Therapeutic Advances in Psychopharmacology最新文献

Background: Many antidepressant users experience the process of stopping as challenging because of withdrawal symptoms. Support factors, such as patients experiencing empathy from their healthcare providers, potentially contribute to successful discontinuation.

Objectives: To examine the relation between experienced empathy and successful antidepressant discontinuation.

Design: Part of a larger prospective cohort study in major depressive disorder patients using sertraline or citalopram recruited through university medical centres and connected general practitioners, pharmacies and mental health institutions. The larger study aimed to identify factors associated with remission and patients' experiences with discontinuing antidepressants.

Method: Patients were followed for 24 months. We measured objective and subjective discontinuation success. Subjective discontinuation was measured with the Discontinuation Success Scale, a scale with three subscales (subjective feeling of success, positive and negative effects of discontinuation). Empathy was measured with the Consultation and Relational Empathy (CARE) measure. To analyse the association between perceived empathy and discontinuation success, we used regression analyses.

Results: Of 918 participants in the larger study, 235 attempted discontinuation and 153 could be included in the analysis. About two-thirds of the participants were successful in discontinuing antidepressant medication. We did not find an association between perceived empathy and objective discontinuation success. Perceived empathy was positively associated with subjective success and negatively associated with the negative effects of discontinuation.

Conclusion: Although we could not demonstrate an association of perceived empathy and objective discontinuation, we consider the finding of a relation between subjective success as relevant because a successful experience regarding antidepressant discontinuation may positively influence the initiation of future attempts.

Background: Intravenous ketamine is effective in treatment-resistant bipolar depression (TRBD) with dosing typically based on actual body weight (ABW).

Objective: This study examined whether alternative normalization formulas are associated with treatment response.

Design: A retrospective exploratory analysis of a naturalistic registry for short-term ketamine use.

Methods: A total of 22 TRBD inpatients received short-term intravenous ketamine. Doses were recalculated using the Boer and Devine formulas for lean body mass (LBM) and ideal body weight (IBW), and the Mosteller formula for body surface area (BSA). Calculated doses were compared with ABW dosing in responders and nonresponders.

Results: Using the Mosteller formula, BSA-normalized doses ranged from 17.63-23.09 mg/m² in nonresponders and 15.73-23.89 mg/m² in responders. LBM- and IBW-based recalculations at 0.5 mg/kg yielded lower relative doses, particularly among nonresponders, suggesting potential underdosing.

Conclusion: These preliminary findings do not support alternative dosing formulas over ABW, but replication in larger controlled studies is warranted.

Background: Physical touch is often included as a supportive or therapeutic tool in psychedelic-assisted therapy (PAT), involving instrumental forms of physical contact, supportive touch and somatic techniques. However, participants under the influence of psychedelics have reduced capacity to provide consent, are more suggestible and may experience and interpret therapeutic touch in ways they did not expect prior to taking the drug. Yet little research has been conducted on the considerations and approaches to therapeutic touch in clinical trials of PAT.

Objectives: This study explored the experiences and perspectives of PAT researchers on the use and consent to therapeutic touch in clinical trials of PAT.

Design: A qualitative study using semi-structured interviews.

Methods: Sixteen PAT researchers involved in clinical trials of PAT were interviewed. Reflexive thematic analysis was used to analyse the data. The reporting of this study conforms to the Consolidated Criteria for Reporting Qualitative Research Checklist (COREQ).

Results: Three themes were uncovered through reflexive thematic analysis: (1) flexible frameworks, (2) therapeutic alliance and (3) boundary management. Researchers discussed consent challenges across the broad spectrum of physical contact existing in PAT protocols at the time. Researchers indicated that consent to therapeutic touch should be established prior to the dosing sessions and continually managed throughout the course of treatment. Flexibility in consent protocols enabled researchers to interpret and approach consent through the development of a strong therapeutic alliance; however, flexibility could also lead to challenges in boundary management. Researchers emphasised the need for greater ethical guidance in instances where trial participants change their established preferences during dosing sessions, and limits on expanding consent after drug administration.

Conclusion: Clear guidelines for obtaining consent, managing changing preferences and training on the management of boundary transgressions were viewed as essential for ethical research and practice of PAT.

Background: Depression affects approximately 5.7% of adults worldwide, and around one-third of these individuals develop treatment-resistant depression (TRD). Intravenous (IV) ketamine and esketamine (administered IV or intranasally (IN)) are novel treatment options for TRD; however, only IN esketamine currently holds FDA approval.

Objectives: Compare the acute effectiveness of IV ketamine with esketamine (IV or IN) in adults with TRD.

Design: Mantel-Haenszel random-effects meta-analysis of head-to-head studies. Response and remission at study end point were co-primary outcomes, expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses explored the impact of diagnosis, study type, and publication format; heterogeneity was quantified with I ².

Data sources and methods: MEDLINE, Embase, Cochrane, APA Psycinfo, and Scopus were searched from inception through 19 March 2025. Eligible studies enrolled adults with unipolar or bipolar depression directly comparing IV ketamine with esketamine and reporting response or remission.

Results: Screening 1089 records identified eight studies (n = 978). Seven observational studies (n = 915) comparing IV ketamine with IN esketamine were included in the meta-analysis, while one randomized controlled trial (RCT) comparing IV formulations was summarized qualitatively. Pooled response from six studies gave OR = 1.26 (95% CI, 0.92-1.71; p = 0.15) and remission from seven studies gave OR = 1.31 (95% CI, 0.93-1.86; p = 0.12), both nonsignificantly favoring IV ketamine with negligible heterogeneity (I ² = 0%). Sensitivity analyses excluding bipolar depression or abstract-only reports yielded similar effect estimates, reinforcing the robustness of the findings. Evidence across three studies for faster onset with IV ketamine ranged from significant in one study to modest trends in two.

Conclusion: Based on the currently available comparative evidence, which is almost entirely observational, IV ketamine and IN esketamine show comparable acute response and remission rates, though IV ketamine may act faster. Large head-to-head RCTs are needed to confirm these findings.

Trial registration: The study protocol was prospectively registered on the Open Science Framework (OSF) at https://osf.io/5jzev.

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Background: Nonadherence jeopardizes treatment outcomes in the psychiatric care continuum. However, there was a paucity of data in the resource-limited life trajectories.

Objectives: This study sought to uncover the psychotropic medications adherence behavior of older adults with severe mental disorders and its modeling predictors.

Design: A hospital-based cross-sectional study was conducted in selected hospitals of the South Gondar Zone from March 1 to August 30, 2024.

Methods: A multistage sampling technique followed by stratified and systematic random sampling methods was employed. Data were collected via interviewer-administered semistructured questionnaire and medical record review. A medication adherence rating scale, medication regimen complexity index instrument, Oslo social support scale, drug attitude inventory scale, and internal stigma monitoring index scale were utilized to assess adherence, treatment regimen complexity, social/family support, attitudes toward treatment, and internal stigma, respectively. Ordinal logistic regression deciphered key predictors using adjusted odds ratios (AORs) with a 95% confidence interval at p < 0.05.

Results: The study sample comprised 423 patients with severe psychiatric disorder (mean (SD) age, 67.3 (±11.9) years; 56.03%, 237 male). Among the participants 255 (60.28%, (95% CI: 58.86-62.11)) had suboptimal adherence behavior. Age, education status, adherence counseling, attitude toward treatment, memory aids, internal stigma, insight, social support, illicit drug use, comorbidity, ADRs, patient-level medication regimen complexity index, and polypharmacy were the predictors identified in the final model.

Conclusion: Despite multiple methodological limitations, this study suggests that suboptimal psychotropic medications adherence behavior was a critical challenge among older adults with severe mental disorders in geriatric mental healthcare in the Ethiopian hospital settings. We urge policymakers to devise evidence-based policies and strategies focusing on the identified predictors early on and intervene accordingly. Special attention should be given to individuals with low literacy levels, negative attitudes toward treatment, high internalized stigma, poor insight into their condition, substance use, comorbidities, adverse drug reactions, high levels of medication regimen complexity score, and those on polytherapy.

Background: Oral contraceptives (OC) offer a range of ethinyl estradiol (EE) doses and progestin types, with evidence indicating marked differences in cognitive and emotional abilities in OC users. However, it remains unclear whether dose variations in EE (low vs high) and progestin androgenicity (androgenic vs anti-androgenic) are associated with variations in cognitive and emotional abilities.

Objectives: Our study aimed to investigate the cognitive and emotional effects of various OC formulations.

Design: Online between-subjects experimental design.

Methods: Based on regular monophasic OC formulation use, 96 participants (26 ± 7 years) were recruited and categorised into one of four groups: low EE androgenic (n = 26), high EE androgenic (n = 24), low EE anti-androgenic (n = 21) and high EE anti-androgenic (n = 25). The Repeatable Battery for the Assessment of Neuropsychological Status, emotion recognition task, and the Positive and Negative Affect Schedule were administered. Visual analogue scales were also administered to assess rejection sensitivity before and after a social exclusion task (Cyberball task). Analysis of variance (2 × 2) models were used to compare cognitive and socio-emotional abilities between groups.

Results: Anti-androgenic users demonstrated higher intensity ratings for emotional faces, and heightened feelings of insecurity after a social stressor. Overall positive and negative affect, as well as performance on objective cognitive tests, were similar across OC formulations.

Conclusion: In OC users, OC formulations containing an anti-androgenic progestin were associated with greater perceived intensity of emotional faces as well as heightened rejection sensitivity. However, these subtle differences in task performance did not translate to differences in overall affect or cognitive performance.

Formal guidelines recommend that opioids should be stopped when risks outweigh benefits. These guidelines generally recommend gradual dose tapering at a rate tolerable to the patient. However, there is considerable variation regarding the pattern of dose tapering recommended, with some suggesting linear tapers (with a fixed reduction of dose at each step), while others recommend increasingly small dose reductions as the total dose gets lower. No biological rationale has been put forward for these recommendations. We examined the pharmacodynamic properties of opioids to derive pharmacologically rational principles for tapering. As dictated by the law of mass action, the relationship between dose of opioid and effect on its principal target, the mu-opioid receptor, is hyperbolic, with diminishing incremental effects for increasing doses. This suggests that in order to mitigate withdrawal symptoms, opioid doses should be tapered according to a corresponding hyperbolic pattern, with dose reductions becoming increasingly small as total dose reduces. This can be approximated by proportional decreases (e.g. 1%-10% reduction of the most recent dose every 1-2 weeks). Dose reductions should be titrated to withdrawal symptoms throughout the process, and final doses before complete cessation will need to be very small (such as 0.1 mg of buprenorphine or 1 mg of methadone, or less). The duration required for this strategy of tolerable tapering after long-term use may require many months or years for some patients. The theoretical proposals in this paper offer a pharmacologically rational strategy that should prompt review of clinical practice and guidelines. Gradual, hyperbolic tapering should be evaluated in randomised controlled trials.

Background: Psychotropic medications are often inappropriately prescribed for behavioural and psychological symptoms of dementia (BPSD), posing significant risks such as falls, stroke and death. Although non-pharmacological interventions (NPIs) are the first-line treatment for BPSD, their use in practice remains limited.

Objectives: This study explored general practitioners' (GPs') and physicians' perspectives on using psychotropic medications compared to NPIs for managing BPSD in Australian residential aged care homes (RACHs).

Design: Semi-structured online in-depth interviews were conducted with GPs and physicians managing BPSD in Australian RACHs.

Methods: The interviews were audio-recorded, transcribed and analysed using inductive thematic analysis, with transcripts coded using NVivo 14 to generate themes.

Results: Four GPs and eleven physicians were interviewed, and four major themes emerged: (1) knowledge of best practices of BPSD management, (2) awareness of current challenges in BPSD management, (3) non-involvement, blame shifting and rationalisation: perceived reasons for the current challenges and (4) suggested solutions. GPs and physicians were aware of best practices in managing BPSD, highlighting the importance of NPIs as more effective first-line strategies, with psychotropic medications reserved as a last resort. They also admitted that psychotropic over-prescription and inadequate NPI implementation persisted in BPSD management in Australian RACHs. Physician participants often distanced themselves from and blamed the GPs, staff and relatives of residents with dementia for the current problems. Systemic barriers, including insufficient resources, limited care continuity and organisational structures, were also reported to hinder psychotropic deprescribing. Implementing NPIs was deemed to be impeded by inadequate training and low confidence in their effectiveness. The participants suggested strengthening workforce capacity, incentivising NPIs and encouraging interdisciplinary collaboration.

Conclusion: The results highlighted the gap between GPs' and physicians' knowledge of best practices and actual prescribing practices for BPSD in Australian RACHs. Improved workforce and support for NPIs could reduce reliance on psychotropics and align BPSD management with best practices.