AtWoRC (Assessment in Work productivity and the Relationship with Cognitive symptoms) was an interventional, open-label, Canadian study (NCT02332954) designed to assess the association between cognitive symptoms and workplace productivity in working patients with major depressive disorder (MDD) receiving vortioxetine.

Eligible patients with MDD received vortioxetine (10–20 mg/day) and were assessed over 52 weeks at visits emulating a real-life setting (n = 199). Partial correlation between changes in patient-reported cognitive symptoms (20-item Perceived Deficits Questionnaire–Depression; PDQ-D-20) and workplace productivity (Work Limitations Questionnaire; WLQ) was assessed at 12 and 52 weeks. Additional assessments included depression severity, cognitive performance, and patient-reported functioning. Structural equations model (SEM) analyses assessed causal relationships between changes in measures of cognition and functioning over time, adjusted for improvements in depressive symptoms.

Statistically significant improvements in all outcomes from baseline to week 52 were seen in the overall population and both subgroups (first treatment and switch). Response and remission rates were 77% and 56%, respectively. Improvements in PDQ-D-20 and WLQ productivity loss scores at weeks 12 and 52 were significantly correlated. SEM analyses found patient-rated cognitive symptoms (PDQ-D-20) at weeks 12 and 26 were significantly predictive (p < 0.05) of patient-reported functioning (Sheehan Disability Scale) at the subsequent visit. Depression severity and objectively measured cognitive performance did not significantly predict functional outcomes at any timepoint.

These results demonstrate the long-term benefits of vortioxetine treatment in working patients with MDD and emphasize the strong association between cognitive symptoms and functioning in a real-world setting.

To compare the tolerability and efficacy of different antipsychotic cross-titration schedules, using data from a brexpiprazole study (Equator; NCT01668797).

Patients with schizophrenia were cross-titrated from other antipsychotics to brexpiprazole monotherapy in a 1–4 week open-label conversion phase, then entered a single-blind brexpiprazole treatment phase. Patients were stratified into four “conversion groups,” according to the amount of time spent in the conversion phase. Discontinuation rates, treatment-emergent adverse events (TEAEs), and efficacy (Positive and Negative Syndrome Scale [PANSS]) were compared between conversion groups.

Of the 404 patients treated with brexpiprazole, the majority (72.0%) spent 22–33 days in the conversion phase. Discontinuation rates due to lack of efficacy or adverse events were low in all conversion groups. Of the 292 patients who successfully switched and completed 8 weeks of brexpiprazole treatment, most were converted to brexpiprazole over 22–33 days (80.1%), and fewer were converted over 1–7 days (2.4%), 8–14 days (6.5%), or 15–21 days (11.0%). The incidence of TEAEs over 8 weeks was lower among those converted over 22–33 days (44.4%) than in other conversion groups (62.5–84.2%), although low patient numbers with shorter conversion times limit the generalizability of this finding. Each conversion group showed comparable improvement in PANSS total score from baseline.

The majority of patients were cross-titrated to brexpiprazole over a period of 22–33 days, by investigators’ choice. Additional data on shorter conversions may help clinicians to choose a switching paradigm that best meets their patients’ needs.

Lamotrigine is a commonly used drug in the treatment of bipolar disorder. Although there are reports of its effectiveness in the management of bipolar disorder and comorbid obsessive-compulsive disorder (OCD), lamotrigine has also been associated with obsessionality in patients with bipolar disorder.

Charts of 8 patients with bipolar disorder who had de novo onset of obsessions and compulsions after the use of lamotrigine were reviewed. The Naranjo scale was used to assess the likelihood of patients developing OCD due to lamotrigine use.

Two to 8 months after the initiation of lamotrigine, patients with no such prior history developed obsessions and compulsions meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for medication-induced OCD. In all except 1 patient, the symptoms resolved within a month of lamotrigine discontinuation.

Some patients with bipolar disorder may develop OCD after initiation of lamotrigine. Due to the inherent limitations of a case series, the findings should be interpreted with caution.

Oxidative stress has been documented in chronic schizophrenia and in the first episode of psychosis, but there are very little data on oxidative stress prior to the disease onset.

This work aimed to compare serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in young individuals at ultra-high risk (UHR) of developing psychosis with a comparison healthy control group (HC).

Thirteen UHR subjects and 29 age- and sex-matched healthy controls (HC) were enrolled in this study. Clinical assessment included the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and the Global Assessment of Functioning (GAF) scale. Activities of SOD and GPx were measured in serum by the spectrophotometric method using enzyme-linked immunosorbent assay kits.

After adjusting for age and years of education, there was a significant lower activity of SOD and lower GPX activity in the UHR group compared to the healthy control group (rate ratio [RR]=0.330, 95% CI 0.187; 0.584, p<0.001 and RR=0.509, 95% CI 0.323; 0.803, p=0.004, respectively). There were also positive correlations between GAF functioning scores and GPx and SOD activities.

Our results suggest that oxidative imbalances could be present prior to the onset of full-blown psychosis, including in at-risk stages. Future studies should replicate and expand these results.

Vortioxetine is an approved antidepressant that has also demonstrated positive effects on anxiety symptoms in subjects with generalized anxiety disorder (GAD). This post-hoc analysis evaluates the efficacy of vortioxetine in GAD subjects who are working and/or pursuing an education.

In study NCT00744627, 301 GAD subjects were randomized to vortioxetine 5 mg or placebo for 8 weeks. Efficacy measures included the Hamilton Anxiety Rating Scale (HAM–A) total score, response/remission, global functioning (Sheehan Disability Scale [SDS]), and quality of life (Short Form–36 Health Survey). In study NCT00788034, 687 GAD subjects were treated open-label with vortioxetine 5 or 10 mg for 20 weeks, after which subjects in remission were randomized to fixed-dose of vortioxetine (5 or 10 mg) or placebo for at least 24 weeks. The primary endpoint was time to relapse. Analyses were completed in subjects working and/or pursuing an education at study entry and the full analysis set.

In study NCT00744627, the effect of vortioxetine versus placebo on HAM–A total score was –4.3 (p=0.0005) in working subjects (60% of total), while the effect in the total population was –3.8 (p=0.0001). The effect was greatest in subjects in professional (–4.5, p=0.0130) and associate professional positions (–7.6, p=0.0086). Greater effects in terms of response, remission, and the SDS and SF–36 were also observed. In NCT00788034, working subjects (69% of total) randomized to placebo were significantly more likely to relapse than subjects treated with vortioxetine (hazard ratio=2.9; p<0.001), while the hazard ratio in the total population was 2.7 (p<0.0001).

The beneficial effects of vortioxetine on anxiety symptoms, functioning, and quality of life are greater in adults with GAD who are working and/or pursuing an education versus the full GAD study population.

Some antidepressants, such as trazodone or clomipramine, can be administered intravenously in patients with major depressive disorder (MDD), with potential benefits compared to the standard oral treatment, but available data about their efficacy are limited. The present study was aimed to compare the effectiveness of trazodone and clomipramine (intravenous [i.v.] followed by oral administration).

Some 42 patients with a diagnosis of MDD according to the DSM–5 were selected and treated with i.v. trazodone or clomipramine according to clinical judgment. The Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Montgomery-Åsberg Depression Rating Scale were administered at baseline, after 2 weeks, and after 6 weeks, as well as after 1 week of intravenous antidepressant administration. Raters were blinded to type of treatment.

No significant differences were found between treatment groups in terms of effectiveness at endpoint. Borderline statistical significance was found in terms of number of responders in favor of trazodone. In addition, patients treated with trazodone reported fewer total side effects than those treated with clomipramine.

Both i.v. trazodone and clomipramine are rapid and effective options for improving depressive symptoms, although trazodone appears to be tolerated better. Further studies with larger samples and double-blind conditions are warranted to confirm our results.

Safety and tolerability of long-term treatment with the long-acting antipsychotic aripiprazole lauroxil (AL) were evaluated in patients with schizophrenia.

This was an international, multicenter, phase 3, 52-week safety study of 2 fixed doses of AL (441 mg or 882 mg intramuscular every 4 weeks). Safety endpoints included adverse events (AEs) and extrapyramidal symptoms (EPS) including akathisia, injection-site reactions (ISRs), and clinically relevant changes in metabolic and endocrine values.

Of 478 patients entering this study, 236 (49%) continued from a previous 12-week, phase 3 efficacy study of AL, and 242 (51%) were newly enrolled. Overall, 77% and 23% of patients received AL 882 mg (N = 368) and 441 mg (N = 110), respectively. AEs occurred in 50.4% of patients; most were mild (28.7%) or moderate (18.2%). The most common AEs were insomnia (8.4%) and increased weight (5.0%). Akathisia was reported as an AE in 3.8% of the overall population, with higher rates in patients initiating AL on study entry than those continuing on AL. EPS-related AEs occurred in 9.4% of patients, and AEs related to metabolic parameters were reported in 4.6% of patients. Weight gain was minimal (0.8 kg), and no clinically relevant changes were observed for metabolic parameters. The overall incidence of ISRs was 3.8%; most were associated with the initial injections in patients receiving their first injection in this study.

Long-term treatment with AL is generally well tolerated, with a safety profile consistent with that of oral aripiprazole. It is a suitable option for patients with schizophrenia.

The Assessment in Work Productivity and the Relationship with Cognitive Symptoms (AtWoRC) study aimed to assess the association between cognitive symptoms and work productivity in gainfully employed patients receiving vortioxetine for a major depressive episode (MDE).

Patients diagnosed with major depressive disorder (MDD) and treated with vortioxetine independently of study enrollment were assessed over 52 weeks at visits that emulated a real-life setting. Patients were classified as those receiving vortioxetine as the first treatment for their current MDE (first treatment) or having shown inadequate response to a previous antidepressant (switch). The primary endpoint was the correlation between changes in patient-reported cognitive symptoms (20-item Perceived Deficits Questionnaire [PDQ-D-20]) and changes in work productivity loss (Work Limitations Questionnaire [WLQ]) at week 12. Additional assessments included changes in symptom and disease severity, cognitive performance, functioning, work loss, and safety.

In the week 12 primary analysis, 196 eligible patients at 26 Canadian sites were enrolled, received at least one treatment dose, and attended at least one postbaseline study visit. This analysis demonstrated a significant, strong correlation between PDQ-D-20 and WLQ productivity loss scores (r=0.634; p<0.001), and this correlation was significant in both first treatment and switch patients (p<0.001). A weaker correlation between Digit Symbol Substitution Test and WLQ scores was found (r=−0.244; p=0.003).

At 12 weeks, improvements in cognitive dysfunction were significantly associated with improvements in workplace productivity in patients with MDD, suggesting a role for vortioxetine in functional recovery in MDD.

It is crucial to clarify the structure of attention-deficit/hyperactivity disorder (ADHD) symptomatology in all age groups to determine how to best conceptualize this disorder across the lifespan. We tested the ADHD factor structure across adulthood and investigated independent associations with executive functions.

Data from 645 adults aged 18–59 and 233 adults aged 60–85 were drawn from the Nathan Kline Institute Rockland Sample. Participants completed the Conners Adult ADHD Rating Scale and tests of executive functioning. Invariance of the ADHD factor structure was investigated using confirmatory factor analyses. Associations with cognition were explored using multiple linear regression.

Results confirmed a bifactor model with 3 specific factors (inattention, hyperactivity, and impulsivity). Factor loadings and item intercepts were invariant across ages. Levels of hyperactivity and impulsivity were lower in older adults. Inattentive symptoms in young adults were positively related to cognitive flexibility. In older adults, ADHD symptoms predicted poorer working memory.

ADHD symptoms manifest similarly across adulthood. The lack of robust associations between ADHD symptomatology and executive functions raises concerns about the usefulness of neuropsychological measures in diagnosing adult ADHD. These results support the validity of the ADHD concept in older adults but suggest a need for age-appropriate normative criteria.

In this study, we compared duration of untreated illness (DUI) in obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD) patients and investigated its correlates, both within specific diagnoses and across the whole sample.

Eighty-eight patients (33 OCD, 24 SAD, and 31 PD) had their diagnosis confirmed by the Mini International Neuropsychiatric Interview, were assessed for treatment-seeking variables, and were evaluated with instruments aimed at quantifying transdiagnostic features (i.e., the Cause subscale of the Illness Perception Questionnaire–Mental Health and the Anxiety Sensitivity Index–Revised) and severity of illness (i.e., Beck Depression and Anxiety Inventories, the Dimensional Obsessive-Compulsive Scale, the Panic and Agoraphobia Scale, and the Social Phobia Inventory).

The only differences between groups with short (<2 years) versus long (>2 years) DUI were greater fear of public display of anxiety in the first group and greater social avoidance in the second group. The DUI was significantly different between groups that sought treatment after the onset of illness, with OCD patients having longer DUI than PD patients and shorter DUI than SAD patients. Further, DUI correlated negatively with the perception of OCD being caused by stress and positively with severity of panic-related disability in SAD patients, but not in PD or OCD patients.

There was substantial delay in treatment seeking among the anxiety and obsessive-compulsive disorder patients, particularly those with OCD or SAD. Perception of stress as a cause of OCD prompted treatment seeking, while severity of panic symptoms delayed treatment seeking.

Enhanced odor sensitivity, particularly toward threat-related cues, may be adaptive during periods of danger. Research also suggests that chronic psychological distress may lead to functional changes in the olfactory system that cause heightened sensitivity to odors. Yet, the association between self-reported odor sensitivity, objective odor detection, and affective psychopathology is currently unclear, and research suggests that persons with affective problems may only be sensitive to specific, threat-related odors.

The current study compared adults with self-reported odor sensitivity that was described as functionally impairing (OSI; n = 32) to those who reported odor sensitivity that was non-impairing (OS; n = 17) on affective variables as well as quantitative odor detection.

Increased anxiety sensitivity, trait anxiety, depression, and life stress, even while controlling for comorbid anxiety and depressive disorders, was found for OSI compared to OS. While OSI, compared to OS, demonstrated only a trend increase in objective odor detection of a smoke-like, but not rose-like, odor, further analysis revealed that increased detection of that smoke-like odor was positively correlated with anxiety sensitivity.

These findings suggest that persons with various forms of psychological distress may find themselves significantly impaired by an intolerance of odors, but that self-reported odor sensitivity does not necessarily relate to enhanced odor detection ability. However, increased sensitivity to a smoke-like odor appears to be associated with sensitivity to aversive anxiogenic stimuli. Implications for the pathophysiology of fear- and anxiety-related disorders are discussed.