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Biomedical subjects

David L Dunner

Publications and source records attributed to David L Dunner.

At least 19 recordsLinked to original sources
PubMed2005

A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) as a treatment for depression has shown statistically significant effects, but the clinical significance of these effects has been questioned. METHODS: Patients with medication-resistant depression were randomized to receive 15 sessions of active or sham repetitive TMS delivered to the left dorsolateral prefrontal cortex at 110% the estimated prefrontal cortex threshold. Each session consisted of 32 trains of 10 Hz repetitive TMS delivered in 5-second trains. The primary end point was treatment response defined as a >or=50% decrease in Hamilton Depression Rating Scale (HDRS) score at both 1 and 2 weeks following the final repetitive TMS treatment. Remission was defined as a HDRS score < 8. RESULTS: The response rate for the TMS group was 30.6% (11/35), significantly (p = .008) greater than the 6.1% (2/33) rate in the sham group. The remission rate for the TMS group was 20% (7/35), significantly (p = .033) greater than the 3% (1/33) rate in the sham group. The HDRS scores showed a significantly (p < .002) greater decrease over time in the TMS group compared with the sham group. CONCLUSIONS: Transcranial magnetic stimulation can produce statistically and clinically significant antidepressant effects in patients with medication-resistant major depression.

Adult↗
PubMed2005

Is treatment-associated hypomania rare with duloxetine: secondary analysis of controlled trials in non-bipolar depression.

BACKGROUND: Selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors (SNRIs) like duloxetine have the efficacy of tricyclic antidepressants (TCAs) with a more tolerable side-effect profile. Bipolar disorder is often undetected, with the most common misdiagnosis being unipolar depression. Studies have suggested that treatment of bipolar and unipolar depression with heterocyclic TCAs may increase the risk of switch rate to mania. Studies of antidepressants in unipolar major depression show a small risk of mania or hypomania, presumably because some bipolar depressives were mistakenly studied. This study investigated the rate of hypomania, mania, and hypomanic-like symptoms observed during treatment with duloxetine in patients with major depression. METHODS: This was a retrospective analysis of data from eight placebo-controlled, double-blind, randomized clinical trials of duloxetine in patients with non-bipolar major depression. LIMITATIONS: The studies were of limited duration. Manic or hypomanic symptoms were not elicited using standardized mania rating scale instruments. RESULTS: One case of mania occurred in the placebo group (0.1%), and two cases of hypomania were observed in the duloxetine-treated group (0.2%). Among hypomanic-like symptoms, only insomnia was significantly higher in the duloxetine group than in the placebo group (p<0.05). CONCLUSIONS: Duloxetine was associated with a low incidence of treatment-emergent hypomania, mania, or hypomanic-like symptoms in patients with major depressive disorder (MDD). The low incidence reported here may be due to greater diagnostic diligence on the part of the investigators. It is possible that the cases reported likely reflect inclusion of misdiagnosed bipolar II patients rather than true unipolar MDD cases. The effect of duloxetine in patients with bipolar depression is not known.

Adult↗
PubMed2005

Bipolar depression.

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Antipsychotic Agents↗
PubMed2005

Self-reported depressive symptom measures: sensitivity to detecting change in a randomized, controlled trial of chronically depressed, nonpsychotic outpatients.

This study evaluated and compared the performance of three self-report measures: (1) 30-item Inventory of Depressive Symptomatology-Self-Report (IDS-SR30); (2) 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16); and (3) Patient Global Impression-Improvement (PGI-I) in assessing clinical outcomes in depressed patients during a 12-week, acute phase, randomized, controlled trial comparing nefazodone, cognitive-behavioral analysis system of psychotherapy (CBASP), and the combination in the treatment of chronic depression. The IDS-SR30, QIDS-SR16, PGI-I, and the 24-item Hamilton Depression Rating Scale (HDRS24) ratings were collected at baseline and at weeks 1-4, 6, 8, 10, and 12. Response was defined a priori as a > or =50% reduction in baseline total score for the IDS-SR30 or for the QIDS-SR16 or as a PGI-I score of 1 or 2 at exit. Overall response rates (LOCF) to nefazodone were 41% (IDS-SR30), 45% (QIDS-SR16), 53% (PCI-I), and 47% (HDRS17). For CBASP, response rates were 41% (IDS-SR30), 45% (QIDS-SR16), 48% (PGI-I), and 46% (HDRS17). For the combination, response rates were 68% (IDS-SR30 and QIDS-SR16), 73% (PGI-I), and 76% (HDRS17). Similarly, remission rates were comparable for nefazodone (IDS-SR30=32%, QIDS-SR16=28%, PGI-I=22%, HDRS17=30%), for CBASP (IDS-SR30=32%, QIDS-SR16=30%, PGI-I=21%, HDRS17=32%), and for the combination (IDS-SR30=52%, QIDS-SR16=50%, PGI-I=25%, HDRS17=49%). Both the IDS-SR30 and QIDS-SR16 closely mirrored and confirmed findings based on the HDRS24. These findings raise the possibility that these two self-reports could provide cost- and time-efficient substitutes for clinician ratings in treatment trials of outpatients with nonpsychotic MDD without cognitive impairment. Global patient ratings such as the PGI-I, as opposed to specific item-based ratings, provide less valid findings.

Adolescent↗
PubMed2005

Dysthymia and double depression.

Dysthymic disorder is a chronic form of depression which is frequently complicated by major depressive episodes. This paper renews the diagnostic status of dysthymic disorder, treatment studies, and makes suggestions for the classification of chronic forms of depression for DSM-V.

Chronic Disease↗
PubMed2005

Safety and tolerability of emerging pharmacological treatments for bipolar disorder.

OBJECTIVES: Over the past few years numerous new agents have been examined for their efficacy in bipolar disorder (BPD). New antiepileptic agents and atypical antipsychotics currently form the bulk of these emerging agents. As the armamentarium for treating BPD increases, it allows for the possibility of choosing drugs on the basis of their tolerability as well as their efficacy, rather than on efficacy alone. METHODS: Efficacy data for newer antiepileptic drugs (lamotrigine, topiramate, gabapentin, oxcarbazepine) and atypical antipsychotics (olanzapine, clozapine, risperidone, quetiapine, ziprasidone, aripiprazole) are briefly reviewed. The article focuses on relative safety and tolerability of these agents. RESULTS: In general, most of these newer agents have better side effect and tolerability profiles than older agents commonly used to treat BPD (lithium, valproate, carbamazepine); however, these must be weighed against efficacy demonstrated to date in randomized, controlled trials. Cognitive impairment is a concern with topiramate, weight gain and risk of diabetes with some of the atypical antipsychotic agents, and rash with lamotrigine. CONCLUSIONS: Side effects of newer emerging agents for the treatment of BPD can be effectively managed and the risks reduced by instituting practical strategies early in management.

Anticonvulsants↗
PubMed2005

Atypical antipsychotics: efficacy across bipolar disorder subpopulations.

Atypical antipsychotic medications, used as monotherapy or as adjunctive therapy with mood stabilizers, have shown efficacy and tolerability for 4 subpopulations of patients with bipolar disorder: patients with mixed mania, patients with psychotic episodes, children and adolescents, and the elderly. Patients experiencing mixed mania generally respond poorly to lithium therapy and are more difficult to treat than patients with pure mania. Atypical antipsychotics are increasingly being considered for this bipolar subpopulation because of their efficacy as antimanic agents, and because they are less likely to cause as many or as severe adverse events as conventional antipsychotics. Atypical antipsychotics have also demonstrated beneficial effects as monotherapy and adjunctive therapy for bipolar I disorder patients experiencing psychotic states. In addition, they have shown effectiveness and tolerability in small-scale and open-label trials and case studies with pediatric and geriatric bipolar patients.

Adolescent↗
PubMed2004

Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder.

BACKGROUND: Prior work reported elevated gray matter (GM) lactate and Glx (glutamate + glutamine + GABA) concentrations in unmedicated patients with bipolar disorder (BP) compared with healthy controls (HC). This study examined whether lithium (Li) and valproic acid (VPA) treatment modulated these chemicals. METHODS: A subset of previously reported BP patients were treated with Li (n = 12, 3.6 +/- 1.9 months) or VPA (n = 9, 1.4 +/- 1.7 months) and compared untreated HC subjects (n = 12, 2.9 +/- 2.4 months) using proton echo-planar spectroscopic imaging. Regression analyses (voxel gray/white composition by chemistry) were performed at each time point, and change scores computed. Metabolite relaxation and regions of interest (ROI) were also examined. RESULTS: Across treatment, Li-treated BP subjects demonstrated GM Glx decreases (Li-HC, p =.08; Li-VPA p =.04) and GM myo-inositol increases (Li-HC p =.07; Li-VPA p =.12). Other measures were not significant. Serum Li levels were positively correlated with Glx decreases at the trend level. CONCLUSIONS: Li treatment of BP was associated with specific GM Glx decreases and myo-inositol increases. Findings are discussed in the context of cellular mechanisms postulated to underlie Li and VPA therapeutic efficacy.

Adult↗
PubMed2004

Frontal lobe gray matter density decreases in bipolar I disorder.

BACKGROUND: This study was conducted to explore differences in gray and white matter density between bipolar and healthy comparison groups using voxel-based morphometry (VBM). METHODS: Brain magnetic resonance imaging was performed for 39 subjects with bipolar I disorder and 43 comparison subjects. Images were registered into a proportional stereotaxic space and segmented into gray matter, white mater, and cerebrospinal fluid. Statistical parametric mapping was used to calculate differences in gray and white matter density between groups. RESULTS: Bipolar subjects had decreased gray matter density in left anterior cingulate gyrus (Brodmann's area [BA] 32, 7.3% decrease), an adjacent left medial frontal gyrus (BA 10, 6.9% decrease), right inferior frontal gyrus (BA 47, 9.2% decrease), and right precentral gyrus (BA 44, 6.2% decrease), relative to comparison subjects. CONCLUSIONS: The observation of a gray matter density decrease in the left anterior cingulate, which processes emotions, in bipolar subjects is consistent with prior reports that used region-of-interest analytic methods. Decreased gray matter density in the right inferior frontal gyrus, which processes nonverbal and intrinsic functions, supports nondominant hemisphere dysfunction as a component of bipolar disorder.

Adolescent↗
PubMed2004

Brain metabolic alterations in medication-free patients with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) has substantial morbidity and incompletely understood neurobiological underpinnings. OBJECTIVE: To investigate brain chemistry in medication-free individuals with BD. DESIGN: Two-dimensional proton echo-planar spectroscopic imaging (PEPSI) (32 x 32, 1-cm(3) voxel matrix) acquired axially through the cingulate gyrus was used to quantify regional brain chemistry. SETTING: The Center for Anxiety and Depression at the University of Washington in Seattle and the Bipolar Research Programs at McLean Hospital and the Massachusetts General Hospital in Boston. PARTICIPANTS: Thirty-two medication-free outpatients with a diagnosis of BD type I (BDI) or BD type II (BDII), predominantly in a depressed or mixed-mood state, were compared with 26 age- and sex-matched healthy controls. MAIN OUTCOME MEASURES: Tissue type (white and gray) and regional analyses were performed to evaluate distribution of lactate; glutamate, glutamine, and gamma-aminobutyric acid (Glx); creatine and phosphocreatine (Cre); choline-containing compounds (Cho); N-acetyl aspartate; and myo-inositol. Chemical relationships for diagnosis and mood state were evaluated. RESULTS: Patients with BD exhibited elevated gray matter lactate (P =.005) and Glx (P =.007) levels; other gray and white matter chemical measures were not significantly different between diagnostic groups. Isolated regional chemical alterations were found. An inverse correlation between 17-item Hamilton Depression Rating Scale scores and white matter Cre levels was observed for BD patients. CONCLUSIONS: Gray matter lactate and Glx elevations in medication-free BD patients suggest a shift in energy redox state from oxidative phosphorylation toward glycolysis. The possibility of mitochondrial alterations underlying these findings is discussed and may provide a theoretical framework for future targeted treatment interventions.

Adult↗
PubMed2004

Cognitive-behavioral analysis system of psychotherapy as a maintenance treatment for chronic depression.

Although the efficacy of maintenance pharmacotherapy for the prevention of recurrence in major depressive disorder (MDD) is well documented, few studies have tested the efficacy of psychotherapy as a maintenance treatment. The authors examined the efficacy of the cognitive-behavioral analysis system of psychotherapy (CBASP) as a maintenance treatment for chronic forms of MDD. Eighty-two patients who had responded to acute and continuation phase CBASP were randomized to monthly CBASP or assessment only for 1 year. Significantly fewer patients in the CBASP than assessment only condition experienced a recurrence. The 2 conditions also differed significantly on change in depressive symptoms over time. These findings support the use of CBASP as a maintenance treatment for chronic forms of MDD.

Adolescent↗
PubMed2004

A review of antidepressant-induced hypomania in major depression: suggestions for DSM-V.

OBJECTIVES: To determine if the classification of 'antidepressant-induced hypomania' in DSM-IV is supported by available data. METHODS: We reviewed the available scientific literature to examine the incidence of mania and hypomania in non-bipolar patients who were treated with antidepressants. RESULTS: Eighty-nine per cent of studies of antidepressants in major depressive disorder patients reported no cases of treatment-induced hypomania. No instances of treatment-induced hypomania were reported in three large studies of patients with chronic forms of depression. CONCLUSIONS: The rate of antidepressant-induced hypomania in major depressive disorder is within the rate of misdiagnosis of bipolar depression as unipolar. Depressed patients who experience antidepressant-associated hypomania are truly bipolar.

Antidepressive Agents↗
PubMed2004

The effectiveness of St. John's Wort in major depressive disorder: a naturalistic phase 2 follow-up in which nonresponders were provided alternate medication.

BACKGROUND: A continuation study of an extract of St. John's wort (Hypericum perforatum) for depression was performed in follow-up to an acute study that found no significant difference between St. John's wort extract and placebo. METHOD: Seventeen subjects with DSM-IV-defined major depressive disorder who responded to St. John's wort extract in the acute-phase study (phase 1) were continued on double-blind treatment with the same preparation for 24 weeks. Ninety-five subjects who did not respond to either St. John's wort or placebo were treated with an antidepressant for 24 weeks. RESULTS: During antidepressant treatment, mean scores on the Hamilton Rating Scale for Depression for phase 1 nonresponders decreased significantly (p <.0001), with no significant difference between St. John's wort nonresponders and placebo nonresponders. Of the 17 subjects continued on treatment with St. John's wort extract, 5 (29.4%) relapsed. CONCLUSIONS: The subjects who did not respond to St. John's wort extract or placebo in phase 1 were, by and large, not resistant to antidepressant treatment. This suggests that the lack of efficacy found by Shelton et al. in the acute-phase study was unlikely to be the result of a high proportion of treatment-resistant subjects.

Adult↗
PubMed2004

Correlates of suicidal behavior and lithium treatment in bipolar disorder.

Individuals with bipolar and major depressive disorders have considerably higher suicide rates than the general population. However, estimating the risk of suicide is complicated, and there exists a general lack of consensus among researchers regarding whether suicide rates are higher in patients with unipolar, bipolar I, or bipolar II depressive disorders. Isolating the specific factors that contribute to the high risk of suicide in patients with affective disorders can be challenging as well; substance and alcohol abuse, family history of suicide, differences in allele distributions, comorbid anxiety, depression recurrence, seasonal effects, rapid cycling, and a history of hospitalizations for depression all appear to contribute to the likelihood that these patients will engage in suicidal behavior. Research does tend to agree that lithium is efficacious in decreasing suicidal behavior in patients with affective disorders.

Anticonvulsants↗
PubMed2003

Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma.

Major depressive disorder is associated with considerable morbidity, disability, and risk for suicide. Treatments for depression most commonly include antidepressants, psychotherapy, or the combination. Little is known about predictors of treatment response for depression. In this study, 681 patients with chronic forms of major depression were treated with an antidepressant (nefazodone), Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or the combination. Overall, the effects of the antidepressant alone and psychotherapy alone were equal and significantly less effective than combination treatment. Among those with a history of early childhood trauma (loss of parents at an early age, physical or sexual abuse, or neglect), psychotherapy alone was superior to antidepressant monotherapy. Moreover, the combination of psychotherapy and pharmacotherapy was only marginally superior to psychotherapy alone among the childhood abuse cohort. Our results suggest that psychotherapy may be an essential element in the treatment of patients with chronic forms of major depression and a history of childhood trauma.

Adolescent↗