Biomedical subjects

Jerrold F Rosenbaum

Publications and source records attributed to Jerrold F Rosenbaum.

At least 19 recordsLinked to original sources

PubMed2007

Treatment-associated suicidal ideation and adverse effects in an open, multicenter trial of fluoxetine for major depressive episodes.

BACKGROUND: Some reports suggest that a subset of depressed patients may experience suicidality - that is increase or emergence of suicidal ideation (SI) or behavior--after initiation of an antidepressant. The time course and clinical correlates of this phenomenon have not been characterized in detail. METHOD: We conducted a secondary analysis of a multicenter, prospective, open, 12-week trial of fluoxetine 20 mg in outpatients with nonpsychotic major depressive episodes. Adverse effects and other clinical features associated with the emergence of suicidality, defined using item 3 of the Hamilton Depression Rating Scale, were examined using Cox regression models. RESULTS: Among 414 subjects without SI at baseline, 59 (14.3%) reported SI on at least 1 postbaseline visit. In a Cox regression, emergence of activation and worsening of depression severity were independently associated with emergence of SI, along with female gender, younger age and having thoughts that life was not worth living prior to treatment. Treatment response and remission were significantly less likely among subjects who developed SI. CONCLUSIONS: New SI was relatively common in this trial of fluoxetine and associated with the emergence of activation and overall symptomatic worsening. Whether prophylaxis against or aggressive treatment of adverse events can decrease emergence of SI merits further study.

Adolescent↗

PubMed2006

Psychopathology in the young offspring of parents with bipolar disorder: a controlled pilot study.

Studies have suggested that the offspring of parents with bipolar disorder are at risk for a spectrum of psychopathology, but few have focused on children in the youngest age ranges or examined the impact of comorbid parental disorders. We utilized a pre-existing sample of young (mean age: 6.8 years) offspring of parents with bipolar disorder (n=34), of parents with panic or major depression (n=179), and of parents with neither mood or anxiety disorder (n=95). Children were assessed blindly to parental diagnoses using the Schedule for Affective Disorders and Schizophrenia-Epidemiologic version (K-SADS-E). Offspring of bipolar parents had significantly higher rates of disruptive behavior and anxiety disorders than offspring from both of the comparison groups, accounted for by elevated rates of ADHD and overanxious disorder. These comparisons were significant even when lifetime histories of the corresponding categories of comorbid disorders in the parents (disruptive behavior disorders and anxiety disorders) were covaried. In addition, offspring of bipolar parents had increased rates of bipolar I disorder, compared with psychiatric controls. Results support the hypotheses of elevated behavior, anxiety, and mood disorders among offspring at risk for bipolar disorder, and suggest that this psychopathology is already evident in early childhood.

Adult↗

PubMed2006

Report by the ACNP Task Force on response and remission in major depressive disorder.

This report summarizes recommendations from the ACNP Task Force on the conceptualization of remission and its implications for defining recovery, relapse, recurrence, and response for clinical investigators and practicing clinicians. Given the strong implications of remission for better function and a better prognosis, remission is a valid, clinically relevant end point for both practitioners and investigators. Not all depressed patients, however, will reach remission. Response is a less desirable primary outcome in trials because it depends highly on the initial (often single) baseline measure of symptom severity. It is recommended that remission be ascribed after 3 consecutive weeks during which minimal symptom status (absence of both sadness and reduced interest/pleasure along with the presence of fewer than three of the remaining seven DSM-IV-TR diagnostic criterion symptoms) is maintained. Once achieved, remission can only be lost if followed by a relapse. Recovery is ascribed after at least 4 months following the onset of remission, during which a relapse has not occurred. Recovery, once achieved, can only be lost if followed by a recurrence. Day-to-day functioning and quality of life are important secondary end points, but they were not included in the proposed definitions of response, remission, recovery, relapse, or recurrence. These recommendations suggest that symptom ratings that measure all nine criterion symptom domains to define a major depressive episode are preferred as they provide a more certain ascertainment of remission. These recommendations were based largely on logic, the need for internal consistency, and clinical experience owing to the lack of empirical evidence to test these concepts. Research to evaluate these recommendations empirically is needed.

Clinical Trials as Topic↗

PubMed2006

Effects of parental anxiety disorders in children at high risk for panic disorder: a controlled study.

BACKGROUND: To examine the association between anxiety disorders in parents and offspring in a sample of children at risk for panic disorder. We hypothesized that individual anxiety disorders will breed true in offspring. METHODS: Comparisons were made between offspring of parents with PD+MD (N=136), PD (N=27), MD (N=27), and Controls (N=103). All subjects were assessed with structured diagnostic interviews. Individual anxiety disorders in the offspring were used as dependent variables in logistic regression models where parental PD status, parental MD, and the same parental anxiety diagnosis were used as independent binary variables. RESULTS: Social phobia and separation anxiety disorder in the offspring were accounted for by the same disorders in the parent, whereas agoraphobia and OCD in the offspring were accounted for by parental panic disorder. CONCLUSIONS: These findings suggest that differing risk factors underlie the expression of individual anxiety disorders in children at risk for panic disorder.

Adolescent↗

PubMed2006

A controlled longitudinal 5-year follow-up study of children at high and low risk for panic disorder and major depression.

BACKGROUND: To evaluate the longitudinal course of psychiatric disorders in children of parents with panic disorder (PD) and major depression (MD) as they transition through the period of risk from childhood into adolescence. METHOD: Over a 5-year follow-up, we compared psychiatric disorders in four groups of children: (1) offspring of parents with PD plus MD (n=136); (2) offspring of parents with PD without MD (n=27); (3) offspring of parents with MD but without PD (n=53); and (4) offspring of non-PD non-MD parents (n=103). RESULTS: Parental PD was significantly associated with increased risk for anxiety disorders, irrespective of parental MD. Parental MD was associated with increased risk for MD, disruptive behavior disorders, and deficits in psychosocial functioning, irrespective of parental PD. CONCLUSIONS: These longitudinal findings confirm and extend previous cross-sectional results documenting significant associations between PD and MD in parents and patterns of psychopathology and dysfunction in their offspring.

Adolescent↗

PubMed2006

Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.

OBJECTIVE: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. METHOD: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of or=11 (HRSD(17)>or=14) defined relapse. RESULTS: The QIDS-SR(16) remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. CONCLUSIONS: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.

Adolescent↗

PubMed2006

Laboratory-observed behavioral disinhibition in the young offspring of parents with bipolar disorder: a high-risk pilot study.

OBJECTIVE: This study tested whether behavioral disinhibition is more prevalent among offspring of parents with bipolar disorder than among offspring of parents without bipolar disorder. METHOD: The authors conducted a secondary analysis of data from a preexisting high-risk study of offspring at risk for panic disorder and depression (N=278) that had included some children with parents who had bipolar disorder (N=34). Children (ages 2-6) had been classified as behaviorally inhibited, disinhibited, or neither in laboratory assessments. RESULTS: Offspring of bipolar parents had significantly higher rates of behavioral disinhibition than offspring of parents without bipolar disorder. Behavioral inhibition did not differ between groups. Differences were not accounted for by parental panic disorder or major depression or by parental history of attention deficit hyperactivity disorder, conduct disorder, antisocial personality, or substance use disorders. CONCLUSIONS: Results suggest a familial link between bipolar disorder in parents and behavioral disinhibition in their offspring. Behavioral disinhibition may be a familially transmitted predisposing factor for dysregulatory distress later in life.

Age Factors↗

PubMed2006

Antecedents to panic disorder in nonreferred adults.

OBJECTIVE: Previous work has shown that childhood anxiety disorders are unique antecedents for panic disorder. The current study examined both childhood and adult comorbid disorders as potential antecedent disorders to panic disorder in a large sample of nonreferred adults. METHODS: Subjects were 1018 adults with (N = 58) and without (N = 960) panic disorder who were derived from a sample originally ascertained through family studies of probands with and without attention-deficit/hyperactivity disorder (ADHD); data were obtained from 1988 to 1996. Classification and regression trees (CART) analysis was used to examine anxiety and nonanxiety disorders antecedent to panic disorder. RESULTS: CART analysis showed that separation anxiety disorder, social phobia, and simple phobia were unique predictors of subsequent panic disorder. CONCLUSION: These results support and expand previously reported findings in referred samples documenting that comorbid anxiety disorders are unique antecedent risk factors for panic disorder.

Adult↗

PubMed2005

The corticotropin-releasing hormone gene and behavioral inhibition in children at risk for panic disorder.

BACKGROUND: Behavioral inhibition to the unfamiliar (BI) is a heritable temperamental phenotype involving the tendency to display fearful, avoidant, or shy behavior in novel situations. BI is a familial and developmental risk factor for panic and phobic anxiety disorders. We previously observed an association between BI and a microsatellite marker linked to the corticotropin releasing hormone (CRH) gene in children at risk for panic disorder. To evaluate this further, we genotyped additional families for this marker and a panel of markers encompassing the CRH locus. METHODS: Sixty-two families that included parents with panic disorder and children who underwent laboratory-based behavioral observations were studied. Family-based association tests and haplotype analysis were used to evaluate the association between BI and polymorphisms spanning the CRH locus. RESULTS: We examined a set of markers which we found to reside in a block of strong linkage disequilibrium encompassing the CRH locus. The BI phenotype was associated with the microsatellite marker (p=.0016) and three single nucleotide polymorphisms (SNPs), including a SNP in the coding sequence of the gene (p=.023). Haplotype-specific tests revealed association with a haplotype comprising all of the markers (p=.015). CONCLUSIONS: These results suggest that the CRH gene influences inhibited temperament, a risk factor for panic and phobic anxiety disorders. Genetic studies of anxiety-related temperament represent an important strategy for identifying the genetic basis of anxiety disorders.

Child↗

PubMed2005

The relationship between serum folate, vitamin B12, and homocysteine levels in major depressive disorder and the timing of improvement with fluoxetine.

The objective of the present study was to examine the relationship between serum folate, vitamin B12, and homocysteine levels and the timing of clinical improvement to fluoxetine in major depressive disorder (MDD) patients. A total of 110 outpatients with MDD who responded to an 8-wk trial of fluoxetine had serum folate, B12, and homocysteine measurements at baseline (prior to fluoxetine initiation). Onset of clinical improvement was defined as a 30% decrease in Hamilton Depression Scale scores that led to a 50% decrease by week 8. Patients with low folate levels ( 0.05). In conclusion, low serum folate levels were found to be associated with a delayed onset of clinical improvement during treatment with fluoxetine in MDD by, on average, 1.5 wk.

Adolescent↗

PubMed2005

Patterns of comorbidity in panic disorder and major depression: findings from a nonreferred sample.

Previous findings in referred adult samples document major depression as having important moderating effects on the patterns of comorbidity for panic disorder and major depression. This study evaluated whether these patterns of comorbidity are moderated by referral bias. Panic disorder (PD) and major depression (MD) were used to predict the risk for comorbid psychiatric disorders and functional outcomes using data from a large sample of adults who had not been ascertained on the basis of clinical referral (N=1,031). Participants were comprehensively assessed with structured diagnostic interview methodology to evaluate childhood and adult comorbid psychiatric disorders. PD increased the risk for anxiety disorders, independently of MD. MD increased the risk for mania, antisocial personality disorder, psychoactive substance use disorder, disruptive behavior disorders, overanxious disorder, social phobia, and generalized anxiety disorder, independently of PD. These results extend to nonreferred samples' previously reported findings documenting that MD has important moderating effects on patterns of comorbidity for PD and indicate that patterns of comorbidity for PD are not due to referral bias.

Adult↗

PubMed2005

Parental predictors of pediatric panic disorder/agoraphobia: a controlled study in high-risk offspring.

Our objective was to evaluate parental risk factors for pediatric-onset panic disorder/agoraphobia (PD/AG) in offspring at high risk for PD/AG. Comparisons were made between parents with PD who had a child with PD or AG (N = 27) and parents with PD without children with PD or AG (N = 79). Comparisons were also made between the spouses of these parents with PD. Separation anxiety disorder, social phobia, obsessive-compulsive disorder, and bipolar disorder in the parents with PD and their spouses accounted for the risk for childhood onset PD/AG in the offspring. This risk was particularly high if both parents were affected with social phobia. These findings suggest that psychiatric comorbidity with other anxiety disorders and with bipolar disorder in parents with PD and their spouses confer a particularly high risk in their offspring to develop PD/AG in childhood.

Adolescent↗

PubMed2005

Childhood antecedents to panic disorder in referred and nonreferred adults.

OBJECTIVE: We used a recursive partitioning method to examine antecedent childhood anxiety disorders in large samples of referred and nonreferred subjects with and without panic disorder. METHODS: Referred subjects included adults treated for panic disorder (n = 131) and comparison adults with neither major anxiety nor mood disorders (n = 61). The nonreferred adult group derived from an opportunistic sample originally ascertained through family studies of probands with and without attention-deficit/hyperactivity disorder (ADHD), yielding 58 adults with panic disorder and 587 who were free of major anxiety and mood disorders. RESULTS: The majority of referred (65%) and nonreferred (52%) adults with panic disorder had antecedent childhood anxiety or disruptive behavior disorders. Classification and Regression Trees (CART) analysis showed that both separation anxiety disorder and overanxious disorder were independent predictors of subsequent panic disorder in both referred and nonreferred samples. CONCLUSIONS: These results confirm and extend previously reported findings by documenting that childhood anxiety disorders are important antecedent risk factors for panic disorder, independently of referral bias.

Adult↗

PubMed2005

A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder.

OBJECTIVE: This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo and fluoxetine. METHOD: After a 1-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate. RESULTS: One hundred thirty-five patients (57% women; mean age, 37.3 +/- 11.0; mean HAMD-17, 19.7 +/- 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean +/- SD, 10.2 +/- 6.6) compared with the fluoxetine group (n = 47; 13.3 +/- 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 +/- 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). Overall, St John's wort appeared to be safe and well tolerated. CONCLUSION: St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25%) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo.

Adolescent↗

PubMed2005

Clinical and demographic features of atypical depression in outpatients with major depressive disorder: preliminary findings from STAR*D.

OBJECTIVE: To determine the frequency and demographic and clinical characteristics of depression with atypical features in a broadly representative sample of outpatients. METHOD: Data derived from the first 1500 patients with DSM-IV major depressive disorder enrolled in the Sequenced Treatment Alternatives to Relieve Depression trial at 41 primary care and nonresearch psychiatric outpatient clinics. An algorithm based on the 30-item Inventory of Depressive Symptomatology-Clinician Rating (IDS-C30) determined presence or absence of depression with atypical features. Odds ratios determined whether a variety of demographic and clinical parameters differed between patients meeting and not meeting atypical criteria. RESULTS: Over 18% of the sample met criteria for atypical features based on items from the IDS-C30. The atypical group was more likely to be female and have an earlier age at onset, greater comorbidity with anxiety symptoms, and greater symptom severity compared with the nonatypical group. CONCLUSION: Previously identified features of atypical depression were confirmed in this large and broadly representative, nonresearch clinical population.

Adult↗

PubMed2005

Attitudes toward benzodiazepines over the years.

Benzodiazepines have been used extensively for the treatment of anxiety and related disorders since the 1960s. Although they have been proven to be effective as first-line treatment for anxiety disorders, during the 1980s public perception and concern for abuse liability and physical dependence with long-term use gave rise to a great deal of controversy. Negative perceptions toward the use of benzodiazepines for treating anxiety not only caused severely ill patients to go untreated or under-treated but also called into question whether the illness itself was worthy of treatment. Although new pharmacologic and psychological treatments for anxiety are available, psychopharmacologists continue to endorse benzodiazepines as primary or adjunct treatment for anxiety disorders. The intent of this article is to provide a historic overview of these issues and to offer some general clinical principles to help minimize the risk of abuse and dependence with benzodiazepine use.

Anti-Anxiety Agents↗

PubMed2004

Does referral bias impact findings in high-risk offspring for anxiety disorders? A controlled study of high-risk children of non-referred parents with panic disorder/agoraphobia and major depression.

BACKGROUND: Previous findings in referred samples documented significant diagnostic specificity in patterns of transmission between parents with panic disorder (PD) and parents with major depression (MD) and their offspring. This study evaluated whether these patterns of transmission between parents and high-risk offspring are moderated by referral bias. METHODS: Parental PD/agoraphobia (AG) and parental MD were used to predict rates of offspring psychiatric disorders and functional outcomes using data from an opportunistic sample of parents (n = 991) and offspring (n = 734) ascertained from case-control family genetic studies of youth with and without attention-deficit hyperactivity disorder. Subjects were comprehensively assessed with structured diagnostic interview methodology to evaluate psychiatric disorders in parents and offspring. RESULTS: Parental PD/AG increased the risk for anxiety disorders in offspring, independently of parental MD while parental MD increased the risk for mood and disruptive behavior disorders in offspring, independently of parental PD/AG. Parental psychopathology was also associated with functional impairment in offspring. LIMITATIONS: The use of a sample ascertained by ADHD and control probands, and parent psychiatric diagnostic reports for children under 12. CONCLUSIONS: These results extend to non-referred samples previous findings from referred samples documenting diagnostic specificity in the familial transmission of PD/AG and MD from parents to offspring, suggesting that these patterns of transmission are not due to referral bias. These results could inform and enhance community programs aimed at screening for and treating pediatric psychopathology.

Adolescent↗

PubMed2004

Hypericum extract in patients with MDD and reversed vegetative signs: re-analysis from data of a double-blind, randomized trial of hypericum extract, fluoxetine, and placebo.

Hypericum extract (HE) might be favourably active in depressed patients with reversed vegetative signs (RVS). Therefore, we performed an exploratory subgroup analysis of a three-armed study to compare HE, fluoxetine, and placebo in patients with major depressive disorder (MDD) in a 12 wk trial. A total of 135 patients were randomized to 12 wk treatment with HE LI 160 (900 mg/d), fluoxetine (20 mg/d), or placebo. Patients with RVS were defined in two steps, according to DSM-IV. First, patients with melancholy-related vegetative signs were excluded. Secondly, patients had to have at least one score of 2 for the items 22-26 of the HAMD-28 scale, which are related to hypersomnia and hyperphagia. Twenty-seven patients remained in the group. Analysis of covariance (ANCOVA) was applied using the HAMD-17 score. Secondly a chi2 test for response was performed, using the same and further an adapted criterium as in recently published studies. ANCOVA revealed a trend to a global difference. Post-hoc analysis showed a trend to superiority of HE compared to placebo and to fluoxetine, but a very large effect size for both differences. Fluoxetine was not different from placebo. The adapted response criterium showed a significant global difference as well as a significant superiority of HE over placebo and over fluoxetine. These data are based on a small sample size and must be considered tentative. A characterization of vegetative features of patients with depression could lead to an overall increased effect size in the treatment with HE.

Analysis of Variance↗