Abstract Background Lithium is an effective mood stabilizer that is used principally for the management of bipolar disorder (BD). Its administration is complex and often requires sophisticated ...management and assiduous monitoring. When considering the use of lithium therapy for bipolar disorder, clinicians are advised to refer to recommendations outlined in clinical practice guidelines (CPGs); but because of varying emphasis placed by different international CPGs, recommendations addressing the practical use of lithium lack consistency. Method In order to inform clinicians of optimal lithium therapy for bipolar disorder, we compared and synthesized recommendations for the treatment of bipolar disorder made by recognized CPGs internationally. We conducted a search of the literature and extracted guidance across multiple clinical issues, including clinical indications, disorder subtypes, additional uses, special populations, practical aspects, and side effects. Results Collectively, CPGS consider lithium most robustly as a first-line intervention for maintenance treatment of bipolar disorder and strongly for the treatment of mania, with relatively modest support for the management of acute bipolar depression. Additionally, there is consensus across the CPGs that lithium tangibly reduces the risk of suicide. Generally, CPGs provide guidance on the many facets of initiating and maintaining patients on lithium therapy, but individually the CPGs varied in terms of depth and practical guidance they provide across these areas. However, consensus was established across many key areas of practice such as the ideal lithium plasma concentration for maintenance and monitoring(0.6 – 0.8 mmol/L), along with the need for regular monitoring of renal and endocrine function. However, with more complex aspects (e.g., atypical presentations) and in special populations (e.g., youth; pregnancy and post-partum; older adults), guidance varied considerably and clear consensus recommendations were more difficult to achieve. In younger adults desirable plasma lithium levels of 0.6–0.8 mmol/L can perhaps be achieved with comparatively lower doses and in the very elderly it may be prudent to target lower plasma levels in the first instance. These are important practical points for consideration that, along with many others offered throughout the article, should assist clinicians in dissecting the more complex aspects of management with greater precision. Limitations This review was limited to CPGs written in English. CPGs are themselves limited by reliance on evidence that often has little resemblance to real-world presentations. An important area that is not sufficiently addressed in the CPGs is clear guidance on the cessation of lithium therapy. Conclusions Further research is needed on many aspects of lithium therapy and this alongside existing knowledge needs to be used more consistently to inform CPGs, which should also incorporate empirical evidence and clinical experience. The recommendations in this paper provide a useful synthesis of guidance available currently.
The Royal College of Psychiatry journals have an outstanding reputation for excellence, integrity and impact in psychiatry. Facilitated by Cambridge University Press, which is equally steeped in ...tradition, the family of College journals remains committed to enriching our understanding of mental science and exploring the clinical issues that matter.
Objectives:
To provide advice and guidance regarding the management of mood disorders, derived from scientific evidence and supplemented by expert clinical consensus to formulate s that maximise ...clinical utility.
Methods:
Articles and information sourced from search engines including PubMed, EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (e.g. books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Relevant information was appraised and discussed in detail by members of the mood disorders committee, with a view to formulating and developing consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous consultation and external review involving: expert and clinical advisors, key stakeholders, professional bodies and specialist groups with interest in mood disorders.
Results:
The Royal Australian and New Zealand College of Psychiatrists mood disorders clinical practice guidelines 2020 (MDcpg2020) provide up-to-date guidance regarding the management of mood disorders that is informed by evidence and clinical experience. The guideline is intended for clinical use by psychiatrists, psychologists, primary care physicians and others with an interest in mental health care.
Conclusion:
The MDcpg2020 builds on the previous 2015 guidelines and maintains its joint focus on both depressive and bipolar disorders. It provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus.
Mood disorders committee:
Gin S Malhi (Chair), Erica Bell, Darryl Bassett, Philip Boyce, Richard Bryant, Philip Hazell, Malcolm Hopwood, Bill Lyndon, Roger Mulder, Richard Porter, Ajeet B Singh and Greg Murray.
Objectives
Bipolar disorder (BD) is associated with significant impairment in cognitive performance across multiple domains of function that often persist after clinical recovery. It remains unclear, ...however, as to whether this process is related to the clinical status of BD being depressed, manic/hypomanic, or euthymic. In this review, we examine the literature on the cross‐sectional and longitudinal relationships between cognitive function and general function depending on the clinical phase of BD.
Methods
A systematic review of original research that studied both cognitive function and general function in adults (18–60 years), restricted to BD, was conducted in a total of 18 studies meeting inclusion/exclusion criteria.
Results
Results show cross‐sectional and prospective relationships between cognitive function and general function in patients with BD in both symptomatic and euthymic patients with BD. While studies using general measures of function (e.g., Global Assessment of Function scale) show more inconsistent associations with cognitive function, those employing assessments of domain specific function, suggest a consistent relationship between social and occupational function and cognitive performance. Executive function is commonly affected by cognitive deficits in these patients, but in addition a variety of domains show associations with functional outcomes (e.g., social function, occupational function). Notably, the emerging evidence suggests that cognitive function may be a better predictor of future general function than affective symptom severity.
Conclusions
Despite some inconsistencies, in sum the literature on the relationship between cognitive function and general function in BD implicates both cross‐sectional and longitudinal associations, both in symptomatic and euthymic patients with BD. And in terms of capturing these changes functional scales in particular domain‐specific measures seem superior to general measures.
Lithium is the most effective and well established treatment for bipolar disorder, and it has a broad array of effects within cellular pathways. However, the specific processes through which ...therapeutic effects occur and are maintained in bipolar disorder remain unclear. This paper provides a timely update to an authoritative review of pertinent findings that was published in CNS Drugs in 2013. A literature search was conducted using the Scopus database, and was limited by year (from 2012). There has been a resurgence of interest in lithium therapy mechanisms, perhaps driven by technical advancements in recent years that permit the examination of cellular mechanisms underpinning the effects of lithium-along with the reuptake of lithium in clinical practice. Recent research has further cemented glycogen synthase kinase 3β (GSK3β) inhibition as a key mechanism, and the inter-associations between GSK3β-mediated neuroprotective, anti-oxidative and neurotransmission mechanisms have been further elucidated. In addition to highly illustrative cellular research, studies examining higher-order biological systems, such as circadian rhythms, as well as employing innovative animal and human models, have increased our understanding of how lithium-induced changes at the cellular level possibly translate to changes at behavioural and clinical levels. Neural circuitry research is yet to identify clear mechanisms of change in bipolar disorder in response to treatment with lithium, but important structural findings have demonstrated links to the modulation of cellular mechanisms, and peripheral marker and pharmacogenetic studies are showing promising findings that will likely inform the exploration for predictors of lithium treatment response. With a deeper understanding of lithium's therapeutic mechanisms-from the cellular to clinical levels of investigation-comes the opportunity to develop predictive models of lithium treatment response and identify novel drug targets, and recent findings have provided important leads towards these goals.
Objectives:
To provide guidance for the management of mood disorders, based on scientific evidence supplemented by expert clinical consensus and formulate recommendations to maximise clinical ...salience and utility.
Methods:
Articles and information sourced from search engines including PubMed and EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (MDC) (e.g., books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Information was reviewed and discussed by members of the MDC and findings were then formulated into consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous successive consultation and external review involving: expert and clinical advisors, the public, key stakeholders, professional bodies and specialist groups with interest in mood disorders.
Results:
The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (Mood Disorders CPG) provide up-to-date guidance and advice regarding the management of mood disorders that is informed by evidence and clinical experience. The Mood Disorders CPG is intended for clinical use by psychiatrists, psychologists, physicians and others with an interest in mental health care.
Conclusions:
The Mood Disorder CPG is the first Clinical Practice Guideline to address both depressive and bipolar disorders. It provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus.
Mood Disorders Committee:
Professor Gin Malhi (Chair), Professor Darryl Bassett, Professor Philip Boyce, Professor Richard Bryant, Professor Paul Fitzgerald, Dr Kristina Fritz, Professor Malcolm Hopwood, Dr Bill Lyndon, Professor Roger Mulder, Professor Greg Murray, Professor Richard Porter and Associate Professor Ajeet Singh.
International expert advisors:
Professor Carlo Altamura, Dr Francesco Colom, Professor Mark George, Professor Guy Goodwin, Professor Roger McIntyre, Dr Roger Ng, Professor John O’Brien, Professor Harold Sackeim, Professor Jan Scott, Dr Nobuhiro Sugiyama, Professor Eduard Vieta, Professor Lakshmi Yatham.
Australian and New Zealand expert advisors:
Professor Marie-Paule Austin, Professor Michael Berk, Dr Yulisha Byrow, Professor Helen Christensen, Dr Nick De Felice, A/Professor Seetal Dodd, A/Professor Megan Galbally, Dr Josh Geffen, Professor Philip Hazell, A/Professor David Horgan, A/Professor Felice Jacka, Professor Gordon Johnson, Professor Anthony Jorm, Dr Jon-Paul Khoo, Professor Jayashri Kulkarni, Dr Cameron Lacey, Dr Noeline Latt, Professor Florence Levy, A/Professor Andrew Lewis, Professor Colleen Loo, Dr Thomas Mayze, Dr Linton Meagher, Professor Philip Mitchell, Professor Daniel O’Connor, Dr Nick O’Connor, Dr Tim Outhred, Dr Mark Rowe, Dr Narelle Shadbolt, Dr Martien Snellen, Professor John Tiller, Dr Bill Watkins, Dr Raymond Wu.
•Substance use disorders (SUDs) are highly prevalent in major depression.•The pooled prevalence of any SUD in major depressive disorder (MDD) was 0.250.•Alcohol use disorder (AUD) had the highest ...pooled prevalence of 0.208.•Males had higher rates of alcohol use compared to females.•Rates of AUD were found to be equally high in MDD and dysthymic disorder.•Comorbid rates of SUD and MDD have changed little over the last three decades.
Comorbidity between Substance Use Disorders (SUDs) and major depression is highly prevalent. This systematic review and meta-analysis aimed to estimate the prevalence of SUDs in subjects diagnosed with a major depressive disorder (MDD) in community, inpatient and outpatient settings.
A comprehensive literature search of Medline, EMBASE, PsycINFO and CINAHL databases was conducted from 1990 to 2019. Prevalence of co-morbid SUDs and MDD were extracted and odds ratios (ORs) were calculated using random effects meta-analysis.
There were 48 articles identified by electronic searches with a total sample size of 348,550 subjects that yielded 14 unique epidemiological studies, 2 national case registry studies, 7 large cohort studies and 20 clinical studies using in- or out-patients. The prevalence of any SUD in individuals with MDD was 0.250. Maximum prevalence was found with alcohol use disorder (0.208), followed by illicit drug use disorder (0.118) and cannabis use disorder (0.117). Meta-analysis showed the pooled variance of any AUD in men with MDD was 36%, which was significantly higher than that for females with MDD (19%, OR 2.628 95% CI 2.502, 2.760).
Few studies were published over the last decade so current prevalence rates of SUD in MDD are needed. Meta-analysis revealed that SUDs in MDD are highly prevalent and rates have not changed over time. The persistently high prevalence suggests there is an urgent need for more informative studies to help develop better prevention and treatment options for reducing prevalence of SUDs in persons with major depression and co-morbid disorders.
N -Acetylcysteine (NAC) targets a diverse array of factors germane to the pathophysiology of multiple neuropsychiatric disorders including glutamatergic transmission, the antioxidant glutathione, ...neurotrophins, apoptosis, mitochondrial function, and inflammatory pathways. This review summarises the areas where the mechanisms of action of NAC overlap with known pathophysiological elements, and offers a précis of current literature regarding the use of NAC in disorders including cocaine, cannabis, and smoking addictions, Alzheimer's and Parkinson's diseases, autism, compulsive and grooming disorders, schizophrenia, depression, and bipolar disorder. There are positive trials of NAC in all these disorders, and although many of these require replication and are methodologically preliminary, this makes it one of the most promising drug candidates in neuropsychiatric disorders. The efficacy pattern of NAC interestingly shows little respect for the current diagnostic systems. Its benign tolerability profile, its action on multiple operative pathways, and the emergence of positive trial data make it an important target to investigate.
