Ajay K. Parsaik

Borderline personality disorder (BPD) is an extremely disabling condition that affects almost every dimension of a patient’s life. The S-enantiomer of ketamine (esketamine) was approved by the Food and Drug Administration (FDA) in 2019 in conjunction with an oral antidepressant for the management of treatment-resistant depression (TRD) in adults. Our patient is a 27-year-old female with a long-standing diagnosis of BPD and treatment-resistant major depressive disorder (MDD) who presented to a tertiary care hospital after a baleful suicide attempt. As per treatment guidelines, “esketamine” intranasal spray in conjunction with citalopram 20 mg was started in the outpatient setting at a dose of 56 mg twice weekly for four weeks, followed by 56 mg once weekly, which was further titrated to 84 mg once weekly. Two years into treatment, the patient and her mother report around 70% improvement in her depression and anxiety with around 80% improvement in her behavioral symptoms. Esketamine’s potential action on patients with BPD can be partially explained by its very well-documented effect on the glutamate receptor antagonism. Additionally, patients with stress-induced suicidal ideations (SI), which are seen in borderline patients, are better responsive to ketamine. In conclusion, we recommend a trial of intranasal esketamine in patients with BPD with treatment-resistant MDD and frequent episodes of self-harm. Treatment with esketamine could potentially reduce the number of emergency room visits for impulsive suicide attempts and help reduce the life burden of BPD and its impact on family members.

Factitious disorder is a form of feigned illness in which the patient provides false information and behaves deceptively but has no other incentive for the behavior other than to be a patient and experience the sick role. Read the case of a patient with hypertensive crisis who underwent extensive workup before receiving a diagnosis of factitious disorder.

Background: The prevalence of childhood trauma and its impact on clinical outcomes in hospitalized patients with mood disorders is unknown. We studied the frequency of childhood trauma among inpatient adults with mood disorders and its association with clinical outcomes. Methods: Patients admitted to our hospital with a primary diagnosis of mood disorders completed the short form of the Early Trauma Inventory–Self-Report (ETISR-SF), the Sheehan Disability Scale, and the Clinician-Rated Dimensions of Psychosis Symptom Severity scale. A regression model adjusted for multiple comparisons was used to examine the association between scores on the ETISR-SF and clinical outcomes. Results: Subjects were 167 patients, all of whom reported ≥1 types of childhood trauma: 90% general trauma, 75% physical abuse, 71% emotional abuse, 50% sexual abuse, and 35% all 4 types of abuse. The subtypes of abuse did not differ by sex or race. Diagnoses in the sample were bipolar disorder 56%, major depressive disorder 24%, schizoaffective disorder 14%, and substance-induced mood disorder 5%. The mean age in the sample was 35±11.5 years, 53% were male, and 64% also had substance abuse disorders. Higher scores on the ETISR-SF were associated with longer hospital stays [odds ratio (OR)=1.13; 95% confidence interval (CI), 1.05-1.22], and greater disruption of work/school life (OR=1.12; 95% CI, 1.04-1.21). There was also a trend for higher ETISR-SF scores to be associated with more severe psychotic symptoms (OR=1.13; 95% CI, 1.01-1.27) and more disruption in social (OR=1.14; 95% CI, 1.06-1.22) and family life (OR=1.09; 95% CI, 1.02-1.17). Conclusion: Childhood trauma was reported by all of the 167 patients, with general trauma the most common and approximately half reporting sexual abuse. Childhood trauma was associated with poor clinical outcomes. Early recognition of trauma and trauma-related therapeutic interventions may improve outcomes.

Background: Use of hypnotics or anxiolytic drugs is common and various studies have reported increased mortality with hypnotics or anxiolytic use. Objective: To consolidate the evidence on mortality risk associated with hypnotics or anxiolytic use Methods: Major databases were searched through April 2014 for studies reporting mortality risk associated with hypnotics or anxiolytics use. A pooled hazard ratio with 95% confidence interval was estimated using random-effects model. Results: After screening 2188 articles, 25 studies (24 cohort, 1 case-control) enrolling 2,350,093 patients with 59% females (age 18–102 years) were included in the meta-analysis. Hypnotics or anxiolytic users had 43% higher risk of mortality than non-users (hazard ratio, 1.43; 95% confidence interval, [1.12, 1.84]). Eight studies reported risk estimates for each gender category and pooled results from these studies showed increased risk of mortality among men (hazard ratio = 1.60, 95% confidence interval = [1.29,1.99]) and women (hazard ratio = 1.68, 95% confidence interval = [1.38, 2.04]). Pooled results from 10 studies showed higher mortality among benzodiazepine users compared to non-users (hazard ratio = 1.60, 95% confidence interval = [1.03, 2.49]), while pooled results from five studies showed an increased risk of mortality with Z-drugs use although the effect could not reach statistical significance (hazard ratio = 1.73, 95% confidence interval = [0.95, 3.16]). Significant heterogeneity was observed in the analyses and the quality of included studies was good. Conclusion: This meta-analysis suggests that hypnotics or anxiolytics drugs use is associated with increased mortality and hence should be used with caution. Future studies focused on underlying mechanism of increased mortality with hypnotics or anxiolytics use are required.

Growing evidence has linked the alteration in the endocrine system, in particular thyroid dysfunction, to the pathogenesis of Alzheimer disease (AD) and other dementias.¹ Therefore, measurement of serum thyroid-stimulating hormone (TSH) has become the standard screening test during the evaluation of patients with cognitive decline.² Subclinical hypothyroidism, which is defined biochemically as a normal serum free thyroxine concentration in the presence of an elevated TSH concentration, has a controversial association with cognitive impairment. Although many investigators have reported positive associations between memory impairment and subclinical hypothyroidism,^3-7 others have reported better performance in some areas of cognitive function among patients with decreased thyroid function⁸ or no association.^9-15

To perform a systematic review and meta-analysis of clinical trials evaluating the efficacy and safety of midodrine in orthostatic hypotension (OH). We searched major databases and related conference proceedings through June 30, 2012. Two reviewers independently selected studies and extracted data. Random-effects meta-analysis was used to pool the outcome measures across studies. Seven trials were included in the efficacy analysis (enrolling 325 patients, mean age 53 years) and two additional trials were included in the safety analysis. Compared to placebo, the mean change in systolic blood pressure was 4.9 mmHg (p = 0.65) and the mean change in mean arterial pressure from supine to standing was −1.7 mmHg (p = 0.45). The change in standing systolic blood pressure before and after giving midodrine was 21.5 mmHg (p < 0.001). A significant improvement was seen in patients’ and investigators’ global assessment symptoms scale (a mean difference of 0.70 [95 % CI 0.30–1.09; p < 0.001] and 0.80 [95 % CI 0.76–0.85; p < 0.001], respectively). There was a significant increase in risk of piloerection, scalp pruritis, urinary hesitancy/retention, supine hypertension and scalp paresthesia after giving midodrine. The quality of evidence was limited by imprecision, heterogeneity and increased risk of bias. There is insufficient and low quality evidence to support the use of midodrine for OH.

The donepezil-memantine combination is a US Food and Drug Administration (FDA)–approved medication to treat Alzheimer’s disease (AD). Galantamine is superior to donepezil because it is a positive allosteric modulator of the alpha-7 nicotinic acetylcholine receptor (α7nAChR). Although galantamine and memantine are both FDA approved for the treatment of AD, the combination is still underutilized in clinical practice. The objective of this review was to critically examine the mechanisms by which the galantamine-memantine combination may be superior to the donepezil-memantine combination in AD by targeting the cholinergic-nicotinic and glutamatergic systems concurrently. PubMed and Google Scholar were searched using the keywords Alzheimer’s disease, cholinergic, glutamatergic, α7nAChR, N-methyl-D-aspartate (NMDA) receptors, donepezil, galantamine, memantine, clinical trials, and biomarkers. AD is associated with several biomarkers such as kynurenine pathway (KP) metabolites, mismatch negativity (MMN), brain-derived neurotrophic factor (BDNF), and oxidative stress. In several preclinical studies, cognitive impairments significantly improved with the galantamine-memantine combination compared to either medication alone. Synergistic benefits were also seen with the combination. In a randomized controlled trial (RCT) in prodrome AD, cognition significantly improved with the galantamine-memantine combination compared to galantamine alone; cognition declined after galantamine was discontinued. However, in an RCT in AD, cognition did not significantly improve with the galantamine-memantine combination compared to galantamine alone. In a retrospective study in AD, the galantamine-memantine combination significantly improved cognition compared to the donepezil-memantine combination. Galantamine and memantine via the α7nACh and NMDA receptors can counteract the effects of kynurenic acid and enhance MMN and BDNF. Future studies with the galantamine-memantine combination with KP metabolites, MMN, and BDNF as biomarkers are warranted. Positive RCTs in AD may lead to FDA approval of the combination, resulting in greater utilization in clinical practice. In the meantime, clinicians may continue to use the galantamine-memantine combination to treat patients with AD.