Evidence from Indian studies on safety and efficacy of therapeutic transcranial magnetic stimulation across neuropsychiatric disorders- A systematic review and meta-analysis.

Repetitive transcranial magnetic stimulation (rTMS) is potentially effective as an augmentation strategy in the treatment of many neuropsychiatric conditions. Several Indian studies have been conducted in this regard. We aimed to quantitatively synthesize evidence from Indian studies assessing efficacy and safety of rTMS across broad range of neuropsychiatric conditions. Fifty two studies- both randomized controlled and non-controlled studies were included for a series of random-effects meta-analyses. Pre-post intervention effects of rTMS efficacy were estimated in "active only" rTMS treatment arms/groups and "active vs sham" (sham-controlled) studies using pooled Standardized Mean Differences (SMDs). The outcomes were 'any depression', depression in unipolar/bipolar depressive disorder, depression in obsessive compulsive disorder (OCD), depression in schizophrenia, schizophrenia symptoms (positive, negative, total psychopathology, auditory hallucinations and cognitive deficits), obsessive compulsive symptoms of OCD, mania, craving/compulsion in substance use disorders (SUDs) and migraine (headache severity and frequency). Frequencies and odds ratios (OR) for adverse events were calculated. Methodological quality of included studies, publication bias and sensitivity assessment for each meta-analyses was conducted. Meta-analyses of "active only" studies suggested a significant effect of rTMS for all outcomes, with moderate to large effect sizes, at both end of treatment as well as at follow-up. However, except for migraine (headache severity and frequency) with large effect sizes at end of treatment only and craving in alcohol dependence where moderate effect size at follow-up only, rTMS was not found to be effective for any outcome in the series of "active vs sham" meta-analyses. Significant heterogeneity was seen. Serious adverse events were rare. Publication bias was common and the sham controlled positive results lost significance in sensitivity analysis. We conclude that rTMS is safe and shows positive results in 'only active' treatment groups for all the studied neuropsychiatric conditions. However, the sham-controlled evidence for efficacy is negative from India. Conclusion: rTMS is safe and shows positive results in "only active" treatment groups for all the studied neuropsychiatric conditions. However, the sham-controlled evidence for efficacy is negative from India.

Safety and Efficacy of Continuous Theta Burst "Intensive" Stimulation in Acute-Phase Bipolar Depression: A Pilot, Exploratory Study.

OBJECTIVES: Repetitive transcranial magnetic stimulation efficacy in unipolar depression is known, but its efficacy in acute-phase bipolar depression is at best modest. Citing differential right dorsolateral prefrontal cortex hyperconnectivity implicated in BD, we aimed to study the effect of novel continuous theta burst stimulation (cTBS) targeting right dorsolateral prefrontal cortex in a randomized rater blinded placebo control design. MATERIAL AND METHODS: Nineteen patients aged 18 to 59 years (baseline Hamilton Depression Rating Scale [HAM-D] 17 severity score >18) were randomly allocated to active cTBS (n = 11) and sham cTBS (n = 9) groups using block randomization method. They received 15 cTBS sessions (burst of 3 pulses delivered at 50 Hz, repeated every 200 ms at 5 Hz, 600 pulses per session), 3 sessions per day (total of 1800 pulses) for 5 days in a week at 80% resting motor threshold. The HAM-D, Beck Depression Inventory, Hamilton Anxiety Rating Scale, World Health Organization's abbreviated quality of life assessment, and Changes in Sexual Functioning Questionnaire were assessed at baseline, after the last session, and at 2 weeks after repetitive transcranial magnetic stimulation. Intention-to-treat analysis was conducted and missing values (2 patients) were replaced using the last observation carried forward method. RESULTS: On repeated measures analysis of variance, a significant within-group time effect (from pretreatment to 2 weeks after TBS) for HAM-D ( F = 15.091, P < 0.001), Beck Depression Inventory ( F = 22.376, P < 0.001), Hamilton Anxiety Rating Scale ( F = 18.290, P < 0.001), Changes in Sexual Functioning Questionnaire ( F = 9.281, P = 0.001), and World Health Organization's abbreviated quality of life assessment ( F = 24.008, P < 0.001). The integrity of the blind assessed by the guess matrix was good. When significant between group*time effect was compared, none of the variables retained statistical significance. No major adverse effects were reported, and none of the patients discontinued the trial because of adverse effects. CONCLUSIONS: Our trial concludes that although safe and well tolerated, the therapeutic efficacy of intensive intermittent TBS in acute-phase bipolar depression is inconclusive. Choice of lower total number to sessions and smaller intersession interval along with small sample size limit the study findings.

Sleep Quality in Patients With Schizophrenia in a Tertiary Care Center in Northern India.

Objective: To assess the quality of sleep among patients with schizophrenia.Methods: A cross-sectional descriptive study was conducted with 100 outpatients with schizophrenia recruited from a tertiary care center in Northern India from July 2022 to December 2022. Eligible participants were required to complete a demographic form, the Pittsburgh Sleep Quality Index (PSQI), and the Insomnia Severity Index (ISI). The severity of psychosis was assessed with the Positive and Negative Syndrome Scale (PANSS).Results: The mean age of the participants was 38.87 years (SD = 10.564). The prevalence of poor sleep quality (PSQI ≥ 5) among the patients with schizophrenia was 78%, and the mean PSQI score was 11.2 (SD = 5.31). Most of the participants in whom the prevalence of poor sleep quality was marginally higher were female (51%). Of the 7 PSQI components, daytime dysfunction was more affected (49%) compared to the other 6 components. There was a positive correlation between PSQI and ISI scores (r = 0.805, P < .001). PSQI (U = 380, P < .001) and ISI scores (U = 517, P < .001) were significantly lower in schizophrenia patients taking benzodiazepines. The PANSS scores were not significantly correlated with PSQI or ISI scores.Conclusions: Most patients with schizophrenia suffered significantly from poor sleep quality. The results showed the deleterious impact of poor sleep on their daytime functioning, suggesting the need for comprehensive management of sleep problems in such patients.Prim Care Companion CNS Disord 2023;25(6):23m03564. Author affiliations are listed at the end of this article.

Sexual dysfunction in bipolar depression: Gender differences.

Objective: To find sexual dysfunction in acute-phase bipolar depression patients and subsequently characterize the gender-wise differences in sexual functioning. Materials and Methods: A cross-sectional, descriptive, observational, purposeful, and hospital-based study was done with 45 patients (age range: 18-59 years) with moderate to severe acute phase bipolar depression (HAM-D scores >18). The domain-wise (Pleasure, Desire/Frequency Desire/Interest, Arousal/Excitement, and Orgasm/Completion) sexual functioning was assessed by the Change in Sexual Functioning Questionnaire (CSFQ-14) (≤41 for females, ≤47 for males as a cut-off for dysfunction). This study is registered in the CTRI (Clinical Trials Registry India, Number: CTRI-2021-07-035182). Results: The prevalence of sexual dysfunction was 91% of bipolar disorder patients with more male participants (53.3%) compared to females (46.7%). The mean HAM-D score for the study sample was 27.93 ± 8.035. The female gender had more dysfunctional scores in desire/frequency (t = 2.229, P = 0.031), desire/interest (t = 2.448, P = 0.019), orgasm/completion (t = 2.974, P = 0.005), and overall total CSFQ (t = 2.946, P = 0.005). The odds of sexual dysfunction were significant given a one-unit increase in suicidal ideation in the index episode (adjusted OR = 1.222, 95% CI: 1.004-1.488, P = .049). Conclusion: Acute-phase bipolar patients have very high sexual dysfunction rates. Females have both global and specific sexual response cycle deficits in comparison to acute phase bipolar depressed males. Future trials shall amuse neurobiology grounded, more individualistic sexual rehabilitation-based interventional paradigms, and longitudinal research models in acute phase bipolar depression.

Pragmatic issues and prescribing patterns in bipolar disorder: A mental health professional's survey.

Background: There is substantial treatment gap between the suggested guidelines and pragmatic clinical practice for psychotropic usage in bipolar disorder (BD) due to the lack of naturalistic studies and not taking into account the transcultural differences and diverse background. We intend to study this treatment gap and elucidate the preference of psychotropics and prescription patterns, critical clinical issues faced and related pragmatics in BD by conducting the mental health professionals survey. Methodology: After focused discussions, Canadian Network for Mood and Anxiety Treatments guidelines being the primary anchor, a 46-item online survey questionnaire was prepared. With 25.4% response rate, 127 psychiatrists were evaluated using Survey Monkey® electronic platform on the demographics, predominant polarity; usage of antipsychotics, antidepressants, and electroconvulsive therapy, psychotropic's preference (monotherapy vs. polytherapy) in the acute and maintenance phase of BD. Results: Majority of the participants were males (70.9%) and placed in government institute or medical colleges. Majority agreed that child and adolescent and old age bipolar probands are not routinely seen but subthreshold BD cases are frequent; did not prefer mood stabilizer in pregnancy (61.4%) and antidepressants, preferred polytherapy in acute but monotherapy in maintenance phase (after 3rd episode), seldom preferred ECT as an option (more in suicidality), agreed to a subset of BD being refractory and neuroprogressive. Conclusion: This study elucidates the importance of treatment preferences, prescribing patterns and pragmatic issues faced by the clinicians. These patterns if studied longitudinally in a systematic manner would help in modifying the potential treatment strategies and reduce treatment gap.

Familial Co-Aggregation of Dementia with Schizophrenia: A Cross Sectional Pedigree Analysis.

Background: Cognitive impairment is the core outcome defining feature in schizophrenia. Schizophrenia, in the context of a broader neurodegenerative conceptualization, may have shared etiology with major neurocognitive disorders (MNCD). To elucidate this association there is definite need to explore the familial loading of dementia, in families of patients with schizophrenia. Methods: The authors compared relatives including parental generation and siblings of 100 cases (schizophrenia probands) and 100 controls (anxiety disorder) in order to assess the familial co-aggregation of MNCD. All cases and control were screened with Mini International Neuropsychiatric Interview screen for psychiatric morbidity. The pedigree analysis was conducted by family history method and Family Interview for Genetic Studies. Cognitive impairment in pedigree was screened by community screening instrument for dementia. Results: There was nonreporting of MNCD in the total 2538 relatives (proband siblings +parental generation) of both cases and controls. Diabetes mellitus was the most common somatic morbidity, found significantly more among the parental generation of cases than healthy controls (χ2 (1, 1713) = 6.452, P < 0.05). The odds of having various psychiatric and medical morbidities in the schizophrenia families compared to control are less than 1. Conclusion: There is no familial co-aggregation of MNCD in schizophrenia probands and common etiology between the two is less likely. Either schizophrenia could be counter-intuitively protective for MNCD or a reversible risk factor that can be prevented by effective treatments.

Motor cortical plasticity in adolescents with early onset schizophrenia: A TMS-EMG study assessing the perturbation effect of intermittent and continuous theta burst stimulation.

BACKGROUND: Neuroplasticity in adolescents is distinct from that of adults. Literature pertaining to neuroplasticity in schizophrenia is limited to adult populations. AIM: We aimed to assess baseline (or resting) cortical excitability and cortical plasticity in adolescents with schizophrenia using the transcranial magnetic stimulation-electromyography (TMS-EMG) protocol. METHODS: Twenty adolescent cases with schizophrenia and 20 age and gender matched healthy controls were studied using a crossover design. Single pulse TMS elicited resting motor threshold (RMT) and motor evoked potentials (MEPs) were assessed. Cortical plasticity was determined by tracking MEPs after a single session continuous theta burst stimulation (cTBS) and intermittent theta burst stimulation (iTBS) up to 120 min at 12 intervals. RESULTS: Baseline (or resting) cortical excitability was found to be significantly lower in cases compared with controls. Response patterns to cTBS and iTBS were similar between the crossover. While cTBS led to inhibitory response, iTBS had an excitatory effect in both the groups. In the cases, while cTBS led to significantly greater initial inhibitory response, iTBS led to significantly lower excitatory response, compared with controls. The time taken to return to baseline excitability was significantly longer after receiving cTBS for cases, compared with controls. CONCLUSIONS: iTBS and cTBS lead to excitatory and inhibitory response, representing classical long-term depression and long-term potentiation effects, respectively, in both cases and controls. We conclude that adolescents with schizophrenia have significantly lower baseline (resting) cortical excitability as well as significantly greater inhibitory plasticity; excitatory plasticity is significantly lower.

"Efficacy of intensive bilateral Temporo-Parietal Continuous theta-burst Stimulation for Auditory VErbal hallucinations (TPC-SAVE) in schizophrenia: A randomized sham-controlled trial"☆.

Transcranial magnetic stimulation (TMS) is a non-invasive tool that moderates specific brain regions to ameliorate auditory verbal hallucinations (AVH) in schizophrenia. Citing the critical involvement of temporoparietal cortex (TPC) in AVH, our study aimed to evaluate the effect of continuous theta burst stimulation (cTBS) targeting bilateral TPC in schizophrenia subjects with AVH, on a randomized rater blinded placebo control trial. 59 patients were randomly allocated to active and sham groups. They received 20 cTBS sessions (2 per day: first right TPC, then left TPC) 5 days a week for 2 weeks. PANSS (Positive and Negative Syndrome Scale), AVHRS (Auditory vocal hallucination rating scale), PSYRAT-AH (Psychiatric symptoms rating scale- Auditory hallucinations scale), CDSS (Calgary depression scale for schizophrenia), SCoRS (Schizophrenia cognition rating scale) and CGI-S (Clinical global impression-severity) were rated at baseline, immediately post 20th session and 2 weeks post-TBS. 50 patients (25-active, 25-sham) completed the study. Conducting an intention to treat analysis, we found a significant group*time effect for PANSS, AVHRS, PSYRAT-AH, CDSS, SCoRS, CGI-S but when controlled for confounding variables and multiple comparisons, only PANSS-PS (F=26.617, p < 0.001), PANSS-TOTAL (F=23.671, p < 0.001), AVHRS (F=17.779, p < 0.001), PSYRAT-AH (F=11.385, p < 0.001) and CGI-S (F=28.462, p < 0.001) retained significance. We conclude that cTBS over TPC is safe and has efficacy in treating AVH in schizophrenia. Limited sample size and lack of integrity assessment for blinding in the study participants are major limitations of the study.

Psychological Resilience, Coping, and Distress in Admitted Patients With COVID-19 Infection.

Objective: To assess psychological resilience, coping, and related psychological distress in admitted COVID-19 patients. Predictors of subsequent development of posttraumatic stress symptoms (PTSS) and disability were also studied.Methods: Stable inpatients with COVID-19 (aged > 18 years with mild symptoms) admitted to a tertiary care hospital from April 2020 to December 2020 were recruited for the study. During admission, the patients were assessed for resilience, coping, and psychological distress using the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), Brief COPE (Coping Orientation to Problems Experienced), and 4-item Patient Health Questionnaire (PHQ-4). Similarly, they were assessed at 4 weeks after discharge using the PTSD Checklist for DSM-5 and World Health Organization Disability Assessment Schedule.Results: A total of 176 patients were recruited for the study and assessed during their admission, and 102 were reassessed during follow-up. Of the patients, 17.6% during admission and 58.8% at follow-up had significant psychological distress (PHQ-4 score > 2). The mean ± SD CD-RISC-10 score was 27.94 ± 5.82. The most used coping strategies were emotional support, religion, and acceptance. Increased resilience was associated with better education (rs[100] = 0.265, P = .007), less psychological distress (r[100] = -0.596, P = .001), and healthy coping strategies. PHQ-4, PCL-5, and disability scores at follow-up were positively correlated (Pearson correlation). The multiple regression model statistically significantly predicted PTSS (F7, 94 = 2.660, P < .015, adjusted R2 = 0.103).Conclusions: COVID-19 patients with better resilience are associated with reduced psychological distress. Better resilient traits and reduced psychological distress may prevent ensuing PTSS and disability.

Management of Psychiatric Disorders in Patients with Endocrine Disorders.

The neuropsychiatric symptoms and disorders among endocrine disorders are discussed in the context of current global and local epidemiological data. Neuropsychiatric symptoms, clinical differentials in hypothyroidism, hyperthyroidism, and parathyroid disorders, and relevant management protocols are described. HPT axis and its interaction with psychotropic usage are mentioned. Stress diathesis, depression, anxiety disorders, and severe mental illnesses and their respective association with diabetes, the relevant mechanisms, and management protocols are stated. The metabolic syndrome, its definition, and its relationship to psychotropic usage are laid out. Moreso, best clinical practices for scenarios such as hyperprolactinemia and psychiatric illnesses, and steroid-induced psychosis are mentioned.

Anxiety among pregnant women during the COVID-19 pandemic in India - A multicentric study.

While higher anxiety during antenatal period cause several maternal and foetal health related complications, lower anxiety levels are found to be associated with lesser "precautionary behaviours" and consequently greater risk of infection, during the COVID-19 pandemic. In this study, we aimed to assess rates and determinants of generalized anxiety at the time of the pandemic as well as anxiety that was specific to the context of being pregnant during the COVID-19 pandemic. (COVID-19-antenatal anxiety) in Indian women. This hospital-based, cross-sectional study using face-to-face interviews was conducted at antenatal clinics of five medical college hospitals in India. The Generalized Anxiety Disorder-7 scale (GAD -7) and a customized scale to assess antenatal COVID-19 anxiety along with other tools that assessed social support and COVID-19-risk perception were administered to 620 pregnant women. We found that the percentage of women with moderate or severe anxiety based on GAD -7 was 11.1%. Multivariate analysis showed that higher COVID-19-risk perception, greater antenatal COVID-19 anxiety and lower perceived support significantly predicted moderate and severe generalized anxiety. Greater number of weeks of gestation, lower education, semiurban habitat and lower perceived social support were significant predictors of antenatal COVID-19 anxiety. We conclude that the rates of anxiety in pregnant women though not very high, still warrant attention and specific interventions.

Evaluation of N-400 Evoked Response Potential in schizophrenia: An endophenotype or a disease marker?

N400 evoked response potentials (ERP) reliably map key semantic deficits in schizophrenia. Assessing them as endophenotypes might help in better understanding of schizophrenia risk and their use as biomarkers. We aimed to study N400 as an endophenotype marker by comparing schizophrenia (SCZ), unaffected first-degree relatives (FDR) and healthy controls (HC) and, by assessing its ability to discriminate these groups. Drug naïve or free SCZ probands (n=30), their unaffected FDRs (n=30) and HC (n=30), underwent a 40-channel ERP recording while performing a custom-made, Hindi- sentence context paradigm task, containing congruent and incongruent conditions. Fifteen centro-parietal (CP) leads, further classified into three regions-midline (CPM), right (CPR) and left (CPL) were selected as electrodes-of-interest for assessing N400. During the incongruent condition, compared to both FDRs and HC, SCZ showed significantly longer N400 latency, at CPM, CPR and CPL, and significantly lesser (more negative) amplitude, at CPM; no significant difference was noted between FDR and HC groups. On discriminant functional analysis, significant N400 predictors could accurately classify 73.3% SCZ from HC and 75% of SCZ from FDR. We conclude that N400 deficits, elicited by the incongruent condition of the sentence task, could be potential biomarkers to define disease state in schizophrenia; they may not be endophenotype markers.