Faculty Bibliography

The authors prospectively followed patients with treatment-resistant obsessive-compulsive disorder (OCD). Between 1988 and 1995, 56 patients with a history of inadequate response to oral clomipramine received 14 infusions of intravenous clomipramine. The follow-up period ranged from 4 to 11 years after treatment. Of the 44 subjects interviewed at follow-up, 70.5% had current OCD and 29.5% had sub-threshold OCD. Almost half reported feeling much improved or very much improved compared to their state prior to treatment with intravenous clomipramine

A common problem in statistical modelling is to distinguish between finite mixture distribution and a homogeneous non-mixture distribution. Finite mixture models are widely used in practice and often mixtures of normal densities are indistinguishable from homogenous non-normal densities. This paper illustrates what happens when the EM algorithm for normal mixtures is applied to a distribution that is a homogeneous non-mixture distribution. In particular, a population-based EM algorithm for finite mixtures is introduced and applied directly to density functions instead of sample data. The population-based EM algorithm is used to find finite mixture approximations to common homogeneous distributions. An example regarding the nature of a placebo response in drug treated depressed subjects is used to illustrate ideas

AIM: To investigate the efficacy of maintenance treatment with bupropion and/or nicotine gum for reducing smoking relapse. DESIGN, SETTING AND PARTICIPANTS: A 48-week study was conducted at a university-based smoking cessation clinic between February 2001 and October 2005. A total of 588 smokers received bupropion and nicotine patch in 8 weeks of open-label treatment (OLT); 289 abstainers during the last 4 weeks of OLT were randomized in double-blind placebo-controlled fashion to one of four arms for 16 weeks of maintenance treatment (MT) followed by 24 weeks of non-treatment follow-up (NTFU). INTERVENTION: Bupropion (300 mg/day) and 2 mg nicotine gum, used alone or combined, and comparable placebo pill and placebo gum. Behavioral counseling at all visits. OUTCOME: Time to relapse (TTR) from randomization. Relapse is defined as the first 7 consecutive days of smoking. Abstinence verified by carbon monoxide <or= 8 parts per million. FINDINGS: TTR was longer with extended active treatments compared to placebo (median days to relapse: bupropion + placebo = 136, nicotine + placebo = 98, bupropion + nicotine = 90, double placebo = 71). Hazard ratios (HR) for relapse were statistically significant for bupropion + placebo versus double placebo during MT (HR = 0.59, 95% CI = 0.37-0.92) and to the end of NTFU (HR = 0.66, 95% CI = 0.42-0.96). However, bupropion's advantage dissipated upon stopping the drug. Gum use was low, preventing a valid assessment; but analysis restricted to gum users suggested a weak effect of extended nicotine gum. CONCLUSION: Maintenance treatment with bupropion exerted a modest benefit for preventing smoking relapse; the optimum duration of bupropion treatment was unclear. Further research is needed to ascertain the merits of extended use of nicotine gum, other nicotine replacement agents and other treatments known to aid smokers for preventing relapse once abstinence is achieved

OBJECTIVE: This study assessed the long-term effects of group behavioral treatment plus individual cognitive behavioral therapy (CBT) and/or fluoxetine in binge eating disorder (BED) patients. RESEARCH METHODS AND PROCEDURES: A total of 116 individuals were randomized to an initial five-month trial and were followed up over two years. Assessments, including binge frequency, weight, and self-report measures, were administered at pre-treatment, post-treatment, and approximately 6, 12, 18, and 24 months after initial treatment. RESULTS: Across treatment groups, there was overall improvement over 29 months in binge frequency and in binge abstinence. The odds of binge abstinence 2 years post-treatment were 1.373 times the odds of binge abstinence immediately post-treatment. There was no significant change in weight over the two-year period. Subjects who received individual CBT evidenced lower binge frequency over the two-year follow-up period than patients who had not received individual CBT. Similarly, CBT was associated with increased rates of binge abstinence. There were no main effects of treatment assignment on weight over the two-year follow-up period. There was a significant advantage for fluoxetine assignment over the two-year follow-up period on depressive symptoms. DISCUSSION: The major significance of the study rests in its examination of the long-term effects of standardized interventions for BED. Our findings provide support for the ideas that short-term treatment may confer long-term benefit and that not all treatments are equivalent in the benefits they confer

OBJECTIVE: No previous research has focused on psychosocial functioning in understanding how personality disorders compound the impairment caused by major depressive disorder over time. This report describes the effects of persistent and remitting comorbid personality disorders on the depressive status and functioning of patients with major depressive disorder over the course of 2 years. METHOD: Longitudinal data on functioning from the first 2 years of the Collaborative Longitudinal Personality Disorders Study were evaluated for 3 groups of subjects with major depressive disorder: subjects with major depressive disorder alone (N = 103), those with persistent comorbid personality disorders (N = 164), and those with comorbid personality disorders that remitted (N = 69). DSM-IV criteria were used for mood and personality disorder diagnoses. The data were gathered from September 1996 to August 2000 and from September 2001 to September 2004. RESULTS: Subjects whose personality disorders remitted were more likely than those with persisting personality disorders to have major depressive disorder remit. Social functioning, as measured by the Longitudinal Interval Follow-up Evaluation and the Global Assessment of Functioning, improved across a range of domains over time, with most gains occurring in the first 6 months of follow-up and with differential improvement by group. As hypothesized, subjects whose personality disorders remitted fared nearly as well as did subjects without personality disorders, whereas subjects whose personality disorders persisted functioned most poorly. CONCLUSIONS: Outcome research on major depressive disorder has often ignored Axis II disorders. Our data indicate that the longitudinal course of personality psychopathology meaningfully influences depressive outcome and psychosocial functioning in patients with major depressive disorder. The findings indicate the need to target both symptom relief and psychosocial functioning and to treat both personality and mood disorders in comorbid patients

OBJECTIVE: Loss of response to a previously effective antidepressant is a common clinical problem. Retrospective analyses have shown that the pattern of response during antidepressant treatment (late onset and persistent versus other patterns) can be used to predict relapse during continuation and maintenance treatment and possibly to identify placebo responses to treatment. This study was designed to test the predictive value of response pattern prospectively and to examine the data for other predictors of relapse. METHOD: Five hundred seventy persons with major depressive disorder were treated with fluoxetine for 12 weeks and their pattern of response was determined. Those who responded (N=292) underwent random assignment, under double-blind conditions, to continue taking fluoxetine or to switch to placebo for 52 weeks or until relapse. Survival analysis was used to examine the effect of covariates on relapse. RESULTS: Although fluoxetine was significantly more effective than placebo during maintenance treatment, this chronically ill group had a high rate of relapse. Contrary to previous findings, a pattern of acute response was not predictive of relapse. Chronicity, symptom severity, a neurovegetative symptom pattern, and female gender were all associated with a significantly greater risk of relapse, with no difference observed between fluoxetine and placebo. CONCLUSIONS: The pattern of response to acute treatment appears to be inconsistently predictive of relapse. There is a high rate of relapse with both active medication and placebo in patients with chronic depression. Illness characteristics predict loss of response both to fluoxetine and to placebo. No variable examined was predictive of differential relapse rates between fluoxetine and placebo

OBJECTIVE: To investigate rates of response and remission in adults with obsessive-compulsive disorder (OCD) after 12 weeks of evidence-based treatment. METHOD: Post hoc analyses of response and remission were conducted using data from a multisite, randomized, controlled trial comparing the effects of 12 weeks of exposure and ritual prevention (EX/RP), clomipramine (CMI), their combination (EX/RP+CMI), or pill placebo (PBO) in 122 adults with OCD (DSM-III-R or DSM-IV criteria). Response was defined as a decrease in symptoms; remission was defined as minimal symptoms after treatment. Different response and remission definitions were constructed based on criteria used in prior studies. For each definition, the proportion of responders or remitters in each treatment group was then compared. RESULTS: There were significant differences (p<.05) among the 4 treatment groups in the proportion of responders and remitters. In pairwise comparisons, EX/RP+CMI and EX/RP each produced significantly more responders and remitters than PBO; CMI produced significantly more responders and remitters than PBO for some definitions but not for others. When remission was defined as a Yale-Brown Obsessive Compulsive Scale (YBOCS) score of 12 or less, significantly more EX/RP+CMI (18/31 [58%]) and EX/RP (15/29 [52%]) patients entering treatment achieved remission than either CMI (9/36 [25%]) or PBO (0/26 [0%]) patients. However, even in treatment completers, many CMI and some EX/RP+CMI and EX/RP patients did not achieve remission (remission rates for YBOCS<or=12: EX/RP+CMI=13/19 [68%]; EX/RP=15/21 [71%]; CMI=8/27 [30%]; PBO=0/20 [0%]). CONCLUSION: EX/RP (with or without CMI) can lead to superior treatment outcome compared with CMI alone in OCD patients without comorbid depression. However, many OCD patients who receive evidence-based treatment do not achieve remission

BACKGROUND: Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions who experience barriers to access to care or a high burden of illness. METHODS: The authors conducted a randomized, controlled trial comparing telemedicine case management to usual care, with blinding of those obtaining outcome data, in 1,665 Medicare recipients with diabetes, aged 55 years or greater, and living in federally designated medically underserved areas of New York State. The primary endpoints were HgbA1c, blood pressure, and low-density lipoprotein (LDL) cholesterol levels. RESULTS: In the intervention group (n = 844), mean HgbA1c improved over one year from 7.35% to 6.97% and from 8.35% to 7.42% in the subgroup with baseline HgbA1c > or =7% (n = 353). In the usual care group (n = 821) mean HgbA1c improved over one year from 7.42% to 7.17%. Adjusted net reductions (one-year minus baseline mean values in each group, compared between groups) favoring the intervention were as follows: HgbA1c, 0.18% (p = 0.006), systolic and diastolic blood pressure, 3.4 (p = 0.001) and 1.9 mm Hg (p < 0.001), and LDL cholesterol, 9.5 mg/dL (p < 0.001). In the subgroup with baseline HgbA1c > or =7%, net adjusted reduction in HgbA1c favoring the intervention group was 0.32% (p = 0.002). Mean LDL cholesterol level in the intervention group at one year was 95.7 mg/dL. The intervention effects were similar in magnitude in the subgroups living in New York City and upstate New York. CONCLUSION: Telemedicine case management improved glycemic control, blood pressure levels, and total and LDL cholesterol levels at one year of follow-up

OBJECTIVE: The aim of this study was to test the hypothesis that desipramine would be an effective treatment in cocaine abusers with current depressive disorders. METHOD: This was a randomized, 12-week, double-blind, 'placebo-controlled trial of outpatients (N = 111) meeting DSM-III-R criteria for cocaine dependence and major depression or dysthymia (by SCID interview). Participants were treated with desipramine, up to 300 mg per day, or matching placebo. All patients received weekly individual manual-guided relapse prevention therapy. Weekly outcome measures included the Clinical Global Impression Scale, self-reported cocaine use and craving, urine toxicology, and the Hamilton Depression Scale (biweekly). Summary measures of mood and cocaine use outcome were compared between treatment groups with chi2- or t-tests. Dichotomous summary measures of depression response and cocaine response were the primary outcomes. Mixed effect models were also fit to explore the relationship of cocaine use to mood improvement and treatment over weeks in the trial. RESULTS: Desipramine was associated with a higher rate of depression response (51%, 28/55) than placebo (32%, 18/56) (p < 0.05), but treatment groups did not differ in rate of cocaine response. Depression improvement was associated with improvement in cocaine use. Desipramine was associated with more dropouts due to side effects and medical adverse events, while placebo was associated with more dropouts due to psychiatric worsening. CONCLUSIONS: Desipramine was an effective treatment for depression among cocaine-dependent patients. Improvement in mood was associated with improvement in cocaine abuse, but a direct effect of medication on cocaine outcome was not clearly established and rates of sustained abstinence were low. Future research should examine newer antidepressant medications with more benign side effect profiles and combinations of behavioral and pharmacological treatments to maximize effects on cocaine use

BACKGROUND: Few studies have compared the related diagnostic constructs of depressive personality disorder (DPD) and dysthymic disorder (DD). The authors attempted to replicate findings of Klein and Shih in longitudinally followed patients with personality disorder or major depressive disorder (MDD) in the Collaborative Longitudinal Personality Disorders Study. METHODS: Subjects (N = 665) were evaluated at baseline and over 2 years (n = 546) by reliably trained clinical interviewers using semistructured interviews and self-report personality questionnaires. RESULTS: Only 44 subjects (24.6% of 179 DPD and 49.4% of 89 early-onset dysthymic subjects) met criteria for both disorders at baseline. Depressive personality disorder was associated with increased comorbidity of some axis I anxiety disorders and other axis II diagnoses, particularly avoidant (71.5%) and borderline (55.9%) personality disorders. Depressive personality disorder was associated with low positive and high negative affectivity on dimensional measures of temperament. Depressive personality disorder subjects had lower likelihood of remission of baseline MDD at 2-year follow-up, whereas DD subjects did not. The DPD diagnosis appeared unstable over 2 years of follow-up, as only 31% (n = 47) of 154 subjects who had DPD at baseline and also had follow-up assessment met criteria on blind retesting. LIMITATIONS: Results from this sample may not generalize to other populations. CONCLUSIONS: Depressive personality disorder and dysthymic disorder appear to be related but differ in diagnostic constructs. Its moderating effect on MDD and predicted relationship to measures of temperament support the validity of DPD, but its diagnostic instability raises questions about its course, utility, and measurement