To assess long-term effectiveness and safety of randomized antidepressant discontinuation after acute recovery from bipolar depression.
In the Systematic Treatment Enhancement Program for Bipolar ...Disorder (STEP-BD) study, conducted between 2000 and 2007, 70 patients with DSM-IV-diagnosed bipolar disorder (72.5% non-rapid cycling, 70% type I) with acute major depression, initially responding to treatment with antidepressants plus mood stabilizers, and euthymic for 2 months, were openly randomly assigned to antidepressant continuation versus discontinuation for 1-3 years. Mood stabilizers were continued in both groups.
The primary outcome was mean change on the depressive subscale of the STEP-BD Clinical Monitoring Form. Antidepressant continuation trended toward less severe depressive symptoms (mean difference in DSM-IV depression criteria = -1.84 95% CI, -0.08 to 3.77) and mildly delayed depressive episode relapse (HR = 2.13 1.00-4.56), without increased manic symptoms (mean difference in DSM-IV mania criteria = +0.23 -0.73 to 1.20). No benefits in prevalence or severity of new depressive or manic episodes, or overall time in remission, occurred. Type II bipolar disorder did not predict enhanced antidepressant response, but rapid-cycling course predicted 3 times more depressive episodes with antidepressant continuation (rapid cycling = 1.29 vs non-rapid cycling = 0.42 episodes/year, P = .04).
This first randomized discontinuation study with modern antidepressants showed no statistically significant symptomatic benefit with those agents in the long-term treatment of bipolar disorder, along with neither robust depressive episode prevention benefit nor enhanced remission rates. Trends toward mild benefits, however, were found in subjects who continued antidepressants. This study also found, similar to studies of tricyclic antidepressants, that rapid-cycling patients had worsened outcomes with modern antidepressant continuation.
clinicaltrials.gov Identifier: NCT00012558.
To assess the relationships among depressive signs and symptoms and left versus right temporal-parietal cerebral blood volumes (CBVs) in elderly patients with a primary complaint of memory loss.
...Total Geriatric Depression Scale Short Form (GDS-SF) scores, left and right temporal-parietal cerebral blood volume values, and other prospectively recorded data were obtained via chart review of 24 patients aged >/=65 years, evaluated between 1995 and 2000 at McLean Hospital for a primary complaint of memory loss. Multivariate regression analyses were carried out with GDS-SF total scores as outcome variables, with CBV values as explanatory factors and with several patient characteristics as covariates.
Depressive symptoms, as measured by the GDS-SF, were significantly associated with decreased left/right temporal-parietal CBV ratios (beta regression coefficient = -20.7; t df = 22 = -2.96, p = 0.007). These findings remained statistically significant after controlling for age, sex, Mini-Mental State Exam (MMSE) score, years of education, years of memory loss, and handedness (beta regression coefficient = -16.7; t df = 16 = -2.67, p = 0.017).
In this study, severity of depressive symptoms as measured by the GDS-SF in patients >/=65 years old who presented with a primary complaint of memory loss was associated with decreased left/right temporal-parietal CBV ratios, independently of age, sex, MMSE score, years of education, years of memory loss, and handedness. These findings suggest that in the presence of cognitive decline, increased depressive signs and symptoms may be associated with decreased left/right temporal-parietal CBV ratios.
Abstract Background Risks of life-threatening behaviors are high among bipolar disorder (BPD) patients, but early rates and associated risk factors for suicides and accidents remain ill-defined. ...Methods We assessed 216 DSM-IV BP-I patients prospectively for 4.2 years from first-lifetime hospitalization, using ordinal logistic-regression to estimate risks and associated demographic and clinical factors among risk-groups with: 1 no suicidal ideation, acts, or accidents, 2 suicidal ideation only, 3 suicides and attempts , 4 accidents , and 5 both suicidal acts and accidents. Results Suicidal thoughts or acts were identified in 127/216 subjects/4.2 years (14%/year), including suicidal ideation in 88 (9.7%/year), and acts in 39 (4.3%/year: 38 attempts 17.6%/year, 1 suicide 0.11%/year); 87% of acts occurred within a year of a first-episode. Life-threatening accidents occurred in 20 cases (2.2%/year) with a mean latency of 3.8 years, including 12 with suicidal ideation or attempts (60% co-occurrence of accidents and suicidality); alcohol was implicated in 25% of accidents. The 53 cases of violent behaviors (5.84%/year) included a fatal car-wreck and a suicide, for a mortality risk of 0.22%/year (2/216/4.2 years). Suicidality was associated with initial mixed-state, proportion of follow-up weeks in mixed-states or depression, and prior suicide attempts; accidents were associated selectively with initial mania or psychosis, later mania or hypomania, and alcohol abuse. Violent acts also were associated with use of more psychotropic medicines/person, and with use of antipsychotics or sedative-anxiolytics. Limitations Treatment was clinical and uncontrolled, illness relatively severe, and statistical power limited. Conclusions Early in BP-I disorder, risks of suicidal acts and accidents were high, inter-related, and associated with particular types of initial and later morbidity, suggesting some predictability and potential for preventive intervention.
Objective: To compare suicide rates with vs. without long‐term lithium treatment in major affective disorders.
Method: Broad searching yielded 22 studies providing suicide rates during lithium ...maintenance; 13 also provide rates without such treatment. Study quality was scored, between‐study variance tested, and suicide rates on vs. off lithium examined by meta‐analyses using random‐effects regression methods to model risk ratios.
Results: Among 5647 patients (33 473 patient‐years of risk) in 22 studies, suicide was 82% less frequent during lithium‐treatment (0.159 vs. 0.875 deaths/100 patient‐years). The computed risk‐ratio in studies with rates on/off lithium was 8.85 (95% CI, 4.12–19.1; P<0.0001). Higher rates off‐lithium were not accounted for by treatment‐discontinuation.
Conclusion: Suicide risk was consistently lower during long‐term treatment of major affective illnesses with lithium in all studies in the meta‐analysis, including the few involving treatment‐randomization.
Objectives: Since bipolar disorder (BPD) patients have high rates of comorbid substance abuse, and the temporal relationships involved are unclear, we evaluated the sequencing of specific substance ...use and affective morbidity.
Methods: Prospective follow‐up (4.7 years) of 166 first‐episode DSM‐IV type I BPD patients with reliable, standardized assessments provided data for longitudinal analysis of temporal distribution of alcohol and cannabis use versus manic or depressive episodes or symptoms, using generalized estimating equation regression modeling.
Results: By quarters, cannabis use selectively and strongly preceded and coincided with mania/hypomania, and alcohol use preceded or coincided with depression, whereas substance use was unassociated with mood states in preceding quarters.
Conclusions: These preliminary findings suggest potentially predictive temporal associations, in which the abuse of cannabis or alcohol anticipated or corresponded with, but did not follow, affective morbidity, including selective association of cannabis with mania and alcohol with depression.
The authors examined the effectiveness of a voluntary memory impairment-screening program for community-dwelling older persons, assessing three factors: appropriateness of screening instrument, ...reliability of complaints of cognitive difficulties, and adherence to screening recommendations. Two cognitive screening instruments, the Mini-Mental State Exam (MMSE) and the Seven-Minute Screen (7MS) were compared in 59 participants. Twenty-nine percent showed signs of impairment on the 7MS. Results suggested that the 7MS and the MMSE may have different sensitivities and specificities for the detection of early dementia. Failure on the 7MS was not predicted by cognitive or functional complaints. The study identified and addressed factors affecting compliance with screening recommendations.
The purpose of this study was to assess the psychometric properties of the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD), the first clinician-administered scale for the ...assessment of change in DSM-IV borderline psychopathology. The questions for the measure were adapted from the BPD module of the Diagnostic Interview for DSM-IV Personality Disorders (DIPD-IV) to reflect a 1-week time frame and each of the nine criteria for BPD is rated on a five-point anchored rating scale of 0 to 4, yielding a total score of 0 to 36. Two diagnostic interviews that assess the presence of BPD were administered to 200 nonpsychotic patients: the BPD module of the DIPD-IV and the Revised Diagnostic Interview for Borderlines (DIB-R). The ZAN-BPD was also administered, blind to diagnostic information. In addition, each patient filled out a self-report measure of general psychopathology that is often used in borderline treatment studies, the Symptom Checklist 90 (SCL-90). The convergent validity of the ZAN-BPD and relevant scales of the SCL-90 and the DIB-R was assessed and found to be highly significant. The discriminant validity of the various scores of the ZAN-BPD was also found to be highly significant, easily discriminating the 139 patients who met the DSM-IV criteria for BPD from the 61 patients who did not. In addition, internal consistency of the ZAN-BPD was found to be high (Cronbach's alpha=0.85). The interrater reliability of the ZAN-BPD was assessed using 32 conjoint interviews, while same day test-retest reliability was assessed in a separate sample of 40 patients. All reliability raters were blind to all previously collected information concerning each subject. All intraclass correlations were in the good to excellent range. Finally, the sensitivity of the ZAN-BPD to change was assessed using a third sample of 41 patients who were reinterviewed by a blind rater 7 to 10 days after the ZAN-BPD was first administered. The SCL-90 was also readministered at this time. The correlations between difference scores of the ZAN-BPD and difference scores of the SCL-90 were found to be significant, indicating that the ZAN-BPD measures change in a clinically meaningful manner. Taken together, the results of this study suggest that the ZAN-BPD is a promising clinician-administered scale for the assessment of change in borderline psychopathology over time.
This study clarified the early characteristics of substance use disorders in patients with first-episode bipolar I disorder.
The authors evaluated substance use disorders, associated factors, and ...clinical course, prospectively, in the first 2 years of DSM-IV bipolar I disorder with standardized methods.
Baseline substance use disorder was found in 33% (37 of 112) of the patients at baseline and in 39% at 24 months. Anxiety disorders were more frequent in the patients with than without substance use disorder (30% and 13%, respectively). Associations of alcohol dependence with depressive symptoms and cannabis dependence with manic symptoms were suggested. Patients using two or more substances had worse outcomes.
Since substance use disorders were frequent from the beginning of bipolar I disorder and were associated with anxiety disorders and poor outcome, early interventions for substance use disorder and anxiety might improve later outcome.
To examine patterns of adherence to mood stabilizers and reasons for nonadherence in patients with bipolar disorder, with and without substance use disorder (SUD).
From December 2003 to October 2004, ...115 patients with DSM-IV-diagnosed bipolar disorder (58 with SUD and 57 without SUD) were administered a structured interview regarding their lifetime experience with mood stabilizers.
Lifetime adherence with mood stabilizers for the SUD group was 65.5%, versus 82.5% for the non-SUD group (p < .05). Lifetime lithium adherence for the SUD group was lower than for the non-SUD group (65.9% vs. 85.0%, p < .05). Substance-related reasons were more commonly cited by the SUD group than the non-SUD group. In contrast, pill- and dosage-related reasons were more frequently endorsed by the non-SUD group than the SUD group.
In bipolar disorder patients, those with co-occurring SUD were less adherent than those without SUD. The SUD group was also less adherent to lithium than the non-SUD group. The reasons for nonadherence differed by presence or absence of a SUD. Physicians should be alert to these differences in their clinical practices while prescribing medications.
