Prazosin has been an accepted treatment for patients with post-traumatic stress disorder (PTSD) who experience sleep disturbances, including nightmares. Results of a recent large randomized control trial did not find benefit of prazosin vs placebo in improving such outcomes. A meta-analysis that includes this most recent trial was conducted to examine the pooled effect of prazosin vs placebo on sleep disturbances and overall PTSD symptoms in patients with PTSD.

A systematic review of the published literature on trials comparing prazosin vs placebo for improvement of overall PTSD scores, nightmares, and sleep quality was conducted. Hedges’ g standardized mean differences (SMD) between prazosin and placebo were calculated for each outcome across studies.

Six randomized placebo-controlled studies representing 429 patients were included in the analysis, including two studies with a crossover design. Results showed prazosin significantly improved overall PTSD scores (SMD = −0.31; 95% confidence intervals [CI]: −0.62, −0.01), nightmares (SMD = −0.75; 95% CI: −1.24, −0.27), and sleep quality (SMD = −0.57; 95% CI: −1.02, −0.13). In the largest trial, prazosin showed a reduction in clinical outcome measures similar to past studies, but a relatively large placebo effect size, particularly for nightmares, contributed to no treatment differences.

Despite the results of a recent, large randomized study, pooled effect estimates show that prazosin has a statistically significant benefit on PTSD symptoms and sleep disturbances. Limitations that should be considered include heterogeneity of study design and study populations as well as the small number of studies conducted and included in this meta-analysis.

Individuals with tardive dyskinesia (TD) who completed a long-term study (KINECT 3 or KINECT 4) of valbenazine (40 or 80 mg/day, once-daily for up to 48 weeks followed by 4-week washout) were enrolled in a subsequent study (NCT02736955) that was primarily designed to further evaluate the long-term safety of valbenazine.

Participants were initiated at 40 mg/day (following prior valbenazine washout). At week 4, dosing was escalated to 80 mg/day based on tolerability and clinical assessment of TD; reduction to 40 mg/day was allowed for tolerability. The study was planned for 72 weeks or until termination due to commercial availability of valbenazine. Assessments included the Clinical Global Impression of Severity-TD (CGIS-TD), Patient Satisfaction Questionnaire (PSQ), and treatment-emergent adverse events (TEAEs).

At study termination, 85.7% (138/161) of participants were still active. Four participants had reached week 60, and none reached week 72. The percentage of participants with a CGIS-TD score ≤2 (normal/not ill or borderline ill) increased from study baseline (14.5% [23/159]) to week 48 (64.3% [36/56]). At baseline, 98.8% (158/160) of participants rated their prior valbenazine experience with a PSQ score ≤2 (very satisfied or somewhat satisfied). At week 48, 98.2% (55/56) remained satisfied. Before week 4 (dose escalation), 9.4% of participants had ≥1 TEAE. After week 4, the TEAE incidence was 49.0%. No TEAE occurred in ≥5% of participants during treatment (before or after week 4).

Valbenazine was well-tolerated and persistent improvements in TD were found in adults who received once-daily treatment for >1 year.

Obsessive-compulsive disorder (OCD) and tic disorder (TD) represent highly disabling, chronic and often comorbid psychiatric conditions. While recent studies showed a high risk of suicide for patients with OCD, little is known about those patients with comorbid TD (OCTD). Aim of this study was to characterize suicidal behaviors among patients with OCD and OCTD.

Three hundred and thirteen outpatients with OCD (n = 157) and OCTD (n = 156) were recruited from nine different psychiatric Italian departments and assessed using an ad-hoc developed questionnaire investigating, among other domains, suicide attempt (SA) and ideation (SI). The sample was divided into four subgroups: OCD with SA (OCD-SA), OCD without SA (OCD-noSA), OCTD with SA (OCTD-SA), and OCTD without SA (OCTD-noSA).

No differences between groups were found in terms of SI, while SA rates were significantly higher in patients with OCTD compared to patients with OCD. OCTD-SA group showed a significant male prevalence and higher unemployment rates compared to OCD-SA and OCD-noSA sample. Both OCTD-groups showed an earlier age of psychiatric comorbidity onset (other than TD) compared to the OCD-SA sample. Moreover, patients with OCTD-SA showed higher rates of other psychiatric comorbidities and positive psychiatric family history compared to the OCD-SA group and to the OCD-noSA groups. OCTD-SA and OCD-SA samples showed higher rates of antipsychotics therapies and treatment resistance compared to OCD-noSA groups.

Patients with OCTD vs with OCD showed a significantly higher rate of SA with no differences in SI. In particular, OCTD-SA group showed different unfavorable epidemiological and clinical features which need to be confirmed in future prospective studies.

The antidepressant effect of low-dose ketamine infusion on Taiwanese patients with anxious vs nonanxious treatment-resistant depression (ANX-TRD vs NANX-TRD) has remained unknown.

In total, 71 patients with TRD were randomized to three groups. Each group had participants who received saline infusions mixed with 0 (a normal saline infusion), 0.2, and 0.5 mg/kg of ketamine. Participants were followed up for 2 weeks. Anxious depression was defined as major depressive disorder with a total score of 7 or more on the 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor. Generalized estimating equation models were used to investigate the effects of treatment (ketamine vs placebo) and depression type (ANX-TRD vs NANX-TRD) in the reduction of depressive symptoms during the follow-up period.

Patients with ANX-TRD were less likely to respond to a single low-dose ketamine infusion than those with NANX-TRD. Among patients with NANX-TRD, low-dose ketamine infusion was significantly superior to placebo for reducing depressive symptoms. However, among patients with ANX-TRD, ketamine was not superior to placebo; nonetheless, approximately 30% of the patients responded to ketamine infusion compared to 13% who responded to the placebo.

Low-dose ketamine infusion was effective for Taiwanese patients with NANX-TRD but not so effective for those with ANX-TRD. A higher level of anxiety severity accompanying depression was related to greater depression severity. This may confound and reduce the antidepressant effect of ketamine infusion.

To examine whether negative symptoms, psychosis, hostility, excitation, and mannerism (PHEM symptoms), formal thought disorders (FTD) and psychomotor retardation (PMR) are interrelated phenomena in major neurocognitive psychosis (MNP) or deficit schizophrenia and whether those domains belong to an underlying latent vector reflecting general psychopathology.

In this study, we recruited 120 patients with MNP or deficit schizophrenia and 54 healthy subjects and measured the above-mentioned symptom domains.

In MNP, there were significant associations between negative and PHEM symptoms, FTD and PMR. A single latent trait, which is essentially unidimensional, underlies these key domains of schizophrenia and MNP and additionally shows excellent internal consistency reliability, convergent validity, and predictive relevance. Confirmatory Tedrad Analysis indicates that this latent vector fits a reflective model. The lack of discriminant validity shows that positive (and PHEM or psychotic) and negative symptoms greatly overlap and probably measure the same latent construct. Soft independent modeling of class analogy (SIMCA) shows that MNP (diagnosis based on negative symptoms) is better modeled using PHEM symptoms, FTD, and PMR than negative symptoms.

In stable phase MNP, which is a restricted sample of the schizophrenia population, negative and PHEM symptoms, FTD and PMR belong to one underlying latent vector reflecting overall severity of schizophrenia (OSOS). The bi-dimensional concept of “positive” and “negative” symptoms cannot be validated and, therefore, future research in stable phase schizophrenia should consider that the latent phenomenon OSOS as well as its reflective manifestations are the key factors of schizophrenia phenomenology.

The Leuven Affect and Pleasure Scale (LAPS) was developed as an outcome measure in major depressive disorder (MDD) tha treflects patient treatment expectations. The present report investigates whether the LAPS negative affect, the LAPS positive affect, and the LAPS hedonic tone have added value on top of the Hamilton Depression Rating Scale (HAMD) in explaining generic as well as patient-centered outcomes.

A total of 109 outpatients with Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria for MDD were assessed over 8 weeks of antidepressant treatment. At baseline and after 2, 4, and 8 weeks, the LAPS, HAMD, Snaith–Hamilton Pleasure Scale (SHAPS), Positive and Negative Affect Scale (PANAS), and Sheehan Disability Scale were administered. The Clinical Global Impression of Improvement (CGI-I) and the Patient Global Impression of Improvement (PGI-I) were also administered at endpoint.

Changes in LAPS negative affect, LAPS positive affect, and LAPS hedonic tone explain 14% of the additional variance in CGI-I, 21% in PGI-I, 37% in cognitive functioning, 32% in overall functioning, 31% in “my life is meaningful,” and 45% in “I feel happy.” Compared to standard scales (PANAS and SHAPS), the LAPS negative affect, LAPS positive affect, and LAPS hedonic tone differentiate better between different levels of CGI-I or PGI-I.

The LAPS has added value (on top of the HAMD) in explaining changes in both generic outcomes (CGI-I/PGI-I) and patient-centered dimensions. The LAPS negative and positive affects and the LAPS hedonic tone differentiate CGI-I and PGI-I scores better than corresponding scales supposed to cover the same domains.

Combination olanzapine and samidorphan (OLZ/SAM), in development for schizophrenia and bipolar I disorder, is intended to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. OLZ/SAM safety, tolerability, and efficacy from a 52-week open-label extension study in patients with schizophrenia are reported.

Patients previously completing the 4-week, double-blind ENLIGHTEN-1 study switched from OLZ/SAM, olanzapine, or placebo to OLZ/SAM. Assessments included adverse events (AEs), weight, vital signs, Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression-Severity (CGI-S) scores. Baseline was prior to first dose of OLZ/SAM in the extension study.

In total, 281 patients enrolled, 277 received ≥1 OLZ/SAM dose, and 183 (66.1%) completed 52 weeks. Reasons for discontinuation included patient withdrawal (15.5%), loss to follow-up (6.9%), AEs (5.8%), and lack of efficacy (1.8%). AEs were reported in 136 (49.1%) patients; increased weight (13%) and somnolence (8%) were most common. Ten serious AEs were reported in eight patients (2.9%); none were considered treatment related. There were no deaths. Mean (SD) baseline weight was 79.1 (17.8) kg. Mean weight change from baseline to week 52 was 1.86 kg (2.79% increase). PANSS total and CGI-S scores continued to decline over 52 weeks (mean [95% CI] changes from baseline to week 52: −16.2 [−18.5, −14.0] and −0.9 [−1.0, −0.8], respectively).

OLZ/SAM was generally well tolerated in this extension study; most patients completed the 52-week treatment period with sustained improvement in schizophrenia symptoms. Mean increases in weight stabilized by week 6 with limited subsequent change through end of treatment.

The Leuven Affect and Pleasure Scale (LAPS) is a depression outcome measure aiming to better reflect patient treatment expectations. We investigated the evolution of the LAPS and some comparator scales during antidepressant treatment and compared scores of remitters with scores of healthy controls.

A total of 109 outpatients with Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) major depressive disorder were assessed over 8 weeks of antidepressant treatment. At baseline and after 2, 4, and 8 weeks, the LAPS as well as the Hamilton Depression Rating Scale (HAMD), the Snaith–Hamilton Pleasure Scale (SHAPS), the Positive and Negative Affect Scale (PANAS), and the Sheehan Disability Scale (SDS) were administered. Healthy controls consisted of 38 Italian adults and 111 Belgian students.

Correlations between baseline positive and negative affect were only moderate (R between −0.20 and −0.41). LAPS positive affect and hedonic tone showed higher correlations with LAPS cognitive functioning, overall functioning, meaningfulness of life, and happiness than HAMD scores or PANAS negative affect. HAMD remission was associated with normal levels of LAPS negative affect but with significantly lower levels of LAPS positive affect, hedonic tone, cognitive functioning, overall functioning, meaningfulness of life, and happiness. The scores on the latter subscales only reached healthy control scores when the HAMD approached a score of 0 or 1.

The standard definition of remission (HAMD cutoff of 7) is probably adequate for remitting negative mood, but not good enough for recovering positive mood, hedonic tone, functioning, or meaningfulness of life.

Brain-derived neurotrophic factor (BDNF) is involved in neurogenesis and in the protection against oxidative damage and neuronal apoptosis. After exercise, there is an increased expression of this myokine, especially in skeletal muscle and brain. Low BDNF levels have been described in neurodegenerative diseases. Alcoholics show both muscle atrophy and brain atrophy. Thus, this study was performed in order to analyze serum BDNF levels among alcoholics and their associations with brain atrophy and muscle strength.

Serum BDNF values were determined to 82 male alcoholics and 27 age-matched controls, and compared with handgrip strength, with the presence of brain atrophy, assessed by computed tomography, and with the intensity of alcoholism and liver function derangement.

BDNF levels and handgrip strength were significantly lower among patients. Handgrip strength was correlated with BDNF values, both in the whole population and in alcoholics, especially in patients over 59 years of age. BDNF was poorly related to liver dysfunction but showed no relationship with brain atrophy or age.

Chronic alcoholics show decreased BDNF serum levels that are related to muscle function impairment rather than to age, brain atrophy, liver dysfunction, or the amount of ethanol consumed.

Primary deficit schizophrenia (DS) is characterized by enduring negative symptoms and represents a qualitatively different disease entity with respect to non-deficit schizophrenia (NDS). No studies investigated the association between the enzyme paraoxonase 1 (PON1) and DS and its phenomenology.

In this case-control study, Thai women and men, aged 18 to 65 years, were divided in DS (n = 40) and NDS (n = 40) and were compared to controls (n = 40). PON1 activities against 4-(chloromethyl)phenyl acetate (CMPA) and phenylacetate were determined. Moreover, subjects were genotyped for their PON1 Q192R polymorphism and immunoglobulin A (IgA) levels responses directed to Gram-negative bacteria were measured.

DS is significantly associated with the QQ genotype and the Q allele as compared with NDS and controls. PON1 activities are significantly and inversely associated with negative symptoms, formal thought disorders, psychomotor retardation, excitation and DS. The presence of the Q allele is associated with increased IgA responses to Pseudomonas aeruginosa, Morganella morganii, and Pseudomonas putida as compared with RR carriers.

The PON1 Q allele and lower PON1 activities especially against CMPA are associated with DS, indicating lowered quorum quenching abilities as well as lowered defenses against lipoperoxidation and immune activation. It is suggested that lowered PON1 activity in DS constitutes an impairment in the innate immune system which together with lowered natural IgM may cause lower immune regulation thereby predisposing toward greater neurotoxic effects of immune-inflammatory, oxidative and nitrosative pathways and Gram-negative microbiota.

While both depression and aging have been associated with oxidative stress and impaired immune response, little is known about redox patterns in elderly depressed subjects. This study investigates the relationship between redox/inflammatory patterns and depression in a sample of elderly adults.

The plasma levels of the advanced products of protein oxidation (AOPP), catalase (CAT), ferric reducing antioxidant power (FRAP), glutathione transferase (GST), interleukin 6 (IL-6), superoxide dismutase (SOD), total thiols (TT), and uric acid (UA) were evaluated in 30 patients with mood disorders with a current depressive episode (depressed patients, DP) as well as in 30 healthy controls (HC) aged 65 years and over. Subjects were assessed with the Hamilton Depression Rating Scale (HAM-D), the Hamilton Rating Scale for Anxiety (HAM-A), the Geriatric Depression Rating Scale (GDS), the Scale for Suicide Ideation (SSI), the Reason for Living Inventory (RFL), the Activities of Daily Living (ADL), and the Instrumental Activity of Daily Living (IADL).

DP showed higher levels than HC of AOPP and IL-6, while displaying lower levels of FRAP, TT, and CAT. In the DP group, specific correlations were found among biochemical parameters. SOD, FRAP, UA, and TT levels were also significantly related to psychometric scale scores.

Specific alterations of redox systems are detectable among elderly DP.