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Cannabidiol (CBD), the main non-intoxicating compound in cannabis, has been hypothesized to reduce the adverse effects of Δ 9 -tetrahydrocannabinol (THC), the main psychoactive and analgesic component of cannabis. This clinical trial investigated the hypothesis that CBD counteracts the adverse effects of THC and thereby potentially improves the tolerability of cannabis as an analgesic. A randomized, double-blind, placebo-controlled, five-way cross-over trial was performed in 37 healthy volunteers. On each visit, a double-placebo, THC 9 mg with placebo CBD, or THC 9 mg with 10, 30, or 450 mg CBD was administered orally. Psychoactive and analgesic effects were quantified using standardized test batteries. Pharmacokinetic sampling was performed. Data were analyzed using mixed-effects model. Co-administration of 450 mg CBD did not reduce, but instead significantly increased subjective, psychomotor, cognitive, and autonomous effects of THC (e.g., VAS "Feeling High" by 60.5% (95% CI: 12.7%, 128.5%, P < 0.01)), whereas THC effects with 10 and 30 mg CBD were not significantly different from THC alone. CBD did not significantly enhance THC analgesia at any dose level. Administration of 450 mg CBD significantly increased AUC last of THC (AUC last ratio: 2.18, 95% CI: 1.54, 3.08, P < 0.0001) and 11-OH-THC (AUC last ratio: 6.24, 95% CI: 4.27, 9.12, P < 0.0001) compared with THC alone, and 30 mg CBD significantly increased AUC last of 11-OH-THC (AUC last ratio: 1.89, 95% CI: 1.30, 2.77, P = 0.0013), and of THC (AUC last ratio: 1.44, 95% CI: 1.01, 2.04, P = 0.0446). Present findings do not support the use of CBD to reduce adverse effects of oral THC or enhance THC analgesia., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Evidence for worsening mental health among individuals with intellectual and developmental disabilities (IDD) during COVID-19 sparked concerns for increased use of psychoactive medications., Objective: To examine the impact of COVID-19 on psychoactive medication use and clinical monitoring among individuals with IDD in Ontario, Canada., Methods: We conducted a repeated cross-sectional study among individuals with IDD and examined weekly trends for psychoactive medication dispensing and outpatient physician visits among those prescribed psychoactive medications between April 7, 2019, and March 25, 2023. We used interventional autoregressive integrated moving average models to determine the impact of the declaration of emergency for COVID-19 (March 17, 2020) on the aforementioned trends., Results: The declaration of emergency for COVID-19 did not significantly impact psychoactive medication use among individuals with IDD. Provision of clinical monitoring remained relatively stable, apart from a short-term decline in the weekly rate of outpatient physician visits following the declaration of emergency for COVID-19 (step estimate: 21.26 per 1000 individuals [p < 0.01]; ramp estimate: 0.88 per 1000 individuals [p = 0.01]). When stratified by mode of delivery, there was a significant shift towards virtual care (step estimate: 78.80 per 1000 individuals; p < 0.01). The weekly rate of in-person physician visits gradually increased, returning to rates observed prior to the COVID-19 pandemic in January 2023., Conclusion: Although access to clinical care remained relatively stable, the shift towards virtual care may have negatively impacted those who encounter challenges communicating via virtual mediums. Future research is required to identify the support systems necessary for individuals with IDD during virtual health care interactions., Competing Interests: Declaration of competing interest The authors have no known conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The acute psychoactive, autonomic, and endocrine effects of the new psychoactive substance (NPS) 5,6-methylenedioxy-2-aminoindane (MDAI; 3.0 mg/kg, range 180-228 mg) were investigated in six healthy volunteers (four males, two females) in a non-blinded fashion without placebo. Subjective, cardiovascular, and endocrine responses were compared with two different doses of 3,4-methylenedioxymethamphetamine (MDMA) (75 mg and 125 mg) described in previously published placebo-controlled studies, which used identical outcome measures including Visual Analogue Scales (VAS), the Adjective Mood Rating Scale (AMRS), and the 5 Dimensions of Altered States of Consciousness (5D-ASC) scale. MDAI was well tolerated and produced subjective effects comparable with those of 125 mg MDMA. MDAI increased blood pressure similar to 125 mg MDMA but did not increase heart rate or body temperature. MDAI increased cortisol and prolactin levels and could be detected in serum about 20 min post ingestion and remained detectable at least for 4 days. In urine, MDAI was detectable over a period of at least 6 days. Further clinical investigations are warranted to assess whether MDAI could serve as drug with medicinal properties., (© 2023 The Authors. Drug Testing and Analysis published by John Wiley & Sons Ltd.)

Background: Psychotropic medications are commonly used to treat several mental health conditions. The aim of this study was to determine the impact of psychotropic medications in patients undergoing primary total knee arthroplasty (TKA) with respect to postoperative opioid use, complications, patient-reported outcome measures, and satisfaction., Methods: This is a retrospective cohort study of 514 consecutive patients undergoing primary TKA. There were 120 patients (23.3%) who were excluded due to preoperative opioid usage. The remaining 394 patients had a minimum 1-year follow-up. Of those, 133 (34%) were on psychotropic medications preoperatively and were compared to the remaining 261 (66%) patients who were not on psychotropics. Clinical data, satisfaction, Knee Society (KS) scores, Western Ontario McMaster Universities Arthritis Index, Patient-Reported Outcomes Measurement Index Score, Forgotten Joint Scores, Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, postoperative opioid medication usage, and complications were compared., Results: The study cohort (psychotropic medications) had significantly lower postoperative KS Function, KS Knee, Forgotten Joint Scores, Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, Western Ontario McMaster Universities Arthritis Index, and Patient-Reported Outcomes Measurement Index Score compared to the control group. The study group had a lower overall satisfaction score (Likert scale 1 to 5) and a lower percentage of patients either satisfied or very satisfied (4.55 versus 4.79, P < .001; 92.0 versus 97.24%, P = .03, respectively). Postoperative opioid usage was significantly greater in the study group at both 6.4 weeks (range, 4 to 8) and 12-month follow-up (52.76 versus 13.33%, P < .001; 5.51 versus 0.39%, P = .002, respectively). There were no differences in complications and revisions between the groups., Conclusions: Patients on psychotropic medications should be educated on the risk of increased opioid consumption, diminished satisfaction, and patient-reported outcome measures following primary TKA. Given the large number of patients on psychotropic medications undergoing TKA, additional studies are needed to further improve clinical outcomes in this group., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: None declared. Refer to the online supplementary files to view the ICMJE form(s).

Introduction Since the last edition of the Black Book, several innovative agents have been approved or are poised to be approved in the coming year. These include novel antidepressants, the first muscarine agonist for the treatment of schizophrenia, the first psychedelic which may be approved for the treatment of PTSD (Post Traumatic Stress Disorder), and the first disease modifying drug for the treatment of Alzheimer's disease. Three new antidepressants have come to the market in the past 18 months. The first of those, Auvelity, the combination of bupropion and dextromethorphan, takes advantage of a pharmacokinetic and pharmacodynamic synergism between the two drugs. 85 Dextromethorphan has several pharmacodynamic properties including actions on the NMDA receptor and the Sigma 1 receptor, adding to the indirect norepinephrine agonist properties of bupropion. How Dextromethorphan is rapidly metabolized via the CYP2D6 isoenzyme to dextrophan that may have mu opioid agonist properties. The combination with bupropion, a CYP2D6 inhibitor, inhibits the metabolism of dextromethorphan allowing for more consistent therapeutic levels. The combination of dextromethorphan 45 mg twice per day and bupropion SR 105 mg twice daily appears to be more effective than an equivalent dose of bupropion alone both in speeding up antidepressant response and achieving remission. However, it's not clear at this time how the combination would compare with a more typical dose of bupropion of 300-450 milligrams a day range. The phase III program for Auvelity, showed that the drug was well tolerated with the most common side effects being dizziness, headache, and dry mouth. 86 Another novel antidepressant agent approved in 2023 is zuranolone (Zurzuvae). Zuranolone is an oral analog of IV brexanalone, and like brexanolone, was approved for the treatment of post-partum depression. 83 The advantages of zuranolone over brexanalone are many. While brexanolone is a 60-hour intravenous infusion that must be administered in a health care facility, zuranolone is a once/day oral medication that is usually taken at home. Like brexanolone, and unlike most antidepressants, zuranolone has a short course of treatment, lasting just 14 days. Zuranolone's, as does brexanolone, is thought to act primarily as allosteric modulator of the GABA-a receptors. Despite only 14 days of treatment, zuranolone produced in depression in post-partum patients a clinically and significantly meaningful improvement at day 15 and continued to day 45 or 1 month past the end of treatment. Zuranolone is a schedule IV drug. The most common side effect in clinical trials was somnolence with 36% of participants reporting this side effect vs only 6% of those on placebo. 84 Other common side effects included dizziness, diarrhea and fatigue. While the FDA declined to approve zuranolone as monotherapy or as an adjunctive treatment to standard antidepressants in major depression itself, there are positive studies in non-post-partum major depression albeit with smaller effect sizes and less consistent duration of activity. It is likely that zuranolone will continue to be studied in other depressive syndromes such as depression with anxious distress. The third "new" antidepressant approved late 2023 was gepirone (Exxua). Gepirone is not exactly a new or novel antidepressant and originally sought approval in the US about 20 years ago. 88 There had been two positive studies of gepirone during the original NDA application but also a number of failed, negative, or non-informative studies as well. Thus, the FDA declined to originally approve the drug. However, failed and negative trials are common with antidepressants and after much internal debate, the FDA ultimately agreed to approve the drug based on the positive trials and a relatively favorable side effect profile. Gepirone, like buspirone, is a partial agonist of the 5HT1a receptor and a 5HT2 antagonist. As such, gepirone does not tend to be associated with sexual side effects, weight gain, or sedation. The most common side effects are dizziness, nausea, and insomnia which tend to improve in many patients over time. Second generation antipsychotics (SGAs) continue to be the only class of agents [other than esketamine (Spravato)] approved in adjunctive treatment of resistant major depression. In addition to olanzapine (combined with fluoxetine; Symbyax), aripiprazole (Abilify), quetiapine (Seroquel), brexpiprazole (Rexulti), cariprazine (Vraylar) became the latest SGA to be approved in 2022. 90 Adjunctive cariprazine at 1.5 mg daily was significantly more effective than adjunctive placebo in patients with MDD who had failed to achieve an adequate response with an antidepressant alone after 6 weeks of treatment. Interestingly, a 3 mg dose of cariprazine was less consistently effective. 91 The major advantage of cariprazine over some of the other approved adjunctive SGA's is easy dosing, with the starting 1.5 mg dose being the optimal therapeutic dose for most people, and a lower metabolic side effect burden with most subjects having limited or no weight gain in short term trials. The most common side effect were akathisia/restlessness, fatigue, and nausea. Lumateperone (Caplyta) is also has positive phase III data in the adjunctive treatment of major depression and is expective file for approval in late 2024. Another recent major development in psychopharmacology is the reemergence of psychedelics in the treatment of psychiatric disorders. The first of these is MDMA (phenethylamine 3,4-methylenedioxymethamphetamine) assisted psychotherapy for the treatment of PTSD. A New Drug Application (NDA) was accepted by the FDA for MDMA in the treatment of PTSD in late 2023. 87 Because the drug is being fast tracked as a "breakthrough" treatment by the FDA, it was expected to see approval in the summer of 2024. The phase II and III data for MDMA assisted psychotherapy in the treatment of PTSD have been quite consistent and impressive. However, independent reviews have pointed to significant deficiencies in these studies including the bias introduced because of functional unblinding; virtually all patients in psychedelic studies can guess whether they got the active drug or placebo. The functional unblinding, the lack of standardization of adjunctive psychotherapy as well as the abuse potential of MDMA, may delay an FDA approval. The typical regimen in these trials included 3 preparatory psychotherapy sessions followed by once/month dosing sessions (lasting about 8 hours) and using doses of 120-160 mg in a split dose. There were typically 3 monthly dosing sessions, each followed by 3 integrative psychotherapy sessions to help subjects process and understand their experiences during the dosing sessions. In the most recent phase 3 trials, over 70% of subjects no longer met criteria for PTDS compared to 46% of those treated with psychotherapy and placebo alone. 89 The only approved medications for treating PTSD are two SSRIs, paroxetine and sertraline. These drugs effect only some dimensions of PTSD with only 20-30% achieving a remission level response with these drugs. Thus, MDMA assisted psychotherapy appears to achieve much higher levels of remission and response than has been true for the SSRIs. Since MDMA is not taken continuously, side effects from MDMA tend to be short lived. Side effects have included muscle tightness, nausea, diminished appetite, excessive sweating, feeling cold and dizziness among others. Since MDMA is currently a schedule I drug, it is likely that a rigorous Risk Evaluation Mitigation (REMs) program will be put in place and a limited number of centers and clinicians will be designated to perform MDMA assisted psychotherapy for PTSD. In addition to MDMA, psilocybin-assisted psychotherapy is in phase 3 trials for treating resistant depression but unlikely to be available before late 2025 at the earliest. An argument can be made that there has not been a truly novel antipsychotic since the introduction of clozapine in the US in 1990. All first-generation antipsychotics have been dopamine 2 antagonists and second-generation drugs have involved some ratio of 5HT2 antagonism to D2 blockade. In 2023, the FDA accepted the application of xenomaline/tropsium (KarXT) which may become the first muscarinic M1M4 agonist approved for the treatment of schizophrenia. 82,83 Tropsium is added as a muscarine antagonist to block the peripheral cholinergic effects of a muscarine agonist. Xenomaline/tropsium appears to be effective in treating both positive and negative symptoms of schizophrenia. In a phase 3 study of 407 patients with schizophrenia, xenomaline/tropsium at doses of xenomaline/50 mg/tropsium 20 mg twice daily up to 125 mg/30 mg twice daily was significantly more effective than placebo in treating both and negative symptoms over 5 weeks of treatment. As would be expected, the side effect profile of xenomaline/tropsium is very different that all currently available antipsychotics. There is no risk of EPS as it is not a dopamine antagonist, and xenomaline/tropsium is not associated with significant metabolic effects. The side effects are cholinergic in nature and include constipation, dry mouth, and nausea. A decision is expected in September of 2024. The year 2023 also saw the approval of the first disease modifying drug in the treatment of Alzheimer's disease, lecanemab (Lequembi). While acetylcholinesterase inhibitors and memantine have been available for decades, these drugs modestly improve cognition in Alzheimer's disease patients and do not alter the progressive course of the illness. Lecanemab is an IV monoclonal antibody that targets the removal of beta-amyloid in the brain as well proto-fibrils that are also known to be toxic to neuronal tissue. When given early in the course of the illness, patients treated with Lecanemab showed 27% less decline on some measures of cognition and function than did patients treated with a placebo over 18 months (about 1 and a half years). It is not known whether treatment for longer than 18 months would show lesser or greater decline over time. However, there are simulation studies that suggest that Lecanemab may modestly reduce the number of patients who progress to severe Alzheimer's disease and require institutional care. The standard dose is 10 mg/kg given via IV over one hour every 2 weeks for 18 months. Lecanemab is typically administered in an infusion center so that side effects can be monitored. The most serious side effects of Lecanemab are amyloid related imaging abnormalities (ARIA) that are associated with brain edema and microhemorrhages. ARIA can occur in up to 15% of patients. More common side effects are headache and nausea. While it remains to be seen how useful these new agents will be in clinical practice, they do represent an approach to treating neuropsychiatric disorders that are a notable departure from the pharmacotherapy of the past half century. It seems likely that some patients who have not been able to respond to or tolerate traditional pharmacotherapy will find hope in these new medications., (Copyright © 1964–2024 by MedWorks Media Inc, Los Angeles, CA All rights reserved. Printed in the United States.)

Background: Particularities in psychiatry care can increase the risk of medication errors (MEs)., Objective: To analyze the MEs that occurred in a psychiatric hospital and to quantify relationships between the use of certain types of medication and the type of MEs., Methods: We conducted a retrospective register based cross-sectional study in a French psychiatric hospital (2014-2021). All MEs were analyzed using ALARM method to identify type, stage of occurring and interception (defenses), consequences, drug involved and root causes. The prevalence-odds ratio (POR) was calculated to estimate relationships between five selected medication situations (long-acting injectable antipsychotics (LAIA), oral liquid dosage forms in a multiple-unit-container (OLDS-MC), psychotropic drugs (PD), controlled medicines (CM) or high-alert drugs) and the type of MEs occurred., Results: Among the 609 MEs reported, wrong dose (32.2%), wrong drug (30.3%), omission (14.2%) and wrong patient (12.9%) were frequently observed. The ME occurrence stage were prescribing (55.3%) and administration (30.2%). Medication order review intercepted 77.9% of MEs. CM or LAIA increased the risk of medication omission (POR: 3.9, 95%CI: 1.8-8.4 and 2.5, 95%CI; 1.2-5.1, respectively) while the use of high-alert medications decreased it (0.2, 95%CI: 0.1-0.8). OLDS-MC and PD were more likely to be administered to the wrong patient (6.1, 95%CI: 3.3-11.4 and 16.1, 95%CI: 7.2-35.8). LAIA were associated with an increased risk of wrong dose (3.4, 95%CI: 1.8-6.3). Actual errors risk was lower with high-alert drugs (0.5, 95%CI: 0.3-09), but higher with CM (3.5, 95%CI: 1.5-8.0), OLDS-MC (2.1, 95%CI: 1.2-3.8) and PD (2.5, 95%CI: 1.8-3.5). Patients exposed to high-alert drugs were likely to have a serious error (3.5, 95%CI: 1.2-10.4)., Conclusions: This study sheds an innovative approach to analyze MEs by demonstrating that certain medication situations were more likely to lead to certain types of error. This enables the most appropriate prevention barriers to be put in place to intercept ME., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite the increasing availability of new psychoactive substances (hereafter referred to as "salts") in Eastern Europe and Central Asia, there is a dearth of epidemiological data on the relationship between injecting "salts" and HIV risk behaviours. This is particularly relevant in settings where injection drug use accounts for a substantial proportion of the HIV burden, such as in Kyrgyzstan, a former Soviet Republic. This study assessed whether injecting "salts" is associated with sexual and injection-related HIV risk behaviours among people who inject drugs in Kyrgyzstan., Methods: The Kyrgyzstan InterSectional Stigma Study is a cohort of people who inject drugs in Kyrgyzstan's capital of Bishkek and the surrounding rural administrative division of Chuy Oblast. We conducted a cross-sectional analysis using survey data collected from cohort participants between July and November 2021, which included information on injection drug use (including "salts") and HIV risk behaviours. To minimize confounding by measured covariates, we used inverse-probability-weighted logistic and Poisson regression models to estimate associations between recent "salt" injection and HIV risk behaviours., Results: Of 181 participants included in the analysis (80.7% men, 19.3% women), the mean age was 40.1 years (standard deviation [SD] = 8.8), and 22% (n = 39) reported that they had injected "salts" in the past 6 months. Among people who injected "salts," 72% (n = 28) were men, and most were ethnically Russian 59% (n = 23), with a mean age of 34.6 (SD = 9.6). Injecting "salts" was significantly associated with a greater number of injections per day (adjusted relative risk [aRR] = 1.59, 95% confidence interval [CI] = 1.30-1.95) but lower odds of using syringe service programmes in the past 6 months (adjusted odds ratio [aOR] = 0.20, 95% CI = 0.12-0.32). Injecting "salts" was also significantly associated with lower odds of condomless sex in the past 6 months (aOR = 0.42, 95% CI = 0.24-0.76) and greater odds of having ever heard of pre-exposure prophylaxis (aOR = 4.80, 95% CI = 2.61-8.83)., Conclusions: (PWID) people who inject drugs who inject "salts" are a potentially emergent group with increased HIV acquisition risk in Kyrgyzstan. Targeted outreach bundled with comprehensive harm reduction and pre-exposure prophylaxis services are needed to prevent transmission of HIV and other blood-borne viruses., (© 2024 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Synthetic cathinones represent one of the largest and most abused new psychoactive substance classes, and have been involved in numerous intoxications and fatalities worldwide. Methcathinone analogues like 3-methylmethcathinone (3-MMC), 3-chloromethcathinone (3-CMC), and 4-CMC currently constitute most of synthetic cathinone seizures in Europe. Documenting their consumption in clinical/forensic casework is therefore essential to tackle this trend. Targeting metabolite markers is a go-to to document consumption in analytical toxicology, and metabolite profiling is crucial to support investigations. We sought to identify 3-CMC, 4-CMC, and 4-bromomethcathinone (4-BMC) human metabolites. The substances were incubated with human hepatocytes; incubates were screened by liquid chromatography-high-resolution tandem mass spectrometry and data were mined with Compound Discoverer (Themo Scientific). 3-CMC-positive blood, urine, and oral fluid and 4-CMC-positive urine and saliva from clinical/forensic casework were analyzed. Analyses were supported by metabolite predictions with GLORYx freeware. Twelve, ten, and ten metabolites were identified for 3-CMC, 4-CMC, and 4-BMC, respectively, with similar transformations occurring for the three cathinones. Major reactions included ketoreduction and N-demethylation. Surprisingly, predominant metabolites were produced by combination of N-demethylation and ω-carboxylation (main metabolite in 3-CMC-positive urine), and combination of β-ketoreduction, oxidative deamination, and O-glucuronidation (main metabolite in 4-CMC-positive urine). These latter metabolites were detected in negative-ionization mode only and their non-conjugated form was not detected after glucuronide hydrolysis; this metabolic pathway was never reported for any methcathinone analogue susceptible to undergo the same transformations. These results support the need for comprehensive screening strategies in metabolite identification studies, to avoid overlooking significant metabolites and major markers of consumption., (© 2024. The Author(s).)

Objective: Understand the motivations and expectations of pregnant women using psychoactive substances during prenatal care., Methods: A qualitative study developed in the light of Alfred Schütz's Theoretical Framework of Phenomenological Sociology, in which 25 pregnant women using psychoactive substances, belonging to a Family Health Strategy, participated. Data production took place between August and November 2022., Results: Two units of meanings emerged: (i) social influences for the performance of prenatal care and (ii) expectation regarding the care to be received by the health professional. Pregnant women do pre-natal due to family influences, for fear of losing their children due to loss of guardianship and concern about the well-being and development of the baby. And, the expectations are that they receive good attention, feel safe when they are attended to by health professionals and also that they are understood and have a relationship of trust., Conclusion: Pregnant women who use psychoactive substances bring motivations for prenatal care linked to the past, such as influences from family members and previous experiences. As for expectations, they are related to the child's health and the care expected by professionals. Finally, strategies to reduce harm during pregnancy of users of psychoactive substances are fundamental for the effectiveness of care., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright� by the Universidad de Antioquia.)

In December 2022, the Ministry of Health, Labour and Welfare (MHLW) of Japan issued and implemented the guideline for evaluating the effects of psychotropic drugs on motor vehicle driving performance. This guideline recommends the use of a tiered approach to assess clinically meaningful driving impairment. It is noted that adverse events cannot be solely explained by pharmacokinetics, as the onset and duration of these events vary. Among these adverse events, those affecting alertness, such as drowsiness caused by psychotropic drugs on driving performance, are more frequently observed during initial treatment stages and dose escalation. Hence, when evaluating the effects of psychotropic drugs on driving performance, it becomes crucial to assess the persistence of clinically meaningful impairment. Therefore, the MHLW guideline, developed by the authors, emphasizes the need to assess the temporal profile of adverse events affecting driving in all clinical trials. Additionally, the guideline states that when conducting driving studies, the timing of multiple dosing should consider not only the pharmacokinetics of the investigational drug but also its tolerance., (© 2024 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Introduction: There is a large body of preclinical data implicating that grapefruit juice (GJ) inhibits many CYP 450 isoforms. The potential of GJ-to-drug is of high relevance to clinical psychiatry, because a wide range of psychotropic medicines undergo CYP 450 metabolism and P-gp transport., Areas Covered: Relevant data were identified by searching the electronic databases up to February 2024. This work constitutes a summary of preclinical and clinical data on GJ impact on CYP 450 metabolism, P-glycoprotein, and organic anion-transporting polypeptides (OATPs), with focus on studies that assessed GJ-to-psychotropic drug interactions. Additionally, an unpublished case series of nine patients is provided., Expert Opinion: The impact of GJ on CYP 3A4 appears to be the critical mechanism for the majority of GJ-to-psychopharmacotherapy interactions described in human studies or case reports. However, there are studies and cases of patients clearly showing that this is not the only route explaining the GJ effect, and at times, this particular is of no relevance and that other CYP 450 isoforms as well as drug transporting proteins might be involved. The risk of GJ-to-psychotropic drugs needs to be further evaluated in a 'real-world' setting and apply not only measures of pharmacokinetics but also treatment effectiveness and safety.

Objective: In psychiatry, polypharmacy or high psychotropic drug doses increase adverse drug event (ADE) prevalence. However, the full relationship between polypharmacy and ADEs is unclear, and few studies have evaluated dose equivalents for psychotropic drugs for ADEs. Thus, we conducted a retrospective analysis to clarify the effects of polypharmacy and chlorpromazine (CP)-, diazepam (DAP)-, and imipramine- equivalent doses on all ADEs in inpatients., Methods: Psychiatric inpatients in a Japanese hospital from April 1, 2016 to March 31, 2018, were enrolled. ADE severity and causality were assessed. Multiple logistic regression analyses were performed to evaluate ADE risk factors., Results: Among 462 patients analyzed, out of 471 patients enrolled, 145 (31.4%) experienced ADEs. The causality assessment determined that "possible" was 96.5%. The most common ADEs were nervous system disorders (35%). Multiple logistic regression analyses indicated an increase in ADE prevalence with the number of drugs used (≥5; p = 0.026); CP-equivalent dose (p = 0.048); and endocrine, nutritional, and metabolic disorders (p = 0.045). DAP-equivalent dose; infectious and parasitic diseases; and injury, poisoning, and consequences of other external causes decreased ADE prevalence (p = 0.047, 0.022, and 0.021, respectively)., Conclusions: Avoiding polypharmacy in psychiatric inpatients and adjusting drug regimens to safe equivalent doses could reduce ADEs during hospitalization., (© 2024 John Wiley & Sons Ltd.)

Introduction: It is known that non-adherence to psychiatric medications has harmful consequences for both patients and society., Objective: To collect information on the incidence of non-adherence, and the factors and causes affecting adherence to psychopharmacological treatment in patients with severe and persistent mental disorders., Methods: A systematic review of scientific articles on adult patients (>17 years) published in the last five years (2015-2020) on specialised databases such as PubMed, Scopus, Scielo and BioMed. Original articles from indexed journals with an impact factor >0.5, in English or Spanish, with an analytical, prospective, retrospective, cross-sectional and randomised design were included. Once the articles were identified, they were analysed, extracting the information necessary to answer the research questions., Results: Fifteen articles were included. Of these, 40% (n = 6) were published in 2020, 20% (n = 3) were produced in China and 53.3% (n = 8) had an observational design. A total of 5,837 patients were included, of which 50.6% were men (n = 2,955), with moderate adherence (n = 10; 66.7%) reported in 10 investigations. Non-adherence varies from 7.7% to 60.6%. The factors that affect adherence are specific to the patient (age and sex), their family support network, and related to the disease or the treatment. The main cause of non-adherence is lack of insight., Conclusions: Adherence to treatment with psychotropic drugs is multifactorial. Access to mental health services should be improved, with an emphasis placed on patient education and providing greater knowledge of mental illness. Interventions to promote education and interaction with the psychiatrist could be beneficial., (Copyright © 2022 Asociación Colombiana de Psiquiatría. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: alcohol and other psychoactive substances have adverse health effects, particularly on young people. This study determined the prevalence of alcohol and other psychoactive substance abuse and its association with depression among Niger Delta University, Bayelsa State, Nigeria, medical students., Methods: a cross-sectional study involving 243 medical students who completed a patient-rated version of the Mini International Neuropsychiatric Interview (MINI-PR). For analyzing the data, descriptive and inferential statistics were employed., Results: most respondents were 18 to 24 years old (67.1%), and 52.7% were male; the prevalence of major depressive episodes (current) and lifetime alcohol and other psychoactive use was 30.5%, 25.5%, and 21%, respectively. Also, the prevalence of current alcohol abuse and dependence was 5.8% and 4.9%, respectively. Alcohol use (χ 2 : 12.57, p = 0.001) and abuse (χ 2 : 22.33, p = 0.001) were significantly associated with depression. Psychoactive substance use was significantly associated with depression (χ 2 : 12.91, p = 0.001). The odds of having depression increased with the use of alcohol (OR: 3.54; 95% CI: 1.71-7.33) and psychoactive substances (OR: 4.52; 95% CI: 1.88-10.88)., Conclusion: alcohol and psychoactive substance use were significantly associated with depression. Organizing interventions to reduce such unhealthy social practices among medical students is necessary., Competing Interests: The authors declare no competing interests., (Copyright: Tamaraemumoemi Emmanuella Okoro et al.)

Background: The increase in the use of psychoactive substances, alcohol and cigarettes in young people has become a public health problem. The identification of factors that increase or reduce the risk of exposure to these substances and the possible relationship between them is essential for planning strategies with a risk approach; hence the reason for this study. The objective was to establish the profile of use of psychoactive substances, alcohol and cigarettes and the factors associated with such use in nursing students of a higher education institution., Methods: Quantitative, observational, analytical cross-sectional study., Results: We included 310 students from 1 st to 9th semester of a Nursing programme from a private higher education institution in Bogotá. The prevalence of psychoactive substance use in the last year was 2.96% (95%CI, 1.36-5.54), with marijuana being the substance most used (55.55%). The prevalence of alcohol and cigarette use during the last 12 months was estimated at 86.64% (95%CI, 83.24-91.0) and 12.16% (95%CI, 8.43-15.88) respectively. A statistically significant association was found between the use of these substances: alcohol use was associated with cigarette use (OR = 3.22; P = 0.006) and smoking was associated with psychoactive substance use (OR = 15.4; P < 0.001)., Conclusions: Alcohol use increases the likelihood of smoking cigarettes, and this in turn increases the likelihood of psychoactive substance use, in this university population., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Introduction: Chemsex is defined by the use of psychoactive substances to facilitate or improve sexual relations. Our objectives were to assess the prevalence of the practice of 'chemsex' in a population of French university students and to identify socio-demographic and clinical factors associated with this practice., Material and Methods: We have used an anonymous online questionnaire comprising 15 questions on socio-demographic characteristics, chemsex use, sexual satisfaction, the type of substances used in this sexual context and their route of administration., Results: A total of 680 people were included in our study. Among them, 22.5% reported chemsex behaviour in the past year. Using a multivariate analysis, factors associated with chemsex were dating application use ( p  = 0.049) and pornography use [viewing more than once per month ( p  = 0.002)]. Having a sexual partner involved in chemsex ( p  < 0.0001), celibacy ( p  = 0.007), sexual orientations other than heterosexual ( p  = 0.0013) and especially bisexuality ( p  = 0.0002) were also significantly associated with chemsex., Conclusion: This is the first study reporting a high prevalence of chemsex in a university student population. Further larger studies should be conducted to confirm these results showing a high prevalence of this at-risk behaviour., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Ethnopharmacological Relevance: Indigenous groups of the Amazon have developed intricate methods for the application of psychoactives, among which particularly the dieta or diet method of Peruvian-Amazonian traditional medicine stands out. It is a retreat-like intervention involving lengthy periods of social, behavioural, and alimentary restrictions, while ingesting specially prepared plant substances. The interplay of the dietary conditions and plants ingested sensitizes the dieter to receive healing, strength, guidance, and knowledge. From a clinical scientific point of view, the method has remained largely underexplored, but seems more pertinent than ever given the increasing interest in Amazonian psychoactive preparations including ayahuasca (Banisteriopsis caapi) and the burgeoning field of psychedelic-assisted therapies in general., Aim of the Study: This study offers a descriptive account and emic interpretation of the Peruvian-Amazonian dieta. More specifically we document in detail the procedure, its context and purpose of application, effects, modes of action, adverse effects, and risks, from the perspectives of a sample of Peruvian traditional healers. The Peruvian-Amazonian dieta is a multi-purpose method for making use of medicinal plants, many of which (but not all), are psychoactive; the current work especially focuses on its therapeutic applications in conjunction with psychoactives., Methods: We interviewed 16 healers working in the Ucayali, San Martín, and Loreto provinces of Peru using a semi-structured interview approach. Interviews were audio-recorded and transcribed verbatim. The extensive data derived from these interviews were analysed by means of computer-assisted manifest qualitative content analysis using a theory-advancing approach. Over 500 coded text segments were categorized, resulting in 7 main theme clusters and corresponding sub-themes., Results: The interviewed healers described a complex intervention with multifaceted applications (treatment, prevention, training) and effects in various domains (body, mind, spirit, energy). The process was portrayed as transformative, with benefits attributed to the effects of the so-called teacher plants in conjunction with the diet's conditions, along with the skill of the healer guiding the intervention. Further, a detailed risk assessment revealed sophisticated safety measures and tools designed to address adverse responses. The importance of adequate training of the healer that administers the diet was particularly highlighted in this context., Conclusions: The dieta is a central therapeutic concept and tool in Peruvian-Amazonian traditional medicine and a unique method for using psychoactive plants. Multidisciplinary health research that includes traditional treatment methods from Indigenous cultures, Amazonian and other, should not be neglected in the current global interest in psychedelic therapies; such research may in the long-term contribute to a more inclusive psychedelic research paradigm as well as healthcare practice in countries where rich traditional healing systems exist, and perhaps beyond. It may also contribute to the recognition of the Indigenous healers as not only historical forerunners, but also current leading experts in psychedelic medicine., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: Psychotropic medications include many drugs that may be inappropriate for older individuals with cognitive impairment. In Sweden, many people become registered in the Swedish Dementia Registry when they are diagnosed with major neurocognitive disorder (NCD). In this study, we aim to describe psychotropic drug use and associated factors among older Swedish people with major NCD., Methods: This study included 38,251 people ≥ 65 years from the Swedish registry for cognitive/dementia disorders diagnosed during 2007-2017. Drug use was defined as one or more filled prescription(s) recorded in the Swedish Prescribed Drug Register during 1 July to 31 December 2017. Associations between psychotropics and age, sex, diagnosis date, Mini-Mental State Examination score and major NCD subtype were analysed through multiple logistic regression., Results: We found that 12.0% of the individuals filled at least one prescription for antipsychotics, 22.0% for anxiolytics, 23.0% for sedatives or hypnotics, 43.2% for antidepressants and 56.7% for antidementia drugs. In brief, psychotropic use was associated with female sex, higher age, longer time since diagnosis and specific subtypes of major NCD; the strongest association was found between antipsychotics and Lewy body dementia (odds ratio 2.40, 95% confidence interval 2.04-2.82)., Conclusion: Psychotropic drugs were frequently dispensed among older Swedish people with major NCD. The use of antipsychotics and medications with sedative properties warrants concern, especially among those with Lewy body dementia who are severely sensitive to antipsychotics. A more restrictive prescribing pattern regarding these medications might reduce the risk of drug-related problems in this vulnerable group of people., (© 2021. The Author(s).)

Resting state fMRI has been employed to identify alterations in functional connectivity within or between brain regions following acute and chronic exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive component in cannabis. Most studies focused a priori on a limited number of local brain areas or circuits, without considering the impact of cannabis on whole-brain network organization. The present study attempted to identify changes in the whole-brain human functional connectome as assessed with ultra-high field (7T) resting state scans of cannabis users (N = 26) during placebo and following vaporization of cannabis. Two distinct data-driven methodologies, i.e. network-based statistics (NBS) and connICA, were used to identify changes in functional connectomes associated with acute cannabis intoxication and history of cannabis use. Both methodologies revealed a broad state of hyperconnectivity within the entire range of major brain networks in chronic cannabis users compared to occasional cannabis users, which might be reflective of an adaptive network reorganization following prolonged cannabis exposure. The connICA methodology also extracted a distinct spatial connectivity pattern of hypoconnectivity involving the dorsal attention, limbic, subcortical and cerebellum networks and of hyperconnectivity between the default mode and ventral attention network, that was associated with the feeling of subjective high during THC intoxication. Whole-brain network approaches identified spatial patterns in functional brain connectomes that distinguished acute from chronic cannabis use, and offer an important utility for probing the interplay between short and long-term alterations in functional brain dynamics when progressing from occasional to chronic use of cannabis., (© 2022. The Author(s).)

Background: Tranylcypromine is the only irreversible monoamine oxidase inhibitor that is approved in the United States and in Europe for the management of treatment-resistant major depressive disorder. Comprehensive data in the literature regarding the efficacy and tolerability of tranylcypromine (TCP) combination strategies have not been systematically investigated yet., Methods: We conducted a systematic review of available literature based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Study types considered eligible for inclusion were studies that reported information on efficacy and/or tolerability/adverse effects of pharmacological TCP add-on or coadministration strategies among people with psychiatric disorders., Results: Ninety-six articles were included in qualitative analyses. A relevant body of evidence shows that TCP combined with first- and second-generation antipsychotics seems relatively safe and might have beneficial effects in some patients with depressive disorders, although caution is needed with some second-generation antipsychotics that have proserotonergic activity. Although evidence is not entirely consistent, amitriptyline as add-on agent might be efficacious and associated with a low rate of severe adverse events. Although available data from case reports are scarce, certain other agents, such as trazodone, but also lithium, seem to have a good risk-benefit profile with regard to TCP that should be further investigated in the context of high-quality studies., Conclusions: Any combination of a psychotropic with TCP should be preceded by an evaluation of drug-to-drug interaction and an informed consent process and followed by close monitoring. Before any combination strategy, doctors should reevaluate factors of pseudo-treatment resistance, such as rapid-metabolizing status, noncompliance, trauma, alternative diagnosis, or drug abuse., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate the relationship between medications used to treat acute agitation (antipsychotics, mood stabilizers, and benzodiazepines) and subsequent assault incidence in the psychiatric emergency department., Methods: Medication orders and assault incident reports were obtained from electronic health records for 17,056 visits to an urban psychiatric emergency department from 2014 to 2019. Assault risk was modeled longitudinally using Poisson mixed-effects regression., Results: Assaults were reported during 0.5% of visits. Intramuscular (IM) medications were ordered in 23.3% of visits overall and predominantly were ordered within the first 4 hours of a visit. IM medication orders were correlated with assault (incident rate ratio [IRR] = 24.2; 95% CI, 5.33-110.0), often because IM medications were ordered immediately subsequent to reported assaults. Interacted with time, IM medications were not significantly associated with reduction in subsequent assaults (IRR = 0.700; 95% CI, 0.467-1.04). Neither benzodiazepines nor mood stabilizers were associated with subsequent changes to the risk of reported assault. By contrast, antipsychotic medications were associated with decreased assault risk across time (IRR = 0.583; 95% CI, 0.360-0.942)., Conclusions: Although assault prevention is not the sole reason for ordering IM medications, IM medication order rates are high relative to overall assault incident risk. Of the 3 major categories of medications ordered commonly in the psychiatric emergency setting, only antipsychotic medications were associated with measurable decreases in subsequent assault risk. As antipsychotic medication can have a significant side effect burden, careful weighing of the risks and benefits of medications is encouraged., (© Copyright 2021 Physicians Postgraduate Press, Inc.)

Background: Opioid-overdose deaths are associated with poisoning with prescription and illicit opioids in the USA. In contrast, opioid-related deaths (ORDs) in the UK often involve drugs and substances of misuse, and may not be associated with a high dose of prescribed opioids. This study aimed to investigate the association between prescribed opioid dose and ORDs in UK primary care., Methods: This case-crossover study used the Clinical Practice Research Datalink and death registration between 2000 and 2015 to identify ORDs. Daily oral morphine equivalent (OMEQ) dose was measured within a 90 day focal window before ORD and three earlier reference windows. Conditional logistic regression models assessed the adjusted odds ratio (aOR) and 95% confidence interval (95% CI) comparing daily OMEQ dose greater than 120 mg in the focal window against the reference windows., Results: Of the 232 ORDs, 62 (26.7%) were not prescribed opioids in the year before death. Of the remaining 170 cases, 50 (29.4%) were never prescribed a daily OMEQ dose greater than 50 mg. Daily OMEQ doses over 120 mg (aOR 2.20; 95% CI: 1.06-4.56), co-prescribing gabapentinoids (aOR 2.32; 95% CI: 1.01-5.33), or some antidepressants (aOR 3.03; 95% CI: 1.02-9.04) significantly increased the risk of ORD., Conclusions: Daily OMEQ dose greater than 120 mg and the concomitant use of psychotropic medicines were related to ORDs in the UK. Prescribers should cautiously avoid prescribing opioids with a daily OMEQ dose greater than 120 mg day -1 and the combination of opioids and gabapentinoids, even with low opioid doses., (Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Psychotropic drugs can induce strong metabolic adverse effects, potentially increasing morbidity and/or mortality of patients. Metabolomic profiling, by studying the levels of numerous metabolic intermediates and products in the blood, allows a more detailed examination of metabolism dysfunctions. We aimed to identify blood metabolomic markers associated with weight gain in psychiatric patients. Sixty-two patients starting a treatment known to induce weight gain were recruited. Two hundred and six selected metabolites implicated in various pathways were analyzed in plasma, at baseline and after 1 month of treatment. Additionally, 15 metabolites of the kynurenine pathway were quantified. This latter analysis was repeated in a confirmatory cohort of 24 patients. Among the 206 metabolites, a plasma metabolomic fingerprint after 1 month of treatment embedded 19 compounds from different chemical classes (amino acids, acylcarnitines, carboxylic acids, catecholamines, nucleosides, pyridine, and tetrapyrrole) potentially involved in metabolic disruption and inflammation processes. The predictive potential of such early metabolite changes on 3 months of weight evolution was then explored using a linear mixed-effects model. Of these 19 metabolites, short-term modifications of kynurenine, hexanoylcarnitine, and biliverdin, as well as kynurenine/tryptophan ratio at 1 month, were associated with 3 months weight evolution. Alterations of the kynurenine pathway were confirmed by quantification, in both exploratory and confirmatory cohorts. Our metabolomic study suggests a specific metabolic dysregulation after 1 month of treatment with psychotropic drugs known to induce weight gain. The identified metabolomic signature could contribute in the future to the prediction of weight gain in patients treated with psychotropic drugs., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Following a decision to require label warnings for concurrent use of opioids and benzodiazepines and increased risk of respiratory depression and death, the US Food and Drug Administratioin (FDA) recognized that other sedative psychotropic drugs may be substituted for benzodiazepines and be used concurrently with opioids. In some cases, data on the ability of these alternatives to depress respiration alone or in conjunction with an opioid are lacking. A nonclinical in vivo model was developed that could detect worsening respiratory depression when a benzodiazepine (diazepam) was used in combination with an opioid (oxycodone) compared to the opioid alone based on an increased arterial partial pressure of carbon dioxide (pCO 2 ). The current study used that model to assess the impact on respiration of non-benzodiazepine sedative psychotropic drugs representative of different drug classes (clozapine, quetiapine, risperidone, zolpidem, trazodone, carisoprodol, cyclobenzaprine, mirtazapine, topiramate, paroxetine, duloxetine, ramelteon, and suvorexant) administered alone and with oxycodone. At clinically relevant exposures, paroxetine, trazodone, and quetiapine given with oxycodone significantly increased pCO 2 above the oxycodone effect. Analyses indicated that most pCO 2 interaction effects were due to pharmacokinetic interactions resulting in increased oxycodone exposure. Increased pCO 2 recorded with oxycodone-paroxetine co-administration exceeded expected effects from only drug exposure suggesting another mechanism for the increased pharmacodynamic response. This study identified drug-drug interaction effects depressing respiration in an animal model when quetiapine or paroxetine were co-administered with oxycodone. Clinical pharmacodynamic drug interaction studies are being conducted with these drugs to assess translatability of these findings., (Published 2021. This article is a U.S. Government work and is in the public domain in the USA. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Background: e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown., Research Question: What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior?, Study Design and Methods: CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed. CT findings and patterns were defined and agreed on via consensus. The parenchymal organizing pneumonia (OP) pattern was defined as regional or diffuse ground-glass opacity (GGO) ± consolidation without centrilobular nodules (CNs). An airway-centered OP pattern was defined as diffuse CNs with little or no GGO, whereas a mixed OP pattern was a combination of the two. Other patterns included diffuse alveolar damage (DAD), acute eosinophilic-like pneumonia, and pulmonary hemorrhage. Cases were classified as atypical if they did not fit into a pattern. Imaging findings, pattern frequencies, and injury severity were correlated with substance vaped (marijuana derives [tetrahydrocannabinol] [THC] only, nicotine derivates only, and both), vaping frequency, regional geography, and state recreational THC legality. One-way analysis of variance, χ 2 test, and multivariable analyses were used for statistical analysis., Results: A total of 160 patients (79.4% men) with a mean age of 28.2 years (range, 15-68 years) with EVALI underwent CT scan. Seventy-seven (48.1%), 15 (9.4%), and 68 (42.5%) patients admitted to vaping THC, nicotine, or both, respectively. Common findings included diffuse or lower lobe GGO with subpleural (78.1%), lobular (59.4%), or peribronchovascular (PBV) sparing (40%). Septal thickening (50.6%), lymphadenopathy (63.1%), and CNs (36.3%) were common. PBV sparing was associated with younger age (P = .02). Of 160 subjects, 156 (97.5%) had one of six defined patterns. Parenchymal, airway-centered, and mixed OP patterns were seen in 89 (55.6%), 14 (8.8%), and 32 (20%) patients, respectively. Acute eosinophilic-like pneumonia (six of 160, 3.8%), DAD (nine of 160, 5.6%), pulmonary hemorrhage (six of 160, 3.8%), and atypical (four of 160, 2.5%) patterns were less common. Increased vaping frequency was associated with more severe injury (P = .008). Multivariable analysis showed a negative association between vaping for > 6 months and DAD pattern (P = .03). Two subjects (1.25%) with DAD pattern died. There was no relation between pattern and injury severity, geographic location, and state legality of recreational use of THC., Interpretation: EVALI typically causes an OP pattern but exists on a spectrum of acute lung injury. Vaping habits do not correlate with CT patterns except for negative correlation between vaping > 6 months and DAD pattern. PBV sparing, not previously described in acute lung injury, is a common finding., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Interpatient variability in cytochrome P450 2D6 (CYP2D6) enzyme activity alters the serum concentrations of most psychotropics, which often have narrow therapeutic indices. Therefore, preemptive knowledge of CYP2D6 activity is desired. However, accessible indicators for deficient CYP2D6 activity are necessary because genotyping all patients prescribed CYP2D6 metabolized drugs is often not feasible or cost-effective., Methods: In this study, the predictive value of the ratio between a CYP2D6 substrate and its metabolite, known as the metabolic ratio (MR), the dose-corrected serum concentration of substrate (CDR), and the dose-corrected sum concentration of substrate and metabolite (Sum CDR) of venlafaxine, risperidone, aripiprazole, and nortriptyline were determined to predict the CYP2D6 poor metabolizer (PM) phenotype. The area-under-the-receiver operator characteristic curve, as well as the sensitivity, specificity, and positive and negative predictive values of the optimal thresholds, were calculated., Results: Although the MR, CDR, and Sum CDR all predicted the CYP2D6 PM phenotype, the predictive value of the MR was most robust for venlafaxine and aripiprazole, and the Sum CDR was inferior for all 3 psychotropics. MRs of venlafaxine, risperidone, and aripiprazole, and CDR of nortriptyline showed an area-under-the-receiver operator characteristics (95% confidence interval) of 97.2% (94.7%-99.6%), 93.0% (88.8%-97.2%), 97.8% (95.4%-100.0%), and 85.6% (78.0%-93.1%), respectively. Thresholds of the log(MR) of ≥0.1 for venlafaxine, ≥0.0 for risperidone, and ≥1.5 for aripiprazole, and log(CDR) ≥0.5 for nortriptyline produced >92% sensitivity and >64% specificity., Conclusions: If therapeutic drug monitoring is available, the thresholds presented here could serve as a diagnostic tool for the CYP2D6 PM phenotype of psychiatric patients prescribed the aforementioned psychotropic medications., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To review medical malpractice trends and to identify the most common claims filed against medical providers for the management of patients with priapism., Methods: Using the Westlaw legal database, a search was done for the keyword "priapism" between July 1, 1980 and July 1, 2020. Cases were evaluated for plaintiff demographics, reasons for filing claims, management outcomes, legal verdicts and awards and further categorized based upon the timing of the alleged malpractice., Results: Alleged negligence during the pre-management period was cited in 30 cases. Administration of psychotropic medications was the most common reasons for filing pre-management claims 22/56 (39.3%). Delay in care accounted for 18/56 (32.1%) and complications of surgery were 5/56 (8.9%) of claims. The majority of the completed cases were in favor of the defendants (39/47; 83.0%). There was no association between type of health care provider or timing of alleged malpractice and ultimate verdict., Conclusions: Prescribing psychoactive medications without warning of the adverse effect profile is the most common reason for claims filed against providers with trazodone as the leading medication. Medical providers should ensure that patients are well informed of this adverse effect prior to prescription. Regardless, the majority of medical malpractice cases carry a verdict in favor of the defendant., (Copyright © 2021. Published by Elsevier Inc.)

Background: Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine [MDMA])-presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not been fully examined in nonhuman primates., Methods: The present studies were conducted to systematically evaluate the discriminative stimulus effects of 5 abused synthetic cathinones (methylenedioxypyrovalerone [MDPV], α-pyrrolidinovalerophenone [α-PVP], methcathinone [MCAT], mephedrone, and methylone) in adult male squirrel monkeys trained to distinguish intramuscular injections of MA (0.1 mg/kg; n = 4) or MDMA (0.6 mg/kg; n = 4) from vehicle., Results: Each training drug produced dose-dependent effects and, at the highest dose, full substitution. MDMA produced predominantly vehicle-like responding in the MA-trained group, whereas the highest dose of MA (0.56 mg/kg) produced partial substitution (approximately 90% appropriate lever responding in one-half of the subjects) in the MDMA-trained group. MDPV, α-PVP, and MCAT produced full substitution in MA-trained subjects, but, at the same or higher doses, only substituted for MDMA in one-half of the subjects, consistent with primarily dopaminergically mediated interoceptive effects. In contrast, mephedrone and methylone fully substituted in MDMA-trained subjects but failed to fully substitute for the training drug in MA-trained subjects, suggesting a primary role for serotonergic actions in their interoceptive effects., Conclusions: These findings suggest that differences in the interoceptive effects of synthetic cathinones in nonhuman primates reflect differing compositions of monoaminergic actions that also may mediate their subjective effects in humans., (© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.)

Rationale: Methamnetamine (MNA; PAL-1046) is a new psychoactive substance that acts as a full biogenic amine transporter (BAT) substrate. BAT substrates promote neurotransmitter release from the nerve terminal and can be abused as stimulants. However, scientific information on the abuse potential of methamnetamine is lacking., Objective: We evaluated the abuse liability of methamnetamine., Methods: The effective dose range of methamnetamine was determined using a climbing behavior test. The rewarding effect and reinforcing effect of the test compound were evaluated in mice by conditioned place preference (CPP) testing and self-administration (SA) testing at the selected doses. Dopamine level changes were analyzed using synaptosomes and in vivo microdialysis to investigate the effects of methamnetamine on the central nervous system. Drug discrimination experiments were used to examine the potential similarity of the interoceptive effects of methamnetamine and cocaine., Results: A significant response was observed in the climbing behavior test with 10 and 40 mg/kg intraperitoneally administered methamnetamine. In the CPP test, mice intraperitoneally administered methamnetamine (10 and 20 mg/kg) showed a significant preference for the drug-paired compartment. In the SA test, mice that intravenously received 1 mg/kg/infusion showed significant active-lever responses. Dopamine was significantly increased in synaptosomes and in in vivo microdialysis tests. Furthermore, methamnetamine showed cross-generalization with cocaine in a dose-dependent manner., Conclusions: Methamnetamine exhibits interceptive stimulus properties similar to those of cocaine and induces rewarding and reinforcing effects, suggesting its dependence liability potential., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Acute cannabis intoxication may induce neurocognitive impairment and is a possible cause of human error, injury and psychological distress. One of the major concerns raised about increasing cannabis legalization and the therapeutic use of cannabis is that it will increase cannabis-related harm. However, the impairing effect of cannabis during intoxication varies among individuals and may not occur in all users. There is evidence that the neurocognitive response to acute cannabis exposure is driven by changes in the activity of the mesocorticolimbic and salience networks, can be exacerbated or mitigated by biological and pharmacological factors, varies with product formulations and frequency of use and can differ between recreational and therapeutic use. It is argued that these determinants of the cannabis-induced neurocognitive state should be taken into account when defining and evaluating levels of cannabis impairment in the legal arena, when prescribing cannabis in therapeutic settings and when informing society about the safe and responsible use of cannabis.

Researchers believe that almost 20% of children and adolescents struggle with chronic and persistent mental health concerns. Mental health is the leading cause of disability in the United States. Youth can struggle with several impairing mental health disorders, such as attention-deficit/hyperactivity disorder, mood disorders, psychotic disorders, and autism spectrum disorder. Inadequately treated chronic mental illnesses can adversely affect the growing brain profoundly, including academic decline, early school dropout, cognitive deficits, interpersonal relationship concerns, aggression, suicide attempts or completion, substance use disorders, frequent hospital admissions, and inability to maintain employment. Even if diagnosed early in their course of illness, many of these individuals struggle to continue medications as prescribed. The factors predicting adherence to medications are underresearched in children and adolescents. Psychotropic medication compliance is a complicated issue that is tied to various aspects of caring for a minor individual. Hence, it is relevant to discuss factors that are predicted to contribute to noncompliance in this age group. The purpose of this review is to carefully consider the gaps in knowledge, suggesting interventions by using established instruments and clinical strategies to resolve the identified barriers for improving medication adherence. Compliance should be targeted at various levels, including the entire family tree and the treatment team.

Objective: Psychiatric patients are at increased risk of contamination, morbidity, and mortality associated with COVID-19, together with potentially more pronounced adverse effects. We present and discuss the adverse effects observed in an acute psychiatric clinic that has admitted COVID-19 patients during the first three months of the pandemic in Turkey., Methods: The COVID-19 treatment schemes were formed in accordance with the national and regional guidelines at the time of admittance, which were mainly based on the use of hydroxychloroquine and other drugs. The sample consisted exclusively of inpatients, and all patients were enrolled in the study regardless of their specific diagnosis or treatment schemes., Results: 4 out of 23 patients (17.4%) had experienced adverse effects, two of which had mild hepatic enzyme elevation and one had mild sinus bradycardia. Of note is that we haven't encountered any serious complications or life-threatening events during inpatient treatment. The most emphasised adverse effect in the literature, namely QTc prolongation and ECG changes, were not observed in our sample. The adverse effects were not found to be significantly associated with patient-related factors nor dose of antipsychotic medication., Conclusions: From our point of view, non-cardiac adverse effects should not be overlooked while treating comorbid psychiatric and COVID-19 patients.KEY POINTSAcute inpatient psychiatric treatment of patients who have comorbid COVID-19 is a complex situation requiring multidisciplinary action.Adverse drug reactions, which may or not result from the interaction of psychiatric and COVID-19 treatment, should be of concern for this patient group.While there is controversy over the benefits of some of the off-label COVID-19 medications, there should also be discussion over safety and concomitant medication use.In order to be adequately prepared for future escalations of COVID-19 pandemic, psychiatric services should thoroughly evaluate their initial experience with COVID-19, including from the point of drug effectiveness and safety.

Background: Despite implementation of HIV prevention programmes for truck drivers in India, unsafe sex behavior among truck drivers has been documented., Objective: The objective of this study was to assess knowledge about HIV Transmission and modes of prevention, pattern of condom use with high risk partners and explore the practice of unsafe sex and its risk factors among truck drivers., Methods: This exploratory cross-sectional study design was conducted on a recruited convenient sample of 100 truck drivers above 18 years from March to May 2015. Binary logistic regression was used to compute unadjusted odds ratio [95% Confidence Interval] for establishing association of risk factors with unsafe sex., Results: Overall, only 7% had complete knowledge about HIV/AIDS transmission and prevention. 54% of truck drivers have sex with a high risk partner (commercial sexual worker or men having sex with men) and thirty-eight percent reported unsafe sexual practices due to inconsistent condom use with them. The various risk factors found significantly associated with unsafe sex were mean age of first intercourse (OR= 0.92, 95% CI: 0.75 - 0.97), access to pornography (OR = 4.4, 95% CI: 1.8 - 10.7) and conuming psychoactive substance before sex (OR = 4.06, 95% CI: 1.09 - 15.02)., Conclusion: Socio-demographic, occupational factors, pornography access and consuming psychoactive substances seems to influence the sexual behaviour of truckers., (© 2021 Pundhir A et al.)

Background: Psychoactive substance use is a major global public health issue. Use of psychoactive substances has been associated with negative consequences among students., Objective: The study assessed the prevalence and socio-demographic correlates of psychoactive substance use among undergraduate students in a Nigerian university., Materials and Methods: This was a cross-sectional descriptive study of 763 undergraduate students of Imo State University, Owerri, Nigeria, recruited using multi-stage sampling technique. Data on the socio-demographic characteristics and pattern of psychoactive substance use were collected using a structured questionnaire., Results: The lifetime rate of psychoactive substance use was 84.5%. Alcohol had the highest rate of lifetime (82.5%) and 12-month (61.1%) use. There was a similar rate of lifetime use of psychoactive substances among males (86.1%) and females (83.4%). Age (p<0.05) and place of residence (p<0.05) were significantly associated with lifetime psychoactive substance use. Catholics (OR:1.43; 1.03 - 1.99), whose friend (OR:1.94; 1.39 - 2.71), roommate (OR:3.06; (1.62 - 5.78) or brother (OR:1.22; 0.77 - 1.93) uses psychoactive substances were significantly more likely to have used substances in the past 12-months., Conclusion: There is a high rate of psychoactive substance use among the students. Age, religion, place of residence, family and peer use of substances are important determinants of psychoactive substance use., (© 2021 Aguocha CM et al.)

The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have synergistic analgesic efficacy in animal models of neuropathic pain when injected systemically. However, the relevance of this preclinical synergy to clinical neuropathic pain studies is unclear because many of the latter use oral administration. We therefore examined the oral effectiveness of these phytocannabinoids and their interactions in a mouse chronic constriction injury (CCI) model of neuropathic pain. THC produced a dose-dependent reduction in mechanical and cold allodynia, but also induced side-effects with similar potency. CBD also reduced allodynia, albeit with lower potency than THC, but did not produce cannabinoid-like side-effects at any dose tested. Combination THC:CBD produced a dose-dependent reduction in allodynia, however, it displayed little to no synergy. Combination THC:CBD produced substantial, synergistic side-effects which increased with the proportion of CBD. These findings demonstrate that oral THC and CBD, alone and in combination, have analgesic efficacy in an animal neuropathic pain model. Unlike prior systemic injection studies, combination THC:CBD lacks analgesic synergy when delivered orally. Furthermore, both THC and combination THC:CBD display a relatively poor therapeutic window when delivered orally. This suggests that CBD provides a safer, albeit lower efficacy, oral treatment for nerve injury induced neuropathic pain than THC-containing preparations. This article is part of the special issue on 'Cannabinoids'., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Psychotropic medication treatment can cause elevated serum prolactin levels and hyperprolactinaemia (HPRL). Reports have suggested that aripiprazole may decrease elevated prolactin. The aim of this review was to assess evidence for the efficacy of adjunct aripiprazole in the treatment of psychotropic-induced HPRL. PubMed and Google Scholar were searched to identify randomised placebo-controlled trials (RCTs) of adjunct aripiprazole in patients with HPRL attributed to primary psychotropic medications. Data for individual patients from case studies, chart reviews and open-label studies were also identified and assessed. Six RCTs, with a total of 609 patients, met inclusion criteria. Primary psychotropics included risperidone, haloperidol, paliperidone, fluphenazine and loxapine. Reductions in prolactin from baseline, before the introduction of aripiprazole, were significantly greater for adjunct aripiprazole than for adjunct placebo in all the studies (p = 0.04 to p < 0.0001). Normalisation of serum prolactin levels was significantly more likely with adjunct aripiprazole than adjunct placebo (p = 0.028 to p < 0.001, data from three studies). Improvement or resolution of HPRL-related symptoms (galactorrhoea, oligomenorrhoea, amenorrhoea and sexual dysfunction) were reported in three studies. Prolactin levels decreased in all case reports and in both of two open-label studies; they normalised in 30/41 patients (73.2%) in case studies and 12/29 (41.4%) in the open-label studies. Adjunct aripiprazole was statistically significantly effective in treating elevated serum prolactin levels in six RCTs. Evidence from case reports and open-label studies suggests a degree of effectiveness in most patients.

The last two decades have seen a revival of interest in the entactogen 3,4-methylenedioxy-N-methylamphetamine (MDMA) as an adjunct to psychotherapy, particularly for the treatment of post-traumatic stress disorder. While clinical results are highly promising, and MDMA is expected to be approved as a treatment in the near future, it is currently the only compound in its class of action that is being actively investigated as a medicine. This lack of alternatives to MDMA may prove detrimental to patients who do not respond well to the particular mechanism of action of MDMA or whose treatment calls for a modification of MDMA's effects. For instance, patients with existing cardiovascular conditions or with a prolonged history of stimulant drug use may not fit into the current model of MDMA-assisted psychotherapy, and could benefit from alternative drugs. This review examines the existing literature on a host of entactogenic drugs, which may prove to be useful alternatives in the future, paying particularly close attention to any neurotoxic risks, neuropharmacological mechanism of action and entactogenic commonalities with MDMA. The substances examined derive from the 1,3-benzodioxole, cathinone, benzofuran, aminoindane, indole and amphetamine classes. Several compounds from these classes are identified as potential alternatives to MDMA.

Objectives: This descriptive and analytical study investigated the consumption rates of psychoactive substances among individuals aged 18-25 years in France. More specifically, it enabled assessment of the extent of the neuroenhancement (NE) phenomenon among students in France (including study of the misuse of psychostimulant medicines)., Study Design: COgnitive enhancement and consumption of psychoactive Substances among Youth Students (COSYS) is a cross-sectional survey of students in France., Methods: Between January and June 2017, a questionnaire was mailed to students. All questionnaires were completed anonymously and included questions regarding the use of all kind of psychoactive substances, motivations for use and socio-economic situations. Statistics for all variables and the results of a multiple correspondence analysis (MCA) are presented., Results: This study recorded 46,203 respondents, mostly in universities (>60%), mostly women (63.4%), with an average age of 21.4 years. In terms of substance use, medications were cited in the third position after alcohol and tobacco by women (22.48%) and in the fourth position after alcohol, tobacco and cannabis by men (15.14%). Among medications, opiates were the most frequently used, followed by benzodiazepines. Students who declared a non-medical use (NMU) of drugs obtained these through various ways (e.g. family medicine cabinet, a friend, a dealer or via the Internet), or by increasing their recommended doses (e.g. codeine). In total, 18.6% of students consumed psychoactive substances for 'stress management' and 14.1% for 'sleep management'. Results indicated that NE in students is a problem, with 18.6% of students in the COSYS survey confirming the use of psychoactive substances for this reason. There was a very low prevalence for psychostimulant medications (0.57% of men), mostly NMU (67%). MCA yielded three different profiles (doping candidate, experimenter and psychiatric profile) of psychostimulant users, which complicates the implementation of prevention programmes., Conclusions: It is evident that NMU and 'conventional' use of medications are highly prevalent in French students, especially females. NMU is associated with substance use disorders, psychopathology and suicidality. Social norms and social media increase NMU of psychoactive substances, but also provide a potential platform for anti-NMU campaigns., Clinical Trial Registration Number: NCT02954679., (Copyright © 2021 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Parkinson's disease (PD) usually presents in older adults and typically has both motor and non-motor dysfunctions. PD is a progressive neurodegenerative disorder resulting from dopaminergic neuronal cell loss in the mid-brain substantia nigra pars compacta region. Outlined here is an integrative medicine and health strategy that highlights five treatment options for people with Parkinson's (PwP): rehabilitate, therapy, restorative, maintenance, and surgery. Rehabilitating begins following the diagnosis and throughout any additional treatment processes, especially vis-à-vis consulting with physical, occupational, and/or speech pathology therapist(s). Therapy uses daily administration of either the dopamine precursor levodopa (with carbidopa) or a dopamine agonist, compounds that preserve residual dopamine, and other specific motor/non-motor-related compounds. Restorative uses strenuous aerobic exercise programs that can be neuroprotective. Maintenance uses complementary and alternative medicine substances that potentially support and protect the brain microenvironment. Finally, surgery, including deep brain stimulation, is pursued when PwP fail to respond positively to other treatment options. There is currently no cure for PD. In conclusion, the best strategy for treating PD is to hope to slow disorder progression and strive to achieve stability with neuroprotection. The ultimate goal of any management program is to improve the quality-of-life for a person with Parkinson's disease.

Background: Psilocybin is a serotonergic psychedelic with psychoactive effects mediated by serotonin 2A receptor (5-HT2AR) activation. It produces an acute psychedelic altered state of consciousness with a unique phenomenology that can be temporally characterized by three intensity phases: onset of psychoactive effect, a peak plateau and return to normal consciousness., Aims: We evaluated whether pre-drug brain 5-HT2AR binding predicted the three phases of psilocybin subjective drug intensity (SDI) and retrospective self-report of mystical type experiences in healthy individuals., Method: Sixteen participants completed a pre-drug [ 11 C]Cimbi-36 positron emission tomography scan to assess 5-HT2AR binding. On a separate day, participants completed a single psilocybin session (oral dose range 0.2-0.3 mg/kg), during which SDI was assessed every 20 min. The Mystical Experience Questionnaire (MEQ) was completed at the end of the session. The three SDI phases were modelled using segmented linear regressions. We evaluated the associations between neocortex 5-HT2AR binding and SDI/MEQ outcomes using linear regression models., Results: Neocortex 5-HT2AR was statistically significantly negatively associated with peak plateau duration and positively with time to return to normal waking consciousness. It was also statistically significantly negatively associated with MEQ total score., Conclusion: This is the first study to investigate how individual brain 5-HT2AR binding predicts subjective effects of a single dose of psilocybin. Our findings reinforce the role of cerebral 5-HT2AR in shaping the temporal and mystical features of the psychedelic experience. Future studies should examine whether individual brain levels of 5-HT2AR have an impact on therapeutic outcomes in clinical studies.

Purpose: Many psychotropic drugs are listed as potentially inappropriate medication (PIM) in the older population. Potentially inappropriate means that prescription of those drugs in older adults may cause significant harm. The objective of this study was to analyze the prevalence and sort of PIM prescribing in a naturalistic, real-world psychiatric setting., Methods: The retrospective analysis gathered data from a large pharmacovigilance study, conducted at 10 psychiatric hospitals. Data from inpatients aged ≥ 65 years were included for the analysis. The number and sort of PIM, as defined by the German PRISCUS list, were controlled by analyzing the patients' medication profile., Results: In total, 4760 patient cases (59.2% female) with a mean (mean ± standard deviation (SD)) age of 77.33 ± 7.77 years were included into the study. Altogether, 1615 cases (33.9%) received at least 1 PRISCUS-PIM per day (regular and as-needed medication included). The most frequently prescribed PRISCUS-PIM (n = 2144) were zopiclone > 3.75 mg/day (n = 310), lorazepam > 2 mg/day (n = 269), haloperidol > 2 mg/day (n = 252), and diazepam (n = 182). Cases with PRISCUS-PIM were younger (75.7 vs. 78.2 years, p < 0.001) and had a longer (26 vs. 22 days, p < 0.001) hospital length of stay. Replacing benzodiazepines and z-substances, haloperidol > 2 mg, tricyclic antidepressants, first generation antihistaminergic drugs, and clonidine by non-PIM could reduce 69.9% of PRISCUS-PIM-prescribing., Conclusions: The prevalence of PRISCUS-PIM is high in the hospitalized psychiatric setting. Rational deprescribing of inappropriate anticholinergics, benzodiazepines, and antipsychotics in the older population is a key component to reduce the risk of adverse drug reactions. More tolerable medications should be prescribed.

Many drugs of abuse are mixed with other psychoactive substances (e.g., caffeine) prior to their sale or use. Synthetic cathinones (e.g., 3,4-methylenedioxypyrovalerone [MDPV]) are commonly mixed with caffeine or other cathinones (e.g., 3,4-methylenedioxy-N-methylcathinone [methylone]), and these "bath salts" mixtures (e.g., MDPV + caffeine) can exhibit supra-additive interactions with regard to their reinforcing and discriminative stimulus properties. However, little is known about relapse-related effects of drug mixtures. In these studies, male Sprague-Dawley rats self-administered 0.032 mg/kg/inf MDPV or a mixture of MDPV + caffeine (0.029 + 0.66 mg/kg/inf, respectively) and then underwent multiple rounds of extinction and reinstatement testing to evaluate the influence of reinforcement history and drug-associated stimuli on the effectiveness of saline (drug-paired stimuli alone), MDPV (0.032-1.0 mg/kg), caffeine (1.0-32 mg/kg), and mixtures of MDPV:caffeine (in 3:1, 1:1, and 1:3 ratios, relative to each drug's ED 50 ) to reinstate responding. Dose-addition analyses were used to determine the nature of the drug-drug interaction for each mixture. MDPV and caffeine dose-dependently reinstated responding and were equally effective, regardless of reinforcement history. Most fixed ratio mixtures of MDPV + caffeine exhibited supra-additive interactions, reinstating responding to levels greater than was observed with caffeine and/or MDPV alone. Drug-associated stimuli also played a key role in reinstating responding, especially for caffeine. Together, these results demonstrate that the composition of drug mixtures can impact relapse-related effects of drug mixtures, and "bath salts" mixtures (MDPV + caffeine) may be more effective at promoting relapse-related behaviors than the constituents alone. Further research is needed to determine how other polysubstance reinforcement histories can impact relapse-related behaviors., (© 2020 Society for the Study of Addiction.)

Abstract: To identify the impact of postdischarge psychiatric medication changes on general medical readmissions among patients with serious mental illness (SMI; bipolar disorder, major depressive disorder, and schizophrenia), claims from a 5% national sample of Medicare fee-for-service (FFS) beneficiaries hospitalized between 2013 and 2016 were studied. A total of 165,490 Medicare FFS beneficiaries with SMI 18 years or older with at least 1 year of continuous Medicare enrollment were identified. Within 30 days of discharge from index admission, 47.4% experienced a psychiatric medication change-including 75,892 beneficiaries experiencing a deletion and 55,713 experiencing an addition. After adjusting for potential confounders, those with a medication change experienced an 10% increase in the odds of 30-day readmission (odds ratio, 1.10; SE, 0.019; p < 0.001). Comorbid drug use disorder was also associated with an increased odds of readmission after controlling for other covariates. These findings suggest important factors that clinicians should be aware of when discharging patients with SMI., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)