Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression.

BACKGROUND: Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied. METHODS: We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression. RESULTS: Of 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P = 0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups. CONCLUSIONS: In a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.).

Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine.

Bipolar disorder's core feature is the pathological disturbances in mood, often accompanied by disrupted thinking and behavior. Its complex and heterogeneous etiology implies that a range of inherited and environmental factors are involved. This heterogeneity and poorly understood neurobiology pose significant challenges to existing drug development paradigms, resulting in scarce treatment options, especially for bipolar depression. Therefore, novel approaches are needed to discover new treatment options. In this review, we first highlight the main molecular mechanisms known to be associated with bipolar depression-mitochondrial dysfunction, inflammation and oxidative stress. We then examine the available literature for the effects of trimetazidine in said alterations. Trimetazidine was identified without a priori hypothesis using a gene-expression signature for the effects of a combination of drugs used to treat bipolar disorder and screening a library of off-patent drugs in cultured human neuronal-like cells. Trimetazidine is used to treat angina pectoris for its cytoprotective and metabolic effects (improved glucose utilization for energy production). The preclinical and clinical literature strongly support trimetazidine's potential to treat bipolar depression, having anti-inflammatory and antioxidant properties while normalizing mitochondrial function only when it is compromised. Further, trimetazidine's demonstrated safety and tolerability provide a strong rationale for clinical trials to test its efficacy to treat bipolar depression that could fast-track its repurposing to address such an unmet need as bipolar depression.

Cognitive Correlates of Visual and Minor Hallucinations in Parkinson's Disease.

INTRODUCTION: Psychosis is one of the incapacitating nonmotor symptoms of Parkinson's disease (PD). Although several risk factors that include older age, rapid eye movement sleep behavior disorder, depression, and cognitive dysfunction have been identified, the exact neural correlates remain elusive. As cognitive impairment has a close association with psychosis in PD, it is useful to know the spectrum of cognitive impairment in PD patients with psychosis (PD-P). METHODS: This cross-sectional study compared various cognitive parameters of PD-P (visual/minor hallucinations) and PD patients with no psychosis (PD-NP). A neuropsychological battery encapsulating several cognitive domains (executive, visuospatial, learning, and memory) was used for the cognitive assessment of 37 PD-P and 51 PD-NP patients who were matched for age, gender, education, and disease duration. RESULTS: The two groups were comparable in terms of disease severity and stage. Although the groups had a comparable mean score on Montreal cognitive assessment, the PD-P group performed poorly in tests focused on executive function (color trail test, forward digit span), verbal learning and memory (Rey auditory and verbal learning test), and visuospatial functions (complex figure test, corsi block tapping test). Those with complex visual hallucinations performed poorly in the color trial test (part A) compared to those with minor hallucinations. CONCLUSION: Psychosis is associated with a multidomain cognitive dysfunction in PD. All PD patients should undergo detailed cognitive assessment as cognitive dysfunction may be a marker of psychosis in the future. Additional longitudinal studies are warranted to obtain detailed insights into this issue.

Efficacy of Repetitive Transcranial Magnetic Stimulation on Comorbid Anxiety and Depression Symptoms in Obsessive-Compulsive Disorder: A Meta-Analysis of Randomized Sham-Controlled Trials.

OBJECTIVE: To systematically evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in reducing comorbid anxiety and depressive symptoms in patients with obsessive-compulsive disorder (OCD). METHODS: Three electronic databases were searched for randomized, sham-controlled clinical trials evaluating rTMS for the treatment of OCD. Hedge's g was calculated as the effect size for anxiety/depression symptom severity (primary outcome) and OCD severity (secondary outcome). Subgroup analyses and meta-regression analyses were carried out to evaluate the most promising target and whether a reduction in OCD severity moderates the change in anxiety or depression scores. RESULTS: Twenty studies (n = 688) were included in the meta-analysis. rTMS had small-medium effect size on OCD (Hedge's g = 0.43; 95% confidence interval [CI]: [0.20, 0.65]; P < 0.001), anxiety (Hedge's g = 0.3; 95% CI: [0.11, 0.48]; P = 0.001) and depression (Hedge's g = 0.24; 95% CI: [0.07, 0.40]; P = 0.003) symptoms. Subgroup analysis showed that protocols targeting dorsolateral prefrontal cortex (DLPFC) were effective for 3 outcome measures. The change in anxiety, but not depression severity, was moderated by a change in OCD symptom scores. However, the findings are uncertain as a majority of the studies had some concerns or a high risk of bias. CONCLUSIONS: Active rTMS protocol targeting DLPFC is effective in reducing the comorbid anxiety/depression symptoms along with OCD severity. The antidepressant effect is not moderated by the anti-obsessive effect of rTMS.

Impact of the COVID-19 Pandemic on the Short-Term Course of Obsessive-Compulsive Disorder.

ABSTRACT: There is an understandable concern that obsessive-compulsive disorder (OCD) may worsen during the COVID-19 pandemic, but there are little empirical data. We report the impact of COVID-19 pandemic on the short-term course of OCD. A cohort of patients with a primary diagnosis of OCD (n = 240) who were on regular follow-up at a tertiary care specialty OCD clinic in India were assessed telephonically, about 2 months after the declaration of the pandemic ("pandemic" cohort). Data from the medical records of an independent set of patients with OCD (n = 207) who were followed up during the same period, 1 year prior, was used for comparison (historical controls). The pandemic group and historical controls did not differ in the trajectories of the Yale-Brown Obsessive-Compulsive Scale scores (chi-square likelihood ratio test of the group × time interaction = 2.73, p = 0.255) and relapse rate (21% vs. 20%; adjusted odds ratio, 0.81; 95% confidence interval, 0.41-1.59; p = 0.535). Preexisting contamination symptoms and COVID-19-related health anxiety measured by the COVID-Threat Scale did not predict relapse. Only a small proportion of patients (6%) reported COVID-19-themed obsessive-compulsive symptoms. The COVID-19 pandemic, at least in the short run, did not influence the course of illness.

Long-term Outcomes of Intensive Inpatient Care for Severe, Resistant Obsessive-Compulsive Disorder: Résultats à long terme de soins intensifs à des patients hospitalisés pour un trouble obsessionnel-compulsif grave et résistant.

OBJECTIVE: A substantial proportion of severely ill patients with obsessive-compulsive disorder (OCD) do not respond to serotonin reuptake inhibitors (SRIs) and are unable to practice cognitive behavioral therapy (CBT) on an out-patient basis. We report the short-term (at discharge) and long-term (up to 2 years) outcome of a multimodal inpatient treatment program that included therapist-assisted intensive CBT with adjunctive pharmacotherapy for severely ill OCD patients who are often resistant to SRIs and are either unresponsive or unable to practice outpatient CBT. METHODS: A total of 420 patients, admitted between January 2012 and December 2017 were eligible for the analysis. They were evaluated using the Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the Clinical Global Impression (CGI) scale. All patients received 4 to 5 therapist-assisted CBT sessions per week along with standard pharmacotherapy. Naturalistic follow-up information at 3, 6, 12, and 24 months were recorded. RESULTS: At baseline, patients were mostly severely ill (YBOCS = 29.9 ± 4.5) and nonresponsive to ≥2 SRIs (83%). Mean duration of inpatient stay was 42.7 ± 25.3 days. At discharge, there was a significant decline in the mean YBOCS score (29.9 ± 4.5 vs. 18.1 ± 7.7, P < .001, Cohen's d = 1.64); 211/420 (50%) were responders (≥35% YBOCS reduction and CGI-I≤2) and an additional 86/420 (21%) were partial responders (25% to 35% YBOCS reduction and CGI-I≤3). Using latent class growth modeling of the follow-up data, 4 distinct classes were identified, which include "remitters" (14.5%), "responders" (36.5%), "minimal responders" (34.7%), and "nonresponders" (14.6%). Shorter duration of illness, better insight, and lesser contamination/washing symptoms predicted better response in both short- and long-term follow-up. CONCLUSION: Intensive, inpatient-based care for OCD may be an effective option for patients with severe OCD and should be considered routinely in those who do not respond with outpatient treatment.

Effectiveness of Venlafaxine in Selective Serotonin Reuptake Inhibitor-Resistant Obsessive-Compulsive Disorder: Experience From a Specialty Clinic in India.

BACKGROUND: Despite its favorable pharmacological profile and efficacy in major depression and anxiety disorders, evidence for the use of venlafaxine in obsessive-compulsive disorder (OCD) is limited. We sought to examine the real-world effectiveness of venlafaxine from a large database of an OCD clinic in India. METHODS: A total of 1704 consecutive patients who registered at the OCD clinic between June 2014 and December 2016 were evaluated with structured interviews and scales. Patients with symptomatic OCD (Yale-Brown Obsessive-Compulsive Severity ≥16) despite treatment with selective serotonin reuptake inhibitors and initiated on venlafaxine were included for analysis. The main outcome measures were response as defined by 35% or more reduction in the Yale-Brown Obsessive-Compulsive Severity total score and "all-cause discontinuation." RESULTS: Of a total of 65 patients who were eligible for analysis, 29(45%) were responders at the end of 16 weeks and 27 (42%) continued to remain on venlafaxine. Repeated measures analysis of variance yielded significant reduction in the Yale-Brown Obsessive-Compulsive Severity total score (F(1.29, 82.4) = 56.54, P < 0.001, partial η = 0.469). On regression analysis, only lower insight (P = 0.048) predicted poor response. CONCLUSIONS: The study suggests that venlafaxine may be useful in a proportion of patients with poor response to selective serotonin reuptake inhibitors and therefore requires to be studied in controlled trials.

Treatments used for obsessive-compulsive disorder-An international perspective.

OBJECTIVE: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive-compulsive disorder (OCD). METHODS: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. RESULTS: The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13.2%) and fluvoxamine (n = 913; 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428; 7.3%) and aripiprazole (n = 415; 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the sample. There was significant variation in the use and accessibility of exposure and response prevention for OCD. CONCLUSIONS: The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended.

A Positron Emission Tomography Study of Norepinephrine Transporter Occupancy and Its Correlation with Symptom Response in Depressed Patients Treated with Quetiapine XR.

Background: Quetiapine is effective in treating depressive symptoms in major depressive disorder and bipolar disorder, but the mechanisms underlying its antidepressants effects are unknown. Norquetiapine, a metabolite of quetiapine, has high affinity for norepinephrine transporter, which might account for its therapeutic efficacy. Methods: In this study, we used positron emission tomography with (S,S)-[11C]O-methyl reboxetine to estimate norepinephrine transporter density and assess the relationship between norepinephrine transporter occupancy by quetiapine XR and improvement in depression in patients with major depressive disorder (n=5) and bipolar disorder (n=5). After the baseline positron emission tomography scan, patients were treated with quetiapine XR with a target dose of 150 mg in major depressive disorder and 300 mg in bipolar disorder. Patients had a second positron emission tomography scan at the end of week 2 and a final scan at week 7. Results: Norepinephrine transporter density was significantly lower in locus ceruleus in patients compared with healthy subjects. Further, there was a significant positive correlation between quetiapine XR dose and norepinephrine transporter occupancy in locus ceruleus at week 2. The norepinephrine transporter occupancy at week 2 in hypothalamus but not in other regions predicted improvement in depression as reflected by reduction in MADRS scores from baseline to week 7. The estimated dose of quetiapine XR associated with 50% norepinephrine transporter occupancy in hypothalamus at week 2 was 256 mg and the estimated plasma levels of norquetiapine to achieve 50% norepinephrine transporter occupancy was 36.8 µg/L. Conclusion: These data provide preliminary support for the hypothesis that norepinephrine transporter occupancy by norquetiapine may be a contributor to the antidepressant effects of quetiapine.

Hippocampal subfield atrophy in patients with Parkinson's disease and psychosis.

Psychosis, manifested through formed visual hallucinations or minor hallucinations, is a common non-motor symptom of Parkinson's disease (PD). The pathogenesis of psychosis in PD remains unclear; however, is possibly linked to structural and functional alterations in the hippocampus. To explore the role of hippocampus in psychosis, a detailed hippocampal subfield analysis was performed on PD patients with (PD-P) and without psychosis (PD-NP), and healthy controls (HC). An automated subfield parcellation was performed on T1 MRI images of 141 subjects (PD-P:42, PD-NP:51, and HC:48). The volumes of 12 subfields on each side were estimated and analyzed between the three groups and were corrected for multiple comparisons using false discovery rates. The volumes were also correlated to psychosis severity and specific neuropsychological tests and finally were employed to predict the psychosis severity in PD-P using a support vector regression (SVR) model. Compared to controls, PD-NP group did not demonstrate any significant differences; however, the PD-P group had significantly lower total hippocampal volume. Bilateral molecular layer, granule cell-dentate gyrus, left subiculum, and hippocampal tail and right CA3, CA4, and HATA illustrated significantly lower volumes, while bilateral hippocampal fissure demonstrated a significant widening. Compared to PD-NP, the PD-P group had higher volume of the bilateral hippocampal fissures. Finally, SVR could significantly predict the psychosis severity from all the subfield volumes. Our findings indicate a higher degeneration of specific hippocampal subfields in PD-P compared to controls and a trend of higher volume of hippocampal fissures in PD-P group than in PD-NP.

Augmentation Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation Over Presupplementary Motor Area in Obsessive-Compulsive Disorder: A Randomized Controlled Trial.

OBJECTIVE: The current study investigated the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) over bilateral presupplementary motor area (pre-SMA) in patients suffering from obsessive-compulsive disorder (OCD) with partial/poor response to pharmacotherapy, in a double-blinded randomized sham controlled trial. METHOD: Forty subjects with OCD, who were on stable medications with partial/poor response to pharmacotherapy were randomly divided into 2 groups (n = 20 in each group), to receive either active or sham low-frequency rTMS over bilateral pre-SMA. Thirty-six patients were eligible for intent-to-treat analysis. There was no significant difference in relevant demographic and clinical variables between the 2 groups at baseline. RESULTS: There were no statistically significant differences between the 2 groups after 3 weeks of treatment in the Yale-Brown Obsessive Compulsive Scale score (time*group interaction, F2.48,84.16 = 0.80, P = 0.40) and other secondary outcome measures including responder rates and depressive and anxiety symptoms. CONCLUSIONS: Low-frequency rTMS over pre-SMA may not be effective as an augmenting agent in partial/poor responders to SRIs. This study underlines the need to explore alternate rTMS protocols in OCD.

Duration of Pupillary Unresponsiveness to Light: A Physiological Adjunct to Electroencephalography and Motor Seizure Duration Monitoring During Electroconvulsive Therapy.

BACKGROUND: During electroconvulsive therapy (ECT) sessions, we observed that the time taken for the return of pupillary response to light (ROPL) outlasted both the electroencephalography (EEG) and the motor seizure duration after the delivery of the electrical stimulus to produce convulsions. OBJECTIVE: The objective of this study was to investigate whether ROPL can be used as a marker of cessation of seizure activity in the brain after ECT and also to study the effect of atropine premedication on seizure activity during ECT. METHODS: Forty-one patients underwent 82 sessions of ECT in a cross-over design study. The duration of motor seizure, EEG seizure, and time for ROPL was observed and compared. RESULTS: The ROPL consistently outlasted EEG and motor seizures; the difference in their mean durations was statistically significant P < 0.05. There was good correlation among the 3 parameters. Atropine premedication did not alter the seizure activity and ROPL after ECT. CONCLUSIONS: The ROPL after ECT stimulus is a good bedside monitor for termination of seizure activity and can be a valuable adjunct to surface EEG in monitoring the duration of epileptic activity after delivery of ECT.

Aripiprazole augmentation in highly treatment-resistant obsessive-compulsive disorder - experience from a specialty clinic in India.

OBJECTIVE: To study the effectiveness and tolerability of aripiprazole augmentation in patients with highly treatment-resistant obsessive-compulsive disorder (OCD) in a real-world scenario. METHODS: We conducted a chart review of patients who were initiated on aripiprazole augmentation at a specialty OCD clinic in India between 2004 and 2014. Primary outcome measure was all-cause discontinuation. RESULTS: 23 patients were eligible for analysis. Patients had not achieved symptom remission despite a mean of over 3 prior SRI trials. Aripiprazole was continued to be used in seven patients (30%) at the time of last follow-up. Thirteen patients (57%) discontinued the drug due to side effects, and three patients (13%) discontinued aripiprazole citing no improvement. Six patients (26%) were noted to have ≥25% reduction on the Yale-Brown Obsessive-Compulsive Scale. CONCLUSIONS: The study demonstrated, in a real-world setting, that aripiprazole may be a useful augmenting agent in a proportion of patients with highly treatment-resistant OCD. However, side effects may lead to premature discontinuation in many of them.

Effectiveness of Risperidone Augmentation in Obsessive-Compulsive Disorder: Experience From a Specialty Clinic in India.

Risperidone is the most widely used augmenting agent in the treatment of obsessive-compulsive disorder (OCD). However, a recent controlled study found risperidone to be no different from placebo, raising doubts about its effectiveness. In this context, we sought to examine the real-world effectiveness of risperidone from the large database of an OCD clinic in India. A total of 1314 consecutive patients who registered at the OCD clinic between 2004 and 2014 were evaluated with structured interviews and scales. Patients with OCD initiated on risperidone augmentation without concurrent cognitive behavior therapy and who were on stable and adequate doses of serotonin reuptake inhibitors for at least 12 preceding weeks were included for analysis. The primary outcome measure was all-cause discontinuation. Logistic regression was performed to identify the factors predicting improvement with risperidone augmentation. A total of 92 patients were eligible for analysis. Risperidone continued to be used in 23 patients (25%) at the time of last follow-up, and the remaining discontinued either because of ineffectiveness or intolerability. The fall in the Yale-Brown Obsessive-Compulsive Scale scores was significantly greater in patients who continued to take risperidone when compared with those who did not (41.6% vs 3.7%, t = 6.95, P < 0.001). A total of 22 patients (24%) were noted to have at least a 25% reduction on the Yale-Brown Obsessive-Compulsive Scale scores. On regression analysis, no predictors of improvement with risperidone augmentation could be identified. The study demonstrated, in a real-world setting, that risperidone may be a useful augmenting agent in a proportion of patients with partial/poor response to serotonin reuptake inhibitors.

Repetitive Transcranial Magnetic Stimulation Over Presupplementary Motor Area May Not Be Helpful in Treatment-Refractory Obsessive-Compulsive Disorder: A Case Series.

BACKGROUND: A significant proportion of patients with obsessive-compulsive disorder (OCD) fail to improve with standard medication and cognitive behavior therapy. Repetitive transcranial magnetic stimulation (rTMS) has been investigated for its role in treating OCD. Low-frequency rTMS over the presupplementary motor area (pre-SMA) has shown mixed results. Moreover, it has not been studied in highly treatment refractory OCD. We analyzed the outcome of low-frequency rTMS over pre-SMA in OCD patients refractory to multiple serotonin reuptake inhibitors (SRIs), augmenting agents, and cognitive behavior therapy. METHODS: Low-frequency (1-Hz stimulus at 100% motor threshold) rTMS was delivered over the pre-SMA using a previously described protocol. At least 25% reduction Yale-Brown Obsessive Compulsive Scale scores and 2-point reduction in Clinical Global Impression-Severity of Illness scores were used to assess treatment response. RESULTS: Seventeen patients were initiated on rTMS. Three of them dropped out within 9 sittings. Only 1 patient met the criteria for response after 1 month of treatment initiation. No major adverse effects were observed in any of them. LIMITATIONS: The study is a retrospective analysis of outcomes when rTMS was administered as part of routine clinical care. Assessments of the patients were done by trained but different raters, and interrater reliability was not measured. CONCLUSIONS: Low-frequency rTMS over the pre-SMA may not be effective in treatment refractory OCD. Further studies, taking note of the possible reasons for ineffectiveness discussed in the study, may help elucidate the role of rTMS in OCD.

Comparison of clinical characteristics of familial and sporadic obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous condition with evidence of familiality in a considerable proportion of patients. A classification into familial and sporadic forms has been proposed to explain the heterogeneity. The current study aims to compare the demographic, clinical and comorbidity patterns of patients with and without a family history of OCD in first-degree relatives. METHOD: 802 consecutive patients who consulted a specialty OCD Clinic at a tertiary care psychiatric hospital in India were evaluated with the Mini-International Neuropsychiatric Interview, the Yale-Brown Obsessive-Compulsive Scale, and the Clinical Global Impression Scale. Family history was assessed by interviewing patients and at least one first-degree relative. RESULTS: Family history of OCD was seen in 152 patients (19%). Family history was associated with juvenile onset (Χ(2)=19.472, p<0.001), obsessions of contamination (Χ(2)=6.658, p=0.01), hoarding (Χ(2)=4.062, p=0.032), need for symmetry (Χ(2)=3.95, p=0.047), washing compulsion (Χ(2)=7.923, p=0.005), ordering compulsions (Χ(2)=6.808, p=0.009), repeating compulsions (Χ(2)=4.950, p=0.026) and compulsions by proxy (Χ(2)=7.963, p=0.005). Family history was also associated with greater severity of OCD (t=-2.31, p=0.022) and compulsions (t=-3.09, p=0.002) and longer duration of illness at presentation (t=-2.93, p=0.004). CONCLUSION: Our findings suggest that familial OCD may have distinctive clinical features. Studying familial forms of OCD may offer unique insight in to understanding the genetic basis of OCD.

Comparative efficacy of repetitive transcranial magnetic stimulation protocols for obsessive-compulsive disorder: A network meta-analysis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been found to be helpful for the treatment of obsessive-compulsive disorder (OCD). However, the relative efficacy of different rTMS protocols is unclear. OBJECTIVE: To conduct a systematic review and network meta-analysis (NMA) of published literature to compare the relative efficacy of different rTMS protocols for decreasing Yale-Brown Obsessive Compulsive Severity (Y-BOCS) scores in patients with OCD. METHOD: Relevant articles published between 1985 to September 2023 were searched from the Cochrane Central Register of Controlled Trials, PubMed and PsycInfo. Double or single-blinded randomized controlled studies conducted on patients with OCD comparing an active rTMS protocol with either another active or sham rTMS protocol were included. Network meta-analysis (NMA) was conducted using a frequentist approach. Standardized mean difference (SMD) of change in Y-BOCS scores was calculated employing Hedge's g. Pairwise meta-analysis using random effects model was conducted which was extended to the NMA using restricted maximum likelihood estimation procedure. Surface under the cumulative ranking (SUCRA) probabilities were used to rank the interventions. RESULTS: Excitatory rTMS of the bilateral dorsolateral prefrontal cortex (DLPFC), inhibitory rTMS of right DLPFC, inhibitory as well as excitatory rTMS of bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and inhibitory rTMS of bilateral supplementary motor area (SMA) were superior to sham stimulation. The DLPFC and mPFC/ACC protocols had a higher probability of being among the top-ranked interventions. The majority of studies had a modest sample size and at least some concerns in the risk of bias assessment. CONCLUSION: rTMS targeting either the medial or lateral prefrontal cortices is a promising intervention for resistant OCD. There is a need to confirm these findings in large systematic studies.

Long-term impact of the COVID-19 pandemic on obsessive-compulsive disorder.

There is limited data on the long-term effect of the COVID-19 pandemic on obsessive-compulsive disorder (OCD). We report on the course of a cohort of individuals with OCD followed-up over a period of one year during the first wave of the COVID-19 pandemic in India. A cohort of 240 individuals registered at a specialty OCD clinic was regularly followed-up using standardized rating tools at three months, six months, and one year into the onset of the COVID-19 pandemic in India. These were compared with clinical ratings recorded in a comparable historical cohort of 207 individuals with OCD, followed up during a non-pandemic year. The pandemic and non-pandemic (historical control) cohorts did not differ in illness severity and rate of relapse. It was found that COVID-19-related anxiety declined over time. Among those patients who were treatment responders prior to the pandemic, COVID-19-related anxiety and non-adherence to medication predicted a relapse of symptoms. Contrary to our expectations, the rate of relapse and illness trajectory in the pandemic cohort did not differ from the non-pandemic cohort, suggesting that the pandemic did not impact our largely medication-adherent cohort. Adherence to treatment seemed to have a protective effect during the pandemic.

Development, validation and clinical utility of short-term adverse-effects of electroconvulsive therapy (SAVE) checklist.

Electroconvulsive therapy (ECT) is one of the most effective treatments in psychiatry. However, it has many cognitive and non-cognitive adverse effects (AEs). There are lacunae in the literature on systematic assessment of non-cognitive AEs. There is a need for a standard, comprehensive and specific clinical tool to evaluate this. Hence, a checklist of short-term AEs of ECT (SAVE) with a 2-phase assessment was developed. Content validation was done using 15 experts' ratings and predefined content validity ratio and index (CVR and CVI) in a two-stage modified Delphi method. The checklist had a good CVR and CVI with a final tool of 39 items. The tool was sensitive and identified the non-cognitive AEs after ECT. Cardiovascular and musculoskeletal systems displayed the highest incidence. Many participants exhibited delayed recovery in orientation, gait, and stance, highlighting a necessity for meticulous monitoring. SAVE is the first standardised tool to assess short-term ECT-related AEs systematically. This checklist likely identifies clinically significant incidences of adverse effects. Its regular use may enhance the safety of ECT and patient comfort by supporting early identification and intervention for AEs. However, given the transient nature of AEs, further studies are needed to determine their predictive validity for long-term consequences.

Neurocognitive Deficits in Recently Diagnosed Young Remitted Bipolar I Disorder and At-Risk Subjects: Potential Endophenotypes?

Background: Neurocognitive deficits have been reported consistently in euthymic bipolar disorder (BD) across studies. Endophenotype potential of such deficits have been reported in a few studies. However, data from the Indian subcontinent is sparse, and no studies had a sample (patients and high-risk group) aged 20-25 years, which is the actual risk period for developing BD. We studied cognitive deficits, as a potential endophenotype for BD, in recently diagnosed BD (FEM-first episode mania) in remission, young unaffected first-degree relatives (HR) of patients with BD, and healthy controls (HC). Methods: Cross-sectional study design using convenient sampling was employed. We recruited FEM (n = 25), HR (n = 25), and age-matched HC (n = 25) between 18 and 30 years. All HR subjects were <25 years of age, which is the period of vulnerability for BD. All the groups were screened using MINI Version 6. Neurocognitive assessments were done using the NIMHANS neuropsychology battery. The cognitive domains assessed were processing speed, attention, working memory, executive functions, and visual and verbal memory. Results: The three groups were comparable in age and sex (all P > 0.06). The mean (SD) age of the FEM subjects was 23.7 (3.47) years, and the mean duration of illness was 5.92 (2.94) months. Compared to the HC group, the FEM group performed poorly on multiple cognitive domains (all P < 0.05). Performance of the HR group was comparable to the FEM group, but they showed significantly poorer performance compared to HC on the verbal fluency test-controlled oral word association (COWA, F = 12.36, P = 0.001), and the visual learning and memory test-complex figure test-immediate recall (CFT-IR, F = 8.10 and p = 0.001). Conclusions: Cognition is impaired very early in the course of BD. Visual memory and executive function (verbal fluency) have endophenotypic potential. These findings are particularly important given that the HR group were still within the vulnerable period to develop BD. These findings imply a tremendous potential for early diagnosis and prevention by early interventions in BD.