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Pharmacotherapy for depression and bipolar disorder during lactation: A framework to aid decision making.
Sprague, J, Wisner, KL, Bogen, DL
Seminars in perinatology. 2020;(3):151224
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OBJECTIVE Breastmilk is recommended as the exclusive source of nutrition for infants younger than 6 months due to the numerous health benefits for both infants and mothers. Although many women are prescribed medications during pregnancy and postpartum, limited data are available to assist women in weighing the benefits compared to the risks of peripartum medication use. The goals of this paper are to discuss the importance of breastmilk for the health of both the mother and infant, evaluate the impact of medication use on women's infant feeding choice, describe the transfer of drugs to breastmilk and infants, and provide a framework for clinicians to support evidence-based counseling for women treated for mood disorders. RECOMMENDATIONS We recommend early pregnancy counseling to discuss the benefits and risks of medications during breastfeeding. The Surgeon General's Call to Action (2011) highlights the short and long-term negative health effects of not providing breastmilk. Integrating recommendations from the pediatric and obstetric teams allows patients to make decisions based on evidence and reach their infant feeding goals. Databases containing summaries of research findings and pharmacologic properties of the drug of interest are an essential resource for clinicians.
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Obesity in Adolescents with Psychiatric Disorders.
Chao, AM, Wadden, TA, Berkowitz, RI
Current psychiatry reports. 2019;(1):3
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PURPOSE OF REVIEW This narrative review synthesized recent research related to obesity in adolescents with psychiatric disorders, with a focus on epidemiology, mechanisms, and weight management approaches. The paper reviews literature on depressive and anxiety disorders, bipolar disorder, and schizophrenia spectrum and other psychotic disorders. RECENT FINDINGS Depression has a bidirectional relationship with obesity. Bipolar disorder and schizophrenia spectrum disorders, and their treatments, increase the risk of developing obesity. Mechanisms underlying this weight gain include lifestyle and environmental factors and psychiatric medications, though emerging evidence has also suggested the role of genetic and neuroendocrine processes. Evidence about the most effective treatments for obesity in adolescents with psychiatric disorders remains limited. Adolescents with psychiatric disorders are at high risk for obesity. Close monitoring for increases in weight and cardiometabolic risk factors with use of antipsychotic and mood-stabilizing medications is recommended. Clinical trials are needed that test the efficacy of weight management strategies for this population.
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Beyond evidence-based treatment of bipolar disorder: Rational pragmatic approaches to management.
Post, RM, Yatham, LN, Vieta, E, Berk, M, Nierenberg, AA
Bipolar disorders. 2019;(7):650-659
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The evidence for efficacy of many currently available treatments for bipolar disorder is based on studies of nonrefractory patients with bipolar disorder. Therefore, not surprisingly, most treatment recommendations and guidelines for the treatment of bipolar disorder and its many comorbidities depend heavily on data from placebo controlled randomized clinical trials (RCTs), but these RCTs provide little direction for the clinician as to what next steps might be optimal in non- or partial-responders and in those with ongoing medical and psychiatric comorbidities. Given this and the paucity of RCTs at later treatment junctures, we thought it appropriate to begin a discussion of the quality of the data that some experts in the field might consider using in choosing and sequencing drugs and their combination. We acknowledge that many other clinical investigators may prefer very different sequences, but thought the suggestions offered here might be useful to some clinicians in the field, might start discussions of other options in the literature, and, at the same time, provide a preliminary outline for a new round of much-needed clinical trials to better inform clinical practice. Given the very wide range of the quality of the data and clinical principles on which the current suggestions are based, only minimal references are included and a comprehensive review of the literature supporting each option would be outside the scope of this manuscript.
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Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder.
Rong, C, Park, C, Rosenblat, JD, Subramaniapillai, M, Zuckerman, H, Fus, D, Lee, YL, Pan, Z, Brietzke, E, Mansur, RB, et al
International journal of environmental research and public health. 2018;(4)
Abstract
OBJECTIVES Extant evidence indicates that ketamine exerts rapid antidepressant effects in treatment-resistant depressive (TRD) symptoms as a part of major depressive disorder (MDD) and bipolar disorder (BD). The identification of depressed sub-populations that are more likely to benefit from ketamine treatment remains a priority. In keeping with this view, the present narrative review aims to identify the pretreatment predictors of response to ketamine in TRD as part of MDD and BD. METHOD Electronic search engines PubMed/MEDLINE, ClinicalTrials.gov, and Scopus were searched for relevant articles from inception to January 2018. The search term ketamine was cross-referenced with the terms depression, major depressive disorder, bipolar disorder, predictors, and response and/or remission. RESULTS Multiple baseline pretreatment predictors of response were identified, including clinical (i.e., Body Mass Index (BMI), history of suicide, family history of alcohol use disorder), peripheral biochemistry (i.e., adiponectin levels, vitamin B12 levels), polysomnography (abnormalities in delta sleep ratio), neurochemistry (i.e., glutamine/glutamate ratio), neuroimaging (i.e., anterior cingulate cortex activity), genetic variation (i.e., Val66Met BDNF allele), and cognitive functioning (i.e., processing speed). High BMI and a positive family history of alcohol use disorder were the most replicated predictors. CONCLUSIONS A pheno-biotype of depression more, or less likely, to benefit with ketamine treatment is far from complete. Notwithstanding, metabolic-inflammatory alterations are emerging as possible pretreatment response predictors of depressive symptom improvement, most notably being cognitive impairment. Sophisticated data-driven computational methods that are iterative and agnostic are more likely to provide actionable baseline pretreatment predictive information.
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Glutamatergic Modulators in Depression.
Henter, ID, de Sousa, RT, Zarate, CA
Harvard review of psychiatry. 2018;(6):307-319
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After participating in this activity, learners should be better able to evaluate the evidence supporting the antidepressant effects of glutamatergic modulators.Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions in depressive symptoms have been noted in response to subanesthetic doses of the glutamatergic modulator ketamine in subjects with major depressive disorder or bipolar depression. These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies. Here, we highlight the evidence supporting the antidepressant effects of various glutamatergic modulators, including (1) broad glutamatergic modulators (ketamine, esketamine, dextromethorphan, dextromethorphan-quinidine [Nuedexta], AVP-786, nitrous oxide [N2O], AZD6765), (2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists (CP-101,606/traxoprodil, MK-0657 [CERC-301]), (3) glycine-site partial agonists (D-cycloserine, GLYX-13, sarcosine, AV-101), and (4) metabotropic glutamate receptor modulators (AZD2066, RO4917523/basimglurant, JNJ40411813/ADX71149, R04995819 [RG1578]).
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Mood stabilizers in pregnancy and child developmental outcomes: A systematic review.
Haskey, C, Galbally, M
The Australian and New Zealand journal of psychiatry. 2017;(11):1087-1097
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BACKGROUND Research suggests that maintaining treatment during pregnancy for women with bipolar affective disorder reduces the risk of relapse. However, one of the key questions for women and clinicians during pregnancy is whether there are implications of exposure to mood stabilizers for longer term child development. Despite these concerns, there are few recent systematic reviews comparing the impact on child developmental outcomes for individual mood-stabilizing agents to inform clinical decisions. OBJECTIVES To examine the strengths and limitations of the existing data on child developmental outcomes following prenatal exposure to mood stabilizers and to explore whether there are any differences between agents for detrimental effects on child development. METHOD Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a rigorous systematic search was carried out of four electronic databases from their respective years of inception to September 2016 to identify studies which examined the effects of mood stabilizers including sodium valproate, carbamazepine, lamotrigine, lithium and second-generation antipsychotics on child developmental outcomes. RESULTS We identified 15 studies for critical review. Of these, 10 examined antiepileptic drugs, 2 studied lithium and 3 studied second-generation antipsychotics. The most consistent finding was a dose-response relationship for valproate with higher doses associated with poorer global cognitive abilities compared to other antiepileptic drugs. The limited data available for lithium found no adverse neurodevelopmental outcomes. The limited second-generation antipsychotic studies included a report of a transient early neurodevelopmental delay which resolved by 12 months of age. CONCLUSION This review found higher neurodevelopmental risk with valproate. While the existing data on lithium and second-generation antipsychotics are reassuring, these data are both limited and lower quality, indicating that further research is required. The information from this review is relevant for patients and clinicians to influence choice of mood-stabilizing agent in childbearing women. This must be balanced against the known risks associated with untreated bipolar affective disorder.
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Sudden valproate-induced hyperammonemia managed with L-carnitine in a medically healthy bipolar patient: Essential review of the literature and case report.
Cattaneo, CI, Ressico, F, Valsesia, R, D'Innella, P, Ballabio, M, Fornaro, M
Medicine. 2017;(39):e8117
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RATIONALE Valproic Acid is a commonly used psychiatric drug primarily used as a mood stabilizer. Mild hyperammonemia is a Valproic Acid common adverse effect. This report presents an example of treated hyperammonemia on Valproic acid therapy managed with L-carnitine administration in BD patients characterized by sudden vulnerability. PATIENT CONCERNS We report the case of a 29-year-old man suffering from bipolar disorder (BD) and substance use disorder who exhibited sudden altered mental status upon admittance to the inpatient unit. The patient was started on Valproic acid with no improvement. DIAGNOSES The patient had remarkably high ammonia levels (594 μg/dL) without hepatic insufficiency, likely due to his valproate treatment. INTERVENTIONS The patient was administered lactulose, intravenous hydration, and i.v. levocarnitine supplementation 4.5 g/day. OUTCOMES The administration leads to reduction of ammonia levels to 99 μg/dL within 12 hours upon initiation of carnitine therapy and progressive restore of his mental status within 24 hours. LESSONS Resolution of hyperammonemia caused by Valproic acid therapy may be enhanced with the administration of L-carnitine. An interesting aspect of this case was how rapidly the patient responded to the carnitine therapy.
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Environmental factors, life events, and trauma in the course of bipolar disorder.
Aldinger, F, Schulze, TG
Psychiatry and clinical neurosciences. 2017;(1):6-17
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The etiology and clinical course of bipolar disorder are considered to be determined by genetic and environmental factors. Although the kindling hypothesis emphasizes the impact of environmental factors on initial onset, their connection to the outcome and clinical course have been poorly established. Hence, there have been numerous research efforts to investigate the impact of environmental factors on the clinical course of illness. Our aim is to outline recent research on the impact of environmental determinants on the clinical course of bipolar disorder. We carried out a computer-aided search to find publications on an association between environmental factors, life events, and the clinical course of bipolar disorder. Publications in the reference lists of suitable papers have also been taken into consideration. We performed a narrative overview on all eligible publications. The available body of data supports an association between environmental factors and the clinical course of bipolar disorder. These factors comprise prenatal, early-life, and entire lifespan aspects. Given varying sample sizes and several methodological limitations, the reported quality and extent of the association between environmental factors and the clinical course of bipolar disorder should be interpreted with utmost caution. Systematic longitudinal long-term follow-up trials are needed to obtain a clearer and more robust picture.
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Significantly Higher Peripheral Insulin-Like Growth Factor-1 Levels in Patients With Major Depressive Disorder or Bipolar Disorder Than in Healthy Controls: A Meta-Analysis and Review Under Guideline of PRISMA.
Tu, KY, Wu, MK, Chen, YW, Lin, PY, Wang, HY, Wu, CK, Tseng, PT
Medicine. 2016;(4):e2411
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An increasing amount of research has focused on insulin-like growth factor-1 (IGF-1) because of multiple neurotrophic effects, including neurogenesis, remyelination, and synaptogenesis. In addition, IGF-1 can mediate an antidepressant effect in patients with major affective disorder, and its levels in the cerebrospinal fluid have been found to vary with antidepressant treatment. Furthermore, it has been proven to crossover the blood-brain barrier, with a reciprocal feedback loop being the central effect. However, recent studies have reported inconclusive findings about the role of IGF-1 in major affective disorder. The aim of the current study was to conduct a thorough meta-analysis of changes in peripheral IGF-1 levels in patients with major depressive disorder (MDD) or bipolar disorder (BD). We conducted a thorough literature search and compared peripheral IGF-1 levels in patients with MDD or BD and in healthy controls, and investigated clinical variables through meta-regression. Electronic research was conducted through platform of PubMed. We used inclusion criteria as clinical trials discussing comparisons of peripheral IGF-1 protein levels in patients with MDD or BD and those in healthy controls. We analyzed the cases from 9 studies with the random-effect model. The main finding was that peripheral IGF-1 levels in the patients were significantly higher than in the healthy controls (P < 0.001), with a significant inverse association with duration of illness (P = 0.03). In meta-analysis comparing peripheral IGF-1 levels in patients with BD or MDD before and after treatment, there was no significant change in peripheral IGF-1 levels after treatment (P = 0.092). The small numbers of studies and lack of correlation data with growth hormone in current studies are the main limitations of this meta-analysis. Our results indicated that peripheral IGF-1 levels may not be an indicator of disease severity, but may be a disease trait marker or an indicator of cognition. However, further investigations on the correlation between cognitive function and peripheral IGF-1 levels are needed to explore the role of IGF-1 in the pathophysiology of MDD and BD.
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Lifestyle interventions targeting dietary habits and exercise in bipolar disorder: A systematic review.
Bauer, IE, Gálvez, JF, Hamilton, JE, Balanzá-Martínez, V, Zunta-Soares, GB, Soares, JC, Meyer, TD
Journal of psychiatric research. 2016;:1-7
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BACKGROUND Bipolar disorder (BD) is a serious mental illness associated with a high risk of medical comorbidities, long-term disability and premature death. This systematic review examined the current literature on therapeutic interventions targeting nutrition, physical activity and wellness in BD and collecting health-related measures such as mood and course of illness. METHODS Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to June 2015, for studies focusing on lifestyle interventions in BD. Search terms were related to bipolar disorder, nutrition, physical activity, wellbeing, psychosocial interventions and course of illness. We hand searched content pages of Bipolar Disorders and Journal of Affective Disorders and checked references of relevant reviews and dissertations to identify additional papers. RESULTS After applying inclusion and exclusion criteria to identified hits, this literature search retrieved six papers. Overall findings point towards a beneficial role of lifestyle interventions on mood, weight, blood pressure, lipid profile, physical activity and overall wellbeing. Methodological limitations include small sample size, gender ratio imbalance, inconsistencies in terms of laboratory measures, and lack of randomized controlled trials and absence of follow-up and longitudinal studies to determine the benefits of these factors on clinical and functional outcomes over time CONCLUSIONS Lifestyle interventions in BD targeting nutrition, exercise, wellbeing alongside beliefs, coping strategies and attitudes towards health show promise in reducing the risk of comorbid ailments in BD. There is still a strong need for studies a) developing interventions which are informed by the patient's input and b) examining the effectiveness of such interventions targeting general wellness using well-controlled trials.