Robert M. A. Hirschfeld

The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members

Members of the National Depressive and Manic-Depressive Association who have bipolar disorder were surveyed. 59% of respondents had their first symptoms during childhood or adolescence. Long delays between symptom onset, treatment-seeking, and receipt of a bipolar diagnosis were common. 45% of respondents currently experience frequent recurrences. Child/adolescent onset was associated with a positive family history, depressive or mixed initial symptoms, and frequent recurrence, with predominantly depressive symptoms. Frequent recurrences were associated with depressive or mixed initial symptoms and depressive episodes, but not with medication non-compliance. Both child/adolescent onset and frequent recurrence were associated with increased social morbidity, which was diminished by effective treatment. Respondents with frequent recurrences were less likely to be treated with mood-stabilizers, more likely to be treated with anti-depressants, or anxiolytics, and more likely to report past anxiety symptoms and diagnoses. 13% of respondents had no medical insurance, and 15% had failed to take medicine for financial reasons. The treatment of bipolar illness could be enhanced by (a) public health efforts to promote early diagnosis and treatment; (b) ensuring adequate trials of mood-stabilizers for patients with frequent recurrences; (c) further research on bipolar disorder with prominent anxiety symptoms; and (c) improved access to mental health care.

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

OBJECTIVE The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders. METHOD An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder. RESULTS There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder. CONCLUSIONS Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

Does psychosocial functioning improve independent of depressive symptoms? A comparison of nefazodone, psychotherapy, and their combination.

BACKGROUND Although it is known that antidepressant treatment improves psychosocial functioning, whether such changes occur independent of depressive symptoms is not known. This study compared efficacy of nefazodone, psychotherapy, and their combination in improving psychosocial functioning in chronically depressed outpatients. METHODS Patients with chronic forms of major depressive disorder were randomized to 12 weeks of nefazodone, Cognitive Behavioral Analysis System of Psychotherapy (CBASP), or combined nefazodone/CBASP. Psychosocial assessments measured overall psychosocial functioning, work functioning, interpersonal functioning, and general health. RESULTS Relative to community norms, patients with chronic major depression evidenced substantially impaired psychosocial functioning at baseline. Combined treatment produced significantly greater psychosocial improvement than either CBASP alone or nefazodone alone on all primary measures. Combined treatment remained superior to nefazodone on primary measures of work, social, and overall functioning, and superior to CBASP on social functioning when depressive symptoms were controlled. Unlike the two groups receiving nefazodone, CBASP alones effect on psychosocial function was relatively independent of symptom change. Psychosocial functioning improved more slowly than depressive symptoms, and moderate psychosocial impairments remained at end point. CONCLUSIONS Combined treatment had greater effect than either monotherapy. Change in depressive symptoms did not fully explain psychosocial improvement. Moderate residual psychosocial impairment remained, suggesting the need for continuation/maintenance treatment.

Maintenance efficacy of divalproex in the prevention of bipolar depression

Breakthrough depression is a common problem in the treatment of bipolar disorder. Only one, recently published, double-blind, placebo-controlled trial has examined the efficacy of divalproex in the prevention of depressive episodes in bipolar patients. This report describes, in further detail, the findings from that trial of the effect of divalproex on multiple dimensions of depressive morbidity in bipolar disorder. A randomized, double-blind, parallel-group, multicenter study was conducted over a 52-week maintenance period. Bipolar I patients, who may have been treated with open-label lithium or divalproex and who met recovery criteria within 3 months of onset of an index manic episode, were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2 : 1 : 1 ratio. Adjunctive paroxetine or sertraline for breakthrough depression was allowed in maintenance phase. Outcome measures were the rate of early discontinuation for depression, time to depressive relapse, proportion of patients with depressive relapse, mean change in Depressive Syndrome Scale score, proportion of patients receiving antidepressants, and time in the study. Among patients taking an antidepressant, a higher percentage of patients on placebo than divalproex discontinued early for depression. Patients who were previously hospitalized for affective episodes or took divalproex in the open period relapsed later on divalproex than on lithium during the maintenance period. Divalproex-treated patients had less worsening of depressive symptoms than lithium-treated patients during maintenance. Indices of severity of prestudy illness course predicted worse outcome in all treatment groups. Divalproex improved several dimensions of depressive morbidity and reduced the probability of depressive relapse in bipolar disorder, particularly in patients who had responded to divalproex when manic, and among patients with a more severe course of illness.

Bipolar II illness: course and outcome over a five-year period.

A five year semi-annual follow-up of patients with non-bipolar (N = 442), bipolar II (N = 64) and bipolar I (N = 53) major depression tracked the courses of prospectively observed major depressive, hypomanic and manic syndromes. In all three groups, depression was much more likely in any given week than was hypomania or mania. However, during the majority of weeks, no full syndrome was present and none of the groups exhibited evidence of continuing psychosocial deterioration. Though all three groups exhibited similar times to recovery from index and subsequent major depressive episodes, both bipolar groups had substantially higher relapse rates and developed more episodes of major depression, hypomania and mania. The two bipolar groups, in turn, differed by the severity of manic-like syndromes and thus remained diagnostically stable; the bipolar II patients were much less likely to develop full manic syndromes or to be hospitalized during follow-up. In conjunction with family study data showing that bipolar II disorder breeds true, these data support the separation of bipolar I and bipolar II affective disorder.

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders, Part III: Maintenance Treatment

Summary As with the two preceding guidelines of this series, these practice guidelines for the pharmacological maintenance treatment of bipolar disorder were developed by an international task force of the World Federation of Societies of Biological Psychiatry (WFSBP). Their purpose is to supply a systematic overview of all scientific evidence relating to maintenance treatment. The data used for these guidelines were extracted from a MEDLINE and EMBASE search, from recent proceedings from key conferences and various national and international treatment guidelines. The scientific justification of support for particular treatments was categorised into four levels of evidence (A-D). As these guidelines are intended for clinical use, the scientific evidence was not only graded, but also reviewed by the experts of the task force to ensure practicality.

Prevalence of bipolar symptoms in epilepsy vs other chronic health disorders

Objective: To estimate the comparative prevalence of bipolar symptoms in respondents with epilepsy vs other chronic medical conditions. Methods: The Mood Disorder Questionnaire (MDQ), a validated screening instrument for bipolar I and II symptoms, in conjunction with questions about current health problems, was sent to a sample of 127,800 people selected to represent the US adult population on selected demographic variables. A total of 85,358 subjects (66.8%) aged 18 or older returned the survey and had usable data. Subjects who identified themselves as having epilepsy were compared to those with migraine, asthma, diabetes mellitus, or a healthy comparison group with regard to relative lifetime prevalence rates of bipolar symptoms and past clinical diagnoses of an affective disorder. Results: Bipolar symptoms, evident in 12.2% of epilepsy patients, were 1.6 to 2.2 times more common in subjects with epilepsy than with migraine, asthma, or diabetes mellitus, and 6.6 times more likely to occur than in the healthy comparison group. A total of 49.7% of patients with epilepsy who screened positive for bipolar symptoms were diagnosed with bipolar disorder by a physician, nearly twice the rate seen in other disorders. However, 26.3% of MDQ positive epilepsy subjects carried a diagnosis of unipolar depression, and 25.8% had neither a uni- nor bipolar depression diagnosis. Conclusion: Bipolar symptoms occurred in 12% of community-based epilepsy patients, and at a rate higher than in other medical disorders. One quarter were unrecognized.

Optimizing outcomes in depression: focus on antidepressant compliance

Major depressive disorder is a chronic and recurrent illness that is associated with significant morbidity and mortality. Patients frequently experience recurrent depressive episodes that are of longer duration and increased severity and which are less responsive to treatment than the index episode. Despite the highly prevalent nature of the illness, depression is frequently unrecognized and undertreated. Compliance with antidepressant medication is essential to consolidate treatment response and prevent relapse and recurrence. However, compliance with antidepressant medication is poor. Education of the patient and physician regarding the nature of depression and its treatment is essential for improving patient compliance. Although psychological mechanisms are a major factor affecting patient compliance, speed of onset of action and poor tolerability of antidepressant medication also have a considerable influence on patient compliance. The newer antidepressants, such as selective serotonin reuptake inhibitors, nonselective serotonin–norepinephrine reuptake inhibitors, and the selective norepinephrine reuptake inhibitors, are better tolerated than tricyclic antidepressants, possibly resulting in improved compliance and treatment outcome.

Personality of recovered patients with bipolar affective disorder

Personality traits of 45 patients with bipolar affective disorder who were fully recovered were compared with those of 78 patients with unipolar affective disorder (also fully recovered) and with those of 1172 never mentally ill first-degree relatives. The most striking finding is the similarity in personality between the recovered bipolar and unipolar patients, who both differed substantially from the never-ill group on measures of emotional strength. Bipolar men had normal levels of extraversion, whereas bipolar women, like unipolar women, were introverted.

Effect of concurrent anxiety on response to sertraline and imipramine in patients with chronic depression

Anxiety commonly complicates the clinical presentation of depression and has been associated with poorer long‐term outcome, but little information is available on the clinical correlates, and comparative effect on treatment response, of subsyndromic or secondary anxiety. Patients diagnosed with chronic major or double depression were randomized to 12 weeks of double‐blind treatment with either sertraline or imipramine in a 2:1 ratio. A high anxiety subgroup was operationally defined by a HAM‐D anxiety/somatization factor score ≥ 7. The effect of study treatment was measured utilizing the HAM‐D, CGI, HAM‐D anxiety/somatization factor, as well as a quality of life measure (Q‐LES‐Q) and a measure of psychosocial functioning (the MOS‐SF‐36). Two hundred nine patients were treated with imipramine and 426 patients were treated with sertraline. Thirty‐six percent of the total met criteria for the high anxiety subgroup. According to Kaplan‐Meier probability estimates, patients with significant concurrent anxiety symptoms were more likely to respond by 12 weeks (66.4%) than those without significant anxiety symptoms (54.2%). There was no significant difference in response rates for sertraline vs. imipramine. Both drugs were effective at treating high baseline levels of anxiety, with 60% of sertraline patients and 58% of imipramine patients having 50% or greater reduction from baseline in HAM‐D anxiety/somatization factor scores, and only 4.6% and 9.9%, respectively, reporting treatment‐emergent worsening in anxiety at study endpoint. Despite the chronicity of depressive illness, acute treatment with both sertraline and imipramine significantly improved psychosocial and quality of life measures. High baseline levels of anxiety did not reduce overall antidepressant response but did somewhat delay the onset of response to sertraline or imipramine in patients with chronic depression. Depression and Anxiety 13:18–27, 2001.