Light therapy for bipolar disorders: Clinical recommendations from the international society for bipolar disorders (ISBD) Chronobiology and Chronotherapy Task Force.

Back to table of contents Previous article Next article Clinical & ResearchFull AccessSpecial Report: Bipolar Disorder II—Frequently Neglected, MisdiagnosedTrisha Suppes, M.D., Ph.D., Holly A. Swartz, M.D., Sara SchleyTrisha SuppesSearch for more papers by this author, M.D., Ph.D., Holly A. SwartzSearch for more papers by this author, M.D., Sara SchleySearch for more papers by this authorPublished Online:23 Feb 2023https://doi.org/10.1176/appi.pn.2023.03.3.22AbstractUnlike its cousin, bipolar I disorder, which has been extensively studied and depicted in popular literature and on screen, bipolar II disorder is poorly understood, underdiagnosed, and insufficiently treated. This has often resulted in an over 10-year delay in diagnosis.Rick Prather/Art by Benjavisa Ruangvaree/Shutterstock/Bipolar II Disorder: Recognition, Understanding, and TreatmentEven experienced clinicians know surprisingly little about bipolar II disorder (BD II), despite its inclusion as a distinct entity in DSM since 1994. An abundance of studies supports conceptualization of BD II as a unique phenotype within the bipolar illness spectrum, although many fail to recognize it as distinct disorder apart from bipolar I disorder (BD I).Alternatively, BD II is considered a “lesser form” of BD I, despite numerous studies showing comparable illness severity and risk of suicide in these two BD subtypes. Perhaps because of its under-recognition, treatment studies of BD II are limited, and too often results from studies of patients with BD I are simply applied to those with BD II with no direct evidence supporting this practice. BD II is an understudied and unmet treatment challenge in psychiatry.In this review, we will provide a broad overview of BD II including differential diagnosis, course of illness, comorbidities, and suicide risk. We will summarize treatment studies specific to BD II, identifying gaps in the literature. This review will reveal similarities between BD I and II, including suicide risk and predominance of depression over the course of illness, but also differences between the phenotypes in treatment response, for example to antidepressants.We highlight the perspective of an expert by experience who discusses her lived experiences of BD II in an accompanying interview (Interview With an Expert by Lived Experience).Diagnosis HistoryAlternating states of mania and melancholia are among the earliest described human diseases, first noted by ancient Greek physicians, philosophers, and poets. Hippocrates (460-337 B.C.E.), who formulated the first known classification of mental disorders, systematically described bipolar mood states: melancholia, mania, and paranoia. More than two millennia later, Emil Kraepelin, recognized as one of the founders of modern psychiatry, described manic-depressive illness as a singular disease characterized by alternating cycles of mania or melancholia. However, Kraepelin was more focused on mood changes and cycling than the polarity of episodes per se. Thus, his concept included what we now term recurrent major depressive disorder (MDD). Nevertheless, his and other formulations from this period provide background for our modern concepts of bipolar disorder, differentiating it from unipolar depression (MDD and related disorders). The hiding in plain sight of patients with BD II was brought to awareness by David L. Dunner, M.D., in the 1960s. When examining a cohort of individuals with mood disorders in a study by the National Institute of Mental Health (NIMH), he identified a subgroup of patients with recurrent episodes of depression who also had a history of at least one period of hypomania and a strong family history of bipolar disorder. This subgroup was found to have a different course of illness compared with those with recurrent depression and a history of mania (BD I). Thanks to this work, BD II was recognized as a distinct disorder, separate from BD I. It finally entered the DSM lexicon in 1994 in DSM-IV and was added to ICD-10 even more recently. Table 1Conceptualization of bipolar disorders continues to evolve as the field learns more; for example, changes were made to the DSM-5 diagnostic criteria for BD such that Criteria A for both mania and hypomania now include increased energy as well as elevated or irritable mood (see Table 1). Thus, BD II is now recognized as a disorder of energy as well as mood.DSM focuses on categorial diagnoses—that is, thresholds for absence or presence of disease. In parallel to this framework, many have argued for considering bipolar disorders along a continuous spectrum of illness. Thus, the term bipolar spectrum is used to describe both the spectrum of severity across BD symptoms as well as combinations of mood symptoms with manic/hypomanic and depressive components. Some refer to BD II as a part of the bipolar spectrum. These concepts reflect a growing awareness that dimensional descriptions of mood disorders may better map onto continuous biological markers of disease, compared with DSM’s categorical approach, but the debate about diagnostic boundaries and disease etiology continues. Importantly, conceptualizations of BD as a spectrum condition versus discrete diagnostic categories (that is, BD I or BD II) are not mutually exclusive but rather speak to ongoing efforts to understand and best describe the phenomenology of BD. Differential Diagnosis The validity of BD II as a separate disorder has been reified through multiple empirical studies. The clinical diagnosis is reliably separable from BD I, as seen in APA clinical trials preparing for DSM-5 and in careful clinical interviews. In DSM-5 field trials to assess reliability of diagnoses, BD I was among the most recognizable, but BD II fell in the acceptable range and well above MDD as a reliable diagnostic entity. Family studies also support the diagnosis of BD II as an independent entity with distinct familial heritability, according to a 1976 study by Dunner et al. and a 1990 study by J. Raymond DePaulo, M.D., et al., and the authors of this report. Finally, genetic studies have found correlations suggesting the heterogeneity between BD I and BD II is “nonrandom,” supporting the concept of distinct conditions. BD II diagnosis requires at least one lifetime hypomanic episode and one major depressive episode. Despite clarity of BD II diagnostic criteria, clinicians struggle to accurately identify it in practice. BD II is often either missed or incorrectly diagnosed, resulting in an over 10-year delay in diagnosis. Difficulties in accurate diagnosis arise from several sources. First, DSM-5 criteria for the depressive phase of BD II are identical to those required for a major depressive episode, which make BD II and MDD cross-sectionally indistinguishable. This is particularly notable as MDD diagnoses make up a substantial percent of the incorrect diagnoses for patients with BD II. Second, hypomania, which by definition is a less severe form of mania, may be difficult for patients to distinguish from a “normal” mood state when accompanied by extra energy and good mood. Third, mixed hypomanic mood states are very common in BD II, and in fact more common than euphoric hypomanic states. Mixed mood states are characterized by the presence of symptoms of opposite polarity during a depressive or hypomanic episode. In a mixed hypomania, patients might believe they are simply irritable and angry in the context of depression rather than recognizing the additional hypomanic symptoms warranting a diagnosis of mixed hypomanic state. Finally, patients rarely present for treatment in the midst of a hypomanic episode, a mood state that is either perceived as ego-syntonic or simply not identified as part of their illness during mixed hypomania. The primary reason patients with BD II seek care is depression. Depression dominates the course of BD II, both in the early and late stages. However, retrospectively identifying episodes of hypomania during a depressive episode can be challenging. Further, many individuals see hypomania (either the euphoric or mixed variant) as part of “normal” mood rather than part of a bipolar spectrum, contributing to misreporting of mood episodes. Especially after unrelenting episodes of depression, it is understandable that many would perceive hypomania as a return to baseline. However, under-recognition of hypomania contributes to incorrect diagnoses. In sum, many individuals with BD II fail to recall, recognize, or report histories of hypomania, leading to an MDD (mis)diagnosis. In psychiatry, all diagnoses are a one-way road. Individuals who have ever met criteria for a manic episode will continue to carry the diagnosis of BD I—even without further manic episodes. Similarly, patients who have a distant episode of hypomania and at least one prior major depressive episode would be considered to have BD II disorder, even in the absence of additional hypomanic episodes that meet symptom and duration criteria. Thus, accurate diagnosis of BD II relies on careful history taking. To improve diagnostic acumen, it is essential that clinicians systematically screen all patients with MDD for BD and ask careful questions about prior episodes of hypomania.Course of Illness and Comorbidity Kraepelin noted before the medication era that the course of illness for patients with BD generally progresses into more persistent and severe depression with aging. While he was primarily referring to manic-depressive illness, which we would call BD I today, the same principle applies to patients with BD II. In the NIMH collaborative study by Lewis Judd, M.D., et al., which included long-term follow-up of up to 20 years, patients with BD II experienced a course of illness characterized by more depressive episodes and fewer well intervals over time. Table 2There is a longstanding debate in the literature whether patients with BD II suffer the same impairments and risks as those with BD I. BD II was previously—and incorrectly—labeled a “less severe” version of BD I. In fact, studies consistently show comparable disease burden in BD I and II. A recent Swedish study by Alina Karanti, M.D., et al. reported higher rates of depressive episodes, illness onset at a younger age, and significantly higher rates of psychiatric comorbidity (anxiety disorders, eating disorders, and ADHD) among patients with BD II compared with those with BD I. In this Swedish sample, (n>8,700) no differences were noted in substance abuse between BD I and BD II. Interestingly, individuals with BD II generally obtained more education and achieved a higher level of independence than those with BD I. Table 3High rates of psychiatric comorbidity in patients with BD II further compound the challenge of differential diagnosis. There is considerable overlap between BD II and anxiety disorders. Attention-deficit/hyperactivity disorder also frequently co-occurs. Approximately 20% of individuals with BD II also meet criteria for borderline personality disorder (BPD), and up to 40% of those with BPD are incorrectly diagnosed as having BD I or II. Tables 2 and 3 show estimated co-occurring psychiatric illnesses for patients with BD II. The diagnosis of BD II requires a careful clinical interview of both past and current symptomatology.Suicide is a significant risk for all patients with BD, and historically patients with BD I were viewed as having a higher risk than BD II due to the extremities of mania. However, data from a number of sources support that suicide risk is high across all patients with BD, and relatively little difference is found in risk for patients with BD I versus BD II. Older studies have suggested this risk may be higher for patients with BD II than BD I, and, indeed, the Swedish bipolar registry database study recently indicated that the rate of suicide attempts was significantly higher in patients with BD II though no data on completed suicides were provided. Overall, the reports from the International Society for Bipolar Disorders Task Force on Suicide found that the risk for suicide was estimated at 164 of 100,000 per year in patients with BD versus 10 of 100,000 per year in the general population (see the reference by Ayal Schaffer, M.D., at the end of this report).Treatment of BD II Treatment guidelines for bipolar disorder often give only a passing nod to distinguishing appropriate treatments for BD I versus BD II. The combined guidelines by the Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) were unusual in making a point of distinguishing the evidence base for BD I versus BD II. They are reported in a 2018 paper by Lakshmi N. Yatham, M.D., et al. (see reference at end of article).These guidelines have a separate section devoted to BD II, and they clearly state that one cannot directly apply studies on patients with BD I to management of patients with BD II. The conclusion of these guidelines is that there are too few controlled studies in patients with BD II to make detailed evidence-based recommendations or develop evidence-based treatment algorithms. Below is a brief overview of our current knowledge of treatments for patients with BD II with medication and/or psychotherapy.Table 4AntidepressantsIt is worth highlighting that, while monotherapy antidepressants would be viewed as an inappropriate practice for patients with BD I depression, studies suggest that the risks and benefits may be different for those with BD I and BD II. In at least one study, risk of switching to hypomania was no greater with lithium than with sertraline monotherapy. Other studies have shown antidepressant monotherapy to be an efficacious monotherapy for BD II. Meta-analyses on risk of antidepressant-induced switches are inconclusive, though the risk of treatment-emergent (hypo)mania due to medication appears to be less in patients with BD II than in patients with BD I depression receiving monotherapy antidepressants. Absent conclusive data on antidepressant switch rates, without a past record of good response to antidepressant monotherapy, current treatment guidelines suggest starting with lithium or a mood stabilizer before adding or switching to antidepressant monotherapy. Additionally, it is important to note that antidepressants in some patients may worsen the overall course of illness and may not be efficacious in some patients with BD II. Any patient who experiences hypomania or mania (which must be distinguished from transient activation symptoms) while on antidepressant medication should be presumed to be on the bipolar spectrum. AntipsychoticsMost atypical antipsychotics have not been studied for the treatment of both BD I and BD II depression, with two notable exceptions. Quetiapine registration trials included individuals with BD II, with post-hoc analyses demonstrating efficacy of quetiapine monotherapy for BD II depression. Lumateperone is the first antipsychotic formally studied for depression response in patients with BD II since quetiapine trials in the early 2000s. Lumateperone, in randomized, controlled trials, performed as well or better for BD II than BD I, according to a 2021 study by Joseph R. Calabrese, M.D., et al. Cariprazine and lurasidone, while both FDA approved to treat bipolar depression, were never formally studied in patients with BD II. There have been case series supporting their use in BD II depression, but no randomized, controlled trials have been carried out. FDA approval to treat patients with BD II depression with lumateperone came in 2021, 15 years after quetiapine was approved. This glacial rate of accruing new FDA-approved compounds for BD II speaks to the need for more studies in this population.Lithium and AnticonvulsantsWhile we might expect lithium to be the frontrunner treatment for managing BD II, study results are varied. Certainly, for hypomania and maintenance treatment of patients with BD II, lithium is a top choice. Lithium has a disappointingly poor track record for treating BD II depression with little indication that response rates are superior to those of antidepressants and atypical antipsychotics. Lamotrigine has good evidence for preventing new depression episodes in the context of BD (both BD II and I). The evidence, however, is less robust for treating acute depression in patients with BD II. In clinical practice, many clinicians prescribe lamotrigine, especially as an adjunctive treatment, for BD II depression, but our ability to make firm recommendations with confidence about lamotrigine is limited.Other TherapiesRapid-acting therapies are on the rise across all treatments for depression. There has been a recent surge of clinical work and research examining transcranial magnetic stimulation (TMS), ketamine, and psychedelics and related compounds. More work is needed specifically focused on BD II depression before firm conclusions may be drawn.There is limited evidence supporting the use of TMS for BD II depression. This evidence base is developing, and more information is forthcoming on the utility of TMS for BD II depression.Ketamine and Psychedelic StudiesRacemic ketamine has been in use for many years as an anesthetic and more recently was approved by the FDA as intranasal esketamine (the s-enantiomer of racemic ketamine) as a treatment for MDD. Three small studies of racemic ketamine suggest that it is effective for BD II depression. A 2022 observational study by Farhan Fancy et al. assessing patients with BD I versus BD II treated with racemic ketamine included more than 60 patients (n=35 BD II). In this largest open observational study to date involving ketamine and BD, patients with BD II demonstrated a more robust response than those with BD I. More studies are in development exploring this new use of an old drug; to date, there is no information on the role of esketamine for bipolar depression, let alone BD II.Recently, it’s been difficult to pick up a journal or look at other media without seeing something about psychedelics and related compounds. There is a surge of interest in psychedelics for MDD, although evidence about their effectiveness is still early and with rare exceptions involves small samples. There is one report on treatment of depression with psilocybin in patients with BD II. In this pilot study, 15 patients with BD II were given a one-time dose of psilocybin (25 mg) and provided preparatory, dosing, and integration therapy consistent with psilocybin studies in MDD. In this small open study by Scott Aaronson, M.D., et al., the rate of response at 3 and 12 weeks was more robust than has been observed in MDD studies. An ongoing study is assessing the durability of patients’ response to psilocybin administered one time for patients with BD II depression. While no notable adverse events or increased mood lability were noted in this small sample to date, further study is needed to assess benefits and harms.PsychotherapyMost information about psychotherapy for BD II is derived from trials of interventions for BD in general that also included a subset of individuals with BD II. A recent systematic review of psychotherapies for BD II identified over 1,000 individuals with BD II who participated in randomized, controlled trials testing psychosocial interventions to treat depression or prevent recurrence of mood symptoms. However, relatively few of these trials—only eight of 27—examined outcomes in those with BD II separately. From this review, we concluded that there is preliminary evidence supporting the efficacy of several evidence-based psychotherapies for BD II: cognitive-behavioral therapy, psychoeducation, family focused therapy, interpersonal and social rhythm therapy (IPSRT), and functional remediation. None of these psychotherapies have undergone rigorous testing in randomized, controlled trials focused specifically on BD II depression, with the exception of IPSRT, pointing to the need for additional research in this area. To our knowledge, no meta-analysis of psychotherapy for BD II has been published. IPSRT, the only psychosocial intervention to be tested in a randomized, controlled trial consisting of participants with BD II only (rather than a mixed patient population of BD I and II), focuses on helping individuals develop more regular routines to stabilize underlying disturbances in circadian rhythms. Because abnormalities in circadian biology have been implicated in the genesis of bipolar disorders, including BD II, a chronobiologic behavioral approach may be especially helpful to mitigate BD II symptoms.ConclusionsBD II is a relatively common disorder affecting approximately 0.4% of the population. Its prevalence, morbidity, and mortality are comparable to that of BD I. Evidence supports conceptualizing BD II as a distinct phenotype, separable from both BD I and MDD. Compared with BD I and MDD, far less is known about BD II and how to treat it. Further, despite being reliably diagnosed in DSM-5 field trials, BD II is frequently misdiagnosed in practice, resulting in a decade-long lag between onset of symptoms and appropriate diagnosis. A neglected condition, BD II causes unnecessary suffering in those who are misdiagnosed or for whom appropriate treatments are unclear. More research is urgently needed to improve identification and treatments for BD II. ■ResourcesDavid L. Dunner, M.D., et al. “Heritable Factors in the Severity of Affective Illness,” Biological Psychiatry, February 1976.J. Raymond DePaulo, M.D., et al. “Bipolar II Disorder in Six Sisters,” Journal of Affective Disorders, August 1990.Lewis Judd, M.D., et al. “Long-Term Symptomatic Status of Bipolar I vs. Bipolar II Disorders,” International Journal of Neuropsychopharmacology, June 2003.Alina Karanti, Ph.D., et al. “Characteristics of Bipolar I and II Disorder: A Study of 8766 Individuals,” Bipolar Disorders, June 2020.Ayal Schaffer, M.D., et al. “A Review of Factors Associated With Greater Likelihood of Suicide Attempts and Suicide Deaths in Bipolar Disorder: Part II of a Report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder,” Australian & New Zealand Journal of Psychiatry, November 2015.Lakshmi N. Yatham, M.D., et al. “Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 Guidelines for the Management of Patients With Bipolar Disorder,” Bipolar Disorders, March 2018.Joseph R. Calabrese, M.D., et al. “Efficacy and Safety of Lumateperone for Major Depressive Episodes Associated With Bipolar I or Bipolar II Disorder: A Phase 3 Randomized Placebo-Controlled Trial,” American Journal of Psychiatry, December 2021.Farhan Fancy, et al. “Real-World Effectiveness of Repeated Ketamine Infusions for Treatment-Resistant Bipolar Depression,” Bipolar Disorders, December 14, 2022.Scott Aaronson, M.D., et al. “COMP360 Psilocybin Therapy Shows Potential in Study in II Bipolar Disorder,” December Suppes, M.D., Ph.D., is a of psychiatry, at the and of the at A. 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BackgroundCognitive impairments are an emerging treatment target in mood disorders, but currently there are no evidence‐based pro‐cognitive treatments indicated for patients in remission. With this systematic review of randomised controlled trials (RCTs), the International Society for Bipolar Disorders (ISBD) Targeting Cognition Task force provides an update of the most promising treatments and methodological recommendations.MethodsThe review included RCTs of candidate pro‐cognitive interventions in fully or partially remitted patients with major depressive disorder or bipolar disorder. We followed the procedures of the Preferred Reporting Items for Systematic reviews and Meta‐Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE and Cochrane Library from January 2015, when two prior systematic reviews were conducted, until February 2021. Two independent authors reviewed the studies with the Revised Cochrane Collaboration's Risk of Bias tool for Randomised trials.ResultsWe identified 16 RCTs (N = 859) investigating cognitive remediation (CR; k = 6; N = 311), direct current or repetitive magnetic stimulation (k = 3; N = 127), or pharmacological interventions (k = 7; N = 421). CR showed most consistent cognitive benefits, with two trials showing improvements on primary outcomes. Neuromodulatory interventions revealed no clear efficacy. Among pharmacological interventions, modafinil and lurasidone showed early positive results. Sources of bias included small samples, lack of pre‐screening for objective cognitive impairment, no primary outcome and no information on allocation sequence masking.ConclusionsEvidence for pro‐cognitive treatments in mood disorders is emerging. Recommendations are to increase sample sizes, pre‐screen for impairment in targeted domain(s), select one primary outcome, aid transfer to real‐world functioning, investigate multimodal interventions and include neuroimaging.

In this article I share my reflections on the 21st Annual Conference of the International Society for Bipolar Disorders, which took place in Australia this year. For a PhD student with a research focus on bipolar disorders like myself, this conference provided an invaluable opportunity to engage with pioneer clinicians and researchers of this field, and interact with people with lived experiences from all around the world. This article will focus on my motivation, expectations and experiences gained attending this conference.

BackgroundThe International Society for Bipolar Disorders Targeting Cognition Task Force recommends the Screen for Cognitive Impairment in Psychiatry (SCIP) to screen for cognitive impairment in bipolar disorder. However, SCIP must be administered by a healthcare professional, which is often impossible due to time and resource constraints. Web-based, self-administered cognition screening tools may enable assessment and monitoring of patients’ cognition at a much larger scale to a reduced cost. For this purpose, we developed the Internet-Based Cognitive Assessment Tool (ICAT) as a modified web-based version of SCIP. This study aimed to investigate the sensitivity and validity of ICAT for cognition assessment in bipolar disorder. MethodThirty-five patients with bipolar disorder in full or partial remission and 35 healthy controls completed ICAT on a computer, the standard paper-and-pencil SCIP and a subjective cognition questionnaire and were rated for mood symptoms and functioning at the Copenhagen Affective Disorders Research Centre. ResultsPatients displayed cognitive impairments compared to controls on the ICAT (t (61)=3.67, p<.001, d=0.93). There was a strong correlation between ICAT and SCIP Total Scores (r(61)=.72, p<.000) and moderate to strong correlations on subtest scores (r=.48-.63, ps<.001). Across all participants, lower ICAT scores correlated with more subjective cognitive complaints (r(59)=-.43, p<.001) and poorer psychosocial functioning (r(62)=-.47, p<.001). ConclusionICAT is a sensitive and valid web-based tool for cognition assessment in patients with bipolar disorder. This highlights ICAT as a novel web-based cognition screening tool that is feasible for largescale assessment and monitoring of cognition in the clinical management of bipolar disorder.

Nine depressed inpatients completed trials with S-adenosylmethionine. Seven showed improvement or remission of their symptoms. As in European studies, no side effects were seen except the apparent induction of mania in two patients with bipolar disorder.

This study investigated the differences in corpus callosum (CC) volumes between women with early-stage and late-stage bipolar I (BP I) disorder using the criteria previously described in the literature. We compared women with early- and late-stage BP I using criteria described in the Staging Systems Task Force Report of the International Society for Bipolar Disorders. We included 20 patients with early stage and 21 patients with late-stage BP I and a group of 25 healthy controls. Patients and controls underwent structural magnetic resonance imaging. Information on the clinical features of bipolar disorder was collected using a standardized questionnaire. Anatomical volumes of five regions of CC were compared between the three groups. Women with late-stage BP I disorder had reduced posterior CC volumes compared with early-stage bipolar I patients and controls (F = 6.05; P = 0.004). The difference was significant after controlling for age, comorbidity with post-traumatic stress disorder, psychotic symptoms during mood episodes, and current use of medication. The posterior CC was significantly decreased in volume in women with late-stage bipolar disorder. These findings suggest that CC may be an anatomical target of neuroprogression in the course of bipolar disorder in women.

There is limited data about the impact of mood disorders treatment guidelines on clinical outcomes. The objective of this study was to investigate the impact of prescribers' adherence to the 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) treatment guidelines recommendations on the readmission rates of patients hospitalized for mania. A retrospective cohort of all individuals admitted due to acute mania to Kingston General Hospital, Kingston, ON, from January 2018 to July 2021 was included in this study. Patient variables and data regarding index admission and subsequent hospitalizations were extracted from medical records up to December 31, 2021. Treatment regimens were classified as first-line, second-line, noncompliant, or no treatment. We explored the associations between treatment regimens and the risk of readmissions using univariate, multivariate, and survival analysis. We identified 211 hospitalizations related to 165 patients. The mean time-to-readmission was 211.8 days (standard deviation [SD] = 247.1); the 30-day rehospitalization rate was 13.7%, and any rehospitalization rate was 40.3%. Compared to no treatment, only first-line treatments were associated with a statistically significant decreased risk of 30-day readmission (odds ratio [OR] = 0.209; 95% CI, 0.058 to 0.670). The risk of any readmission was reduced by first-line (OR = 0.387; 95% CI, 0.173 to 0.848) and noncompliant regimens (OR = 0.414; 95% CI, 0.174 to 0.982) compared to no treatment. On survival analysis, no treatment group was associated with shorter time-to-readmission (log-rank test, p = 0.014) and increased risk of readmission (hazard ratio = 2.27; 95% CI, 1.30 to 3.96) when compared to first-line medications. Treatment with first-line medications was associated with lower 30-day rehospitalization rates and longer time-to-readmission. Physicians' adherence to treatments with higher-ranked evidence for efficacy, safety, and tolerability may improve bipolar disorder outcomes.

BackgroundGiven the likelihood of progressive illness in bipolar disorder (BD), it is important to understand the benefits and risks of interventions administered early in illness course. We conducted a systematic review of the effectiveness of interventions in the early course of BD I or II.MethodsWe completed a systematic search on MEDLINE, PsycINFO, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL and Google Scholar from 1/1/1979 till 14/9/2022. We included controlled trials examining intervention effects on symptomatic, course, functional and tolerability outcomes of patients in the ‘early course’ of BD I or II. We classified patients to be in early course if they (a) were seeking help for the first time for a manic episode, (b) had a lifetime history of up to 3 manic episodes, or (c) had up to 6 lifetime mood episodes. Evidence quality was assessed using the GRADE approach.ResultsFrom 4135 unique publications we included 25 reports representing 2212 participants in 16 randomized studies, and 17,714 participants from nine non-randomized studies. Available evidence suggested that in early illness course, lithium use was associated with lower recurrence risk compared with other mood stabilizers. Mood stabilizers were also associated with better global functioning, compared with the use of antipsychotics in the medium term. While summative findings regarding psychological therapies were limited by heterogeneity, family-focused and cognitive-behavioral interventions were associated with reduced recurrence risk or improved symptomatic outcomes. There was some evidence that the same pharmacological interventions were more efficacious in preventing recurrences when utilized in earlier rather than later illness course.Conclusions and recommendationsWhile there are promising initial findings, there is a need for more adequately powered trials to examine the efficacy and tolerability of interventions in youth and adults in early illness course. Specifically, there is a compelling need to compare the relative benefits of lithium with other pharmacological agents in preventing recurrences. In addition to symptomatic outcomes, there should be a greater focus on functional impact and tolerability. Effective pharmacological and psychological interventions should be offered to those in early course of BD, balancing potential risks using shared decision-making approaches.

Bipolar DisordersVolume 18, Issue S1 p. 26-27 Abstracts Neuroinflammation in Bipolar Disorder: What Can We See? Chair: Bartholomeus C.M. Haarman First published: 03 July 2016 https://doi.org/10.1111/bdi.11_12404Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume18, IssueS1Special Issue: 18th Annual Conference of the International Society for Bipolar Disorders & 8th Biennial Conference of the International Society for Affective Disorders, July 13–16, 2016, Amsterdam, The NetherlandsJuly 2016Pages 26-27 RelatedInformation

Delirium is highly prevalent within critical care and is linked to adverse clinical outcomes, increased mortality and impaired quality of life. Development of delirium is thought to be caused by multiple risk factors, including disruption of the circadian rhythm. Chronotherapeutic interventions, such as light therapy, music and use of eye shades, have been suggested as an option to improve circadian rhythm within intensive care units. This review aims to answer the question: Can chronotherapy reduce the prevalence of delirium in adult patients in critical care? This study is a systematic review of quantitative studies. Six major electronic databases were searched, and a hand search was undertaken using selected key search terms. Research quality was assessed using the critical appraisal skills programme tools. The studies were critically appraised by both authors independently, and data were extracted. Four themes addressing the research question were identified and critically evaluated. Six primary research articles that investigated different methods of chronotherapy were identified, and the results suggest that multi-component non-pharmacological interventions are the most effective for reducing the prevalence of delirium in critical care. The melatonergic agonist Ramelteon demonstrated statistically significant reductions in delirium; however, the reliability of the results in answering the review question was limited by the research design. The use of bright light therapy (BLT) and dynamic light application had mixed results, with issues with the research design and outcomes measured limiting the validity of the findings. Multi-component non-pharmacological interventions, such as noise and light control, can reduce delirium in critical care, whereas other interventions, such as BLT, have mixed outcomes. Melatonin, as a drug, may be a useful alternative to sedative-hypnotics. Chronotherapy can reduce the incidence of delirium within critical care, although further research is warranted. Staff education is essential in the implementation of chronotherapy.

Bipolar disorder (BD) is challenging to treat, and fewer treatments are available for depressive episodes compared to mania. Light therapy is an evidence-based nonpharmacological treatment for seasonal and nonseasonal major depression, but fewer studies have examined its efficacy for patients with BD. Hence, we reviewed the evidence for adjunctive light therapy as a treatment for bipolar depression. We conducted a systematic review of databases from inception to June 30, 2019, for randomized, double-blind, placebo-controlled trials of light therapy in patients with BD (CRD42019128996). The primary outcome was change in clinician-rated depressive symptom score; secondary outcomes included clinical response, remission, acceptability, and treatment-emergent mood switches. We quantitatively pooled outcomes using meta-analysis with random-effects models. We identified seven trials representing 259 patients with BD. Light therapy was associated with a significant improvement in Hamilton Depression Rating Scale score (standardized mean difference = 0.43, 95% confidence interval [CI], 0.04 to 0.82, P = 0.03). There was also a significant difference in favor of light therapy for clinical response (odds ratio [OR] = 2.32; 95% CI, 1.12 to 4.81; P = 0.024) but not for remission. There was no difference in affective switches between active light and control conditions (OR = 1.30; 95% CI, 0.38 to 4.44; P = 0.67). Study limitations included different light treatment parameters, small sample sizes, short treatment durations, and variable quality across trials. There is positive but nonconclusive evidence that adjunctive light therapy reduces symptoms of bipolar depression and increases clinical response. Light therapy is well tolerated with no increased risk of affective switch.

Light-therapy applications for DSM-IV-TR disease entities

Objectives. This systematic review evaluates nonpharmacologic treatments for mental health conditions during the perinatal period (pregnancy and up to 12 months postpartum). We evaluated nonpharmacologic treatments for perinatal individuals with depressive disorders, anxiety disorders, bipolar disorder, post-traumatic stress disorder (PTSD), or obsessive-compulsive disorder (OCD). Data sources and review methods. We searched MEDLINE®, PsycINFO®, Embase®, CINAHL®, the Cochrane Register of Clinical Trials, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from January 1, 2000, to January 17, 2024, to identify relevant randomized controlled trials (RCTs). Nonpharmacologic interventions of interest included, among others, cognitive behavioral therapy (CBT), interpersonal therapy (IPT), exercise, non-directive counseling, behavioral activation, bright light therapy, eye movement desensitization and reprocessing (EMDR), and acupuncture. Outcomes of interest were improvement in scores on psychological assessment tools, cure or resolution of symptoms, suicide-related outcomes, and adherence to treatment. PROSPERO registration number: CRD42023440650. Results. We identified 103 RCTs. Nonpharmacologic treatments were compared to control or each other in 101 RCTs and to pharmacologic treatments in 2 RCTs. The risk of bias was moderate for the majority of included studies, mostly related to lack of blinding. For perinatal individuals with depressive disorders, CBT was more effective than treatment as usual (TAU) to reduce depressive and anxiety symptoms (both moderate strength of evidence [SoE]); IPT was more effective than TAU to treat depressive symptoms (moderate SoE) and anxiety symptoms (low SoE); and both behavioral activation (a CBT technique, with low SoE) and exercise interventions (moderate SoE) were more effective than TAU to reduce depressive symptoms. Remission rates for depressive symptoms were higher with CBT and IPT compared to TAU (both low SoE) and higher with specific acupuncture than nonspecific or sham acupuncture (low SoE). There were no differences between CBT and non-directive counseling (an active patient-led intervention), between counseling and TAU, and between bright light and placebo light therapy (all low SoE). CBT was more effective than TAU to reduce anxiety and depressive symptoms for individuals with combined depressive and anxiety disorders (low SoE). Few (or no) eligible studies evaluated individuals with anxiety disorder, PTSD, OCD, or bipolar disorders, precluding conclusions for these conditions. There was also insufficient evidence for suicide-related outcomes, potential harms of treatment, and adherence to treatment, and for comparisons of nonpharmacologic with pharmacologic treatments. Conclusion. Several nonpharmacologic treatments are more effective than TAU for perinatal mental health conditions, with the strongest evidence for CBT and IPT to reduce depressive symptoms among perinatal individuals with depressive disorders or combined depressive and anxiety disorders. Future research is needed to evaluate the comparative effectiveness of lesser studied nonpharmacologic interventions and lesser studied perinatal mental health conditions.

There was high quality evidence to support the effectiveness of topical azelaic acid, topical ivermectin, brimonidine, doxycycline and isotretinoin for rosacea. Moderate quality evidence was available for topical metronidazole and oral tetracycline. There was low quality evidence for low dose minocycline, laser and intense pulsed light therapy and ciclosporin ophthalmic emulsion for ocular rosacea. Time needed to response and response duration should be addressed more completely, with more rigorous reporting of adverse events. Further studies on treatment of ocular rosacea are warranted.

The Seasonal Pattern Assessment Questionnaire (SPAQ), by Rosenthal et al. (1984), is by far the most used questionnaire to evaluate seasonal effects on mood and behavior. It includes a general seasonality score (GSS), composed of 6 items, from which cutoffs have been established to screen for seasonal affective disorder (SAD). However, it has never been validated in French and associations with circadian rhythm and symptoms of depression and bipolarity remain unclear. In this study, including 165 subjects (95 controls and 70 patients with depression or bipolar disorder), we confirmed the validity of the French version of the SPAQ, with a two-factor structure (a psychological factor: energy, mood, social activity and sleep length; and a food factor: weight and appetite) and a good fit was observed by all indicators. Mood and social activity dimensions were significantly affected by seasons in the depressed/bipolar group and a stronger global seasonality score (GSS) was associated with more severe phenotypes of depression and mania. Subjects meeting SAD and subsyndromal-SAD criteria also showed a delayed circadian rhythm compared to controls. Simple tools, such as the SPAQ, can aid the identification of significant seasonal changes and have direct implications on therapeutics including the use of bright light therapy in order to enhance personalized treatments, but also to prevent adverse seasonal effects.