Treatment resistant bipolar depression

Bipolar depression constitutes a major problem in psychiatry. It correlates with high suicidality, treatment resistance, chronicity, and poor quality of life. Registered treatment for bipolar depression is limited and insufficient. There is an urgent need for implementing new therapeutic strategies. Intranasal ketamine's enantiomer-esketamine is a novel rapid-acting antidepressant with proven efficacy in treatment-resistant depression. Research on bipolar depression, although not as comprehensive, indicates that it may be a viable and safe substitute with minimal risk for mood polarity changes...

OBJECTIVE: We conducted an open-label clinical trial ("Bio-K") using IV ketamine for treatment-resistant depression to identify biomarkers linked to remission. Here, we report the clinical efficacy and side effect outcomes of Bio-K. METHODS: Across 4 US sites, 75 patients ages 18-65 with treatment-refractory unipolar or bipolar depression received 3 IV ketamine infusions over an 11-day period. Key exclusion criteria were psychotic symptoms, significant substance abuse, unstable medical conditions, and any use of cannabis...

Ketamine has shown rapid antidepressant and anti-suicidal effects in treatment-resistant depression (TRD) with single and serial intravenous (IV) infusions, but the effectiveness for depressive episodes of bipolar disorder is less clear. We conducted an updated systematic review and meta-analysis to appraise the current evidence on the efficacy and tolerability of ketamine/esketamine in bipolar depression. A search was conducted to identify randomized controlled trials (RCTs) and non-randomized studies examining single or multiple infusions of ketamine or esketamine treatments...

BACKGROUND: Electroconvulsive therapy (ECT) is a well-accepted intervention for treatment-resistant, serious mental illnesses. Its acceptability, efficacy, and tolerability are well documented in high-income settings, but less so in lower- and middle-income countries (LMICs). This report is a narrative review of ECT practice in the latter setting. METHODS: A literature search was conducted using Medline and PubMed. Initial results yielded 81 publications in English...

IMPORTANCE: Bipolar II disorder (BDII) is a debilitating condition frequently associated with difficult-to-treat depressive episodes. Psilocybin has evidence for rapid-acting antidepressant effects but has not been investigated in bipolar depression. OBJECTIVE: To establish the safety and efficacy of psilocybin in patients with BDII in a current depressive episode. DESIGN, SETTING, AND PARTICIPANTS: This was a 12-week, open-label nonrandomized controlled trial conducted at Sheppard Pratt Hospital...

INTRODUCTION: Many depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There are currently no specific and effective treatments for anhedonia. Some trials have shown that dopamine agonist pramipexole is efficacious for treating depression, but more data is needed before it could become ready for clinical prime time. Given its mechanism of action, pramipexole might be a useful treatment for a depression subtype characterised by significant anhedonia and lack of motivation-symptoms associated with dopaminergic hypofunction...

A delicate balance between quiescence and division of the radial glia-like stem cells (RGLs) ensures continuation of adult hippocampal neurogenesis (AHN) over the lifespan. Transient or persistent perturbations of this balance due to a brain pathology, drug administration, or therapy can lead to unfavorable long-term outcomes such as premature depletion of the RGLs, decreased AHN, and cognitive deficit. Memantine, a drug used for alleviating the symptoms of Alzheimer's disease, and electroconvulsive seizure (ECS), a procedure used for treating drug-resistant major depression or bipolar disorder, are known strong AHN inducers; they were earlier demonstrated to increase numbers of dividing RGLs...

INTRODUCTION: A new era of treatment for adults with treatment-resistant depression (TRD), which involves psychedelic substances, is dawning. Emerging evidence indicates that psychedelics can exert antidepressant effects through multiple neurobiological and psychological mechanisms. However, it remains to be seen if these new treatments will revolutionize the treatment of TRD. AREAS COVERED: The present review focuses on the efficacy of serotoninergic psychedelics psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and mescaline (3,4,5-trimethoxyphenethylamine), as well as 3,4-methylenedioxymethamphetamine (MDMA), for TRD...

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Electroconvulsive Therapy (ECT) is an effective treatment for mood and psychotic disorders but there is growing evidence of treatment resistant to ECT. Our study aimed to investigate the relationship between the number of previous illness episodes and the symptomatic improvement after acute ECT treatment. We conducted a retrospective naturalistic cohort analysis of patients' ECT registry data from March 2017 to February 2023. We categorized the number of previous illness episodes into "0-3″ and ">3 episodes", paired T-tests were used to compare the changes in scores of clinical assessments, generalized linear models were used to analyze the association between the number of previous illness episodes and change in symptomatic scores...

OBJECTIVES: One of the current challenges in psychiatry is the search for answers on how to effectively manage drug-resistant depression. The occurrence of drug resistance in patients is an indication for the use of electroconvulsive therapy (ECT). This method is highly effective and usually results in relatively quick health improvement. Despite the knowledge of how ECT works, not all of the biological pathways activated during its use have been identified. Hence, based on the neuroinflammatory hypothesis of depression, we investigated the concentration of two opposite-acting adipokines (anti-inflammatory adiponectin and proinflammatory resistin) and BDNF in antidepressant-resistant patients undergoing ECT...

INTRODUCTION: Despite the growing number of different therapeutic options, treatment of depression is still a challenge. A broader perspective reveals the benefits of bright light therapy (BLT). It stimulates intrinsically photosensitive retinal ganglion cells, which induces a complex cascade of events, including alterations in melatonergic, neurotrophic, GABAergic, glutamatergic, noradrenergic, serotonergic systems, and HPA axis, suggesting that BLT effects expand beyond the circadian pacemaker...

Bipolar disorder (BD) is a disabling disorder with heterogeneous symptom profiles and trajectories. Like many other neuropsychiatric disorders, clinical decision making related to diagnoses and choice of treatment is based on clinical assessments alone, and risk prediction for treatment success or resistance at an individual level remains sparse. An enormous effort to add biological markers to this risk prediction is ongoing. The role of lipids in normal brain functioning is well established, and several hypotheses about the role of lipids in the pathogenesis of neuropsychiatric disorders, including BD, have been made...

INTRODUCTION: The challenges posed by treatment-resistant schizophrenia and depressive symptoms have led to ongoing difficulties despite the availability of antipsychotics and antidepressants. This review addresses the potential of amisulpride analogs, particularly SEP-4199, in addressing these challenges through enhanced efficacy and reduced side effects. AREAS COVERED: This review focuses on the pharmacological profile of amisulpride analogs, exemplified by LB-102 and its derivative SEP-4199...

There has been an increase in research on the topic of psychedelic substances and their effects as treatment options in neuropsychiatric conditions. Psilocybin is a psychedelic drug that has recently garnered increased interest as an effective treatment modality for treatment-resistant depression, depression associated with terminal conditions, certain substance use disorders, and obsessive-compulsive disorder. However, sparse data exist as to the effects that psilocybin might have on patients at risk for mania, in large part secondary to the exclusion of this patient population from studies due to the concern for inducing mania or worsening illness course...

AIM: The use of deep brain stimulation (DBS) has been recently extended for treating resistant psychiatric disorders, but the experience in patients with schizophrenia-related disorders and bipolar disorder (BD) is scarce. METHOD: We conducted an observational, one-year longitudinal study to evaluate the effects of DBS in four treatment-resistant patients with schizophrenia, schizoaffective, and BD, included in a pilot, last-resource protocol. Patients were digitally monitored for objective assessment of behavioral changes...

Objective: To analyze the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder, schizophrenia, and obsessive-compulsive disorder (OCD) via umbrella meta-analysis. Data Sources: Meta-analysis studies were searched in PubMed from inception to May 2021 using the keywords anxiety , depression , ADHD , schizophrenia , mood disorder , OCD , psychiatric disorders , GAD , bipolar disorders , ASD , PTSD , transcranial magnetic stimulation , transcranial , magnetic , stimulation ...

BACKGROUND/OBJECTIVE: Electroconvulsive therapy (ECT) is effective for treatment-resistant and psychotic depression. One previously reported side effect of ECT is the disruption of memory reconsolidation. This study examines whether this disruption induced by ECT can be detected in routine neuropsychological assessments. METHODS: In this retrospective study, the Autobiographical Memory Interview (AMI) was applied before and after ECT. Memories of the same events and facts were tested pre and post ECT treatments...

Background : in a recent double-blind, placebo controlled RCT we demonstrated that selective inhibition of cyclo-oxygenase 2 (COX2) is an effective adjunctive strategy in treatment-resistant bipolar depression (TRBDD). To better clarify the mechanisms underlying TRBDD and treatment response, we conducted a retrospective exploratory analysis of the systemic inflammatory response index (SIRI = absolute neutrophils × absolute monocytes/absolute lymphocytes) in relation to other biomarkers and clinical outcomes after escitalopram (ESC), combined with the COX-2 inhibitor, celecoxib (CBX), versus placebo...

BACKGROUND: The efficacy of esketamine in treatment-resistant depression (TRD) has been confirmed. However, its administration is expensive and restrictive, with limited knowledge on how long the treatment should be continued. Predicting the treatment outcome would benefit patients and alleviate the global treatment cost. We aimed to define distinct trajectories of treatment response and assess their predictability. METHODS: In this longitudinal study, two independent samples of patients with unipolar or bipolar TRD were treated with esketamine in real-world settings...