Nicolau-Subires E, Irigoyen-Otiñano M, Arenas-Pijoan L
… +6 more, Adrados-Pérez M, Albert-Porcar C, Ibarra-Pertusa L, Mur-Laín M, Lopez-Castroman J, Llorca-Bofí V
Suicide is a leading cause of death globally. Although prior suicidal behavior is the strongest predictor of future attempts, clinical outcomes following a first suicide attempt (FSA) remain poorly understood. This study...Suicide is a leading cause of death globally. Although prior suicidal behavior is the strongest predictor of future attempts, clinical outcomes following a first suicide attempt (FSA) remain poorly understood. This study evaluates 5-year outcomes after an FSA, focusing on recurrence, lethality, and mortality to address gaps in understanding clinical trajectories and risk factors. A cohort of 387 FSA patients was followed for 5 years. Sociodemographic and clinical data were collected at baseline and during follow-up. Outcomes included recurrence, lethality of subsequent attempts, and all-cause mortality. Multivariable logistic and Cox regression models were used to identify risk factors. During follow-up, 37.2% of patients experienced recurrence, with 27.8% classified as frequent reattempters (≥3 attempts). Overall, 5.7% of participants died, including 1.8% by suicide. High-lethality FSAs were observed in 17.3% of the sample and were strongly associated with alcohol use (odds ratio [OR], 2.142; 95% CI, 1.231-3.724; =.021). Female sex was a significant risk factor for multiple reattempts (OR, 2.388; 95% CI, 1.036-5.507; =.041). High-lethality FSAs significantly increased the risk of suicide deaths (hazard ratio [HR], 5.430; 95% CI, 1.189-24.792; =.029), while older age was associated with a higher risk of nonsuicidal deaths (HR, 1.093; 95% CI, 1.035-1.153; =.001). Lethality, recurrence, and mortality following an FSA are influenced by distinct risk factors. Alcohol use predicted high-lethality FSAs, female sex predicted multiple reattempts, high-lethality FSAs predicted suicide deaths, and age predicted nonsuicidal deaths. Targeted interventions for these high-risk populations are needed.
Back SE, Gray K, Jarnecke AM
… +12 more, Saraiya TC, Santa Ana EJ, Killeen T, Joseph JE, Prisciandaro JJ, Brown DG, Nietert PJ, Stecker T, Rothbaum A, Jones JL, Flanagan JC, Brady KT
Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are common co-occurring conditions associated with a more severe clinical profile and poorer treatment outcomes than either disorder alone. To date, no...Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) are common co-occurring conditions associated with a more severe clinical profile and poorer treatment outcomes than either disorder alone. To date, no medications have proven efficacious in the treatment of co-occurring PTSD/AUD. This randomized, double-blind, placebo-controlled trial examined the efficacy of acetylcysteine (NAC; 2,400 mg/day) among individuals (N=182, aged 21-65 years) who met criteria for current PTSD/AUD. Participants were randomized 1:1 to receive 12 weeks of NAC (n=93) or placebo (n=89). All participants received weekly, individual, cognitive behavioral therapy (CBT) for AUD. Follow-up visits occurred at 3-, 6-, and 12-months posttreatment. Primary outcomes included the Clinician Administered PTSD Scale for (CAPS-5), PTSD Checklist for (PCL-5), Timeline Follow-Back (TLFB), and the Obsessive Compulsive Drinking Scale at 12 weeks. The TLFB evaluated the frequency and amount of alcohol consumption. A secondary measure evaluated depression symptoms. Intent-to-treat analyses showed that participants in both the NAC and placebo groups evidenced significant reductions in the CAPS-5 (B=-0.19, <.001) and PCL-5 (B=-0.20, <.001) during treatment, with no significant group differences. Both groups also showed significant reductions in alcohol use (drinks per drinking day [B=-0.02, <.001], percent heavy drinking days [B=-0.14, <.001], percent days abstinent [B=0.29, =.022]) and craving (B=-0.12, <.001) during treatment, but with no significant group differences. There were no group differences in retention or adverse events. Although NAC was well tolerated, it was not more effective than placebo in improving symptoms of PTSD or AUD when added to individual CBT for AUD. ClinicalTrials.gov identifier: NCT02966873.
There has been increasing interest in the use of artificial intelligence (AI)-enabled clinical decision support systems (CDSS) for the personalization of major depressive disorder (MDD) treatment selection and management...There has been increasing interest in the use of artificial intelligence (AI)-enabled clinical decision support systems (CDSS) for the personalization of major depressive disorder (MDD) treatment selection and management, but clinical studies are lacking. We tested whether a CDSS that combines an AI which predicts remission probabilities for individual antidepressants and a clinical algorithm based on treatment can improve MDD outcomes. This was a multicenter, cluster randomized, patient-and-rater blinded and clinician-partially-blinded, active-controlled trial that recruited outpatient adults with moderate or greater severity MDD. All patients had access to a patient portal to complete questionnaires. Clinicians in the active group had access to the CDSS; clinicians in the active-control group received patient questionnaires; both groups received guideline training. Primary outcome was remission (<11 points on the Montgomery-Asberg Depression Rating Scale [MADRS]) at study exit. Forty-seven clinicians were recruited at 9 sites. Of 74 eligible patients, 61 patients completed a postbaseline MADRS and were analyzed. There were no differences in baseline MADRS ( = .153). There were more remitters in the active (n = 12, 28.6%) than in the active-control (0%) group ( = .012, Fisher's exact). Of 3 serious adverse events, none were caused by the CDSS. Speed of improvement was higher in the active than the control group (1.26 vs 0.37, = .03). While limited by sample size and the lack of primary care clinicians, these results demonstrate preliminary evidence that longitudinal use of an AI-CDSS can improve outcomes in moderate and greater severity MDD. ClinicalTrials.gov identifier: NCT04655924.
Schizophrenia is a major mental illness with a median lifetime prevalence, across studies, of 0.5%. Across definitions of treatment resistance, about 37% of schizophrenia patients do not respond to treatment, and about 2...Schizophrenia is a major mental illness with a median lifetime prevalence, across studies, of 0.5%. Across definitions of treatment resistance, about 37% of schizophrenia patients do not respond to treatment, and about 24% are treatment resistant from the first-episode, itself. Treatment resistance is addressed by trialing different antipsychotics and with antipsychotic augmentation strategies; what augmenting agent is used depends on what the target symptoms are. A landmark study in 1988 demonstrated the efficacy of clozapine in treatment resistant schizophrenia (TRS). Confirmatory studies and meta-analyses followed, establishing clozapine as the drug of choice for TRS in schizophrenia treatment guidelines across the world. Between 2016 and 2025, 2 network meta analyses (NMAs) and 1 individual participant data meta-analysis (IPD-MA) examined randomized controlled trials (RCTs) of clozapine vs other antipsychotics in TRS. The NMAs found that clozapine was superior to first-generation antipsychotics; however, clozapine did not head rankings for overall symptoms, positive symptoms, or negative symptoms, and, in pairwise analyses, there was little difference between clozapine and olanzapine and clozapine and risperidone for overall symptoms, positive symptoms, and negative symptoms. The IPD-MA found that clozapine was no better than comparator second-generation antipsychotics, considered singly or together, for overall symptoms, positive symptoms, and negative symptoms, in the short term, intermediate term, and long term. These findings fly in the face of clinical experience and treatment guideline recommendations. Among possible explanations, notable was that clozapine was significantly superior to comparator drugs when disregarding RCTs sponsored by the manufacturer of olanzapine. Clozapine is associated with many inconveniencing, distressing, and serious adverse effects that may be rare or common. Given the findings that olanzapine and risperidone may be as good as clozapine in TRS, it may be worth trialing these drugs before clozapine in patients with TRS. These and related issues, including nuances, are discussed.
The primary aim of this study was to establish that levomilnacipran potently inhibits norepinephrine (NE) reuptake in human participants starting at a minimally efficacious regimen in major depressive disorder (MDD) and...The primary aim of this study was to establish that levomilnacipran potently inhibits norepinephrine (NE) reuptake in human participants starting at a minimally efficacious regimen in major depressive disorder (MDD) and to determine the dose needed to significantly inhibit serotonin (5-HT) reuptake. The secondary aim was to confirm that duloxetine is a selective 5-HT reuptake inhibitor at its minimally effective regimen in MDD and that it significantly inhibits NE reuptake only with dose escalation. Inhibition of the NE reuptake process was estimated by assessing the attenuation of the systolic blood pressure produced by intravenous injections of small doses of tyramine. Inhibition of the 5-HT reuptake process was estimated using depletion of whole blood 5-HT. Healthy male participants took ascending daily doses of levomilnacipran (40, 80, and 120 mg), duloxetine (60, 90, and 120 mg) each for 7 days, or a placebo pill (n=10, 9, and 10, respectively), and all assays were carried out 2-6 hours after the last dose. The study took place between February 2018 and October 2022. Plasma levels of both medications increased in dose-dependent levels. Neither the tyramine pressor responses nor 5-HT levels were significantly altered in the placebo group. For the attenuation of the tyramine pressor response, levomilnacipran separated from baseline starting at 40 mg and duloxetine separated from baseline only at 120 mg. Both drugs robustly decreased 5-HT levels to the same extent at all 3 doses. Levomilnacipran is a potent dual reuptake inhibitor from its minimally effective dose in MDD, whereas the dose of duloxetine needs to reach 120 mg/day to consistently inhibit NE reuptake. ClinicalTrials.gov identifier: NCT03249311.
Lumateperone, a mechanistically novel antipsychotic, simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This phase 3, randomized, double-blind, placebo-controlled trial investigated efficacy a...Lumateperone, a mechanistically novel antipsychotic, simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This phase 3, randomized, double-blind, placebo-controlled trial investigated efficacy and safety of adjunctive lumateperone 42 mg in patients with major depressive disorder (MDD) with inadequate antidepressant therapy (ADT) response. From July 2021 to February 2024, eligible adult outpatients (18-65 years) had -defined MDD with inadequate response to 1 or 2 ADTs in the current depressive episode and Montgomery-Åsberg Depression Rating Scale (MADRS) Total score ≥24, Clinical Global Impression Scale-Severity (CGI-S) score ≥4, and Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥14. Patients were randomized to 6-week oral adjunctive placebo (n=243) or adjunctive lumateperone 42 mg (n=242). Primary and key secondary end points were change from baseline to day 43 in MADRS Total and CGI-S scores. Safety was assessed. Lumateperone + ADT met primary and key secondary end points, with significantly greater improvement at day 43 vs placebo + ADT in MADRS Total score (least squares mean difference [LSMD] vs placebo= -4.9; effect size [ES]= -0.61; < .0001) and CGI-S score (LSMD =-0.7; ES = -0.67; <.0001). Lumateperone + ADT significantly improved patient-reported depression vs placebo + ADT at day 43 (QIDS-SR-16 Total score, LSMD= -2.4; ES= -0.50; < .0001). Lumateperone + ADT was generally well tolerated. Treatment-emergent adverse events (≥5%, twice placebo) were dry mouth (placebo + ADT, 2.1%; lumateperone + ADT, 10.8%), fatigue (2.1%; 9.5%), and tremor (0.4%; 5.0%), with minimal risk for weight gain or cardiometabolic abnormalities. Emergence of suicidal ideation was low (placebo + ADT, 3.5%; lumateperone + ADT, 1.4%). Lumateperone 42 mg adjunctive to ADT significantly improved depression symptoms and disease severity vs adjunctive placebo and was generally well tolerated in patients with MDD with inadequate ADT response. ClinicalTrials.gov identifier: NCT04985942.
Aripiprazole is a second-generation partial dopamine D₂ receptor agonist antipsychotic approved for the treatment of schizophrenia and maintenance treatment of bipolar I disorder. As the only partial dopamine D₂ receptor...Aripiprazole is a second-generation partial dopamine D₂ receptor agonist antipsychotic approved for the treatment of schizophrenia and maintenance treatment of bipolar I disorder. As the only partial dopamine D₂ receptor agonist available in both oral and long-acting injectable (LAI) formulations, it provides flexibility for tailoring treatment across different phases of the illness. Two LAI formulations of aripiprazole monohydrate are available: aripiprazole once-monthly 400 mg and aripiprazole 2-month ready-to-use 960 mg, offering options to accommodate patient needs and preferences and support adherence. The aripiprazole monohydrate LAIs are well-supported options for early intervention and maintenance treatment, with evidence demonstrating clinical effectiveness in reducing relapse and hospitalizations while supporting enhanced adherence. LAI antipsychotics, including aripiprazole monohydrate, offer practical benefits for patients with schizophrenia, particularly those at risk for nonadherence or recurrent episodes. However, these formulations are often underutilized due to lingering stigma and misperceptions, leading many clinicians to defer use of these agents until later in the treatment course. To support earlier and more informed use of aripiprazole monohydrate LAIs, a panel of psychiatric experts convened to review the latest evidence and share clinical strategies for integrating this agent into a comprehensive treatment plan. This Academic Highlights section presents the main points of their consensus recommendations, offering practical guidance for prescribers seeking to optimize outcomes in patients with schizophrenia.
Bipolar I disorder (BP-I) is a severe and chronic psychiatric condition characterized by recurrent episodes of mania and depression that significantly impact quality of life and functioning. Early recurrence, high relaps...Bipolar I disorder (BP-I) is a severe and chronic psychiatric condition characterized by recurrent episodes of mania and depression that significantly impact quality of life and functioning. Early recurrence, high relapse rates, and poor adherence to daily oral medications complicate long-term management and increase the risk of hospitalization and suicide. Long-acting injectable antipsychotics (LAIs) offer a potential solution to these challenges by promoting sustained medication delivery and efficacy, reducing pharmacokinetic variability, and improving treatment adherence. Among available LAIs, aripiprazole is the only partial dopamine D₂ receptor agonist, which may contribute to its favorable tolerability and mood-stabilizing properties. Despite the robust evidence for the efficacy and tolerability of aripiprazole monohydrate LAIs in patients with BP-I, this agent remains underutilized in this population. Misperceptions about efficacy and tolerability, coupled with systemic and prescriber-level barriers, have limited broader clinical adoption. To address these issues, a round table panel of experts in psychopharmacology, the clinical treatment of bipolar disorder, and antipsychotic prescribing was convened to evaluate the clinical rationale for earlier use of aripiprazole monohydrate LAIs in BP-I and to identify key challenges limiting its use. This article summarizes their consensus on the pharmacological distinctiveness, practical advantages, and potential of aripiprazole monohydrate LAIs in improving long-term outcomes in individuals with BP-I.
To estimate prevalence and impact of cognitive impairments in schizophrenia in the US. Retrospective analyses of the Medical Expenditure Panel Survey (1997-2021) were conducted to identify adults living with schizophren...To estimate prevalence and impact of cognitive impairments in schizophrenia in the US. Retrospective analyses of the Medical Expenditure Panel Survey (1997-2021) were conducted to identify adults living with schizophrenia and cognitive impairments. Cognitive limitations (CL; 1997-2021) were defined as interference with daily activities, confusion/memory loss, problems making decisions, or requiring supervision for safety. Cognitive difficulties (CD; 2013-2021) were defined as difficulty in concentration/memory/decision-making. Descriptive analyses covered demographic, clinical, and socioeconomic characteristics, health care resource utilization (HCRU), humanistic, and indirect burdens. Multivariable regression analyses were conducted for hospitalizations, emergency department (ED) visits, and total costs. Sampling weights were applied. Among 661,243 weighted adults living with schizophrenia (mean age: 45.6 years; male: 56.7%), 57.7% reported CL, and 53.8% reported CD. Compared to no CL, CL was associated with lower education (no degree: +2.2%) and annual income (-$4,332) and higher Charlson Comorbidity Index (0.89 vs 0.55) and HCRU. Total health care costs were higher for CL ($18,478 vs $11,689), demonstrating greater economic burden. Individuals reporting CL reported more limitations in activities of daily living (+13.3%) and lower health utilities scores with higher percentage of poor perceived health (+10.1%), indicating higher humanistic burden. For indirect burden, CL was associated with higher unemployment (+15.3%) (all <.05). Multivariable regression analysis showed that CL was associated with higher odds of hospitalizations (1.47; 95% CI, 1.05-2.06), ED visits (1.64; 95% CI, 1.22-2.20), and total health care costs (1.56; 95% CI, 1.30-1.86). CD showed similar results except that CD was not significantly associated with hospitalizations or ED visits. Cognitive impairments in schizophrenia are associated with higher multilevel burdens compared to those without, highlighting the need for targeted interventions.
This study compared the effects of augmenting antidepressants with aripiprazole or repetitive transcranial magnetic stimulation (rTMS) versus switching to venlafaxine XR/duloxetine on quality of life (QoL) among patients...This study compared the effects of augmenting antidepressants with aripiprazole or repetitive transcranial magnetic stimulation (rTMS) versus switching to venlafaxine XR/duloxetine on quality of life (QoL) among patients with treatment resistant depression (TRD). In a predefined secondary analysis of a multisite, open-label, effectiveness trial, patients with TRD were randomly assigned to aripiprazole augmentation, rTMS augmentation, or switching to venlafaxine XR/duloxetine in a 1:1:1 ratio, and they were treated for 8 weeks. TRD was defined as an inadequate response to 2 or more antidepressant trials of adequate dose and duration, as defined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire. QoL was predefined as a key secondary end point for this study and assessed using the short form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF). A mixed-effects model with repeated measures was applied. This study was conducted from July 13, 2017, to December 22, 2021. Among 258 randomized participants with at least 1 postbaseline Q-LES-Q-SF measurement, augmentation with aripiprazole demonstrated statistically significant superiority over switching on the Q-LES-Q-SF (=.002), while rTMS did not (=.326). At end point, changes from baseline in the Q-LES-Q-SF scores were 10.61 (SE=1.0) for aripiprazole augmentation, 11.59 (SE=1.1) for rTMS augmentation, and 8.68 (SE=0.9) for venlafaxine XR/duloxetine switch. Augmentation with aripiprazole, but not rTMS, improved QoL significantly versus venlafaxine XR/duloxetine switch in TRD patients. However, a much smaller than expected sample size for the rTMS group may explain the lack of statistical significance rendering the latter finding of indeterminate nature. ClinicalTrials.gov identifier: NCT02977299.
Excessive alcohol use is a recognized modifiable risk factor for the development of dementia; however, the neuropsychological profile of cognitive impairment seen with alcohol use is heterogeneous. We studied cognitive c...Excessive alcohol use is a recognized modifiable risk factor for the development of dementia; however, the neuropsychological profile of cognitive impairment seen with alcohol use is heterogeneous. We studied cognitive characteristics associated with alcohol use in a "real-world" memory clinic cohort of patients with neurocognitive disorders. We used the Toronto Dementia Research Alliance memory clinic research database to generate an age, sex, and education matched sample of individuals with alcohol-related cognitive impairment (ARCI group; n=51) and twice as many individuals without such history (Comparator group; n=102). We compared cognitive domain and subdomain Toronto Cognitive Assessment scores between the two groups using linear regression.while controlling for age, sex, education, concurrent psychiatric disorders, global cognition, and traumatic brain injury. Mean (SD) age was 67.67 (13.01) years for the ARCI group and 67.96 (12.82) years for the Comparator group. The ARCI and Comparator groups had 35% and 36% females, respectively. Neither global cognition nor other cognitive domains differed significantly between the two groups. Among cognitive subdomains, only the intrusion rates on the delayed recall task were higher (worse performance) in the ARCI group (mean [SD]=0.79 [1.21]) relative to the Comparator group (mean [SD]=0.34 [0.69]; =.018). Our study suggests that ARCI results in specific deficits involving cognitive control during delayed recall task. This may help advance development of markers to delineate ARCI from other causes of cognitive impairment. Future work may test these findings in larger, well-characterized samples.
To examine differences in treatment use and preference among women with mood disorders based on race, ethnicity, and type of health insurance. Women (N = 2,877) with depression, anxiety, and bipolar disorders were surve...To examine differences in treatment use and preference among women with mood disorders based on race, ethnicity, and type of health insurance. Women (N = 2,877) with depression, anxiety, and bipolar disorders were surveyed in primary care and specialty clinics affiliated with the National Network of Depression Centers from January 2018 to December 2020. Logistic regression was employed to examine the probabilities of Black, White, and Hispanic women, who varied on public (government-funded) vs private insurance, using and preferring medication, psychotherapy, or complementary treatments. Black women had lower odds of receiving medications for treatment of all mood disorders, while White women had higher odds. For example, in treatment of depression, the odds ratio (OR) for Black women was 0.435 (=.011), while the OR for White women was 2.048 (=.009). Hispanic women had higher odds of using complementary treatments than other women. For example, in treatment of anxiety, their OR was 2.346 (=.008). Across mood disorders, government-funded (Medicaid/Medicare) coverage was associated with greater use of psychotherapy and complementary treatments (ORs ranging from 1.529 to 5.011) as well as greater medication use for bipolar disorder (OR=5.805, =.027). Psychotherapy was preferred by the majority of all women (55.5%), although preferences for other treatments differed between racial/ethnic groups. Research is needed regarding the degree to which clinicians are offering varied treatments to diverse women with mood disorders and how clinicians consider women's preferences. Results highlight the necessity for treatment that integrates culturally based values and preferences, along with policies that ensure treatment access for women who are privately insured.
Shelton RC, Litman RE, Hassman H
… +14 more, Walling DP, Ros Montalbán S, Salvà-Coll J, Zajecka J, Sverdlov O, Gomez-Mancilla B, Healy MP, Shanker YG, Berkheimer M, Faller T, von Raison F, Serban C, Cha JH, Ghaemi SN
Onfasprodil (MIJ821) is a highly potent and novel selective NR2B subunit negative allosteric modulator. This phase 2, randomized, placebo-controlled, proof-of-concept study evaluated efficacy and safety of onfasprodil in...Onfasprodil (MIJ821) is a highly potent and novel selective NR2B subunit negative allosteric modulator. This phase 2, randomized, placebo-controlled, proof-of-concept study evaluated efficacy and safety of onfasprodil in patients with treatment-resistant major depression (TRD). Adults with TRD who did not respond to ≥2 antidepressants were randomized (3:3:3:3:6:4) to receive a 40-minute intravenous infusion of onfasprodil 0.16 mg/kg weekly (n = 11), onfasprodil 0.16 mg/kg biweekly (n = 10), onfasprodil 0.32 mg/kg weekly (n = 10), onfasprodil 0.32 mg/kg biweekly (n = 9), placebo weekly (n=20), or ketamine 0.5 mg/kg weekly (n= 10) for 6 weeks. Primary end point was change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) score at 24 hours. Secondary end points were change in MADRS score at 48 hours and at final follow-up at 6 weeks. Safety and tolerability were assessed during the study. Of 70 randomized patients, 53 (75.7%) completed the study. At 24 hours, adjusted mean differences versus placebo for pooled onfasprodil 0.16 mg/kg, 0.32 mg/kg, and ketamine groups were -8.25 ( = .001), -5.71 ( = .019), and -5.67 ( = .046), and at 48 hours, -7.06 ( = .013), -7.37 ( = .013), and -11.02 ( = .019), respectively. At Week 6, adjusted arithmetic mean MADRS difference between ketamine and placebo was -5.24 (80% CI, -10.42 to -0.06; = .0974). At Week 6, the difference versus placebo on MADRS was -5.78 (= .0427) for pooled 0.16 mg/kg and -4.24 (= .1133) for pooled 0.32 mg/kg groups. The commonest treatment-emergent adverse events in the onfasprodil groups were dizziness (14.3%), transient amnesia (14.3%), and somnolence (11.4%). It had overall a good safety profile and was well tolerated. Onfasprodil appeared to be effective and well-tolerated across all dosing regimens in patients with TRD and demonstrated rapid onset of action (24 hours) with evidence of antidepressant effects to be maintained at Week 6, particularly for the lower-dose group. ClinicalTrials.gov identifier: NCT03756129.
J Clin Psychiatry
· 2025 Jul · PMID 40767786
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This study evaluated whether depressive symptom severity improved early with extended-release naltrexone and bupropion combination (naltrexone bupropion) compared to a placebo in individuals with moderate/severe methamph...This study evaluated whether depressive symptom severity improved early with extended-release naltrexone and bupropion combination (naltrexone bupropion) compared to a placebo in individuals with moderate/severe methamphetamine use disorder and predicted subsequent use of methamphetamine. This secondary analysis from the Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT-2) trial, which was conducted from May 23, 2017-July 25, 2019, included 326 individuals with a 9-item Patient Health Questionnaire (PHQ-9) score ≥5 at baseline. Repeated-measures mixed model analyses evaluated early (baseline-to-week-4) changes in depressive symptom severity with naltrexone-bupropion versus placebo and provided slope estimates for PHQ-9 change. Additional depression outcomes included response (≥50% reduction in PHQ-9 from baseline) and remission (PHQ-9 ≤4). Methamphetamine treatment response was ascribed if 3 out of 4 urine drug screens were negative during weeks 5 and 6. Logistic regression analyses evaluated whether changes in depression predicted methamphetamine treatment response. Covariates included age, sex, race, ethnicity, and baseline PHQ-9. There was a greater reduction in PHQ-9 scores at week 4 with naltrexone-bupropion versus placebo (estimate = -2.52; standard error = 0.81). At week 4, depression response (odds ratio [OR] = 2.54; 95% confidence limit [CL], 1.42-4.55) and remission (OR = 3.04; 95% CL, 1.57-5.87) were more likely with naltrexone-bupropion versus placebo. Greater baseline-to-week 4 reduction in PHQ-9 was associated with a higher likelihood of methamphetamine treatment response (OR = 3.74, 95% CL, 1.28-10.93) and explained 24.8% (95% CI, 6.7%-60.3%) of the effect of naltrexone-bupropion on methamphetamine treatment response. Use of naltrexone bupropion was associated with early reduction in depressive symptom severity compared to a placebo, which was associated with a higher likelihood of reduction in subsequent methamphetamine use. ClinicalTrials.gov identifier: NCT03078075.
Singh B, Pazdernik VK, Kung S
… +1 more, Vande Voort JL
J Clin Psychiatry
· 2025 Jul · PMID 40767785
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This study examines the durability (defined as time between treatments) of intravenous ketamine (IV-KET) and intranasal esketamine (IN-ESKET) for treatment-resistant depression (TRD), in a real-world clinical setting wit...This study examines the durability (defined as time between treatments) of intravenous ketamine (IV-KET) and intranasal esketamine (IN-ESKET) for treatment-resistant depression (TRD), in a real-world clinical setting with repeated ketamine/esketamine maintenance therapy. This was a single-center, observational study of adults with TRD who completed acute-phase treatment between August 17, 2017, and June 24, 2021, and received IV-KET (0.5 mg/kg) or IN-ESK (56/84 mg) maintenance therapy. Maintenance cycle duration was measured from the first treatment after the acute phase to the final treatment. Depressive symptoms were assessed using the Quick Inventory of Depressive Symptomatology before each treatment. Linear mixed-effects models and generalized linear mixed models (GLMM) evaluated treatment effects. The number of days between treatments (treatment intervals) was modeled using a negative binomial GLMM. Fifty-six maintenance cycles from 38 patients were included. The median baseline age was 46.2 years (78.9% female). Sixty-eight percent (n = 26) received IV-KET, and 32% (n = 12) received IN-ESKET. The median duration of the longest maintenance cycle was 61 weeks for IV-KET and 48 weeks for IN-ESKET, with 14 and 28 median treatments, respectively. IV-KET patients had longer intervals between treatments compared to IN-ESKET (incidence rate ratio: 1.75, < .001). Mean treatment intervals were 18.9 days for IV-KET vs 10.8 days for IN-ESKET. Both treatments showed stable systolic blood pressure trajectories. This study provides evidence regarding longer durability of IV-KET compared to IN-ESKET. These findings need to be replicated in larger prospective studies and confirmed in a randomized controlled trial comparing these two treatment interventions.
Caregivers of people with dementia (PWD) often face burdens, but engaging in traditional mindfulness practices and spending time in nature can enhance positive emotions. This study aimed to assess the effectiveness and f...Caregivers of people with dementia (PWD) often face burdens, but engaging in traditional mindfulness practices and spending time in nature can enhance positive emotions. This study aimed to assess the effectiveness and feasibility of nature videos in reducing burden, anxiety, and depression among caregivers of PWD in Thailand. As caregivers are often time poor, a brief 10-minute online mindfulness session was designed to make participation more feasible. This randomized controlled trial assigned 47 eligible individuals to 2 groups. The experimental group received dailynature videos for 4 weeks, while the control group received daily self-care guidance. The 12-item Zarit Burden Interview (12-item ZBI), the Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder-7 (GAD-7), and the Connor Davidson Resilience Scale (CD-RISC) were used to assess caregivers' burden at baseline and the 4-week follow-up. Recruitment occurred from March 2023 to February 2024. The mean age was 50.59 years. On average, participants watched videos for 11.49 minutes per day, and the duration was 23 days. Both groups showed a significant decrease in burden at follow-up, but the between-group changes of 12-item ZBI were not significantly different. Brief mindfulness interventions reduced PHQ-9 scores by 4.14 points (<.001) and increased CD-RISC scores by 5.68 points (=.001). GAD-7 and PHQ-9 were significantly positively correlated with the 12-item ZBI (=0.55, <.001, and =0.42, =.005, respectively). Brief mindfulness interventions through nature videos and receiving self-care advice can reduce the burden among caregivers of PWD and reduce levels of depression. Dataset from study at Thaiclinicaltrials.org identifier: TCTR20230216001.
Niacin-induced skin flushing response (NSFR) attenuation is a well documented biomarker for psychosis and has also been used in studies of bipolar affective disorder. It appears not only in later stages but also in first...Niacin-induced skin flushing response (NSFR) attenuation is a well documented biomarker for psychosis and has also been used in studies of bipolar affective disorder. It appears not only in later stages but also in first episodes and in clinical high-risk (CHR) stages. NSFR tests were conducted on healthy controls (HC), CHR individuals, and first-episode psychosis (FEP) patients from January 2019 to March 2024. The tests involved applying niacin patches at different concentrations and recording skin responses at multiple time points. A newly introduced slope variable was used to evaluate response efficiency. CHR participants were followed for 3 years to assess the predictive value of NSFR efficiency and attenuation degree for psychosis onset. This study included 98 CHR individuals (mean age: 18.4 years, 42.9% male), 54 FEP patients (24.7 years, 50% male), and 61 HC (25.8 years, 54.1% male). Over the 3-year follow-up, 23 (23.5%) CHR individuals converted to psychosis. CHR individuals showed NSFR attenuation levels between those of FEP patients and HC. Lower response efficiency was associated with a higher risk of developing psychosis, specifically at 10 M and 10 M concentrations ( = .001 and = .039, respectively). The area under the curve for predicting psychosis onset using slope values at 10 M was 0.645 ( = .034). For discriminating CHR from HC, significant factors included slope at 10 M concentration ( = .006), total scores at 5 minutes ( = .001) and 15 minutes ( = .005), and total scores at 10 M ( = .002) and 10 M ( = .001). For discriminating FEP from HC, significant factors were the slope at 10 M concentration ( = .023), total score at 5 minutes ( = .003), and total score at 10 M concentration ( = .040). NSFR efficiency is a sensitive marker for early psychosis risk, highlighting the need for precise and comprehensive detection methods.