Adolescent and Adult Transitions From Major Depressive Disorder to Bipolar Disorder.

Importance: Bipolar disorder (BD) often first appears in adolescence after onset of major depressive disorder (MDD), but diagnosis and treatment are commonly delayed. This delay is a concern because untreated BD is associated with adverse long-term outcomes, a more recurrent disease course and difficult-to-treat illness, and suicide attempts and deaths. Objective: To examine the association of age at MDD onset with early transition to BD and the subsequent use of psychiatric inpatient services as a severity indicator. Design, Setting, and Participants: This retrospective cohort study analyzed comprehensive data sourced from the Stockholm MDD Cohort data from 1997 to 2018, which encompass both outpatient and inpatient care. Individuals with an initial MDD episode from January 1, 2010, to December 31, 2013, who transitioned to BD by December 31, 2018, were identified. Data were analyzed between September 5 and December 28, 2023. Exposures: Post MDD assessments included a depression severity index, comorbidities, psychotherapy, psychotropic drugs, and electroconvulsive therapy. Main Outcomes and Measures: The main outcome was the transition from MDD to BD, dichotomized as occurring early (within 3 years of MDD onset) or late (3 years after MDD onset). Secondary outcomes encompassed the use of psychiatric inpatient services post transition and patterns of medication usage. A robust propensity score matching framework was used to estimate outcomes. Results: The final balanced cohort included 228 individuals, with an equal distribution between adults (n = 114; mean [SD] age, 24.5 [6.3] years; 96 female [84.2%]; 20 experiencing an early transition to BD [17.5%]) and youths (n = 114; mean [SD] age, 15.3 [1.6] years; 93 female [81.6%]; 8 experiencing an early transition to BD [7.0%]). Youths were substantially less likely to transition early (odds ratio, 0.42; 95% CI, 0.20-0.88; P = .02), despite having more outpatient visits (mean [SD] visits per month, 1.21 [1.07] vs 0.97 [0.98] for adults; P = .01). Both groups experienced substantially reduced inpatient care following a BD diagnosis, concurring with a marked decline in antidepressant use without increased lithium use. Conclusions and Relevance: These findings suggest that adolescents may experience delayed BD progression and that diagnosis substantially reduced inpatient care in all age groups, which coincided with a reduction in the use of antidepressants. These findings may inform pharmacologic strategies in patients with first-episode MDD at risk for BD.

[Psychedelic psychiatry]. / Psykedelisk psykiatri ­ det finns anledning att vara optimistisk.

In the last 20 years there has been an increased interest in research on psychedelic compounds for treatment of psychiatric conditions such as depression, anxiety and substance use disorders. Despite existing treatments being efficacious for many patients, this is not the case for up to a third of the patients with depression. Additionally, treatments are often long and associated with side effects. This review focuses on the psychedelic compound psilocybin, a serotonin-2A-receptor agonist that has been seen to reduce depression and anxiety in patients after administration of only a single dose, with effects lasting several weeks. Recent findings from phase II studies suggest that psilocybin treatment for depression is safe and efficacious. A phase III study is currently recruiting. Whether psychedelics will become a part of standard healthcare remains to be seen, but findings do give rise to cautious optimism.

Utilization of antidepressants, anxiolytics, and hypnotics during the COVID-19 pandemic.

Since the onset of the COVID-19 pandemic, there have been concerns over the mental health impact of COVID-19. This is a review of the utilization of antidepressants, anxiolytics, and hypnotics since the COVID-19 pandemic was declared on March the 11th 2020. A number of reports so far have been based on large prescription databases for administrative use at the national or regional level, but mainly in high-income countries. We found studies reporting increased prescription rates of antidepressants, anxiolytics, and hypnotics during March 2020, which has been interpreted as hoarding of such medications. In the following months, most studies of antidepressant prescription rates did not display a clear pattern of change compared with prepandemic trends. In later phases of the pandemic small increases in utilization of antidepressants, with higher than predicted prescription rates, have been the most consistent finding, especially in youth. In most high-income countries, there were increasing trends in utilization of antidepressants also before 2020, which needs to be considered when estimating utilization during the pandemic, whereas for anxiolytics and hypnotics, the prepandemic patterns of prescriptions were more varying. Overall, after March 2020 we could not find any distinct changes in the utilization of anxiolytics and hypnotics during the COVID-19 pandemic. Most studies did not contain information about the prevalence of indicated psychiatric disorders in the studied populations. More studies are needed about the long-term effects of COVID-19, particularly regarding utilization of antidepressants. Research relating antidepressant utilization with the prevalence of major depression and anxiety disorders would promote a better understanding of how well antidepressant prescription rates reflect the needs of the population.

2.5-Minute Fast Brain MRI with Multiple Contrasts in Acute Ischemic Stroke.

PURPOSE: To assess the performance of a 2.5-minute multi-contrast brain MRI sequence (NeuroMix) in diagnosing acute cerebral infarctions. METHODS: Adult patients with a clinical suspicion of acute ischemic stroke were retrospectively included. Brain MRI at 3 T included NeuroMix and routine clinical MRI (cMRI) sequences, with DWI/ADC, T2-FLAIR, T2-weighted, T2*, SWI-EPI, and T1-weighted contrasts. Three radiologists (R1-3) independently assessed NeuroMix and cMRI for the presence of acute infarcts (DWI ↑, ADC = or ↓) and infarct-associated abnormalities on other image contrasts. Sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) were calculated and compared using DeLong's test. Inter- and intra-rater agreements were studied with kappa statistics. Relative DWI (rDWI) and T2-FLAIR (rT2-FLAIR) signal intensity for infarctions were semi-automatically rendered, and the correlation between methods was evaluated. RESULTS: According to the reference standard, acute infarction was present in 34 out of 44 (77%) patients (63 ± 17 years, 31 men). Other infarct-associated signal abnormalities were reported in similar frequencies on NeuroMix and cMRI (p > .08). Sensitivity for infarction detection was 94%, 100%, and 94% evaluated by R1, R2, R3, for NeuroMix and 94%, 100%, and 100% for cMRI. Specificity was 100%, 90%, and 100% for NeuroMix and 100%, 100%, and 100% for cMRI. AUC for NeuroMix was .97, .95, and .97 and .97, 1, and 1 for cMRI (DeLong p = 1, .32, .15), respectively. Inter- and intra-rater agreement was κ = .88-1. The correlation between NeuroMix and cMRI was R = .73 for rDWI and R = .83 for rT2-FLAIR. CONCLUSION: Fast multi-contrast MRI NeuroMix has high diagnostic performance for detecting acute cerebral infarctions.

Endovascular transplantation of mRNA-enhanced mesenchymal stromal cells results in superior therapeutic protein expression in swine heart.

Heart failure has a poor prognosis and no curative treatment exists. Clinical trials are investigating gene- and cell-based therapies to improve cardiac function. The safe and efficient delivery of these therapies to solid organs is challenging. Herein, we demonstrate the feasibility of using an endovascular intramyocardial delivery approach to safely administer mRNA drug products and perform cell transplantation procedures in swine. Using a trans-vessel wall (TW) device, we delivered chemically modified mRNAs (modRNA) and mRNA-enhanced mesenchymal stromal cells expressing vascular endothelial growth factor A (VEGF-A) directly to the heart. We monitored and mapped the cellular distribution, protein expression, and safety tolerability of such an approach. The delivery of modRNA-enhanced cells via the TW device with different flow rates and cell concentrations marginally affect cell viability and protein expression in situ. Implanted cells were found within the myocardium for at least 3 days following administration, without the use of immunomodulation and minimal impact on tissue integrity. Finally, we could increase the protein expression of VEGF-A over 500-fold in the heart using a cell-mediated modRNA delivery system compared with modRNA delivered in saline solution. Ultimately, this method paves the way for future research to pioneer new treatments for cardiac disease.

Challenges and opportunities in the diagnosis and treatment of early-onset psychosis: a case series from the youth affective disorders clinic in Stockholm, Sweden.

Early-onset psychosis is linked to adverse long-term outcomes, recurrent disease course, and prolonged periods of untreated illness; thus highlighting the urgency of improving early identification and intervention. This paper discusses three cases where initial emphasis on psychosocial treatments led to diagnostic and therapeutic delays: (1) a 15-year-old misdiagnosed with emotionally unstable personality disorder and autism, who improved on bipolar medication and antipsychotics; (2) another 15-year-old misdiagnosed with autism, who stabilized on lithium and antipsychotics, subsequently allowing for gender dysphoria evaluation; (3) a 9-year-old autistic boy incorrectly treated for ADHD, who recovered with appropriate antipsychotic treatment. These cases illuminate the vital importance of adhering to a diagnostic hierarchy, prioritizing diagnostic utility, and conducting longitudinal evaluations to facilitate early targeted treatment of psychotic symptoms in early-onset psychosis. Adherence to such strategies can minimize delays in managing early-onset psychosis and improve long-term prognoses.

Electroconvulsive Therapy Versus Repetitive Transcranial Magnetic Stimulation in Patients With a Depressive Episode: A Register-Based Study.

OBJECTIVES: Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating depression. Although rTMS induces fewer adverse effects, its effectiveness relative to ECT is not well established. The aim of this study was to investigate the treatment outcomes of ECT and rTMS in patients who have received both interventions. METHODS: This was a register-based observational crossover study in patients with depression who had undergone ECT and rTMS in Sweden between 2012 and 2021. Primary outcome was reduction in the Montgomery-Åsberg Depression Rating Scale-Self-report (MADRS-S) score. Secondary outcome was response defined as a 50% or greater decrease in the MADRS-S score. Subgroup analyses were performed to identify factors that predicted differential responses between rTMS and ECT. Continuous and categorical variables were analyzed using paired-samples t tests and McNemar tests, respectively. RESULTS: In total, 138 patients across 19 hospitals were included. The MADRS-S score after ECT and rTMS was reduced by 15.0 and 5.6 (P = 0.0001) points, respectively. Response rates to ECT and rTMS were 38% and 15% (P = 0.0001), respectively. Electroconvulsive therapy was superior across all subgroups classified according to age and severity of depression. CONCLUSIONS: Our results suggest that ECT is more effective than rTMS in treating depression among patients who have received both interventions. Age and baseline depression severity did not predict who would similarly benefit from rTMS and ECT.

Phenotyping of Macrophages After Radiolabeling and Safety of Intra-arterial Transplantation Assessed by SPECT/CT and MRI.

Cell therapy is an integral modality of regenerative medicine. Macrophages are known for their sensitivity to activation stimuli and capability to recruit other immune cells to the sites of injury and healing. In addition, the route of administration can impact engraftment and efficacy of cell therapy, and modern neuro-interventional techniques provide the possibility for selective intra-arterial (IA) delivery to the central nervous system (CNS) with very low risk. The effects of radiolabelling and catheter transport on differentially activated macrophages were evaluated. Furthermore, the safety of selective IA administration of these macrophages to the rabbit brain was assessed by single-photon emission computed tomography/computed tomography (SPECT/CT) and ultra-high-field (9.4 T) magnetic resonance imaging (MRI). Cells were successfully labeled with (111In)In-(oxinate)3 and passed through a microcatheter with preserved phenotype. No cells were retained in the healthy rabbit brain after IA administration, and no adverse events could be observed either 1 h (n = 6) or 24 h (n = 2) after cell administration. The procedure affected both lipopolysaccharide/gamma interferon (LPS/IFNγ) activated cells and interleukin 4 (IL4), interleukin 10 (IL10)/transforming growth factor beta 1 (TGFß1) activated cells to some degree. The LPS/IFNγ activated cells had a significant increase in their phagocytotic function. Overall, the major impact on the cell phenotypes was due to the radiolabeling and not passage through the catheter. Unstimulated cells were substantially affected by both radiolabeling and catheter administration and are hence not suited for this procedure, while both activated macrophages retained their initial phenotypes. In conclusion, activated macrophages are suitable candidates for targeted IA administration without adverse effects on normal, healthy brain parenchyma.

Determinants and Outcomes of Suicidal Behavior Among Patients With Major Depressive Disorder.

Importance: Major depressive disorder (MDD) is an important risk factor of suicidal behavior, but the added burden of suicidal behavior and MDD on the patient and societal level, including all-cause mortality, is not well studied. Also, the contribution of various prognostic factors for suicidal behavior has not been quantified in larger samples. Objective: To describe the clinical and societal outcomes, including all-cause mortality, of suicidal behavior in patients with MDD and to explore associated risk factors and clinical management to inform future research and guidelines. Design, Setting, and Participants: This population-based cohort study used health care data from the Stockholm MDD Cohort. Patients aged 18 years or older with episodes of MDD diagnosed between January 1, 2012, and December 31, 2017, in any health care setting were included. The dates of the data analysis were February 1 to November 1, 2022. Exposures: Patients with MDD with and without records of suicidal behavior. Main Outcomes and Measures: The main outcome was all-cause mortality. Secondary outcomes were comorbid conditions, medications, health care resource utilization (HCRU), and work loss. Using Region Stockholm registry variables, a risk score for factors associated with suicidal behavior within 1 year after the start of an MDD episode was calculated. Results: A total of 158 169 unipolar MDD episodes were identified in 145 577 patients; 2240 (1.4%) of these episodes, in 2219 patients, included records of suicidal behavior (mean [SD] patient age, 40.9 [18.6] years; 1415 episodes [63.2%] in women and 825 [36.8%] in men). A total of 11 109 MDD episodes in 9574 matched patients with MDD without records of suicidal behavior were included as controls (mean [SD] patient age, 40.8 [18.5] years; 7046 episodes [63.4%] in women and 4063 [36.6%] in men). The all-cause mortality rate was 2.5 per 100 person-years at risk for the MDD-SB group and 1.0 per 100 person-years at risk for the MDD-non-SB group, based on 466 deaths. Suicidal behavior was associated with higher all-cause mortality (hazard ratio, 2.62 [95% CI, 2.15-3.20]), as well as with HCRU and work loss, compared with the matched controls. Patients with MDD and suicidal behavior were younger and more prone to have psychiatric comorbid conditions, such as personality disorders, substance use, and anxiety, at the start of their episode. The most important factors associated with suicidal behavior within 1 year after the start of an MDD episode were history of suicidal behavior and age, history of substance use and sleep disorders, and care setting in which MDD was diagnosed. Conclusions and Relevance: This cohort study's findings suggest that high mortality, morbidity, HCRU, and work loss associated with MDD may be substantially accentuated in patients with MDD and suicidal behavior. Use of medication aimed at decreasing the risk of all-cause mortality during MDD episodes should be systematically evaluated to improve long-term outcomes.

Inverse association of anti-inflammatory prescription fills and suicide-related mortality in young adults: Evidence from a nationwide study of Swedish regions, 2006-2021.

Background: This cross-sectional study examined nationwide real-world associations between anti-inflammatory agent fills and suicide-related death rates in 20-24-year-olds across the 21 Swedish regions during 2006-2021. Methods: Nationwide Swedish registers were used to compare regional year-wise suicide-related mortality (SRM) and dispensations for anti-inflammatory agents (ATC-code: M01) in 20-24-year-olds. Dispensations for paracetamol (ATC-code: N02BE01) was applied as a control variable. Associations between regional year-wise SRM and dispensation rates were analyzed by sex-stratified zero-inflated generalized linear mixed effect models (GLMM). Dispensation rates of paracetamol and inflammatory agents were designated as independent fixed effects variables, and year and region constituted random-intercept effects. Results: Acetic acid derivatives and related substances (M01AB) and propionic acid derivates (M01A3) accounted for ∼71% of measured dispensation fills for anti-inflammatory agents. Diclofenac fills constituted ∼98% of the former category, whereas dispensations for Ibuprofen (∼21%), Naproxen (∼62%) and Ketoprofen (∼13%) constituted the most prescribed agents in the latter category. Regional yearly dispensation rates of anti-inflammatory agents in 20-24-year-old females were inversely associated with female SRM (ß = -0.095, p = 0.0393, 95% CI -0.186, -0.005) - independent of paracetamol rates, which were unassociated to SRM (p = 0.2094). Results were confirmed in validation analyses for anti-inflammatory agents (OR = 0.7232, p = 0.0354, 95% CI [OR] 0.5347, 0.9781). No association was demonstrated in males (p = 0.833). Conclusion: Anti-inflammatory agent dispensation rates were independently associated to lower suicide-related death rates in female 20-24-year-olds. This adds to growing evidence implicating inflammatory processes in mental disorders, warranting trials focusing on the suicide preventative potential of anti-inflammatories in young adults.

Impact of general anaesthesia on breast cancer survival: a 5-year follow up of a pragmatic, randomised, controlled trial, the CAN-study, comparing propofol and sevoflurane.

Background: Anaesthesia may impact long-term cancer survival. In the Cancer and Anaesthesia study, we hypothesised that the hypnotic drug propofol will have an advantage of at least five percentage points in five-year survival over the inhalational anaesthetic sevoflurane for breast cancer surgery. Methods: From 2118 eligible breast cancer patients scheduled for primary curable, invasive breast cancer surgery, 1764 were recruited after ethical approval and individual informed consent to this open label, single-blind, randomised trial at four county- and three university hospitals in Sweden and one Chinese university hospital. Of surveyed patients, 354 were excluded, mainly due to refusal to participate. Patients were randomised by computer at the monitoring organisation to general anaesthesia maintenance with either intravenous propofol or inhaled sevoflurane in a 1:1 ratio in permuted blocks. Data related to anaesthesia, surgery, oncology, and demographics were registered. The primary endpoint was five-year overall survival. Data are presented as Kaplan-Meier survival curves and Hazard Ratios based on Cox univariable regression analyses by both intention-to-treat and per-protocol. EudraCT, 2013-002380-25 and ClinicalTrials.gov, NCT01975064. Findings: Of 1764 patients, included from December 3, 2013, to September 29, 2017, 1670 remained for analysis. The numbers who survived at least five years were 773/841 (91.9% (95% CI 90.1-93.8)) in the propofol group and 764/829 (92.2% (90.3-94.0)) in the sevoflurane group, (HR 1.03 (0.73-1.44); P = 0.875); the corresponding results in the per-protocol-analysis were: 733/798 (91.9% (90.0-93.8)) and 653/710 (92.0% (90.0-94.0)) (HR = 1.01 (0.71-1.44); P = 0.955). Survival after a median follow-up of 76.7 months did not indicate any difference between the groups (HR 0.97, 0.72-1.29; P = 0.829, log rank test). Interpretation: No difference in overall survival was found between general anaesthesia with propofol or sevoflurane for breast cancer surgery. Funding: Swedish Research Council; Uppsala-Örebro Regional Research Council; Västmanland Regional Research Fund; Västmanland Cancer Foundation; Stig and Ragna Gohrton Foundation; Birgit and Henry Knutsson Foundation.

Cardiopulmonary haemodynamic effects and gas exchange during apnoeic oxygenation with high-flow and low-flow nasal oxygen: A large animal study.

BACKGROUND: Apnoeic oxygenation with high-flow nasal oxygen prolongs the safe apnoeic period during induction of general anaesthesia. However, central haemodynamic effects and the characteristics of central gaseous exchange remain unexplored. OBJECTIVE: To describe mean pulmonary arterial pressure along with arterial and mixed venous blood gases and central haemodynamic parameters during apnoeic oxygenation with low-flow and high-flow nasal oxygen in pigs. DESIGN: Experimental crossover study. SETTING: Animal study of 10 healthy Swedish landrace pigs at Karolinska Institutet, Sweden, April-May 2021. INTERVENTION: The pigs were anaesthetised, their tracheas intubated and their pulmonary arteries catheterised. The animals were preoxygenated and paralysed before apnoea. Apnoeic periods between 45 and 60 min were implemented with either 70 or 10 l min -1 100% O 2 delivered via nasal catheters. In addition, seven animals underwent an apnoea without fresh gas flow. Cardiopulmonary parameters and blood gases were measured repeatedly. MAIN OUTCOME MEASURES: Mean pulmonary arterial pressure during apnoeic oxygenation with high-flow and low-flow oxygen. RESULTS: Nine pigs completed two apnoeic periods of at least 45 min with a Pa O 2 not lower than 13 kPa. The mean pulmonary arterial pressure increased during 45 min of apnoea, from 18 ±â€Š1 to 33 ±â€Š2 mmHg and 18 ±â€Š1 to 35 ±â€Š2 mmHg, at 70 and 10 l min -1 O 2 , respectively ( P  < 0.001); there was no difference between the groups ( P  = 0.87). The Pa CO 2 increased by 0.48 ±â€Š0.07 and 0.52 ±â€Š0.04 kPa min -1 , at 70 and 10 l min -1 O 2 , respectively; there was no difference between the groups ( P  = 0.22). During apnoea without fresh gas flow, the SpO 2 declined to less than 85% after 155 ±â€Š11 s. CONCLUSION: During apnoeic oxygenation in pigs, the mean pulmonary arterial pressure increased two-fold and Pa CO 2 five-fold after 45 min, while the arterial oxygen levels were maintained over 13 kPa, irrespective of high-flow or low-flow oxygen.

Association of Bipolar Disorder Diagnosis With Suicide Mortality Rates in Adolescents in Sweden.

Importance: The association of early diagnosis and management of bipolar disorder with adolescent suicide mortality (ASM) is unknown. Objective: To assess regional associations between ASM and bipolar disorder diagnosis frequencies. Design, Setting, and Participants: This cross-sectional study investigated the association between annual regional ASM and bipolar disorder diagnosis rates in Swedish adolescents aged 15 to 19 years in January 1, 2008, through December 31, 2021. Aggregated data without exclusions reported at the regional level encompassed 585 suicide deaths, constituting 588 unique observations (ie, 21 regions, 14 years, 2 sexes). Exposures: Bipolar disorder diagnosis frequencies and lithium dispensation rates were designated as fixed-effects variables (interaction term in the case of males). An interaction term between psychiatric care affiliation rates and the proportion of psychiatric visits to inpatient and outpatient clinics constituted independent fixed-effects variables. Region and year comprised random intercept effect modifiers. Variables were population adjusted and corrected for heterogeneity in reporting standards. Main Outcomes and Measures: The main outcomes were sex-stratified, regional, and annual ASM rates in adolescents aged 15 to 19 years per 100 000 inhabitants as analyzed using generalized linear mixed-effects models. Results: Female adolescents were diagnosed with bipolar disorder almost 3 times more often than male adolescents (mean [SD], 149.0 [19.6] vs 55.3 [6.1] per 100 000 inhabitants, respectively). Median regional prevalence rates of bipolar disorder varied over the national median by a factor of 0.46 to 2.61 and 0.00 to 1.82 in females and males, respectively. Bipolar disorder diagnosis rates were inversely associated with male ASM (ß = -0.00429; SE, 0.002; 95% CI, -0.0081 to -0.0004; P = .03) independent of lithium treatment and psychiatric care affiliation rates. This association was replicated by ß-binomial models of a dichotomized quartile 4 ASM variable (odds ratio, 0.630; 95% CI, 0.457-0.869; P = .005), and both models were robust after adjusting for annual regional diagnosis rates of major depressive disorder and schizophrenia. No such association was observed in females. Conclusions and Relevance: In this cross-sectional study, lower suicide death rates in adolescent males was robustly associated with regional diagnosis rates of bipolar disorder at an estimated magnitude of approximately 4.7% of the mean national suicide death rate. The associations could be due to treatment efficacy, early diagnosis and management, or other factors not accounted for.

Anorexia Nervosa With Comorbid Severe Depression: A Systematic Scoping Review of Brain Stimulation Treatments.

ABSTRACT: Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the PubMed, PsycInfo, and MEDLINE databases were searched until July 2022 using specific key words related to AN and brain stimulation treatments. A total of 373 citations were identified, and 49 treatment studies that met the inclusion criteria were included in the review. The initial evidence suggests that electroconvulsive therapy, repetitive transcranial magnetic stimulation, and deep-brain stimulation may be effective in managing comorbid MDD in AN. Emerging evidence suggests that transcranial direct current stimulation may have a positive effect on body mass index in individuals with severe to extreme AN. However, there is a need for the development of better measurement techniques for assessing the severity of depression in the context of AN. Controlled trials that are adequately designed to account for these limitations are highly warranted for deep-brain stimulation, electroconvulsive therapy, and repetitive transcranial magnetic stimulation and hold promise for providing clinically meaningful results.

Regional clozapine, ECT and lithium usage inversely associated with excess suicide rates in male adolescents.

Advanced psychiatric treatments remain uncertain in preventing suicide among adolescents. Across the 21 Swedish regions, using nationwide registers between 2016-2020, we found negative correlation between adolescent excess suicide mortality (AESM) and regional frequencies of clozapine, ECT, and lithium (CEL) usage among adolescents (ß = -0.613, p = 0.0003, 95% CI: -0.338, -0.889) and males (ß = -0.404, p = 0.009, 95% CI: -0.130, -0.678). No correlation was found among females (p = 0.197). Highest CEL usage among male adolescents was seen in regions with lowest quartile (Q1) AESM (W = 74, p = 0.012). Regional CEL treatment frequency in 15-19-year-olds was related to lower AESM in males, reflecting potential treatment efficacy, treatment compliance or better-quality mental health care. Suicide prevention may benefit from early recognition and CEL treatment for severe mental illness in male adolescents. The results indicate association but further research, using independent samples and both prospective and observational methodologies, is needed to confirm causality.

Outcome of transcranial magnetic intermittent theta-burst stimulation in the treatment of depression - A Swedish register-based study.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment of depression. The more recently introduced intermittent Theta-burst stimulation (iTBS) has shown significant superiority over sham-stimulation and equal effect sizes to a 10 Hz protocol in one clinical trial. The aim of the current study was to investigate the effectiveness and tolerability of iTBS in a naturalistic, clinical setting. Further, we explored demographical and clinical predictors of response. METHODS: Data was collected from seventeen rTMS-sites in Sweden between January 2018 and May 2021, through the Swedish National Quality register for repetitive Transcranial Magnetic Stimulation (Q-rTMS). We included 542 iTBS-treated patients with unipolar or bipolar depression. Outcome was assessed with Clinical Global Impression Severity and Improvement scores in an intention to treat analysis. RESULTS: The response rate was 42.1 % and 16.1 % reached remission. The response rate was significantly larger in the oldest age group compared to the youngest (odds ratio 3.46, 95 % confidence interval 1.65-7.22). Less severe level of depression (Montgomery-Åsberg depression rating scale self-assessment < 36) at baseline predicted response and remission. Only <1 % were much or very much worse after treatment. Drop-out rate was 10.9 %. No serious adverse events were reported. LIMITATIONS: Retrospective analysis of register data. No comparison group. CONCLUSIONS: In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials. Older age-group and less severe illness predicted response.