Pharmacopsychiatry最新文献

Introduction: Pharmacoepidemiological data suggest that lithium prescriptions for bipolar disorder are gradually decreasing, with less attention having been paid to other indications.

Methods: We examined lithium prescriptions between 1994 and 2017 in data provided by the Drug Safety in Psychiatry Program AMSP, including psychiatric hospitals in Germany, Austria and Switzerland. We compared lithium use for different diagnoses before and after 2001 and in three periods (T1: 1994-2001, T2: 2002-2009, and T3: 2010-2017).

Results: In a total of 158,384 adult inpatients (54% female, mean age 47.4±17.0 years), we observed a statistically significant decrease in lithium prescriptions between 1994-2000 and 2001-2017 in patients with schizophrenia spectrum disorder from 7.7% to 5.1% and in patients with affective disorders from 16.8% to 9.6%. Decreases in use were also observed for diagnostic subgroups: schizoaffective disorder (ICD-10 F25: 27.8% to 17.4%), bipolar disorder (F31: 41.3% to 31%), depressive episode (F32: 8.1% to 3.4%), recurrent depression (F33: 17.9% to 7.5%, all: p<0.001) and emotionally unstable (borderline) personality disorder (6.3% to 3.9%, p=0.01). The results in T1 vs. T2 vs. T3 were for F25: 26.7% vs. 18.2% vs. 16.2%, F32: 7.7% vs. 4.2% vs. 2.7%, F33: 17.2% vs. 8.6% vs. 6.6% and for F31: 40.8% vs. 31.7% vs 30.0%, i. e. there was no further decrease for lithium use in bipolar disorder after 2002. Lithium's main psychotropic co-medications were quetiapine (21.1%), lorazepam (20.6%), and olanzapine (15.2%).

Discussion: In inpatients, the use of lithium has decreased in patients with bipolar disorder and also with various other psychiatric diagnoses.

Introduction: There have been substantial increases in the use of Schedule II stimulants in the United States. Schedule II stimulants are the gold standard treatment for attention-deficit hyperactivity disorder (ADHD), but also carry the risk of addiction. Since the neurocognitive deficits seen in ADHD resemble those of chronic cannabis use, and the rise in stimulant use is incompletely understood, this study sought to determine if recreational cannabis (RC) legalization increased distribution rates of Schedule II stimulants.

Methods: The distribution of amphetamine, lisdexamfetamine, and methylphenidate were extracted from the ARCOS database of the Drug Enforcement Administration. The three-year population-corrected slopes of distribution before and after RC sales were evaluated.

Results: Total stimulant distribution rates were significantly higher in states with RC sales after (p=0.049), but not before (p=0.221), program implementation compared to states without RC. Significant effects of time (p<0.001) and RC sales status (p=0.045) were observed, while time x RC sales status interaction effects were not significant (p=0.406).

Discussion: RC legalization did not contribute to a more pronounced rise in Schedule II stimulant distribution in states. Future studies could explore the impact of illicit cannabis use on stimulant rates and the impact of cannabis sales on distribution rates of non-stimulant ADHD pharmacotherapies and ADHD diagnoses.

Introduction: People addicted to illegal drugs were discussed as a risk group for SARS-CoV-2 infections, with increased susceptibility and a severe course of infection.

Methods: In this study, the frequency of SARS-CoV-2 infections of drug-dependent persons admitted to inpatient detoxification treatment in five psychiatric hospitals was determined by implementing routine polymerase chain reaction (PCR)-testing at admission (9/2020) up to one year. Main substance-related diagnosis, comorbid respiratory disease, housing situation, and current opioid maintenance treatment (OMT) were documented. An age-matched control group of psychiatric inpatients without dependence from illegal drugs was established.

Results: Data from 1675 patients (male 79.5%; mean age 39.5 years; opioid dependence 81.5% homelessness; 2.4%; chronic respiratory disease 6.3%) were included. Out of 1365 patients dependent on opioids, 50.2% were currently in OMT. Six (3 female; mean age 40.3 years) patients tested positive for SARS-CoV-2 by PCR (0.36%), and none showed symptoms of COVID-19. All six were opioid dependent, 5 currently not in OMT. In the control group, 11 out of 1811 inpatients tested positive (0.61%).

Discussion: The rate of SARS-CoV-2-infections in persons with dependence on illegal drugs was not increased compared to a control group of psychiatric patients. OMT is presumably a protective factor, e. g. in the participating cities, OMT facilities offered an easy access to vaccination programs. In contrast, drug addicts in the USA were severely affected by the pandemic. Differences between countries might partially be explained by social factors such as the higher availability of OMT in Germany and a much lower frequency of homelessness.

Introduction: Lurasidone (LUR) was compared with quetiapine extended release (QUE-ER) regarding 1-year discontinuation in patients with bipolar depression (n=317).

Methods: This is a retrospective cohort study.

Results: Although the time to all-cause discontinuation was estimated using the Kaplan-Meier survival curve with log-rank tests to compare treatment groups, no difference was found (p=0.317). The Cox proportional hazard model revealed that only the presence of adverse events (AEs) is associated with increased treatment discontinuation (p<0.0001). The most common AEs were akathisia for LUR (17.7%) and somnolence for QUE-ER (34.7%). In other Cox models divided by LUR or QUE-ER, the presence of akathisia or somnolence was associated with increased LUR (p=0.0205) or QUE-ER (p<0.0001) discontinuation, respectively.

Discussion: The acceptability of both antipsychotics to bipolar depression in clinical practice may be similar. However, specific AEs for each antipsychotic (LUR: akathisia and QUE-ER: somnolence) were associated with high treatment discontinuation.

Introduction: Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents.

Methods: A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases.

Results: Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function.

Discussion: Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.

Introduction: Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, CYP2C19, CYP2D6, CYP3A4, and ABCB1, and its effect on these outcomes.

Methods: The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole. DNAm quantitative trait loci (mQTL), identified by SNP-CpG associations between 20 SNPs and 60 CpG sites in whole blood, were tested for associations with our outcomes, followed by causal inference tests (CITs) to identify methylation-mediated genetic effects.

Results: Eleven cis-SNP-CpG pairs (q<0.05) constituting four unique SNPs were identified. Although no significant associations were observed between mQTLs and response/remission, CYP2C19 rs4244285 was associated with treatment-related weight gain (q=0.027) and serum concentrations of ESC_adj (q<0.001). Between weeks 2-4, 6.7% and 14.9% of those with *1/*1 (normal metabolizers) and *1/*2 (intermediate metabolizers) genotypes, respectively, reported ≥2 lbs of weight gain. In contrast, the *2/*2 genotype (poor metabolizers) did not report weight gain during this period and demonstrated the highest ESC_adj concentrations. CITs did not indicate that these effects were epigenetically mediated.

Discussion: These results elucidate functional mechanisms underlying the established associations between CYP2C19 rs4244285 and ESC pharmacokinetics. This mQTL SNP as a marker for antidepressant-related weight gain needs to be further explored.

Introduction: Whether psychiatric symptoms after recovery from coronavirus disease 2019 (COVID-19) are specific to this illness remains unclear.

Methods: In this retrospective study, the Diagnosis Procedure Combination data and outpatient clinic data were used for patients who received inpatient treatment in Saiseikai-affiliated hospitals for COVID-19 or other respiratory tract infections (non-COVID) from 2020 to 2022. The primary outcome was new prescriptions of psychotropic drugs after discharge (i. e., prescriptions of psychotropics to patients who had not received them before or during their hospitalization). Values of interest were compared between groups using the chi-square test or Fisher's exact test. A COX proportional-hazards model was used to examine factors associated with psychotropic prescriptions after discharge in age- and sex-matched COVID-19 and non-COVID patients.

Results: Of 31,993 chart records, 19,613 were excluded due to a positive history with psychiatric disorders (n=2,445), prescriptions of psychotropics (n=744), and no follow-ups (n=16,424). Thus, 3,648 COVID-19 and 8,732 non-COVID patients were included (mean [range] duration of follow-up, days: 146.9 [1-727] and 239.2 [1-729], respectively). Two hundred and four (5.6%) of the 3,648 patients with COVID-19 received psychotropic prescriptions after discharge. No statistically significant differences were observed in the prescription rates of any psychotropic category between the COVID-19 and non-COVID groups. An increase in severity during hospitalization was significantly associated with more frequent psychotropic prescriptions (hazard ratio 1.83, p<0.001).

Discussion: The development of psychiatric symptoms should be closely observed, especially in patients who experienced increased severity during hospitalization, regardless of whether they suffered from COVID-19.

Introduction: Cariprazine is an atypical dopamine receptor partial agonist antipsychotic available in the form of capsules. Although capsules are one of the most desirable routes of administration, there are certain situations (e. g., in an acute psychiatric setting, or when swallowing difficulties, or liquid shortages are present) when they cannot be administered. Therefore, alternative solutions like orodispersible tablets are needed. This study aimed to investigate the bioequivalence of a newly developed orodispersible tablet to the commercially available hard gelatine capsule of cariprazine 1.5 mg.

Methods: This was a phase I, open-label, randomized, single-dose bioequivalence study. It had a 2-period, 2-sequence, cross-over design, where each subject received one test and one reference product in a randomized sequence, separated by a wash-out period of 55 days. Blood sampling was performed over 72 h after dosing. Cariprazine concentrations were analyzed by a validated HPLC-MS/MS method. Standard bioequivalence statistics was applied to PK parameters calculated by non-compartmental analysis. Safety measures were analyzed descriptively.

Result: Pharmacokinetic data of 43 healthy volunteers and safety data of 54 subjects was analyzed. Cariprazine AUC_0-72h and C_max geometric mean ratios were 117.76% and 100.88%, respectively. The 90% confidence intervals were within the pre-defined bioequivalence acceptance limits of 80.00% - 125.00%. Safety data was in line with the Summary of Product Characteristics of Cariprazine.

Discussion: The result of this clinical trial proved the bioequivalence of the new orodispersible tablet formulation when compared to hard gelatine capsules, enabling an alternative option for treatment of those suffering from schizophrenia.

Background: Evidence indicates an association between immune dysregulation and major depressive disorder (MDD). Pentoxifylline (PTX), a phosphodiesterase inhibitor, has been shown to reduce pro-inflammatory activities. The aim of this study was to evaluate changes in depressive symptoms and pro-inflammatory markers after administration of PTX as an adjunctive agent to citalopram in patients with MDD.

Methods: One hundred patients were randomly assigned to either citalopram (20 mg/day) plus placebo (twice daily) (n=50) or citalopram (20 mg/day) plus PTX (400 mg) (twice daily) (n=50). The Hamilton Depression Rating Scale-17 (HAM-D-17) scores at baseline, weeks 2, 4, 6, 8, 10, and 12 and serum levels of interleukin1-β (IL-1-β), tumor necrosis factor-α, C-reactive protein, IL-6, serotonin, IL-10, and brain-derived neurotrophic factor (BDNF) at baseline and week 12 were evaluated.

Results: HAM-D-17 score in the PTX group significantly reduced in comparison to the control group after weeks 4, 6, 8,10, and 12 ((LSMD): - 2.193, p=0.021; - 2.597, p=0.036; - 2.916, p=0.019; - 4.336, p=0.005; and - 4.087, p=0.008, respectively). Patients who received PTX had a better response (83%) and remission rate (79%) compared to the placebo group (49% and 40%, p=0.006 and p=0.01, respectively). Moreover, the reduction in serum concentrations of pro-inflammatory factors and increase in serotonin and BDNF in the PTX group was significantly greater than in the placebo group (p<0.001).

Conclusion: These findings support the safety and efficacy of PTX as an adjunctive antidepressant agent with anti-inflammatory effects in patients with MDD.