Journal of Psychopharmacology最新文献

Rationale: Transcranial magnetic stimulation (TMS) is a well-established, noninvasive method for modulating cortical activity and has demonstrated efficacy in the treatment of depression. This study investigated potential interaction effects between antipsychotic augmentation and TMS efficacy using clinical records from two independent sites. In addition, exploratory analyses examined the association between resting motor threshold (RMT) and treatment outcomes.

Methods: We analyzed naturalistic data from patients with depressive symptoms treated at the TMS outpatient departments in Augsburg (n = 53) and Regensburg (n = 120). Depressive symptom severity was assessed using the Beck Depression Inventory, Hamilton Rating Scale for Depression-17, and Major Depression Inventory at baseline, during treatment, and upon treatment completion. Patients were grouped according to whether or not they received antipsychotic augmentation. Group comparisons were conducted using Mann-Whitney U tests. For secondary analyses, scatter plots explored associations between baseline RMT and improvements in depressive symptoms, and correlation coefficients were calculated.

Results: At the Augsburg site, 2 weeks after treatment initiation, patients not receiving antipsychotic augmentation exhibited significantly greater improvement in depressive symptom severity. However, differences between groups were not significant at treatment initiation or upon completion. Further, RMT analysis at Augsburg indicated a numerical but nonsignificant correlation with treatment outcome. At the Regensburg site, no consistent interaction effects were observed, and RMT analyses revealed nonsignificant correlations.

Conclusions: Taken together, these findings suggest that TMS can remain effective in patients receiving concomitant antipsychotic augmentation alongside antidepressant and TMS treatment. Future research could usefully examine whether TMS remains effective in patients receiving different kinds of antipsychotic medication.

Background: Negative allosteric modulators (NAMs) of gamma-aminobutyric acid (GABA_A) receptors targeting the α₅-subunit, primarily expressed on glutamate pyramidal neurons in the hippocampus and cortex, reduce inhibitory tone and enhance α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor throughput. The α₅-GABA_A-NAM, L-655,708, has shown rapid and sustained antidepressant-like effects in rodents.

Aim: This study aimed to investigate the effects of L-655,708 on the monoamine and glutamate systems in rats in relation to the antidepressant-like response.

Methods: Male Sprague-Dawley rats received a single dose of L-655,708 (3 mg/kg, i.p.) or vehicle. In vivo extracellular recordings were conducted in the dorsal raphe nucleus (DRN), locus coeruleus (LC), ventral tegmental area (VTA), and medial prefrontal cortex (mPFC) acutely, 1 day, 1 week, and 2 weeks post-injection. AMPA and N-methyl-D-aspartate (NMDA) responsiveness in the hippocampal CA1 region was assessed using microiontophoresis.

Results: The NMDA-induced response in the CA1 hippocampus was significantly reduced 1 day post-injection of L655,708, while the AMPA response remained unchanged. Although mPFC pyramidal neurons' firing was not changed, there was a two-fold increase in population activity of VTA dopamine (DA) neurons 1 day post-injection, lasting up to 1 week. Flumazenil, the benzodiazepine site antagonist, and 2,3-dioxo-6-nitro-7-sulfamoyl-benzo[f]quinoxaline (NBQX), an AMPA receptor antagonist, blocked this effect. L-655,708 had no acute effect on firing activity of serotonin or norepinephrine neurons.

Conclusion: L-655,708 enhanced VTA DA neuron population activity for up to 1 week after a single injection. This effect was dependent on AMPA and took place through action on the benzodiazepine site.

Background: Most individuals diagnosed with borderline personality disorder (BPD) use psychotropic medications. BPD symptom severity is elevated in young adulthood, but medication utilisation studies in young adults with BPD are lacking.

Aims: To investigate the use of central nervous system (CNS) acting medications among young adults (aged 18-24), who were diagnosed with BPD, focusing on the years around the first established diagnosis.

Methods: A cohort study of all individuals with a registered BPD diagnosis in Sweden was conducted using national population register data. Dispensed prescriptions between July 2005 and June 2020 were utilised. Prevalent use, long-term use, and co-medication were investigated during specific 1-year periods: the year before, and then the first, second, and third year after diagnosis.

Results: Medication use peaked for all three measures in the year following the first BPD diagnosis: 90.3% used CNS-acting medication during that year, and antidepressants were the most used group (70.1%). Furthermore, 74.5% used medication for >12 months, and 34.8% used ⩾3 medication groups in co-medication. Compared to a reference group of individuals diagnosed with depression, the BPD group used more medication. In the depression group, 87.5% used medication, 55.2% used medication for >12 months, and 3.8% used ⩾3 medication groups in co-medication. Moreover, medication use increased from 2006 to 2019.

Conclusion: This indicates the importance of continuously evaluating risks and benefits with medication use, and in having easy access to up-to-date guidance about best clinical practice for individuals diagnosed with BPD, to facilitate appropriate and safe medication use.

We carried out a systematic review of modern-era (1990-2025) placebo-controlled studies assessing the acute and post-acute effects of lysergic acid diethylamide, dimethyltryptamine and psilocybin on cognitive and psychological functions. From February 28 to March 19, 2025, PubMed and APA PsychINFO were systematically searched for placebo-controlled studies examining the influence of psychedelics on empathy, reaction time, attention, inhibition, emotional processing, memory, cognitive flexibility, and related cognitive functions using experimental methods. Additional searches were done in Google Scholar. The systematic review included 32 studies. Psychedelics tended to enhance emotional empathy but had no effect on cognitive empathy. Psychedelics impaired, enhanced or had no effect on memory depending on the task and timing of the assessment. Dose-dependent impairments were seen in many of the reaction time, attention, and inhibition tasks, although some studies found no effects. Some studies found impaired recognition of negative stimuli under the acute effects of psychedelics. The findings regarding cognitive flexibility were mixed. Many studies had small samples, and it is hard to find a reliable placebo due to psychedelics' unique subjective effects. Future studies should use bigger samples and also study more longitudinal effects of psychedelics on cognitive and psychological functions.

Background: Incretin therapies have shown promise in managing antipsychotic-associated weight gain and psychological benefits in individuals with mental health disorders. In populations at high risk for suicidal behaviors, it is crucial to understand how these therapies affect risk of suicidality or self-harm.

Aims: This study investigates the effect of incretin therapy on suicidality or self-harm in individuals with severe mental disorders (SMDs).

Methods: A retrospective cohort study was developed using the TriNetX Research Network, a federated database collating de-identified data from electronic health records. Adult individuals diagnosed with a psychotic disorder and treated with an antipsychotic were included. Cohorts were differentiated based on concomitant incretin therapy and balanced using 1:1 propensity score matching. Psychiatric outcomes were compared during the 5 years following the index date.

Results: After matching, each cohort consisted of 21,984 individuals. Receipt of incretin therapy was associated with reduced relative risk (RR) for suicidal ideation (RR: 0.48; 95% CI: 0.45-0.51; p < 0.0001), suicide attempts (RR: 0.64; 95% CI: 0.52-0.78; p < 0.0001), and self-harm (RR: 0.61; 95% CI: 0.56-0.67; p < 0.0001) compared to the no treatment group. Additionally, individuals receiving incretin therapy had lower risk for all-cause mortality (RR: 0.50; 95% CI: 0.46-0.53; p < 0.0001), overdose (RR: 0.57; 95% CI: 0.49-0.65; p < 0.0001), and substance use disorders (RR: 0.76; 95% CI: 0.74-0.77; p < 0.0001).

Conclusions: Our findings suggest incretin therapies may have protective effects against various psychiatric and behavioral risks in individuals with SMD.

A popular model organism for studying neural and molecular mechanisms of behavior, the zebrafish (Danio rerio) displays a wide range of robust and quantifiable social phenotypes, including shoaling/schooling, social preference and learning, as well as aggression and mating behaviors. Zebrafish social behavior is influenced by various neurotransmitters and hormones (including serotonin, dopamine, isotocin, cortisol, and endocannabinoids) and can be modulated experimentally, including genetically and pharmacologically. Here, we summarize current knowledge on neurobiology and neuropharmacology of zebrafish social behavior, and discuss various effects of drugs and other manipulations that target this critical behavioral domain.

Objective: Clozapine is a gold-standard antipsychotic for treatment-resistant schizophrenia, increasingly used off-label for severe autism spectrum disorder (ASD) with irritability or disruptive behaviors. This study evaluated clozapine's efficacy and tolerability in children and adolescents with ASD or schizophrenia spectrum disorders (SSDs).

Methods: A retrospective review of 26 inpatients (ASD: n = 8; SSD: n = 18) treated with clozapine included demographics, dosing, and hospitalization data. Symptom severity was assessed with the Clinical Global Impression-Severity Scale (CGI-S), Scale for the Assessment of Negative Symptoms (SANSs), Scale for the Assessment of Positive Symptoms (SAPSs), and Aberrant Behavior Checklist (ABC). Side effects were evaluated with the Ugvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale. Hematological parameters-white blood cells, neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR)-were compared pre-treatment and at 6 months.

Results: Of the 26 patients, 50% had early-onset schizophrenia, 30.8% had ASD, and 19.2% had schizoaffective disorder. Clozapine was initiated at a mean age of 15.8 years, with a mean dose of 284.6 mg/day. Both SSD (p < 0.001) and ASD (p = 0.01) groups showed significant CGI improvement. SANS and SAPS improved in SSD (p = 0.001, p < 0.001); ABC improved in ASD (p = 0.012). UKU scores decreased in SSD (p < 0.001) and trended downward in ASD (p = 0.38). Hypersalivation (61.5%), increased appetite (53.8%), and sedation (34.6%) were common; no discontinuations occurred. Neutrophils increased (p = 0.007), and lymphocytes decreased (p = 0.037), with significant NLR elevation in SSD (p = 0.006).

Conclusion: Clozapine demonstrated strong efficacy and improved tolerability, reducing side effects compared to prior polypharmacy in refractory pediatric ASD and SSD.

Background: Lithium monotherapy has been recommended as first-line maintenance or long-term pharmacological therapy for bipolar disorder (BD). Previous research has linked early lithium use with better outcomes for people with BD. Despite extensive evidence as an effective treatment for BD, lithium prescribing continues to decline.

Aims: Our primary aim was to determine the time between initial assessment by mental health services and lithium initiation in people with BD who were prescribed and concordant with lithium. Secondary objectives included determining the time between the first assessment and recorded BD diagnosis, number of prior mood episodes, polarity when lithium was prescribed and number of antipsychotics before lithium initiation.

Methods: Free-text clinical notes were extracted from a de-identified electronic health record database. Eligible records comprised adults with a BD diagnosis who were concordant with lithium treatment.

Results: Eighty-eight people were identified, based on inclusion and exclusion criteria. Median time between first assessment and lithium initiation was 659 days. Median time between first assessment and BD diagnosis was 220 days, with a median of 2.5 mood episodes and 2 antipsychotics prescribed prior to lithium. Around 30% of people presented with manic symptoms at the time of lithium prescription. There is a significant delay between first contact with services and initiation of lithium in people with BD.

Conclusions: This highlights the potential for earlier intervention with lithium, which could improve outcomes for people with BD.

Rationale: Classical psychedelics-a broad class of compounds that include psilocybin, lysergic acid diethylamide, dimethyltryptamine, and mescaline-have shown significant promise for the treatment of mental health conditions in recent clinical trials. Organizations such as the National Network of Depression Centers (NNDCs) can play a pivotal role in uniting researchers and clinicians working in this field to explore and synthesize existing evidence as well as characterize emerging challenges.

Objectives: We outline several categories of challenges that have emerged in the context of clinical trials with psychedelic drugs, drawing from our collective empirical observations as well as the extant literature. While these challenges have been presented in the context of clinical trial environments, many of them are likely to persist if and when psychedelic treatments become approved and are implemented in psychiatric clinical practice.

Results: We describe four categories of challenges in the context of clinical trial participants-(1) treatment nonresponse, (2) expectancy effects and functional unblinding, (3) post-session psychological difficulties, and (4) contagion effects-and provide management strategies for study teams to mitigate associated risks.

Conclusions: Classical psychedelics show therapeutic promise as mental health treatments. Studying them properly presents unique and unprecedented challenges that require researchers to develop sophisticated strategies to navigate nonresponse, expectancy effects, functional unblinding, post-session psychological issues, and possible contagion effects to responsibly advance this field. The NNDC and similar organizations are well-positioned to guide best practices and ensure the responsible advancement of this promising field.