Long-term nature of depression.
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Acute Disease↗
Biomedical subjects
R M Hirschfeld
Publications and source records attributed to R M Hirschfeld.
Sexual dysfunction in depression: disease- or drug-related?
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Antidepressive Agents↗
Tolerability of oral loading of divalproex sodium in the treatment of acute mania.
OBJECTIVE: To conduct a pilot study on the safety and tolerability of a dosage strategy for divalproex sodium beginning with 30 mg/kg/day. It is hypothesized that loading at this level will reach therapeutic levels of valproate more quickly, which in turn will decrease the latency of the therapeutic effect. METHOD: We conducted a retrospective chart review of all acutely manic patients admitted to our facility over a 12-month period. Those inpatients treated with initial divalproex sodium dosages of 30 mg/kg/day for 2 days, followed by 20 mg/kg/day thereafter, were then included in the study. The serum valproate levels and daily Brief Psychiatric Rating Scale (BPRS) scores were documented for each subject. Any adverse changes in daily vital signs, serum liver enzymes, and blood cell counts were noted as well. Nursing and physician notes were then reviewed for any observed or reported adverse effects. RESULTS: Twelve acutely manic inpatients were enrolled in the study. Three subjects did not complete the treatment and are not included in this analysis. The remaining nine subjects completed the treatment, had a mean decrease in BPRS scores of 33.3%, and were discharged at least in partial remission. Six subjects had serum valproate levels drawn within 48-72 h of the initial dose, with a mean valproate level of 93.5 mcg/ml. All nine subjects tolerated the treatment reasonably well, with one subject reporting sedation, one reporting sedation and constipation, and one reporting nausea, emesis, and urinary frequency. A transient, asymptomatic decrease in white blood cell count and a low granulocyte count were also noted in one subject. CONCLUSION: A divalproex dosage strategy beginning with 30 mg/kg/day for 2 days, followed by 20 mg/kg/day thereafter, was reasonably well tolerated in this group of acutely manic patients, even with the concurrent use of other psychotropic medications. Blood levels of 56 to 124 mcg/ml were observed within 3 days after initiating treatment.
Acute Disease↗
Assessment and treatment of suicidal patients.
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Adolescent↗
Protecting subjects and fostering research. Striking the proper balance.
Bonnie reminds us of the heritage and limitations of human subjects research. He points out that over the years, the protection of human subjects in research has enjoyed progress, experienced false starts, and endured inflated expectations. Both he and Elliott call attention to the fact that IRB review rarely probes how researchers propose to deal with impairments to subjects' decision-making capacities. We agree to IRBs should be encouraged to rethink their roles. But, as Bonnie argues, this requires a systematic review of the roles and functions of IRB rather than ad hoc adjustments by individual institutional IRBs. His proposal that IRBs should be encouraged to be more vigilant and through in their monitoring of research is sound, especially if the subjects are vulnerable or the research is risky. A strength of Bonnie's review is that it suggests both specific ways to test competency and a range of options for IRBs to ensure that vulnerable subjects are protected from overzealous or overreaching researchers. His historical review and normative proposals are objective, balanced, and thoughtful. Elliott's critique seems to single out psychiatric research with depressed patients as a special problem area. Although his title emphasizes severely depressed patients, he sometimes appears to neglect the fact that depression ranges across a spectrum from mild to severe. Elliott's point is well taken that severely depressed patients who are clearly incompetent should not, unless proper safeguards are provided, be enrolled in research. But his analysis falters because his position does not in the end respect personal autonomy.
Depressive Disorder↗
Double depression: a distinctive subtype of unipolar depression.
Whether depression is a single disease that varies from mild to severe, with varying episode durations and difficult course patterns, or whether it is an umbrella diagnosis representing depressive subtypes with different psychological and biological characteristics has been debated by clinicians and researchers for many years. However, most scientists now agree that understanding the heterogeneous subtypes of depression allows for greater accuracy in describing and differentiating patients suffering from depression and, therefore, greater precision in describing the most efficacious treatment plan. This article will focus on the distinctions between unipolar major depression, double depression and dysthymia, and will review the history of the DSM classifications for these "subtypes" of major depressive disorder, clinicians and researchers continue to subclassify major depression and, particularly, for the purpose of testing the efficacy of new psychopharmocologic and psychosocial treatments. There continues to be a need for future research to more clearly establish the predictive value in terms of course, recovery, rates of relapse and treatment in regard to distinguishing type of depression as well as to validate the current nosology.
Age of Onset↗
Pharmacotherapy of borderline personality disorder.
Borderline personality disorder can be classified into four groups of symptoms: affective, impulsive, ego-interpersonal, and psychotic. Pharmacotherapy of borderline personality disorder should be directed at the severity of the symptoms in each of these groups, rather than by the presence or absence of the overall syndrome. This article reviews the pharmacotherapy of borderline personality disorder, with special emphasis on affective and impulsive symptoms. Overall, the MAOIs, the SSRIs, and the newer antidepressants (such as venlafaxine) provide the widest spectrum of effective treatment for the symptoms of borderline personality disorder.
Antidepressive Agents, Second-Generation↗
Maintenance clinical trials in bipolar disorder: design implications of the divalproex-lithium-placebo study.
Maintenance studies in bipolar disorder have received increased attention in recent years. The interest is driven by apparent contradictions between results of early placebo-controlled trials of lithium and recent open studies, as well as interest in a new group of drugs with mood-stabilizing properties. The multiple outcome indices that require attention in prophylactic bipolar disorder studies add a dimension not present in acute studies of bipolar disorder. We present the methodology of a recently completed randomized, double-blind, placebo-controlled, parallel-group comparison of divalproex and lithium. We examine the consequences of salient design features, along with their implications for future studies. A fundamental conclusion is that such maintenance studies should be designed and executed to emphasize enrollment of patients with relatively active, severe forms of the illness. This goal is not achieved simply, as inherent features of long-term, placebo-controlled studies drive recruitment and enrollment in the direction of patients with milder forms of bipolar disorder. Attention to the frequency of both manic and depressive episodes and the severity of an index manic episode may aid in the selection of patients most suitable for studies designed to achieve adequate statistical power.
Adult↗
Symptomatology in dysthymic and major depressive disorder.
The lists of associated symptoms included in the DSM-III, DSM-III-R, and DSM-IV criteria for dysthymic disorder have been criticized for lacking content and discriminant validity. The literature on the content and discriminant validity of dysthymic symptoms was reviewed and relevant data from the DSM-IV Mood Disorders Field Trial were presented. These data indicate that cognitive and social-motivational symptoms are much more characteristic of dysthymic disorder than are vegetative and psychomotor symptoms. In addition, subjects with major depressive disorder exhibit higher rates of most depressive symptoms than do subjects with dysthymic disorder, but there is little evidence of qualitative distinctions in symptomatology between these conditions. Finally, after taking course and exclusion criteria into account, variations in the symptom criteria do not have a major effect on case definition.
Chronic Disease↗
Reliability of diagnosis in mood disorders.
The reliability of diagnosing mood disorders is reviewed for previous and current versions of the American Psychiatric Association's DMS. Reliability is shown to improve with the increasing specificity of diagnostic criteria. The new specifiers for the course of major depression in relation to dysthymia also are shown to be reliable.
Adult↗
Chronic mood disorder and depressive personality.
This article considers the relationship between chronic mood disorders and depressive personality from several perspectives. A historical overview of various theoretical, descriptive, and empirically based typologies is provided as well as a review of the relevant classifications from the psychiatric nomenclatures. The defining features of the different conceptions of chronic depression and depressive personality then are considered within the framework of dimensional models of personality, including the dimensions of positive and negative affectivity, and the five-factor model. It is proposed that these dimensional models may provide a useful integrating framework for future work in this area.
Chronic Disease↗
Long-term drug treatment of unipolar depression.
Depression is characterized by a recurrent course in many patients, and as a potentially chronic illness. It therefore often requires a long-term treatment strategy. This article proposes answers to the questions involved in devising such a strategy, using the available literature. Cessation of treatment immediately after the observation of a response is associated with a high relapse rate, especially within the following 4 months, and all patients should therefore be treated for at least 3-6 months after the acute response to secure a stable remission. Patients at risk of recurrence should be considered for maintenance therapy thereafter. Such patients include those with prior episodes of depression within the last 5 years, those with a particularly severe or chronic depressive episode, those with residual symptoms scoring HAMD > 8 and also those whose age at onset was < 25 or < 60 years. Those who need maintenance therapy are likely to need it for a number of years, or indefinitely. SSRIs are better tolerated than TCAs or MAOIs and display similar efficacy in acute, continuation and maintenance treatment. They are less likely to be fatally toxic if taken in overdosage. There is growing evidence to support the use of a full therapeutic dose of antidepressant in maintenance treatment.
Antidepressive Agents↗
Placebo response in the treatment of panic disorder.
A review of key placebo-controlled studies of benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) over the past decade challenges the widespread view that placebo response rates resulting from clinical trials of pharmacotherapy for panic disorder are excessively high. Statistically and clinically significant drug-placebo differences have been demonstrated in large-scale trials. Further research is needed on the impact of pharmacological treatments on the medium- and long-term course of the disorder.
Benzodiazepines↗
Panic disorder: diagnosis, epidemiology, and clinical course.
Panic disorder occurs frequently and present in a wide variety of medical settings. It is often comorbid with mood disorders, substance abuse disorders, and other anxiety disorders. Individuals with panic disorder have lower recovery rates than those with depression, as well as high rates of relapse, and many have a chronic course. Panic disorder is associated with numerous adverse psychological consequences, including poor general medical and emotional health, increased risk of alcohol abuse, marital and occupational dysfunction, greater use of medication, and increased emergency room use. In addition, rates of suicide attempts among individuals with panic disorder may be as high as 20% and exceed the 15% rate of suicide attempts among individuals with depression. This paper will examine the development of panic disorder and its psychological and clinical consequences.
Adolescent↗
Results of the DSM-IV mood disorders field trial.
OBJECTIVE: The DSM-IV mood disorders field trial, a multisite collaborative study, was designed to explore the reliability of a course-based diagnostic classification system for major depression, evaluate the symptom criteria for dysthymia, and explore the need for additional diagnostic categories for milder forms of mood disorder (e.g., minor and recurrent brief depression). METHOD: Five hundred twenty-four depressed subjects were recruited from inpatient, outpatient, and community settings at five sites and evaluated with structured interviews according to DSM-III and DSM-III-R criteria, with careful attention to longitudinal course. Within- and across-site interrater reliability studies and 6-month test-retest reliability studies were also conducted on subsets of the sample. RESULTS: For evaluations of major depression and dysthymia, intrasite reliability was good to excellent and intersite reliability was fair to good; 6-month test-retest reliability was fair for dysthymia and poor to fair for major depression. Interrater reliability for six course of illness specifiers was fair to good, and almost all subjects could be assigned to a specific type of course. CONCLUSIONS: The results supported the use of a course-based classification system for major depression. They also suggested that the content validity of the DSM-III-R symptom criteria for dysthymia could be improved by emphasizing cognitive and social/motivational symptoms, although such changes are unlikely to sharpen the distinction between dysthymia and major depression. Finally, 91% of the subjects met the criteria for current or lifetime major depression or dysthymia, suggesting that additional categories for milder forms of depression are not needed.
Adult↗
Treatment of chronic depression with sertraline or imipramine: preliminary blinded response rates and high rates of undertreatment in the community.
Despite the prevalence of chronic depression and its associated morbidity, there has been little systematic study of pharmacotherapy for this disorder. In this article, we report a preliminary analysis of the first 12-week phase of a multicenter clinical trial that will eventually include approximately 635 patients in acute, continuation, crossover, and maintenance studies of sertraline, a selective serotonin reuptake inhibitor (SSRI), and imipramine, a tricyclic antidepressant, for the treatment of chronic depression. Of the first 212 patients to enter the study, 168 completed all 12 weeks; of these, 61.3 percent were responders, including 58.9 percent of the 73 patients with chronic major depression and 63.2 percent of the 95 patients with double depression. Only 26.8 percent of the 198 patients for whom such data were available had ever had an adequate trial of an antidepressant medication, defined as 150 mg/day of imipramine or its equivalent taken for at least 4 consecutive weeks. In general, demographic and diagnostic characteristics were more similar than different for patients with chronic major and double depression. However, comorbid generalized anxiety disorder was significantly more common in patients with chronic major depression (11.2% threshold for chronic versus 4.9% threshold for double depression, p = .02). The results of this study provide preliminary evidence of the responsiveness of patients with chronic major or double depression to an SSRI or a tricyclic antidepressant.
1-Naphthylamine↗
The impact of health care reform on social phobia.
According to the National Comorbidity Survey, social phobia is the third most frequent psychiatric disorder in the United States. Its lifetime prevalence rate of 13.3% ranks behind only major depressive episode (17.1%) and alcohol dependence (14.1%). As was the case with depression 15 years ago, social phobia has often been trivialized and stigmatized. For example, some with social phobia may be dismissed as having mere "stage fright" or excessive shyness, while, in fact, social phobia is a serious mental illness associated with substantial psychosocial distress, comorbidity, and morbidity. Typical onset of social phobia is in the midteens and often continues throughout an individual's lifetime, leading to severe social and occupational impairment. Several excellent, efficacious treatments are available. Access to these treatments for social phobia may be more difficult in the future due to managed care initiatives and health care reform. Various proposals are now being considered as a part of health care reform that may have significant impact on the diagnosis and treatment of social phobia.
Adolescent↗
Long-term management of depression.
Major depression is often a chronic and recurrent disorder. Findings from a landmark study, the Pittsburgh Study of Maintenance Therapies in Recurrent Depression, demonstrate that full doses of antidepressants prevent recurrent depression and that maintenance therapy lasting at least 5 years may be required for patients with severely recurrent disease. In addition, psychotherapy is a useful adjunct to antidepressant maintenance therapy in prolonging the duration between recurrent episodes. The currently accepted approach to preventing recurrent depression is to treat the acute episode to full remission and follow up by maintaining the patient on the full, acute dose used to achieve the initial response. The selective serotonin reuptake inhibitors (SSRIs) have been studied in recurrent depression and are rational choices for initial maintenance therapy because of demonstrated efficacy, safety, and tolerance during long-term therapy.
Antidepressive Agents↗