Journal of Psychopharmacology最新文献

Background: Behavioral and psychological symptoms of dementia (BPSD) affect patients' and caregivers' well-being. Cannabinoids may offer a promising therapeutic option for managing BPSD.

Aims: This systematic review aims to explore the strengths of using this class of substances in the context of dementia care.

Methods: We conducted a comprehensive search across Embase Ovid, PubMed, Cochrane Library, APA PsycInfo, and Web of Science, identifying 1839 studies, with 14 selected for full review. Quality was assessed using the Newcastle-Ottawa and the modified Jadad Scales.

Results/outcomes: Ten studies (278 participants) were finally included. They showed cannabinoids helped reduce agitation and nocturnal disturbances.

Conclusions/interpretation: In conclusion, cannabinoids show promise in managing BPSD in dementia, with good tolerability and safety. Further studies could solidify these findings.

Human facial emotion recognition (FER) is an evolutionarily preserved process that influences affiliative behaviours, approach/avoidance and fight-or-flight responses in the face of detecting threat cues, thus enhancing adaptation and survival in social groups. Here, we provide a narrative literature review on how human FER is modulated by neurotransmitters and pharmacological agents, classifying the documented effects by central neurotransmitter systems. Synthesising the findings from studies involving functional neuroimaging and FER tasks, we highlight several emerging themes; for example, noradrenaline promotes an overall positive bias in FER, while serotonin, dopamine and gamma-aminobutyric acid modulate emotions relating to self-preservation. Finally, other neurotransmitters including the cholinergic and glutamatergic systems are responsible for rather non-specific pro-cognitive effects in FER. With the ongoing accumulation of evidence further characterising the individual contributions of each neurotransmitter system, we argue that a sensible next step would be the integration of experimental neuropharmacology with computational models to infer further insights into the temporal dynamics of different neurotransmitter systems modulating FER.

Background: Lithium, a mainstay treatment for bipolar disorders, has shown promise in treating cognitive impairments. However, concerns about cognition-related side effects persist.

Aims: We aimed to synthesise the evidence on how lithium affects cognition by comparing cognitive performance before and after starting lithium treatment.

Methods: A systematic search was conducted to identify studies examining lithium's effects on cognition. The review considered studies with adult human participants that reported quantitative cognitive outcomes using within-subject comparisons between lithium-absent and lithium-present conditions.

Results: Thirty-two articles describing 30 studies were included (727 participants, approximately 54% female, mean age ± 50 years old). The studies exhibited significant heterogeneity within cognitive domains, including global cognition (15 studies), memory (19 studies), processing and psychomotor speed (8 studies), attention (9 studies), verbal fluency (4 studies) and executive function (6 studies). The included studies comprised 16 randomised controlled trials (RCTs) and 14 non-RCTs, with study populations ranging from individuals with affective disorders (13 studies) to neurocognitive disorders (11 studies) and healthy individuals (6 studies). Some studies reported cognitive enhancements, particularly in individuals with affective disorders, while others documented declines or mixed results.

Conclusions: Definitive conclusions regarding lithium's isolated cognitive effects remain elusive, particularly considering the influence of factors such as affective state, population and methodological heterogeneity among studies. Further research is needed to conclusively determine the raw cognitive impacts of lithium therapy, requiring larger RCTs across distinct populations. Prioritising the resolution of main symptoms should remain the primary therapeutic goal of lithium treatment.

Background: Neuroimaging studies have linked the beneficial effects of subanaesthetic ketamine doses in psychiatric conditions characterized by chronic stress pathology (CSP) to altered functional connectivity (FC) within the pregenual anterior cingulate cortex (pgACC). Previous research indicates a potential role of glutamate concentration in FC changes; however, the precise relationship between glutamate release and increased FC remains unclear. Lamotrigine, a glutamate-release inhibitor, allows deeper exploration of this relationship. Additionally, CSP and treatment efficacy are closely associated with alterations in working memory (WM), necessitating the examination of FC during resting state and WM tasks.

Aims: This study aimed to investigate the acute and sustained effects of altered glutamate transmission induced by ketamine and lamotrigine on pgACC FC during rest and WM.

Methods: In this double-blind, placebo-controlled, randomized, single-dose, parallel-group study, resting-state and task-related functional Magnetic Resonance Imaging (fMRI) data were collected at baseline, during and 24 h after ketamine administration in 75 healthy participants. Participants were randomized to receive ketamine, ketamine with lamotrigine pretreatment or placebo. FC analyses utilized pgACC masks derived from the Julich Brain Atlas.

Results: Ketamine infusion significantly enhanced FC between the pgACC and dorsomedial prefrontal cortex during the WM task, and increased resting-state FC between the pgACC and left insula. These effects were absent following lamotrigine pretreatment.

Conclusions: The findings support the hypothesis that ketamine's favourable effects, reflected by enhanced FC within key neural networks, may be attributable to glutamate release.

Background: Major depressive disorder (MDD) is a prevalent psychiatric illness, significantly contributing to disability and suicide rates. While dysfunctions in neurotransmission, notably monoaminergic transmission, are commonly attributed to MDD, involvement of the glutamatergic system in comorbid depressive disorders suggests its potential as a target for antidepressant therapy. Despite evidence of diminished glutamatergic neuron activity in the midbrain ventrolateral periaqueductal gray (vlPAG) in rodent models of depression-which projects to the ventral tegmental area (VTA), a region regulating depression-like behaviors-the precise neurocircuit mechanisms within the vlPAG remain unclear.

Methods: To investigate dysregulation of glutamatergic transmission in the vlPAG and its role in depression-like behavior, we combined behavioral testing, pharmacological manipulation, retrograde tracing, and electrophysiological recording in male C57BL/6 mice.

Results: Mice receiving intravlPAG infusion of the mGlu2/3 receptor antagonist LY341495 exhibited reversal of depression-like behaviors. Chronic restraint stress (CRS) elicited depression-like behavior, whereas intravlPAG administration of LY341495 reversed these behaviors. VTA-projecting vlPAG neurons exhibited reduced frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) and decreased neuronal excitability. Blocking mGlu2/3 receptors, which act as autoreceptors inhibiting glutamate release, in the vlPAG rescued these effects. Moreover, intravlPAG microinjection of the L-type voltage-dependent calcium channel (VDCC) blocker verapamil, tropomyosin-related kinase B (TrkB) receptor antagonist ANA-12, mammalian target of rapamycin complex 1 inhibitor rapamycin, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione prevented LY341495-induced reversal of depression-like behaviors.

Conclusions: This provides the first direct evidence that blockade of mGlu2/3 receptors in the vlPAG ameliorates depression-like behavior, highlighting their role in regulating vlPAG-VTA neurocircuits implicated in MDD pathophysiology.

Ketamine has emerged as a putative rapid-acting treatment option for psychiatric disorders, particularly treatment-resistant depression. Chronic recreational ketamine use is associated with ketamine-induced urological toxicity, raising concerns over the safety of repeated ketamine treatments. This systematic review aimed to synthesise urological findings from clinical trials and observational studies using ketamine for the treatment of psychiatric disorders. Electronic databases were searched up until 4th April 2024 for trials and observational studies using ketamine treatment for psychiatric disorders in adults, and which reported assessment of urinary, bladder or renal symptoms. Twenty-seven studies were included, mostly in depressive disorders (N = 24). Urological symptoms were reported in 0%-24.5% of patients receiving ketamine treatment; symptoms tended to be mild or moderate in severity. Where reported, continuous outcome measures (urinary parameters and symptom questionnaires) did not show significant changes from baseline to follow-up. Only 15% of studies were rated low risk of bias. Most studies did not assess long-term ketamine treatment, and many included undefined or passive monitoring of urological symptoms rather than systematic assessment. Based on the limited data available, ketamine treatment does not appear to be associated with elevated risk of urological symptoms; however, further long-term studies are required.

Background: The optimal lumateperone dose for bipolar depression remains uncertain.

Aims: To examine its dose-response relationship for efficacy and safety.

Methods: We systematically searched major databases to 1 July 2025. Efficacy outcomes included change in depression severity, global illness severity, quality of life, responder, and remitter rates. Safety outcomes included all-cause dropout, discontinuations due to adverse event (AE), treatment-emergent AE, mania, suicidality, extrapyramidal symptoms, body weight, lipid profile, and fasting glucose. A one-step dose-response meta-analysis generated effect sizes, reported as standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs).

Results: Three randomized controlled trials involving 1454 patients showed that a 42-mg daily dose of lumateperone significantly improved depressive symptoms (SMD = -0.26; 95% CI: -0.51, -0.02), Clinical Global Impression-Bipolar-Severity (CGI-BP-S) overall bipolar illness (SMD = -0.31; 95% CI: -0.45, -0.16), CGI-BP-S bipolar depression (SMD = -0.33; 95% CI: -0.48, -0.17), quality of life (SMD = 0.22; 95% CI: 0.07, 0.36), and responder rate (RR = 1.27; 95% CI: 1.05, 1.53), but not remitter rate (1.06; 95% CI: 0.81, 1.38). Compared with placebo, discontinuation due to AE significantly increased at the 42 mg dose (RR = 3.12; 95% CI: 1.68, 5.80), but not at 28 mg (1.58; 95% CI: 0.25, 9.89). Moreover, dropout rates (42 mg RR = 1.15; 95% CI: 0.76, 1.73) and other safety outcomes did not exhibit a dose-response trend.

Conclusions: Preliminary evidence suggests that 42 mg daily of lumateperone may provide clinical benefit in bipolar depression, yet the higher rate of AE-related discontinuation warrants caution in practice. However, current data remain limited, requiring further studies to establish the optimal dosing range balancing efficacy and safety.

Classic psychedelics are increasingly studied as potential treatments for different psychiatric disorders. Current research protocols often require patients to discontinue antidepressants (ADs) for at least 2 weeks before psychedelic administration to decrease the risk of serotonin syndrome and limit their effect on efficacy and the acute subjective effects of psychedelics. Moreover, the discontinuation of ADs represents a significant burden to patients that could also worsen their depression status and increase suicidal ideation. Together, this suggests that the general recommendation for AD discontinuation might be unnecessary and even detrimental to the therapeutic efficacy of psychedelics. In this scoping review, we summarise the existing literature on the concomitant use of conventional ADs with classic psychedelics in humans with the aims to assess safety, tolerability, efficacy, and subjective effects. Following PRISMA-ScR guidelines, we searched MEDLINE, Embase, and Scopus databases to retrieve relevant literature from inception to March 3, 2025. Data were systematically charted from included studies. We included 18 studies and found that the concomitant use of ADs and classic psychedelics is generally safe and tolerable, with no increased risk of serotonin syndrome, particularly for psilocybin. Some studies reported significant improvements in depression and other mental health symptoms. While some evidence indicates a potential attenuation of acute subjective psychedelic effects, this was not observed in all studies. Accordingly, we conclude that the use of ADs can be maintained to enhance patient access to psychedelic treatments and avoid the risk of AD discontinuation syndrome. Finally, this review highlights limitations and several knowledge gaps in the current literature that need to be addressed in future randomized double-blind, placebo-controlled trials.

Background: The societal burden of depression continues to increase despite the greater use of antidepressants. It is not clear why wider antidepressant prescribing has not reduced the impact of depression at a population level. One possible explanation is that intermittent use of antidepressants at an individual level might reduce responsiveness to antidepressants.

Methods: We searched EMBASE and PubMed from the beginning of records to June 2024 for articles describing loss of response to antidepressants (in any psychiatric condition) occurring as a result of interruption in treatment. We did not restrict our search with respect to language or date.

Results: We found 6869 articles of potential interest, of which 5360 were excluded after initial screening by title, and 1453 were excluded as duplicates. We ultimately included 12 studies that provided data on 594 participants. Non-response was reported in 4%-57% of people who stopped and restarted antidepressant treatment that was previously effective.

Conclusion: Non-continuous consumption of antidepressants leads to a loss of responsiveness in an important proportion of people. Intermittent adherence to antidepressants may lessen their effectiveness and explain the relationship between wider antidepressant use and increased societal burden of depression.