Biomedical subjects

A A Nierenberg

Publications and source records attributed to A A Nierenberg.

At least 19 recordsLinked to original sources

PubMed2006

Prospective 12-month course of bipolar disorder in out-patients with and without comorbid anxiety disorders.

BACKGROUND: The impact of anxiety disorders has not been well delineated in prospective studies of bipolar disorder. AIMS: To examine the association between anxiety and course of bipolar disorder, as defined by mood episodes, quality of life and role functioning. METHOD: A thousand thousand out-patients with bipolar disorder were followed prospectively for 1 year. RESULTS: A current comorbid anxiety disorder (present in 31.9% of participants) was associated with fewer days well, a lower likelihood of timely recovery from depression, risk of earlier relapse, lower quality of life and diminished role function over I year of prospective study. The negative impact was greater with multiple anxiety disorders. CONCLUSIONS: Anxiety disorders, including those present during relative euthymia, predicted a poorer bipolar course. The detrimental effects of anxiety were not simply a feature of mood state. Treatment studies targeting anxiety disorders will help to clarify the nature of the impact of anxiety on bipolar course.

Adolescent↗

PubMed2003

Clinical and sociodemographic predictors of response to augmentation, or dose increase among depressed outpatients resistant to fluoxetine 20 mg/day.

OBJECTIVE: Patients with major depressive disorder often show only partial or no response to antidepressants, necessitating next-step interventions such as dose increase or augmentation. Factors moderating response to these next-step interventions are not well-studied. METHOD: In this randomized, double-blind investigation of next-step treatments in 101 outpatients who failed to respond to fluoxetine 20 mg for 8 weeks, the impact of depressive course and sociodemographic factors on likelihood of treatment response following dose increase or lithium or desipramine augmentation was examined. RESULTS: After controlling for depression severity at baseline, current marriage and earlier onset of depression were associated with greater likelihood of response in a logistic regression. Intervention strategy was not predictive of response. CONCLUSION: Marital status and earlier onset of depression may be clinically useful in predicting outcome following any next-step intervention for treatment resistance, rather than with particular strategies.

Adult↗

PubMed2002

Personality disorders and depression.

BACKGROUND: Personality disorders (PDs) were assessed among depressed out-patients by clinical interview before and after antidepressant treatment with fluoxetine to assess the degree of stability of PD diagnoses and determine whether changes in PD diagnoses across treatment are related to the degree of improvement in depressive symptoms. METHOD: Three hundred and eighty-four out-patients (55% women; mean age = 39.9 +/- 10.5) with major depressive disorder (MDD) diagnosed with the SCID-P were enrolled into an 8 week trial of open treatment with fluoxetine 20 mg/day. The SCID-II was administered to diagnose PDs at baseline and endpoint. RESULTS: A significant proportion (64%) of our depressed out-patients met criteria for at least one co-morbid personality disorder. Following 8 weeks of fluoxetine treatment, there was a significant reduction in the proportion of patients meeting criteria for avoidant, dependent, passive-aggressive, paranoid and narcissistic PDs. From baseline to endpoint, there was also a significant reduction in the mean number of criteria met for paranoid, schizotypal, narcissistic, borderline, avoidant, dependent, obsessive-compulsive, passive aggressive and self-defeating personality disorders. While changes in cluster diagnoses were not significantly related to improvement in depressive symptoms, there were significant relationships between degree of reduction in depressive symptoms (percentage change in HAM-D-17 scores) and degree of change in the number of criteria met for paranoid, narcissistic, borderline and dependent personality disorders. CONCLUSIONS: Personality disorder diagnoses were found to be common among untreated out-patients with major depressive disorder. A significant proportion of these patients no longer met criteria for personality disorders following antidepressant treatment, and changes in personality disorder traits were significantly related to degree of improvement in depressive symptoms in some but not all personality disorders. These findings suggest that the lack of stability of PD diagnoses among patients with current MDD may be attributable in part to a direct effect of antidepressant treatment on behaviours and attitudes that comprise PDs.

Adolescent↗

PubMed2002

Bipolar depression: relationship between episode length and antidepressant treatment.

BACKGROUND: The role of antidepressant medications in bipolar depression remains controversial, mainly due to a lack of research in this area. In this study the authors examined the episode length in bipolar depression and the relationship between antidepressant therapy and episode length. METHOD: A retrospective chart review of 165 subjects identified 50 (30%) with bipolar illness who experienced a major depressive episode between 1 January 1998 and 15 December 2000. Data gathered utilized a structured instrument completed by the clinician at each visit. This instrument includes modified SCID mood modules as well as continuous ratings for each associated symptom of depression and mood elevation. Survival analysis was employed to calculate the median length of the depressive episodes for the entire group. Further survival analysis compared the episode length for subjects treated with antidepressants during the depression (N = 33) with those who did not receive antidepressants (N = 17). The rate of switch into elevated mood states was compared for the two groups. RESULTS: The survival analysis for the entire sample demonstrated 25%, 50% and 75% probability of recovery at 33 (S.E. 8.7), 66 (S.E. 17.9) and 215 (S.E. 109.9) days, respectively. Comparing those who received (N = 33) and those who did not receive (N = 17) antidepressants during the episode did not reveal any difference in the length of the depressive episode. Switch rates were not significantly different between those receiving antidepressants and those not taking these medications (15.2% v. 17.6%, respectively). CONCLUSIONS: Over the past 20 years little progress has been made in reducing the length of depressive episodes in those with bipolar illness. This is despite increasing pharmacological options available for treating depression. Clinicians treating bipolar depression should discuss with their patients the likelihood that the episode will last between 2-3 months. Our results also suggest that antidepressant treatment may not reduce the length of depressive episodes, neither did it appear to contribute to affective switch in our sample.

Adult↗

PubMed2002

Screening for major depression in Asian-Americans: a comparison of the Beck and the Chinese Depression Inventory.

OBJECTIVE: This study compares the effectiveness of the Chinese version of the Beck Depression Inventory (CBDI) and the Chinese Depression Inventory (CDI) in screening for depression among Chinese Americans. METHOD: Five hundred and three Chinese-Americans in primary care were administered the CBDI and the CDI for depression screening. The results were compared with standard semistructured interview. RESULTS: With empirically determined cutoff scores of the CBDI (> or =13) and the CDI (>/=16), both instruments have good sensitivity (0.78) and excellent specificity (0.91 and 0.93, respectively). The correlation between the total scores of the two instruments was high (0.785, P < 0.01). The areas under the Receiver Operating Characteristic (ROC) curve of the CBDI and the CDI were 0.94 and 0.95, respectively, and were not significantly different. CONCLUSION: When administered by interviewers, the CBDI and the CDI have comparable effectiveness. Low participation among Chinese-Americans with self-report measures limits both scales as efficient depression screening instruments.

Asian↗

PubMed2001

Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder.

BACKGROUND: As interventions for severe, treatment-refractory obsessive compulsive disorder (OCD), neurosurgical procedures are associated with only modest efficacy. The purpose of this study was to identify cerebral metabolic correlates as potential predictors of treatment response to anterior cingulotomy for OCD. METHODS: Clinical data were analyzed in the context of a retrospective design. Subjects were 11 patients who underwent stereotactic anterior cingulotomy for OCD. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and at approximately 6 months postoperative. Preoperative F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) data were available. Statistical parametric mapping methods were used to identify loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in Y-BOCS scores. RESULTS: One locus within right posterior cingulate cortex was identified, where preoperative metabolism was significantly correlated with improvement in OCD symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at that locus were associated with better postoperative outcome. CONCLUSIONS: A possible predictor of treatment response was identified for patients with OCD undergoing anterior cingulotomy. Further research, utilizing a prospective design, is indicated to determine the validity and reliability of this finding. If confirmed, an index for noninvasively predicting response to cingulotomy for OCD would be of great value.

Adult↗

PubMed2001

Tryptophan depletion in SSRI-recovered depressed outpatients.

RATIONALE: Recently, a number of studies have challenged the finding that acute tryptophan depletion (TD) increases depressive symptoms in medicated, formerly depressed patients. The present study examined the effects of acute nutritional TD on remitted depressed patients currently treated with selective serotonin reuptake inhibitors. In an attempt to clarify conflicting earlier findings, the effects of a number of clinical variables on outcome were also investigated. METHODS: Ten patients underwent TD in a double-blind, controlled, balanced crossover fashion. The control session followed the procedure of Krahn et al. (1996 Neuropsychopharmacology 15:325-328). Sessions were 5-8 days apart. RESULTS: TD was significantly related to increased scores on clinician-rated depression and anxiety scales, and on self-rated depression, anxiety, and somatic symptoms. The control challenge had no effect, despite the fact that the reductions in plasma tryptophan during the control session were unexpectedly high. Some evidence was found for a threshold in the relationship between reduction of plasma tryptophan and mood response. CONCLUSIONS: The mood effect of TD in medicated, formerly depressed patients was confirmed. A threshold may exist for mood effects following TD, implying that recent negative findings may have been caused by insufficient depletion. No other predicting or mediating factors were identified, although the variable "history of response pattern to medication" deserves further study.

Adolescent↗

PubMed2001

Deficits in visual cognition and attention following bilateral anterior cingulotomy.

A series of eight tests of visual cognitive abilities was used to examine pre- to post-operative performance changes in a patient receiving bilateral anterior cingulotomy. Compared with a set of eight matched control participants, post-operatively, the patient exhibited deficits in (a) the ability to sequence novel cognitive operations required to generate multipart images or rotate perceptual stimuli; (b) the ability to search for, select, and compare images of objects when the instructions did not specify precisely which objects should be visualized; and, (c) the ability to select a controlled and unpracticed response over an automatic one. Other imagery and cognitive tasks were not affected. Results are consistent with the hypothesis that anterior cingulate cortex is a component of an executive control system. One of the anterior cingulate's roles may be to monitor on-line processing and signal the motivational significance of current actions or cognitions.

Adult↗

PubMed2001

Treatment resistant depression and axis I co-morbidity.

BACKGROUND: Treatment resistant depression (TRD) continues to present a formidable challenge to clinicians, accounts for over half of the annual costs associated with treatment for depression and causes great frustration to patients. Although there have been studies attempting to define TRD, little information is available as to the cause of TRD. One suggestion is that patients with TRD have a greater frequency of co-morbid psychiatric disorders, which explains their resistance to standard antidepressant treatments. The objective of this study was to compare the co-morbidity of Axis I disorders between a sample of TRD patients and a sample of non-TRD patients. METHODS: TRD and non-TRD patients, recruited from two separate antidepressant treatment studies, were assessed for Axis I co-morbidity using the SCID-P for the DSM-III-R. Patients for the two samples were then matched for baseline HAM-D-17 total score and gender. RESULTS: Results reveal that non-TRD patients had a higher rate of both lifetime and current generalized anxiety disorder co-morbidity than did the TRD patients. No other statistically significant differences in Axis I co-morbidity were found. CONCLUSIONS: These findings do not support the idea that current or lifetime Axis I co-morbidity is more common in TRD than non-TRD patients. In fact, the only statistical difference showed non-TRD patients with higher co-morbidity rates.

Adolescent↗

PubMed2001

T3 blood levels and treatment outcome in depression.

OBJECTIVE: We examined the correlation between the basal triiodothyronine resin uptake (T3-RU) levels in depressed subjects and the response to anti-depressant treatment. METHOD: We treated with fluoxetine 235 outpatients meeting DSM-IV criteria for major depression. We measured T3 resin uptake (T3-RU) levels before the onset of treatment. The 17-item Hamilton Rating Scale for Depression (Ham-D-17) was administered before, during and after the eight weeks of treatment to assess changes in depressive symptoms. RESULTS: 16 patients (6.8 percent) had low T3-RU levels (range 16.5-21), and 7 patients (3.0 percent) had high T3-RU levels (range 36-38). No relationship was found between T3-RU levels and clinical improvement, defined as either total Ham-D-17 score change or Ham-D-17 score < or = 7 in the last 3 weeks of treatment, even after adjusting for baseline severity of depression. CONCLUSION: Abnormal T3-RU levels are rather uncommon in outpatient depression and do not correlate with the response to antidepressant treatment or lack thereof.

Adolescent↗

PubMed2001

Efficacy of mirtazapine for prevention of depressive relapse: a placebo-controlled double-blind trial of recently remitted high-risk patients.

BACKGROUND: The necessity of antidepressant continuation-phase therapy following acute-phase response has resulted in the need to characterize the longer-term efficacy and safety of all new medications. Previous studies using "extension" protocols suggest that mirtazapine has sustained antidepressant effects. The current study was performed to evaluate the efficacy and safety of up to 1 year of mirtazapine therapy, using a more rigorous, randomized, placebo-controlled discontinuation design. METHOD: An intent-to-treat sample of 410 patients meeting DSM-IV criteria for moderate-to-severe recurrent or chronic major depressive episodes began 8 to 12 weeks of open-label therapy with mirtazapine (flexibly titrated, 15-45 mg/day). Thereafter, 156 fully remitted patients (according to Hamilton Rating Scale for Depression and Clinical Global Impressions-Improvement scores) were randomly assigned to receive 40 weeks of double-blind continuation-phase therapy with either mirtazapine or placebo. RESULTS: Mirtazapine therapy reduced the rate of depressive relapse by more than half, with 43.8% of patients relapsing on treatment with placebo as compared with 19.7% of the mirtazapine-treated patients. The discontinuation rate due to adverse events was 11.8% for active mirtazapine therapy versus 2.5% for placebo. Although weight gain was significantly greater in the group receiving active medication during the double-blind phase (p = .001), patients taking mirtazapine gained only 1.4 kg (3.1 lb) across the 40 weeks of continuation therapy, and there was no difference in the rates of weight gain as a newonset adverse event. CONCLUSION: Continuation-phase therapy with mirtazapine is effective and well tolerated.

Adult↗

PubMed2001

Improvement in severe self-mutilation following limbic leucotomy: a series of 5 consecutive cases.

BACKGROUND: The efficacy of neurosurgical intervention for self-mutilation behavior associated with severe, intractable psychiatric disorders remains undetermined. We report the effects of limbic leucotomy in 5 consecutive patients with severe self-mutilation behaviors. METHOD: After unsolicited referrals from their psychiatrists and careful consideration by the Massachusetts General Hospital Cingulotomy Assessment Committee (MGH-CAC), 5 patients were treated with limbic leucotomy. Their primary DSM-IV psychiatric diagnoses were either obsessive-compulsive disorder or schizoaffective disorder. Comorbid severe, treatment-refractory self-mutilation was an additional target symptom. Outcome was measured by an independent observer using the Clinical Global Improvement. Current Global Psychiatric-Social Status Rating, and DSM-IV Global Assessment of Functioning scales in addition to telephone interviews with patients, families, their psychiatrists, and treatment teams. The mean postoperative follow-up period was 31.5 months. RESULTS: All measures indicated sustained improvement in 4 of 5 patients. In particular, there was a substantial decrease in self-mutilation behaviors. Postoperative complications were transient in nature. and postoperative compared with preoperative neuropsychological assessments revealed no clinically significant deficits. CONCLUSION: In carefully selected patients as described in this report, limbic leucotomy may be an appropriate therapeutic consideration for self-mutilation associated with severe, intractable psychiatric disorders.

Adult↗

PubMed2001

Evidence of early onset of antidepressant effect in randomized controlled trials.

Although antidepressant medications are effective in approximately 70% of patients with major depressive disorder, they have a delayed onset of therapeutic effect. This latency is problematic in that it prolongs the impairments associated with depression, leaves patients vulnerable to an increased risk of suicide, increases the likelihood that a patient will prematurely discontinue therapy, and increases medical costs associated with severe depression. No adequately designed prospective trials have been conducted to evaluate comparative time to onset of antidepressant effect. However, evidence suggests that some antidepressant agents may begin to work faster than others. Citalopram, venlafaxine, and mirtazapine each have exhibited statistically significant differences in some measures of antidepressant action within the first 2 weeks of treatment, both in placebo-controlled trials and in head-to-head comparisons with other antidepressants. This article reviews the data that hint at these drug-specific differences in time to onset of action. Given the potential benefits of early-acting antidepressant treatments, the possibility of superior speed of onset of citalopram, venlafaxine, and mirtazapine presented here merits further study in adequately designed, prospective clinical trials.

Antidepressive Agents↗

PubMed2001

An ideal trial to test differential onset of antidepressant effect.

Although various published clinical studies have suggested that some antidepressants may have a more rapid onset of therapeutic effect than others, none of these trials was adequately designed to measure differential time to onset of effect. Thus, existing data do not support claims that one drug reduces the symptoms of depression faster than another. In this article, we propose a study that would be ideal for measuring comparative onset of antidepressant effect. The key features of this ideal trial include (1) a prospective definition of early onset of action, (2) increased frequency of assessment, (3) a data-analytic approach capable of capturing the dynamic nature of symptomatic change, and (4) various strategies to minimize bias and heterogeneity of response.

Antidepressive Agents↗

PubMed2001

Long-term management of chronic depression.

Untreated major depression tends to either wax and wane, with repeated acute episodes, or persist in a chronic unremitting state, which occurs in up to 35% of depressed patients. After acute remission, those with treated chronic major depression are at high risk of depressive relapse and recurrence. Strategies to reduce the risk of relapse and recurrence include achieving full acute remission, continuing antidepressant treatment with optimal patient adherence, and adding modified cognitive-behavioral psychotherapy. This article will review data relevant to the long-term management of chronic major depression.

Antidepressive Agents↗

PubMed2001

Do some antidepressants work faster than others?

The clinical utility of antidepressant drugs is impaired by the delay in onset of their therapeutic action. It is becoming increasingly clear that differences exist between antidepressants with respect to this property, both within and between pharmacologic classes. Post hoc analyses of comparisons between selective serotonin reuptake inhibitors and dual-action antidepressants such as mirtazapine and venlafaxine indicate that the dual-action drugs may have a faster onset of action. At least in the case of mirtazapine, the earlier onset appears to be via a specific antidepressant effect and not an effect on sleep or other accessory symptoms. Studies that compare mirtazapine and venlafaxine are relatively rare and lack sufficient statistical power to determine a difference in the onset of action. Although these differences have been shown in clinical efficacy studies not specifically designed to detect differences in onset of action, a definitive demonstration of early onset of action awaits the results of appropriately designed and powered clinical studies currently planned or in progress.

Antidepressive Agents↗

PubMed2001

Definitions of antidepressant treatment response, remission, nonresponse, partial response, and other relevant outcomes: a focus on treatment-resistant depression.

Multiple definitions have been used to characterize the outcome of treatments for depression. Beyond the simple criterion of a statistically significant improvement in depression rating scale scores, researchers have had to use more clinically relevant categorical outcomes: response (without remission), remission, nonresponse, partial response, relapse, recurrence, recovery, and, more recently, depressive breakthrough. This article reviews the definitions of these terms and their relevance for the study of treatment-resistant depression.

Antidepressive Agents↗

PubMed2001

Current perspectives on the diagnosis and treatment of major depressive disorder.

Each year in America approximately 6 million people suffer from depression at a cost of more than $16 billion. People who are depressed have more medical illnesses than those without depression and make greater use of healthcare services. In a 15-month period after having been diagnosed with depression, sufferers are 4 times more likely to die as those who do not have depression. Almost 60% of suicides have their roots in major depression, and 15% of those admitted to a psychiatric hospital for depression eventually kill themselves. Although depression is highly treatable, only one third of sufferers receive suitable treatment. The reason for underdiagnosis is 2-fold. Physicians may fail to recognize depression and sufferers may actively deny it. A family history of depression is an important cause in those who suffer recurrent episodes. Major depressive disorder is the most common type of depression and, unless treated, resolves by itself in 6 months to a year less than 40% of the time. Depressive symptoms can be found in as many as 30% of those who abuse alcohol, so abstinence is crucial to treatment. Contrary to popular belief, depression is not a normal part of aging, although it can occur in elderly people who have severe medical and psychosocial problems. The goal of pharmacotherapy is the reduction and ultimate removal of all signs and symptoms of depression. More than 2 dozen drugs with 7 distinct mechanisms of action are available to treat depression, with the clinical goal being remission. Whereas psychotherapy is a treatment option, by itself it tends to be effective in only a limited group of highly motivated individuals who have less severe forms of depression. As a result, treatment outcomes are better when pharmacologic antidepressant treatment and psychotherapy are combined.

Antidepressive Agents↗