Association between benzodiazepine receptor agonist use and mortality in patients hospitalised for COVID-19: a multicentre observational study.

AIMS: To examine the association between benzodiazepine receptor agonist (BZRA) use and mortality in patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: A multicentre observational study was performed at Greater Paris University hospitals. The sample involved 14 381 patients hospitalised for COVID-19. A total of 686 (4.8%) inpatients received a BZRA at hospital admission at a mean daily diazepam-equivalent dose of 19.7 mg (standard deviation (s.d.) = 25.4). The study baseline was the date of admission, and the primary endpoint was death. We compared this endpoint between patients who received BZRAs and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, medical comorbidities and other medications. The primary analysis was a Cox regression model with inverse probability weighting (IPW). RESULTS: Over a mean follow-up of 14.5 days (s.d. = 18.1), the primary endpoint occurred in 186 patients (27.1%) who received BZRAs and in 1134 patients (8.3%) who did not. There was a significant association between BZRA use and increased mortality both in the crude analysis (hazard ratio (HR) = 3.20; 95% confidence interval (CI) = 2.74-3.74; p < 0.01) and in the IPW analysis (HR = 1.61; 95% CI = 1.31-1.98, p < 0.01), with a significant dose-dependent relationship (HR = 1.55; 95% CI = 1.08-2.22; p = 0.02). This association remained significant in sensitivity analyses. Exploratory analyses indicate that most BZRAs may be associated with an increased mortality among patients hospitalised for COVID-19, except for diazepam, which may be associated with a reduced mortality compared with any other BZRA treatment. CONCLUSIONS: BZRA use may be associated with an increased mortality among patients hospitalised for COVID-19, suggesting the potential benefit of decreasing dose or tapering off gradually these medications when possible.

Examining heterotypic continuity of psychopathology: a prospective national study.

BACKGROUND: Individuals with one psychiatric disorder are at increased risk for incidence and recurrence of other disorders. We characterize whether the magnitude of such heterotypic continuity varies based on whether the first disorder remits or persists over time. METHOD: Cohorts were selected from participants in the National Epidemiologic Survey on Alcohol and Related Conditions wave 1 (2001-2002) and wave 2 (2004-2005) surveys with ⩾1 mood, anxiety, or substance use disorder at wave 1. Among respondents remitting (n = 6719) or not remitting (n = 3435) from ⩾1 of disorder at wave 2, the analyses compared the odds of developing new disorders. RESULTS: As compared with adults whose disorders persisted from wave 1 to wave 2, those with ⩾1 remission had lower odds of incidence or recurrence of another disorder. Remission from alcohol dependence [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.3-0.5] and drug dependence (OR 0.4, 95% CI 0.3-0.6) were associated with the lowest odds of incidence of another disorder. Social anxiety disorder was associated with the lowest adjusted odds of recurrence (adjusted OR = 0.2, 95% CI 0.1-0.6). Remission of disorders within one class (mood, anxiety, substance use) was consistently associated with lower odds of incidence or recurrence of disorders from the same class than with developing disorders from the other classes. CONCLUSIONS: Remission from common psychiatric disorders tends to decrease the risk for incidence or recurrence of disorders and this effect is stronger within than across disorder classes. These results do not support the concept of heterotypic continuity as a substitution of one disorder for another.

Reexamining associations between mania, depression, anxiety and substance use disorders: results from a prospective national cohort.

Separate inheritance of mania and depression together with high rates of clinical overlap of mania with anxiety and substance use disorders provide a basis for re-examining the specificity of the prospective association of manic and depression episodes that is a hallmark of bipolar disorder. We analyzed information from 34 653 adults in Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, a longitudinal nationally representative survey of US adults interviewed 3 years apart. Psychiatric disorders were assessed by a structured interview. We used logistic regression analyses to estimate the strength of associations between Wave 1 manic episodes and Wave 2 depression, anxiety and substance use disorders controlling for background characteristics and lifetime Wave 1 disorders. Corresponding analyses examined associations between Wave 1 major depressive episode with manic episodes and other psychiatric disorders. In multivariable models, Wave 1 manic episodes significantly increased the odds of Wave 2 major depressive episodes (adjusted odds ratio (AOR): 1.7; 95% confidence interval: 1.3-2.2) and any anxiety disorder (AOR: 1.8; 1.4-2.2), although not of substance use disorders (AOR: 1.2; 0.9-1.5). Conversely, Wave 1 major depressive episodes significantly increased risk of Wave 2 manic episodes (AOR: 2.2; 1.7-2.9) and anxiety disorders (AOR: 1.7; 1.5-2.0), although not substance use disorders (AOR: 1.0; 0.9-1.2). Adults with manic episodes have an approximately equivalent relative risk of developing depression episodes and anxiety disorders. Greater research and clinical focus is warranted on connections between manic episodes and anxiety disorders.

Comparative mortality risks of antipsychotic medications in community-dwelling older adults.

BACKGROUND: All antipsychotic medications carry warnings of increased mortality for older adults, but little is known about comparative mortality risks between individual agents. AIMS: To estimate the comparative mortality risks of commonly prescribed antipsychotic agents in older people living in the community. METHOD: A retrospective, claims-based cohort study was conducted of people over 65 years old living in the community who had been newly prescribed risperidone, olanzapine, quetiapine, haloperidol, aripiprazole or ziprasidone (n = 136 393). Propensity score-adjusted Cox proportional hazards models assessed the 180-day mortality risk of each antipsychotic compared with risperidone. RESULTS: Risperidone, olanzapine and haloperidol showed a dose-response relation in mortality risk. After controlling for propensity score and dose, mortality risk was found to be increased for haloperidol (hazard ratio (HR) = 1.18, 95% CI 1.06-1.33) and decreased for quetiapine (HR = 0.81, 95% CI 0.73-0.89) and olanzapine (HR = 0.82, 95% CI 0.74-0.90). CONCLUSIONS: Significant variation in mortality risk across commonly prescribed antipsychotics suggests that antipsychotic selection and dosing may affect survival of older people living in the community.

Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study.

OBJECTIVE: To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes. DESIGN: Population based cohort study with linked data from Medicaid, Medicare, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality. SETTING: Nursing homes in the United States. PARTICIPANTS: 75,445 new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). All participants were aged ≥ 65, were eligible for Medicaid, and lived in a nursing home in 2001-5. MAIN OUTCOME MEASURES: Cox proportional hazards models were used to compare 180 day risks of all cause and cause specific mortality by individual drug, with propensity score adjustment to control for potential confounders. RESULTS: Compared with risperidone, users of haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to 0.88). The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for the other drugs. There was no evidence that the effect measure modification in those with dementia or behavioural disturbances. There was a dose-response relation for all drugs except quetiapine. CONCLUSIONS: Though these findings cannot prove causality, and we cannot rule out the possibility of residual confounding, they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need. The data suggest that the risk of mortality with these drugs is generally increased with higher doses and seems to be highest for haloperidol and least for quetiapine.

Barriers to mental health treatment: results from the National Comorbidity Survey Replication.

BACKGROUND: The aim was to examine barriers to initiation and continuation of treatment among individuals with common mental disorders in the US general population. METHOD: Respondents in the National Comorbidity Survey Replication with common 12-month DSM-IV mood, anxiety, substance, impulse control and childhood disorders were asked about perceived need for treatment, structural barriers and attitudinal/evaluative barriers to initiation and continuation of treatment. RESULTS: Low perceived need was reported by 44.8% of respondents with a disorder who did not seek treatment. Desire to handle the problem on one's own was the most common reason among respondents with perceived need both for not seeking treatment (72.6%) and for dropping out of treatment (42.2%). Attitudinal/evaluative factors were much more important than structural barriers both to initiating (97.4% v. 22.2%) and to continuing (81.9% v. 31.8%) of treatment. Reasons for not seeking treatment varied with illness severity. Low perceived need was a more common reason for not seeking treatment among individuals with mild (57.0%) than moderate (39.3%) or severe (25.9%) disorders, whereas structural and attitudinal/evaluative barriers were more common among respondents with more severe conditions. CONCLUSIONS: Low perceived need and attitudinal/evaluative barriers are the major barriers to treatment seeking and staying in treatment among individuals with common mental disorders. Efforts to increase treatment seeking and reduce treatment drop-out need to take these barriers into consideration as well as to recognize that barriers differ as a function of sociodemographic and clinical characteristics.

Stigma and treatment for alcohol disorders in the United States.

Among a nationally representative sample of adults with an alcohol use disorder, the authors tested whether perceived stigmatization of alcoholism was associated with a lower likelihood of receiving alcohol-related services. Data were drawn from a face-to-face epidemiologic survey of 34,653 adults interviewed in 2004-2005 who were aged 20 years or older and residing in households and group quarters in the United States. Alcohol abuse/dependence was diagnosed by using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, version (AUDADIS-IV). The stigma measure used was the Perceived Devaluation-Discrimination Scale. The main outcome was lifetime intervention including professional services and 12-step groups for alcohol disorders. Individuals with a lifetime diagnosis of an alcohol use disorder were less likely to utilize alcohol services if they perceived higher stigma toward individuals with alcohol disorders (odds ratio = 0.37, 95% confidence interval: 0.18, 0.76). Higher perceived stigma was associated with male gender (ß = -0.75; P < 0.01), nonwhite compared with non-Hispanic white race/ethnicity, lower income (ß = 1.0; P < 0.01), education (ß = 1.48; P < 0.01), and being previously married (ß = 0.47; P = 0.02). Individuals reporting close contact with an alcohol-disordered individual (e.g., relative with an alcohol problem) reported lower perceived stigma (ß = -1.70; P < 0.01). A link between highly stigmatized views of alcoholism and lack of services suggests that stigma reduction should be integrated into public health efforts to promote alcohol treatment.

Panic and suicidal ideation in primary care.

The objective of this article is to examine the relationship between panic attacks, panic disorder, and suicidal ideation among primary care patients. A probability sample of 1,007 primary care attenders from a large urban university practice was assessed for current mental disorders and suicidal ideation (past 2 week prevalence) with the PRIME-MD Patient Health Questionnaire. Controlling for major depression, substance use disorders, and sociodemographic variables simultaneously, patients with either panic attacks or panic disorder had significantly increased risks of suicidal ideation. Suicidal ideation was highly associated with major depression and comorbid panic disorder (OR = 15.4) or panic attacks (OR = 7.9). There is need for detection and possible treatment of patients with panic attacks or disorder in primary care, especially among those with co-occurring major depression.

Patterns and predictors of treatment seeking after onset of a substance use disorder.

BACKGROUND: We studied survey respondents aged 18 through 54 years to determine consistent predictors of treatment seeking after onset of a DSM-III-R substance use disorder. METHODS: Survey populations included a regional sample in Ontario (n = 6261), a national sample in the United States (n = 5388), and local samples in Fresno, Calif (n = 2874) and Mexico City, Mexico (n = 1734). The analysis examined the effects of demographics, symptoms, and types of substances on treatment seeking. RESULTS: Between 50% (Ontario) and 85% (Fresno) of people with substance use disorders seek treatment but the time lag between onset and treatment seeking averages a decade or more. Consistent predictors of treatment seeking include: (1) late onset of disorder (odds ratio [OR], 3.8; 95% confidence interval [CI], 2.6-5.6 for late [> or =30 years] vs early [1-15 years] age at first symptom of disorder); (2) recency of cohort (OR, 3.4; 95% CI, 2.3-5.0 for most recent [aged 15-24 years at interview] vs earliest [aged > or =45 years] cohorts); (3) 4 specific dependence symptoms (using larger amounts than intended, unsuccessful attempts to cut down use, tolerance, and withdrawal symptoms), with ORs ranging between 1.6 (95% CI, 1.3-2.0) and 2.7 (95% CI, 2.1-3.6) for people with vs without these symptoms; and (4) use vs nonuse of cocaine (OR, 2.1; 95% CI, 1.6-2.7) and heroin (OR, 2.6; 95% CI, 1.1-6.0). CONCLUSIONS: Although most people with substance use disorders eventually seek treatment, treatment seeking often occurs a decade or more after the onset of symptoms of disorder. While treatment seeking has increased in recent years, it is not clear whether this is because of increased access, increased demand, increased societal pressures, or other factors.

Comorbidity, impairment, and suicidality in subthreshold PTSD.

OBJECTIVE: Reliance on the categorical model of psychiatric disorders has led to neglected study of posttraumatic sequelae that fall short of full criteria for posttraumatic stress disorder (PTSD). Substantial disability and suicidal risk is associated with subthreshold PTSD, but this association has not been well studied. In addition, no studies have examined the role of comorbidity in explaining disability and impairment in subthreshold PTSD. METHOD: On National Anxiety Disorders Screening Day 1997, 2,608 out of 9,358 individuals screened for affective and anxiety disorders at 1,521 sites across the United States reported at least one PTSD symptom of at least 1 month's duration. Impairment, comorbid anxiety disorders, major depressive disorder, and rates of suicidality were determined and compared for individuals with no, one, two, three, or four (full PTSD) symptoms on a screening questionnaire. Regression analyses examined the relative contribution of subthreshold PTSD and comorbid disorders to impairment and suicidal ideation. RESULTS: Impairment, number of comorbid disorders, rates of comorbid major depressive disorder, and current suicidal ideation increased linearly and significantly with each increasing number of subthreshold PTSD symptoms. Individuals with subthreshold PTSD were at greater risk for suicidal ideation even after the authors controlled for the presence of comorbid major depressive disorder. CONCLUSIONS: Higher numbers of subthreshold PTSD symptoms were associated with greater impairment, comorbidity, and suicidal ideation. Disability and impairment found in previous studies of subthreshold PTSD symptoms may be related in part to the presence of comorbid disorders. However, the presence of subthreshold PTSD symptoms significantly raised the risk for suicidal ideation even after the authors controlled for major depressive disorder. Given the broad public health implications of these findings, more efforts are needed to identify subthreshold PTSD symptoms in clinical populations, epidemiologic surveys, and treatment studies.

Electro-convulsive therapy practices in the community.

BACKGROUND: Controlled studies have demonstrated that variations in electro-convulsive therapy (ECT) technique impacts on efficacy and cognitive side effects. However, there is little information on the extent of variation in how ECT is practiced in community settings in the United States. METHODS: A survey of practice patterns was conducted at ECT facilities in the greater New York City metropolitan area. RESULTS: The 59 facilities varied considerably in many aspects of ECT practice, often clearly departing from the standards in the field. The more intensive the form of ECT used at facilities, the less likely was cognitive status assessed following the treatment course. CONCLUSION: There is marked variability in the nature of ECT practices in community settings. The extent to which this variability impacts on the benefits and risks of ECT needs to be examined.

Prescription of psychotropic medications to youths in office-based practice.

OBJECTIVE: This study sought to determine sociodemographic characteristics of treatment of children and adolescents for whom psychotropic medications are prescribed and to describe the clinical management approaches associated with the prescription of each major class of psychotropic medication in office-based medical practices in the United States. METHODS: Data for a four-year period (1992-1996) were drawn from the National Ambulatory Medical Care Survey, a nationally representative survey of office-based medical practices, to determine prescribing patterns, patients' sociodemographic characteristics, and clinical management approaches associated with visits during which psychotropic medications were prescribed to patients aged 19 years or under. RESULTS: Psychotropic medications were prescribed during 2.2 percent of all visits. A majority of the prescriptions for psychotropic medications (84.8 percent) were provided by general practitioners or pediatricians. For the visits during which a psychotropic medication was prescribed, stimulants were the most commonly prescribed (53.9 percent of such visits), but prescription of other classes of medications was not uncommon: antidepressants (30 percent), anxiolytics (7.2 percent), antipsychotics (7.2 percent), and mood stabilizers (12.7 percent). Significant differences were observed in the prescription of each class of medication by sex, race, and payment source. CONCLUSIONS: General practitioners and pediatricians have a role in the office-based treatment of youths with psychotropic medications.

Treatment of panic attack and risk of major depressive disorder in the community.

OBJECTIVE: The authors' goal was to determine whether treatment of panic attacks has a protective effect on the risk of major depression in the community. METHOD: Data were drawn from the National Comorbidity Survey, a community-based household sample representative of the U.S. adult population. A Cox proportional hazard model was used to estimate the association between risk of first-onset major depression and panic among subjects who had or had not received treatment for panic. RESULTS: A significantly smaller proportion of individuals who received treatment for panic (19%) than those who did not receive treatment (45%) developed major depression. This difference remained significant in a Cox proportional hazard analysis adjusted for age at onset of panic and differences in demographic characteristics. CONCLUSIONS: Detection and treatment of panic may reduce the risk of developing major depression.

Medication supervision and adherence of persons with psychotic disorders in residential treatment settings: a pilot study.

BACKGROUND: Little is known about risk factors for and predictors of medication nonadherence within residential facilities. This pilot study examined the association between medication adherence and level of supervision and other environmental and clinical variables among patients with schizophrenia and related psychotic disorders living in supported housing. METHOD: A convenience sample of 74 adult residents with schizophrenia and related psychotic disorders (DSM-IV criteria) living in 4 supported housing facilities in New York City were assessed by their treating psychiatrist for medication cessation during the previous month. Demographic characteristics, medications, supervision, global function as measured by the Global Assessment of Functioning (GAF), and substance abuse were also assessed. A priori hypotheses were that regimen complexity would be directly and medication supervision would be inversely related to medication nonadherence. RESULTS: In multivariate models, lack of direct medication supervision, negative medication attitude, and lower GAF score were associated with increased medication nonadherence in the recent past. CONCLUSION: This pilot study suggests that direct supervision of medication is associated with better adherence in residential treatment settings. This finding is relevant for mental health service planners and clinicians working in these settings.

Medically unexplained symptoms in an urban general medicine practice.

The authors investigated the prevalence of multiple medically unexplained symptoms (MMUS) as identified by primary care physicians (PCPs) in a systematic sample of 172 patients. Patients were from a university-affiliated urban primary care practice serving a low-income population. Patients with a history of MMUS were older (mean: 57.2 vs. 53.0 years), more likely to be female (90.5% vs. 72.3%), and less likely to be married or living with a partner (14.4% vs. 36.2%) than those without MMUS. Patients with MMUS had over twice the rate of any current psychiatric disorder, almost two-and-a-half times the rate of any current anxiety disorder, and greater functional impairment. These data suggest that patients with MMUS are as common in urban primary care clinics as in more affluent clinics and reinforce the need for PCPs to screen these patients for common and treatable psychiatric conditions.

Is gender a factor in psychiatrists' evaluation and treatment of patients with major depression?

BACKGROUND: Gender differences in clinical assessment and treatment have been reported in several areas of medicine. We examine whether differences exist in the routine outpatient psychiatric management of men and women with major depression. METHODS: Psychiatrists practicing in the community completed case forms on a systematic sample of their adult outpatients with major depression. Comparisons are presented between male (n=261) and female (n=472) patients focusing on their background characteristics, clinical presentation, assessment, and treatment. Significant gender disparities in assessment and treatment are also examined with respect to the gender of the treating psychiatrist. RESULTS: Although male and female patients had generally similar clinical profiles, a significantly greater proportion of males than females had psychomotor retardation and substance use disorders. No significant gender differences were observed in the assessment of depressive symptoms, psychiatric comorbidities, and treatment with antidepressant medications or psychotherapy. However, a significantly smaller percentage of depressed women than men received assessments of sexual function and medication-related sexual side effects. Female patients were also less likely to have discussed their treatment preferences with their psychiatrists. LIMITATIONS: Only a minority (33.2%) of psychiatrists invited to participate contributed patients to this study. The results are based on structured assessments completed by practicing psychiatrists rather than patient self-assessments or independent research assessments. CONCLUSIONS: Although we find overall little evidence of gender bias in the clinical management of major depression, both male and female psychiatrists need to further explore sexual function and treatment preferences in female patients.

A comparison of three scales for assessing social functioning in primary care.

OBJECTIVE: Assessment of functional status is increasingly important in clinical trials and outcome research. Although several scales for assessing functioning are widely used, they vary in coverage, and direct comparisons among them are rare. Comparative information is useful in guiding selection of appropriate scales for research applications. METHOD: Results from three scales that measure functioning-the Medical Outcomes Study 36-item Short-Form Health Survey, the Social Adjustment Scale Self-Report, and the Social Adaptation Self-Evaluation Scale-were compared in a consecutively selected sample of 211 patients coming to primary care. Patients also received psychiatric assessments. RESULTS: All three scales were acceptable to patients, showed few significant correlations with demographic variables, and were able to differentiate psychiatrically ill and well patients. Correlations among scales, even among scale items that assessed similar domains of functioning, were modest. CONCLUSIONS: Although all three scales are presumed to assess functional status, their item content and coverage differ. Selection of a scale requires a review of the scale items and consideration of research priorities and the characteristics of the study group. If functional status is a critical outcome measure, use of more than one scale may be necessary.

Is the substance abuse of inpatients with schizophrenia overlooked?

The utility of medical records and clinician reports for assessing substance abuse among inpatients with schizophrenia or schizoaffective disorder was assessed in a sample of 296 patients recruited from four general hospitals in New York City. Measures derived from the medical record, the discharge summary, and primary clinician reports are compared to the results of a structured diagnostic interview. Analysis of the sensitivity, specificity, positive predictive value, and overall accuracy of the nondiagnostic sources found unexpectedly high levels of detection. Discharge summaries had the lowest sensitivity when compared to the diagnostic interview, raising concern that inpatient staff and clinicians may fail to communicate substance abuse problems to outpatient providers.