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Background: Prescription drug misuse (PDM) is a critical mental health issue relating to psychiatric morbidity. This study investigated the prevalence of PDM and its associated psychopathology and psychosocial factors in the general population in Taiwan., Methods: The survey randomly selected a representative sample >15 year-olds using the stratified proportional randomization method. The measurements included demographic variables, previous experience with PDM, self-rated physical and mental health, health self-efficacy, risk factors for suicidality, and psychological distress., Results: The weighted one-year prevalence of PDM was 8.5% ( n = 180) among 2126 participants. Those with psychological distress and lifetime suicide ideation (23.3%) or suicide attempts (5.0%) were significantly associated with PDM. PDM was also prevalent among those with poorer self-rated health and lower self-efficacy. Insomnia (OR = 1.52), depression (OR = 1.77), and low self-efficacy (OR = 2.29) had higher odds of PDM after adjustment in the logistic regression model., Conclusions: Individuals who misused prescription drugs had a higher prevalence of psychological distress and suicidality and lower levels of self-rated health. Prescription drug misuse problems should be screened for early prevention when prescribing medications for people with insomnia, depression, or lower perceived health beliefs or conditions.

Persistent ketamine use causes susceptibility to addiction and bladder toxicity. We examined the association of lower urinary tract symptoms and levels of Nectin-4, a member of the cell adhesion molecules that is essential for maintaining the urothelium barrier in chronic ketamine abusers. We measured the plasma levels of Nectin-4 in 88 patients with ketamine dependence and 69 controls. Patients with ketamine dependence were assessed for ketamine use variables, psychological symptoms, and lower urinary tract symptoms. We found Nectin-4 levels were increased in ketamine-dependent patients compared to the controls (p < 0.0001). Patients with urinary tract symptoms exhibited lower Nectin-4 levels than those without (p = 0.021). Our results suggest an up-regulation of Nectin-4 following chronic and heavy ketamine use. Patients with ketamine dependence with a compromised upregulation of Nectin-4 are likely to have more severe urinary tract symptoms. The mechanisms underlying the involvement of Nectin-4 in ketamine addiction and bladder toxicity warrant future investigation., (Copyright © 2021. Published by Elsevier B.V.)

Chronic ketamine abuse is associated with bladder dysfunction and cystitis. However, the effects of ketamine abuse on the urinary proteome profile and the correlations among urinary proteins, urinary ketamine (and metabolites) and clinicopathological features of ketamine-induced bladder dysfunction remain to be established. Here, we recruited 56 ketamine abusers (KA) and 40 age-matched healthy controls (HC) and applied the iTRAQ-based proteomics approach to unravel quantitative changes in the urine proteome profile between the two groups. Many of the differentially regulated proteins are involved in the complement and coagulation cascades and/or fibrotic disease. Among them, a significant increase in APOA1 levels in KA relative to control samples (392.1 ± 59.9 ng/ml vs. 13.7 ± 32.6 ng/ml, p < 0.0001) was detected via ELISA. Moreover, urinary ketamine, norketamine and dehydronorketamine contents (measured via LC-SRM-MS) were found to be positively correlated with overactive bladder syndrome score (OABSS) and APOA1 levels with urinary RBC, WBC, OABSS and numeric pain rating scale in KA. Collectively, our results may aid in developing new molecular tool(s) for management of ketamine-induced bladder dysfunction. Moreover, information regarding the differentially regulated proteins in urine of KA provides valuable clues to establish the molecular mechanisms underlying ketamine-induced cystitis.

Background: Ketamine has emerged as a major substance of abuse worldwide. Evidence suggests a role of orexin system in reward processing, withdrawal, and stress response. It also interacts with the stress mechanisms of hypothalamic-pituitary-adrenal (HPA) axis to regulate drug-taking behavior. The study aimed to explore the relevance of orexin and stress hormones to chronic ketamine abuse., Methods: We enrolled 67 ketamine-dependent (KD) patients and 64 controls. The levels of orexin-A, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline, 1 week, and 2 weeks after ketamine discontinuation. KD patients were assessed by Beck Depression Inventory, Beck Anxiety Inventory, and Visual Analogue Scale for ketamine craving at baseline., Results: Compared with the controls, KD patients had significantly lower orexin-A (0.65 ± 0.12 vs. 0.74 ± 0.10 ng/mL, p < 0.001) and increased ACTH (32.3 ± 16.3 vs. 22.3 ± 11.0 pg/mL, p = 0.008) levels at baseline, whereas cortisol levels were similar between two groups. Levels of the three markers did not correlate with ketamine use variables, craving, depression, or anxiety symptoms. The levels did not alter after 1 or 2 weeks of ketamine discontinuation. Notably, those with higher anxiety had lower orexin-A but increased cortisol levels than did those with lower anxiety., Conclusions: This study showed that KD patients had persistent orexin-A reduction and stress hormone dysregulation in early abstinence. The anxious phenotype of KD might be associated with a lower orexin-A expression. These results point to a promising pathway to investigate the neurochemical mechanisms of ketamine addiction.

Background: Nitrous oxide (N2O), a commonly used anesthetic agent in dentistry, has emerged as a global public health threat in young population. Although N2O-related neurological sequelae such as spinal cord degeneration and sensorimotor peripheral neuropathy are well known, psychiatric manifestations of heavy N2O use remain unclear. Here, we presented 7 treatment-seeking patients with severe N2O use disorder to delineate the psychiatric profiles of N2O users in Asia., Methods: Seven patients with severe N2O use disorder who sought treatment in Taipei City Psychiatric Center between 2017 and 2018 were enrolled. We used chart review method to retrospectively collect their clinical information including sociodemographics, psychiatric and substance history, urine toxicology findings, and treatment course., Results: These N2O users all had diagnoses of severe N2O use disorder. They usually initiated N2O use in late adolescence and early adulthood. Six of them had histories of mood disorders; all of them reported other illicit substance use before using N2O. The main reasons for treatment seeking were irritability, psychotic symptoms, self-harm, or violent behaviors as four of them were given a diagnosis of substance-induced psychotic disorder. Urine drug screen showed negative for other illicit drug use except for 1 positive case for cannabis and 1 for amphetamine. Three of 7 cases were hospitalized because of the severity of their psychiatric symptoms and suicidal risk., Conclusions: These cases with severe N2O use disorder showed high prevalence of psychotic symptoms and dangerous behaviors such as suicide or violence. This study highlights the addiction potential of N2O and its related adverse consequences in the psychiatric aspect.

Cigarette smoking is highly prevalent among persons living with the human immunodeficiency virus (HIV) (PLWH), with rates as high 50% as compared to 14% in the general U.S. population. Tobacco use causes morbidity and mortality in PLWH, and tobacco-related harm is substantially higher in PLWH than smokers in the general population, providing the scientific premise for developing effective tobacco cessation interventions in this population. To better address this issue, we conducted six focus group sessions with 45 African American smokers who are living with HIV to understand the barriers to smoking cessation and the strategies that would be helpful to overcome these barriers. We organized our findings by the Phase-Based Model of Smoking Treatment to understand the intervention components that are needed at each phase to help PLWH successfully quit smoking. Participants in our focus group sessions articulated key components for incorporation into tobacco cessation intervention for PLWH: a personalized plan for quitting, reminders about that plan, and a support system. Participants thought that their HIV and tobacco use were disassociated. Participants described barriers to the use of pharmacotherapy, including adverse side effects of the gum and patch and concerns about the negative health effects of some oral medications. Substance use was identified as a commonly co-occurring condition as well as a barrier to successfully ceasing to smoke tobacco products. In summary, these findings offer information on the components of a tobacco cessation intervention for PLWH, namely reminders, a support system, substance use treatment, and monitoring to prevent relapse.

Background: Ketamine has been used to probe the biology of psychosis and cognitive dysfunction in humans. High levels of ketamine abuse are associated with persisting psychosis (KPP) in a minority of users. However, relatively little is known about cognitive function among KPP patients and whether the cognitive impairments associated with KPP resemble those of schizophrenia (SZ)., Methods: We recruited 149 treatment-seeking patients, including nonpsychotic ketamine users (KNP, n=51), KPP (n=23), and SZ (n=75) patients. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychopathology and the Cogstate Brief Battery to assess cognitive function including psychomotor processing speed, attention, working memory, verbal and visual learning and memory, spatial problem solving, and social-emotional cognition., Results: Ketamine-dependent patients had an extensive history of ketamine use (average duration=7.1±4.2years, average consumption=3.8±2.7g per day). Although KPP patients used relatively less average ketamine daily dose than KNP patients, KPP patients exhibited significantly greater total PANSS score and subscale scores, while these scores in KPP and SZ patients did not differ significantly. After adjusting for demographic characteristics and antipsychotic dose, KPP and SZ patients showed impairments in spatial problem solving and verbal memory compared to KNP patients, but KPP and SZ patients did not significantly differ from each other., Conclusion: These data suggest that the symptom profile and cognitive impairments associated with persisting psychosis due to chronic heavy ketamine abuse resemble those of schizophrenia, while KNP patients showed significantly less severe symptom profile and cognitive impairment than KPP and SZ., (Copyright © 2018. Published by Elsevier B.V.)

Objective: Bipolar-I disorder (BPI) often co-occurred with anxiety (ANX) and substance use disorders (SUD), which poses challenges in public health and clinical treatment, and adds complexity in searching for relevant etiologic factors. The present study sought to identify subgroups of BPI patients using comorbidity patterns with ANX and SUD., Methods: Clinical patients (N=306) diagnosed with BPI were recruited and interviewed using the Composite International Diagnostic Interview to collect data on demographics and clinical features, including episodic information, impairments, and lifetime diagnoses of ANX (panic, agoraphobia, generalized anxiety disorder, specific and social phobia) and SUD (nicotine dependence, alcohol use and drug use disorder). We applied latent class analysis to empirically derive classes of BPI. A number of exogenous variables were examined for each class., Results: A three-class model provides excellent discriminability for subgrouping BPI patients with different comorbidity patterns. The BPI-LOW class (83.99%) had more pure mania without most lifetime comorbidity, higher numbers of last year mania episodes, and less suicidality and impairments. The BPI-ANX class (3.60%) was female predominant, tended to comorbid with multiple anxiety disorders but no SUD, and had early onset age. The BPI-SUD class (12.42%) was male predominant, had high prevalence of lifetime SUD and frequent mood episodes in the last year. Both the BPI-ANX and BPI-SUD classes had severe functional impairments and suicidal behaviors., Limitations: Clinical information was retrospectively collected. Besides, we did not comprehensively access lifetime comorbidity for all psychiatric disorders., Conclusion: The three empirically identified subgroups of BPI patients exhibited distinguished comorbidity patterns and clinical features, including suicidal behaviors, frequent mood episodes and functional impairments. Our findings have clinical implication in intervention and treatment as well as to explore their different underlying mechanisms., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Methamphetamine is one of the fastest growing illicit drugs worldwide, causing multiple organ damage and excessive natural deaths. The authors aimed to identify potential laboratory indices and clinical characteristics associated with natural death through a two-phase study., Methods: Methamphetamine-dependent patients (n = 1,254) admitted to a psychiatric center in Taiwan between 1990 and 2007 were linked with a national mortality database for causes of death. Forty-eight subjects died of natural causes, and were defined as the case subjects. A time-efficient sex- and age-matched nested case-control study derived from the cohort was conducted first to explore the potential factors associated with natural death through a time-consuming standardized review of medical records. Then the identified potential factors were evaluated in the whole cohort to validate the findings., Results: In phase I, several potential factors associated with natural death were identified, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), comorbid alcohol use disorder, and the prescription of antipsychotic drugs. In phase II, these factors were confirmed in the whole cohort using survival analysis. For the characteristics at the latest hospital admission, Cox proportional hazards models showed that the adjusted hazard ratios for natural death were 6.75 (p<0.001) in the group with markedly elevated AST (>80 U/L) and 2.66 (p<0.05) in the group with mildly elevated AST (40-80 U/L), with reference to the control group (<40 U/L). As for ALT, the adjusted hazard ratios were 5.41 (p<0.001), and 1.44 (p>0.05). Comorbid alcohol use disorder was associated with an increased risk of natural death, whereas administration of antipsychotic drugs was not associated with lowered risk., Conclusions: This study highlights the necessity of intensive follow-up for those with elevated AST and ALT levels and comorbid alcohol use disorder for preventing excessive natural deaths.