Bipolar Depression – Phenomenological Overview and Clinical Characteristics

Video  |  Audio (Length:  17 min.)

Philip B. Mitchell, M.D., FRANZCP, FRCPsych
Bibliography

P.B. Mitchell
University of New South Wales, Sydney, Australia

Abstract
Introduction:  For many patients with bipolar disorder, the depressed phase of the illness predominates in terms of duration and/or disability, and often proves refractory to treatment. It is only in recent years that management of this ‘forgotten’ component of bipolar disorder has been seriously addressed.
Clinical characteristics: Most studies report that the average duration of bipolar depressive episodes is approximately three months, with some finding depressive episodes to be more prolonged than periods of mania or hypomania. A recent report suggests no difference in duration between treated and untreated subjects. Pure depressive episodes are more common in female patients.
Phenomenology: Compared to major depressive disorders (unipolar depression), bipolar I depression is characterized by a greater likelihood of psychomotor retardation, atypical features (hypersomnia, hyperphagia and ‘leaden paralysis’), pathological guilt and psychotic symptoms. Neuropsychological studies indicate greater frontal lobe dysfunction in bipolar compared to unipolar depression. The psychomotor retardation has been found to correlate with reduced metabolism in a number of right brain regions.
Disability, morbidity and mortality: Suicidal ideation and suicide attempts are more likely during depressed and mixed, compared to manic episodes. Bipolar patients are twice as likely to attempt suicide as unipolar subjects. Completed suicide rates are 15 times those of the general population; second only to those with unipolar depression.  In a study of health care costs in a privately insured population, bipolar disorder patients in a depressed episode incurred higher costs than those in manic or mixed episodes, indicating a higher degree of disability.  Furthermore, the significant disability of subsyndromal bipolar depression has been emphasized with a recent report finding a significant correlation in such patients between HAM-D and GAF scores.
Conclusion: Bipolar depression is phenomenologically distinct from unipolar depression, is frequently prolonged in duration, and is associated with high levels of disability, morbidity and mortality. As available therapies appear to be of limited benefit, there is a critical need for more effective treatments.

Bipolar Depression: Course of Illness

Video  |  Audio (Length:  19 min.)

Mauricio Tohen, M.D., Dr.P.H.
Bibliography

M. Tohen
Lilly Research Laboratories, Indianapolis, IN; Harvard Medical School, Boston, MA, USA

Abstract
Bipolar depression, represents a disabling form of depression. Patients with bipolar disorder spend longer time in and take longer to recover from the depressive phase than the manic phase. 1) Judd et al. reported that bipolar patients experience depressive symptoms more than 3 times longer than they suffer manic symptoms. 2) Keller et al, found that median rate of recovery from the depressive phase was twice as long than recovery from bipolar mania. Keller and colleagues also found that close to one fourth of patients suffering from bipolar depression remain ill for at least 1 year, in contrast to less than 10% of those suffering from mania. 3) Moreover, Hlastala et al, found that the median time to full remission was also twice as long for bipolar depression compared to bipolar mania. In addition to being longer and more persistent, the depressive phase of bipolar disorder is associated with higher rates of morbidity and mortality. Tohen et al, found that the presence of depressive symptoms during an episode of mania predicts relapse to an episode of depression. 4) Dilsaver et al, reported the risk of suicide attempts among patients with bipolar depression to be 35 times greater than for bipolar mania. Depressive symptoms have also been found to be a strong predictor of disability in patients with bipolar disorder.

Advances in the Pharmacological Treatment of Bipolar Depression

Video  |  Audio (Length:  23 min.)

Paul E. Keck, Jr., M.D.
Bibliography

P.E. Keck
University of Cincinnati, Collage of Medicine, Cincinnati, OH, USA

Abstract:
Background: Until relatively recently, there were very few randomized, controlled trials of mood stabilizers, antidepressants or their combination in the treatment of bipolar depression. Thus, many fundamental questions regarding the efficacy, tolerability, risk of mood switching and relapse with specific agents remained unanswered.
Method: Data from randomized, controlled trials and informative naturalistic treatment studies of bipolar depression published or presented over the last 6 years were reviewed. Evidence of efficacy, tolerability, switch risk, protective effects of combination treatment with antidepressants and mood stabilizers, and risk of relapse after antidepressant discontinuation was examined.
Results: Six randomized, controlled trials of medications in the acute treatment of bipolar depression have been recently reported, including studies of monotherapy trials of lamotrigine, divalproex and gabapentin, and combination therapy studies of paroxetine versus lithium or valproate added to a mood stabilizer, paroxetine versus imipramine or placebo added to a mood stabilizer, sertraline versus bupropion versus venlafaxine added to a mood stabilizer, and the combination of olanzapine and fluoxetine versus olanzapine or placebo. In addition, seven randomized, controlled trials examined the efficacy of lamotrigine, olanzapine, lithium and divalproex in relapse prevention of bipolar depression. A number of naturalistic studies provided data regarding the risk of switching with maintenance antidepressant and mood stabilizer combinations and the risk of depressive relapse with antidepressant discontinuation during maintenance treatment.
Conclusions: Lamotrigine and olanzapine have demonstrated efficacy in the acute treatment of bipolar depression as monotherapy. The efficacy of olanzapine was greatest when administered with fluoxetine. Lamotrigine, lithium, divalproex, and olanzapine also appeared to reduce the risk of depressive relapse during maintenance treatment in most long-term trials, although some differences emerged. Co-administration of mood stabilizers with antidepressants appears to substantially reduce but not entirely eliminate the risk of switching into mania or hypomania.

What is the Role for Psychotherapy in Bipolar Disorders?

Video  |  Audio (Length:  18 min.)

Jan Scott, M.D., FRCPsych.
Bibliography

J. Scott
Institute of Psychiatry, London, UK

Abstract
The basic aims of any treatments in bipolar disorders (BP) are to alleviate acute symptoms, restore psychosocial functioning, and prevent relapse and recurrence. The mainstay of treatment has been and currently remains pharmacotherapy. However, there is a significant efficacy-effectiveness gap in response rates to all mood stabilizers and even under optimal clinical conditions, prophylaxis is only effective in about 50% of individuals with BP. Furthermore, there is evidence that psychosocial factors may adversely affect prognosis in individuals with BP and evidence of significant inter-episode morbidity. Given this scenario, the development of adjunctive psychotherapies appears both helpful and necessary. Whilst many patients and carers have argued strongly in favour of the use of combined pharmacological and psychological treatments, the relative lack of empirical support (few randomized controlled trials have ever been published) meant that for many decades clinicians received little advice on how to incorporate such approaches into day-to-day practice.  Between 1960-1999, there were just over 30 published studies describing the use of psychological treatments in BP. However, the majority were small scale and the combined sample size for all studies was about 1000 subjects. Three quarters of the papers addressed group or family approaches, but less than half of all studies (about 13) were randomized controlled trials. Although the studies had many methodological limitations, there were trends in many trials for those receiving adjunctive psychological treatments to have better subjective and objective clinical and social outcomes than those receiving usual treatments (mainly mood stabilizers and outpatient support). Since 1999, the situation has changed dramatically with about 20 randomized controlled trials either published, in press or underway on both sides of the Atlantic. Given the recent emphasis on the use of brief evidence-based therapies, it is not surprising that the majority of these new studies have focused on psycho-educational models or the three specific brief ‘manualized’ therapies: interpersonal social rhythms therapy (IPSRT), cognitive behaviour therapy (CT) and family focused therapy (FFT). This paper will highlight the key characteristics of potentially effective psychotherapies. Psychotherapy outcome studies are reviewed and guidance is provided on which therapies may be most helpful given the many different problems faced by individuals with bipolar disorder and by their family or significant others.  The paper concludes that that the use of adjunctive psychological therapies may led to significant reductions in relapse rates and symptom levels and improvements in social functioning. A number of studies reported significant improvements in medication adherence in those receiving psychotherapy, although this alone did not account for the improved outcomes of subjects in the intervention group. However, there is a need for further research on underlying theoretical model s of the role of psychosocial issues in relapse and a need to extent psychological treatment studies to larger more representative populations of patients.

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