Dementia: Management and Controversies in Management.

Dementia management requires individualized patient encounters that focus on education and realistic expectations. Numerous vitamins and supplements are promoted for memory enhancement, but they lack evidence to support their use. Nonpharmacotherapy should be used through all stages of dementia. Common initial pharmacotherapy includes cholinesterase inhibitors and memantine, with use guided by dementia type, tolerability, patient goals, and disease stage. Assessment of benefit should incorporate caregiver input, functional improvements, behavioral symptoms, and tolerability. Management length is individualized. When a drug is discontinued, physicians should evaluate the patient for early worsening of cognitive or functional symptoms. Newer treatments, such as aducanumab, can reduce beta-amyloid plaques, but evidence for cognitive improvements is lacking; these treatments also are expensive and patient access is limited, resulting in barriers to widespread use. As dementia progresses, patients often develop behavioral and psychological symptoms, which are challenging for patients and caregivers. Nonpharmacotherapy is the first-line treatment for behavioral and psychological symptoms of dementia. Use of antipsychotics and benzodiazepines should be limited unless symptoms are placing the patient or others in imminent danger. Pharmacotherapy for these symptoms should be individualized, often requiring trials of various therapeutic options.

Characterization of antipsychotic utilization before clozapine initiation for individuals with schizophrenia: an innovative visualization of trajectories using French National Health Insurance data.

AIMS: Despite recommendations to initiate clozapine after two unsuccessful trials of antipsychotics, clozapine is underprescribed and initiated too late. The aim of this study was to describe different antipsychotic treatment sequences in the 36 months before the initiation of clozapine and to characterize clusters of treatment trajectories. METHODS: Using the French National Health Insurance database, a historical cohort study of the population in an area in western France was performed. The data from all new users of clozapine with a diagnosis of schizophrenia or schizoaffective disorder in the period of 2017-2018 were evaluated. All outpatient reimbursements for antipsychotics during the 36 months before clozapine initiation were analysed. Successive reimbursements for identical treatments were grouped into treatment trials (TTs), and different trajectories were clustered using a state sequence analysis. RESULTS: The results showed 1191 TTs for 287 individuals. The mean number of TTs per individual was 3.2. Risperidone, aripiprazole and haloperidol were the main treatments delivered. The frequencies of antipsychotics used differed between monotherapies and combination therapies. A three-cluster typology was identified: one cluster (n = 133) of 'less treated' younger individuals with fewer TTs and shorter TT durations; a second cluster (n = 53) of 'more treated' individuals with higher numbers of TTs and combinations of antipsychotics; and a third cluster (n = 103) of 'treatment-stable' older individuals with longer TT durations. CONCLUSIONS: The results indicate that the median number of TTs during the 36 months before clozapine prescription was higher than the two recommended. The different trajectories were associated with individual characteristics and treatment differences, suggesting that additional studies of clinical parameters are needed to understand barriers to clozapine prescription.

Guidelines and treatment for illicit drug related presentations in emergency departments: A scoping review.

OBJECTIVE: This review aimed to identify current pharmacological and non-pharmacological treatment employed in emergency departments (EDs) for the management of patients presenting with illicit drug-related presentations (IDP) and compare current treatments with recommendations provided in guidelines. METHOD: The review consists of English peer-reviewed journal articles and grey literature published in electronic databases: Ovid MEDLINE, PubMed, Embase Classic+Embase, Ovid Emcare and APA PsycInfo between 2015 and 2022. RESULTS: Twelve studies were identified from the search, with agitation and aggression being the most common presentations, and cannabis being the most prevalent illicit drug. Ventilatory support and restraints were the most reported non-pharmacological interventions while benzodiazepines and antipsychotics were the most commonly prescribed pharmacological agents. Non-coercive de-escalation strategies were recommended in all guidelines, with verbal de-escalation being the initial approach before other interventions, such as medications and restraints. However, de-escalation strategies were not reported in any studies. CONCLUSIONS: Pharmacological interventions for patients with IDP and related symptoms were in accordance with guidelines. Use of restraints was identified in included studies with notable lack of reporting of de-escalation strategies which may have been deemed insignificant and not reported. Future research could investigate the appropriateness of restrictive interventions as well as the employment of non-restrictive de-escalation strategies.

Effects of a six-month yoga intervention on the immune-inflammatory pathway in antipsychotic-stabilized schizophrenia patients: A randomized controlled trial.

BACKGROUND: Schizophrenia is a complex neuropsychiatric disorder for which several etiopathological theories have been proposed, one of the prominent ones being immune dysfunction. Recent studies on yoga as an add-on therapy have shown improvement in negative symptoms, cognition, and quality of life in schizophrenia patients. However, the biological mechanism/s of action of yoga in schizophrenia are not clear. The current study was aimed at exploring the effects of long-term (6 months) add-on yoga therapy on the immune inflammatory pathway in schizophrenia patients. METHODS: Sixty schizophrenia patients were randomized to add-on yoga therapy (YT=30) and treatment-as-usual (TAU=30) groups of which 21 patients in YT and 20 in TAU group completed the study. Blood samples and clinical assessments were obtained at baseline and at the end of 6 months. The plasma levels of nine cytokines (IL-2, IL-4, IL-5, IL-10, IL-12(p70), IL-13, GM-CSF, IFN-γ, and TNF-α) were quantified using multiplex suspension array. The clinical assessments included SAPS, SANS, BPRS, PSS, CGI, SOFS and WHOQUOL-BREF. RESULTS: Patients in the yoga group showed significant reductions in plasma TNF-α (Z = 2.99, p = 0.003) and IL-5 levels (Z = 2.20, p = 0.03) and greater clinical improvements in SAPS, SANS, PSS, and SOFS scores as compared to TAU group. Further, plasma TNF-α levels exhibited a positive correlation with negative symptoms (rs =0.45, p = 0.02) and socio-occupational functioning (rs =0.61, p = 0.002) in the YT group. CONCLUSIONS: The findings of the study suggest that improvements in schizophrenia psychopathology with yoga interventions are associated with immuno-modulatory effects.

Does celecoxib with sodium valproate have an augmentation effect on acute mania in bipolar disorder? A double-blind controlled clinical trial in Iran.

Inflammatory processes in the brain play a role in acute mania etiopathogenesis. There is little evidence indicating the efficacy of celecoxib adjuvant therapy in treatmenting of manic episodes of bipolar disorder. Therefore, this clinical trial aimed to assess the celecoxib effect on treating acute mania. In a double-blind, placebo-controlled trial, 58 patients meeting the criteria for acute mania were enrolled. After considering eligibility, 45 patients were included in the study and randomly divided into two groups. The first group (23 patients) received sodium valproate 400 mg/day along with celecoxib 400 mg/day, and the second group (22 patients) received sodium valproate 400 mg/day and a placebo. The subjects were evaluated by the Young Mania Rating Scale (YMRS) at the beginning of the study and 9, 18, and 28 days following the initiation of the medication. Evaluation of baseline factors indicated a significant difference in age ( P = 0.01) and psychiatric history ( P = 0.02) between the two groups. However, other factors were similar between groups ( P ≥ 0.05). Comparing the YMRS score between celecoxib and placebo groups revealed no significant difference on days 0, 9, 18, and 28. However, the YMRS score at the end of the study decreased by 16.05 ± 7.65 in the intervention group ( P < 0.001) and 12.50 ± 5.98 in controls ( P < 0.001) compared to the baseline, the trend of change was not significant between the two groups during the time of the study ( F = 0.38; P = 0.84). Although celecoxib adjuvant therapy indicated no considerable side effects, a longer treatment duration may be needed to detect its beneficial effects for treating acute mania in bipolar patients. Trial registration: Iran clinical trial register: IRCT20200306046708N1.

Efficacy of transcutaneous electrical acupoint stimulation for patients with first-episode schizophrenia: An 8-week, preliminary, randomized controlled trial.

Combination therapy with antipsychotics has been investigated for treating schizophrenia, and has shown clear advantages among non-invasive therapies. Transcutaneous electrical acupoint stimulation (TEAS) is a novel non-invasive treatment with definite efficacy in treating mental disorders. The current study aimed to investigate the efficacy of TEAS in further improving the psychotic symptoms in patients with first-episode schizophrenia (FES) being treated with pharmacological drugs. This 8-week, preliminary, sham-controlled, randomized clinical trial was conducted in patients with FES to compare the efficacy of TEAS and sham TEAS in combination with aripiprazole treatment. The primary outcome was a change in the Positive and Negative Syndrome Scale (PANSS) score after ending the intervention (Week 8). A total of 49 participants completed the whole treatment cycle. The linear mixed-effects regression for PANSS indicated a significant time × group interaction (F(2, 116)=9.79, p <0.001). The PANSS score differed by 8.77 points (95% CI, -2.07 to -15.47 points; p=.01) between the TEAS group and the sham TEAS group after 8 weeks of treatment; this difference was significant. This study indicates that 8 weeks of TEAS combined with aripiprazole treatment can effectively treat FES. Thus, TEAS is an effective combination therapy to improve the psychiatric symptoms of FES.

Complementary/Integrative Medicine Treatment and Prevention of Youth Psychosis.

The rationale for CIM treatments in youth psychoses is to optimize treatment by targeting symptoms not resolved by antipsychotics, such as negative symptoms (major drivers of disability). Adjunctive omega-3 fatty acids (ω-3 FA) or N-acetyl cystine (NAC usage for > 24-week) can potentially reduce negative symptoms and improve function. ω-3 FA or exercise may prevent progression to psychosis in youth (in prodromal stage). Weekly 90-minute moderate to vigorous physical activity or aerobic exercise can reduce positive and negative symptoms. Awaiting better research, CIM agents are also recommended because they are devoid of any serious side-effects.

An update on potential pharmacotherapies for cognitive impairment in bipolar disorder.

INTRODUCTION: Cognitive impairment is a core feature of bipolar disorder (BD) that impedes recovery by preventing the return to optimal socio-occupational functioning and reducing quality of life. Presently, there are no efficacious treatments for cognitive impairment in BD, but many pharmacological interventions are being considered as they have the potential to target the underlying pathophysiology of the disorder. AREAS COVERED: This review summarizes the available evidence for pharmacological interventions for cognitive impairment in bipolar disorder. We searched PubMed, MedLine, and PsycInfo from inception to December 1st, 2022. Traditional treatments, such as lithium, anticonvulsants (lamotrigine), antipsychotics (aripiprazole, asenapine, cariprazine, lurasidone, and olanzapine), antidepressants (vortioxetine, fluoxetine, and tianeptine) and psychostimulants (modafinil), and emerging interventions, such as acetylcholinesterase inhibitors (galantamine and donepezil), dopamine agonists (pramipexole), erythropoietin, glucocorticoid receptor antagonists (mifepristone), immune modulators (infliximab, minocycline and doxycycline), ketamine, metabolic agents (insulin, metformin, and liraglutide), probiotic supplements, and Withania somnifera are discussed. EXPERT OPINION: The investigation of interventions for cognitive impairment in BD is a relatively under-researched area. In the past, methodological pitfalls in BD cognition trials have also been a critical limiting factor. Expanding on the existing literature and identifying novel pharmacological and non-pharmacological treatments for cognitive impairment in BD should be a priority.

Music rhythm perception and production relate to treatment response in schizophrenia.

Accumulating evidence indicates that pathophysiology of schizophrenia involves abnormalities in the dopamine and glutamatergic neuronal systems. Antipsychotic medications are currently used to normalize dopaminergic function for schizophrenia. However, approximately 30 % of the patients have no response to antipsychotic medications, which is classified as treatment-resistant schizophrenia (TRS). Furthermore, dopamine and glutamate levels in the neural basis have been reported to differ between TRS and non-TRS. In this study, we assumed that these differences may affect music rhythm perception and production abilities between the two groups. We examined fifty-seven schizophrenia (26 TRS, 31 non-TRS) and thirty-one healthy controls (HCs) by using the Harvard Beat Assessment Test (H-BAT). As a result, we found that rhythm production was worse in patients with TRS compared to patients with non-TRS and HCs, while no difference was observed between patients with non-TRS and HCs. In addition, rhythm perception and production abilities were impaired in the whole patient group compared with HCs. Furthermore, in the patient group, the deficits were correlated with cognitive impairments. Collectively, these results suggest that patients with schizophrenia may have rhythm processing deficits, with particular a rhythm production problem in the TRS group.

Effectiveness of adjunctive low-frequency repetitive transcranial magnetic stimulation therapy over the left dorsolateral prefrontal cortex in patients with obsessive-compulsive disorder refractory to medical treatment:A double-blind, randomized clinical trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a common psychiatric disorder. The Food and Drug Administration (FDA) approved repetitive transcranial magnetic stimulation (rTMS) to treat OCD in 2018. So far, various approaches to treat this disorder have been evaluated. We evaluated the effect of adjunctive low-frequency rtMS over the left dorsolateral prefrontal cortex in patients with OCD refractory to treatment. METHODS: The present clinical trial was done on 37 patients with OCD referring from the psychiatry clinic, 22 Bahman Hospital, Qazvin province, between 2018 and 2020 and patients were randomly divided into two groups. The intervention group received rTMS treatment at 1 Hz for 20 min (1200 pulses/day) over the left DLPFC area as adjunctive to the medical treatment three times a week and for five weeks, whereas those in the control group were subjected to only the sham condition plus their medical treatment. The Yale-Brown Obsessive-Compulsive Scale (Y-BOC.S) was completed by patients before the study, following sessions 5 and 10 during the intervention, at the end of the intervention, and three to six months after the intervention under the direct supervision of a psychiatrist. SPSS software version 26 was used to compare the results between the two groups. RESULTS: The intervention group showed significantly lower mean Y-BOCS scores after the intervention and at follow-up (P < 0.05) and all patients of the intervention group showed significantly lower Y-BOCS scores than their own baseline scores (P < 0.05). Also, using antipsychotic agents along with the serotonergic agents yielded significantly lower scores in the intervention group at the end of the intervention (P < 0.05). All the patients were found with higher follow-up scores than their scores at the end of the intervention; however, this difference was not significant (p > 0.05). CONCLUSION: Adjunctive low-frequency (1 Hz) rTMS over the left DLPFC is able to effectively reduce Y-BOCS score in OCD patients refractory to treatment following 15 sessions, and the reduction was durable even after three to six months. Using antipsychotic agents as an adjuvant with serotonergic agents was identified as a possible predictor for response to adjunctive rTMS therapy.

Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation.

Schizophrenia is a widespread psychiatric disorder that affects 0.5-1.0% of the world's population and induces significant, long-term disability that exacts high personal and societal cost. Negative symptoms, which respond poorly to available antipsychotic drugs, are the primary cause of this disability. Association of negative symptoms with cortical atrophy and cell loss is widely reported. Psychedelic drugs are undergoing a significant renaissance in psychiatric disorders with efficacy reported in several conditions including depression, in individuals facing terminal cancer, posttraumatic stress disorder, and addiction. There is considerable evidence from preclinical studies and some support from human studies that psychedelics enhance neuroplasticity. In this Perspective, we consider the possibility that psychedelic drugs could have a role in treating cortical atrophy and cell loss in schizophrenia, and ameliorating the negative symptoms associated with these pathological manifestations. The foremost concern in treating schizophrenia patients with psychedelic drugs is induction or exacerbation of psychosis. We consider several strategies that could be implemented to mitigate the danger of psychotogenic effects and allow treatment of schizophrenia patients with psychedelics to be implemented. These include use of non-hallucinogenic derivatives, which are currently the focus of intense study, implementation of sub-psychedelic or microdosing, harnessing of entourage effects in extracts of psychedelic mushrooms, and blocking 5-HT2A receptor-mediated hallucinogenic effects. Preclinical studies that employ appropriate animal models are a prerequisite and clinical studies will need to be carefully designed on the basis of preclinical and translational data. Careful research in this area could significantly impact the treatment of one of the most severe and socially debilitating psychiatric disorders and open an exciting new frontier in psychopharmacology.

A Case Report of Treatment-Resistant Agitation in Dementia With Lewy Bodies: Medical Marijuana as an Alternative to Antipsychotics.

Palliative care teams are often consulted to assist in treating persistent dementia-related behavioral issues. Delta-9-tetrahydrocannabinol (THC) offers an alternative to traditional antipsychotic drugs in the long-term management of dementia with behavioral change. We present the case of an 85-year-old man with dementia with Lewy bodies with worsening aggression refractory to antipsychotic management. Multiple regimens of antipsychotics failed both in the outpatient and inpatient settings. After exhausting other options and in the setting of worsening agitation, a tincture of THC was prescribed. After starting THC tincture, the patient's behavior rapidly improved, and he was discharged home to the care of his spouse. The challenges of prescribing and obtaining THC are discussed.

Medicine use in people with intellectual disabilities: a Finnish nationwide register study.

BACKGROUND: People with intellectual disability (ID) are a vulnerable group in our society; many of them depend on other people for assistance in their everyday lives. Compared with the general population, people with ID have poorer general health and, therefore, need more healthcare services and use more medicines. The aim of this study is to define the population of all Finnish people with ID using administrative data and to compare their medicine use and expenditure on medicines to those of the age-matched and sex-matched controls. METHODS: People with ID and their age-matched and sex-matched controls (1:1) were extracted from nationwide healthcare and social allowance registers. Administrative register data on all prescription medicine purchases in 2019 were used to determine the prevalence of medicine use in both groups on a general level and by medicine categories. The differences in the prevalence of medicine use between the two groups were analysed using the logistic regression model. In addition, we studied the total expenditure on reimbursable medicine purchases covered by the National Health Insurance between people with ID and control group. RESULTS: The subpopulation of people with ID consisted 37 196 individuals, of whom 82.7% purchased prescription medicines in 2019. The corresponding share of individuals purchasing prescription medicines in the control group was 70.3%. The differences in the prevalence of medicine use between the two populations were highest in the younger age groups (0-6, 7-12 and 13-17). In the study population, 28.1% (OR = 12.28; 95% CI: 11.54-13.07) of the people used antipsychotics, making it the most used medicine category in people with ID. In the control group, 3.3% of people used antipsychotics. Compared with the control group, the use of antiepileptics, drugs for constipation, mineral supplements and anxiolytics was four to seven times higher among people with ID. Furthermore, the median expenditure on medicine use among people with ID was four times higher than in the control group. CONCLUSIONS: Compared with the control group, people with ID used more medicines, especially psychotropics, and their expenditure on medicine use was higher.

Mindfulness-based intervention improves residual negative symptoms and cognitive impairment in schizophrenia: a randomized controlled follow-up study.

BACKGROUND: Residual negative symptoms and cognitive impairment are common for chronic schizophrenia patients. The aim of this study was to investigate the efficacy of a mindfulness-based intervention (MBI) on negative and cognitive symptoms of schizophrenia patients with residual negative symptoms. METHODS: In this 6-week, randomized, single-blind, controlled study, a total of 100 schizophrenia patients with residual negative symptoms were randomly assigned to the MBI or control group. The 6-week MBI group and the control group with general rehabilitation programs maintained their original antipsychotic treatments. The scores for the Positive and Negative Syndrome Scale (PANSS), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the Symptom Checklist 90 (SCL-90) were recorded at baseline and week 6 to assess psychotic symptoms, cognitive performance, and emotional state, respectively. RESULTS: Compared with general rehabilitation programs, MBI alleviated the PANSS-negative subscore, general psychopathology subscore, and PANSS total score in schizophrenia patients with residual negative symptoms (F = 33.77, pBonferroni < 0.001; F = 42.01, pBonferroni < 0.001; F = 52.41, pBonferroni < 0.001, respectively). Furthermore, MBI improved RBANS total score and immediate memory subscore (F = 8.80, pBonferroni = 0.024; F = 11.37, pBonferroni = 0.006), as well as SCL-90 total score in schizophrenia patients with residual negative symptoms (F = 18.39, pBonferroni < 0.001). CONCLUSIONS: Our results demonstrate that MBI helps schizophrenia patients with residual negative symptoms improve clinical symptoms including negative symptom, general psychopathology symptom, and cognitive impairment. TRIAL REGISTRATION: ChiCTR2100043803.

Predictors of successful discontinuation of antipsychotics and antidepressants.

BACKGROUND: To offer support for patients who decide to discontinue antipsychotic and antidepressant medication, identifying which potentially modifiable factors correlate with discontinuation success is crucial. Here, we analyzed the predictive value of the professional support received, circumstances prior to discontinuation, a strategy of discontinuation, and use of functional and non-functional coping strategies during discontinuation on self-reported discontinuation success and on objective discontinuation. METHODS: Patients who had attempted discontinuing antipsychotics (AP) and/or antidepressants (AD) during the past 5 years (n = 316) completed an online survey including questions on subjective and objective discontinuation success, sociodemographic, clinical and medication-related factors, and scales to assess the putative predictors. RESULTS: A regression model with all significant predictors explained 20-30% of the variance in discontinuation success for AD and 30-40% for AP. After controlling for baseline sociodemographic, clinical and medication-related factors, the most consistent predictor of subjective discontinuation success was self-care behavior, in particular mindfulness, relaxation and making use of supportive relationships. Other predictors depended on the type of medication: For AD, good alliance with the prescribing physician predicted higher subjective success whereas gradual tapering per se was associated with lower subjective success and a lower chance of full discontinuation. In those tapering off AP, leaving time to adjust between dose reductions was associated with higher subjective success and fewer negative effects. CONCLUSIONS: The findings can inform evidence-based clinical guidelines and interventions aiming to support patients during discontinuation. Further studies powered to take interactions between variables into account are needed to improve the prediction of successful discontinuation.

Reviewing the Potential Therapeutic Approaches Targeting the Modulation of Gastrointestinal Microflora in Schizophrenia.

Schizophrenia (SCZ) is a severe brain disorder characterized by an intriguing clinical panel that has begun to gain interest due to its particular phenotype. Having considered the role of gut microflora in psychiatry, the latest discoveries might offer further insight into the underlying mechanisms. Thus, we aimed to offer an updated overview of the therapeutic potential of microorganism-derived supplements alongside dedicated protocols that target the re-establishment of the host's eubiosis. Based on combinations of specific keywords, we performed searches in four databases (PubMed/Medline, ISI Web of Knowledge, Scopus, and ScienceDirect) for the established interval (2018-2022) and identified twenty two eligible cases, restricted only to human patients' experiences. Up until the writing of this manuscript, it has been revealed that the administration of specific lactic acid bacteria strains (Lactobacillus and Bifidobacterium), or those combined with vitamin D and selenium, maintain the integrity of the gut flora, preventing antagonistic effects including inflammation, antipsychotic-related body weight gain (olanzapine) and other metabolic dysfunctionalities. However, there are multiple antipsychotics that exert a potent effect upon gut flora, influencing a plethora of pathways and creating a dysbalance ratio between beneficial and opportunistic pathogens. Risperidone, amisulpride, and clozapine are just a few examples, but the current literature is unfortunately inconsistent and reported data is contradictory, which is why we support additional studies in this context. Moreover, we further argue the utility of studying how distinct controlled substances influence microbial communities, considering that ketamine is proved to alleviate depressive-like behavior as opposed to amphetamine and phencyclidine, which are known substances to trigger SCZ-like symptoms in experimental models. Probiotics may be regarded as the most consequential vehicle through which the gut flora can be successfully influenced, in adequate doses exerting a beneficial role as an alternative approach to alleviate SCZ symptoms.

Lurasidone use in Cannabis-Induced Psychosis: A Novel Therapeutic Strategy and Clinical Considerations in Four Cases Report.

BACKGROUND: Lurasidone is an atypical antipsychotic approved for the acute and maintenance treatment of schizophrenia. Recently, lurasidone was also extended FDA approval for adults with major depressive episodes associated with bipolar I disorder (bipolar depression), as either a monotherapy or as adjunctive therapy with lithium or valproate. The use of low doses of atypical antipsychotics is an essential component of early intervention in psychosis, but little has yet been studied on first episode cannabis-induced psychosis. For its particular performance and tolerability, lurasidone is becoming an important option for the treatment of first-episode psychosis in youth. Case presentation four patients experiencing first cannabis-induced psychotic episode were treated with lurasidone. In all patients, there was an improvement in the clinical picture of psychosis. The recovery was positive, not only with the remission of positive and negative symptoms, but also regarding disruptive behaviour, with the return of functioning. All the patients were treated with lurasidone, with a target dose of 74-128 mg/day. No significant side effects were reported. CONCLUSION: There are non-controlled studies for the use of lurasidone in first episode psychosis cannabis induced. These findings suggest that lurasidone is an atypical antipsychotic beneficial in this clinical picture. Treatment with medium-high doses of lurasidone could be effective and tolerable in this phase of the disorder. Randomized control trials with longer follow-up are recommended to confirm these positive results.

A Randomized, Double-Blind, Controlled Clinical Trial of Omega-3 Fatty Acids and Inositol as Monotherapies and in Combination for the Treatment of Pediatric Bipolar Spectrum Disorder in Children Age 5-12.

Objectives: The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (FAs) and inositol alone and in combination for the treatment of pediatric bipolar (BP) spectrum disorder in young children. Methods: Participants were male and female children ages 5-12 meeting DSM-IV diagnostic criteria for a BP spectrum disorder and displaying mixed, manic, or hypomanic symptoms without psychotic features at the time of evaluation. Results: Participants concomitantly taking psychotropic medication were excluded from efficacy analyses. There were significant reductions in YMRS and HDRS mean scores in the inositol and combination treatment groups (all p < 0.05) and in CDRS mean scores in the combination treatment group (p < 0.001), with the largest changes seen in the combination group. Those receiving the combination treatment had the highest rates of antimanic and antidepressant response. The odds ratios for the combination group compared to the omega-3 FAs and inositol groups were clinically meaningful (ORs ≥2) for 50% improvement on the YMRS, normalization of the YMRS (score <12) (vs. inositol group only), 50% improvement on the HDRS, 50% improvement on CDRS (vs. omega-3 FAs group only), and CGI-I Mania, CGI-I MDD, and CGI-I Anxiety scores <2. Conclusion: The antimanic and antidepressant effects of the combination treatment of omega-3 FAs and inositol were consistently superior to either treatment used alone. This combination may offer a safe and effective alternative or augmenting treatment for youth with BP spectrum disorder, but more work is needed to confirm the statistical significance of this finding.

Effect of add-on alpha lipoic acid on psychopathology in patients with treatment-resistant schizophrenia: a pilot randomized double-blind placebo-controlled trial.

RATIONALE: Alpha lipoic acid is known to reverse NMDA receptor hypofunction in addition to dopamine receptor blockade activity. It also enhances neurotrophic factors and has antioxidant potential. These properties combined together may be beneficial for treatment-resistant schizophrenia (TRS). OBJECTIVES: This study evaluates the effect of alpha lipoic acid (ALA) on psychopathological scores (positive, negative, cognitive), neurotrophic factors and oxidative stress in TRS. METHODS: A pilot randomized double-blind placebo-controlled parallel design trial was conducted in 20 patients with TRS. After initial screening, participants were randomized into test (add-on ALA) and control (add-on placebo) groups. After recruitment, clinical evaluations with scale for assessment of positive symptoms and negative symptoms (SAPS and SANS), schizophrenia cognitive rating scale (SCoRS), UKU side effect rating scale were done. Serum levels of BDNF, MDA, and GSH were estimated. Patients were followed up for 8 weeks, and clinical and biochemical evaluations were repeated. Adherence to medication was evaluated at follow-up. RESULTS: A significantly greater improvement was found in SANS score in the test group when compared to control (Mann-Whitney U = 17.0; p = 0.021), whereas there was no significant improvement in SAPS score (Mann-Whitney U = 41.5; p = 0.780). A significant increase in BDNF levels was observed in the control group when compared to ALA (U = 20.0; p = 0.041). No significant differences were found between the test and control groups in serum MDA (U = 30.0; p = 0.221), serum GSH (U = 40.0; p = 0.683), and medication adherence rating scale (MARS) scores (U = 44.0; p = 0.934). CONCLUSIONS: ALA supplementation improved psychopathology and decreased oxidative stress in patients with TRS. This study thus shows the potential of adjunctive ALA in TRS. TRIAL REGISTRATION: The study was prospectively registered in Clinical Trial Registry of India (CTRI/2020/03/023707 dated 02.03.2020).