Mg Of Risperidone Research Articles

Dissolving microarray patches for transdermal delivery of risperidone for schizophrenia management

Schizophrenia is a psychiatric disorder that results from abnormal levels of neurotransmitters in the brain. Risperidone (RIS) is a common drug prescribed for the treatment of schizophrenia. RIS is a hydrophobic drug that is typically administered orally or intramuscularly. Transdermal drug delivery (TDD) could potentially improve the delivery of RIS. This study focused on the development of RIS nanocrystals (NCs), for the first time, which were incorporated into dissolving microneedle array patches (DMAPs) to facilitate the drug delivery of RIS. RIS NCs were formulated via wet-media milling technique using poly(vinylalcohol) (PVA) as a stabiliser. NCs with particle size of 300 nm were produced and showed an enhanced release profile up to 80 % over 28 days. Ex vivo results showed that 1.16 ± 0.04 mg of RIS was delivered to both the receiver compartment and full-thickness skin from NCs loaded DMAPs compared to 0.75 ± 0.07 mg from bulk RIS DMAPs. In an in vivo study conducted using female Sprague Dawley rats, both RIS and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) were detected in plasma samples for 5 days. In comparison with the oral group, DMAPs improved the overall pharmacokinetic profile in plasma with a ∼ 15 folds higher area under the curve (AUC) value. This work has represented the novel delivery of the antipsychotic drug, RIS, through microneedles. It also offers substantial evidence to support the broader application of MAPs for the transdermal delivery of poorly water-soluble drugs.

Use of monthly extended-release risperidone injection in schizophrenia: clinical experience

IntroductionMonthly extended-release injectable risperidone is the new antipsychotic formulation of risperidone available in doses of 75 mg and 100 mg, approved for the treatment of schizophrenia. It contains microcrystals of risperidone that are deposited following intramuscular injection. A fraction of the active ingredient of risperidone is already solubilized and rapidly enters the bloodstream, providing plasma levels similar to oral risperidone on the first day. The microcrystals continue to release risperidone steadily over a period of 4 weeks. No oral supplementation or loading doses are required.ObjectivesThe objective of this study is to demonstrate the effectiveness of treatment with monthly extended-release injectable risperidone in patients with schizophrenia who are followed up as outpatients from the Mental Health Center. The study aims to show that this treatment improves symptoms associated with schizophrenia, leading to an enhancement in the quality of life for these patients.MethodsAnalysis and evaluation were conducted on 9 patients diagnosed with Paranoid Schizophrenia and treated with monthly extended-release injectable risperidone from a Mental Health Unit and the Hospital Emergency System during the months of January to April 2023. Among the nine patients, six were previously on oral risperidone treatment exceeding 4 mg, and three were on doses less than 4 mg. The first group received a monthly injectable dose of 100 mg of risperidone, while the second group received 75 mg.ResultsAll nine patients showed improvement in positive and anxious symptomatology. Seven of them exhibited improvement in affective and cognitive profiles. None of the patients experienced significant metabolic alterations, and only one of them reported akathisia as a side effect. Furthermore, all patients improved their sleep patterns, and the seven who had behavioral disturbances with a tendency towards aggression no longer exhibited these behaviors.ConclusionsMonthly extended-release injectable risperidone is beneficial in reducing positive and affective symptoms in patients with schizophrenia. It also improves anxious, cognitive, and behavioral symptomatology. It is considered effective, safe, and well-tolerated for long-term treatment of this disease, regardless of its initial severity. Therefore, it is advisable to consider it as the first therapeutic option in patients with schizophrenia who have responded well to oral risperidone previously.Disclosure of InterestNone Declared

Adrenaline-resistant anaphylactic shock caused by contrast medium in a patient after risperidone overdose: a case report

BackgroundIn Japan, the use of risperidone in combination with adrenaline is contraindicated, except in cases of anaphylaxis. Therefore, there is limited clinical evidence regarding the interaction of these two drugs. Here, we report the clinical course of a case of adrenaline-resistant anaphylactic shock induced by a contrast medium injection after a risperidone overdose.Case presentationA man in his 30s was transported to our hospital after attempting suicide by taking 10 mg of risperidone and jumping from a height of 10 m. To determine the location and severity of his injuries, he was injected with an iodinated contrast medium, after which he developed generalized erythema and hypotension and was diagnosed with anaphylactic shock. A 0.5 mg dose of adrenaline was administered with no improvement, followed by another 0.5 mg dose that did not change his blood pressure. After infusion of a sodium bicarbonate solution (8.4%), administration of fresh frozen plasma, and additional administration of adrenaline (0.6–1.2 µg/min), his blood pressure improved, and he recovered from the anaphylactic shock.ConclusionsThis was a rare case of a risperidone overdose followed by adrenaline-resistant anaphylactic shock. The resistance is likely associated with the high blood concentration of risperidone. Our findings indicate that the potential for decreased adrenergic responsiveness should be considered in patients undergoing risperidone treatment in the event of anaphylactic shock.

Risperidone and fluvoxamine; two directions of augmentation: a case report

IntroductionOnly 40%–70% of patients have an adequate response to the first-line treatment of OCD with SSRIs. Antipsychotic augmentation is effective in the management of both obsessions and compulsions and these drugs are currently the first-line pharmacological augmenting agents for OCD. (Jaisoorya T, Thamby A. Antipsychotic augmentation in the treatment of obsessive-compulsive disorder. Indian Journal of Psychiatry. 2019;61(7):51)ObjectivesWe present the cases of a 31-year-old man and a 21- year-old girl. A 31 -year old man experienced hygienic obsessive and compulsive symptoms with excessive showering for one year (YBCOS 20). First, he was treated with 100 mg of fluvoxamine daily which helped him gain partial remission of symptoms. After a stressful period at work and his showering compulsions got worse. Our female patient suffered from compulsive hand washing and disinfection with fear of getting contaminated by other people (YBCOS 24). She was also treated for anorexia nervosa. At the moment of referral to our outpatient clinic, she had already been taking 2 mg of risperidone daily, but still, her compulsions persisted.MethodsBoth patients were included in outpatient service treatment. They were followed up weekly, psychotherapeutically supported and their psychopharmacotherapy was titrated. In the case of our male patient, risperidone of 1 mg/day was added to the ongoing fluvoxamine of 100 mg/day. Our female patient was given fluvoxamine 50 mg/a day and gradually increased to 100 mg/day with an ongoing 2 mg/day of risperidone.ResultsAfter two weeks, the hygiene compulsions of the 31-year-old-man completely remitted (YBCOS 6). He stopped excessive showering and became fully functional at work and in family relations. Our female patient also continued to take risperidone in augmentation with fluvoxamine as recommended. Her compulsions improved, and she returned to her hobbies and her college lectures (YBCOS 8). They have both been advised to continue outpatient psychiatric treatment and to regularly use pharmacotherapy.ConclusionsThe condition of both of our patients improved after adding an augmentative agent to the therapy. In the first case, it was risperidone as a fluvoxamine augmentation, and in the second, fluvoxamine was added as a risperidone augmentation. The combination of these two drugs, rather than each other being used on its own, proved to be a powerful therapeutic tool in the treatment of OCD. Further clinical studies are required for a better understanding of the underlying neurobiological mechanism of this effective combination.Disclosure of InterestNone Declared

Risperidone induced tardive movements in an elderly male-a case of cognitive decline masked by behavioral abnormalities

Tardive dyskinesia is a drug emergent side effect associated with long-term exposure to neuroleptics. Risperidone has lesser propensity to cause tardive movements. A 67-year-old male presented with tardive symptoms. He had oromasticatory and limb movements. He was started on 2 mg of risperidone for agitation and behavioral disturbance 4 years ago. He also developed cognitive decline over the years. Clinician must be aware of the possibility of tardive movements with risperidone and the need for frequent evaluation of cognitive function in any elderly male.

Bipolar disorder and grey matter heterotopia : a case report

IntroductionThe grey matter heterotopias are a relatively common group of conditions characterized by interruption of normal neuronal migration from near the ventricle to the cortex. Subependymal grey matter heterotopia, also known as periventricular heterotopia, is the most common form.ObjectivesTo search a link between bipolar disorder and grey matter heterotopiaMethodsA case report of a woman with grey matter heterotopia who is diagnosed as bipolarResults A 34 year old woman was admitted at Razi psychiatric hospital 3 months after childbirth. She was agitated, logorrheic with multiple projects and insomniac. The diagnosis was a manic episod with a marked score of 28/44 at The Bech-Rafaelsen Mania Scale (MAS). The patient was treated with 4 mg of risperidone and 1000 mg of sodium valproate with partial remission after two weeks. One month after her discharge, she had depressive mood, asthenia, anhedonia and insomnia. She had a score of 19 at Hamilton Depression Rating Scale (HDRS). She was switched from risperidone to olanzapine 15mg/j with partial remission after two weeks. In front of persistent symptoms with labile mood, she took lithium 1000 mg/j. She was complaining of a headache and a fluctuating heaviness of the right upper limb. At brain imaging, she had periventricular nodular heterotopia. The patient was adressed to neurology department.ConclusionsGrey matter heterotopia can cause a variety of neuropsychiatrc symptoms which can lead to diagnosis difficulties. Therefore, in front of atypical symptoms or drug-resistance, patients should be referred for brain imaging.DisclosureNo significant relationships.

The double penalty of the coronavirus: Decidedly this virus has not yet revealed all its secrets!

IntroductionThe direct and indirect effects of the COVID-19 pandemic on the mental health of the population have become a concern in the field of research in psychiatry. First psychotic episodes following infection with SARS cov2 have been reported.ObjectivesThrough a clinical case, we will illustrate the association of psychiatric symptoms with SARS cov2 infection.MethodsWe discussed , through a clinical case, the association of psychiatric symptoms with infection by the coronavirus 19.ResultsL.R, Tunisian 52-year-old, diabetic (type 2) women, with no personal or family psychiatric history and no toxic habits. she did not receive receive covid 19 vaccination. Twenty days before her admission to the psychiatry departement, she had fever, cough, myalgia, and anosmia .The diagnosis of a SARS COv2 infection was retained by her general practitioner. Two weeks later she suddenly presented a persecutory delirium, distressing auditory hallucinations, and attempted rat poison suicide. On admission, The patient had a delirium of persecution towards her entourage and an auditory hallucinatory syndrome with distressing content. She was put on 1 mg of Risperidone with restitution ad integrum after 7 days. COVID-19 serology test detected IgM antibodies which allowed us to conclude that the symptomatology was related to the infection by this virus. For the etiological research, we performed a serology that confirmed the recent exposure to SARS COV2 and. The diagnosis retained is a brief psychotic disorder post-Sars Cov2.ConclusionsThe advanced hypothesis that infection with SARS CoV-2 could be the cause of the psychiatric manifestations remains unclear to this day.DisclosureNo significant relationships.

Valproate-induced hypothyroidism in schizoaffective disorder

IntroductionValproate is widely used in the treatment of maniac and mixed episodes and is well known to be safe with side effects being mostly related to hepatic disorders and psychomotor retardation.ObjectivesRaising attention to valproate-induced hypothyroidism that despite the increasing evidence tends to be neglected.MethodsHere, we report a case of a 55-year-old woman, with a previous diagnosis of schizophrenia, treated for many years with 200mg of zuclopenthixol triweekly and 2mg of risperidone daily. Patient developed a maniac episode characterized by elevated mood, sense of grandiosity, increased energy and psychomotor activity, disinhibition and insomnia. No laboratory abnormalities were detected and inpatient treatment was initiated with paliperidone up to 12mg/day and valproate 1000mg/day.ResultsPatient showed progressive clinical recovery attaining full remission within 2 weeks. Despite the absence of clinical side effects and the valproate serum levels of 74.9μg/mL (range 50–100μg/mL), laboratory testing found progressive reduction F-T4 down to 0.45ng/dL (range 0.8–1.5 ng/dL) and a concomitant upregulation of TSH to 73.99mUI/L (range 0.55–4.8mUI/L). Thyroid autoantibodies and thyroid echography were negative. Considering that patient was previously medicated with risperidone, it was suspected that her hypothyroidism was caused by valproate. Normalization of thyroid function was observed after 21 days valproate withdrawal. Patient is currently being treated with 150 mg paliperidone (monthly) with no recurrence of mood or psychotic episodes and maintain normal thyroid function.ConclusionsOur case emphasizes the need for extended laboratory testing upon prescription of new pharmacological medications as severe analytic alterations can take place in the absence of immediate clinical manifestation.DisclosureNo significant relationships.

Optimal Doses of Specific Antipsychotics for Relapse Prevention in a Nationwide Cohort of Patients with Schizophrenia.

Background and HypothesisOptimal doses of most antipsychotics in the maintenance treatment of schizophrenia are unknown. We aimed to study the risk of severe relapse indicated by rehospitalization for different dose categories of 15 most frequently used antipsychotics in monotherapy in Finland. Study MethodsWe studied the risk of rehospitalization (Adjusted Hazard Ratio, aHR) associated with six antipsychotic monotherapy dose categories (as time-varying dose, measured in defined daily dose, DDDs/day) in a nationwide cohort of persons diagnosed with schizophrenia (n = 61 889), using within-individual analyses to eliminate selection bias. Study ResultsAmong the 15 most widely used antipsychotics, 13 had a U- or J-shaped dose-response curve, showing the lowest risks of relapse for doses of 0.6–<1.1 DDDs/day vs nonuse of antipsychotics. The exceptions were oral perphenazine (aHR = 0.72, 95% CI = 0.68–0.76, <0.6 DDDs/day), and olanzapine-long-acting injectable (LAI), which had the lowest aHR of any antipsychotic (aHR = 0.17, 95% CI = 0.11–0.25, 1.4–<1.6 DDDs/day). Certain risperidone and perphenazine doses <0.9 DDD/day were associated with 21%–45% lower risk of rehospitalization (P < .001) than the standard dose of 0.9–1.1 DDD/day (ie, 5 mg for risperidone and 30 mg for perphenazine). ConclusionsFor most antipsychotics, the risk of severe relapse was the lowest during use of standard dose. Our results suggest that olanzapine LAI is highly effective in dose ranges >0.9 DDD/day, and especially at 1.4–<1.6 DDDs/day (405 mg/4 weeks) associated with substantially lower risk of rehospitalization than any dose of any other antipsychotic. The current WHO standard dose definitions appear to be clearly too high for perphenazine and somewhat too high for risperidone.

The effect of risperidone on reward-related brain activity is robust to drug-induced vascular changes.

Dopamine (DA) mediated brain activity is intimately linked to reward‐driven cerebral responses, while aberrant reward processing has been implicated in several psychiatric disorders. fMRI has been a valuable tool in understanding the mechanism by which DA modulators alter reward‐driven responses and how they may exert their therapeutic effect. However, the potential effects of a pharmacological compound on aspects of neurovascular coupling may cloud the interpretability of the BOLD contrast. Here, we assess the effects of risperidone on reward driven BOLD signals produced by reward anticipation and outcome, while attempting to control for potential drug effects on regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR). Healthy male volunteers (n = 21) each received a single oral dose of either 0.5 mg, 2 mg of risperidone or placebo in a double‐blind, placebo‐controlled, randomised, three‐period cross‐over study design. Participants underwent fMRI scanning while performing the widely used Monetary Incentive Delay (MID) task to assess drug impact on reward function. Measures of CBF (Arterial Spin Labelling) and breath‐hold challenge induced BOLD signal changes (as a proxy for CVR) were also acquired and included as covariates. Risperidone produced divergent, dose‐dependent effects on separate phases of reward processing, even after controlling for potential nonneuronal influences on the BOLD signal. These data suggest the D2 antagonist risperidone has a wide‐ranging influence on DA‐mediated reward function independent of nonneuronal factors. We also illustrate that assessment of potential vascular confounds on the BOLD signal may be advantageous when investigating CNS drug action and advocate for the inclusion of these additional measures into future study designs.

Finding Early Improvement Threshold to Predict Response After 8 Weeks of Treatment Using Risperidone in First-Episode Psychosis.

The study aims to assess whether the early response can predict the outcome at the endpoint for the treatment of first-episode psychosis with risperidone and identify the relationship between initial symptom reduction and late response. A prospective observational study with 4 points follow-up (weeks 2, 3, 4, and 8) was conducted in 48 adult first-episode psychosis patients. Symptoms were quantified by the Positive and Negative Syndrome Scale (PANSS) score. The initial recommended dose was 2 mg of risperidone once daily before sleep. The PANSS score on day 1 (before initiation of drug therapy) was considered as the baseline score. Treatment responses were considered as a reduction of more than 20%, 25%, 30% and 50% from the baseline score on first, second, third, and final follow-up, respectively. Receiver operating characteristic curves were generated for predicting response at the endpoint. Thirty-one (65%) patients achieved more than 50% reduction (responders) in PANSS score. The mean total PANSS score of the study population after 8 weeks of therapy was found to be 49.77 (95% confidence interval, 46.10-53.43). The mean percentage reduction in PANSS score after 8 weeks of therapy was found to be 52.92% (95% confidence interval, 48.83-57.01). Week 2 response can be taken as the early response (area under the curve = 81.9, P < 0.001). However, the more accurate prediction was possible with week 4 response (area under the curve = 88.7%, P < 0.001). Our study suggests that patients with an early response at week 2 are likely to achieve positive response after 8 weeks.

Discontinuation of antipsychotics treatment for elderly patients within a specialized behavioural unit: a retrospective review.

Background Best practice guidelines recommend regular evaluation of antipsychotics in managing behaviours for dementia patients with a view to de-prescribing, given its significant mortality and adverse outcomes (Reus et al. in Am J Psychiatry 173(5):543-546, 2016, Deprescribing Guidelines and Algorithms in https://deprescribing.org/resources/deprescribing-guidelines-algorithms/ , 2019). The relationship between the dose of antipsychotic and the probability of discontinuation remains unknown in hospitalized dementia patients. Objectives This study aims to examine the relationship between high dose antipsychotic (greater than 62mg chlorpromazine equivalent daily dose) and antipsychotics discontinuation in hospitalized dementia patients. Setting Specialized Dementia Behavioral Health Program in Hamilton, Ontario, Canada. Method A retrospective chart review was completed from August to December of 2019. A univariate logistic regression model was applied to antipsychotic doss (in chlorpromazine equivalent) and antipsychotic discontinuation outcome at 60days (Narayan and Nishtala in Eur J Clin Pharmacol 73(12):1665-1672, 2017). A multivariant model was used to assess potential confounders, including other psychiatric medication exposure and Medicines Comorbidity Index (Luthra in J Gerontol Geriatr Res 4(260):2, 2015). Regression and dose-response models were utilized to identify the threshold dose (maximum daily dose). Main outcome measures Antipsychotic discontinuation at 60days after the last dose. Results A total of 42 patients were eligible for outcome analysis. High dose antipsychotic was associated with worse discontinuation outcomes in both unadjusted (odds ratio, 0.09; 95% confidence interval, 0.02-0.37; p < 0.01) and adjusted generalized estimation equation models (odds ratio 0.65; 95% confidence interval, 0.59-0.72; p = 0.01). There were no statistically significant associations between baseline comorbidities (Medicines Comorbidity Index) (p = 0.68), mood stabilizer (p = 0.14), benzodiazepines (p = 0.93) and antidepressant exposure (p = 0.68) with antipsychotic discontinuation. The logistic regression model identified 40.7mg of quetiapine, 1.7mg of olanzapine and 0.51mg of risperidone as the threshold dose, balancing sensitivity and specificity. The dose-response model also identified similar doses of 42mg of quetiapine, 1.76mg of olanzapine and 0.53mg of risperidone. Conclusion The use of high dose antipsychotics is associated with worse discontinuation outcomes in hospitalized dementia patients. Therefore, our results suggest not exceeding a daily dose of 50mg of quetiapine, 1.75mg of olanzapine and 0.5mg of risperidone when used for responsive behaviours and reassess the benefits and risks for each patient regularly.

S216. CASE REPORT OF TREATMENT OF NEUROLEPTIC MALIGNANT SYNDROME IN CHILD ADOLESCENT

BackgroundNeuroleptic Malignant Syndrome is a rare clinical syndrome occurring due to idiosyncratic reaction after use of neuroleptics. We report a case of neuroleptic malignant syndrome in an adolescent patient with schizophrenia after treatment with antipsychotics.MethodsCase report.ResultsA 15-year-old male Schizophrenic patient was admitted to the psychiatric closed ward due to worsening of psychotic symptoms on July of 2017. Pineal cystoma and pituitary microadenoma were detected incidentally on MRI, and consultation with the department of pediatrics recommended close observation.After treatment with 6mg of risperidone in combination with 300 mg of quetiapine, psychotic symptoms improved enough to be discharged.Since March 25th of 2019, due to manifestation of paralytic ileus from worsening of underlying constipation, all the oral medications were stopped along with NPO for treatment; in addition, IM injection of haloperidol was only allowed for the symptom control. The day before the onset of neuroleptic malignant syndrome, IM injection of 15 mg of haloperidol and 10 mg of lorazepam resulted in vomiting, headache, fever of 39℃, systemic tremor and stiffness, confusion in consciousness, tachycardia and sweating. On April 1st of 2019, with suspicion of neuroleptic malignant syndrome, the patient was transferred to ICU at our institution. Blood work-up performed on day of admission at ICU indicated CPK 2836 IU/L and myoglobulin 337.2 ng/ml, and CPK, after peaking at 4493 IU/L, continuously decreased and was normalized by the 18th day at ICU. Diazepam (IV), dantrolene, domperidone, L-Dopa/benserazideand and cold blanket were applied because the patient continuously screamed due to fever, stiffness, tremor, and psychotic symptoms. Even though confusion improved after 3 days, nausea and vomiting persisted for 8 days. Tremor, stiffness, and fever were stabilized after 3 days. Tachycardia improved after 17 days. Recovery of hematologic abnormalities such as increased CPK and myoglobulin and leukocytosis were followed by stabilization of tremor, stiffness, and high fever on the 18th day.The patient was transferred out of ICU after 18 days, and symptoms were all stabilized after treatment with clozapine.DiscussionEvaluation of risk factors of NMS in patients requiring neuroleptics is most critical in order for prompt differentials and early intervention.Known risk factors are 1) male, 2) combination of more than two antipsychotic, 3) history of previous EPS symptoms or NMS, 4) psychiatric disorders such as severe agitation, mood disorder, or delirium, 5) recent initiation or increasing dose of antipsychotics, 6) IM injection of antipsychotics, 7) poor physical conditions like dehydration, infection, malnutrition, brain tumor, encephalitis, or AIDS, 8) use of zuclopenthixol acetat (clopixol acuphase), and 9) substance abuse.In this case, because the patient had 6 of the risk factors described above, which are biological vulnerabilities due to pineal cystoma and pituitary micro adenoma, dehydration and malnutrition caused by paralytic ileus, and sudden change in IM antipsychotics and dosage, it was critical to consider more carefully in medication injection and changes in dosage.Once diagnosed with NMS, immediate hydration and efforts to lower body temperature are critical to prevent complications like acute renal failure, and use of dantrolene, bromocriptine, and benzodiazepine is helpful in shortening the treatment period.In cases of NMS in patients who cannot terminate use of neuroleptics due to underlying mental disorders, ECT is an effective method to treat both NMS and mental disorders. Safety and efficacy of ECT have been already proven, and it is highly recommended when needed.

Risperidone-induced Somnambulism: A Case Report and Brief Review of Literature

Atypical antipsychotic drugs have been recommended as the first-line agents in the treatment of schizophrenia. They are usually not associated with extrapyramidal symptoms and hyperprolactinemia. There is no previously reported case on somnambulism associated with risperidone intake. We report a case of risperidone-induced somnambulism in a schizophrenic patient. Somnambulism occurred while the patient was on a dose of 3 mg of risperidone per day. The dose was reduced to 2 mg per day along with the addition of clonazepam 0.5 mg daily at night. No further episode of somnambulism was reported after this. This case suggests the association of risperidone with occurrence of somnambulism. Further evidence to strengthen the causality of this needs to be gathered. This calls for prompt pharmacovigilance reporting of adverse drug events associated especially with antipsychotics.

What Antipsychotic Dose Is Most Effective?

Back to table of contents Previous article Next article Clinical & ResearchFull AccessWhat Antipsychotic Dose Is Most Effective?Nick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:10 Jan 2020https://doi.org/10.1176/appi.pn.2020.1b3AbstractA large meta-analysis calculated optimal doses for 19 different antipsychotics and found that for several medications, doses above the maximum licensed dose might be most effective. Combining clinical data from 68 separate studies, a research team has estimated the most effective dose for 19 different antipsychotic medications, including both oral and long-acting injectable (LAI) formulations. The researchers also calculated the dose equivalents of these 19 medications to guide physicians who may be considering switching patients from one antipsychotic to another. This meta-analysis was published in December 2019 in AJP in Advance.The minimum and maximum effective doses of antipsychotic drugs are not well understood, wrote Stefan Leucht, M.D., of the Technical University of Munich and colleagues. Though approved medications are licensed within a specific range of doses, these amounts are usually calculated early in the drug development process and may not reflect the optimal range for patients.Leucht and colleagues identified clinical trials that compared multiple doses of the same antipsychotics relative to placebo in people with acute schizophrenia symptoms. They then calculated how well symptoms improved in those taking different doses of the following medications: amisulpride, aripiprazole (oral and LAI), asenapine, brexpiprazole, cariprazine, clozapine, haloperidol, iloperidone, lurasidone, olanzapine (oral and LAI), paliperidone (oral and LAI), quetiapine, risperidone (oral and LAI), sertindole, and ziprasidone.he dose-response profiles for these 19 medications fell into two major classes. The first were antipsychotics whose effects plateaued or started dropping at higher tested doses, suggesting the optimal dose is within the currently licensed range. These medications included the following: amisulpride, oral and LAI aripiprazole, asenapine, brexpiprazole, cariprazine, haloperidol, oral olanzapine (when given to patients with predominantly negative symptoms), quetiapine, and oral and LAI risperidone.In some instances, the most effective dose was well below the upper prescribing limits. For example, the most effective dose of oral risperidone—which is approved up to 16 mg/day—is 6.3 mg/day, according to the analysis.“Clinicians often use relatively high doses of antipsychotics in practice,” Leucht told Psychiatric News. “Our analysis shows that for many antipsychotics such doses are not generally recommendable.”For the other medications—including clozapine, iloperidone, lurasidone, oral olanzapine (in patients with predominantly positive symptoms), LAI olanzapine, oral and LAI paliperidone, sertindole, and ziprasidone—there was no indication that the dose-response was plateauing. The authors said that this finding suggests that doses above the licensed limit might be more effective.Leucht cautioned that the dosing analysis considered only symptom improvements and that patients prescribed higher doses of these medications might experience worse side effects. Further controlled studies on dosing are needed to assess the risk-benefit profile of these antipsychotics at elevated doses, he said.“Clinicians need to be aware that if they go beyond the officially licensed doses, they are applying the drug ‘off label’ and should be careful in this regard.”Leucht also noted that the dose estimates for clozapine, haloperidol, LAI aripipazole, LAI olanzapine, and LAI risperidone were each based on a single dosing study, so the data should be interpreted with caution.The researchers also calculated the dose equivalencies of the antipsychotics, using haloperidol, olanzapine, and risperidone as reference drugs (for example, 1 mg of risperidone = x amount of the other medications). These equivalencies can help physicians considering prescribing a different medication, but the researchers cautioned that physicians should look at the full profiles of each medication and not just rely on the conversion calculator. For example, 20 mg/day olanzapine corresponds to 8.25 mg/day risperidone, but an 8.25 mg/day dose of risperidone may be less effective than the optimal level of 6.3 mg/day.“We stress that our results provide some guidance based on ‘average’ patients with chronic illness,” Leucht and colleagues wrote in the article. “The dose-response relationships in specific populations, such as first-episode patients, elderly patients (who need lower doses), and patients with treatment-resistant illness, are likely to be different.” Physicians should use these data as a starting point and then base individual dosing decisions on the properties of each medication, patient characteristics, and any other treatments that might influence antipsychotic response, they concluded.The authors reported no funding information in the article. ■ “Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia” is posted here. ISSUES NewArchived

Clinical Trial of Efficacy Evaluation of Omega-3 with Risperidone on Seizures Frequency in Children with Refractory Epilepsy and Attention-Deficit/Hyperactivity Disorder.

We aimed to answer the question whether or not previous antiepileptic drugs with combination of omega-3 and risperidone are more efficient than previous antiepileptic drugs with risperidone alone in decreasing of seizures monthly frequency of children with refractory epilepsy and attention-deficit/hyperactivity disorder (ADHD). In a randomized clinical trial (IRCT201604212639N18), participants referred to Pediatric Neurology Clinic of Shahid Sadoughi Hospital, Yazd, Iran from Jun 2015 were distributed randomly into two groups. In group I, one capsule of omega-3 daily and 0.5 mg of risperidone was divided into two doses with previous antiepileptic drugs and in group II, 0.5 mg of risperidone was divided into two doses with previous antiepileptic drugs were given. The drugs use was continued for three months and the children were followed up monthly for three consecutive months. Primary outcomes included seizure monthly frequency and good response (more than 50% of reduction in seizures monthly frequency). Secondary outcome was clinical side effects. Overall, 23 girls and 33 boys with mean age of 9.24+0.15 yr (29 children in omega-3 group and 27 children in control group) were evaluated. Omega-3 therapy was effective in decreasing of seizures monthly frequency (10.41±3.92 times vs. 17.01±4.98, P=0.03). Good response was seen in three children (11.1%) in control (95% confidence interval: 8%-22.8%) and in 9 children (31%) in omega-3 (95% CI: 47.83%-14.17%) group, which showed that omega-3 was more effective in seizure control. (P=0.001). Frequency of side effects was not different in the two groups (14.8 % in control vs. 20.7% in omega-3 groups, P=0.5). Omega-3 might be used as an effective and safe drug in seizures control of children with refractory epilepsy and ADHD.

A case of delusional parasitosis responded to blonanserin

Sir, Delusional parasitosis is characterized by delusion of being infested by pathogens without any medical or microbiological evidence.[1] It has variously been described as entomophobia, parasitophobia, dermatozoenwahn, Ekbom's syndrome, parasitophobic neurodermatitis, and delusional parasitosis.[12] It can occur secondary to dementia, psychosis, or medical conditions such as Vitamin B12 deficiency, pellagra, severe renal disease, diabetes mellitus, multiple sclerosis, hepatitis, cerebrovascular disease, temporal lobe epilepsy, and leprosy.[34] We report the case of a patient of delusional parasitosis of leg who responded to blonanserin, a new atypical antipsychotic. A 34-year-old, Hindu, high school passed, married male, working in an electronic shop, belonging to middle socioeconomic background, was referred from dermatology department with a 1-year history of feeling of an insect crawling across his both legs during the night, which he attributed to infestation of bedding by insects. He had washed all the beddings of the house numerous times, resorted to sleeping only in undergarments, and used insecticides and mosquito repellent creams for removing insects, but felt no relief. On examination, he was found to have intertrigo (candidal infection) of the axilla and groin but no evidence of any parasitic infestation. He was prescribed 1% clotrimazole cream for topical application, tablet fluconazole 150 mg weekly, and tablet cetirizine 10 mg at bedtime for intertrigo. After 2 weeks of treatment, his intertrigo resolved, but this complaint of crawling of insect across his lower limbs persisted, for which he was referred to the department of psychiatry. Detailed assessment revealed preoccupation with the complaint that there is an insect which crawls over his lower limb. There had been no change in the symptoms since the onset. He said that he was unaware of the source of infestation but believed that it might be present in the bedding, but was not sure as his wife did not have similar complaints. Due to this infestation, he had developed anxiety and sleeplessness and was unable to do his job efficiently. He did not believe the suggestion of his friends and wife that there is no such infestation with insects and was firm in his belief that there are indeed insects which crawl over his lower limbs. Detailed systemic examination including neurological examination did not reveal any abnormality. His relevant investigations were normal. There was no history of chronic physical disease or drug abuse. There was no family history of any psychiatric illness. Mental state examination revealed no perceptual abnormality. He was anxious. Thinking revealed the presence of delusions of insect repeatedly crawling over his lower limbs. No other psychopathology was detected. Higher mental functions were normal. The patient was explained the treatment options available. He was also told that an antipsychotic pimozide was the most accepted treatment for this disorder but was explained the need for regular cardiac monitoring to which he refused. He was given options of using atypical antipsychotics, most of which have shown efficacy in this condition. The patient was started on 2 mg of risperidone but could not tolerate it because of excessive sedation. The patient reported features of akathisia on 10 mg of aripiprazole. He conveyed an inability to afford amisulpride. Due to all these issues, after discussion, he was started on tablet blonanserin 4 mg/day (in divided doses), which was increased to 8 mg/day after 2 weeks and tablet lorazepam 2 mg at night for sleep (on SOS basis). There was partial improvement after 4 weeks of treatment. The dose was further increased to 12 mg/day after 4 weeks. There was complete remission of the patient's delusion at 6 weeks of treatment. On following him up at 3 months, he did not develop the delusion again. The exact mechanism of this disorder is not known. One hypothesis is that these patients suffer a profound breakdown in their ability to discriminate between normal and abnormal somatic perceptions and the delusion may be mediated by a pathological overactivity of the dopaminergic system. There are reports mentioning the usefulness of second-generation antipsychotics in the treatment of delusional parasitosis.[245] Blonanserin is used for the treatment of schizophrenia and has not been tried in the treatment of delusional infestation. The present case responded completely to blonanserin. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

An investigation of regional cerebral blood flow and tissue structure changes after acute administration of antipsychotics in healthy male volunteers.

Chronic administration of antipsychotic drugs has been linked to structural brain changes observed in patients with schizophrenia. Recent MRI studies have shown rapid changes in regional brain volume following just a single dose of these drugs. However, it is not clear if these changes represent real volume changes or are artefacts ("apparent" volume changes) due to drug-induced physiological changes, such as increased cerebral blood flow (CBF). To address this, we examined the effects of a single, clinical dose of three commonly prescribed antipsychotics on quantitative measures of T1 and regional blood flow of the healthy human brain. Males (n = 42) were randomly assigned to one of two parallel groups in a double-blind, placebo-controlled, randomized, three-period cross-over study design. One group received a single oral dose of either 0.5 or 2 mg of risperidone or placebo during each visit. The other received olanzapine (7.5 mg), haloperidol (3 mg), or placebo. MR measures of quantitative T1, CBF, and T1-weighted images were acquired at the estimated peak plasma concentration of the drug. All three drugs caused localized increases in striatal blood flow, although drug and region specific effects were also apparent. In contrast, all assessments of T1 and brain volume remained stable across sessions, even in those areas experiencing large changes in CBF. This illustrates that a single clinically relevant oral dose of an antipsychotic has no detectable acute effect on T1 in healthy volunteers. We further provide a methodology for applying quantitative imaging methods to assess the acute effects of other compounds on structural MRI metrics. Hum Brain Mapp 39:319-331, 2018. © 2017 Wiley Periodicals, Inc.

Clinical practice guidelines for Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a common psychiatric illness with lifetime prevalence of 1-3% [1]. It is the fourth-most common psychiatric illness and a leading cause of disability. OCD is associated with significant impairment in functioning, quality of life and disability. If untreated, OCD is a chronic illness with a waxing and waning of symptoms. A recent meta-analysis of long-term naturalistic prospective studies demonstrated that nearly a half of patients experience remission with much higher rates of remission in Indian patients compared to those in the west [2]. Early diagnosis and appropriate treatment may improve outcomes. Despite OCD being a common mental illness, most seek treatment after several years of suffering. Those who suffer from OCD tend to be secretive about their symptoms and suffer from shame and embarrassment. Less than a third of OCD sufferers receive appropriate pharmacotherapy and even less receive evidence-based psychotherapy. Symptoms The hallmarks of OCD are presence of obsessions and compulsions. Obsessions are repetitive, unwanted, intrusive thoughts, images or urges that are mostly ego-dystonic and cause severe distress or anxiety. Compulsions (or rituals) are repetitive behaviours or mental acts that are performed in response to an obsession to reduce anxiety/distress or prevent a dreaded consequence. Obsessions and compulsions are time consuming, distressing and are often resisted unsuccessfully. Clinical manifestations of OCD are remarkably similar across cultures and geographic locations. Common obsessions and compulsions and symptom dimensions identified through factor-analytical studies are shown in Table 1. Table 1 Common symptoms of OCD

THE ANXIOLYSIS CONUNDRUM: BENZODIAZEPINE VS LOW DOSE ANTIPSYCHOTIC

Background: The unprecedented and unaccounted use of benzodiazepines is running havoc in many countries in terms of substance abuse problems and is exponentially increasing. The prescription of benzodiazepines should be minimized and the search for and use of better alternatives be incorporated into clinical practice of Psychiatry.&#x0D; Aim: The aim of this study is to compare the efficacy of low dose Risperidone and relatively higher dosage of Clonazepam in moderate to severe anxiety states when used in combination with an SSRI.&#x0D; Method: A group of 60 patients having moderate to severe anxiety level, as measured by Hamilton Anxiety Rating Scale (HARS) were randomly divided into two groups. First group was given 1 mg of Risperidone with 50 mg Sertraline and the second group was given 2 mg of Clonazepam with 50 mg Sertraline. The anxiety levels of patients in both groups were again calculated on the 10th post treatment day and compared to each other. Moreover, the Side Effect profiling of Risperidone was also done in all the Patients by using the Glasgow Anti-psychotic Side-effect Scale (GASS)’. Result: The first group receiving sertraline and risperidone showed a significant decrease in the level of anxiety as measured by HARS with a mean score of 29.16 on day 0 to a mean score of 9.60 on day 10 (p=0.0125). The second group receiving sertraline and clonazepam also showed a significant decrease in the anxiety levels with a mean HARS score of 31.12 on day 0 to 12.36 on day 10(p=0.019). One way anova showed that there was no significant difference between the two groups (p=0.989).&#x0D; Conclusion: The efficacy of low dose risperidone is comparable to that of relatively high dose of clonazepam in treating moderate to severe anxiety states. Use of risperidone for symptomatic relief from anxiety is a viable alternative to benzodiazapines