticonvulsants. We hypothesized that improvement would be fastest in patients who received only ECT. We conducted a randomized controlled trial in which patients prescribed ECT while being treated with anticonvulsants were randomized into 3 groups: full-dose (FD), half-dose (HD), and stop anticonvulsant. A blind rater assessed clinical improvement in patients using rating scales [Young's Mania Rating Scale (YMRS) and Clinical Global Impression] for clinical improvement and cognitive adverse effects (Postgraduate Institute memory scale). Analysis was done using mixed-effects modeling to delineate differences in clinical and cognitive outcomes across the 3 arms of the study over the course of ECT. Of the 54 patients recruited, 36 patients went into treatment allocation arms per the initial randomization plan. The main anticonvulsants prescribed were sodium valproate and carbamazepine. Patients in the 3 groups were comparable on clinical features. The most common diagnosis was bipolar affective disorder-with current episode of mania. Overall, there was no difference across the 3 groups in final clinical outcome scores (YMRS and Clinical Global Impression) when analyzed as intention to treat (ITT) or "as treated." In both analyses, group × time interaction was significant when comparing trend of YMRS scores between the FD anticonvulsant group and the HD group from baseline to last ECT (P = 0.0435 in ITT and P = 0.0055 in as treated). Patients in the FD group improved faster than those in the HD group. There were no differences across the 3 groups with regard to their cognitive adverse effects in the ITT analysis; "as-treated analysis" showed the HD patients to have performed poorly on some domains. Seizure parameters showed no significant difference across the 3 groups. This is a preliminary prospective study examining whether coprescription of anticonvulsants with ECT affected clinical or cognitive outcomes. The most important takeaway point from this study is the significant reduction in YMRS scores when ECT was given with FD anticonvulsant compared with halving the dose (HD) of anticonvulsant. This difference was shown in both ITT and as-treated analysis. There is a need for more prospective studies to examine this clinical question.