We investigated the association between clinical outcome and the recommendations of a pharmacogenetic test (Neuropharmagen) in patients with a variety of psychiatric conditions whose previous treatment regimen had failed.

This retrospective, naturalistic, multicenter study included adult psychiatric patients (depression, psychosis, anxiety, bipolar, etc.) who had been seen at 3 private clinics. All patients had received pharmacogenetic testing (Neuropharmagen) and were classified depending on whether or not their post-test treatment regimen followed the test recommendations. Clinical severity was assessed with the Clinical Global Impression of Severity (CGI-S) at baseline (pre-test) and 3-month follow-up, and adverse events were recorded.

182 patients were available for analysis. After multivariate adjustment, patients whose treatment followed the test recommendations had odds of improvement about 4 times greater than patients whose treatment did not follow the recommendations (adjusted OR=3.86, 95%CI 1.36–10.95; p=0.011). Importantly, psychiatric diagnosis did not significantly affect the odds of improvement. Also, in the subpopulation with baseline CGI-S score >3 (N=170), the rate of stabilization at follow-up (defined as CGI-S≤3) was significantly higher in patients whose treatment followed the pharmacogenetic recommendations (p=0.033). There was no apparent difference in the incidence of adverse events (6 patients in each group).

Non–drug naïve patients whose treatment followed the recommendations of pharmacogenetic testing were more likely to improve their condition than patients whose treatment did not. These results are consistent with previous clinical research on depressed patients, and this study also suggests that this benefit can be extended to psychiatric conditions other than depression.

Bipolar disorders (BDs) comprise different variants of chronic, comorbid, and disabling conditions, with relevant suicide and suicide attempt rates. The hypothesis that BD types I (BDI) and II (BDII) represent more and less severe forms of illness, respectively, has been increasingly questioned over recent years, justifying additional investigation to better characterize related sociodemographic and clinical profiles.

A sample of 217 outpatients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)–described BD (141 BDI, 76 BDII), without a current syndromal mood episode, was recruited, and sociodemographic and clinical characteristics of BDI and II patients were compared.

BDII patients had significantly more favorable sociodemographics, in relation to occupational stability, cohabitation, and marital status. However, BDII compared with BDI patients had significantly longer duration of untreated illness, more frequent lifetime anxiety disorders comorbidity, longer most recent episode duration, higher rate of depressive first/most recent episode, and more current antidepressant use. In contrast, BDI compared with BDII patients had significantly more severe illness in terms of earlier age at onset; higher rate of elevated first/most recent episode, lifetime hospitalizations, and involuntary commitments; lower Global Assessment of Functioning score; and more current antipsychotic use. BDI and II patients had similar duration of illness, psychiatric family history, lifetime number of suicide attempts, current subthreshold symptoms, history of stressful life events, and overall psychiatric/medical comorbidity.

BDII compared with BDI patients had more favorable sociodemographic features, but a mixture of specific unfavorable illness characteristics, confirming that BDII is not just a milder form of BD and requires further investigation in the field.

Evaluate the efficacy and safety of asenapine 2.5 mg twice daily (bid; n=97) or 5 mg bid (n=113) versus placebo (n=101) in adults with acute exacerbation of schizophrenia.

Adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) schizophrenia diagnosis were randomized to asenapine 2.5 mg bid, 5 mg bid, placebo, or olanzapine 15 mg once daily. The primary objective was to test superiority of asenapine versus placebo as measured by the change from baseline to day 42 in the Positive and Negative Syndrome Scale (PANSS) total score. The key safety objective was to evaluate weight change in asenapine versus olanzapine at day 42.

The primary efficacy endpoint was met; the difference in least squares mean change from baseline to day 42 in PANSS total score between asenapine 5 mg bid and placebo was −5.5 points (unadjusted 95% CI: −10.1, −1.0; multiplicity adjusted P=0.0356). Neither asenapine 2.5 mg bid nor olanzapine 15mg were superior to placebo.

Both asenapine groups demonstrated significantly less weight gain than olanzapine at day 42. Significantly higher incidences of oral hypoesthesia and dysgeusia (combined) for asenapine 2.5 mg bid (5.2% vs 0.0%; P=0.0217) and 5 mg bid (7.1% vs 0.0%; P=0.0033) were observed versus placebo. There were no significant differences between asenapine and placebo for insomnia, extrapyramidal symptoms, akathisia, dizziness, or combination of somnolence/sedation/hypersomnia.

This study supports previous efficacy and safety findings of asenapine; asenapine 5 mg bid is the lowest effective dose in adults with schizophrenia. Asenapine was associated with significantly less weight gain than olanzapine at day 42.

Agomelatine is a newer antidepressant but, to date, no studies have been carried out investigating its effects on C-reactive protein (CRP) levels in major depressive disorder (MDD) before and after treatment. The present study aimed (i) to investigate the effects of agomelatine treatment on CRP levels in a sample of patients with MDD and (ii) to investigate if CRP variations were correlated with clinical improvement in such patients.

30 adult outpatients (12 males, 18 females) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of MDD were recruited in “real-world,” everyday clinical practice and treated with a flexible dose of agomelatine for 12 weeks. The Hamilton Rating Scale for Depression (HAM-D) and the Snaith-Hamilton Pleasure Scale (SHAPS) were used to evaluate depressive symptoms and anhedonia, respectively. Moreover, serum CRP was measured at baseline and after 12 weeks of treatment.

Agomelatine was effective in the treatment of MDD, with a significant reduction in HAM-D and SHAPS scores from baseline to endpoint. CRP levels were reduced in the whole sample, with remitters showing a significant difference in CRP levels after 12 weeks of agomelatine. A multivariate stepwise linear regression analysis showed that higher CRP level variation was associated with higher baseline HAM-D scores, controlling for age, gender, smoking, BMI, and agomelatine dose.

Agomelatine’s antidepressant properties were associated with a reduction in circulating CRP levels in MDD patients who achieved remission after 12 weeks of treatment. Moreover, more prominent CRP level variation was associated with more severe depressive symptoms at baseline.

These post hoc analyses evaluate the efficacy, safety, and tolerability of vortioxetine versus placebo in patients aged ≥55 years with major depressive disorder (MDD).

Study-level efficacy data from 12 short-term, fixed-dose, randomized, placebo-controlled trials of vortioxetine 5–20 mg/day were assessed using a random-effects meta-analysis. Adverse events (AEs), vital signs, ECG values, liver enzymes, and body weight were pooled from the same studies. Patients had baseline Montgomery–Åsberg Depression Rating Scale (MADRS) total scores ranging from 22–30.

1508 patients (mean age=62.4 years; range, 55–88 years) were included. Mean differences from placebo in change from baseline to study end (6/8 weeks) in MADRS were –2.56 (5 mg, n=324, P=0.035), –2.87 (10 mg, n=222, P=0.007), –1.32 (15 mg, n=90, P=NS), and –4.65 (20 mg, n=165, P=0.012). Odds ratios for response versus placebo were 1.6 (5 mg, P=NS), 1.8 (10 mg, P=0.002), 1.2 (15 mg, P=NS), and 2.5 (20 mg, P<0.001), and for remission versus placebo were 1.5 (5 mg, P=NS), 1.5 (10 mg, P=NS), 1.4 (15 mg, P=NS), and 2.7 (20 mg, P=0.001). The proportion of patients with AEs for placebo and vortioxetine 5–20 mg was 61.5% and 62.3%, respectively, with no increase at increased doses. Vortioxetine demonstrated a placebo-level incidence of serious AEs (1.2%). AEs occurring in ≥5% of any treatment group were nausea, headache, diarrhea, dizziness, dry mouth, constipation, fatigue, vomiting, and anxiety. No clinically significant mean changes in vital signs, ECG values, liver enzymes, or body weight emerged during treatment.

Vortioxetine 5–20 mg/day is efficacious and well tolerated in MDD patients aged ≥55 years, a group that is often comorbid with other conditions and treated with other medications.

Many studies have reported hippocampal volume reductions associated with posttraumatic stress disorder (PTSD), while others have not. Here we provide an updated meta-analysis of such reductions associated with PTSD and evaluate the association between symptom severity and hippocampal volume.

A total of 37 studies met the criteria for inclusion in the meta-analysis. Mean effect sizes (Hedges’ g) and 95% confidence intervals (CI95%) were computed for each study and then averaged to obtain an overall mean effect size across studies. Meta-regression was employed to examine the relationship between PTSD symptom severity and hippocampal volume.

Results showed that PTSD is associated with significant bilateral reduction of the hippocampus (left hippocampus effect size=–0.400, p<0.001, 5.24% reduction; right hippocampus effect size=–0.462, p<0.001, 5.23% reduction). Symptom severity, as measured by the Clinician-Administered PTSD Scale (CAPS), was significantly associated with decreased left, but not right, hippocampal volume.

PTSD was associated with significant bilateral volume reduction of the hippocampus. Increased symptom severity was significantly associated with reduced left hippocampal volume. This finding is consistent with the hypothesis that PTSD is more neurotoxic to the left hippocampus than to the right. However, whether the association between PTSD and lower hippocampal volume reflects a consequence of or a predisposition to PTSD remains unclear. More prospective studies are needed in this area.