Psychopharmacology bulletin最新文献

~ Nightmares are psychologically distressing events that may cause significant effects on mental health, physical well-being and overall quality of life, in addition to their negative impact on quality and duration of sleep. Drug dreams are a variant of nightmares and a known phenomenon in addiction medicine, and have been studied as a potential causative factor in relapse of substance use. Recent studies have noted that addictive behaviors and drug dreams share a similar neurobiological pathway, and that certain neurotransmitters, most notably those of the noradrenergic system, may underlie these complex processes. This has led to the theory that alleviation of drug dreams and suppression of involved neurocircuits may potentially reduce subsequent craving and relapse in the treatment of substance use disorders, with an important potential agent being the alpha-1 antagonist, prazosin.

Purpose of review: This is a comprehensive review of the literature regarding the use of asenapine for the treatment of schizophrenia (SZ) in adults. It covers an introduction, epidemiology, risk factors, pathophysiology, and current treatment modalities regarding SZ, provides a background on the mechanism of action of asenapine, and then reviews the existing evidence for use of asenapine in both its sublingual and transdermal formulation in the treatment of SZ.

Recent findings: SZ is a complex and multifactorial mental disorder which is thought to combine several genetic, epigenetic, and environmental factors causing abnormalities in the dopaminergic system. Symptoms are categorized in delusions, hallucinations, disorganization, and negative presentations like affective flattening and apathy. Current treatment focuses on antipsychotic medications by means of oral administration or long-acting injection. Asenapine is a second-generation antipsychotic with 5HT-2A antagonist and 5HT-1A/1B partial agonist properties, which provides a favorable profile in targeting schizophrenic symptoms, while reducing motor side effects and improving mood and cognition. Asenapine in its sublingual formulation was FDA approved for treatment of SZ and bipolar I disorder in adults in August of 2009 and has been proven to be both effective and safe. Transdermal patch of asenapine (Secuado) was FDA approved in October of 2019, the first and only FDA approved patch for SZ in adults, which offers another strategy for treatment to improve compliance and ease of administration.

Summary: SZ is a chronic and debilitating disease which is still not well understood and comes at great cost with regards to the quality of life for patients. Medication side-effects and compliance are enormous issues which take a toll on health care systems in industrialized nations and keep patients from achieving stability with their disease. Transdermal asenapine is a new first-in-class dosage form and provides a novel modality of administration. It has been shown to be effective in reducing positive, as well as negative symptoms, while still maintaining a favorable side-effect profile.

Objective: To investigate whether the efficacy of antidepressants can be understood in terms of patient response-trajectory classes.

Experimental design: Patient-level data were analysed from 1357 adults with MDD randomised to either escitalopram 20 mg/day (n = 676) or placebo (n = 681) in five 8-week randomised placebo-controlled trials. Growth mixture models (GMMs) were used to identify the response trajectories; longitudinal latent class analysis (LLCA) was used to corroborate the findings.

Principal observations: Three classes of response were identified for escitalopram and placebo based on the trajectory of the patients' Montgomery-Åsberg Depression Rating Scale (MADRS) total scores during treatment. All three classes had similar mean baseline MADRS scores, but the change from baseline after 8 weeks differed: -4.2 MADRS points for non-responders, -18.4 MADRS points for slow responders, and -26.7 points for fast responders. The proportions of non-responders, slow responders and fast responders were 53%, 38% and 9%, respectively, with placebo and 27%, 58% and 14%, respectively, with escitalopram. Receiver operating curve analysis showed that a cut-off of ≥43% improvement from baseline to week 2 predicted fast responders, and a cut-off of ≥28% improvement from baseline to week 4 predicted responders (fast or slow). There were no clinically useful differences at baseline that predicted the trajectory class to which a patient would belong.

Conclusions: The presence of fast-, slow- and non-responder classes has a clear clinical relevance for guiding treatment decisions; individual patients can be classified by the change in their MADRS score from baseline at 2 or 4 weeks.

Background: Patients with Borderline Personality Disorder (BPD) have a high prevalence of mood disorders. Lamotrigine (LAM) is often used as an off-label therapeutic option for BPD. We aimed to conduct a systematic review and meta-analysis to assess the efficacy and tolerability of LAM for the treatment of BPD.

Methods: We comprehensively searched electronic databases for eligible studies from the inception of databases to September 2019. Outcomes investigated were BPD dimensions, tolerability, and adverse events. Quality assessments were completed for the included studies. Data were summarized using random-effects model.

Results: Of the 619 records, five studies, including three randomized controlled trials (RCT; N = 330) were included for the qualitative analysis. A meta-analysis conducted on two RCTs measuring LAM efficacy at 12 weeks, showed no statistically significant difference at 12 weeks (SMD: -0.04; 95% CI: -0.49, 0.41; p = 0.87; I² = 38%) and at study endpoints (SMD: 0.18, 95%CI: -0.89, 1.26; p = 0.74; I² = 86%) as compared to placebo. Sensitivity analysis on three RCTs measuring impulsivity/aggression showed no statistically significant difference between LAM and placebo (SMD: -1.84, 95% CI: -3.94, 0.23; p = 0.08; I² = 95%). LAM was well tolerated, and quality assessment of the included trials was good.

Conclusions: Our results suggest there is limited data regarding efficacy of lamotrigine in BPD. There was no consistent evidence of lamotrigine's efficacy for the core symptom domains of BPD. Future studies should focus on examining targeted domains of BPD to clarify sub-phenotypes and individualized treatment for patients with BPD.

Objective: Aim of the study is to evaluate sociodemographic and clinical features that may be associated with the development of Tardive dyskinesia (TD).

Methods: 80 patients attending an outpatient psychiatry clinic in Istanbul, Turkey were divided into TD (n = 50) and control groups (CG) (n = 30). Sociodemographic and clinical data was collected through face-to-face interviews and a retrospective search of medical records.

Results: There was a significant difference between TD and control group (CG) in terms of mean; onset of psychiatric disease at or after 35 years of age; first use of APD at or after 35 years of age; use of long-acting injectable APD; history of extrapyramidal side-effects; history of akathisia and family history of psychiatric disease. There was no significant difference between the two groups in terms of DSM- IV-based psychiatric diagnosis distributions, the existence of complete recovery periods during the course of the disease; total duration of APD use for at least 10 years; APD holidays; regular APD use; history of ECT and smoking or alcohol and substance abuse/addiction.

Conclusion: Advancing age seemed to be the most significant risk factor in the development of TD. Clinicians need to be cautious about TD when prescribing APD for elderly patients.

Introduction: Duloxetine is commonly prescribed to patients with recurrent depressive disorder. Some part of patients in this group do not respond adequately to treatment regimen containing duloxetine, while many of them experience dose-dependent adverse drug reactions. Previous research investigated that CYP2D6 is involved in the biotransformation of duloxetine, the activity of which is highly dependent on the polymorphism of the gene encoding it.

Objective: The objective of this study was to evaluate the influence of 1846G > A polymorphism of the CYP2D6 gene on the concentration/dose indicator of duloxetine, using findings on enzymatic activity of CYP2D6 (as evaluated by the 6M-THBC/pinoline ratio measurement) and on CYP2D6 expression level obtained by measuring the hsa-miR-370-3p plasma concentration levels in patients suffering from recurrent depressive disorder.

Material and methods: This study enrolled 118 patients with recurrent depressive disorder (average age - 40.6±17.1 years). Therapy included duloxetine in an average daily dose of 103.7±37.1 mg per day. Treatment efficacy was assessed using the international psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping we performed the real-time polymerase chain reaction (PCR Real-time). Therapeutic drug monitoring has been performed using HPLC-MS/MS.

Results: Our findings revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMD scores at the end of the treatment course): (GG) 9.0 [7.0; 10.0] and (GA) 11.0 [8.5; 14.0], p < 0.001; at the same time, the statistical significance in the safety profile was obtained (the UKU scores): (GG) 3.0 [3.0; 4.0] and (GA) 4.0 [3.0; 4.0], p = 0.007. We revealed a statistical significance for concentration/dose indicator of duloxetine in patients with different genotypes: (GG) 0.776 [0.529; 1.067] and (GA) 1.388 [0.942; 1.732], p < 0.001.

Conclusion: Thus, the effect of genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of duloxetine was demonstrated in a group of 118 patients with recurrent depressive disorder.

Patients with treatment-resistant schizophrenia receiving clozapine therapy are at risk of potentially serious complications in the general hospital setting, due to the complex pharmacokinetic and pharmacodynamic profile of clozapine. We summarize common clinical challenges that face clinicians who care for clozapine patients in the general hospital, and make recommendations based on the available literature and clinical experience. Early collaborative management between consultation-liaison psychiatry and other clinical teams in the general hospital is paramount to improve clinical outcomes and avoid serious complications in this patient group.