Patients with body integrity identity disorder (BIID) experience a strong desire for amputation from very early on. BIID patients are often dismissed when they share their wish for amputation with surgeons. Consequently, patients resort to self-amputation, including complications and sometimes death. BIID patients are not psychotic and are mentally competent to oversee the consequences of an elective amputation. The authors offer arguments in favor of elective amputation.

Cognitive dysfunction is common in major depressive disorder (MDD) and a critical determinant of health outcome. Anhedonia is a criterion item toward the diagnosis of a major depressive episode (MDE) and a well-characterized domain in MDD. We sought to determine the extent to which variability in self-reported cognitive function correlates with anhedonia.

A post hoc analysis was conducted using data from (N=369) participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)-defined diagnosis of MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. The IMDCP is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Canada, and the Cleveland Clinic, Cleveland, Ohio. Measures of cognitive function, anhedonia, and depression severity were analyzed using linear regression equations.

A total of 369 adults with DSM-IV-TR–defined MDD were included in this analysis. Self-rated cognitive impairment [ie, as measured by the Adult ADHD Self-Report Scale (ASRS)] was significantly correlated with a proxy measure of anhedonia (r=0.131, p=0.012). Moreover, total depression symptom severity, as measured by the total Montgomery–Åsberg Depression Rating Scale (MADRS) score, was also significantly correlated with self-rated measures of cognitive dysfunction (r=0.147, p=0.005). The association between anhedonia and self-rated cognitive dysfunction remained significant after adjusting for illness severity (r=0.162, p=0.007).

These preliminary results provide empirical data for the testable hypothesis that anhedonia and self-reported cognitive function in MDD are correlated yet dissociable domains. The foregoing observation supports the hypothesis of overlapping yet discrete neurobiological substrates for these domains.

Antidepressants are frequently associated with treatment-emergent sexual dysfunction (TESD). Vortioxetine, which was approved for patients with major depressive disorder (MDD), has a receptor profile that suggests limited impact on sexual functioning.

Arizona Sexual Experiences Scale (ASEX) patient-level data were pooled from 7 short-term vortioxetine trials (6 in MDD, 1 in generalized anxiety disorder) and analyzed for incidence of TESD at any post-baseline visit in patients without sexual dysfunction at baseline (defined as ASEX total score ≥19; individual ASEX item score ≥5; or a score ≥4 on any 3 ASEX items). The primary objective was to confirm the non-inferiority of vortioxetine 5–20 mg/day to placebo on the incidence of TESD. Comparisons were based on the common risk difference (95% confidence interval). Additional analyses compared vortioxetine to duloxetine and duloxetine to placebo. A sensitivity analysis, defined as TESD at 2 consecutive post-baseline visits, was conducted.

TESD incidence, relative to placebo, generally increased with vortioxetine dose with vortioxetine 5 mg non-inferior to placebo. Vortioxetine 10, 15, and 20 mg did not meet the non-inferiority criterion, but no dose had a significantly higher risk of developing TESD versus placebo. Changes in ASEX individual item scores supported the similarity of vortioxetine doses to placebo. Significantly higher TESD risk occurred with duloxetine 60 mg/day versus placebo and versus vortioxetine 5 or 10 mg. The sensitivity analysis was generally consistent with the primary analysis. Rates of spontaneously reported sexual adverse events were low.

Vortioxetine was associated with rates of TESD that were not significantly different from placebo in short-term clinical trials.

While extensive literature on the role of the serotonin receptor 1A (5-HT1A-R) in cognition exists, the findings are largely from animal studies. There has been little research conducted into 5-HT1A-R genotypes and cognitive function in humans. This article evaluates the role of 5-HT1A-R genotypes on the profile of cognitive function in patients with major depressive disorder (MDD).

The study sample was 455 MDD patients aged between 18 and 55 years. They had enrolled into a clinical trial and were tested prior to dosing on the baseline study day using the CDR System, an integrated set of 3 attention tests, 2 working memory tests, and 4 episodic memory tests. 5-HT1A-R genotyping for (SNP ID rs6295) had been conducted during the study screening period.

Validated factor scores were derived from the 9 tests. It was found that patients with the C/C genotype for the C(1019)G polymorphism of the 5-HT1A-R were significantly superior in retaining and retrieving information, in both working and episodic memory, than those with either the C/G or the G/G genotypes. No differences were found in measures of attention or in the speed of retrieval of information from memory.

This is, to our knowledge, the first relationship found between objective tests of cognitive function and 5-HT1A-R genotypes in MDD.

A post hoc analysis evaluated the effects of levomilnacipran ER on individual symptoms and symptom domains in adults with major depressive disorder (MDD).

Data were pooled from 5 Phase III trials comprising 2598 patients. Effects on depression symptoms were analyzed based on change from baseline in individual Montgomery–Åsberg Depression Rating Scale (MADRS) item scores. A1dditional evaluations included resolution of individual symptoms (defined as a MADRS item score ≤1 at end of treatment) and concurrent resolution of all 10 MADRS items, all MADRS6 subscale items, and all items included in different symptom clusters (Dysphoria, Retardation, Vegetative Symptoms, Anhedonia).

Significantly greater mean improvements were found on all MADRS items except Reduced Appetite with levomilnacipran ER treatment compared with placebo. Resolution of individual symptoms occurred more frequently with levomilnacipran ER than placebo for each MADRS item (all P<.05), with odds ratios (ORs) ranging from 1.26 to 1.75; resolution of all 10 items was also greater with levomilnacipran ER (OR=1.57; P=.0051). Significant results were found for the MADRS6 subscale (OR=1.73; P<.0001) and each symptom cluster (OR range, 1.39 [Vegetative Symptoms] to 1.84 [Retardation]; all clusters, P<.01).

Adult MDD patients treated with levomilnacipran ER improved across a range of depression symptoms and symptom domains.

To evaluate the safety and effectiveness of lurasidone in the long-term treatment of patients with schizophrenia.

Patients who completed a 6-week, double-blind (DB), placebo-controlled trial continued in a 22-month, open-label (OL) study during which they received once-daily, flexible-doses of lurasidone, 40–120 mg. Change in the Positive and Negative Syndrome Scale (PANSS) was analyzed using both observed case (OC) and last observation carried forward (LOCF) analyses.

Of the 251 patients who entered the OL extension, 51.4% completed 6 months, 36.7% completed 12 months, and 26.7% completed 22 months of OL treatment. Treatment with lurasidone was associated with a mean change from DB baseline, in weight of +0.4 kg at Month 12 (n=99), and +0.8 kg at Month 24 (n=67; OC analyses). Median change from DB baseline to Month 12 and Month 24, respectively, was -1.0 and -9.0 mg/dL for total cholesterol; 0.0 and -1.0 mg/dL for LDL; +1.0 and -11.0 mg/dL for triglycerides; and 0.0 and +0.1/% for HbA1c (OC analyses). The mean PANSS total score was 96.5 at DB baseline and 69.5 at OL baseline. The mean change from DB baseline in the PANSS total score at Month 24 was -43.6 (OC) and -28.4 (LOCF). Thirty-seven patients (14.7%) discontinued due to an adverse event (AE) during OL treatment. Three AEs occurred in ≥10% of patients: schizophrenia (12.4%), akathisia (10.8%), and somnolence (10.8%); and 19.2% reported at least one movement disorder–related AE. Discontinuations due to AEs occurred in 14.8% of patients.

In this 22-month, open-label extension study, treatment with lurasidone was associated with minimal effects on weight, glucose, lipids, and prolactin. Patients demonstrated sustained improvement in the PANSS total score for up to 24 months of lurasidone treatment.

To meta-analytically summarize lamotrigine’s effectiveness and safety in unipolar and bipolar depression.

We conducted systematic PubMed and SCOPUS reviews (last search =10/01/2015) of randomized controlled trials comparing lamotrigine to placebo or other agents with antidepressant activity in unipolar or bipolar depression. We performed a random-effects meta-analysis of depression ratings, response, remission, and adverse effects calculating standardized mean difference (SMD) and risk ratio (RR) ±95% confidence intervals (CIs).

Eighteen studies (n=2152, duration=9.83 weeks) in patients with unipolar depression (studies=4, n=187; monotherapy vs lithium=1, augmentation of antidepressants vs placebo=3) or bipolar depression (studies=14, n=1965; monotherapy vs placebo=5, monotherapy vs lithium or olanzapine+fluoxetine=2, augmentation of antidepressants vs placebo=1, augmentation of mood stabilizers vs placebo=3, augmentation of mood stabilizers vs trancylpromine, citalopram, or inositol=3) were meta-analyzed. Lamotrigine’s efficacy for depressive symptoms did not differ significantly in monotherapy vs augmentation studies (vs. placebo: p=0.98, I2=0%; vs active agents: p=0.48, I2=0%) or in unipolar vs bipolar patients (vs placebo: p=0.60, I2=0%), allowing pooling of each placebo-controlled and active-controlled trials. Lamotrigine outperformed placebo regarding depressive symptoms (studies=11, n=713 vs n=696; SMD=–0.15, 95% CI=–0.27, –0.02, p=0.02, heterogeneity: p=0.24) and response (after removing one extreme outlier; RR=1.42, 95% CI=1.13–1.78; p=0.003, heterogeneity: p=0.08). Conversely, lamotrigine did not differ regarding efficacy on depressive symptoms, response, or remission from lithium, olanzapine+fluoxetine, citalopram, or inositol (studies=6, n=306 vs n=318, p-values=0.85–0.92). Adverse effects and all-cause/specific-cause discontinuation were similar across all comparisons.

Lamotrigine was superior to placebo in improving unipolar and bipolar depressive symptoms, without causing more frequent adverse effects/discontinuations. Lamotrigine did not differ from lithium, olanzapine+fluoxetine, citalopram, or inositol.