Diagnosing bipolar disorder : how can we do it better?

• Accurate diagnosis of bipolar disorder is essential for effective treatment.

• The diagnosis of bipolar disorder is particularly complex, resulting in lengthy delays between first presentation and initiation of appropriate therapy. Inappropriate therapy destabilises the course and outcome of the disease.

• Although the defining features of bipolar disorder are manic or hypomanic episodes, patients typically present for treatment of depression and commonly deny symptoms of mood elevation.

• A correct diagnosis can easily be masked by comorbidities, personality issues and complex phenomenology.

• A diagnosis of bipolar disorder can be assisted by:

   → asking about symptoms of mania or hypomania in every patient presenting with symptoms of depression.

   → recognising mixed states in which manic and depressive symptoms occur simultaneously.

   → identifying the features of bipolar depression that distinguish it from unipolar depression.

• There is a risk of over-diagnosis of bipolar disorder among patients who are histrionic, show abnormal illness behaviour MJA 2006; 184: 459–462 and/or have issues of secondary gain.

Efficacy of atypical antipsychotics in bipolar disorder

Bipolar disorder is a severe and recurrent disorder. Atypical antipsychotics have emerged as both an alternative and adjunct to conventional mood stabilisers. The manic phase of the illness is the best studied, and it appears that a class effect with regards to efficacy is present in both monotherapy and augmentation studies. Evidence for efficacy of atypical antipsychotics in depression is emerging. At this stage controlled data are available for both olanzapine and quetiapine. Maintenance data demonstrating efficacy are available for olanzapine. Atypical antipsychotics have utility in treating acute agitation and aggression in manic episodes of bipolar disorder. Subgroup analyses from trials treating manic phase bipolar disorder, and an open-label study of rapid cycling, have suggested that atypical antipsychotics may be useful for the treatment of mixed states and rapid cycling. Several studies have suggested that atypical antipsychotics may be useful in treatment-refractory episodes of bipolar disorder. The current available data suggest greater efficacy of the atypical antipsychotics in mania than in depression, although the data are fairly clear that induction of depression is not an issue with the atypical antipsychotics. A number of trials are underway that will hopefully address many of the questions still pending.

The management of bipolar disorder in primary care : a review of existing and emerging therapies

Recent evidence suggests that the prevalence of bipolar disorder is as much as fivefold higher than previously believed, and may amount to nearly 5% of the population, making it almost as common as unipolar major depression. It is, therefore, not unrealistic to assume that primary care or family physicians will frequently encounter bipolar patients in their practice. Such patients may present with a depressive episode, for a variety of medical reasons, for longer-term maintenance after stabilization, and even with an acute manic episode. Whatever the reason, a working knowledge of current trends in the acute and longer-term management of bipolar disorder would be helpful to the primary care physician. In addition, an understanding of important side-effects and drug interactions that occur with drugs used to treat bipolar disorder, which may be encountered in the medical setting, are paramount. This paper will attempt to review existing and emerging therapies in bipolar disorder, as well as their common drug interactions and side-effects.

The validity and internal structure of the bipolar depression rating scale (BDRS): data from a clinical trial of N-acetylcysteine as adjunctive therapy in bipolar disorder

Background: The phenomenology of unipolar and bipolar disorders differ in a number of ways, such as the presence of mixed states and atypical features. Conventional depression rating instruments are designed to capture the characteristics of unipolar depression and have limitations in capturing the breadth of bipolar disorder.

Method: The Bipolar Depression Rating Scale (BDRS) was administered together with the Montgomery Asberg Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) in a double-blind randomised placebo-controlled clinical trial of N-acetyl cysteine for bipolar disorder (N = 75).

Results: A factor analysis showed a two-factor solution: depression and mixed symptom clusters. The BDRS has strong internal consistency (Cronbach's alpha = 0.917), the depression cluster showed robust correlation with the MADRS (r = 0.865) and the mixed subscale correlated with the YMRS (r = 0.750).

Conclusion: The BDRS has good internal validity and inter-rater reliability and is sensitive to change in the context of a clinical trial.

Bipolar missed states : the diagnosis and clinical salience of bipolar mixed states

Objective: To explore diagnostic and treatment issues concerning bipolar mixed states.

Method: Bipolar mixed states are described and concerns about diagnostic and treatment difficulties are summarized and discussed.

Result: Mixed states can present with equal admixtures of depressive or manic symptoms, or more commonly one component predominates. There is fair consensus, although little data, regarding the management of manic mixed states. However depressive mixed states are far more complex both in terms of recognition and management. People suffering from mixed states characteristically present with complaints of depression.

Conclusions: The boundaries between depressive mixed states and agitated depression are vague, yet carry substantial therapeutic implications. Bipolar mixed states are often difficult to treat, and tend to take much longer to settle than either pure mania or depression.  Furthermore there is data that treatment with antidepressants can worsen the course of mixed states. Hence missed diagnoses can potentially have negative clinical implications.  Therefore in this paper the clinical presentation, diagnosis and therapy of mixed states is reviewed with a view to improving management.

The impact of age at onset of bipolar I disorder on functioning and clinical presentation

Objectives: Recent studies have proposed the existence of three distinct subgroups of bipolar 1 disorder based on age at onset (AAO). The present study aims to investigate potential clinical and functional differences between these subgroups in an Australian sample.

Methods: Participants (n = 239) were enrolled in the Bipolar Comprehensive Outcomes Study (BCOS), a 2-year longitudinal, observational, cross-sectional study. Assessment measures included the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD21), Clinical Global Impressions Scale (CGI-BP), SF-36, SLICE/Life Scale, and the EuroQol (EQ-5D). Participants were also asked about their age at the first major affective episode.

Results: Three AAO groups were compared: early (AAO < 20, mean = 15.5 ± 2.72; 44.4% of the participants); intermediate (AAO 20–39, mean = 26.1 ± 4.8; 48.14% of the participants) and late (AAO > 40, mean = 50.6 ± 9.04; 7.4% of the participants). Higher rates of depression, suicidal ideation and binge drinking were reported by the early AAO group. This group also reported poorer quality of life in a number of areas. The early AAO group had a predominant depressive initial polarity and the intermediate group had a manic predominance.

Conclusion: Early AAO is associated with an adverse outcome.

Olanzapine / fluoxetine combination for treatment resistant depression : efficacy and clinical utility

Antidepressant monotherapy is a first-line treatment for depression; however, not all sufferers will adequately respond to treatment. When treating a patient with treatment-resistant depression, the clinician needs to consider all factors which may contribute to an inadequate response to an antidepressant. These include accuracy of diagnosis and medication adherence, as well as the patient’s personality, lifestyle, life events and social circumstances. If it is determined that treatment resistance is due to failure of efficacy of antidepressant monotherapy, then an augmentation strategy using an atypical antipsychotic may be considered. Treatment using olanzapine/fluoxetine combination (OFC) is one of many options. Four randomized, acute-phase trials have suggested OFC is useful for reducing Montgomery–Åsberg Depression Rating Scale scores after inadequate response to antidepressant monotherapy. OFC has been useful at doses of olanzapine/fluoxetine 6/25, 6/50, 12/25 and 12/50 mg/day, with 1/5 mg/day suggested to be an ineffective dose. Treatment with OFC has been associated with some side effects, including weight gain and the metabolic syndrome, somnolence, dry mouth, increased appetite and headache. Treatment decisions therefore need to be made to balance the risks and benefits.

A prospective study of the impact of subthreshold mixed states on the 24-month clinical outcomes of bipolar I disorder or schizoaffective disorder

Objectives: Subthreshold mixed states are common, yet their clinical significance is unclear. This study investigated the clinical outcomes of subthreshold mixed states in participants with bipolarI disorder or schizoaffective disorder, using the Cassidy and Benazzi criteria for manic and depressive mixed states, respectively.

Methods: The Bipolar Comprehensive Outcomes Study (BCOS) is a prospective observational study of treatment and outcomes for patients with bipolar I or schizoaffective disorder, bipolar type. Participants (N=239) were grouped based on study entry clinical presentation as having pure depression (n=63) if they satisfied DSM-IV-TR criteria for a Major Depressive Episode (MDE), depressive mixed state (DMX) if they also had at least three concurrent hypomanic symptoms (n=33), or not depressed (n=143) if they did not satisfy the criteria for MDE. Participants were similarly grouped as having pure mania (n=3) if they satisfied DSM-IV criteria for a Manic Episode, manic mixed state (MMX) if they also had at least two concurrent depressive symptoms (n=33), or not manic (n=203). Clinical data were collected by interview every 3-months over a 24-month period.

Results: Measures of quality of life, mental and physical health over the 24-month period were significantly worse for participants who were classified as having mixed states at study entry on most outcome measures compared to participants who were not in an illness episode at study entry. DMX was predictive of greater manic symptomatology over the 24 months compared to participants with pure depression.

Conclusion: In participants with a current episode of mood disorder, the presence of subthreshold symptoms of opposite polarity was associated with poorer clinical outcomes over a 24-month period.