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Biomedical subjects

D L Dunner

Publications and source records attributed to D L Dunner.

At least 19 recordsLinked to original sources

Differential diagnosis of bipolar disorder.

The historical antecedents of the current diagnostic criteria for mania involve the German phenomenologic descriptions of the late 1800s, the introduction of lithium for treatment and prevention of mania (which broadened the definition of mania in this country), the attempts to subclassify bipolar disorder into at least two subtypes, and the differentiation of patients with mania and hypomania from those with depression alone. Current diagnostic criteria for bipolar disorder are delineated in DSM-III-R. The differential diagnosis of bipolar disorder includes other conditions that may have manic-like symptoms, including organic mood disorders such as endocrine or metabolic conditions, drug intoxications, and tumors. Mania occurring in the context of substance abuse would be called a secondary mania. In addition, schizoaffective disorder can be diagnosed if there is a manic syndrome superimposed in the context of schizophrenia. Because of the absence of duration criteria for mania in DSM-III-R, the differential diagnosis within the bipolar disorders is largely based on severity and duration of depression. A problem in studying mania at present is that the prototypic cases have largely disappeared from treatment centers because of the success of lithium maintenance treatment. Patients available for study at psychiatric treatment facilities are largely treatment resistant, atypical, and likely to have experienced considerable amounts of substance abuse in their histories. Among the changes being considered for DSM-IV are to include duration criteria for mania, to separate bipolar II patients (depression and hypomania) from bipolar not otherwise specified, to refine the criteria for hypomania, and to add rapid cycling to the list of parenthetical modifiers for bipolar disorder with mania and bipolar disorder with hypomania.

Bipolar Disorder

Coping in panic and major depressive disorder. Relative effects of symptom severity and diagnostic comorbidity.

This study used the Ways of Coping Checklist to examine coping style in patients with panic and major depressive disorders. The relative contribution of distress (symptom severity) and diagnostic comorbidity was determined in three sets of diagnostic subgroups: patients suffering from both panic and major depressive disorders (compared with either disorder alone); panic patients with and without agoraphobia (regardless of concurrent depression); and patients with versus without a concurrent axis II personality disorder. Use of less problem-focused and more emotion-focused coping was strongly correlated with level of distress and was associated with all three examples of diagnostic comorbidity when level of distress was used as a covariate. Regression analyses showed that, except for the presence of a personality disorder, distress was a much stronger predictor of coping than diagnostic subtype.

Adaptation, Psychological

Optimal dose regimen for paroxetine.

The dose regimen for paroxetine in the treatment of depression has been well established through a number of individual dosing studies and analyses from the worldwide clinical data base. The starting dose, which is also the minimal effective dose, is 20 mg/day. For most patients, 20 mg/day will also be the optimal dose. For patients who do not show an adequate therapeutic response within 1 to 3 weeks of initiating therapy, the dose of paroxetine should be increased in 10-mg increments no more often than at weekly intervals to a maximum of 50 mg/day. Medication should be given as a single daily dose, usually in the morning. The therapeutic dose range in the elderly is 20 mg to 40 mg of paroxetine.

Administration, Oral

Two combined, multicenter double-blind studies of paroxetine and doxepin in geriatric patients with major depression.

Depressive illness among the elderly is an important public health concern. However, treatment of the elderly may be complicated by age-related changes in physiology, general medical status, and susceptibility to side effects. There is therefore a need for improved treatment modalities for depressed elderly patients. Paroxetine is an antidepressant that acts through selective inhibition of serotonin reuptake. It lacks the anticholinergic and cardiovascular side effects of most first- and second-generation antidepressants. The authors present the combined data from two similarly designed comparisons of paroxetine and doxepin in outpatients over 60 years of age with major depression. The results show that paroxetine was an effective as doxepin in alleviating depression as measured on the Hamilton Rating Scale for Depression (HAM-D) total score, the Montgomery and Asberg Depression Rating Scale (MADRS), and the Hopkins Symptom Checklist (SCL) depression factor score. Paroxetine was significantly superior to doxepin on the Clinical Global Impressions (CGI) scale for severity of illness, the HAM-D retardation factor, and the HAM-D depressed mood item. Doxepin produced significantly more anticholinergic effects, sedation, and confusion. Paroxetine was associated with more reports of nausea and headache. These results suggest that paroxetine may be a valuable tool for the treatment of major depression in the elderly.

Age Factors

Lactate vulnerability after alprazolam versus placebo treatment of panic disorder.

Thirty-six patients with panic disorder underwent sodium lactate infusion before and after 8 weeks of treatment with alprazolam or placebo. With reinfusion, those patients panic-free with chronic alprazolam treatment displayed significantly decreased reactivity to lactate, as measured by subjective symptom ratings, duration of infusion before developing peak lactate-induced symptoms, and the proportion of patients experiencing lactate-induced anxiety or panic. Patients panic-free on placebo, as well as nonresponders to alprazolam treatment, displayed some, although less striking, decreases in reactivity to lactate with reinfusion. As a group, patients clinically unchanged with placebo treatment showed no systematic change in lactate response with reinfusion. Although the small numbers of patients in each treatment outcome group prohibit drawing definitive conclusions, these findings suggest that decreases in lactate-induced panic after successful alprazolam treatment of panic may result from a combination of changes in clinical state and direct effects of the medication.

Adult

Morning or evening bright light treatment of winter depression? The significance of hypersomnia.

In a randomized crossover design 19 patients with winter depression were treated with 7 days of bright morning light (6:00 to 8:00 AM) and 7 days of evening light (7:00 to 9:00 PM). Bright light in the morning reduced the Hamilton Depression Rating Scale score from 22.3 to 5.5; bright light in the evening decreased the Hamilton score from 21.0 to 12.2. Improvement in the depression as measured by the Hamilton Depression Rating scores was greater with morning light compared with evening lights. Hypersomnia was associated (p less than 0.05) with a superior response to morning light.

Adult

The prophylactic efficacy of tricyclic antidepressants--a five year followup.

1. In order to evaluate the efficacy of antidepressants in the prevention of recurrent depression, a longitudinal life-table analysis was carried out involving 217 unipolar patients whose depressive symptoms had remitted following treatment with one of five standard tricyclics (imipramine, amitriptyline, desipramine, nortriptyline, and doxepin). 2. Following six months continued euthymic mood these patients were maintained on the medication to which they initially responded to in a clinical setting over a 5 year period. These patients were compared against a group of 28 individuals who were treated acutely for their depression and responded to one of the above the 5 standard antidepressants, but following 5-6 months continuation treatment were taken off the antidepressant at their own request. 3. Though there was a lower rate of relapse in patients receiving active medication vs the no treatment group, the frequency of relapse was high for the group on active drug. 4. Using the longitudinal life-table method of Fleiss there was a pessimistic-optimistic average relapse rate of 30%, 50%, and 60%, at 1, 2, and 3 years respectively while on active drug vs a 51%, 74%, and 83% relapse rate on no treatment. Overall 87 of 217 patients on active drug (40.1%) were observed to have suffered a depressive relapse over the 5 year course.

Adult

Chronicity of depressive episode in relation to antidepressant-placebo response.

Pooled data from three 6-week placebo-controlled, double-blind, phase III clinical trials, designed to assess the efficacy of newer antidepressants, were retrospectively analyzed to study the relationship between chronicity of presenting depressive episode and response to placebo, imipramine, and adinazolam. One hundred forty-six depressed outpatients met criteria for inclusion into this study; 80 received placebo treatment, 27 imipramine and 39 adinazolam treatment. Consistent with our hypothesis the response to placebo was low in subjects who were depressed for 1 year or longer (22.6%) as compared to a higher response rate (44.9%) among those who were not as chronically depressed. The response to imipramine and adinazolam was not related to the duration of presenting depressive episode. The implications of these findings are discussed.

Adult

Depression: challenges for the future.

The author reviews the current status of mood disorders with regard to expectations and challenges for the future. Mood disorders are among the most prevalent of the psychiatric illnesses. Fortunately, in the 1990s the benefits of research into depression from the 1970s and onward are beginning to be reaped. Changes in diagnosis and treatment have enabled patients with depression to lead normal lives and avoid the complications of this illness (such as hospitalization and suicide). In this paper, the author focuses on four areas regarding mood disorders that are challenges for the future: diagnosis, psychotherapy, pharmacotherapy, and maintenance therapy.

Antidepressive Agents

A report of trazodone-associated laboratory abnormalities.

A 6-week multicenter, double-blind, controlled study comparing the therapeutic efficacy of two antidepressant drugs, trazodone and fluoxetine, was conducted. The hematocrit, hemoglobin, red blood cell count, serum cholesterol, serum calcium, and serum albumin levels were all significantly decreased after six weeks of trazodone treatment. Similar findings were not obvious for the fluoxetine treatment group. Trazodone caused the development of a pseudoanemia in 36% of the trazodone treatment patients compared with 20% of the fluoxetine treatment patients. The anemia was not regarded as clinically significant. Of the decreases in the patients' chemistries, only the decrease in cholesterol could not be reconciled.

Double-Blind Method

Bright light treatment of winter depression: morning versus evening light.

In a randomized crossover design, 7 patients with winter depression were treated with 7 d of bright morning light (0600 to 0800) and 7 d of evening light (2000 to 2200). Bright lights in the morning significantly reduced the Hamilton Rating Scale for Depression (HRSD) score (18.4 to 5.0); the bright light in the evening moderately decreased the HRSD score (19.4 to 15.1). The improvement in the HRSD score was significantly greater with morning light than with evening light.

Adult

Characteristics of placebo response during long-term treatment of panic disorder.

Mixed-panic disorder patients (16/60, 27%) randomly assigned to receive blind placebo during a 40-week treatment study were defined as placebo responders based on combined criteria of Hamilton Anxiety Scale score percentage decreases below the median point (-42%), moderate to marked improvement on both clinician and patient Clinical Global Impressions scores, and panic-free at final treatment visit. These criteria applied separately also resulted in a similar clinical grouping and pattern of response. Differential patterns of response between responders and nonresponders occurred across most clinical measures of panic/anxiety. Responders experienced early improvement within the first week of double-blind treatment. This response progressed during treatment and tended to persist during taper and at followup 1 month later. Post-hoc analysis of demographic and clinical features at entrance into the study failed to characterize this stringently defined group of placebo responders.

Adult

Double-blind, placebo-controlled, fixed dose trial of minaprine in patients with major depression.

Minaprine dihydrochloride is a novel psychotropic drug possessing both antidepressant and psycho-stimulant properties. Prior clinical studies have shown minaprine to be as effective as standard antidepressant agents in the treatment of endogenous depression. The present study examined the safety and efficacy of minaprine at four different doses compared to placebo in 190 outpatients with major depression. Overall, minaprine demonstrated a significant antidepressant action compared to placebo, which was most evident at the maximum dose of 400 mg daily. These data, together with a favorable side effects profile, suggest that minaprine may be an effective antidepressant agent for the treatment of major depression.

Adult

Relapse and rebound following discontinuation of benzodiazepine treatment of panic attacks: alprazolam versus diazepam.

The authors assessed the effects of partial tapering followed by abrupt discontinuation of alprazolam, diazepam, and placebo in 40 patients with panic attacks. The anxiety scores and frequency of panic attacks of the three groups did not differ at the end of the initial 2-week taper, but 1 week after abrupt discontinuation of the remaining medication, patients formerly taking alprazolam had greater increases in anxiety but no more panic attacks than did the other patients. Because of low statistical power, differences in benzodiazepine half-lives, absence of multiple ratings, and imbalances between groups in clinical characteristics, these findings must be viewed as preliminary.

Adult

DST results in nonpsychotic depressed outpatients.

In two studies using the dexamethasone suppression test (DST) to evaluate the efficacy of newer antidepressants in depressed outpatients, the authors found a DST nonsuppression rate of 13% (11 of 86 patients). Thirty-three of the DST suppressors received an antidepressant and 42 received placebo; the drug-treated group showed a significant therapeutic response. The low rate of DST nonsuppression in these depressed outpatients, a finding consistent with that of other investigators, does not confirm or refute reports that these patients are relatively resistant to placebo in comparison with active medication. The authors recommend that DST results not be used as selection criteria in studies assessing newer therapies for depressed outpatients.

Adult

Biological markers in panic states: lactate-induced panic and mitral valve prolapse.

Anxious patients, and more specifically, patients experiencing panic attacks, are thought to have a significant biological component to their illness. This study looks at two promising biological markers associated with this patient population-mitral valve prolapse and lactate-induced panic. We present our findings, which further characterize clinical and biological aspects of these two markers.

Adolescent