Complex psychotropic polypharmacy in bipolar disorder across varying mood polarities: A prospective cohort study of 2712 inpatients.

BACKGROUND: It is common for patients with bipolar disorder (BP) to receive multiple psychotropics, but few studies have assessed demographic and clinical features associated with risk for receiving complex psychotropic polypharmacy. METHODS: This longitudinal cohort study examined 2712 inpatients with a DSM-IV clinical diagnosis of BP to assess associations between complex polypharmacy (defined as ≥4 psychotropics) and demographic and clinical features; associations with risk of rehospitalization were also examined. Logistic regressions were performed with the sample as a whole and with each of four DSM-IV BP subtypes individually. RESULTS: Complex polypharmacy was present in 21.0%. BP-I depressed patients were more likely to receive complex regimens than BP-I manic, BP-I mixed or BP-II patients. In the sample as a whole, variables significantly associated with complex polypharmacy included female, white, psychotic features and a co-diagnosis of borderline personality, post-traumatic stress or another anxiety disorder. The only examined medication not significantly associated with complex polypharmacy was lithium, although only in BP-I depressed and BP-I mixed. Complex polypharmacy was associated with rehospitalization in BP-I mania within 15 and 30days post index hospitalization. LIMITATIONS: All data were from one clinical facility; results may not generalize to other settings and patient populations. CONCLUSIONS: BP-I depression may pose a greater treatment challenge than the other BP subtypes. Lithium may confer an overall advantage compared to other medications in BP-I depressed and BP-I mixed. Further research is needed to guide pharmacotherapy decisions in BP patients.

Hospital patients' perceptions during treatment and early discontinuation of serotonin selective reuptake inhibitor antidepressants.

Studies have suggested that discontinuation of treatment in depressed patients is associated with their perceptions about their treatment. We surveyed 403 adults treated for major depressive disorder with a selective serotonin reuptake inhibitor (SSRI) 3 months after onset of treatment to assess their interactions with clinicians, reasons they stopped SSRI treatment, and SSRI side effects (SEs). Bothersome SEs, poorer instruction by physicians about SSRI SEs, and self-reported change in depression, sex, marital status, and employment were significantly (P < 0.05) associated with discontinuation. Logistic regression examined the associations between patients' perceptions during treatment planning and SSRI discontinuation. Seventeen percent of patients felt uninvolved in treatment decisions, 9% disagreed with the diagnosis, and 24% subsequently stopped treatment. Elevated risk of discontinuation was found among patients who felt uninvolved in treatment decisions (unadjusted risk ratio [RR], 2.3; 95% confidence interval [CI], 1.2-4.3) and those who disagreed with the diagnosis (RR, 2.0; CI, 0.9-4.4). Patients who both felt uninvolved and disagreed with the diagnosis were 7-fold as likely to discontinue their SSRI (RR, 7.3; CI, 1.5-36.3) compared with those who felt neither uninvolved nor disagreed. Selective serotonin reuptake inhibitor SEs, specific interactions with clinicians, self-assessed outcomes, and sociodemographics did not explain these associations. To improve adherence to medications, clinicians should consider patients' perceptions about their involvement in treatment decisions and agreement with their diagnosis.

Last-observation-carried-forward imputation method in clinical efficacy trials: review of 352 antidepressant studies.

STUDY OBJECTIVE: To determine the prevalence, over 40 years, of using the last-observation-carried-forward (LOCF) imputation method in clinical trials, the association between use of LOCF and how the trials were conducted, and the extent of information about attrition and LOCF use in published reports. DESIGN: Retrospective analysis of the reports of randomized antidepressant efficacy trials published over a 40-year period (1965-2004). DATA SOURCES: MEDLINE database, Cochrane reviews, reference- and bibliography-based manual search, and publication list services. MEASUREMENTS AND MAIN RESULTS: A total of 352 trials met the following criteria for analysis: antidepressant comparative efficacy trial, randomized design, patients with major depressive disorder, English-language article, published during 1965-2004, and first report of a trial. Design, attrition, and data analysis characteristics were recorded by investigators and trained assistants. Analyses included descriptive statistics of the trial size, duration, and number of patients who dropped out in LOCF versus non-LOCF studies, as well as the extent to which dropouts and the potential bias associated with attrition was discussed in the published report. The frequency of published antidepressant clinical trials increased from less than 1 trial/year (1965-1974) to 19 trials/year (1990-1994). Trials using the LOCF method were significantly larger than non-LOCF trials (p<0.01), and the proportion of subjects dropping out was significantly greater (p<0.05) in LOCF versus non-LOCF trials. The proportion of subjects dropping out remained relatively constant over time (approximately 30%) but was significantly greater among LOCF (30.9%) than non-LOCF (28.8%) trials (p<0.01). The LOCF study articles were more likely to report dropouts, but only 7% of these articles reported outcomes recorded for subjects before they dropped out. Less than 16% of articles discussed bias associated with dropouts, 6.8% discussed the direction of bias, and only about 2% suggested the magnitude of the bias. CONCLUSION: The percentage of clinical antidepressant trials using the LOCF method and the percentage of study subjects' data imputed by using LOCF increased many-fold during 1965-2004. Published reports of trials provided little information to allow readers to assess possible bias introduced by use of the LOCF method.

The association between self-reported anxiety symptoms and suicidality.

This cross-sectional study assessed the association between self-reported anxiety symptoms and self-reported suicidality among a mixed diagnostic sample of psychiatric outpatients. Data were obtained from chart review of 2,778 outpatients who completed a routine diagnostic clinical interview and a standardized self-report of psychiatric symptoms on admission. Bivariate analyses indicated that those with >or= moderate anxiety symptoms were over three times as likely to report >or= moderate difficulty with suicidality. Self-reported anxiety symptoms were associated with a 2-fold increased likelihood of reporting suicidality after controlling for confounding (demographics, depressive symptoms, and diagnoses). These data are consistent with a growing literature demonstrating an association between anxiety symptoms and suicidality, and suggest that this association is not accounted for by coexisting mood symptoms or diagnoses. A single item, self-report may be a useful screening tool for symptoms that are pertinent to assessment of suicide risk.

Headache complaints and the risk of suicidal thoughts or behaviors.

The association between severe headaches and suicidal thoughts or behaviors is generally attributed to underlying depression, but it is plausible that severe headaches can lead to suicidal thoughts/behaviors, independent of the effects of psychiatric conditions. This association has been observed in only 1 previous study. Our multivariate analysis examined the longitudinal association between severe headaches and development of suicidal thoughts/behaviors over a period of 1 to 2 years among 6832 community-dwelling adults interviewed during the Epidemiologic Catchment Area Study. Severe headaches were significantly associated with developing suicidal thoughts/behaviors after adjusting for psychiatric diagnoses and demographics [adjusted odds ratio (ORa) = 1.48; 95% confidence interval (CI) = 1.04, 2.11], or additionally adjusting for interaction between anxiety and depression (ORa = 1.52; 95% CI = 1.07, 2.16). These results suggest that individuals with severe headaches should be screened for suicidal thoughts/behaviors, irrespective of the presence of a psychiatric condition.

Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence.

OBJECTIVE: Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. METHOD: Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. RESULTS: Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. CONCLUSION: The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation.

Signs and symptoms associated with the metabolic syndrome in psychiatric inpatients receiving antipsychotics: a retrospective chart review.

OBJECTIVE: The metabolic syndrome has been recognized as a major health risk for patients taking atypical antipsychotics. Few studies, however, have examined large samples of psychiatric patients to explore the prevalence of the signs and symptoms associated with this condition. METHOD: The investigators retrospectively identified all inpatient admissions at the study site who were treated with antipsychotics during 2003 (N = 1691) and extracted demographic and clinical data (including measures associated with the syndrome: body mass index > 30 kg/m2, dyslipidemia, diagnosis of hypertension or diabetes). Stepwise logistic regression was used to identify variables associated with each correlate of the syndrome. RESULTS: In the majority of this sample (69.3%), at least 1 correlate of the metabolic syndrome was present. The odds that a patient would have 1 or more of these measures were approximately 8 times greater for those receiving clozapine than for those receiving another anti-psychotic medication. These patients also had increased odds (odds ratio = 2.5) of having hypertension or diabetes. In the subsample of patients with documentation for all 5 correlates of the metabolic syndrome (N = 362), 18.8% had > or = 3 of 5. CONCLUSION: The prevalence of at least 3 correlates in psychiatric inpatients receiving antipsychotics is probably an underestimate, because diagnosis was substituted for the blood pressure and glucose measures. Nonetheless, these findings support the call for routine screening for metabolic symptoms in patients receiving antipsychotics. The risk for these symptoms may be particularly high in some subgroups identified, such as patients older than 50 years and those taking clozapine or multiple antipsychotics.