{"title":"ADHD medications for cognitive impairment in bipolar disorders","authors":"Virginio Salvi","doi":"10.1111/bdi.13459","DOIUrl":"10.1111/bdi.13459","url":null,"abstract":"<p>People with bipolar disorders (BD) often display cognitive dysfunction, especially in verbal and working memory, processing speed and executive functions, which lead to poor occupational outcomes even more than residual symptoms.<span><sup>1</sup></span> Consequently, there is a constant effort to find treatments that might improve cognition and eventually global functioning in BD.</p><p>Several observations point to hypodopaminergic state as a driver of cognitive impairment in BD; therefore, increasing dopamine levels has been attempted as a strategy to ameliorate cognition.</p><p>Both stimulant and non-stimulant ADHD medications increase dopamine and norepinephrine brain levels, making them good candidates for treating cognitive dysfunction in BD. However, there has been a concern as to whether these medications are well tolerated, and specifically whether their use may induce (hypo)manic symptoms or episodes in persons with BD.</p><p>Stemming from these premises, the Targeting Cognition task force of the International Society for Bipolar Disorders (ISBD) conducted a systematic review on the efficacy and tolerability of ADHD medications in treating cognitive dysfunction in BD.<span><sup>2</sup></span></p><p>The review reassures on tolerability, concluding that when BD is properly stabilized, the risk of treatment-emergent manic episodes due to the use of stimulant or non-stimulant ADHD medications is not higher than with placebo or other control conditions. Thus, methylphenidate, lisdexamfetamine, armodafinil, modafinil or bupropion can be safely employed unless BD is pharmacologically stabilized. Beyond the reviewed evidence coming from Randomized Controlled Trials, a large Swedish registry study on 2307 adults with BD who later initiated methylphenidate for concurrent ADHD found no evidence for an association between methylphenidate and treatment-emergent mania among those on concomitant mood stabilizers. On the other hand, those treated with the stimulant alone had a 6.7 times increased rate of manic episodes within 3 months of medication initiation.<span><sup>3</sup></span> Hence, we might say that there is sufficient evidence not to discourage the use of ADHD medications in adequately stabilized BD.</p><p>However, the most compelling research aim was to review the efficacy of ADHD medications as cognitive enhancers in BD: the authors, based on evidence coming from three studies, concluded that there is insufficient data to assert that ADHD medications can improve cognition in BD. The first reviewed study was designed to assess the efficacy of adjunctive methylphenidate in reducing manic symptoms in acutely manic subjects. For safety reasons, the study lasted 2.5 days, after which methylphenidate was deemed ineffective and therefore stopped. The very short period of observation likely speaks for the observed lack of cognitive effect of methylphenidate. The second study, which evaluated the pro-cognitive effects of clonidine on manic subj","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"26 6","pages":"620-621"},"PeriodicalIF":5.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.13459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Revisiting cariprazine for bipolar I disorder maintenance treatment","authors":"Maxwell Z. Price, Richard L. Price","doi":"10.1111/bdi.13453","DOIUrl":"10.1111/bdi.13453","url":null,"abstract":"<p>We read with interest the study by McIntyre et al. “Cariprazine as a maintenance therapy in the prevention of mood episodes in adults with bipolar I disorder”<span><sup>1</sup></span> concluding that cariprazine was not superior to placebo in relapse prevention. However, based on our clinical experience successfully utilizing cariprazine to treat acute depressive, manic, and mixed episodes of bipolar I disorder, we have also found cariprazine helpful in preventing recurrence for the vast majority of patients who have remained on cariprazine over the past decade, when the dosing regimen is individualized to meet their needs.<span><sup>2</sup></span> Unfortunately, this was not the case for this study protocol, which may have contributed to an incorrect conclusion.</p><p>As a partial dopamine agonist with eightfold greater affinity for D3 than D2 receptors, and higher D3 affinity than one's endogenous dopamine,<span><sup>3</sup></span> cariprazine is a dynamic medication whereby finding the correct dose is critical to optimizing effects and minimizing side effects. Lower doses function as a dopamine agonist such that 1.5 mg daily can rapidly improve bipolar I depression within 2 weeks.<span><sup>3</sup></span> In contrast, higher approved doses, such as 4.5 mg and 6 mg, which function as a dopamine antagonist, may be required for rapid control of mania and psychosis over several days.<span><sup>3</sup></span> At times, patients who are stable on 1.5 mg cannot tolerate 3 mg due to akathisia. The 3 mg dose lies somewhere in between; it may be too dopamine blocking for some depressed patients yet insufficient for control of mania and psychosis. The unique pharmacodynamic features of cariprazine allow the prescriber to dial in the precise dose to meet patients' needs: lower doses for bipolar I depression; higher doses for bipolar mania and mixed episodes, potentially achieving full spectrum coverage as a relatively well-tolerated monotherapy.</p><p>Another unique aspect of cariprazine is the exceedingly long half-life of its active metabolites, and the protracted time to reach a steady state, which can surpass 12 weeks.<span><sup>3</sup></span> Occasionally, dose reduction is appropriate for late-occurring side effects, such as insomnia. It can also take up to 12 weeks following discontinuation for total cariprazine metabolites to become undetectable, and even longer for poor 3A4 metabolizers or for those taking 3A4 inhibitors,<span><sup>3</sup></span> such as cannabis (permitted in this study). This feature enables effective intermittent dosing schedules for those who either cannot tolerate daily dosing,<span><sup>3</sup></span> prefer intermittent dosing, or face challenges with adherence. Unlike many other antipsychotics, we do not typically encounter withdrawal effects with cariprazine due to low binding affinities for acetylcholine and histamine.<span><sup>3</sup></span> In our experience, bipolar I disorder patients who have taken cariprazine ","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"26 5","pages":"491-492"},"PeriodicalIF":5.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.13453","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Haenen, A. M. Kamperman, A. Prodan, W. A. Nolen, M. P. Boks, R. Wesseloo
{"title":"The efficacy of lamotrigine in bipolar disorder: A systematic review and meta-analysis","authors":"N. Haenen, A. M. Kamperman, A. Prodan, W. A. Nolen, M. P. Boks, R. Wesseloo","doi":"10.1111/bdi.13452","DOIUrl":"10.1111/bdi.13452","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To provide up-to-date clinical guidance on the efficacy of lamotrigine in bipolar disorder (BD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eligible studies were identified during a systematic literature search according to PRISMA-guidelines. We included randomized controlled trials (RCTs) and cohort studies that quantitatively assessed lamotrigine's efficacy in BD. We divided the included studies into three groups: 1. acute treatment of depression, 2. acute treatment of mania and hypomania, and 3. maintenance treatment. Analyses were stratified by control group (placebo vs active comparator) and treatment strategy (monotherapy vs add-on treatment).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We included 20 RCTs (<i>n</i> = 1166 lamotrigine users) and 20 cohort studies (<i>n</i> = 11,141 lamotrigine users). Twenty-four of these studies were included in meta-analyses. During depressive episodes, greater decreases in depressive symptomatology were associated with initiation of lamotrigine as add-on treatment than with placebo (SMD −0.30 [95% CI = −0.51, −0.10], df = 3, <i>p</i> = 0.004). Decreases in depressive symptomatology did not differ significantly between lamotrigine and the active comparator (SMD −0.28 [95% CI = −1.06, 0.50], df = 3, <i>p</i> = 0.488).</p>\u0000 \u0000 <p>As a maintenance treatment, lamotrigine was associated with a significantly lower relapse/recurrence rate than placebo (risk ratio (RR) 0.84 [95% CI = 0.71, 0.99], df = 2, <i>p</i> = 0.037). Relapse/recurrence rates did not differ significantly between lamotrigine and lithium (RR 1.06 [95% CI = 0.89, 1.25], df = 2, <i>p</i> = 0.513). A qualitative assessment of high-quality register-based studies found that lamotrigine was associated with lower hospital admission rates than other commonly used treatment regimes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There is substantial evidence for the efficacy of lamotrigine in BD, specifically as add-on treatment during acute depressive episodes and as maintenance treatment for preventing relapse and recurrence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"26 5","pages":"431-441"},"PeriodicalIF":5.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sacha Koutsikas, Antoine Yrondi, Laura Hatchondo, Rachel Debs
{"title":"Back to the future: May Kleine-Levin syndrome be an emerging psychiatric disorder?","authors":"Sacha Koutsikas, Antoine Yrondi, Laura Hatchondo, Rachel Debs","doi":"10.1111/bdi.13455","DOIUrl":"10.1111/bdi.13455","url":null,"abstract":"<p>Since the 20th century, atypical cases of recurrent hypersomnia are no longer related to mood disorders but are grouped together in the new Kleine-Levin syndrome (KLS).</p><p>Between neurology and psychiatry, the KLS symptoms include hypersomnia (up to 20 h of sleep/day), which may or may not be accompanied by disinhibition, derealisation, extreme apathy, cognitive dysfunction, childishness, anxiety, hallucinations, ideas of reference and delusions of grandeur. At the point of diagnosis, additional examinations (biology, imaging) are not diagnostic and are even less pathognomonic, just as is the case for psychiatric disorders.</p><p>The indication for long-term treatment based on thymoregulatory depends on the intensity and frequency of the episodes.</p><p>Today, the international literature insists on a dichotomy between BPD and very recent KLS despite the redundancy of such a distinction<span><sup>1</sup></span> (Figure 1).</p><p>KLS is commonly recognised as a neurological disease with inflammatory markers on functional imaging during episodes, between episodes and post-mortem. This has enabled it to be distinguished from mood disorders. However, recent studies on BPD have shown that it too.</p><p>In addition, studies of both patients with BPD and their relatives have found that cognitive impairment and sleep problems appear 5–6 years before the first decompensation.<span><sup>2</sup></span></p><p>At the same time, studies report that KLS leads to psychiatric decompensation in 20% of cases, with some cases being premorbid.<span><sup>3</sup></span> Following the revision of the criteria for KLS,<span><sup>4</sup></span> the number of cases being diagnosed has been increasing. Of all newly diagnosed cases of KLS, the diagnosis is in doubt in 20% of these cases, that is, in those involving latent or overt psychiatric comorbidities. These cases could, therefore, involve undiagnosed psychiatric pathologies.</p><p>While there may be doubt regarding 20% of KLS cases, 80% are genuine. The question then arises as to which symptoms are useful in diagnosis: the old triad or the new paradigm of the 2000s?</p><p>For Kleine, a neurologist, Levin, a psychiatrist, and their predecessors, it was a syndrome, not a disorder, that they were investigating. Ultimately, it was not a disorder that they were referring to, but rather an invitation for the scientific community to communicate with each other and a request for help with treatment.</p><p>Recent studies have shown that the onset of BPD is associated with frustrating and unspecific symptoms, particularly anxiety, dissociative symptoms, and issues with sleeping. The mood-related component appears much later.<span><sup>5</sup></span></p><p>One might wonder why the scientific community is resistant to the idea of classifying KLS as a mood disorder, given the heterogenic nature of bipolar spectrum disorder, which covers different types of BPD (Akiskal classification).</p><p>In practice, these are young patien","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"26 6","pages":"617-619"},"PeriodicalIF":5.0,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.13455","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Featured Cover","authors":"Anne Duffy, Paul Grof","doi":"10.1111/bdi.13456","DOIUrl":"https://doi.org/10.1111/bdi.13456","url":null,"abstract":"<p>The cover image is based on the Commentary <i>Advancing clinical practice and discovery research through revised taxonomy: Case in point bipolar disorder diagnosis</i> by Anne Duffy and Paul Grof, https://doi.org/10.1111/bdi.13415.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"26 3","pages":"i"},"PeriodicalIF":5.4,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.13456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140919234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nausicaa Christodoulou, Karine Laaidi, Pierre A. Geoffroy
{"title":"Eco-anxiety: Towards a medical model and the new framework of ecolalgia","authors":"Nausicaa Christodoulou, Karine Laaidi, Pierre A. Geoffroy","doi":"10.1111/bdi.13446","DOIUrl":"10.1111/bdi.13446","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>In the context of global warming, new terms emerged in the global media and in the psychology field to embody the negative feelings which come along with climate change such as ‘eco-anxiety’ or ‘solastalgia’. The pathological character of these emotions is denied although medical opinion is often required for helping people to handle them. Also, no proper medical framework in the field exists to study and care for these patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this narrative review, we aim to (1) analyse the concept of eco-anxiety by focusing on its history and developed concepts, (2) summarize the different scales built to assess eco-anxiety and (3) propose a new medical framework.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We came out with a framework based on the transformation of a physiological adaptative behaviour the ‘eco-distress’. It is composed of three dimensions: eco-anger, eco-grief and eco-worry, it is not debilitating in daily life and promotes coping strategies such as management of negative emotions and pro-environmental behaviours (PEB). It can transform itself into a pathological state, the ‘ecolalgia’, composed of two core dimensions: eco-anxiety and eco-depression, leading to functional impairment and decrease in PEB. If ecolalgia maintains over 15 days, we propose to consider it as a full psychiatric disorder needing medical advice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This new framework enables a novel approach that is necessary for the improved management of mental health issues related to climate change.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"26 6","pages":"532-547"},"PeriodicalIF":5.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"First manic episode induced by abrupt discontinuation of sertraline in a patient with OCD: A case report","authors":"Bedirhan Şenol, Rabia Nazik Ekinci, Erol Göka","doi":"10.1111/bdi.13450","DOIUrl":"10.1111/bdi.13450","url":null,"abstract":"","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"26 6","pages":"630-632"},"PeriodicalIF":5.0,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-term management of a perpetual mixed state with minimal medication and sleep regulation","authors":"Verinder Sharma, Katelyn N. Wood","doi":"10.1111/bdi.13454","DOIUrl":"10.1111/bdi.13454","url":null,"abstract":"<p>A 72-year-old married nurse was referred to our clinic 16 years ago for the management of treatment-resistant bipolar II disorder. The illness began after the birth of her first child when she was 27 years old. She had a recurrence of depression after the birth of her other two children. Each postpartum episode lasted 4–6 weeks and remitted spontaneously. She first sought professional help when she was 45, and the following year was hospitalized for depression for the first time. In 8 years, she required 13 hospital admissions (see Figure 1), including one hospitalization after an intentional drug overdose. She spent a total of 382 days with hospitalizations ranging in duration between 3 and 83 days. She had to quit her job due to the persistent and disabling nature of the disorder. Following her last hospitalization, her mood continued to fluctuate between periods of mixed depression and hypomania without intervening euthymic intervals. Due to rapid shifts in her moods, she was also thought to have borderline personality disorder and histrionic traits. Her family history was positive for bipolar disorder in at least nine members across three generations including her grandfather, grandmother, aunts, mother, brother, and daughter. Several family members had been treated with lithium and some had received electroconvulsive therapy.</p><p>Past efforts to treat the mood disorder involved trials of antidepressants including amitriptyline, fluvoxamine, nefazodone, moclobemide, and desipramine; lithium, carbamazepine, valproic acid, aripiprazole, paliperidone, methylphenidate, and benzodiazepines. Pindolol was used to augment some of the antidepressants. She developed tachyphylaxis to some of the antidepressants while others were ineffective. She had both unilateral and bilateral electroconvulsive therapy (a total of 19 treatments) that led to confusion and made her more anxious and agitated. Except for amitriptyline, the doses of antidepressants were either adequate or high (e.g., fluvoxamine 400 mg daily). She developed neutropenia requiring discontinuation of carbamazepine; valproate was ineffective, and there was no response to two trials of lithium in combination with antidepressants. She had individual psychotherapy and dialectical behavior therapy without benefit. In terms of her physical health, she had fibromyalgia, migraine, hyperthyroidism (treated with radioactive iodine), and hypertension.</p><p>At the time of her referral to our program, she was taking topiramate 50 mg, bupropion XL 450 mg, gabapentin 2800 mg, and zopiclone 15 mg a day. Aided by collateral information from her family, the diagnosis of bipolar II disorder was confirmed using the DSM-IV. Since the unmedicated illness was marked by episodes of “pure” depression with full inter-episodic recovery, we surmised that the continuous use of antidepressants (alone or in combination with other psychotropic drugs) over the previous 15 years had likely contributed to a perpetual mix","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"26 7","pages":"750-752"},"PeriodicalIF":5.0,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bdi.13454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annemiek Dols, Ralph W. Kupka, Henk Mathijssen, Eline J. Regeer
{"title":"The time has come to question the infinite maintenance treatment for bipolar disorders","authors":"Annemiek Dols, Ralph W. Kupka, Henk Mathijssen, Eline J. Regeer","doi":"10.1111/bdi.13447","DOIUrl":"10.1111/bdi.13447","url":null,"abstract":"","PeriodicalId":8959,"journal":{"name":"Bipolar Disorders","volume":"26 5","pages":"415-417"},"PeriodicalIF":5.0,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}