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R M Hirschfeld

Publications and source records attributed to R M Hirschfeld.

At least 37 records · Page 2Linked to original sources
PubMed1999

Efficacy of SSRIs and newer antidepressants in severe depression: comparison with TCAs.

BACKGROUND: The significant morbidity and mortality associated with severe depression and its psychotic or melancholic subtypes necessitate effective and well-tolerated therapy. This review evaluates antidepressant treatments for patients with severe depression. DATA SOURCES: Comparative clinical trials conducted on patients with severe depression were found by an English-language MEDLINE search (1985 to present). Additional studies were identified in article bibliographies. Search terms included depressive disorders, depression and severe, hospitalized, melancholic or melancholia, psychotic, and endogenous. STUDY FINDINGS: Evidence for efficacy of SSRIs in severe or melancholic depression comes from a small but growing number of controlled studies with adequate samples, as well as meta-analyses and retrospective subgroup analysis of premarketing trials. In studies that defined response as a 50% or greater reduction in Hamilton Rating Scale for Depression (HAM-D) scores, response rates ranged from 53% to 64% for SSRIs and 43% to 70% for TCAs. In separate trials on severe depression, venlafaxine and mirtazapine were both more effective than placebo and an active comparator. Nefazodone and bupropion were each found to be more effective than placebo in studies of severe depression. Venlafaxine and mirtazapine have been found to be more effective than fluoxetine. CONCLUSION: SSRIs and TCAs are comparably effective for the treatment of severe or melancholic depression. SSRIs and other newer agents appear to be better tolerated than TCAs, specifically lacking adverse anticholinergic and cardiovascular effects that may limit the use of TCAs. Emerging data with venlafaxine and mirtazapine in severely depressed patients with or without melancholia support the efficacy of these treatments. Nefazodone and bupropion were found to be effective in hospitalized depressed patients. Electroconvulsive therapy (ECT) or combined antidepressant therapy may be useful in some patients with severe depression. Patients with severe psychotic depression may respond better to an antipsychotic-antidepressant combination.

Aged↗
PubMed1999

Safety and tolerability of oral loading divalproex sodium in acutely manic bipolar patients.

BACKGROUND: Achieving therapeutic blood levels of a mood stabilizer as quickly as possible is desirable in patients with acute mania. We examined the feasibility and safety of an accelerated oral loading strategy (divalproex, 30 mg/kg/day, on days 1 and 2, followed by 20 mg/kg/day on days 3-10) designed to bring serum valproate concentrations to therapeutic levels (i.e., above 50 microg/mL). METHOD: Fifty-nine patients who met DSM-IV diagnostic criteria for current manic episode and who had a Mania Rating Scale score > or = 14 were randomly assigned on a double-blind basis to receive divalproex oral loading (N = 20); divalproex nonloading (N = 20) at a starting dose of 250 mg t.i.d. on days 1 and 2, followed by standard dose titration for days 3 to 10; or lithium carbonate (N = 19) at a starting dose of 300 mg t.i.d., followed by standard dose titration for days 3 to 10. RESULTS: Eighty-four percent of the divalproex-loading patients, but only 30% of the divalproex-nonloading patients, had valproate serum levels above 50 microg/mL at day 3 of the study. None of the lithium-treated patients had serum lithium levels above 0.8 mEq/L at study day 3. No patient was removed from the study because of an adverse event. There were no significant differences between the groups in the frequencies or types of adverse events. CONCLUSION: Accelerated oral loading with divalproex sodium is a feasible and safe method to bring serum valproate concentrations to effective levels rapidly.

Acute Disease↗
PubMed1999

The Texas Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Major Depressive Disorder.

BACKGROUND: This article describes the development of consensus medication algorithms for the treatment of patients with major depressive disorder in the Texas public mental health system. To the best of our knowledge, the Texas Medication Algorithm Project (TMAP) is the first attempt to develop and prospectively evaluate consensus-based medication algorithms for the treatment of individuals with severe and persistent mental illnesses. The goals of the algorithm project are to increase the consistency of appropriate treatment of major depressive disorder and to improve clinical outcomes of patients with the disorder. METHOD: A consensus conference composed of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families was convened to develop evidence-based consensus algorithms for the pharmacotherapy of major depressive disorder in the Texas mental health system. After a series of presentations and panel discussions, the consensus panel met and drafted the algorithms. RESULTS: The panel consensually agreed on algorithms developed for both nonpsychotic and psychotic depression. The algorithms consist of systematic strategies to define appropriate treatment interventions and tactics to assure optimal implementation of the strategies. Subsequent to the consensus process, the algorithms were further modified and expanded iteratively to facilitate implementation on a local basis. CONCLUSION: These algorithms serve as the initial foundation for the development and implementation of medication treatment algorithms for patients treated in public mental health systems. Specific issues related to adaptation, implementation, feasibility testing, and evaluation of outcomes with the pharmacotherapeutic algorithms will be described in future articles.

Algorithms↗
PubMed1999

Management of sexual side effects of antidepressant therapy.

Sexual dysfunction occurs in over one third of the general population and has many causes, including psychosocial factors, general medical illness, nonpsychiatric medication, psychiatric disorders, and psychotropic medications. Psychosocial causes are the most prevalent, but many frequently used medications, such as diuretics, beta-blockers, and H2-blockers, can also cause sexual dysfunction. Sexual dysfunctions occur in many psychiatric disorders, including mood disorders, schizophrenia, substance abuse, and anxiety disorders. In addition, over half the patients with major depression will have some sexual dysfunction. Although much attention has been paid to sexual dysfunction associated with the selective serotonin reuptake inhibitors (SSRIs), many other commonly used psychotropics are associated with a variety of sexual dysfunction, including haloperidol, benzodiazepines, stimulants, and drugs of abuse. With regard to SSRIs, sexual dysfunction occurs in 50% or more of such patients, which is substantially higher than the rates reported in the Physicians' Desk Reference. The reason for this discrepancy is that patients will not spontaneously report sexual problems and must be questioned about such problems directly. A variety of strategies exist to manage antidepressant-induced sexual dysfunction, including waiting, reducing the antidepressant dose, use of drug holidays, use of adjunctive pharmacotherapy, and switching antidepressants. Use of an antidepressant with a low prevalence of sexual side effects, such as bupropion, nefazodone, and mirtazapine, may also be considered.

Antidepressive Agents↗
PubMed1999

Care of the sexually active depressed patient.

There are several possible causes of sexual dysfunction in depressed patients. A core symptom of depression is anhedonia, including loss of libido. Therefore, determining a cause of sexual dysfunction in a depressed patient can be very difficult, and the differential diagnosis must include a primary sexual dysfunction, sexual dysfunction associated with general medical and psychiatric disorders, and sexual dysfunction associated with treatments for psychiatric disorders. Of particular clinical interest is sexual dysfunction associated with different classes of antidepressant drugs, such as tricyclic antidepressants, selective serotonin reuptake inhibitors, or venlafaxine. Sexual dysfunction's pharmacologic basis is thought to be stimulation of 5-HT2 receptors. Antidepressant-induced sexual dysfunction, most frequently presenting as a reduction in libido or delayed orgasm, may not pose a large burden for patients in acute treatment. However, in long-term treatment, patients are generally well, and anything that interferes with sexual functioning will be a greater problem and will contribute strongly to noncompliance. Different strategies are advised when dealing with sexual dysfunction in depressed patients treated with antidepressant drugs: waiting for a spontaneous resolution of a problem, reduction in antidepressant drug dosages, drug holidays, adjunctive pharmacotherapy, or switching antidepressants. Perhaps the best way is to avoid sexual dysfunction by starting treatment with an antidepressant with proven acute and long-term efficacy that is devoid of sexual side effects, for example, mirtazapine, bupropion, or nefazodone.

Antidepressive Agents, Second-Generation↗
PubMed1998

The suicidal patient.

Patients at imminent risk of suicide (within 48 hours) generally require psychiatric hospitalization. Short-term risk is an indication for aggressive, closely supervised medical therapy, with possible referral to a substance abuse program. If risk is low but chronic, drug treatment or psychotherapy may reduce underlying stressors.

Adolescent↗
PubMed1998

The treatment of chronic depression, part 2: a double-blind, randomized trial of sertraline and imipramine.

BACKGROUND: Chronic depression appears to be a common, frequently disabling illness that is often inadequately treated. Unlike episodic depressions with shorter illness duration, neither acute nor long-term treatment approaches for chronic depression have been well studied. METHOD: 635 outpatients at 12 sites who met DSM-III-R criteria for chronic major depression or double depression were randomly assigned to 12 weeks of double-blind treatment with either sertraline (in daily doses of 50-200 mg) or imipramine (in daily doses of 50-300 mg). Efficacy and safety were assessed either weekly or every 2 weeks during the 12 weeks of acute treatment. RESULTS: Despite high rates of chronicity (mean duration of major depression = 8.9+/-9.1 years; mean duration of dysthymia = 23+/-13 years) and high rates of comorbidity, 52% of patients achieved a satisfactory therapeutic response to sertraline or imipramine (by a conservative, intent-to-treat analysis). Approximately 21% of the patients who had achieved a therapeutic response at week 12 had not done so at week 8, confirming the longer time to response in depressions with high chronicity. Patients treated with sertraline reported significantly fewer adverse events and were significantly less likely to discontinue treatment due to side effects than imipramine-treated patients (6.3% vs. 12.0%). CONCLUSION: These results indicate that patients suffering from depression with high chronicity can achieve a good therapeutic response to acute treatment with either sertraline or imipramine, although sertraline is better tolerated.

Adult↗
PubMed1998

Predictors of response to acute treatment of chronic and double depression with sertraline or imipramine.

BACKGROUND: The literature on predictors of response to treatment of nonchronic major depression has identified shorter duration of illness, acute onset, and less severity of illness as positive predictors. Unfortunately, there are almost no data on predictors of response to treatment for chronic depression. This study examined predictors of response to pharmacotherapy (sertraline or imipramine) in the treatment of outpatients who had DSM-III-R-defined chronic major or double depression. METHOD: The acute phase of the Chronic Major Depression and Double Depression Study is a double-blind, randomized, parallel-group 12-week comparison of sertraline and imipramine. Analyses are based on 623 patients who comprised the intent-to-treat sample, of whom 299 were nonresponders and 324 were responders, defined by a priori criteria as either remission or satisfactory therapeutic response. A stepwise logistic multiple regression analysis was performed on candidate clinical, psychosocial, and demographic variables previously identified as statistically significant in an attempt to develop a predictive model of positive antidepressant response. RESULTS: The sociodemographic variables that were predictive of positive response included living with spouse or partner or being at least a high school graduate. With regard to symptomatology and clinical history, responders had significantly lower baseline depression severity scores. In general, comorbid anxiety, substance abuse, and personality disorders did not influence rates of response. However, the presence of depressive personality traits was associated with a higher nonresponse rate. Among psychosocial variables, longer duration of personal relationships as well as higher baseline quality of life were associated with positive response. A stepwise logistic multiple regression identified 5 variables-living with spouse or partner, higher educational level, passive-aggressive personality, lower introverted-tense personality traits, and higher quality of life--that significantly and independently contributed to the predictive model. This model correctly classified 67% of patients. CONCLUSION: A higher baseline quality of life, living with spouse or partner, and having more education were the strongest predictors of response to acute pharmacotherapy among chronically depressed patients. Clinical variables and comorbidity were not identified as independent predictors, although personality traits did appear to influence treatment response. Overall, the predictive value of these baseline measures was modest, and therefore of limited clinical utility.

Adult↗
PubMed1998

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↗
PubMed1998

The treatment of chronic depression, part 1: study design and rationale for evaluating the comparative efficacy of sertraline and imipramine as acute, crossover, continuation, and maintenance phase therapies.

BACKGROUND: Chronic depressions are common, disabling, and undertreated, and prior chronicity predicts future chronicity. However, few studies directly inform the acute or maintenance phase treatments of chronic depressions and even less is known about the effects of treatment on psychosocial functioning. METHOD: We describe the design and rationale for 2 parallel double-blind, randomized, multicenter acute and maintenance phase treatment trials. One focused on DSM-III-R major depression currently in a chronic (> or = 2 years) major depressive episode, the other on DSM-III-R major depression with concurrent DSM-III-R dysthymia ("double depression"). RESULTS: Considering the critical knowledge deficits, we designed a 12-week acute phase safety and efficacy trial of sertraline versus imipramine, followed by a 16-week continuation treatment phase for subjects with a satisfactory therapeutic response. Patients receiving sertraline who successfully completed the continuation phase entered a 76-week maintenance trial to compare sertraline with placebo; those taking imipramine continued without a placebo substitution. As part of the acute trial, subjects completing but failing to respond to the initial 12-week acute phase medication were crossed over (double-blind) to the alternative medication for a 12-week acute phase trial. We obtained naturalistic follow-up data (up to 18 months) for subjects exiting the protocol at any time. CONCLUSION: Multiphase protocols for chronic depression can test efficacy by randomized contrasts as well as shed light on key clinical issues such as the degree of response or attrition expected at particular times in a trial or the preferred medication sequence in a potential multistep treatment program.

Antidepressive Agents, Tricyclic↗
PubMed1998

American health care systems and depression: the past, present, and the future.

American medicine has witnessed 3 major periods in this century that have all played key roles in the evolution of today's medical systems, practice, and education. The first of these periods followed the publication of the Flexner report in the early 1900s that was critical of the then current medical education system. The second came with the development of specialties in the 1920s and 1930s, and the third with the growth of HMOs and managed care and with the reemergence of primary care. Mental health practice has also evolved, moving from a specialist-based direct access to a primary care model. Although great strides have been made regarding the treatment of depression, an overwhelming majority of patients are still undertreated. Treatments for the future must focus on programs to improve recognition of depression, reduce stigma, and increase compliance.

Antidepressive Agents↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗