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Journal of Affective Disorders Jun 2024While theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing...
Continuous theta burst stimulation for bipolar depression: A multicenter, double-blind randomized controlled study exploring treatment efficacy and predictive potential of kynurenine metabolites.
BACKGROUND
While theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing treatment parameters is crucial in the pursuit of rapid symptom relief. Moreover, aligning with personalized treatment strategies and increased interest in immunopsychiatry, biomarker-based stratification of patients most likely to benefit from TBS might improve remission rates. We investigated treatment effectiveness of continuous TBS (cTBS) compared to sham in BD-D, and assessed the capacity of plasma kynurenine pathway metabolites to predict treatment outcome.
METHODS
Thirty-seven patients with BD-D underwent accelerated active or sham cTBS treatment in a multicenter, double-blind, randomized controlled trial. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before treatment (T0), 3-4 days posttreatment (T1) and 10-11 days posttreatment (T2). Plasma tryptophan, kynurenine, kynurenic acid and quinolinic acid concentrations were quantified with ELISA. Linear mixed models were used for statistical analyses.
RESULTS
Although the total sample showed depressive symptom improvement, active cTBS did not demonstrate greater symptom alleviation compared to sham. However, higher baseline quinolinic acid significantly predicted symptom improvement in the active treatment group, not in sham-stimulated patients.
LIMITATIONS
The modest sample size limited the power to detect significant differences with regard to treatment effect. Also, the follow-up period was 10-11 days, whereas similar studies usually follow up for at least one month.
CONCLUSION
More research is required to optimize cTBS for BD-D and explore the involvement of quinolinic acid in treatment outcome.
PubMed: 38936704
DOI: 10.1016/j.jad.2024.06.078 -
Journal of Clinical Psychopharmacology
Topics: Humans; Bipolar Disorder; Female; Pregnancy; Pregnancy Complications; Antimanic Agents; Antipsychotic Agents; Adult
PubMed: 38935569
DOI: 10.1097/JCP.0000000000001887 -
Revista de Neurologia Jul 2024The presence of psychiatric comorbidity in some neurological disorders is common. A bi-directional influence between some psychiatric and neurological disorders has been...
INTRODUCTION
The presence of psychiatric comorbidity in some neurological disorders is common. A bi-directional influence between some psychiatric and neurological disorders has been discussed, but not widely studied. There is an absence of literature on the typology and rates of neurology consultations in different types of psychiatric inpatients.
MATERIALS AND METHODS
Cross-sectional study based on real world data on patients who had a neurological consultation during hospitalization on a psychiatric ward.
RESULTS
The most frequent reasons for visits to neurologists in our study were cluster 'Epilepsy/other types of non-epileptic seizures' (n = 177, 36.44%), followed by cluster 'Movement disorders' (n = 77, 20.48%), 'Cognitive disorder' (n = 69, 18.35%), and finally cluster 'Neuropathy' (n = 21, 5.59%). The most frequent type of psychiatric patient who required neurologic consultation presented a psychotic disorder (n = 100, 26.60%), follow by problem behavior (n = 82, 21.81%), bipolar disorder (n = 78, 20.78%), depressive disorder (n = 42, 11.17%) and autism spectrum disorder (n = 20, 5.32%). We found a statistically significant relationship between (problem behavior and intellectual disability) and neurologic consultation for epilepsy/other types of non-epileptic seizures, and between (depressive disorder, bipolar disorder, autism spectrum disorder and intellectual disability) and neurologic consultation for movement disorders.
CONCLUSIONS
This is the first study in the literature which analyzes the rates and typology of neurologic consultations in people hospitalized with psychiatric disorders. A deep knowledge of epilepsy, movement disorders and cognitive disorders should be required for health professionals to treat psychiatric inpatients appropriately. Patients with particular psychiatric disorders seem to require a higher number of neurologic consultations than others during their hospitalization.
Topics: Humans; Cross-Sectional Studies; Female; Mental Disorders; Male; Spain; Nervous System Diseases; Middle Aged; Referral and Consultation; Adult; Comorbidity; Neurology; Inpatients; Aged; Epilepsy
PubMed: 38934945
DOI: 10.33588/rn.7901.2024054 -
Cureus May 2024Clozapine is an atypical antipsychotic that acts by blocking mainly dopamine 4 receptors. It is usually prescribed for treatment-resistant schizophrenia as well as...
Clozapine is an atypical antipsychotic that acts by blocking mainly dopamine 4 receptors. It is usually prescribed for treatment-resistant schizophrenia as well as treatment-resistant bipolar disorder. Clozapine has a wide profile of side effects that result from blocking different receptors all over the body. A 42-year-old Middle Eastern female is known to have suffered from schizoaffective disorder for many years and had frequent relapses despite compliance with treatment. She was commenced on Clozapine; the patient started complaining of an electric shock sensation throughout her body that resulted in recurrent falls with bilateral leg fractures. She was started on sodium valproate to exclude the possibility of seizure activity but the electric shock sensation did not subside. The decision was made to switch her to aripiprazole and gradually taper down and stop Clozapine which improved her symptoms. Careful monitoring of patients who receive Clozapine is recommended especially during the tapering phase due to the risky adverse events it can bring about. It is essential to understand the side effects in order to tackle them as soon as they arise.
PubMed: 38933635
DOI: 10.7759/cureus.61143 -
Cureus May 2024Background Motivation dysregulation is common in several psychiatric disorders. However, little is known about the relationships between motivation and the regional...
Background Motivation dysregulation is common in several psychiatric disorders. However, little is known about the relationships between motivation and the regional brain areas involved. We evaluated the relationships between brain microstructural features and causality orientation in patients with schizophrenia, major depressive disorder (MDD), and bipolar disorder (BD) using diffusional kurtosis imaging (DKI) techniques. Methods Forty patients with MDD, 36 with BD, and 30 with schizophrenia underwent DKI and assessment using the General Causality Orientation Scale (GCOS). We analyzed the DKI index and the GCOS subscales. Results The psychiatric patients showed significant positive correlations between the GCOS-autonomy orientation score and the mean kurtosis (MK) values in the prefrontal regions, orbitofrontal regions, and posterior cingulate cortex. When the analyses were performed separately by disease and gender, a positive correlation was found between the GCOS-autonomy orientation score and the MK values in the left prefrontal regions transdiagnostically, especially among female patients with MDD, BD, and schizophrenia. Conclusions A similar association between intrinsic motivation and MK value in the left prefrontal cortex was suggested in patients with schizophrenia, MDD, and BD. The commonality of this association among these disorders might lead to the discovery of a new biomarker for psychiatric clinical research.
PubMed: 38933632
DOI: 10.7759/cureus.61138 -
Neuropsychopharmacology Reports Jun 2024Bipolar disorder (BD) has a significant impact on global health, yet its neurophysiological basis remains poorly understood. Conventional treatments have limitations,... (Review)
Review
AIM
Bipolar disorder (BD) has a significant impact on global health, yet its neurophysiological basis remains poorly understood. Conventional treatments have limitations, highlighting the need for a better understanding of the neurophysiology of BD for early diagnosis and novel therapeutic strategies.
DESIGN
Employing a systematic review approach of the PRISMA guidelines, this study assessed the usefulness and validity of transcranial magnetic stimulation (TMS) neurophysiology in patients with BD.
METHODS
Databases searched included PubMed, MEDLINE, Embase, and PsycINFO, covering studies from January 1985 to January 2024.
RESULTS
Out of 6597 articles screened, nine studies met the inclusion criteria, providing neurophysiological insights into the pathophysiological basis of BD using TMS-electromyography and TMS-electroencephalography methods. Findings revealed significant neurophysiological impairments in patients with BD compared to healthy controls, specifically in cortical inhibition and excitability. In particular, short-interval cortical inhibition (SICI) was consistently diminished in BD across the studies, which suggests a fundamental impairment of cortical inhibitory function in BD. This systematic review corroborates the potential utility of TMS neurophysiology in elucidating the pathophysiological basis of BD. Specifically, the reduced cortical inhibition in the SICI paradigm observed in patients with BD suggests gamma-aminobutyric acid (GABA)-A receptor-mediated dysfunction, but results from other TMS paradigms have been inconsistent. Thus, complex neurophysiological processes may be involved in the pathological basis underlying BD. This study demonstrated that BD has a neural basis involving impaired GABAergic function, and it is highly expected that further research on TMS neurophysiology will further elucidate the pathophysiological basis of BD.
PubMed: 38932486
DOI: 10.1002/npr2.12458 -
Journal of Clinical Medicine Jun 2024Social rhythm dysregulation has been identified as a determining factor in bipolar disorder (BD) relapses. It directly impacts individuals' quality of life (QoL). This...
Social rhythm dysregulation has been identified as a determining factor in bipolar disorder (BD) relapses. It directly impacts individuals' quality of life (QoL). This study aims to present preliminary data on the efficacy of an e-health psychoeducational intervention for BD for improving clinical outcomes. This study used an open-label, crossover, randomized controlled trial design. The inclusion criteria consisted of a BD diagnosis, affiliation with the Consultation Psychiatry and Psychosomatic Center at the University Hospital in Cagliari, Italy, age over 18, and the obtaining of informed consent. Anxiety and depressive symptoms, QoL, and social and biological rhythms were measured using standardized instruments validated in Italian. A total of 36 individuals were included in the experimental group (EG) and 18 in the control group (CG). The final sample consisted of 25 in the EG and 14 in the CG. A statistically significant improvement in QoL was found in the EG post-treatment ( = 0.011). Significant correlations were found between QoL and the dysregulation of biorhythms in the EG at T0 ( = 0.0048) and T1 ( = 0.0014). This study shows that, during extreme distress, an e-health group psychoeducation intervention for people with BD could significantly improve the perception of QoL. The results must be confirmed by studies conducted with larger-sized samples.
PubMed: 38929997
DOI: 10.3390/jcm13123468 -
Medicina (Kaunas, Lithuania) Jun 2024: Options for treatment-resistant bipolar depression (TRBPD) are limited. Electroconvulsive therapy (ECT) has shown efficacy in TRBPD. However, the cognitive deficits...
: Options for treatment-resistant bipolar depression (TRBPD) are limited. Electroconvulsive therapy (ECT) has shown efficacy in TRBPD. However, the cognitive deficits and memory concerns associated with ECT are problematic for a significant number of patients. It remains unclear what the next step is for patients with TRBPD who fail ECT. In this case report, we present a patient with TRBPD who sequentially received 12 sessions of brief-pulse right unilateral ECT, 22 sessions of ketamine infusion at 0.5-0.75 mg/kg for 40 min, and 39 sessions of deep repetitive transcranial magnetic stimulation (dTMS). The patient had some benefit from ECT, but declined continuation of ECT due to memory concerns. The patient tolerated ketamine infusion well but had limited benefit. However, the patient responded well to acute treatment with dTMS and maintained relative stability for more than 2 years. This case suggests that patients with TRBPD who fail ECT and/or ketamine infusion might benefit from dTMS.
Topics: Humans; Ketamine; Electroconvulsive Therapy; Bipolar Disorder; Transcranial Magnetic Stimulation; Depressive Disorder, Treatment-Resistant; Female; Male; Middle Aged; Adult; Treatment Outcome
PubMed: 38929552
DOI: 10.3390/medicina60060936 -
Brain Sciences Jun 2024Correct classification of irritability is extremely important to assess prognosis and treatment indications of juvenile mood disorders. We assessed factors associated...
Correct classification of irritability is extremely important to assess prognosis and treatment indications of juvenile mood disorders. We assessed factors associated with low versus high parent- and self-rated irritability using the affective reactivity index (ARI) in a sample of 289 adolescents diagnosed with a bipolar or a major depressive disorder. Bivariate analyses were followed by multilinear logistic regression model. Factors significantly and independently associated with high versus low parent-rated ARI score were: more severe emotional dysregulation and bipolar disorders diagnosis. Factors significantly and independently associated with high versus low self-rated ARI score were: lower children depression rating scale (CDRS-R) difficulty of having fun item score, greater children depression inventory (CDI-2) self-report score, more severe emotional dysregulation, and greater CDRS-R appetite disturbance item score. High parent-rated irritability was strictly related with a bipolar disorder diagnosis, whereas high youth-rated irritability was related to depressive phenotype characterized by appetite/food-intake dysregulation, mood lability, and less anhedonia and apathy.
PubMed: 38928611
DOI: 10.3390/brainsci14060611 -
International Journal of Molecular... Jun 2024NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain... (Review)
Review
NMDA receptor antagonists have potential for therapeutics in neurological and psychiatric diseases, including neurodegenerative diseases, epilepsy, traumatic brain injury, substance abuse disorder (SUD), and major depressive disorder (MDD). ()-ketamine was the first of a novel class of antidepressants, rapid-acting antidepressants, to be approved for medical use. The stereoisomer, ()-ketamine (arketamine), is currently under development for treatment-resistant depression (TRD). The compound has demonstrated efficacy in multiple animal models. Two clinical studies disclosed efficacy in TRD and bipolar depression. A study by the drug sponsor recently failed to reach a priori clinical endpoints but post hoc analysis revealed efficacy. The clinical value of ()-ketamine is supported by experimental data in humans and rodents, showing that it is less sedating, does not produce marked psychotomimetic or dissociative effects, has less abuse potential than ()-ketamine, and produces efficacy in animal models of a range of neurological and psychiatric disorders. The mechanisms of action of the antidepressant effects of ()-ketamine are hypothesized to be due to NMDA receptor antagonism and/or non-NMDA receptor mechanisms. We suggest that further clinical experimentation with ()-ketamine will create novel and improved medicines for some of the neurological and psychiatric disorders that are underserved by current medications.
Topics: Ketamine; Humans; Animals; Antidepressive Agents; Nervous System Diseases; Receptors, N-Methyl-D-Aspartate; Mental Disorders; Stereoisomerism
PubMed: 38928508
DOI: 10.3390/ijms25126804