Anxiety psychopathology predictive of outcome in patients with panic disorder and depression treated with imipramine, alprazolam and placebo

This study examines clinical predictors of outcome for patients with panic disorder and depression in a 16 week, placebo-controlled trial of alprazolam and imipramine (n = 126). Baseline global severity of illness and phobic avoidance were differentially predictive of acute response to treatment. Patients in the mild to moderate range of global distress experienced smaller degrees of improvement on alprazolam than on imipramine at week 4. At endpoint, the relative effectiveness of the active medication versus placebo was diminished in patients with higher levels of phobic avoidance. This relationship was not evident for completers, suggesting that the adverse effects of avoidance on outcome after sustained treatment was reduced.     

A double-blind comparison of fluvoxamine, imipramine and placebo in depressed patients

In a placebo-controlled, double-blind study of 91 out-patient depressives, the anti-depressant effect of fluvoxamine, a selective serotonin uptake inhibitor was compared to that of imipramine. Overall drug effects were relatively weak but analyses in selected sub-groups showed both active drugs superior to placebo. Effects of fluvoxamine were more marked in non-situational depressives and it did not improve sleep while effects of imipramine were more marked in retarded depressives and on retardation ratings, suggesting that fluvoxamine may have a different pattern of clinical effects. Side effects of Fluvoxamine were predominantly gastrointestinal and it did not produce postural hypotension or anticholinergic side-effects.     

Prediction of response to fluoxetine and placebo in children and adolescents with major depression: a hypothesis generating study.

BACKGROUND: The results of multivariate analyses to identify potential predictors of response to fluoxetine or placebo separately in 96 child and adolescent outpatients with major depressive disorder from a recent controlled trial are presented. METHODS: A variety of clinical, demographic and laboratory factors were examined as possible predictors of response to fluoxetine or placebo using logistic regression models. RESULTS: No single variable or combination of variables strongly predicted response to fluoxetine. For the placebo group, a younger age, a shorter duration of depressive episode, and a lower socioeconomic status predicted response with an overall predictive power of 81%. CONCLUSIONS: This study is limited by the small sample size and should be considered hypothesis generating rather than confirming.     

A randomised,double-blind comparison of milnacipran and imipramine in the treatment of depression

This multicentre, double-blind, randomised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressant milnacipran (50 mg twice daily, n=53) with the established tricyclic agent imipramine (75 mg twice daily, n=56) over a period of 6 weeks, in patients with major depression (Montgomery-Asberg depression rating score (MADRS) > or =25). Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation, after a 3- to 7-day washout period. Concomitant psychiatric medication was limited to lorazepam, cyamemazine, chloral hydrate and long-term uncomplicated lithium therapy. Assessment for efficacy using the MADRS and Hamilton rating scales of depression, a visual analogue scale and global evaluation revealed both agents to be highly effective (P=0.0001) in this group of patients. Milnacipran was found to be of similar efficacy to imipramine. Tolerance, assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events, revealed a clear advantage for milnacipran. The incidence of anticholinergic events with milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with milnacipran than with imipramine. Furthermore, the patient drop-out rate with imipramine was double that experienced with milnacipran. Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance. Therefore, milnacipran constitutes an important new treatment option in major depression.     

Comparison of the effects of pre-exercise feeding of glucose,glycerol and placebo on endurance and fuel homeostasis in man

Summary Six men were studied during exercise to exhaustion on a cycle ergometer at 73% of following ingestion of glycerol, glucose or placebo. Five of the subjects exercised for longer on the glucose trial compared to the placebo trial (p<0.1; 108.8 vs 95.9 min). Exercise time to exhaustion on the glucose trial was longer (p<0.01) than on the glycerol trial (86.0 min). No difference in performance was found between the glycerol and placebo trials. The ingestion of glucose (lg · kg^–1 body weight) 45 min before exercise produced a 50% rise in blood glucose and a 3-fold rise in plasma insulin at zero min of exercise. Total carbohydrate oxidation was increased by 26% compared to placebo and none of the subjects exhibited a fall in blood glucose below 4 mmol · l^–1 during the exercise. The ingestion of glycerol (lg · kg^–1 body weight) 45 min before exercise produced a 340-fold increase in blood glycerol concentration at zero min of exercise, but did not affect resting blood glucose or plasma insulin levels; blood glucose levels were up to 14% higher (p<0.05) in the later stages of exercise and at exhaustion compared to the placebo or glucose trials. Both glycerol and glucose feedings lowered the magnitude of the rise in plasma FFA during exercise compared to placebo. Levels of blood lactate and alanine during exercise were not different on the 3 dietary treatments. These data contrast with previous reports that have indicated glucose feeding pre-exercise produces hypoglycaemia during strenuous submaximal exercise and reduces endurance performance. It appears that man cannot use glycerol as a gluconeogenic substrate rapidly enough to serve as a major energy source during this type of exercise.     

Effect of imipramine treatment on the prolactin response to fenfluramine and placebo challenge in depressed patients

As an index of central serotonergic function, plasma prolactin response to fenfluramine (60 mg orally) and placebo challenge was examined in 10 depressed patients before and after treatment with imipramine 200 mg/day for 3 weeks. Although baseline prolactin levels were not altered by imipramine, the prolactin response to fenfluramine was significantly (P = 0.01) increased compared to the response in the untreated state. The response to placebo was also enhanced but this effect was of lesser magnitude and not statistically significant. These findings complement previous reports and suggest that tricyclic antidepressant treatment enhances serotonergically mediated neuroendocrine responses.     

Platelet serotonin uptake dynamic changes in depression: effects of long-term imipramine treatment and clinical recovery

The characteristics of the serotonin uptake mechanism were measured in blood platelets of depressed patients before treatment and after 3 weeks and 2 months of imipramine therapy. The results were then compared with data from normal volunteers. In the unmedicated, depressed patients, platelets showed two affinity components of serotonin uptake. Both affinity states differed, in opposite directions, from the platelet serotonin uptake in normal volunteers. In the latter, a two-state model was more difficult to establish. Successful imipramine treatment progressively normalized the platelet serotonin uptake changes seen in unmedicated patients. Those changes allowed the membrane to deal with a wider than normal range of extracellular serotonin concentration; they might reflect neuronal compensatory changes resulting from altered extraneuronal serotonin concentrations and leading, directly or via presynaptic receptors, to balancing them. Imipramine treatment assists the adaptive process and accelerates the clinical recovery.     

Comparison of early maladaptive schemas between borderline personality disorder and chronic depression

Borderline personality disorder (BPD) and chronic depression (CD) are common and challenging mental disorders. Maladaptive cognitive schemas have been proposed to increase vulnerability to both disorders. In order to elucidate the role of maladaptive cognitive schemas in BPD and CD, this study compared psychiatric outpatients with BPD (N = 30) and CD (N = 30) in terms of early maladaptive schemas (EMSs). The groups were compared using the Young Schema Questionnaire short form‐extended (YSQ‐S2‐extended) and the 15D health status questionnaire. BPD patients showed higher endorsement on the majority of EMSs, poorer social functioning, and greater concurrent distress than CD patients. However, after controlling for concurrent effects of psychological distress, the groups did not differ in 14 out of the 18 EMSs. These findings point to significant similarities in maladaptive beliefs between the 2 disorders and do not support broad, specific patterns of EMSs associated with either disorder. The results highlight the need for further study of the role of maladaptive schemas in the development and treatment of chronic mental disorders.     

The impact of depression and fluoxetine treatment on obstetrical outcome

Summary Introduction: This study prospectively followed women over the course of pregnancy to assess the impact of depression and/or antidepressant treatment on obstetrical outcome.Method: Sixty-four outpatient women with an Axis I diagnosis of major depressive disorder or no psychiatric history were followed in each trimester of pregnancy with administration of the CES-D. A subset of the women with depression received treatment with fluoxetine during pregnancy. Subjects with a CES-D score greater than 16 at any time point were further assessed for the presence of an active major or minor depressive episode. Primary outcome variables included infant gestational age, birth weight, Apgar score, and admission to the neonatal intensive care unit.Results: Analyzable data were available for 62 women. No significant differences were found in outcome variables between those women with exposure to medication and/or prenatal depressed mood and those women without a history of depression.Conclusions: In contrast to other studies, our study did not demonstrate an adverse effect of fluoxetine exposure per se on obstetrical outcome. In addition, we did not find a significant impact of depression during pregnancy on obstetrical outcome.     

Social adjustment in depression: the impact of depression severity,personality, and clinic versus community sampling

BACKGROUND: Impaired social adjustment in depression has been associated with clinical variables, although results have been inconsistent. Previous research has not examined how social adjustment in depression varies by source of sample (clinical vs. community) or the associations with personality. METHODS: A total of 260 depressed outpatients from two samples completed the Social Adjustment Scale and were assessed on a number of clinical variables including depression severity, age, duration of depression, and personality symptoms. RESULTS: Overall social adjustment scores in our clinical samples were similar to those of an overseas clinical sample although there were some differences by subscales. In addition, the social adjustment scores of our clinical sample were significantly more impaired than those of individuals identified as depressed from a local epidemiological sample. Finally, in multiple regression equations, social adjustment scores were predicted by the clinical variables, severity of depression, younger age and personality symptoms. However, these only explained a small amount of variance in scores. CONCLUSION: Social adjustment in depression does not vary across different countries but varies according to the sample source (clinic vs. community). Some clinical variables are emerging as consistently associated with impaired social adjustment in depression. The associations with personality suggest this must be considered when assessing social adjustment in depressed patients.     

Neuroticism and personality disorder in depression

Neuroticism and DSM-III personality disorder were studied in 39 depressed inpatients. Interrelationships between these variables and their relationship to depressive typology were compared. The relationship of neuroticism, DSM-III personality type and adequacy of personality to MAOI treatment are also examined. Neuroticism scores were unaffected by short-term treatment, and no differences in neuroticism were observed between melancholics and nonmelancholics, or between endogenous and nonendogenous depressives. Higher neuroticism scores were associated with DSM-III personality disorder. Personality disorder occurred significantly more often in nonmelancholia; borderline, antisocial and histrionic personality disorders occurred exclusively in nonmelancholia, while passive-aggressive, dependent and avoidant disorders occurred in both kinds of depression. Response to MAO inhibitor treatment was similar in patients with high and low neuroticism, adequate and inadequate personality, DSM-III personality disorder and no DSM-III personality disorder. Ambiguities of Eysenck's neuroticism scale are discussed in relationship to depression.     

Onset of response in relation to outcome in depressed outpatients with placebo and imipramine

We have retrospectively analyzed the results of the pooled data from three 6-week placebo controlled double blind phase III clinical trials, initially designed to assess the efficacy of newer antidepressants, in order to study the relationship of early onset improvement with later outcome in 145 depressed outpatients receiving placebo (n = 98) or imipramine (n = 47). The early onset response was seen in a subgroup of subjects receiving either imipramine or placebo and appeared to be independent of treatment assignment. Furthermore, the early onset response predicted outcome for the duration of the trial and was not selective as defined by specific changes in subscales measuring insomnia, anxiety or endogenous features. Exclusion of early onset responders resulted in the augmentation of the difference in outcome with drug and placebo. We recommend that future placebo controlled trials assessing therapeutic efficacy of active treatments in depressed outpatients take into account the early onset response in the analysis of results.     

MMPI, personality dysfunction and the dexamethasone suppression test in major depression

In this study we examined the relationship of psychopathology and personality dysfunction to neuroendocrine functioning. MMPI profiles were examined for 30 psychiatric inpatients with major depression who were suppressors (60%) and nonsuppressors (40%) on the dexamethasone suppression test. There were no differences between suppressors and nonsuppressors on any of the MMPI scales or on DSM-III Axis-II diagnosis. When subdivided according to T-score elevations above 70 on MMPI scales 4 and 6, or 4 and 9, 30% of the sample, however, met criteria for personality dysfunction. Furthermore, a significantly higher proportion of suppressors (50%) evidenced personality dysfunction than did the nonsuppressors (8%). This suggests that certain MMPI scales are able to identify a subgroup of depressed patients with personality disturbances who also have a hypothalamic-pituitary-adrenal dysfunction.     

Cognitive, physiological, and personality correlates of recurrence of depression

BACKGROUND: The risk of recurrence in depressive disorder is high and increases with the number of episodes. We investigated whether individuals with a history of recurrent depression deviate from individuals with a single episode, as regards risk-related variables in 3 different domains of depression research. METHODS: Participants were 102 outpatients with major depressive disorder remitted from an episode (60 recurrent, 42 nonrecurrent). We assessed the perception of emotions from vocal stimuli, 24-h urinary free cortisol, and neuroticism. RESULTS: The recurrent group had higher cortisol levels than the nonrecurrent group, and recurrent women also had a more negative perception than nonrecurrent women. These results were independent of each other, and could also not be accounted for by neuroticism or residual symptoms. Gender differences were found in all 3 domains. LIMITATIONS: The cross-sectional design limits the possibility to draw conclusions on the causality of the observed effects. CONCLUSIONS: Remitted outpatients with recurrent depression deviate from remitted outpatients with single episode depression as regards physiology and social cognition, in a way that may increase their risk of the development of subsequent episodes. The results may have implications for prophylactic treatment strategies.     

Severity and duration of depression, not personality factors, predict short term outcome in the treatment of major depression

BACKGROUND: Prediction of treatment outcome has important clinical consequences. Personality factors have rarely been tested as predictors of acute outcome. Personality, demographic and illness-related characteristics were assessed at baseline for prediction of outcome of treatment in depressed out-patients. METHODS: One hundred and ninety-three patients with major depressive disorder (MDD) were enrolled in a 12 to 16 week trial. The treatment consisted of nefazodone, nefazodone in combination with interpersonal psychotherapy (IPT), IPT in combination with placebo and IPT alone. Demographic and illness related variables were collected at baseline. Personality was assessed using the NEO-FFI. This instrument measures five dimensions of personality. A hierarchical logistic regression was carried out to test for significant predictors of remittance. Further a multiple regression analysis was used to investigate variables predictive of changes on the Hamilton Depression Rating Scale as dependent variable. RESULTS: Univariate analysis showed a significant relationship of outcome with severity, duration of index episode, and use of medical services (UMS). None of the personality variables was predictive of outcome. Regression analyses showed that these disease related variables each uniquely predicted outcome, but that personality factors did not significantly contribute to the prediction model. LIMITATIONS: The study was carried out in secondary and tertiary care centers and may not be generalizable to other populations. Personality dimensions were assessed with a self-report instrument and may be prone to bias. CONCLUSIONS: Severity and duration of the index episode, and to a lesser extent, UMS, and not personality factors, predict outcome in the short term treatment of MDD.