Combination pharmacotherapy in unipolar depression

It is estimated that between 60 and 80% of those with major depressive disorder do not achieve full symptomatic remission from first-line antidepressant monotherapy. Residual depressive symptoms substantially impair quality of life and add to the risk of recurrence. It is now clear that depression would benefit from more vigorous treatment, in order to ameliorate its disease burden. While there are established algorithms in situations of treatment resistance, the use of combination pharmacotherapy in unipolar depression is a relatively under-investigated area of treatment and may be an effective and tolerable strategy that maximizes the available resources. This paper reviews the current evidence for combination pharmacotherapy in unipolar depression and discusses its clinical applications.

Lifestyle management of unipolar depression

Objective To be used in conjunction with ‘Pharmacological management of unipolar depression’ [Malhi et al. Acta Psychiatr Scand 2013;127(Suppl. 443):6–23] and ‘Psychological management of unipolar depression’ [Lampe et al. Acta Psychiatr Scand 2013;127(Suppl. 443):24–37]. To provide clinically relevant recommendations for lifestyle modifications in depression, derived from a literature review.

Method A search of pertinent literature was conducted up to August 2012 in the area of lifestyle factors and depression. A narrative review was then conducted.

Results There is evidence that level of physical activity plays a role in the risk of depression, and there is a large and validated evidence base for exercise as a therapeutic modality. Smoking and alcohol and substance misuse appear to be independent risk factors for depression, while the new epidemiological evidence supports the contention that diet is a risk factor for depression; good quality diets appear protective and poor diets increase risk.

Conclusion Lifestyle modification, with a focus on exercise, diet, smoking and alcohol, may be of substantial value in reducing the burden of depression in individuals and the community.

Pharmacological management of unipolar depression

Objective : To be used in conjunction with ‘Psychological management of unipolar depression’ [Lampe et al. Acta Psychiatr Scand 2013;127(Suppl. 443):24–37] and ‘Lifestyle management of unipolar depression’ [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38–54]. To provide clinically relevant recommendations for the use of pharmacological treatments in depression derived from a literature review.

Method : Using our previous Clinical Practice Guidelines [Malhi et al. Clinical practice recommendations for bipolar disorder. Acta Psychiatr Scand 2009;119(Suppl. 439):27–46] as a foundation, these clinician guidelines target key practical considerations when prescribing pharmacotherapy. A comprehensive review of the literature was conducted using electronic database searches (PubMed, MEDLINE), and the findings have been synthesized and integrated alongside clinical experience.

Results : The pharmacotherapy of depression is an iterative process that often results in partial and non-response. Beyond the initiation of antidepressants, the options within widely used strategies, such as combining agents and switching between agents, are difficult to proscribe because of the paucity of pertinent research. However, there is some evidence for second-line strategies, and a non-prescriptive algorithm can be derived that is based broadly on principles rather than specific steps.

Conclusion : Depression is by its very nature a heterogeneous illness that is consequently difficult to treat. Invariably, situation-specific factors often play a significant role and must be considered, especially in the case of partial and non-response. Consulting with colleagues and trialling alternate treatment paradigms are essential strategies in the management of depression.

Psychological management of unipolar depression

Objective: To be used in conjunction with 'Pharmacological management of unipolar depression' [Malhi et al. Acta Psychiatr Scand 2013;127(Suppl. 443):6-23] and 'Lifestyle management of unipolar depression' [Berk et al. Acta Psychiatr Scand 2013;127(Suppl. 443):38-54]. To provide clinically relevant recommendations for the use of psychological treatments in depression derived from a literature review. Method: Medical databases including MEDLINE and PubMed were searched for pertinent literature, with an emphasis on recent publications. Results: Structured psychological treatments such as cognitive behaviour therapy and interpersonal therapy (IPT) have a robust evidence base for efficacy in treating depression, even in severe cases of depression. However, they may not offer benefit as quickly as antidepressants, and maximal efficacy requires well-trained and experienced therapists. These therapies are effective across the lifespan and may be preferred where it is desired to avoid pharmacotherapy. In some instances, combination with pharmacotherapy may enhance outcome. Psychological therapy may have more enduring protective effects than medication and be effective in relapse prevention. Newer structured psychological therapies such as mindfulness-based cognitive therapy and acceptance and commitment therapy lack an extensive outcome literature, but the few published studies yielding positive outcomes suggest they should be considered options for treatment. Conclusion: Cognitive behaviour therapy and IPT can be effective in alleviating acute depression for all levels of severity and in maintaining improvement. Psychological treatments for depression have demonstrated efficacy across the lifespan and may present a preferred treatment option in some groups, for example, children and adolescents and women who are pregnant or postnatal. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Is life dissatisfaction the opposite of life satisfaction?

The circumplex model of affect proposes that states of affect can be categorised according to the two dimensions of valence and arousal. According to this model, satisfaction and dissatisfaction are located on the pleasant and unpleasant ends of the valence axis as bipolar opposites. This study investigated the relationship between these two adjectives when assessed with unipolar or bipolar response formats. This suggests that a reciprocal relationship exists between life satisfaction and dissatisfaction when a unipolar response format is employed, but not when a bipolar response format was used. These results are discussed in relation to current affect theory and subject wellbeing research.

The role of omega-3 fatty acids in mood disorders

Research has established that docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid (PUFA), plays a fundamental role in brain structure and function. Epidemiological and cross-sectional studies have also identified a role for long-chain omega-3 PUFA, which includes DHA, eicosapentaenoic acid, and docosapentaenoic acid, in the etiology of depression. In the past ten years, there have been 12 intervention studies conducted using various preparations of longchain omega-3 PUFA in unipolar and bipolar depression. The majority of these studies administered long-chain omega-3 PUFA as an adjunct therapy. The studies have been conducted over 4 to 16 weeks of intervention and have often included small cohorts. In four out of the seven studies conducted in depressed individuals and in two out of the five studies in bipolar patients, individuals have reported a positive outcome following supplementation with ethyl-eicosapentaenoic acid or fish oil containing long-chain omega-3 PUFA. In the three trials that researched the influence of DHA-rich preparations, no significant effects were reported. The mechanisms that have been invoked to account for the benefits of long-chain omega-3 PUFA in depression include reductions in prostaglandins derived from arachidonic acid, which lead to decreased brain-derived neurotrophic factor levels and/or alterations in blood flow to the brain.

The bipolar depression rating scale (BDRS) : its development, validation and utility

Objectives: Unipolar and bipolar depression differ neurobiologically and in clinical presentation. Existing depression rating instruments, used in bipolar depression, fail to capture the necessary phenomenological nuances, as they are based on and skewed towards the characteristics of unipolar depression. Both clinically and in research there is a growing need for a new observer-rated scale that is specifically designed to assess bipolar depression.

Methods: An instrument reflecting the characteristics of bipolar depression was drafted by the authors, and administered to 122 participants aged 18–65 (44 males and 78 females) with a diagnosis of DSM-IV bipolar disorder, who were currently experiencing symptoms of depression. The Bipolar Depression Rating Scale (BDRS) was administered together with the Hamilton Depression Rating Scale (HAM-D), Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS).

Results: The BDRS has strong internal consistency (Cronbach's alpha = 0.917), and robust correlation coefficients with the MADRS (r = 0.906) and HAM-D (r = 0.744), and the mixed subscale correlated with the YMRS (r = 0.757). Exploratory factor analysis showed a three-factor solution gave the best account of the data. These factors corresponded to depression (somatic), depression (psychological) and mixed symptom clusters.

Conclusions: This study provides evidence for the validity of the BDRS for the measurement of depression in bipolar disorder. These results suggest good internal validity, provisional evidence of inter-rater reliability and strong correlations with other depression rating scales.

Scale matters : the need for a Bipolar Depression Rating Scale (BDRS)

Objective: To briefly review the clinical and biological distinctions between unipolar and bipolar depression critiquing in particular currently available depression rating scales and discuss the need for a new observer-rated scale tailored to bipolar depression.

Method: Relevant literature pertaining to the symptomatic differences between bipolar disorder and unipolar disorder as well as their measurement using existing assessment scales was identified by computerized searches and reviews of scientific journals known to the authors.

Results: Bipolar depression is distinct from unipolar depression in terms of phenomenology and clinical characteristics. These distinguishing features can be used to identify bipolarity in patients that present with recurrent depressive episodes. This is important because current self-report and observer-rated scales are optimized for unipolar depression, and hence limited in their ability to accurately assess bipolar depression.

Conclusion: The development of a specific bipolar depression rating scale will improve the assessment of bipolar depression in both research and clinical settings and assist the development of better treatments and interventions.

Diet quality in bipolar disorder in a population-based sample of women

Background : Recent epidemiological evidence has indicated a role for diet quality in unipolar depressive illness. This study examined the association between diet quality and bipolar disorder (BD) in an epidemiological cohort of randomly selected, population-based women aged 20–93 years.

Methods : An a priori diet quality score was derived from food frequency questionnaire data, a factor analysis identified habitual dietary patterns and glycemic load was assessed. Mental health was assessed using the SCID-I/NP.

Results : BD was identified in 23 women and there were 691 participants with no history of psychopathology. Compared to those with no psychopathology, those with BD had a higher glycemic load (p = 0.06) and higher scores on a ‘western’ dietary factor (p = 0.03) and the ‘modern’ dietary factor (p = 0.02). For each standard deviation increase in a ‘western’ and ‘modern’ dietary pattern and glycemic load, the odds ratios for BD were increased (‘western’ OR = 1.88, 95% CI 1.33–2.65; ‘modern’ OR = 1.72, 95% CI 1.14–2.39; GL OR = 1.56, 95% CI 1.13–2.14). Conversely, a ‘traditional’ dietary pattern was associated with reduced odds for BD (OR = 0.53 95% CI 0.32–0.89) after adjustments for overall energy intake.

Limitations : The small sample size did not allow for multivariate analyses and the cross-sectional study design precludes any determinations regarding the direction of the relationships between diet quality and BD.

Conclusion : These data are largely concordant with results from dietary studies in unipolar depression. However, clinical recommendations cannot be made until the direction of the relationship between diet quality and BD is determined. Longitudinal studies are warranted.

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.

Bipolar II disorder : a review

Objectives: To review the current knowledge of bipolar II disorder.

Methods: Literature was reviewed after conducting a Medline search and a hand search of relevant literature.

Results: Bipolar II disorder is a common disorder, with a prevalence of approximately 3–5%. Distinct clinical features of bipolar II disorder have been described. The key to diagnosis is the recognition of past hypomania, while depression is the typical presenting feature of the illness. This is responsible for a significant rate of missed diagnosis, and consequent management according to unipolar guidelines. It is unclear if bipolar II disorder is over-represented amongst resistant depression populations and if abrupt offset of antidepressant action is a phenomenon over represented in bipolar II disorder, reflecting induction of predominantly depressive cycling. A few mood-stabilizer studies available provide provisional suggestion of utility. A supportive role for psychosocial therapies is suggested, however, there is a sparsity of published studies specific to bipolar II disorder cohorts. A small number of short-term antidepressant trials have suggested efficacy, however, compelling long-term maintenance data is absent.

Conclusions: An emerging literature on the specific clinical signature and management of the disorder exists, however, this is disproportionately small relative to the epidemiology and clinical significance of the disorder.