Psychopharmacology bulletin最新文献

Objective: Self-management of bipolar disorder (BD) is an important component of treatment.

Methods: We developed a patient-centered computational software system based on concepts from nonlinear systems (chaos) theory with mobile access to assist in managing BD known as KIOS. KIOS tracks interacting symptoms to determine theprecise state of a BD patient. Once the patient's state is identified and the trajectory of the patient established, specific advice is generated to help manage the course of the disease. KIOS also provides analytics that can be used by clinicians and researchers to track outcomes and the course of illness. A 12-week field test was completed.

Results: In 20 BD subjects, use of KIOS was associated with improvements in primary symptom categories of BD. Usability and generated advice were rated as a median of 6 out of a maximum of 7.

Conclusions: The KIOS focus on change illuminates problems in the same way that humans experience them, implying that the future state will be consequent to changes made to impact the current state. Randomized clinical trial is indicated.

Objectives: Although clozapine exhibited high efficacy for treating the symptoms of patients with treatment-resistant schizophrenia (TRS), its precise action mechanisms have not been fully understood. Recently, accumulating evidence has suggested the presence of abnormalities in the gamma-aminobutyric acid (GABA) systems in patients with schizophrenia, and the potential effects of clozapine on GABA receptors have gained a great deal of attention.

Experimental designs: In the present study, the cortical silent period (CSP), an electrophysiological parameter of GABA function via GABA_B receptors, was measured using with the transcranial magnetic stimulation in patients with schizophrenia and healthy control subjects. Then the CSP of patients treated with clozapine (N = 12) was compared with that of patients treated with other antipsychotics (N = 25) and with that of healthy controls (N = 27).

Principal observations: The CSP of the patients treated with clozapine was significantly longer compared to those of the other two groups. The CSP of patients treated with other antipsychotics was similar to that of healthy subjects. There was a positive correlation between CSP and global assessment of function (GAF) in patients with TRS.

Conclusions: The present study indicated that CSP was prolonged in patients receiving clozapine, and suggested that clozapine enhances the transmission signal via GABAB receptors.

Mood and psychotic disorders are a group of illnesses that affect behavior and cognition. Schizophrenia is characterized by positive symptoms, such as delusions and hallucinations, as well as negative symptoms. Major depressive disorder (MDD) is a mood disorder that affects the patient's emotions, energy, and motivation. Brexpiprazole works as a partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A. Schizophrenia and MDD have a wide range of risk factors, both biological and environmental. Third generation antipsychotics, which include brexpiprazole, are the latest group of drugs to reach the market, demonstrating efficacy and tolerability. Patients with acute schizophrenia have responded well to brexpiprazole. In this regard, in patients who have MDD plus anxiety symptoms, brexpiprazole can be effective as an adjunctive therapy and can reduce anxiety symptoms. In summary, brexpiprazole has proved to be an effective alternative to typical or first and second-generation atypical antipsychotics.

Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related-common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs. Genetics also play a role as several human leukocyte antigen (HLA) genotypes within certain ethnic groups have been implicated in adverse reactions to specific drugs. HLAB*15:02 has been identified in the Chinese and others of Southeast Asian origin to increase susceptibility to lamotrigine and carbamazepine-induced SJS. Furthermore, patients of Japanese origin with HLAB*31:01 and Koreans with HLA-B*44:03 are also at increased risk of SJS after receiving the same two drugs. Of the antiepileptics, one most commonly associated with SJS is lamotrigine, a pre-synaptic voltage-gated sodium channel inhibitor. Lamotrigine is an antiepileptic drug of the phenyltriazine class that is indicated for the prevention of focal and generalized seizures in epileptic patients as well as monotherapy or adjunctive maintenance treatment for Bipolar disorder. The occurrence of SJS is not a rigid contraindication to lamotrigine reintroduction in the same patient. To facilitate this, manufacturers have developed a strict re-challenge dosing regimen to facilitate successful reintroduction of lamotrigine. In order to prevent the recurrence of SJS during a re-challenge, timing of re-dose and initial rash severity must be considered. Therefore, to prevent SJS recurrence, prime lamotrigine re-challenge patients are those with mild initial rash that has not occurred within the previous 4 weeks. The Federal Food and Drug Administration recommends the testing HLA subtypes for those associated with SJS prior to starting lamotrigine.

Objectives: Three Phase 3 trials have demonstrated the efficacy and safety of SPN-812 in pediatric subjects with ADHD. Here, we report the results of a fourth trial.

Methods: Eligible adolescent subjects (N = 297) were randomized to SPN-812 (400- or 600-mg/day) or placebo. The primary efficacy endpoint was change from baseline (CFB) at end of study (EOS) in the ADHD Rating Scale-5 (ADHD-RS-5) Total score. Statistical analyses included sequential testing for multiple treatment comparisons. Key secondary endpoints included: Clinical Global Impression-Improvement (CGI-I) score at EOS and CFB at EOS in the Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and Weiss Functional Impairment Rating Scale-Parent (WFIRS-P) Total average score.

Results: The CFB at EOS ADHD-RS-5 Total score (least square [LS] means ± SE) for 400-mg/day, 600-mg/day SPN-812, and placebo was -18.3 ± 1.36, -16.7 ± 1.39, and -13.2 ± 1.38, respectively. The difference vs. placebo was statistically significant only for the 400-mg/day SPN-812 treatment group (600 mg/day: p = 0.0712; 400 mg/day: p = 0.0082). Neither dose could be considered superior to placebo due to the use of statistical method of sequential testing. Significant improvements were observed on a number of secondary endpoints. SPN-812 was well tolerated at both doses, with <5% discontinuation rate due to adverse events.

Conclusions: Treatment with 400- but not 600-mg/day SPN-812 resulted in statistically significant improvement in the primary endpoint. The negative result seen in the 600-mg/day SPN-812 group was likely due to an unusually high placebo response. Safety data were consistent across all doses in the SPN-812 trials.

Infertility, the inability to establish a clinical pregnancy after 12 months of regular unprotected sexual intercourse, is caused by a wide variety of both male and female factors. Infertility is estimated to affect between 8-12% of couples trying to conceive globally. Female factor infertility can be subdivided into the following broad categories: ovulatory dysfunction, fallopian tubal disease, uterine causes, and oocyte quality. Hyperprolactinemia causes ovulary dysfunction along with other hormonal abnormalities, such as decreased estrogen, which can lead to infertility. In this regard, antipsychotics are commonly used for both schizophrenia and bipolar disorder. The use of these medications can be associated with hyperprolactinemia and hyperprolactinemia associated infertility. Antipsychotic-induced hyperprolactinemia occurs through blockade of D₂ receptors on lactotroph cells of the anterior pituitary gland. Discontinuation of the hyperprolactinemia-inducing antipsychotic is an option, but this may worsen the patient's psychosis or mood. If antipsychotics are determined to be the culprit of infertility, the degree of hyperprolactinemia symptoms, length of treatment with the antipsychotic, and risk of relapse should be assessed prior to discontinuation, reduction, or switching of antipsychotic medications. The treatment of a women's mental health and her desire to have children should always be considered as treatment may influence fertility while on the medication.

Introduction: Mirtazapine is commonly administered to patients with recurrent depressive disorder. Some of these patients do not show adequate response to the therapy with mirtazapine, whereas many of them experience dose-dependent adverse drug reactions. Previous research revealed that CYP2D6 is involved in the metabolism of mirtazapine, the activity of which is highly dependent on the polymorphism of the gene encoding it.

Objective: The objective of this study was to investigate the effect of polymorphisms of the CYP3A4, CYP2C9, CYP3A5, ABCB1, CYP2C19, SCL6A4, and 5-HTR2A genes on the concentration/dose indicator of mirtazapine and on the CYP3A expression level obtained by measuring the miR-27b plasma concentration levels in patients suffering from a recurrent depressive disorder.

Material and methods: Our study included 108 patients with recurrent depressive disorder (average age - 35.2 ± 15.1 years). The treatment regimen included mirtazapine in an average daily dose of 45.0 [30.0; 60.0] mg per week. Therapy efficacy was assessed using the international psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP3A was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of the given isoenzyme and its metabolite in urine (6b-HC/cortisol). Therapeutic drug monitoring has been performed using HPLC-MS/MS.

Results: Our study didn't reveal any statistically significant results in terms of the treatment efficacy and safety of the therapy. We also didn't reveal a statistical significance for the concentration/dose indicator of mirtazapine in patients with different genotypes. Analysis of the results of the pharmacotranscriptomic part of the study didn't demonstrate the statistically significant difference in the miR-27b plasma levels in patients with different genotypes. At the same time, correlation analysis didn't reveal a statistically significant relationship between the mirtazapine efficacy profile evaluated by changes in HAMD scale scores and the miR-27b plasma concentration: rs = -0.2, p = 0.46. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.029, p = 0.93. In addition, we didn't reveal the relationship between the CYP3A enzymatic activity and the miR-27b plasma concentration: rs = -0,188, p = 0.85. However, the difference in the CYP3A enzymatic activity in carriers of AG and GG genotypes of the 6986A > G polymorphism of CYP3A5 gene has been revealed: (AG) 4.75 [1.28; 7.34] vs (GG) 8.83 [4.73; 13.62], p-value = 0.023.

Conclusion: Thus, the effect of genetic polymor

ZULRESSO (Brexanolone) is a novel FDA-approved treatment for moderate-to-severe postpartum depression. Postpartum depression may be diagnosed in women experiencing depressive symptoms which can manifest as cognitive, behavioral, or emotional disturbances as early as the third trimester to 4 weeks following delivery. The efficacy of brexanolone suggests that neurosteroids such as allopregnanolone are important to treat PPD. However, it is currently unclear if brexanolone provides lasting relief of depressive symptoms at or beyond 30 days following administration. Further studies are necessary to make this determination.

Purpose: we aimed 1) to evaluate the risk factors associated to the benzodiazepines intake; 2) to assess the impact about the use of long acting injectables antipsychotics (LAIs); 3) to assess the risk in severe and affective disorders and 4) to identify the prescription patterns of use in mental health in a cohort of patients from Spain.

Methods: 735 outpatients from Mental Health were included. Demographic and clinical data were collected. In order to compare the use of benzodiazepines we calculated the daily dose equivalents (mg/day) to diazepam as standard.

Results: The most commonly prescribed benzodiazepine was clonazepam (33%) and the mean daily dose of diazepam equivalents was 24.9 mg. It was higher in affective disorders (40.35 ± 3.36) and lower in patients using LAIs antipsychotics (17.50 ± 1.39; p = 0.001). Multivariate analysis showed that to be women (OR = 1.559, 95% CI = 1.059-2.295, p = 0.024), the use of drugs (OR = 1.671, 95% CI = 1.127-2.477, p = 0.011) and suffering any affective disorder (OR = 1.542, 95% CI = 1.355-1.826, p = 0.040) increased the risk of benzodiazepine intake. In contrast, the use of LAIs antipsychotics significantly reduced it versus oral antipsychotics (OR = 5.226, 95% CI = 3.185-8.575, p = 0.001).

Conclusions: benzodiazepines are widely prescribed, mainly clonazepam followed by lorazepam and diazepam. Most of patients used at least one benzodiazepine and the mean daily intake was 25 mg diazepam equivalents. Therefore, benzodiazepines are extensively prescribed and used at higher doses than desirable. These, findings could be useful for clinicians and their practice.