Key questions on the long term renal effects of lithium: a review of pertinent data.

For over half a century, it has been widely known that lithium is the most efficacious maintenance treatment for bipolar disorder. Despite thorough research on the long-term effects of lithium on renal function, a number of important questions relevant to clinical practice remain. The risk of polyuria, reflecting renal tubular dysfunction, is seen in a substantial proportion of patients treated with long term lithium therapy. The duration of lithium may be the most important risk factor for lithium-induced polyuria. Most, but not all, studies find that lithium is associated with higher rates of chronic kidney disease compared to either age matched controls or patients treated with other mood stabilizers. Age, duration of lithium therapy and medical disorders such as hypertension and diabetes mellitus are risk factors for chronic kidney disease in lithium-treated patients. The relationship between polyuria and chronic kidney disease is inconsistent but poorly studied. Although not all studies agree, it is likely that lithium may increase the risk for end stage renal disease but in a very small proportion of treated patients. Patients whose renal function is relatively preserved will show either no progression or improvement of renal function after lithium discontinuation. In contrast, patients with more renal damage frequently show continued deterioration of renal function even after lithium discontinuation. Optimal management of lithium treatment requires obtaining a baseline measure of renal function (typically estimated glomerular filtration rate [eGFR]) and regular monitoring of eGFR during treatment. Should the eGFR fall rapidly or below 60 ml/minute, patients should consider a consultation with a nephrologist. A decision as to whether lithium should be discontinued due to progressive renal insufficiency should be made using a risk/benefit analysis that takes into account other potential etiologies of renal dysfunction, current renal function, and the efficacy of lithium in that individual patient.

Countering the declining use of lithium therapy: a call to arms.

For over half a century, it has been widely known that lithium is the most efficacious treatment for bipolar disorder. Yet, despite this, its prescription has consistently declined over this same period of time. A number of reasons for this apparent disparity between evidence and clinical practice have been proposed, including a lack of confidence amongst clinicians possibly because of an absence of training and lack of familiarity with the molecule. Simultaneously, competition has grown within the pharmacological armamentarium for bipolar disorder with newer treatments promoting an image of being safer and easier to prescribe primarily because of not necessitating plasma monitoring, which understandably is appealing to patients who then exercise their preferences accordingly. However, these somewhat incipient agents are yet to reach the standard lithium has attained in terms of its efficacy in providing prophylaxis against the seemingly inevitable recrudescence of acute episodes that punctuates the course of bipolar disorder. In addition, none of these mimics have the additional benefits of preventing suicide and perhaps providing neuroprotection. Thus, a change in strategy is urgently required, wherein myths regarding the supposed difficulties in prescribing lithium and the gravity of its side-effects are resolutely dispelled. It is this cause to which we have pledged our allegiance and it is to this end that we have penned this article.

Responding to a Tragedy: Evaluation of a Postvention Protocol Among Adult Psychiatry Residents.

OBJECTIVE: In a time of "zero suicide" initiatives and rising suicide rates, resident physicians are particularly susceptible to the psychological and professional ramifications of patient suicide. An adult psychiatry residency program developed and implemented a postvention protocol to address the impact of patient suicide among resident physicians. The current study is a formal evaluation of a training program's postvention protocol from June 2018 to April 2020. METHODS: Process and outcome indicators were identified to assess protocol implementation and effectiveness. Process indicators included were postvention protocol adherence. Outcome indicators were perceived helpfulness of postvention protocol-related supports, occupational and general health measures, posttraumatic growth, and posttraumatic stress symptoms following resident participation in the postvention protocol. RESULTS: Study response rate was 97% (n = 57/59) and 81% completed the entire survey (n = 48/59). Twenty percent of residents (n = 10/48) experienced patient suicide during residency. Postvention protocol adherence was between 57 and 100%. Protocol-related supports, such as speaking with attendings who had previously experienced an adverse event, were more helpful than other supports (p < 0.01). Compared to residents who had not experienced patient suicide, mean work empowerment, burnout, mental health, and quality of life scores were not significantly different from residents who participated in the postvention protocol (p > 0.05). Posttraumatic growth was positively correlated with self-determination at work (p = 0.01). CONCLUSIONS: The postvention protocol was helpful to residents and potentially effective at mitigating the psychological and professional consequences of patient suicide. Study findings may inform standardization of postvention protocols among psychiatry training programs.

The 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders: Major depression summary.

OBJECTIVES: To provide a succinct, clinically useful summary of the management of major depression, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg2020 ). METHODS: To develop the MDcpg2020 , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg2020 , these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on major depression. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of major depression. RESULTS: The depression summary provides a systematic approach to diagnosis, and a logical clinical framework for management. The latter begins with Actions, which include important strategies that should be implemented from the outset. These include lifestyle changes, psychoeducation and psychological interventions. The summary advocates the use of antidepressants in the management of depression as Choices and nominates seven medications that can be trialled as clinically indicated before moving to Alternatives for managing depression. Subsequent strategies regarding Medication include Increasing Dose, Augmenting and Switching (MIDAS). The summary also recommends the use of electroconvulsive therapy (ECT), and discusses how to approach non-response. CONCLUSIONS: The major depression summary provides up to date guidance regarding the management of major depressive disorder, as set out in the MDcpg2020 . The recommendations are informed by research evidence in conjunction with clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians, but will be of interest to all clinicians and carers involved in the management of patients with depressive disorders.

The 2020 Royal Australian and New Zealand College of psychiatrists clinical practice guidelines for mood disorders: Bipolar disorder summary.

OBJECTIVES: To provide a succinct, clinically useful summary of the management of bipolar disorder, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg2020 ). METHODS: To develop the MDcpg2020 , the mood disorders committee conducted an extensive review of the available literature to develop evidence-based recommendations (EBR) based on National Health and Medical Research Council (NHMRC) guidelines. In the MDcpg2020 , these recommendations sit alongside consensus-based recommendations (CBR) that were derived from extensive deliberations of the mood disorders committee, drawing on their expertise and clinical experience. This guideline summary is an abridged version that focuses on bipolar disorder. In collaboration with international experts in the field, it synthesises the key recommendations made in relation to the diagnosis and management of bipolar disorder. RESULTS: The bipolar disorder summary provides a systematic approach to diagnosis, and a logical clinical framework for management. It addresses the acute phases of bipolar disorder (mania, depression and mixed states) and its longer-term management (maintenance and prophylaxis). For each phase it begins with Actions, which include important strategies that should be implemented from the outset wherever possible. These include for example, lifestyle changes, psychoeducation and psychological interventions. In each phase, the summary advocates the use of Choice medications for pharmacotherapy, which are then used in combinations along with additional Alternatives to manage acute symptoms or maintain mood stability and provide prophylaxis. The summary also recommends the use of electroconvulsive therapy (ECT) for each of the acute phases but not for maintenance therapy. Finally, it briefly considers bipolar disorder in children and its overlap in adults with borderline personality disorder. CONCLUSIONS: The bipolar disorder summary provides up to date guidance regarding the management of bipolar disorder, as set out in the MDcpg2020 . The recommendations are informed by evidence and clinical expertise and experience. The summary is intended for use by psychiatrists, psychologists and primary care physicians but will be of interest to anyone involved in the management of patients with bipolar disorder.

Potential Drug interactions with Drugs used for Bipolar Disorder: A Comparison of 6 Drug Interaction Database Programs.

BACKGROUND: Patients with bipolar disorder frequently experience polypharmacy, putting them at risk for clinically significant drug-drug interactions (DDI). Online drug interaction database programs are used to alert physicians, but there are no internationally recognized standards to define DDI. This study compared the category of potential DDI returned by 6 commercial drug interaction database programs for drug interaction pairs involving drugs commonly prescribed for bipolar disorder. METHODS: The category of potential DDI provided by 6 drug interaction database programs (3 subscription, 3 open access) was obtained for 125 drug interaction pairs. The pairs involved 103 drugs (38 psychiatric, 65 nonpsychiatric); 88 pairs included a psychiatric and nonpsychiatric drug; 37 pairs included 2 psychiatric drugs. Every pair contained at least 1 mood stabilizer or antidepressant. The category provided by 6 drug interaction database programs was compared using percent agreement and Fleiss kappa statistic of interrater reliability. RESULTS: For the 125 drug pairs, the overall percent agreement among the 6 drug interaction database programs was 60%; the Fleiss kappa agreement was slight. For drug interaction pairs with any category rating of severe (contraindicated), the kappa agreement was moderate. For drug interaction pairs with any category rating of major, the kappa agreement was slight. CONCLUSION: There is poor agreement among drug interaction database programs for the category of potential DDI involving psychiatric drugs. Drug interaction database programs provide valuable information, but the lack of consistency should be recognized as a limitation. When assistance is needed, physicians should check more than 1 drug interaction database program.

Smartphones in mental health: a critical review of background issues, current status and future concerns.

There has been increasing interest in the use of smartphone applications (apps) and other consumer technology in mental health care for a number of years. However, the vision of data from apps seamlessly returned to, and integrated in, the electronic medical record (EMR) to assist both psychiatrists and patients has not been widely achieved, due in part to complex issues involved in the use of smartphone and other consumer technology in psychiatry. These issues include consumer technology usage, clinical utility, commercialization, and evolving consumer technology. Technological, legal and commercial issues, as well as medical issues, will determine the role of consumer technology in psychiatry. Recommendations for a more productive direction for the use of consumer technology in psychiatry are provided.

The existential crisis of bipolar II disorder.

The issue of categorical vs. dimensional classification of bipolar disorder continues to generate controversy as it has for generations. Despite the evidence that no psychiatric disorder has discrete boundaries separating pathological and nonpathological states, and within a disorder, no clear differences separate subtypes-which would suggest a more dimensional approach-there are valid reasons to continue with our current categorical system, which distinguishes bipolar I from bipolar II disorder. Complicating the issue, a number of interested constituencies, including patients and their families, clinicians, scientists/researchers, and governmental agencies and insurance companies have different interests and needs in this controversy. This paper reviews both the advantages and disadvantages of continuing the bipolar I/bipolar II split vs. redefining bipolar disorder as one unified diagnosis. Even with one unified diagnosis, other aspects of psychopathology can be used to further describe and classify the disorder. These include both predominant polarity and categorizing symptoms by ACE-activity, cognition and energy. As a field, we must decide whether changing our current classification before we have a defining biology and genetic profile of bipolar disorder is worth the disruption in our current diagnostic system.

Enhancing return to work or school after a first episode of schizophrenia: the UCLA RCT of Individual Placement and Support and Workplace Fundamentals Module training.

BACKGROUND: This study evaluated in a rigorous 18-month randomized controlled trial the efficacy of an enhanced vocational intervention for helping individuals with a recent first schizophrenia episode to return to and remain in competitive work or regular schooling. METHODS: Individual Placement and Support (IPS) was adapted to meet the goals of individuals whose goals might involve either employment or schooling. IPS was combined with a Workplace Fundamentals Module (WFM) for an enhanced, outpatient, vocational intervention. Random assignment to the enhanced integrated rehabilitation program (N = 46) was contrasted with equally intensive clinical treatment at UCLA, including social skills training groups, and conventional vocational rehabilitation by state agencies (N = 23). All patients were provided case management and psychiatric services by the same clinical team and received oral atypical antipsychotic medication. RESULTS: The IPS-WFM combination led to 83% of patients participating in competitive employment or school in the first 6 months of intensive treatment, compared with 41% in the comparison group (p < 0.005). During the subsequent year, IPS-WFM continued to yield higher rates of schooling/employment (92% v. 60%, p < 0.03). Cumulative number of weeks of schooling and/or employment was also substantially greater with the IPS-WFM intervention (45 v. 26 weeks, p < 0.004). CONCLUSIONS: The results clearly support the efficacy of an enhanced intervention focused on recovery of participation in normative work and school settings in the initial phase of schizophrenia, suggesting potential for prevention of disability.

Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms.

BACKGROUND: Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression. METHODS: Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI). RESULTS: Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877). CONCLUSIONS: This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients. Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012-Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839.

Automation to optimise physician treatment of individual patients: examples in psychiatry.

There is widespread agreement by health-care providers, medical associations, industry, and governments that automation using digital technology could improve the delivery and quality of care in psychiatry, and reduce costs. Many benefits from technology have already been realised, along with the identification of many challenges. In this Review, we discuss some of the challenges to developing effective automation for psychiatry to optimise physician treatment of individual patients. Using the perspective of automation experts in other industries, three examples of automation in the delivery of routine care are reviewed: (1) effects of electronic medical records on the patient interview; (2) effects of complex systems integration on e-prescribing; and (3) use of clinical decision support to assist with clinical decision making. An increased understanding of the experience of automation from other sectors might allow for more effective deployment of technology in psychiatry.

Antidepressants in Bipolar Depression: An Enduring Controversy.

(Reprinted with permission from Int J Bipolar Discord (2018) 6:25).

Antidepressants in bipolar depression: an enduring controversy.

The proper place and the optimal use of antidepressants in treating bipolar depression continues to be an area of great interest and greater controversy with passionate opinions more common than good studies. Even the handful of meta-analyses in the area disagree with each other. Overall, the evidence that antidepressants are effective in treating bipolar depression is weak. Additionally, many experts and clinicians worry greatly about the capacity of antidepressants to cause affective switching or mood destabilization. Yet, in short term controlled studies, with most patients also taking mood stabilizers, antidepressants are not associated with switches into mania/hypomania. Evidence of cycle acceleration with antidepressants primarily reflects treatment with older antidepressants, e.g., tricyclics. Similar evidence with modern antidepressants such as selective serotonin reuptake inhibitors (SSRIs) is lacking. The key questions should not be: are antidepressants effective in bipolar depression?; And: do antidepressants worsen the course of bipolar disorder? Rather, the question should be focused on subgroups: for which patients are antidepressants helpful and safe, and for which patients will they be harmful? Predictors of affective switching with antidepressants include: bipolar I disorder (vs. bipolar II), mixed features during depression, tricyclics vs. modern antidepressants, rapid cycling and possibly a history of drug abuse, especially stimulant abuse. Additionally, a number of recent studies have demonstrated both the safety and efficacy of antidepressant monotherapy in treating bipolar II depression. Finally, a subgroup of bipolar individuals need antidepressants in addition to mood stabilizers as part of an optimal maintenance treatment regimen.