Human Psychopharmacology: Clinical and Experimental最新文献

Objective

Despite the historical neurological use of Withania somnifera, limited evidence supports its efficacy for conditions like anxiety and insomnia. Given its known anti-stress properties, this review evaluated its safety and efficacy for anxiety and insomnia.

Methods

We searched Medline, Cochrane Library, and Google Scholar until August 2023 for randomized controlled trials (RCTs) comparing W. somnifera to placebo in patients with anxiety and/or insomnia. Outcome measures included changes in anxiety levels via the Hamilton Anxiety Scale (HAM-A), Sleep Onset Latency (SOL), Total Sleep Time (TST), Wake After Sleep Onset (WASO), Total Time in Bed (TIB), Sleep Efficiency (SE), and Pittsburgh Sleep Quality Index (PSQI) score. We utilized a random-effect model for pooling Mean Differences (MD) with a 95% Confidence Interval (CI). Heterogeneity was assessed through sensitivity and subgroup analysis, and the quality of RCTs was evaluated using the Cochrane revised risk of bias tool.

Results

Pooled results from five RCTs (n = 254) demonstrated that W. somnifera significantly reduced HAM-A scores (MD = −5.96; [95% CI −10.34, −1.59]; P = 0.008; I² = 98%), as well as sleep parameters such as SOL, TST, PSQI, and SE, but not WASO and TIB.

Conclusion

While W. somnifera extracts yielded promising results, further research with larger sample sizes is needed to confirm its effects on anxiety and insomnia.

Objective

To compare the pharmacology and abuse potential of oral dexamphetamine and lisdexamfetamine (LDX).

Methods

A search of Medline and Embase was conducted to identify relevant articles for this literature review.

Results

Dexamphetamine and LDX, a prodrug of dexamphetamine, are indicated for the treatment of attention-deficit/hyperactivity disorder. It has been suggested that LDX may have a reduced potential for oral abuse compared to immediate-release dexamphetamine. As a prodrug, LDX has the same pharmacodynamic properties as dexamphetamine. A study in healthy adults showed that the pharmacokinetic profile of dexamphetamine following oral administration of LDX is essentially identical to that of an equimolar dose of dexamphetamine administered 1 h later. In addition, dexamphetamine produced subjective drug liking effects comparable to those produced by LDX. LDX showed linear dose proportional pharmacokinetics up to a dose of 250 mg, indicating a lack of overdose protection at supratherapeutic doses. Furthermore, the exposure to dexamphetamine released from LDX may be prolonged by the consumption of alkalizing agents.

Conclusions

The available evidence from pharmacodynamic, pharmacokinetic and abuse liability studies suggests a comparable potential for oral abuse of dexamphetamine and LDX.

Aim

To compare opioid use disorder (OUD) patients who continue to use opioids and are in remission with buprenorphine-naloxone (B/N) in terms of some parameters and to evaluate the relationship between B/N dose and these parameters.

Method

We included 141 OUD patients in remission with B/N maintenance treatment for at least 6 months, 141 who still used opioids, and 141 healthy volunteers. Substance Craving Scale (SCS), Pittsburgh Sleep Quality Index (PSQI), Arizona Sexual Experiences Scale (ASEX), and Short Form 36 (SF-36) were administered.

Results

PSQI scores and ASEX scores were higher in those who continued to use opiates than in OUD in remission, and in OUD in remission compared to controls. OUD patients with current opioid use also had lower SF-36 scores compared to both patients in remission and healthy controls. SCS, PSQI, ASEX, and SF-36 scores were similar when the three groups were examined based on the dosage of B/N (below 8, 8–15, and 16 mg/day and above) use in OUD in remission.

Conclusions

Quality of life, craving, sleep and sexual functions improved significantly with B/N; however, these effects are not dependent on B/N dosage.

Objectives

Stimuli that are separated by a short window of space or time, known as spatial and temporal binding windows (SBW/TBWs), may be perceived as separate. Widened TBWs are evidenced in schizophrenia, although it is unclear if the SBW is similarly affected. The current study aimed to assess if dexamphetamine (DEX) may increase SBWs in a multimodal visuo-tactile illusion, potentially validating usefulness as an experimental model for multimodal visuo-tactile hallucinations in schizophrenia, and to examine a possible association between altered binding windows (BWs) and working memory (WM) suggested by previous research.

Methods

A placebo-controlled, double-blinded, and counter-balanced crossover design was employed. Permuted block randomisation was used for drug order. Healthy participants received DEX (0.45 mg/kg, PO, b.i.d.) or placebo (glucose powder) in capsules. The Rubber Hand Illusion (RHI) and Wechsler Adult Intelligence Scale Spatial Span was employed to determine whether DEX would alter SBWs and WM, respectively. Schizotypy was assessed with a variety of psychological scales.

Results

Most participants did not experience the RHI even under normal circumstances. Bi-directional and multimodal effects of DEX on individual SBWs and schizotypy were observed, but not on WM.

Conclusions

Bidirectional multimodal effects of DEX on the RHI and SBWs were observed in individuals, although not associated with alterations in WM.

Background

In this cross-sectional study, we compared fasting serum asprosin levels and metabolic parameters between patients receiving one of three atypical antipsychotics (olanzapine, risperidone, or aripiprazole) and healthy subjects.

Methods

The study population included 62 adult outpatients with schizophrenia and 22 healthy controls, matched for age and gender. Patients were in remission and had been on stable monotherapy with one of these atypical antipsychotics for over 6 months. Body Mass Index (BMI) and fasting serum levels of asprosin, glucose, HA1c, insulin, and lipid profile were compared across the investigated groups. Additionally, the number of participants meeting the insulin resistance criterion, defined as homeostasis model assessment for insulin resistance (HOMA-IR) >2.5, as well as the number of participants with elevated BMI levels (men >27 kg/m², women >25 kg/m²) were compared among the groups.

Results

We observed statistically significant differences in BMI and fasting serum levels of glucose, HA1c, insulin, triglyceride (TG), high-density lipoprotein cholesterol, and asprosin among patients receiving olanzapine or risperidone, as compared to those receiving aripiprazole and healthy subjects. Patients on aripiprazole exhibited values comparable to healthy subjects, whereas those on risperidone or olanzapine showed significantly higher values, with the highest observed in the olanzapine group. Additionally, the prevalence of participants meeting the insulin resistance criterion and those with elevated BMI was also greater in individuals receiving olanzapine or risperidone compared to those on aripiprazole and healthy subjects. Serum asprosin levels showed a significant positive correlation with BMI and several metabolic parameters, including HbA1c, fasting insulin, HOMA-IR, and TG. No significant differences were observed among the investigated groups in terms of serum levels of total cholesterol and low-density lipoprotein cholesterol.

Conclusions

Our cross-sectional study highlights the association between elevated asprosin levels, weight gain, and metabolic disorders in patients treated with olanzapine and risperidone. Given the bidirectional nature of the relationship between serum asprosin levels and these metabolic disturbances, further research is warranted to elucidate potential causative pathways.

Introduction

Obsessive-compulsive disorder (OCD) is marked by a high rate of treatment resistance. Patients are often left trialing medications within multiple drug classes with little response, causing heterogeneity to emerge in prescribing patterns. This analysis seeks to investigate the selection and dosing of the pharmacotherapy utilized, to portray an overview of prescribing trends in the United States.

Methods

This retrospective, single center, review of electronic medical records investigated the pharmacotherapy utilization of patients with a primary diagnosis of OCD. Two hundred and ninety-five patients who received OCD treatment at an urban, academic medical center were included in the study. Patients were included in the review if they were at least eighteen years of age and were assigned a diagnosis of OCD according to DSM-5 criteria.

Results

Psychotropic pharmacotherapy was integrated into the care of 93% of patients. Selective serotonin reuptake inhibitors were the most utilized medication class at 85% followed by benzodiazepines (47%) and second-generation antipsychotics (37%). Tricyclic antidepressants and first-generation antipsychotics were the two medication classes utilized the least at 13% and 2% respectively. Additionally, mood stabilizers and serotonin-norepinephrine reuptake inhibitors were utilized at rates of 8% and 16%, respectively.

Conclusions

Evidence-based treatment guidelines are being followed with varying augmentation strategies widely prevalent, thus displaying the heterogeneity in treating OCD. A high rate of benzodiazepine utilization highlights a practice trend with potential ties to clinical factors, such as the latency to treatment effect of other first-line pharmacotherapies. Future prospective studies are required to determine the cultural, pharmacoeconomic and pharmacogenomic factors that contribute to the variation in prescribing practices and whether these variations influence treatment outcomes.

Background

Endoxifen, a protein kinase C inhibitor and selective estrogen receptor modulator, primarily used in breast cancer treatment, has recently emerged as a potential therapeutic option for managing manic episodes associated with bipolar disorder (BD). This review aims to assess the existing evidence base for endoxifen in BD treatment and evaluate the strengths and limitations of current research findings.

Methods

A systematic search was conducted on Medline, Embase, and Web of Science databases. We included studies published in English that used endoxifen in BD, alongside any relevant studies identified through manual searching and conference papers with full-text availability. Information pertaining to dose, duration, clinical effects, and safety profiles was extracted from the included studies. The Cochrane Risk of Bias 2 tool was used to assess the risk of bias in clinical trials.

Results

The final review included seven case reports (including two conference presentations), two clinical trials, and one prospective study. Most studies administered endoxifen 8 mg and reported an improvement in manic symptoms. Several case reports included patients with comorbid substance use, and most patients received mood stabilizers concurrently. Few reports lacked any structured outcome measures. The clinical trials used divalproex 1000 mg as an active comparator, which was deemed sub-therapeutic. Despite being multicentric, the first trial lacked data on center-wise recruitment, and certain methodological concerns were observed across the included trials. There were no serious adverse effects noted, except for a significant elevation in lipid profile within a 3-week period. Limited data were available regarding endoxifen efficacy and safety in mixed episodes, depressive episodes, and maintenance treatment.

Conclusion

There is a paucity of research on the efficacy and safety of endoxifen in BD. While existing evidence suggests short-term efficacy in manic episodes, significant limitations were identified in most of the included studies. Further research is imperative to establish the efficacy and safety of endoxifen in BD before considering its recommendation as a viable treatment option.

Objectives

The pathology of Tardive Dyskinesia (TD) has yet to be fully understood, but there have been proposed hypotheses for the cause of this condition. Our team previously reported a possible association of TD with the Complement Component C4 gene in the HLA region. In this study, we explored the HLA region further by examining two previously identified schizophrenia-associated HLA-region single-nucleotide polymorphisms (SNPs), namely rs13194504 and rs210133.

Methods

The SNPs rs13194504 and rs210133 were tested for association with the occurrence and severity of TD in a sample of 172 schizophrenia patients who were recruited for four studies from three different clinical sites in Canada and USA.

Results

The rs13194504 AA genotype was associated with decreased severity for TD as measured by Abnormal Involuntary Movement Scale (AIMS) scores (p = 0.047) but not for TD occurrence. SNP rs210133 was not significantly associated with either TD occurrence or AIMS scores.

Conclusion

Our findings suggest that the rs13194504 AA genotype may play a role in TD severity, while SNP rs210133 may not have a major role in the risk or severity of TD.

Objective

To determine the occurrence of constipation in local patients on clozapine treatment, and to compare the demographical and clinical characteristics of patients on clozapine treatment with or without constipation.

Methods

This is a cross-sectional, observational study. All adult psychiatric out-patients on clozapine treatment attending follow-up at a regional hospital were recruited for clinical interview and medical record review. The Enhanced Asian Rome III Questionnaire (EAR3Q) was used to define patients with constipation. The Bristol Stool Form Scale (BSFS) was used to assess stool form. The Brief Psychiatric Rating Scale-Anchored (BPRS-A) was used to measure psychiatric symptoms. The Brief Medication Adherence Scale (BMAS) was used to assess treatment adherence. Logistic regression was conducted to identify independent associating factors of constipation in patients on clozapine treatment.

Results

The prevalence of constipation in patients on clozapine treatment was 26.3%, (95% CI [21.5%, 31.6%]). Independent associating factors included disorder of psychological development (aOR = 6.98, 95% CI [1.24, 39.18]), anxiety (very mild: aOR = 9.23, 95% CI [2.59, 32.87]; mild: aOR = 2.66, 95% CI [1.26, 5.62]), prescription with combination of laxatives (aOR = 0.40, 95% CI [0.17, 0.95]), and concomitant use of amisulpride (aOR = 2.52, 95% CI [1.09, 5.82]), quetiapine (aOR = 5.92, 95% CI [1.11, 31.56]) and metamucil (aOR = 9.30, 95% CI [1.53, 56.58]).

Conclusion

This study examined the prevalence of clozapine-associated constipation in Hong Kong using a validated questionnaire. The identification of independent factors associated with constipation could facilitate better risk stratification and risk modification in clinical practice.

Objectives

“WKUP GT”, a low caffeine beverage consisting of carob, Guarana, Green Tea and Elderberry extracts was studied on attention and cognitive functions post-lunch in a pilot randomized double blind placebo controlled trial.

Methods

Thirty healthy volunteers were included in a crossover design trial, presenting five beverages randomly assigned to the following groups: placebo, “WKUP GT” (single, double or triple doses), or “caffeine” as an active control. Hemodynamic measurements were assessed as safety outcomes.

The Cambridge Neuropsychological Test Automated Battery (CANTAB), was used to evaluate the patients when beverages were consumed 30 and 120 min after lunch (respectively Delta30 and Delta120 considering baseline).

Results

Drinking “caffeine” or “WKUP GT” after lunch, showed significant improvement (p < 0.05) in rapid visual information processing compared to placebo (Delta120 of “caffeine”, “WKUP” single and double). In addition, improvement in Multitasking Test (Delta30 for “WKUP” double, and Delta120 for “caffeine” and “WKUP” triple compared to placebo) was observed. “WKUP” triple also showed significant improvement for “memory” when compared to placebo (Delta120). Compared to “caffeine”, WKUP GT did not increase systolic blood pressure.

Conclusion

“WKUP GT” showed improvements for attention, memory, psychomotor and executive function tasks after lunch without increase in pulse rate.