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Psychiatry

Cohort Study: GIP/GLP-1 Receptor Agonist Prescriptions Linked to Reduced Opioid Overdose and Alcohol Intoxication

20 Oct, 2024 | 18:36h | UTC

Background: Opioid use disorder (OUD) and alcohol use disorder (AUD) are prevalent conditions leading to significant morbidity and mortality, including overdose and intoxication. Current pharmacotherapies for OUD and AUD are underutilized due to barriers like access and stigma. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), used for type 2 diabetes and obesity, have shown potential in modulating reward pathways associated with substance use, suggesting a possible role in reducing substance-related harms.

Objective: To estimate the association between prescriptions of glucose-dependent insulinotropic polypeptide (GIP) and/or GLP-1 receptor agonists and the incidence of opioid overdose and alcohol intoxication in patients with OUD and AUD, respectively, and to assess this association among patients with comorbid type 2 diabetes and obesity.

Methods: This retrospective cohort study analyzed de-identified electronic health record data from 136 U.S. health systems in the Oracle Cerner Real-World Data, covering over 100 million patients from January 2014 to September 2022. Adults aged 18 years or older with a history of OUD (n = 503,747) or AUD (n = 817,309) were included. The exposure was defined as having one or more prescriptions of GIP/GLP-1 RAs after the first OUD or AUD diagnosis. The primary outcomes were the incidence rates of opioid overdose in the OUD cohort and alcohol intoxication in the AUD cohort.

Results: Patients with GIP/GLP-1 RA prescriptions had significantly lower rates of opioid overdose (aIRR in OUD patients: 0.60; 95% CI, 0.43–0.83) and alcohol intoxication (aIRR in AUD patients: 0.50; 95% CI, 0.40–0.63) compared to those without such prescriptions. The protective association remained significant among patients with comorbid type 2 diabetes and obesity.

Conclusions: Prescriptions of GIP and/or GLP-1 receptor agonists are associated with lower rates of opioid overdose and alcohol intoxication in patients with OUD and AUD. These protective effects persist across various subgroups, including those with comorbid type 2 diabetes and obesity.

Implications for Practice: GLP-1 RAs show promise for reducing substance-related harms in patients with OUD and AUD. Clinicians may consider the potential benefits of GIP/GLP-1 RA prescriptions in this population, while recognizing the need for further research to establish causality and understand underlying mechanisms.

Study Strengths and Limitations: Strengths include a large, diverse patient population and adjustment for multiple confounders. Limitations involve the retrospective observational design limiting causal inference and reliance on data from Cerner-affiliated health systems, which may affect generalizability.

Future Research: Prospective clinical trials are needed to validate these findings, elucidate underlying mechanisms, and assess the efficacy and safety of GIP/GLP-1 RAs as treatments for substance use disorders.

Reference: Qeadan F, et al. (2024). The association between glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonist prescriptions and substance-related outcomes in patients with opioid and alcohol use disorders: A real-world data analysis. Addiction. DOI: http://doi.org/10.1111/add.16679

 


Psychedelic-Assisted Therapy May Reduce Anxiety and Depression in Patients with Life-Threatening Diseases

20 Oct, 2024 | 18:02h | UTC

Background: Anxiety, depression, and existential distress are prevalent among individuals facing life-threatening illnesses, significantly impacting their quality of life. Traditional treatments often have limited efficacy in this population. Psychedelic-assisted therapy, involving substances like psilocybin and LSD under professional supervision, has been proposed as a potential intervention. However, these substances are illegal in most countries and pose potential risks.

Objective: To assess the benefits and harms of psychedelic-assisted therapy compared to placebo or active comparators in treating anxiety, depression, and existential distress in people with life-threatening diseases.

Methods: This Cochrane systematic review included six randomized controlled trials conducted in the USA and Switzerland between 2011 and 2022. A total of 149 participants (140 analyzed), aged 36 to 64 years with life-threatening illnesses (e.g., cancer), were randomized to receive psychedelic-assisted therapy using classical psychedelics (psilocybin or LSD) or MDMA. Interventions included preparatory sessions, the psychedelic experience, and integration sessions. Comparators were active placebos (e.g., low-dose psychedelic or niacin) or placebo. Primary outcomes were anxiety, depression, and existential distress measured 1 to 12 weeks post-intervention.

Results: Psychedelic-assisted therapy with classical psychedelics may reduce anxiety and depression compared to active placebo:

  • Anxiety: Mean difference (MD) of −8.41 points on the STAI-Trait scale (20–80 range; 95% CI, −12.92 to −3.89; 5 studies, 122 participants; low-certainty evidence).
  • Depression: MD of −4.92 points on the Beck Depression Inventory (0–63 range; 95% CI, −8.97 to −0.87; 4 studies, 112 participants; low-certainty evidence).

The effect on existential distress was mixed and very uncertain. No treatment-related serious adverse events or grade 3/4 adverse events were reported. Common mild to moderate adverse events included elevated blood pressure, nausea, anxiety, and transient psychotic-like symptoms, which resolved shortly after the sessions.

Conclusions: Psychedelic-assisted therapy with classical psychedelics may reduce symptoms of anxiety and depression in patients with life-threatening diseases, but the evidence is of low certainty due to methodological limitations and small sample sizes. The effects of MDMA-assisted therapy are very uncertain.

Implications for Practice: While findings are promising, clinicians should exercise caution due to the low certainty of evidence and legal restrictions surrounding psychedelic substances.

Study Strengths and Limitations: Strengths include randomized designs and standardized therapeutic protocols involving preparation and integration sessions. Limitations are high risk of bias due to unblinding, small sample sizes, potential expectation bias, and cross-over designs with carry-over effects.

Future Research: Larger, well-designed RCTs with rigorous blinding are needed to confirm these findings. Future studies should explore long-term outcomes, diverse patient populations, and strategies to mitigate bias, such as using active placebos and measuring expectancy effects.

Reference: Schipper S, et al. (2024). Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases. Cochrane Database of Systematic Reviews. DOI: https://doi.org/10.1002/14651858.CD015383.pub2

 


Summary of the review “Neuroleptic Malignant Syndrome”

6 Oct, 2024 | 16:20h | UTC

In a comprehensive review published in the New England Journal of Medicine, Wijdicks and Ropper discuss neuroleptic malignant syndrome (NMS), a rare but potentially fatal complication of antipsychotic therapy characterized by fever, muscle rigidity, and autonomic dysfunction. Given the widespread use of dopamine-blocking agents across various medical specialties, it is crucial for practicing physicians to recognize and manage this syndrome promptly to improve patient outcomes.

Key Aspects Influencing Patient Care:

  • Epidemiology and Risk Factors:
    • NMS occurs in approximately 0.02 to 3% of patients exposed to dopamine-blocking agents.
    • Risk factors include dehydration, high doses of antipsychotics, rapid dose escalation, intramuscular administration, and prior episodes of NMS.
    • Both first-generation (typical) and second-generation (atypical) antipsychotics can cause NMS, though it may be less severe with atypical agents.
  • Clinical Presentation:
    • Hyperthermia: Elevated temperatures often exceeding 40°C.
    • Muscle Rigidity: Lead-pipe rigidity leading to rhabdomyolysis and elevated creatine kinase levels.
    • Autonomic Dysfunction: Tachycardia, fluctuating blood pressure, diaphoresis.
    • Altered Mental Status: Ranges from agitation to stupor or catatonia.
    • Laboratory Findings: Leukocytosis, electrolyte imbalances, and signs of renal impairment.
  • Diagnosis:
    • Based on clinical criteria including recent exposure to dopamine antagonists and presence of key symptoms.
    • Important to differentiate from serotonin syndrome, malignant hyperthermia, heat stroke, and severe catatonia.
  • Management:
    • Immediate Discontinuation of the offending agent.
    • Supportive Care in ICU:
      • Stabilize vital signs and manage autonomic instability.
      • Aggressive hydration to prevent renal failure from rhabdomyolysis.
      • Cooling measures for hyperthermia.
    • Pharmacologic Interventions:
      • Dantrolene: Reduces muscle rigidity and hyperthermia.
      • Dopamine Agonists: Bromocriptine or amantadine may reverse dopamine blockade.
      • Benzodiazepines: Lorazepam for sedation and muscle relaxation.
    • Monitoring for Complications:
      • Watch for respiratory failure, renal dysfunction, electrolyte disturbances, and cardiac arrhythmias.
    • Electroconvulsive Therapy (ECT):
      • Considered in refractory cases unresponsive to medical management.
  • Outcome and Prognosis:
    • Recovery typically occurs within 7 to 11 days with appropriate treatment.
    • Mortality rates have decreased but can reach up to 15% within one year due to complications.
    • Rechallenge with Antipsychotics:
      • If necessary, reintroduce antipsychotics cautiously after full recovery, using low doses and slow titration.
      • Prefer atypical agents and monitor closely for recurrence.

Clinical Implications:

  • Early Recognition: Timely identification of NMS is critical for initiating life-saving interventions.
  • Interdisciplinary Approach: Collaboration among psychiatrists, intensivists, neurologists, and other specialists enhances patient care.
  • Education and Prevention:
    • Educate healthcare providers about the signs and risk factors of NMS.
    • Monitor patients on antipsychotics closely, especially during dose changes or when using high-potency agents.

Reference: Wijdicks, E. F. M., & Ropper, A. H. (2024). Neuroleptic Malignant Syndrome. New England Journal of Medicine, 391(12), 1130–1138. DOI: 10.1056/NEJMra2404606

 


Meta-Analysis: High-Dose Psilocybin Shows Small Advantage Over Escitalopram for Depression – The BMJ

24 Aug, 2024 | 16:41h | UTC

Study Design and Population: This systematic review and Bayesian network meta-analysis evaluated the effectiveness of oral monotherapy with psychedelics (psilocybin, LSD, MDMA, ayahuasca) compared to escitalopram in adults with depressive symptoms. The analysis included 15 trials with psychedelics and 5 trials with escitalopram, covering a total of 811 participants in psychedelic trials and 1968 in escitalopram trials.

Main Findings: The analysis revealed that only high-dose psilocybin demonstrated a significant improvement in depressive symptoms compared to placebo when considered in the context of antidepressant trials, but the effect size was small (standardized mean difference of 0.31). High-dose psilocybin also outperformed escitalopram (10 mg and 20 mg), with a mean difference exceeding the minimal important difference. However, the placebo response was generally lower in psychedelic trials compared to antidepressant trials, suggesting potential overestimation of effect sizes in psychedelic studies.

Implications for Practice: The findings suggest that while high-dose psilocybin may offer a small advantage over escitalopram for treating depression, the overall effect size is comparable to traditional antidepressants. The results highlight the importance of considering the impact of blinding and placebo response in psychedelic trials, and suggest that improved blinding and standardized psychotherapies could help better assess the true efficacy of these treatments.

Reference: Hsu, T.-W., Tsai, C.-K., Kao, Y.-C., Thompson, T., Carvalho, A. F., Yang, F.-C., Tseng, P.-T., Hsu, C.-W., Yu, C.-L., Tu, Y.-K., & Liang, C.-S. (2024). Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis. BMJ, 386, e078607. DOI: https://doi.org/10.1136/bmj-2023-078607

 


Cohort Study: Prenatal Exposure to Buprenorphine with Naloxone Appears Safe and More Effective than Buprenorphine Alone for Neonates and Mothers – JAMA

18 Aug, 2024 | 18:06h | UTC

Study Design and Population: This population-based cohort study used healthcare data from Medicaid-insured pregnancies in the US between 2000 and 2018. The study included 8,695 pregnant individuals linked to their liveborn infants. Participants were exposed to either buprenorphine combined with naloxone or buprenorphine alone during the first trimester.

Main Findings: The study found that prenatal exposure to buprenorphine with naloxone was associated with a lower risk of neonatal abstinence syndrome (37.4% vs 55.8%) and modest reductions in neonatal intensive care unit admission (30.6% vs 34.9%) and small for gestational age (10.0% vs 12.4%) compared to buprenorphine alone. No significant differences were observed for congenital malformations, low birth weight, preterm birth, respiratory symptoms, or cesarean delivery.

Implications for Practice: These findings suggest that buprenorphine combined with naloxone is a safe and potentially preferable option for treating opioid use disorder during pregnancy, providing more flexibility in treatment choices for pregnant individuals.

Reference: Straub, L., Bateman, B. T., Hernández-Díaz, S., et al. (2024). Comparative safety of in utero exposure to buprenorphine combined with naloxone vs buprenorphine alone. JAMA. Published online August 12, 2024. DOI: 10.1001/jama.2024.11501.

 


Meta-Analysis: Effects of Psychological, Psychosocial, Pharmacological, Physical and Combined Treatments for Adults with a New Episode of Depression – eClinicalMedicine

17 Aug, 2024 | 19:49h | UTC

Study Design and Population: This systematic review and network meta-analysis examined 676 randomized controlled trials (RCTs) involving 105,477 participants, comparing psychological, psychosocial, pharmacological, physical, and combined treatments for adults with a new episode of unipolar depression. The study stratified interventions based on depressive symptom severity (less severe and more severe).

Main Findings: For less severe depression, group cognitive behavioral therapy (CBT) was the only treatment class that significantly improved depressive symptoms compared to treatment as usual (TAU). For more severe depression, effective interventions included combined individual CBT with antidepressants, individual behavioral therapies, and combined treatments like acupuncture or exercise with antidepressants. Notably, antidepressants alone did not show significant effects in less severe depression.

Implications for Practice: These findings suggest that group CBT may be an effective first-line treatment for less severe depression, while combined therapies, particularly those involving antidepressants and individual psychological interventions, are more effective in treating more severe depression. This evidence could guide clinical decision-making and inform updates to treatment guidelines.

Reference: Mavranezouli I et al. (2024). A systematic review and network meta-analysis of psychological, psychosocial, pharmacological, physical and combined treatments for adults with a new episode of depression. eClinicalMedicine, 75: 102780. DOI: 10.1016/j.eclinm.2024.102780.

 


Randomized Phase 2 Trial: Extended-Release Ketamine Tablets Reduce Depression Scores in Treatment-Resistant Depression Without Significant Adverse Effects – Nat Med

14 Aug, 2024 | 13:30h | UTC

Study Design and Population: This phase 2 multicenter, randomized, placebo-controlled trial evaluated the efficacy and safety of extended-release ketamine tablets (R-107) in adults with treatment-resistant depression (TRD). A total of 231 patients underwent an initial open-label phase where they received 120 mg of R-107 daily for 5 days. Responders, defined by a ≥50% reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) scores, were randomized to receive one of four doses of R-107 (30, 60, 120, or 180 mg) or placebo twice weekly for 12 weeks.

Main Findings: The primary endpoint, change in MADRS score at week 13, showed a significant reduction of 6.1 points in the 180 mg R-107 group compared to placebo (P = 0.019). This dose also had the lowest relapse rate (42.9%) compared to 70.6% for placebo. Secondary outcomes, including response and remission rates, were generally higher for active treatment arms but reached statistical significance only in the 120 mg dose group for treatment response. The treatment was well-tolerated, with no significant increases in blood pressure or sedation.

Implications for Practice: Extended-release ketamine tablets could be a promising treatment for TRD, offering significant symptom improvement with minimal adverse effects, particularly at higher doses. The favorable safety profile and potential for at-home administration make this formulation a convenient option for wider use, though further research is needed to confirm these findings in broader populations.

Reference: Glue, P. et al. (2024). Extended-release ketamine tablets for treatment-resistant depression: A randomized placebo-controlled phase 2 trial. Nature Medicine, 30(7), 2004–2009. DOI: 10.1038/s41591-024-03063-x.

 


RCT: KarXT (xanomeline–trospium) demonstrates significant symptom reduction in schizophrenia compared to placebo – The Lancet

11 May, 2024 | 13:42h | UTC

Study Design and Population: The EMERGENT-2 study was a randomized, double-blind, placebo-controlled, flexible-dose, 5-week phase 3 trial conducted across 22 inpatient sites in the USA. It targeted adults aged 18–65 years diagnosed with schizophrenia, exhibiting a recent exacerbation in psychotic symptoms. A total of 252 participants, each with a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher and a Clinical Global Impression-Severity score of 4 or more, were enrolled and randomized equally into two groups to receive either the muscarinic receptor agonist KarXT (xanomeline–trospium) or a placebo.

Main Findings: KarXT significantly reduced the PANSS total scores from baseline to week 5, with a mean decrease of 21.2 points compared to 11.6 points in the placebo group (least squares mean difference -9.6; 95% CI -13.9 to -5.2; p<0.0001; Cohen’s d=0.61). All secondary endpoints were also met favorably for KarXT. Common adverse events for KarXT included constipation, dyspepsia, and nausea, but rates of extrapyramidal symptoms were similar between the two groups. The treatment was generally well tolerated with comparable discontinuation rates due to adverse events.

Implications for Practice: These results indicate that KarXT could represent a new class of antipsychotic treatment, diverging from traditional D2 dopamine receptor antagonists and instead leveraging muscarinic receptor activation. The promising outcomes observed in EMERGENT-2 suggest that KarXT has the potential to improve both positive and negative symptoms of schizophrenia while maintaining a favorable safety profile. Ongoing and future studies (EMERGENT-3, EMERGENT-4, and EMERGENT-5) will further elucidate the long-term efficacy and safety of KarXT.

 

Reference (link to abstract – $ for full-text):

Inder Kaul et al. (2023). Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline–trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial. The Lancet, DOI: https://doi.org/10.1016/S0140-6736(23)02190-6

 


Meta-analysis reveals 24% prevalence of eating disorders among individuals with insulin-dependent diabetes – Eat Behav

11 May, 2024 | 13:41h | UTC

This systematic review and meta-analysis evaluated the prevalence of eating disorder symptoms (EDS) in individuals aged 16 and older with insulin-dependent diabetes, covering both type 1 and type 2 diabetes. The study involved an extensive search across several databases including PubMed, Embase, Scopus, PsycINFO, and CINAHL, culminating in the inclusion of 45 studies. The meta-analysis revealed a pooled prevalence of EDS at 24% (95% CI 0.21–0.28), with prevalence reaching 27% (95% CI 0.24–0.31) among studies using the Diabetes Eating Problem Survey-Revised (DEPS-R), the most frequently utilized screening tool. Notably, the prevalence of EDS varied based on the screening tool used and was significantly associated with sex distribution; studies with a higher percentage of female participants (over 58%) reported a higher prevalence of EDS (30% vs. 18%, prevalence ratio 1.7). The study also highlighted a concerning prevalence of insulin omission, reported at 21% (95% CI 0.13–0.33). This analysis underscores the substantial occurrence of eating disorder symptoms among this patient population, emphasizing the need for tailored screening and interventions.

 

Reference (link to abstract – $ for full-text):

Pia E. Niemelä et al. (2024). Prevalence of eating disorder symptoms in people with insulin-dependent-diabetes: A systematic review and meta-analysis. Eating Behaviors, 53, 101863. DOI: https://doi.org/10.1016/j.eatbeh.2024.101863

 


RCT: Cytisinicline shows promising results in enhancing vaping cessation among adults – JAMA Intern Med

11 May, 2024 | 13:35h | UTC

Study Design and Population: The ORCA-V1 study was a double-blind, placebo-controlled randomized clinical trial conducted across five US clinical sites from July 2022 to February 2023. It enrolled 160 adults who used nicotine e-cigarettes daily and expressed a desire to quit, but were not current cigarette smokers. Participants were predominantly middle-aged (mean age 33.6 years), with a slight female majority (51.9%).

Main Findings: The trial assessed cytisinicline, a plant-based alkaloid, compared to placebo over a 12-week period with follow-up to 16 weeks. Results showed that cytisinicline significantly increased continuous abstinence from e-cigarette use during the last four weeks of treatment (31.8% vs 15.1% with placebo; odds ratio, 2.64; 95% CI, 1.06-7.10; P = .04). The effect was less pronounced but still present during the four weeks post-treatment (23.4% vs 13.2% with placebo; odds ratio, 2.00; 95% CI, 0.82-5.32; P = .15). The medication was well-tolerated, with only 3.8% of the cytisinicline group discontinuing due to adverse events.

Implications for Practice: Cytisinicline offers a promising pharmacotherapy option for adults seeking to quit vaping, demonstrating both efficacy and safety in this trial. Further research in larger populations and over longer periods is needed to confirm these findings and fully establish cytisinicline’s role in treating nicotine e-cigarette dependence.

 

Reference (link to abstract – $ for full-text):

Rigotti NA et al. (2024). Efficacy and Safety of Cytisinicline in Adult E-Cigarette Vaping Cessation: Findings from the ORCA-V1 Randomized Clinical Trial. JAMA Intern Med. Published online May 6, 2024. DOI: 10.1001/jamainternmed.2024.1313

 


Meta-Analysis: Acute adverse effects of therapeutic psilocybin doses in treating depression and anxiety – JAMA Netw Open

7 May, 2024 | 15:29h | UTC

This meta-analysis examined the acute adverse effects of psilocybin when used in therapeutic doses for treating depression and anxiety. The study analyzed data from six randomized, double-blind clinical trials involving a total of 528 participants. Significant adverse effects identified included headaches, nausea, anxiety, dizziness, and elevated blood pressure, compared to controls. No significant risks of paranoia or transient thought disorder were associated with psilocybin use. Overall, the adverse effects were tolerable and typically resolved within 48 hours, although the study calls for further research into their management.

 

Reference (link to free full-text):

Akhila Yerubandi et al. (2024). Acute Adverse Effects of Therapeutic Doses of Psilocybin A Systematic Review and Meta-Analysis. JAMA Network Open, 7(4): e245960. DOI: 10.1001/jamanetworkopen.2024.5960

 


RCT: Acute impact of provoked anger on endothelial health in healthy adults – J Am Heart Assoc

4 May, 2024 | 13:00h | UTC

This study explored the immediate effects of negative emotions on vascular endothelial health in a sample of 280 healthy adults. Participants were assigned to recall tasks that induced feelings of anger, anxiety, sadness, or a neutral emotional state, followed by assessments of endothelial health. The primary measure, endothelium-dependent vasodilation (reactive hyperemia index), significantly deteriorated in the anger group compared to the neutral condition (mean change: 0.20±0.67 vs. 0.50±0.60; P=0.007). Anxiety and sadness did not significantly affect this measure. Additionally, there were no significant changes in endothelial cell-derived microparticles or endothelial progenitor cells across all conditions. The findings indicate that short-term anger provocation can impair endothelial function, suggesting a specific pathway by which anger could increase cardiovascular disease risk.

 

Reference (link to free full-text):

Daichi Shimbo et al. (2024). Translational Research of the Acute Effects of Negative Emotions on Vascular Endothelial Health: Findings From a Randomized Controlled Study. Journal of the American Heart Association, 0:e032698. DOI: https://doi.org/10.1161/JAHA.123.032698

 


M-A: Psilocybin significantly reduces depression symptoms across diverse populations – The BMJ

4 May, 2024 | 12:51h | UTC

Study Design and Population:

This systematic review and meta-analysis synthesized data from randomized trials assessing the efficacy of psilocybin as a treatment for depression in adults. Researchers utilized five electronic databases for published literature and four databases for unpublished and international studies. The analysis included 436 participants, aged 36 to 60 years, from seven randomized trials, with both genders represented and varying comorbidities such as cancer.

 

Main Findings:

The meta-analysis revealed a significant reduction in depression scores among participants treated with psilocybin, with a Hedges’ g value of 1.64, indicating a large effect size. Notably, the improvement was more pronounced among those with secondary depression and those assessed using self-report depression scales. Subgroup analyses and metaregression also highlighted that older age and previous use of psychedelics correlated with greater symptom improvement. Despite the robust findings, high heterogeneity and a risk of small study bias led to a low certainty of evidence.

 

Implications for Practice:

The findings support psilocybin’s potential as an effective antidepressant, particularly among specific subgroups such as those with secondary depression. However, the presence of high heterogeneity and small study biases suggests that further research is needed to explore the impact of expectancy effects, moderating factors, and treatment modalities. Clinicians should consider these elements when discussing psilocybin as a treatment option with patients, and further high-quality studies are necessary to solidify its role in clinical practice.

 

Reference (link to free full-text):

Reference: Metaxa, A.-M. et al. (2024). Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis. BMJ, 385. DOI: https://doi.org/10.1136/bmj-2023-078084.

 


RCT: Xanomeline-trospium reduces psychosis symptoms in patients with schizophrenia – JAMA Psychiatry

2 May, 2024 | 23:24h | UTC

Study Design and Population:

This study, titled EMERGENT-3 (NCT04738123), is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted to evaluate the efficacy and safety of xanomeline-trospium chloride in adults with schizophrenia experiencing acute psychosis. It involved 256 participants across 30 inpatient sites in the US and Ukraine, with the study period running from April 1, 2021, to December 7, 2022. Data analysis occurred from February to June 2023.

 

Main Findings:

The primary outcome was the change from baseline to week 5 in the Positive and Negative Syndrome Scale (PANSS) total score. Xanomeline-trospium significantly reduced the PANSS total score compared to placebo, with a least squares mean difference of -8.4 and a Cohen’s d effect size of 0.60. The most common adverse events were gastrointestinal, mild to moderate in intensity, and generally transient. Safety and tolerability profiles were favorable, with similar discontinuation rates due to adverse events between the xanomeline-trospium and placebo groups.

 

Implications for Practice:

The results of EMERGENT-3, alongside the consistent findings from earlier phases of the trial, affirm xanomeline-trospium’s potential as a novel class of antipsychotic medication. Its mechanism of action, which does not involve D2 dopamine receptor blocking, offers a promising alternative to traditional antipsychotics, particularly for patients who may benefit from different therapeutic approaches due to issues with current treatments.

 

Commentary on X:

 

Reference (link to free full-text):

Kaul, I. et al. (2024). Efficacy and Safety of Xanomeline-Trospium Chloride in Schizophrenia: A Randomized Clinical Trial. JAMA Psychiatry. Published online May 1, 2024. doi:10.1001/jamapsychiatry.2024.0785

 


Cohort Study: Metabolic biomarkers and long-term risk of psychiatric disorders in over 200,000 individuals

27 Apr, 2024 | 18:29h | UTC

Study Design and Population:

This population-based cohort study assessed 211,200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort, who underwent occupational health screening primarily in the Stockholm region of Sweden from 1985 to 1996. Participants were followed longitudinally, with statistical analysis performed between 2022 and 2023. The study included extensive biomarker measurements such as glucose, triglycerides, and high-density lipoprotein.

 

Main Findings:

The study found significant associations between certain metabolic biomarkers and the risk of developing psychiatric disorders such as depression, anxiety, and stress-related disorders. Specifically, high levels of glucose (HR, 1.30) and triglycerides (HR, 1.15) were linked to an increased risk of these disorders, while high levels of high-density lipoprotein (HR, 0.88) were associated with a reduced risk. These findings held true across both genders and all disorders tested, with nested case-control analyses confirming these trends.

 

Implications for Practice:

The study suggests that metabolic dysregulation, as indicated by specific biomarkers, may either increase the risk or be a marker of increased risk for the development of common psychiatric disorders. These findings support the potential for closer monitoring and follow-up of individuals with abnormal metabolic profiles to aid in the prevention and early diagnosis of psychiatric conditions.

 

Reference (free full-text):

Chourpiliadis, C. et al. (2024). Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders. JAMA Network Open, 7(4), e244525. DOI: 10.1001/jamanetworkopen.2024.4525


RCT | Field sobriety tests display insufficient accuracy for detecting THC-specific driving impairment

11 Aug, 2023 | 15:14h | UTC

Evaluation of Field Sobriety Tests for Identifying Drivers Under the Influence of Cannabis: A Randomized Clinical Trial – JAMA Psychiatry

See also: Visual Abstract

News Release: Can field sobriety tests identify drivers under the influence of cannabis? – University of California – San Diego

Commentary: Trained Officers Using Current Field Sobriety Tests May Misclassify Cannabis-Impaired Drivers – Psychiatric News Alert

 

Commentary on Twitter

 


Review | Adverse effects of antidepressant medications and their management in children and adolescents

9 Aug, 2023 | 15:25h | UTC

Adverse Effects of Antidepressant Medications and their Management in Children and Adolescents – Pharmacotherapy

 


M-A | Absence of evidence for antipsychotics in youth unipolar depression; limited evidence in bipolar depression

9 Aug, 2023 | 15:23h | UTC

Effectiveness of atypical antipsychotics for unipolar and bipolar depression in adolescents and young adults: A systematic review and meta-analysis – Journal of Affective Disorders

 


Cohort Study | Clozapine, but not olanzapine or quetiapine, linked with higher perimyocarditis and heart failure risk

8 Aug, 2023 | 13:14h | UTC

The association between exposure to clozapine, olanzapine, and quetiapine and the outcomes perimyocarditis and heart failure: A population-based cohort study – Psychiatry Research

 


Study | Gastric bypass linked to increased risk of non-alcohol substance use disorder

7 Aug, 2023 | 14:23h | UTC

Non-alcohol substance use disorder after bariatric surgery in the prospective, controlled Swedish Obese Subjects study – Obesity

News Release: Gastric bypass surgery associated with non-alcohol substance use disorder – Obesity – The Obesity Society

 


RCT | 52-week antidepressant adjunctive therapy did not lead to a statistically significant benefit over 8-week therapy in bipolar I depression

4 Aug, 2023 | 12:11h | UTC

Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression – New England Journal of Medicine (link to abstract – $ for full-text)

News Release: Modern antidepressants may reduce risk of relapse for patients with bipolar depression – University of British Columbia

 

Commentary on Twitter

 


Cohort Study | Increased mortality rates in delirium tremens patients versus alcohol withdrawal or dependence

3 Aug, 2023 | 13:35h | UTC

Mortality and alcohol-related morbidity in patients with delirium tremens, alcohol withdrawal state or alcohol dependence in Norway: A register-based prospective cohort study – Addiction

 


Study | Increasing alcohol-related mortality rates in US women, 1999-2020

3 Aug, 2023 | 13:20h | UTC

Trends in Alcohol-Related Deaths by Sex in the US, 1999-2020 – JAMA Network Open

Commentary: As alcohol-related deaths rise in the US, women are increasingly at risk, study shows – CNN

 


Evidence Review | AA and other 12-step programs outperform CBT for alcohol use disorder

2 Aug, 2023 | 14:05h | UTC

Alcohol dependence: evidence and experience on 12 steps to recovery – Evidently Cochrane

Original study: Alcoholics Anonymous and other 12‐step programs for alcohol use disorder – Cochrane Library

 


Cohort Study | Depression at any life stage linked to increased dementia incidence

2 Aug, 2023 | 13:49h | UTC

Association of Early-, Middle-, and Late-Life Depression With Incident Dementia in a Danish Cohort – JAMA Neurology (link to abstract – $ for full-text)

Commentary: Depression Over Adulthood May Increase Risk of Dementia – Psychiatric News Alert

 


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