Pharmacopsychiatry最新文献

Background: Electroconvulsive therapy (ECT) is an effective short-term treatment for schizophrenia and depression, amongst other disorders. Lidocaine is typically added to reduce pain from intravenous propofol injection. However, depending on the dose used in the ECT setting, it can shorten seizure duration. The aim of this study was to investigate the effect of lidocaine dose on seizure duration.

Methods: This retrospective, naturalistic cohort study included 169 patients treated with ECT. We examined 4714 ECT sessions with propofol or propofol plus lidocaine. Ictal quality was manually rated by visual inspection. The main outcome of this study was the relation of lidocaine with seizure duration after controlling for socio-demographic, ECT, and other anesthetic variables.

Results: There was a significant negative association between lidocaine usage and seizure duration. Multivariate analyses showed that seizure duration was shortened by an average of 3.21 s in sessions with lidocaine. Moreover, in this subgroup, there was a significant negative dose-dependent association between lidocaine dose and seizure length. Complementarily, a significant positive association between preictal BIS and seizure length was found in the subgroup of sessions where preictal was used.

Conclusions: We provide additional evidence highlighting the importance of caution regarding lidocaine dosing due to the effect on seizure length in the ECT setting. It is advisable for clinicians to exercise caution when administering lidocaine regarding its dosing and seizure length in ECT settings. Future investigation is needed to assess causal relationships by studying certain vulnerable groups or employing other charge calculation techniques, such as the titration method.

Background: Serotonin reuptake inhibitor (SRI) antidepressants are commonly associated with withdrawal reactions. The Discontinuation Emergent Signs and Symptoms (DESS) checklist has been considered the gold standard research and screening tool for SRI withdrawal but has several limitations, including its length, lack of specificity, and omission of baseline symptom and symptom severity scores, making it impractical for use in clinical or research settings. We investigated the prevalence and severity of common SRI withdrawal symptoms to determine whether a very small subset of symptoms can capture most occurrences of SRI withdrawal.

Methods: We surveyed 344 members of online peer-support communities aged 18-65, reporting withdrawal symptoms after chronic SRI treatment. The severity of nine common withdrawal symptoms was evaluated at baseline and during the withdrawal period.

Results: Dizziness, brain zaps, irritability/agitation, and anxiety/nervousness demonstrated the largest increase in severity during withdrawal relative to baseline. Nearly all (97.7%) of the 344 subjects and all (100%) 153 subjects with relatively low baseline symptom scores (total<5) reported a worsening of one of these four symptoms. The presence of a baseline anxiety disorder did not affect rates of withdrawal-emergent anxiety/nervousness.

Conclusion: Nearly all surveyed subjects reported worsening either of dizziness, brain zaps, irritability/agitation, or anxiety/nervousness in acute withdrawal. A screening test incorporating these four core symptoms may be sufficiently sensitive to rule out SRI withdrawal and may be valuable in clinical and research settings. Incorporating withdrawal symptom severity may further enhance specificity.

Introduction: There is a need for novel anxiolytics with improved side effect profiles compared to benzodiazepines. A promising candidate with alternative pharmacodynamics is the translocator protein ligand, etifoxine.

Methods: To get further insight into its mechanisms of action and side effects compared to the benzodiazepine alprazolam, we performed a double-blind, placebo-controlled, repeated-measures study in 36 healthy male subjects. Participants were examined for trait anxiety and side effects and underwent repeated transcranial magnetic stimulation (TMS) assessments, including motor evoked potentials (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP).

Results: We observed attenuation of MEPs by alprazolam but not by etifoxine. SICI was not significantly affected by alprazolam or etifoxine. However, the response pattern indicated a lowered SICI threshold after the administration of etifoxine and alprazolam compared to the placebo. ICF and CSP were influenced by neither medication. Alprazolam led to higher sedation and subjective impairment of concentration compared to etifoxine. Individual anxiety trait scores did not affect TMS parameters.

Discussion: This study indicated a favorable side effect profile of etifoxine in healthy volunteers. Moreover, it revealed differential GABA-related effects on neuromuscular function by means of TMS. The side effects and TMS profile of etifoxine are compatible with the involvement of neurosteroidogenesis and a predominant α3 subunit modulation compared to alprazolam.

Introduction: The effectiveness of ECT relies on the induction of a generalized cerebral seizure. Among others, seizure quality (SQ) is potentially influenced by the anesthetic drug used. Commonly used anesthetics comprise barbiturates, etomidate, propofol, and esketamine, with different characteristics and impacts on seizure parameters. So far, no studies have compared the influence of methohexital vs. a combination of propofol/esketamine on established SQ parameters.

Methods: This retrospective longitudinal study compared eight established SQ parameters (PSI, ASEI, MSC, midictal amplitude, motor and electroencephalography (EEG) seizure duration, concordance, PHR) before and after the change from propofol/esketamine to methohexital in 34 patients under maintenance ECT. Each patient contributed four measurements, two before and two after the anesthesia change. Anesthesia dose, stimulus dose, electrode placement, and concomitant medication remained unchanged throughout the analyzed treatments.

Results: Under methohexital (M=88.97 mg), ASEI (p=0.039 to 0.013) and midictal amplitude (p=0.022 to<0.001) were significantly lower, whereas seizure duration (motor and EEG) was significantly longer when compared to propofol/esketamine (M=64.26 mg/51.18 mg; p=0.012 to<0.001). PSI, MSC, seizure concordance, and PHR were not affected by the anesthetic used.

Discussion: Although to what extent these parameters correlate with the therapeutic effectiveness remains ambiguous, a decision for or against a particular anesthetic could be considered if a specific SQ parameter needs optimization. However, no general superiority for one specific substance or combination was found in this study. In the next step, anesthetic effects on treatment response and tolerability should be focused on.

Background: Z-drugs are nonbenzodiazepine hypnotics used for sleep initiation and maintenance; these drugs increase the risk of fall-related injuries in older adults. The American Geriatrics Society's Beers criteria classifies Z-drugs as high-risk and strongly recommends avoiding prescribing Z-drugs to older adults due to adverse effects. The study objectives were to determine the prevalence of Z-drug prescribing among Medicare Part D patients and identify state or specialty-dependent prescribing differences. This study also aimed to determine prescribing patterns of Z-drugs to Medicare patients.

Methods: Z-drug prescription data was extracted from the Centers for Medicare and Medicaid Services State Drug Utilization Data for 2018. For all 50 states, the number of prescriptions per 100 Medicare enrollees and days-supply per prescription was determined. The percentage of total prescriptions prescribed by each specialty and the average number of prescriptions per provider within each specialty was also determined.

Results: Zolpidem was the most prescribed Z-drug (95.0%). Prescriptions per 100 enrollees were significantly high in Utah (28.2) and Arkansas (26.7) and significantly low in Hawaii (9.3) relative to the national average (17.5). Family medicine (32.1%), internal medicine (31.4%), and psychiatry (11.7%) made up the largest percentages of total prescriptions. The number of prescriptions per provider was significantly high among psychiatrists.

Discussion: Contrary to the Beers criteria, Z-drugs are prescribed to older adults at high rates.

Introduction: Many nations have implemented lockdowns to prevent and minimize the spread of infections in healthcare settings. However, the impact of lockdown duration on mental health remains controversial.

Methods: We conducted a retrospective study using online questionnaires to assess the mental health status of the general population during the Shanghai lockdown period from March to May 2022. The mental health of the participants was evaluated by the 12-item General Health Questionnaire (GHQ-12), in which a cut-off score of 12 or more indicated psychological distress. A logistic regression model was used to evaluate the relationship between lockdown duration and mental health.

Results: Among 2139 participants (mean age: 26.12 years, standard deviation: 6.37, 731 females; 1378 unmarried; 1099 Shanghai residents), approximately 47% reported psychological distress (GHQ-12≥12). Participants exposed to lockdown reported significantly higher GHQ-12 scores (11.93±6.81 vs. 8.73±6.35, p<0.001). In our logistic regression model, participants who experienced the longest lockdown (43-61 days) had a significantly higher risk of psychological distress compared with those who did not (odds ratio: 3.10, 95% confidence interval: 2.06-4.70, p<0.001).

Discussion: Lockdown duration significantly affects mental health, with longer lockdown duration being associated with worse mental health status. The relationship between lockdown and mental health should not be neglected in case of lockdown in response to future pandemics.

Circadian rhythms are biological oscillations, that perpetuate themselves even in the absence of "zeitgebers" (external time cues), with a period of approximately 24 hours. The master pacemaker is the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is entrained by environmental factors, particularly light, to the 24-hour light-dark cycle by the Earth's rotation. Peripheral circadian oscillators, located in multiple cell types and tissues, are controlled by signals arising from the SCN and from the environment, particularly food intake, hormonal signals and body-temperature fluctuations. Circadian rhythmicity is observable in almost every cell of living organisms including humans and, for example in cell cultures, these rhythms persist even without the SCN 1 2.

Background: The existing literature on the use of mood stabilizers (MS) in children and adolescents with anorexia nervosa (AN) is limited, for the most part, to small case studies.

Methods: This was an observational, naturalistic, propensity score-matched study. Subjects treated and not-treated with MS were compared by being matched via propensity score on age, sex, concurrent atypical antipsychotics, and concurrent antidepressants. General and AN-specific psychopathology was assessed with Symptom Check List-90-R, Beck Depression Inventory-II, Eating Disorders Inventory-3, and Body Uneasiness Test-A. Potential differences in admission-discharge modifications (body mass index (BMI), psychopathology) among the two groups were assessed. Finally, re-hospitalizations after 1-year follow-up were assessed with Kaplan-Meier analyses.

Results: The study enrolled 234 hospitalized patients (15.9+/-3.3 years; 26, 11.1% receiving MS). After propensity-score matching, 26 MS patients matched with 26 MS-not-treated subjects were included. MS were used for a mean of 126.1 (+/-87.3) days, and two cases of side effects were documented (alopecia and somnolence with valproate). No significant difference between MS-treated and not-treated patients emerged concerning admission-discharge improvements in BMI and AN-specific or general psychopathology. The cumulative survival from re-hospitalization at 12 months was 64,4% (95%-CI, 31.3-97.5) for MS and 58.7% (95%-CI, 22.2-95.2) for MS-not-treated subjects. No significant difference in survival rate emerged (hazard ratio, 0.04; Log-rank test: p=0.846).

Conclusions: This propensity score-matched study expands on the scant existing evidence of the use and side effects of MS in children and adolescents with AN. These results should be assessed in wider longitudinal samples.

The central oscillator for the inner clock is the suprachiasmatic nuclei of the hypothalamus. Furthermore, many peripheral oscillators are present in tissues such as skin. Human derived fibroblasts provide an advantageous model to study circadian rhythmicity as well as the influence of pharmacological drugs on circadian gene expression. Importantly, the synchronization of the circadian system of fibroblasts can be done by different methods. The review presents an overview of the current knowledge of different synchronization methods mostly used in mice or rat fibroblasts. Furthermore, the review sums up and discusses the role of norepinephrine as a possible synchronizer agent.