Biomedical subjects

Timothy Petersen

Publications and source records attributed to Timothy Petersen.

34 records · Page 2Linked to original sources

PubMed2003

Switching to bupropion in fluoxetine-resistant major depressive disorder.

Up to 50% of patients with major depressive disorder (MDD) fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as an initial treatment. Switching to bupropion, for depressed patients not responding to SSRIs, is a popular strategy among clinicians. This study assesses the efficacy of bupropion SR in the management of MDD resistant to a prospective trial of fluoxetine. Twenty-nine patients with MDD refractory to an 8- to 12-week open-trial of fluoxetine were enrolled in an 8-week open-trial of bupropion SR. Both a completer analysis (n = 20) and a modified intent-to-treat analysis (n = 26) were performed to evaluate bupropion SR response rates. Using a completer analysis, seven patients (35.0%) were classified as responders, five (25.0%) partial responders, and eight (40.0%) nonresponders. A modified intent to treat analysis resulted in nine (34.6%) patients classified as responders, eight (30.8%) partial responders, and nine (34.6%) nonresponders. The overall proportion of remitters was 6/20 (30.0%) using a completer analysis and 6/26 (23.1%) using an MITT analysis. Approximately 60% of patients with MDD resistant to a prospective trial of fluoxetine experienced a full or partial response to bupropion SR. Bupropion SR should be considered as a potential treatment for patients who remain depressed despite treatment with SSRIs

Adult↗

PubMed2003

Lithium augmentation of nortriptyline for subjects resistant to multiple antidepressants.

Lithium augmentation, the most studied augmentation strategy for depression, has not been evaluated in patients with a history of non-response to multiple antidepressants. The objective of this study was to assess the efficacy of lithium augmentation for patients with a history of treatment resistant depression who also failed a prospective trial of nortriptyline. We enrolled 92 subjects with treatment resistant depression. Treatment resistance was defined by at least one, but no more than five, adequate trials of antidepressants during the current episode. Subjects were treated with nortriptyline (NT) for 6 weeks. Those subjects who tolerated NT for 6 weeks and whose depression did not respond (n=35) were randomized to receive either lithium (n=18) or placebo (N=17) augmentation of nortriptyline for an additional 6 weeks. Response was defined as an equal to or greater than 50% decrease in HAM-D-17 scores. After 6 weeks of double-blind augmentation, 12.5 % of subjects responded to lithium and 20.0% to placebo. Our results revealed no significant difference between lithium and placebo augmentation. While lithium augmentation seems to be useful in depression refractory to a single medication in some studies, our data suggest limited usefulness of this option for patients refractory to multiple treatments. More definitive data await the outcome of the NIMH Sequential Treatment Alternatives to Relieve Depression (STAR*D) study.

Adolescent↗

PubMed2003

A pilot, open study of sertraline in outpatients with treatment-resistant depression (TRD) or with a history of TRD who responded but later relapsed.

While most depressed patients are prescribed a selective serotonin reuptake inhibitor (SSRI) as an initial treatment, the use of SSRIs as a second or third-line treatment for depression is not as prevalent. This trial assessed the efficacy of sertraline for patients with treatment-resistant depression (TRD) or patients with a history of TRD who responded but later relapsed. Twelve patients with TRD who had not responded to a number of antidepressant trials (n=7), or had responded but subsequently suffered a relapse (n=5), were enrolled in an 8-week, open trial of sertraline. Both a completer analysis (n=6) and an intent-to-treat (ITT) analysis (n=12) were performed to evaluate sertraline response rates. Using a completer analysis, four patients (66.6%) were classified as responders; one (16.7%) as a partial responder and one (16.7%) as a non-responder. An ITT analysis resulted in five (41.7%) patients being classified as responders; one (8.3%) as a partial responder and six (50%) as non-responders. Of the four responders in the completer analysis, three (50%) achieved remission. Of the five responders in the ITT analysis, four (33.3%) achieved remission. Overall, two of seven (28.6%) non-responders and three of five (60.0%) relapsers responded to sertraline. The present results suggest the potential utility of sertraline for patients with TRD, or those with a history of TRD who responded but later relapsed, and warrant larger, placebo-controlled studies to further explore the potential role of sertraline for such patients.

Adult↗

PubMed2003

Hopelessness and suicidal ideation in outpatients with treatment-resistant depression: prevalence and impact on treatment outcome.

Depression and hopelessness are risk factors for suicide. The purpose of this study was to examine the extent of suicidal ideation and hopelessness in outpatients with treatment-resistant depression (TRD) and to study the impact of suicidal ideation and hopelessness on treatment with nortriptyline (NT). The degree of suicidal ideation and hopelessness was assessed during the screen visit with the use of items #3 and #30 of the Hamilton Depression Rating Scale (HAM-D) in 89 patients with TRD who entered a 6-week open trial of NT. Forty of these patients also completed the Beck Hopelessness Index (BHI) during the screen visit. In separate logistic regressions, the scores from the BHI and the two HAM-D items were then tested as predictors of clinical response to the 6-week trial with NT, controlling for the severity of depression. More than half of patients reported thoughts or wishes of death to self and significant hopelessness. A greater degree of hopelessness before treatment in completers, reflected by the score on the HAM-D item #30, predicted response to NT. More than half of patients with prominent hopelessness who completed the trial responded. Patients with TRD are more likely than not to report prominent suicidal ideation and hopelessness. Furthermore, a full 6-week trial of NT, a relatively noradrenergic tricyclic antidepressant, may be particularly useful in patients who have failed to respond to several antidepressants and also report significant hopelessness.

Adolescent↗

PubMed2003

Serum cholesterol in treatment-resistant depression.

OBJECTIVE: Patients with major depressive disorder (MDD) may have significant differences in cholesterol levels compared with healthy controls. A previous study by our group reported that depressed patients with elevated cholesterol levels (>or=200 mg/dl) were significantly more likely to be nonresponders to fluoxetine treatment than depressed patients with nonelevated cholesterol levels. However, very little is known regarding cholesterol in patients with treatment-resistant depression (TRD). The purpose of this study was to compare cholesterol levels at baseline between depressed patients with and without TRD and to test whether cholesterol levels at baseline can predict clinical response in patients with TRD treated with open-label nortriptyline (NT). METHODS: Ninety-two patients with TRD entered a 6-week open trial of NT. Baseline cholesterol levels were randomly collected for 59 of these patients. Controlling for age and gender, we compared baseline cholesterol and triglyceride levels for 35 patients with TRD who did not respond to NT with 205 non-TRD patients who responded to an 8-week open trial of fluoxetine. Furthermore, with the use of logistic regression, we tested whether baseline cholesterol levels predicted clinical response to NT in the patients with TRD. RESULTS: Patients with TRD had higher triglyceride levels at baseline compared with depressed patients without TRD. Cholesterol defined as a dichotomous variable being elevated if equal to or greater than 200 mg/dl, predicted poor response to a 6-week open trial of NT in patients with TRD. CONCLUSIONS: The results of this study confirm the relationship between hypercholesterolemia and poor outcome in the treatment of MDD for patients with TRD.

Adolescent↗

PubMed2003

Nortriptyline for treatment-resistant depression.

BACKGROUND: Up to 30% of patients with major depression fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as initial treatment. While the tricyclic antidepressants might be effective for SSRI nonresponders, they have been relegated to third- and fourth-line treatment. This study assesses the efficacy of nortriptyline for patients with treatment-resistant major depression. METHOD: 92 patients with treatment-resistant DSM-III-R major depression, with resistance defined by at least 1, but no more than 5, well-documented adequate trials of antidepressants during the current episode, were treated openly with nortriptyline for 6 weeks. Patients were titrated up to full target doses of nortriptyline within 1 week, with target blood levels of 100 ng/mL. Response was defined as a 50% or greater decrease of baseline 17-item Hamilton Rating Scale for Depression score. We performed an intent-to-treat analysis with the last observation carried forward. RESULTS: Approximately 40% of patients were responders (N = 39) and 12% were remitters (N = 11) after 6 weeks of nortriptyline. Over a third of patients were unable to complete the trial. CONCLUSION: Nortriptyline was effective for over a third of patients with treatment-resistant depression, and nortriptyline should be considered as potential treatment if patients fail to respond to other antidepressants.

Adolescent↗

PubMed2002

NEO-FFI factor scores as predictors of clinical response to fluoxetine in depressed outpatients.

Research in unipolar depression suggests that neuroticism is associated with poor long-term outcome and greater chronicity. The objective of this study was to determine whether baseline neuroticism scores predict response to treatment with fluoxetine in depressed outpatients. Seventy-six depressed outpatients participating in a clinical trial of fluoxetine (fixed/flexible dosing) completed the NEO-FFI (five factor inventory short form) at baseline. Clinical response was defined as a 50% or greater decrease in the 17-item Hamilton Depression Rating Scale (HAM-D-17) total score (final visit--baseline). Logistic regression evaluated NEO-FFI factor scores as predictors of treatment outcome within an intent-to-treat model. Scores on the neuroticism scale were not found to significantly predict treatment response as measured by the HAM-D-17. Strengths of this study include a standardized treatment protocol and use of structured interview instruments, while limitations include a modest sample size, lack of continuation data, state/trait effects, and lack of generalizability to other antidepressant treatments.

Adolescent↗

PubMed2002

A survey of prescribing practices in the treatment of depression.

BACKGROUND: With the increasing number and type of antidepressants available to clinicians, there is a need to better understand current prescribing practices and to what degree these practices reflect research findings. The purpose of this study was to examine prescribing practices in a sample of psychiatrists attending a psychopharmacology review course and compare these results with empirical evidence. METHOD: 439 of 800 clinicians asked (55%) responded to a 10-item questionnaire that was given prior to beginning the review course. Items covered three major content areas: first-line preferences in the treatment of depression, antidepressant agents most associated with certain side effects, and first-line preferences in the treatment of certain depressive subtypes. RESULTS: 214 (49%) clinicians indicated a belief that one antidepressant type is more efficacious than others. Of these 214 clinicians, 103 (48%) indicated selective serotonin reuptake inhibitors (SSRIs) as being most efficacious, while 53 (25%) indicated venlafaxine as being most efficacious; 378 (93%) clinicians indicated SSRIs as their first-line treatment preference. Mirtazapine (56%) was endorsed as most likely to be associated with weight gain, fluoxetine (57%) with sexual dysfunction, paroxetine (48%) with a discontinuation syndrome, and fluoxetine (52%) with agitation. For the treatment of anxious, atypical, and melancholic depression, SSRIs were the first choice of treatment (58%, 57%, and 57%), and for depression with prominent insomnia, mirtazapine and nefazadone (31% and 27%) were the first choices of treatment. CONCLUSIONS: Despite the lack of evidence of a significant difference in efficacy between older and newer agents, clinicians perceive the newer agents to be more efficacious than the older drugs [tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs)] even in the melancholic and anxious depressive subtypes. Similarly, although sexual dysfunction and agitation appear to occur at similar rates with all the SSRIs, fluoxetine was perceived to be most likely to cause these side effects. These findings are significant as they highlight the discrepancy between empirical evidence and clinical practices and suggest that other factors influence clinicians' medication choices in the treatment of depression.

Antidepressive Agents↗

PubMedDate not supplied

Relationships between major depressive disorder and comorbid anxiety and personality disorders.

OBJECTIVE: The aim of the study was to examine whether comorbid anxiety disorders influence depressed patients' likelihood of meeting criteria for a personality disorder (PD) and whether comorbid anxiety disorders influence the stability of the PDs in patients with remitted depression. METHODS: The initial sample consisted of 373 outpatients who met criteria for major depressive disorder (MDD) (by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition-Patient Edition) and who were enrolled in the 8-week acute treatment phase of a study of fluoxetine for MDD. Sixty-four subjects who responded to fluoxetine treatment in the acute phase met criteria for remission throughout a 26-week continuation phase during which they remained on fluoxetine with or without cognitive behavioral therapy. Stability of PDs was defined as meeting criteria for a PD at both beginning and end point of the continuation treatment phase. RESULTS: Before fluoxetine treatment, anxious depressed patients (defined as meeting criteria for MDD as well as at least one comorbid anxiety disorder) were significantly more likely to meet criteria for any comorbid PD diagnosis compared with depressed patients without comorbid anxiety disorders. In particular, there was a significant relationship between the presence of Cluster A and C PDs and the presence of anxious depression at baseline before antidepressant treatment. After successful treatment of MDD, we found a significant relationship between anxious depression diagnosed at baseline and the stability of a Cluster C PD diagnosis. CONCLUSION: Anxious depression may place patients at greater risk of having a PD diagnosis, especially one from Cluster A or C. Once the depression remits, patients who initially met criteria for anxious depression may be more likely to maintain a Cluster C PD diagnosis compared with patients initially diagnosed with MDD alone.

Adult↗

PubMedDate not supplied

Quality of life assessments in major depressive disorder: a review of the literature.

According to the DSM-IV classification, a diagnosis of Major Depressive Disorder (MDD) is possible only when there is evidence of significant inference with functioning. However, despite the high prevalence of MDD in the general population, it is uncommon for clinicians to assess overall functioning in a systematic way before making such diagnosis. An important correlate of functioning is quality of life, which is typically defined as "patients' own assessments of how they feel about what they have, how they are functioning, and their ability to derive pleasure from their life activities". In the present article, we review studies focusing on the relationship between depression and quality of life, particularly focusing on the impact of the treatment of depression on quality of life. Studies focusing on the quality of life in MDD are reviewed. Candidate studies published between 1970 and recently were initially identified by Pubmed and Ovid search cross-referencing the terms "quality of life," "psychosocial functioning" with "major depression" and "treatment." A number of studies report poorer quality of life in MDD patients compared to controls. Several studies also report an improvement in quality of life measures during various phases of treatment with antidepressants and/or psychotherapy. However, trials comparing the role of newer psychopharmacologic agents in the acute phase of treatment, and the role of newer psychotherapies in the continuation and maintenance phases of treatment in restoring psychosocial functioning and improving the quality of life in MDD are lacking. Exploring the impact of these modalities on psychosocial function and quality of life in MDD are necessary to help translate clinical response into restoration of psychosocial function and to thus further improve the standard of care.

Major Depressive Disorder↗

PubMedDate not supplied

A direct comparison of presenting characteristics of depressed outpatients from primary vs. specialty care settings: preliminary findings from the STAR*D clinical trial.

PURPOSE: No study has directly compared the clinical features of depression for patients entering clinical trials using identical enrollment criteria at primary care (PC) and specialty care (SC) settings. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (http://www.star-d.org) provides a unique opportunity to provide this comparison for patients with a major depressive disorder (MDD) requiring treatment. SUBJECTS AND METHODS: We report baseline data for the first 1500 patients enrolled in this trial involving 41 clinic sites (18 PC, 23 SC). Broadly inclusive eligibility criteria required that patients have a DSM-IV diagnosis of nonpsychotic MDD, have not failed an adequate medication trial during their current episode and score>or=14 on the 17-item Hamilton Rating Scale for Depression (HAM-D17). Primary outcomes included the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) and the HAM-D17. RESULTS: Specialty care and PC patients had equivalent degrees of depressive severity (IDS-C30=35.8; HAM-D17=20.4). Specialty care patients were almost twice as likely to report a prior suicide attempt than PC patients (21% vs. 12%, P<.0001) and slightly less likely to endorse suicidal ideation in the past week (45.0% vs. 50.8%, P=.006). The only other distinguishing core symptoms were a slightly lower likelihood of PC patients endorsing depressed mood (95.2% vs. 97.7%, P=.032) or anhedonia (66.3% vs. 70.7%, P=.042, IDS-C30) and a lower likelihood of PC patients endorsing weight loss (IDS-C30). HAM-D17 results were identical. CONCLUSION: Depressive severity was not different, and symptomatic presentations did not differ substantially. Major depressive disorder is more similar than different among patients at SC and PC settings. Thus, similar clinical and research methods for screening, detecting and measuring treatment outcomes can be applied in both settings.

Ambulatory Care↗

PubMedDate not supplied

Treatment-related adverse events and outcome in a clinical trial of fluoxetine for major depressive disorder.

Treatment-related adverse events (TRAEs), particularly those that occur early on, may increase the likelihood for premature discontinuation of antidepressants. The purpose of this study was to examine the relationship between TRAEs and outcome in depressed outpatients enrolled in an 8-week, 20 mg, open trial of fluoxetine. A total of 384 patients (54.7% women, mean age 39.9 +/- 10.5 years) were enrolled in the trial. Study visits occurred at baseline and every other week. Somatic complaints were assessed during each study visit. Somatic complaints that, in the opinion of the evaluating physician, were probably related or related to treatment with fluoxetine were entered in the analysis as TRAEs. We then tested whether 1) developing at least one TRAE, 2) developing at least one moderate or severe TRAE, 3) the number of TRAEs reported during the entire trial, or 4) the number of TRAEs reported during each 2-week interval predicted whether patients would respond to fluoxetine, or prematurely discontinue treatment. None of the above scores predicted whether patients responded to or prematurely discontinued the trial. These findings failed to reveal any relationship between side effects and treatment outcome for patients with MDD enrolled in an 8-week, 20 mg, fixed dose, open trial of fluoxetine.

Adolescent↗

PubMedDate not supplied

Functioning and interpersonal relationships as predictors of response in treatment-resistant depression.

The purpose of this study was to examine whether occupational functioning or the quality of interpersonal relationships is predictive of clinical response to a 6-week open trial of nortriptyline (NT) in patients with treatment-resistant depression (TRD). Ninety-two subjects with TRD were treated openly with NT for 6 weeks. The longitudinal interval follow-up evaluation (LIFE) scale was administered at baseline. A logistic regression was performed using occupational functioning and interpersonal relationships (over the past month and over the past 5 years) as predictors of treatment response. Unpaired t tests were performed to examine mean composite LIFE score values between responders and nonresponders. The composite scores that were statistically significant were used as single predictors of treatment status in separate logistic regression equations. Better occupational function over the past 5 years predicted better response to treatment with NT in patients with TRD. Beyond a history of nonresponse to antidepressants, long-term occupational function may be a predictor of outcome in the treatment of TRD.

Adolescent↗

PubMedDate not supplied

Cardiovascular risk factors may moderate pharmacological treatment effects in major depressive disorder.

OBJECTIVE: An increased association between depression and cardiovascular disease, as well as cardiovascular risk factors, led to the "vascular depression" hypothesis. This subtype of depression is postulated to have a different clinical presentation and to be more treatment-resistant. In this study, we measured the impact of cardiovascular risk factors on the outcome of antidepressant treatment in major depressive disorder (MDD). METHOD: We enrolled 348 MDD subjects, ages 19 to 65 years, in an 8-week treatment study with 20 mg fluoxetine per day. We recorded for each subject 6 cardiovascular risk factors: age (male > or =45, female > or =55), smoking, family history, hypertension, diabetes, hypercholesterolemia; and we defined a cardiovascular risk score (range, 0-6) by the number of risk factors present. Treatment outcome was measured as response (> or =50% improvement on the 17-item Hamilton Rating Scale for Depression [Ham-D-17]) and remission (final Ham-D-17< or =7). RESULTS: In logistic regression analyses, the cardiovascular risk score was significantly associated with treatment nonresponse and lack of remission when adjusting for age of onset of MDD and baseline severity of depression. The cardiovascular risk score remained significantly associated with treatment nonresponse when we additionally controlled for overall medical burden (measured with the Cumulative Illness Rating Scale). Among individual cardiovascular risk factors, elevated total cholesterol was a significant predictor of treatment nonresponse and lack of remission. CONCLUSION: Cardiovascular risk factors may have negative effects on the course of treatment in MDD. These results support the concept of "vascular depression" in younger subjects.

Adolescent↗

PubMedDate not supplied

Treatment-resistant depression and Axis II comorbidity.

BACKGROUND: Researchers of unipolar depression have speculated that personality disturbance is a contributing factor in the development of treatment resistance. The purpose of this study was to compare the prevalence of Axis II disorders between a sample of rigorously defined, treatment-resistant depressed outpatients and a sample of depressed outpatients not having experienced treatment resistance. METHODS: 53 patients with treatment-resistant depression (TRD) and 105 patients with non-treatment-resistant depression (non-TRD) were recruited through respective outpatient clinical trials at the Massachusetts General Hospital's Depression Clinical and Research Program. Diagnosis of Major Depressive Disorder was made using the Structured Clinical Interview for the DSM-III-R, personality disorders were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders, and antidepressant treatment resistance was defined using the McLean Hospital Antidepressant Treatment Record. Participants from both studies were matched for baseline HAM-D-17 total score and gender. Multiple chi-square analysis was used to compare frequencies of Axis II disorders between TRD and non-TRD patients as well as to compare categorical baseline demographic variables. Unpaired t tests were used to compare baseline demographic and clinical variables measured in a continuous manner. RESULTS: Non-TRD patients had a higher rate of obsessive-compulsive personality disorder than TRD patients, but this difference was not statistically significant after adjusting for multiple comparisons. No other differences were found to be statistically significant. Range of Axis II comorbidity was 0.0-30.2% for TRD patients and 2.9-37.1% for non-TRD patients. CONCLUSIONS: In this sample, treatment resistance in a current major depressive episode was not associated with an increased rate of Axis II disorders. Strengths of this study include the use of structured interview instruments to assess Axis I and II conditions, and having the two study groups matched for gender and baseline severity of depression. Limitations of this study include a modest sample size and reliance on DSM personality constructs.

Adult↗

PubMedDate not supplied

Behavioral and emotional disturbances in the offspring of depressed parents with anger attacks.

BACKGROUND: To examine the emotional and behavioral characteristics of the offspring of depressed parents with and without anger attacks. METHODS: Forty-three parents who met criteria for major depressive disorder (MDD) completed the Achenbach Child Behavior Checklist - Parent Report Version (CBCL) for each of their birth children (n = 58, age range 6-17 years). Unpaired t tests were used to evaluate the CBCL scale score differences between children of parents with and children of parents without anger attacks. Baseline demographics and clinical differences between the two groups of parents were also evaluated. RESULTS: Parents with anger attacks had a significantly younger age of onset of MDD. Offspring of depressed parents with anger attacks were found to have significantly lower social and school competency scale scores and higher scores for delinquency, attention problems, and aggressive behavior. In addition, this group was found to have a significantly higher total T score (a global measure of psychopathology). CONCLUSIONS: There are some important differences between offspring of depressed parents with and without anger attacks. This finding may be important in identifying and formulating intervention strategies for childhood problems in the offspring of depressed parents.

Achievement↗