Life and its limits

Faith, hope and charity

The sessions started in the morning with a talk by Professor Pompili from Italy, one of the countries with the lowest reported suicide rates and chaired by Professor Rihmer from Hungary, a country with one of the highest.

Prof. Pompili, a highly respected and well-published authors on suicide, gave a talk with (to my mind anyway) a strong Italian flavour, with themes of suidcidality as a result of loss of faith (personal, rather than necessarily religious), and the importance of love in creating an empathetic link with patients.

Interestingly, the first question from the delegates was one challenging Prof. Rihmer’s original statement regarding the low incidence of suicide in Catholic countries, and inItaly in particular, and asking whether it was in part due to low reporting. Prof. Pompili agreed, citing historical trials of suicides, confiscation of their property and pauper’s graves as creating stigma against suicide (and its accurate reporting) that still remains today.

During Professor Øegaard’s presentation on the sociocultural challenges of bipolar management, he also noted that in some cultures mental illness is considered a result of sin, which can limit treatment-seeking behaviours and acceptance of treatment.

Lust for life

The afternoon session kicked off with a presentation by Doctor Hantouche’s examining cyclothymic temperaments and their relation to suicidality. The data he presented showed that cyclothymic (and to a lesser extent depressive) affective temperaments, when combined with a family history of suicide place patients at a very high risk of suicidality.

This discussion of temperaments continued in Prof. Rihmer’s presentation on the effects of a hyperthymic temperament on suicide risk. He confirmed the cyclothymic temperaments as a risk factor for suicidality in bipolar patients, but also added depressive, irritable and anxious temperaments to the list of risk factors as well. This data was supported by Professor Karam’s presentation later in the day, with a fascinating addendum: while these factors are predictive risk factors in patients with disorders, in the general population only an anxious temperament is a predictive factor for suicidality.

Unsurprisingly, given the cheerful, exuberant aspects of hyperthymic temperaments, Prof. Rihmer stated it was associated with a lower risk of suicide. This data was supported by the under-representation of hyperthymic temperaments in both suicide attempts and suicidal ideation. Interestingly, in bipolar I disorder a hyperthymic temperament is also associated with an increased risk of manic episodes.

Turning temperament on its head

The seemingly widespread acceptance of the protective effects of hyperthymic temperaments in suicidality set the stage for this correspondant’s pick for the most unexpected presentation of the day: Prof. Karam’s presentation data showing that as well as having protective effects, hyperthymic temperaments might actually be risk factors for suicidality in some female bipolar I disorder patients.

In fact, this data is not as contradictory as it may seem; temperaments are defined by a number of different aspects, and these different aspects of the hyperthymic temperament may each have different protective or risk-enhancing effects.

The aspects of the hyperthymic temperament that (when present at the same time) enhanced the risk of suicide were a need to be in charge, a need to be in control of their own actions, and low self-confidence. It appears that while the lack of self-worth influences the suicidal ideation, the other two more dynamic temperamental aspects enable the bipolar patient to act on those ideas.

Down the rabbit hole

This correspondent found Prof. Karam’s presentation a perfect example of both the challenges and the joys of mental health research; no matter how well you think you understand an aspect of the human psyche, there are always more dimensions and more layers to discover.

The importance of early recognition – prodromes and predictors

Despite the tempting lure of a Sunday afternoon siesta in the Greek sunshine, we headed to the afternoon session, which delved into the early recognition of bipolarity and psychosis. Ms Khalsa, USA, started off by presenting her findings from the McLean Harvard First Episode Project. The project looked at a cohort of patients with psychotic disorders, treated according to community standards and evaluated their remission and recovery, their relapse or recurrence and their diagnostic stability to identify predictors of outcome and to consider the course of the disorder.

Some key findings from the study were that:

• Functional recovery after initial episodes was uncommon
• Full symptomatic recovery was much slower than syndromal remission
• By 2 years, 41% initially diagnosed with psychotic depression met the criteria for bipolar I disorder or schizoaffective disorders

Predictors of mania and relapse in bipolar patients

The following characteristics predicted an earlier manic relapse:

• Patients who initially presented with manic rather than mixed symptoms
• Patients with initial mood-congruent psychotic features
• Patients with a relatively low premorbid occupational status

Patients who initially presented with first-episode psychotic depression were more likely to change to bipolar I disorder if they had mood lability of subsyndromal hypomanic symptoms.

The talk really highlighted the importance of correct diagnosis and thorough monitoring of patients to try to predict relapses. A very interesting closing point for me was that in the cohort, 20% of patients had homicidal ideation, even higher than suicidal ideation, which made Ms Khalsa ask: are we overlooking the risk of homicide?

A place for prodromes?

Doctor Faedda, USA went on to consider the concept of prodromes and their importance for early identification. There is often a significant delay to first treatment, and considering patients with an earlier age of onset have a longer time to diagnosis and treatment, this makes the early identification and treatment of patients even more important.

The term prodrome has not been entirely defined and there is still a need for a clear definition. However, for bipolar disorder it can be described as the phase preceding the syndromal onset characterised by signs and symptoms, deficits or a departure from normal development.

What are the clinical features that predict bipolar disorder?

Dr Faedda performed a large systematic review to establish clinical features prior to a bipolar disorder diagnosis. Some of the key findings were:

• Dysthymia and minor depression are strong predictors of bipolar I disorder, especially when presenting with euphoria or grandiosity
• Lifetime hypomanic symptoms and lifetime depressive symptoms predict bipolar disorder
• There is some evidence that anxiety is linked with general psychopathology; separation anxiety in particular has been found to have a strong predictive value for bipolar disorder in males
• Panic anxiety has also been associated with bipolar disorder and is likely to precede mania rather than depressive symptoms

He noted the results suggest there are several clinical predictors of developing bipolar disorder, from mood symptoms, to anxiety and aggression. However the sensitivity and specificity of these clinical predictors remains to be elucidated and it is unknown how long this prodromal phase will last – possibly for several years. So for now, family history of bipolar or depressive disorder remains the best predictor of bipolar disorder.

The hows and whys of switching

Switching a patient to a different antipsychotic treatment can be a frequent part of clinical practice, either due to lack of efficacy, or lack of tolerability of the current antipsychotic. Doctor Murru, Spain, gave an overview of when and how to switch atypical antipsychotics in bipolar affective patients.

There are some key considerations when considering how and why to switch antipsychotics. The method of switching (i.e. abrupt or tapering) can affect the risk of relapse or side-effects. Binding affinities are potentially important, as they can help to predict side effects. Another consideration should be cardiovascular risk as different antipsychotics have different impacts on cardiovascular risk.

The issue of adherence

Adherence is another area where antipsychotic choice should be considered. Dr Murru noted that some psychiatrists underestimate non-adherence to antipsychotics. In one study, a third of patients believed that they were non-adherent, whereas the psychiatrists estimated non-adherence at only 6%. After efficacy considerations have been taken into account, weight gain and somnolence are very common reasons for patient discontinuation, suggesting that the choice of antipsychotic should reflect those with a positive side-effect balance for these traits.

For patients, one of their biggest concerns about treatment is becoming dependent on their drugs, suggesting that involving patients in treatment decisions and explaining the role of treatment may help increase their acceptance and long-term persistence.

Should we switch at all?

There is actually limited evidence for switching drugs in bipolar disorder – switching an antipsychotic too early may be an inefficient strategy, as treatment options that could in fact be effective might be ruled out, when in reality they just have not been prescribed appropriately in the past. Therefore, the decision to switch shouldn’t be made lightly and should of course take into account the potential impact on the patient’s long term outcomes.

A new scale to assess quality of life for bipolar patients

Bringing my Sunday session nicely to a close, Professor Michalak, Canada, discussed whether we are measuring quality of life (QoL) for patients with bipolar disorder in the right way. Patients have a very individual perspective of what brings them a positive quality of life depending on what they value, such as feeling balanced, creativity or confidence. Therefore, it’s important to talk to patients about their individual needs when discussing their quality of life. She noted that over the past 10 years, more and more publications are looking at quality of life in bipolar disorder, which can only be a positive thing. However, despite the growing interest in this area, there is a lack of information about the longitudinal course of bipolar disorder in the long-term.

A specific scale for bipolar disorder

Although there are some general scales to measure quality of life, there aren’t any scales that measure quality of life in bipolar disorder specifically. Prof. Michalak proposed a new scale, the QoL.BD, which has been developed as both a long and short version and has already been translated into several languages worldwide. It has been designed to focus on the areas that are really important to patients in terms of quality of life such as:

• Social support
• Cognition
• Spirituality
• Independence
• Identity
• Finances

Web-based self-assessment and self-management resources

The scale has been very successful but Prof. Michalak soon found that there was a demand for a web-based self-assessment tool for patients. Two years of research later, working with both patients and healthcare professionals, and her tool is almost ready to launch. Once the patients have filled in the assessment online, they are presented with the key areas or domains that require more attention, such as physical or leisure. One useful feature that may improve the success of the tool is that the patient is provided with web links to useful resources, which may help them improve their quality of life in the domains they are struggling with.

The individual vs the population

The tool did spark quite a bit of debate amongst the audience. One delegate was unsure that a single tool could capture the differences in QoL between countries. He made the point that in his country, material gain has a much higher impact on happiness than in Canada. Prof. Michalak acknowledged that in an ideal world, QoL ratings should be as individualised as possible as each patient has different priorities that change over time, so physicians should be encouraged to engage with their patient as much as possible. However, for the purposes of research and our understanding of the impact of QoL on patients, perhaps a specific tool such as the QoL.BD is warranted.

After three days of research and evidence discussion, it seemed appropriate to this correspondent to finish with a presentation by Professor Grunze on how the evidence actually matches up with clinical practice in the long-term.

Limited by the evidence

Prof. Grunze started his talk with a discussion of the limitations of current guidelines, as clinical practice will be dictated by which set of guidelines the treatment centre in question follows.

In particular, Prof. Grunze noted that all guidelines are, by their nature, restricted and narrow in their approach due to a number of factors. Firstly, they suffer from being based on studies with designs that are neither long-term nor open enough to reflect clinical practice, as they are usually designed to test one very particular aspect of a drug or drugs. Secondly, the studies involved suffer from an efficacy-effectiveness gap, with highly selected study populations and efficacy criteria that are too narrow. Finally, there are questions over the validity of the data, due to sponsor and publication bias, and overestimations of the role of meta-analysis.

The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the Biological Treatment of Bipolar Disorders, which Prof. Grunze was involved in, attempt to avoid these issues by basing their advice around efficacy, safety and tolerability, practicality of use, and the anti-suicidal properties of a drug, a factor that is highly important in bipolar I disorder.

As well as these criteria, the WFSBP group also developed a level of recommendation based on both the quality of evidence and the risk-benefit ratio for the treatment.

Freed by the data

Prof. Grunze concluded his presentation with the results of an 8-month, prospective, multicentre, non-interventional study that he had been involved in, which was conducted in 761 German outpatients, and was designed to provide an accurate reflection of clinical practice.

Despite the range of problems that had been discussed regarding current randomised clinical trials, it was heartening to hear that the results of this ‘more representative’ study actually matched the efficacy data shown by previous clinical trials.

Although there is definitely a need to keep pushing for studies that more accurately represent the way treatments and interventions are used day-to-day by psychiatrists, it is good to have some reassurance that the work that has gone before has not been in vain.

Afterthoughts on Athens

After four days of fascinating insight, engaging controversy, and informed debate, this correspondent has remained fascinated and inspired by the presentations and discussions, and in awe of the quality and quantity of novel thinking that is directed towards improving the lives of bipolar patients worldwide.

We hope you’ve enjoyed your time with us on bipolarmania.net and at the conference, and we’d encourage you to keep checking back, as we’ll continue to add new content over the coming months.