A naturalistic effectiveness study of maintenance therapies for the bipolar disorders.

BACKGROUND: Treatment decision-making for individuals with bipolar disorder can be difficult. Recommendations from clinical practice guidelines can be affected by multiple methodological limitations, while pharmaco-epidemiological data suggest great variety in prescription practices across regions. Given these inconsistencies, this study aimed to provide an alternative perspective on the effectiveness of common bipolar disorder maintenance treatments through considering naturalistic data. METHODS: A total of 246 individuals with bipolar disorder (84 bipolar I [BP-I], 162 bipolar II [BP-II]) were recruited through clinics and/or websites. All were euthymic and had trialled at least one mood stabiliser. They completed an online survey containing questions on demographics, clinical variables, symptomatology, and the effectiveness/side effect profiles of any mood stabilisers (MSTs) or atypical antipsychotics (AAPs) that they have taken. RESULTS: Lithium and lamotrigine were the most commonly prescribed MSTs and the most effective at mood stabilisation. Lithium and lamotrigine appeared marginally more effective for BP-I and BP-II respectively, however, only the latter difference was statistically significant. Furthermore, lamotrigine had the more favourable side effect profile. Amongst the AAPs, quetiapine and olanzapine were the most commonly prescribed, but they were negligibly superior to other AAPs. CONCLUSION: This study clearly established a preference for lamotrigine in the maintenance treatment of BP-II. While the literature consistently emphasises the primacy of lithium in bipolar disorder treatment, its side effect profile as observed in this study remains a concern. Future research considering moderators of treatment response and concomitant medications could help to identify further nuances to consider for treatment decision-making.

A revisionist model for treatment-resistant and difficult-to-treat depression.

OBJECTIVE: The aim of this study is to consider limitations to the heuristics 'treatment-resistant depression' (TRD) and 'difficult-to-treat' depression (DTD) and to offer a revisionist model. METHODS: A number of limitations to the two constructs are noted, particularly the risk of each positioning clinical depression as an entity and then applying a linear sequencing management model. RESULTS: Arguing that clinical depression is heterogenous in nature (with categorical and 'fuzzy set conditions), in cause and in response to treatment, allows an alternate model for addressing depressive conditions that are not readily responsive to treatment. A skeletal model for proceeding is offered for consideration and development. CONCLUSION: If such a model is accepted, then differing criteria for defining treatment resistance and treatment failure might be generated for differing depressive conditions, and condition-specific sequencing algorithms (embracing drug and non-drug strategies) developed for their management.

An observer-rated strategy for differentiating schizophrenic and manic states in inpatient settings.

OBJECTIVES: Differentiating schizophrenia from mania in acutely psychotic patients can be difficult, but is important in determining immediate and subsequent management. Such differentiation is generally addressed by clinical interviews, but an observational approach may assist. This paper therefore describes the development of a relevant observational measure. METHODS: We developed a provisional list of 49 items (weighting features with suggested specificity to schizophrenia and mania) for independent completion by two nurses and judged its ability to predict diagnosis provided by consultant psychiatrists. RESULTS: Eighty-seven psychotic patients were recruited, and 173 completed data sets were analysed. We refined the item set to two sets of 10 items that best-differentiated schizophrenia from mania and vice versa. Optimal differentiation was achieved with a score of at least 7 on both the schizophrenia and mania item sets. Difference scores (i.e. schizophrenia items affirmed minus mania items affirmed) were also generated, with a difference score of +1 (i.e. one or more schizophrenia items being affirmed than mania items) showing optimal differentiation (sensitivity 0.67, specificity 0.82) between the two conditions. Evaluating all potential difference scores, we demonstrated that, as difference scores increased, diagnostic accuracy in identifying each condition was very high. CONCLUSION: Analyses allow the properties of an observational measure (the 20-item Sydney Psychosis Observation Tool) to be described. While a single cut-off difference score was derived with acceptable discriminatory ability, we also established the capacity of varying difference scores to assign both schizophrenia and mania diagnoses with high accuracy.

Impact of mood stabilizers on creativity.

OBJECTIVE: While a DSM-5 criterion for both hypomania and mania is impaired functioning, the majority of those with a bipolar condition report improved functioning. When offered a mood stabilizer, many express concerns about any impact on their creativity. This piece seeks to address the question and attendant issues. METHOD: Reference is made to the impact of differing mood stabilizers on cognitive performance and the limited data on any specific impact on creativity, while some personal observations are offered. RESULTS: There appears to be a distinctive gradient in the cognitive impacts of differing mood stabilizers, with lithium offering the highest risk, carbamazepine and valproate providing a slight risk, and lamotrigine seemingly without cognitive side-effects. CONCLUSIONS: The question not only invites a nuanced response from the clinician but argues for close observation of any cognitive side-effects when lithium is introduced.

ADDing up?

OBJECTIVE: To hypothesise that a possible increased prevalence of adult-onset attention-deficit disorder (ADD) and attention-deficit hyperactivity disorder (ADHD) may reflect mobile technology and digital media use being an aetiological factor. CONCLUSIONS: Data and clinical observations support but do not prove the hypothesis.

Differentiating 'pure' and comorbid self-identified burnout: Diagnostic and management implications.

OBJECTIVE: A previous study identified categorically differing scores on the Sydney Burnout Measure (SBM) between individuals with self-identified burnout with (n = 354) or without (n = 188) a history of mental illness. The current study examined whether the SBM's validity held in both scenarios. METHOD: The factorial structure and scores on the SBM measure were compared between the two groups. RESULTS: Similar underlying symptom constructs were identified. The group with a mental illness history had higher general factor scores, suggesting more severe burnout. The group without such a history (and thus a 'purer' burnout state) had higher scores on the empathy loss factor, suggesting its greater specificity to burnout than to other psychological states. CONCLUSIONS: Burnout appears to be experienced similarly by those with and without a mental illness history as measured by the SBM.

A chat about bipolar disorder.

OBJECTIVES: This study aimed to assess the capabilities of ChatGPT (Chat Generative Pre-Trained Transformer) in generating informative content related to bipolar disorders. The objectives were to evaluate its ability to provide accurate information on symptoms, classification, causes, and management of bipolar disorder and to explore its creativity in generating topic-related songs. METHODS: ChatGPT3 was used for the study, and a series of clinically relevant questions were asked to test its knowledge and creativity. Questions ranged from common symptom descriptions to more artistic requests for songs related to bipolar disorder. RESULTS: ChatGPT demonstrated the capacity to provide basic and informative material on bipolar disorders, including descriptions of symptoms, classification types, causes, and treatment options. It also showed creativity in generating songs that capture the nuances of bipolar symptoms, both during high and low states. CONCLUSIONS: While ChatGPT3 can offer superficial information on psychiatric topics like bipolar disorder, its inability to provide accurate and up-to-date references limits its utility for creating a comprehensive review article for scientific journals. However, it may be helpful in generating educational material and assisting in component tasks for those with bipolar disorder or other psychiatric conditions. As newer versions of AI models are continually developed, their capabilities in producing more accurate and advanced content will need further evaluation.

Comorbid attention-deficit hyperactivity disorder and bipolar disorder.

The rate of comorbid attention-deficit hyperactivity disorder and bipolar disorder far exceeds chance if the two are independent conditions. Explanations for such a high comorbid prevalence and management implications are considered.

Modelling self-diagnosed burnout as a categorical syndrome.

OBJECTIVE: There is currently little consensus as to how burnout is best defined and measured, and whether the syndrome should be afforded clinical status. The latter issue would be advanced by determining whether burnout is a singular dimensional construct varying only by severity (and with some level of severity perhaps indicating clinical status), or whether a categorical model is superior, presumably reflecting differing 'sub-clinical' versus 'clinical' or 'burning out' vs 'burnt out' sub-groups. This study sought to determine whether self-diagnosed burnout was best modelled dimensionally or categorically. METHODS: We recently developed a new measure of burnout which includes symptoms of exhaustion, cognitive impairment, social withdrawal, insularity, and other psychological symptoms. Mixture modelling was utilised to determine if scores from 622 participants on the measure were best modelled dimensionally or categorically. RESULTS: A categorical model was supported, with the suggestion of a sub-syndromal class and, after excluding such putative members of that class, two other classes. Analyses indicated that the latter bimodal pattern was not likely related to current working status or differences in depression symptomatology between participants, but reflected subsets of participants with and without a previous diagnosis of a mental health condition. CONCLUSION: Findings indicated that sub-categories of self-identified burnout experienced by the lay population may exist. A previous diagnosis of a mental illness from a mental health professional, and therefore potentially a psychological vulnerability factor, was the most likely determinant of the bimodal data, a finding which has theoretical implications relating to how best to model burnout.

Pseudo-hallucinations are for real in some patients with a bipolar disorder.

OBJECTIVE: To provide exemplars of pseudo-hallucinations experienced by six individuals with bipolar disorder, suggest that they may be preferentially overrepresented in those with that condition and argue that their presence does not indicate that the individual is necessarily psychotic. METHOD: Historical definitions of pseudo-hallucinations are overviewed and six profiles are presented considering manifestations in those with a bipolar disorder, their sequencing and response to medication. RESULTS: The six patients initially judged such experiences as true hallucinations and, only over time, did they recognize their falsity. Clinical observation suggests that pseudo-hallucinations may be more common in those with a bipolar disorder and that they can precede, cooccur or follow disorder onset, can manifest during any phase of the condition and that they may or may not respond to medication prescribed for the bipolar disorder. CONCLUSIONS: The exemplars of pseudo-hallucinations overviewed here indicate their richness of expression, their variable time course with illness stages and their variable response to medications prescribed for the bipolar condition.

Staging the bipolar disorders: Are early stages at too early a stage for intervention?

OBJECTIVES: A number of staging models have been generated for the bipolar disorders, which include pre-onset as well as post-onset stages. Some models propose treatments for those at the pre-onset stage, a recommendation which is critiqued here. METHODS: Several exemplar staging models are overviewed, and a critique is provided. RESULTS: The critique argues against intervention at a pre-onset stage, in light of there being limited risk factors, unquantified sensitivity and specificity data for most putative onset illness risk factors, and thus there is the risk of overtreatment. Also, it is possible that many of the recommended interventions for those at risk of a bipolar disorder may have general non-specific benefits for those at risk. CONCLUSIONS: While retaining a pre-onset phase in the staging model, it would appear wiser for it to not be populated with recommended interventions until they have a firmer empirical base.

The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression.

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.

The Diagnosis of Burnout: Some Challenges.

ABSTRACT: Burnout is a topic of high public and research interest, but debate remains as to how the syndrome should best be defined, measured, and diagnosed. In this article, we overview how issues relating to burnout's definition and measurement as well as the debate surrounding its overlap with depression have led to ambiguity surrounding its diagnostic status. We argue for a broader conceptualization of burnout and detail why we position it as distinct from depression, before providing recommendations for clinicians when considering a burnout diagnosis. We highlight that all measures of burnout risk "false-positive" diagnoses and that they should more be viewed as screening strategies with a definitive diagnosis (of "burning out" or "being burnt out") requiring close clinical assessment and exclusion of alternate psychological and physical conditions.

Psychostimulants as antidepressants: Their nuanced role?

While effectively the 'first antidepressants', the psychostimulants are rarely prescribed as antidepressant drugs seemingly in light of their judged low effectiveness, side effects, tolerance as well as concerns about dependency and abuse. Recent meta-analyses do find some support for them as being effective antidepressants for those with major depression, but they have not been closely evaluated in terms of their specific nuanced role for treating treatment-resistant (unipolar and bipolar) melancholic depression. The author has so prescribed them for over a decade and offers a case for their benefits for a distinct percentage of those with such conditions and notes their relatively few side effects.

In search of logotherapy.

In his authoritative and extraordinarily influential book Man's Search for Meaning, psychiatrist Viktor Frankl proposed that any individual's life task is to find meaning, that meaning cannot be obtained without suffering, and that suffering allows meaning to be identified. He also articulated his therapeutic model-logotherapy, the so-called third Viennese school of psychotherapy. This article contemplates why logotherapy currently has seemingly little salience and suggests that the most likely reasons reflect some components being taken over by other therapies and by tenets of positive psychology articulated in recent decades.

Is burnout simply a stress reaction?

Whether burnout is synonymous with stress is a question of clinical importance when considering the nosological status and management of both states. The biological changes associated with both stress and burnout suggest considerable overlap. However, we argue that the widespread acceptance by the lay community of burnout as a distinct and relatable syndrome suggests it is worthy of independent designation.

The AREDOC project and its implications for the definition and measurement of the bipolar disorders: A summary report.

OBJECTIVES: Judging that the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria for defining mania/hypomania (and thus bipolar I/II disorders, respectively) would benefit from review, we formed an expert taskforce to derive modified criteria for consideration. The aim of this paper is to summarise the component stages and detail the final recommended criteria. METHODS: We first sought taskforce members' views on the Diagnostic and Statistical Manual of Mental Disorders criteria and how they might be modified. Next, members recruited patients with a bipolar I or II disorder, and who were asked to judge new definitional options and complete a symptom checklist to determine the most differentiating items. The latter task was also completed by a small comparison group of unipolar depressed patients to determine the mood state items that best differentiate unipolar from bipolar subjects. Subsequent reports overviewed analyses arguing for bipolar I and II as being categorically distinct and generated empirically derived diagnostic criteria. RESULTS: Alternatives to all the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria were generated. Modifications included recognising that impairment is not a necessary criterion, removing hospitalisation as automatically assigning bipolar I status, adding an irritable/angry symptom construct to the symptom list, deleting a mandatory duration period for manic/hypomanic episodes, and requiring a greater number of affirmed symptoms for a bipolar diagnosis to manage the risk of overdiagnosis. Granular symptom criteria were identified by analyses and constructed to assist clinician assessment. A potential bipolar screening measure was developed with analyses showing that it could clearly distinguish bipolar versus unipolar status, whether symptom items were assigned as having equal status or weighted by their quantified diagnostic contribution. CONCLUSION: While requiring further validation, we suggest that the revised criteria overcome several current Diagnostic and Statistical Manual of Mental Disorders (5th ed.) limitations to defining and differentiating the two bipolar sub-types, while still respecting and preserving the Diagnostic and Statistical Manual of Mental Disorders template. It will be necessary to determine whether the bipolar screening measure has superiority to currently accepted measures.

Ask depressed patients about brain fog to ensure melancholia is not mist.

OBJECTIVE: This study aims to highlight cognitive 'brain fog' as a key depression sub-typing symptom, being weighted to melancholic (as against non-melancholic) depression and note its common persistence after episode remission. METHOD: This paper weights clinical observation but considers several salient overview papers and research findings. RESULTS: While 'brain fog' is intrinsically non-specific in that it has multiple causes, when assessed as a second-order depressive sub-typing symptom, it has seemingly distinctive specificity to the melancholic sub-type, with many patients with melancholia resonating with such a descriptor question. As it may persist (albeit attenuated) after episode remission, psychostimulant medication may be of benefit in some patients. CONCLUSION: In the clinical assessment and differential diagnosis of those with a depressive disorder, inquiring into 'brain fog' can have distinct diagnostic benefit in differentiating melancholic and non-melancholic depression.

Quality control concerns in relation to lamotrigine and their impact.

OBJECTIVE: To pursue explanations for compromised efficacy and induction of side-effects in some generic brands of lamotrigine distributed in Australia. METHOD: Bioassays of the non-generic and five generic lamotrigine tablets were undertaken (also after exposure to heat and cold), as well as assays of two generic drugs generating concerning side-effects in two patients, while enquiries were made of manufacturing companies. RESULTS: Mass spectrometry of the six tested products showed comparable properties and no compromising when those tablets were heated and cooled, while analyses of the products taken by the two patients reporting significant side-effects showed an increase in the peak area lamotrigine concentration. CONCLUSIONS: We failed to identify any intrinsically compromised product in our comparison analyses of the six preparations. We consider alternate explanations for an issue leading to widespread international reporting of distinct side-effects and deaths following brand switching, with analyses of the two problematic preparations supporting a 'faulty' batch explanation.

A Single-Blind Randomized Comparison of Lithium and Lamotrigine as Maintenance Treatments for Managing Bipolar II Disorder.

PURPOSE/BACKGROUND: No study to date has compared lithium and lamotrigine as maintenance mood stabilizers for bipolar II disorder. The aim of this study was to evaluate and compare these two medications in terms of their maintenance efficacy and side effect profile, thus evaluating their comparative cost/benefit profile. METHODS/PROCEDURES: Forty-four subjects with a newly diagnosed bipolar II disorder were randomly assigned to receive either lithium or lamotrigine treatment in a 20-week single-blinded study. Subjects received either slow-release lithium progressively up-titrated to achieve a serum level of 0.8 mEq/L, or lamotrigine increased progressively to a maintenance dose of 200 mg/d. Our primary outcome measure examined daily data on hypomanic and depressive symptoms. Secondary measures evaluated hypomanic and depressive symptom severity, global functioning, and global improvement in hypomanic and depressive symptoms. FINDINGS/RESULTS: We terminated the trial principally because of severe ongoing side effects experienced by many of those receiving lithium, and with additional concerns about initial severe side effects (including psychosis) experienced by several assigned to lamotrigine. Analyses of study completer data for 28 participants suggested comparable efficacy of both medications; however, lamotrigine had a distinctly lower rate of severe side effects across the study. We calculated that if study trends on outcome measures were valid, then an extremely large sample would be required to demonstrate superiority of either drug, thus making it unlikely that any such adequately powered study will be mounted in the future. IMPLICATIONS/CONCLUSIONS: The small sample size limits any definitive conclusions, but our data suggest that lithium and lamotrigine are likely to have equal efficacy as mood stabilizers for those with a bipolar II condition but that, as maintenance treatments, lithium has more distinctive side effects.