To determine whether supportive-expressive psychotherapy (SET), a form of dynamic psychotherapy, and pharmacotherapy + clinical management (MED) for major depressive disorder (MDD) are more effective than pill-placebo + clinical management (PBO).
This National Institute of Mental Health (NIMH)-sponsored randomized controlled trial was conducted (from November 2001 through June 2007) at the University of Pennsylvania Medical School. The sample included 156 patients diagnosed with MDD (DSM-IV) and having a 17-item Hamilton Rating Scale for Depression (HRSD(17)) score ≥ 14 for at least 2 consecutive weeks. This was an underserved sample in which 41% were male, 52% were self-designated minorities, and 76% had an annual income under $30,000. Treatment lasted 16 weeks. Medication patients not responsive by week 8 (maximum dose 200 mg/d of sertraline) were switched to venlafaxine (maximum dose 375 mg/d). Nonresponsive placebo patients at week 8 were switched to a different placebo.
Patients' depression improved over the 16 weeks (P < .0001), with no between-group differences (P = .95), even among severely (HRSD(17) score ≥ 20) depressed patients (P = .45). Response rates did not differ between groups (P = .73). Gender and minority status moderated outcome (P = .014), with psychotherapy more efficacious for minority men than MED (P = .027, Cohen d = 1.02) and PBO (P = .019, d = 1.09). PBO was more efficacious for white men than MED (P = .03, d = 0.62) and SET (P = .003, d = 1.07). For white women, MED (P = .005, d = 0.77) and SET (P = .033, d = 0.71) were more efficacious than placebo. No differences among treatments were found for minority women.
This trial of urban MDD patients failed to confirm that either active treatment was better than placebo. Minority status and gender had significant and differential effects on outcome that warrant replication in future studies.
clinicaltrials.gov Identifier: NCT00043550.
"It has long been known that dysfunction of ascending serotonergic pathways is crucially implicated in psychiatric disorders, such as panic, depression, and suicide. Several lines of evidence support this viewpoint, including that (1) low levels of serotonin (5- hydroxytriptophan; 5-HT) metabolites were found in depressed suicides , (2) depletion of 5-HT in volunteers triggers relapse of depressive episodes , (3) affective disorders appear to be linked to changes in the activity of serotonin transporter (SERT) , and (4) treatment with 5-HT reuptake inhibitors mitigates depressive symptoms, at least in a subpopulation of patients . In addition, in depressed patients a number of structural defects were observed in the dorsal raphe nucleus (DRN), the brainstem region which provides the majority of cortical serotonergic fibers. "
[Show abstract][Hide abstract] ABSTRACT: Mood disorders and major depression are frequently comorbid with epilepsy. While the nature of this comorbidity is not fully understood, multiple lines of evidence suggest that changes in serotonin (5-HT) neurotransmission may be an underlying mechanism. In this study, we tested the hypothesis that chronic epilepsy in rats can be associated with loss of 5-HT neurons in the dorsal raphe (DR) nuclear complex, the main source of 5-HT projections to the cerebral cortex, which would help to explain respective behavioral deficits. Epilepsy was induced using the kainate model of status epilepticus in adult Wistar rats. After a 3-month recovery period, all kainate-treated rats that had experienced status epilepticus showed spontaneous seizures and reduced sucrose preference (anhedonia), a core symptom of depression. No changes in the forced swim test were detected. The total numbers of 5-HT immunoreactive cells were estimated in all DR subdivisions of control and epileptic rats. Interestingly, epilepsy-related loss of 5-HT neurons (approximately 35%) was observed only in the interfascicular part of the DR complex, which is known to innervate brain regions involved in depression. These findings support the notion that mental health impairments observed in epilepsy may be related to loss of a specific population of the DR 5-HT neurons projecting to limbic brain areas.
Behavioural brain research 10/2015; 297. DOI:10.1016/j.bbr.2015.10.010 · 3.03 Impact Factor
"Depression is associated with a substantial decrease in QOL, and is a major contributor to decrement in general health (Rapaport et al., 2005, Moussavi et al., 2007). Medication, psychodynamic psychotherapy, and even placebo have been shown to effectively reduce observer-rated depressive symptoms of patients with MDD when compared in a recent RCT (Barber et al., 2012). However, whether these treatments lead to improvement in other areas of functioning in patients with MDD throughout and between treatments has not been previously evaluated. "
[Show abstract][Hide abstract] ABSTRACT: Major depressive disorder (MDD) is associated with a decrease in quality of life (QOL) and well-being. Therefore, researchers are increasingly complementing traditional symptom measurements with QOL and well-being assessments in order to broaden the evaluation of treatment outcomes. The current prospective study investigated the effectiveness of supportive-expressive therapy (SET), antidepressant medication (MED) and placebo (PBO) in improving QOL and well-being in patients with MDD.
Data from a randomized controlled trial (trial registration: NCT00043550) comparing SET, MED and PBO for the treatment of depression (N=156) were analyzed. Outcome measures addressed patients' QOL and physical and mental well-being. Changes in outcomes were assessed across and between treatments using linear mixed models.
Across treatments, patients showed significant improvement in QOL and mental and physical health measures, as well as a reduction in interpersonal distress and depressive and anxiety symptoms (p≤.002 for all measures). Those changes were not only the products of a decrease in depressive symptoms, but also predicted subsequent reduction in symptoms. No significant differences were found between the three treatment conditions.
The limitation is the study's moderate sample size.
Current treatments for depression significantly improve patients' QOL and well-being. No significant differences were found between the three conditions examined in this study. The current study highlights the role of well-being in predicting subsequent symptomatic change.
[Show abstract][Hide abstract] ABSTRACT: Previous studies reported inconsistent findings regarding the association of interpersonal problems with therapy outcome. The current study investigates if interpersonal problems predict process and outcome of three different treatments for depression.
The data originate from a randomized clinical trial comparing supportive-expressive psychotherapy, antidepressant medication and pill-placebo for treatment of depression. Interpersonal problems were used as predictors of alliance, symptomatic improvement and premature termination of treatment.
Interpersonal problems related to communion predicted better alliances, but slower symptomatic improvement. Low agency predicted slower symptomatic improvement in supportive-expressive psychotherapy, but not in the medication or placebo condition. Lower interpersonal distress was associated with an increased likelihood to terminate treatment prematurely.
The sample size did not allow the detection of small effects within the treatment groups.
Interpersonal problems are influential for the treatment of depression, but parts of their effects depend on the type of treatment.
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