scholarly journals Time course of improvement with antipsychotic medication in treatment-resistant schizophrenia

2011 ◽  
Vol 199 (4) ◽  
pp. 275-280 ◽  
Author(s):  
Takefumi Suzuki ◽  
Gary Remington ◽  
Tamara Arenovich ◽  
Hiroyuki Uchida ◽  
Ofer Agid ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Time Course ◽  
Rating Scale ◽  
Antipsychotic Treatment ◽  
Treatment Resistant ◽  
Item Score ◽  
Double Blind ◽  
The Mean ◽  
Meta Regression ◽  
Item Scores

BackgroundImprovements are greatest in the earlier weeks of antipsychotic treatment of patients with non-resistant schizophrenia.AimsTo address the early time-line for improvement with antipsychotics in treatment-resistant schizophrenia.MethodRandomised double-blind trials of antipsychotic medication in adult patients with treatment-resistant schizophrenia were investigated (last search June 2010). A series of meta-regression analyses were carried out to examine the effect of time on the average item scores in the Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) at three or more distinct time points within the first 6 weeks of treatment.ResultsStudy duration varied from 4 weeks to 1 year and the definitions of treatment resistance as well as of treatment response were not necessarily consistent across 19 identified studies, resulting in highly variable rates of response (0–76%). The mean standardised baseline item score in the PANSS or BPRS was 3.4 (s.e. = 0.06) in the five studies included in the meta-regression analysis, with the average baseline Clinical Global Impression – Severity score being 5.2 (marked illness). For the pooled population treated with a range of antipsychotics (n = 1019), significant reductions in the mean item scores occurred during the first 4 weeks; improvements observed in later weeks were smaller and non-significant. In contrast, weekly improvement with clozapine was significant throughout (n = 356).ConclusionsOur findings provide preliminary evidence that the majority of improvement with antipsychotics may occur relatively early. More consistent improvements with clozapine may be associated with a gradual titration. To further elucidate response patterns, future studies are needed to provide data over regular intervals during earlier stages of treatment.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Nalbuphine ER Tablets for Uremic Pruritus

2017 ◽  
Vol 46 (6) ◽  
pp. 450-458 ◽  
Author(s):  
Vandana S. Mathur ◽  
Jayant Kumar ◽  
Paul W. Crawford ◽  
Howard Hait ◽  
Thomas Sciascia ◽  
...  
Keyword(s):  
Rating Scale ◽  
Numerical Rating Scale ◽  
Controlled Trial ◽  
Hemodialysis Patients ◽  
Opioid Antagonist ◽  
Opioid Agonist ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Uremic Pruritus ◽  
The Mean

Background: Pruritus is a distressing hallmark of the uremic condition, affecting approximately 60% of hemodialysis patients. Abnormal endogenous opioid ligand activity at μ and κ-opioid receptors has been postulated as a mechanism in uremic pruritus. Nalbuphine is a μ-opioid antagonist and κ-opioid agonist. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 373 hemodialysis patients with moderate or severe uremic pruritus were randomized in a 1: 1:1 ratio to nalbuphine extended-release tablets 120 mg (NAL 120), 60 mg (NAL 60), or placebo and treated for 8 weeks. Three hundred seventy-one were analyzed for efficacy. The primary endpoint was the change from baseline to treatment weeks 7 and 8 in itching intensity on a Numerical Rating Scale (NRS, 0 [no itching]; 10 [worst possible itching]) using an intent-to-treat approach. The aim was to evaluate the safety and antipruritic efficacy of NAL. Results: The mean duration of itching was 3.2 years. From a baseline NRS of 6.9 (1.5), the mean NRS declined by 3.5 (2.4) and by 2.8 (2.2) in NAL 120 mg and the placebo groups, respectively (p = 0.017). There was no evidence of tolerance. A trend for less sleep disruption due to itching (p = 0.062, NAL 120 vs. placebo) was also observed. There were no significant differences between NAL 60 vs. placebo. Serious adverse events occurred in 6.7, 12.7, and 15.4% in the NAL 120, NAL 60, and placebo groups respectively. Conclusions: In this largest-to-date randomized controlled trial in uremic pruritus, NAL 120 durably and significantly reduced the itching intensity among hemodialysis patients.

scholarly journals Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

2018 ◽  
Vol 49 (4) ◽  
pp. 655-663 ◽  
Author(s):  
Fernanda Palhano-Fontes ◽  
Dayanna Barreto ◽  
Heloisa Onias ◽  
Katia C. Andrade ◽  
Morgana M. Novaes ◽  
...  
Keyword(s):  
Rating Scale ◽  
Remission Rate ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Double Blind ◽  
Therapeutic Value ◽  
Antidepressant Effects ◽  
Resistant Depression

AbstractBackgroundRecent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.MethodsTo test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.ResultsWe observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p= 0.04), and at D7 (p< 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen'sd= 0.84; D2: Cohen'sd= 0.84; D7: Cohen'sd= 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64%v.27%;p= 0.04). Remission rate showed a trend toward significance at D7 (36%v.7%,p= 0.054).ConclusionsTo our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression. This study is registered athttp://clinicaltrials.gov(NCT02914769).

scholarly journals A Prospective Pilot Study of Levetiracetam for Body Dysmorphic Disorder

CNS Spectrums ◽  
2009 ◽  
Vol 14 (5) ◽  
pp. 252-260 ◽  
Author(s):  
Katharine A. Phillips ◽  
William Menard
Keyword(s):  
Pilot Study ◽  
Body Dysmorphic Disorder ◽  
Rating Scale ◽  
Primary Outcome Measure ◽  
Obsessive Compulsive ◽  
Open Label ◽  
Double Blind ◽  
The Social ◽  
Scale Scores ◽  
The Mean

ABSTRACTIntroduction: Body dysmorphic disorder (BDD) is an often severe disorder, but few treatment studies have been conducted.Objective: This pilot study explored the efficacy and safety of the antiepileptic medication levetiracetam for BDD.Methods: Seventeen subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition BDD participated in a 12-week open-label levetiracetam trial. Subjects were assessed at regular intervals with standard measures.Results: In intent-to-treat analyses, scores on the Yale-Brown Obsessive Compulsive Scale Modified for BDD (BDD-YBOCS), the primary outcome measure, decreased from 32.5±4.7 at baseline to 21.5±11.0 at endpoint (P<.001). Approximately 60% (n=9) of subjects were responders (≥30% decrease on the BDD-YBOCS). The mean time to response was 4.6±2.8 (range: 2-10) weeks. Scores also significantly improved on the Brown Assessment of Beliefs Scale, the Hamilton Rating Scale for Depression, the Global Assessment of Functioning Scale, and the Social and Occupational Functioning Assessment Scale. Scores did not significantly improve on the Quality of Life Enjoyment and Satisfaction Questionnaire, the Beck Anxiety Inventory, or the Social Phobia Inventory. The mean endpoint dose of levetiracetam was 2,044.1±1,065.2 (range: 250–3,000) mg/day, and it was relatively well-tolerated.Conclusion: Randomized, double-blind placebo-controlled studies of levetiracetam for BDD are needed to confirm these preliminary findings.

A Controlled Comparative Trial of a New Antidepressant, Ciclazindol

1979 ◽  
Vol 7 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Sidney Levine
Keyword(s):  
Rating Scale ◽  
Comparative Trial ◽  
Poor Response ◽  
Endogenous Depression ◽  
Depressive Illness ◽  
Double Blind ◽  
Significant Difference ◽  
Severity Of Depression ◽  
The Mean ◽  
Rate Of Response

The author describes a controlled, double-blind, comparative trial of a new tetracyclic compound, ciclazindol (WY 23409), against amitriptyline in the treatment of thirty-five patients admitted to hospital with depressive illness. Each patient was randomly allocated to three weeks treatment with either 50 mg b.d. ciclazindol or 50 mg b.d. amitriptyline. In the event of a poor response the dose level was raised to 75 mg b.d. Separation of cases of endogenous depression and severity of depression were assessed by the Levine-Pilowsky Depression Questionnaire, a self-rating technique. Severity of depression was also assessed using the Hamilton Rating Scale. No significant difference was noted between the drugs in either the degree or the rate of response nor when the endogenous cases alone were studied. The interesting observation was made that only one-third of ciclazindol patients gained weight compared to almost three-quarters of the amitriptyline group and the mean weight gain of the latter was over double that of the ciclazindol group. The author concludes that ciclazindol offers promise and merits further study using higher dosage levels once its full safety trials have been completed.

scholarly journals Evolution of pain at 3 months by oral resveratrol in knee osteoarthritis (ARTHROL): protocol for a multicentre randomised double-blind placebo-controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e017652 ◽  
Author(s):  
Christelle Nguyen ◽  
Isabelle Boutron ◽  
Gabriel Baron ◽  
Emmanuel Coudeyre ◽  
Francis Berenbaum ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Knee Pain ◽  
Rating Scale ◽  
Controlled Trial ◽  
Tertiary Care ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Knee Oa ◽  
The Mean ◽  
Anti Inflammatory

IntroductionOsteoarthritis (OA) pathophysiology is driven in part by joint inflammation. Resveratrol has in vitro anti-inflammatory properties. We aim to assess the efficacy of oral resveratrol for knee pain at 3 months in people with knee OA.Methods and analysisWe will conduct a randomised double-blind placebo-controlled trial. Overall, 164 individuals with knee OA fulfilling 1986 American College of Rheumatology criteria will be recruited in three tertiary care centres in France and randomised to receive oral resveratrol, 40 mg (two caplets) two times per day for 1 week, then 20 mg (one caplet) two times per day or a matching placebo for a total of 6 months. Randomisation will be centralised and stratified by centre. The allocation ratio of assignments will be 1:1. The primary outcome will be the mean change from baseline in knee pain on a self-administered 11-point pain Numeric Rating Scale at 3 months. Secondary outcomes will be the mean change in knee pain at 6 months, the function subscore of the Western Ontario and McMaster Universities Arthritis Index score, patient global assessment, proportion of responders according to the Osteoarthritis Research Society International–Outcome Measures in Rheumatology criteria at 3 and 6 months, and self-reported number of intra-articular injections of corticosteroids or hyaluronic acid and consumption of analgesics and non-steroidal anti-inflammatory drugs since the last contact. Other interventions will be allowed and self-reported. Adherence will be monitored by capsule counts and a booklet and adverse events recorded at 3 and 6 months. Statisticians, treating physicians and participants will be blinded to the allocated treatment.Ethics and disseminationThe oral resveratrol in knee osteoarthritis (ARTHROL) trial has been authorised by theAgenceNationale de Sécurité du Médicament et des Produits de Santéand ethics were approved by theComité deProtection des Personnes Île-de-FranceIII. The findings of the study will be published in a peer-reviewed journal and disseminated at conferences. The design of ARTHROL will warrant the translation of its findings into clinical practice.Trial registration numberClinicalTrials.gov identifier:NCT02905799. Pre-results. First received: 14 September 2016. Last updated: 16 September 2016. Status: not yet recruiting.

scholarly journals The Effectiveness of Non-clozapine Antipsychotics Combined with Electroconvulsive Therapy versus Clozapine Combined with Electroconvulsive Therapy for Treatment-resistant Schizophrenia

2021 ◽  
Vol 16 (2) ◽  
pp. 263-273
Author(s):  
Pichai Ittasakul ◽  
Keyword(s):  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Mmse Score ◽  
Subscale Score ◽  
Mean Difference ◽  
Response To Treatment ◽  
Treatment Resistant ◽  
Mini Mental Status Exam ◽  
The Mean ◽  
Safe Treatment Option

The study aimed to compare the effectiveness and safety of other atypical antipsychotics (non-clozapine) plus electroconvulsive therapy (ECT) (NC+ECT) versus clozapine plus ECT (C+ECT) for treating treatment-resistant schizophrenia (TRS). Data of 32 patients with TRS who was receiving ECT were analysed. We compared clinical characteristics, response to treatment [defined as an improvement of 40% in the Brief Psychotic Rating Scale (BPRS) psychotic symptom subscale from pretreatment scores], change of Mini-mental Status Exam (MMSE) scores, and other adverse effects between the NC+ECT group (N= 16) and C+ECT group (N =16). We found that the overall response rate was 65.6% (75.8% for the NC+ECT group and 56.3% for the C+ECT group, p=0.26). The overall BPRS score in both groups decreased significantly. The mean difference in total BPRS psychotic subscale score between pre-ECT and after last ECT was 10.4 + 5.8 (p<0.001) for the NC+ECT group and 6.6 + 7.3 (p = 0.002) for the C+ECT group. When comparing the NC+ECT group to the C+ECT group, the mean difference in total BPRS psychotic subscale score was not significant. (p = 0.104). The mean difference in MMSE score between pre-ECT and after the last ECT was -1.1 + 5.1 (p =0.45) for the NC+ECT group and 0.2 + 4.3 (p=0.855) for the C+ECT group. The change of MMSE score in the NC+ECT group was not significant different compare to the C+ECT group (p = 0.461). We concluded the combination of antipsychotics and ECT is an effective and safe treatment option for patients with TRS. Other NC+ECT groups’ efficacy may be comparable to that of clozapine plus ECT.

Antipsychotic Treatment of 22q11.2 Deletion Syndrome-Related Psychoses

2017 ◽  
Vol 50 (04) ◽  
pp. 162-163 ◽  
Author(s):  
Elias Angelopoulos ◽  
Christos Theleritis ◽  
Marina Economou ◽  
Korina Georgatou ◽  
Charalambos Papageorgiou ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
Combination Treatment ◽  
Pharmacological Treatment ◽  
22Q11.2 Deletion Syndrome ◽  
Deletion Syndrome ◽  
Antipsychotic Treatment ◽  
Treatment Resistant ◽  
22Q11.2 Deletion ◽  
Recent Letter ◽  
Letter To The Editor

AbstractIn the recent study by Verhoeven and Egger, 2015 and the recent letter to the editor by Boot et al. 2015 an emphasis is given to the best possible pharmacological treatment of 22q11-2 Deletion-Syndrome related psychoses. We would like to present the case of a 23-year old Cypriot patient with 22q11.2 deletion syndrome who fulfilled criteria for treatment resistant schizophrenia (TRS). He was sequentially treated with aripiprazole, risperidone, olanzapine, haloperidol and a combination treatment with olanzapine and haloperidol. Clozapine was the only antipsychotic medication that has improved his condition.

scholarly journals Adjunctive simvastatin for treatment-resistant depression: study protocol of a 12-week randomised controlled trial

BJPsych Open ◽  
2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Muhammad I. Husain ◽  
Imran B. Chaudhry ◽  
Ameer B. Khoso ◽  
Mohammad Omair Husain ◽  
Raza R. Rahman ◽  
...  
Keyword(s):  
Rating Scale ◽  
Plasma Lipids ◽  
Controlled Trial ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Double Blind ◽  
Treatment As Usual ◽  
Novel Treatments ◽  
Resistant Depression ◽  
Secondary Outcomes

BackgroundA third of patients diagnosed with major depressive disorder (MDD) experience treatment-resistant depression (TRD). Relatively few pharmacological agents have established efficacy for TRD. Therefore, the evaluation of novel treatments for TRD is a pressing priority. Statins are pleiotropic agents and preclinical studies as well as preliminary clinical trials have suggested that these drugs may have antidepressant properties.AimsTo report on a protocol for a 12-week, randomised, double-blind, placebo-controlled trial of add-on treatment with simvastatin for patients meeting DSM-5 criteria for MDD who have failed to respond to at least two adequate trials with approved antidepressants. The trial has been registered with Clinicaltrials.gov in (ClinicalTrials.gov identifier: NCT03435744).MethodAfter screening and randomisation to the two parallel arms of the trial, 75 patients will receive simvastatin and 75 patients will receive placebo as adjuncts to treatment as usual. The primary outcome is change in Montgomery–Åsberg Depression Rating Scale scores from baseline to week 12 and secondary outcomes include changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. Assessments will take place at screening, baseline, and weeks 2, 4, 8 and 12. Checklists for adverse effects will be undertaken at each visit. Simvastatin (20 mg) will be given once daily. Other secondary outcomes include C-reactive protein and plasma lipids measured at baseline and week 12.ResultsThis trial will assess simvastatin's efficacy and tolerability as an add-on treatment option for patients with TRD and provide insights into its putative mechanisms of action.ConclusionsAs the first trial investigating the use of simvastatin as an augmentation strategy in patients with TRD, if the results indicate that adjuvant simvastatin is efficacious in reducing depressive symptoms, it will deliver immediate clinical benefit.Declaration of interestI.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. R.R. and M.M.H. have received educational grants and support for academic meetings from Pfizer, Roche, Novartis and Nabiqasim. A.H.Y. has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. A.H.Y. has undertaken investigator-initiated studies from Astra Zeneca, Eli Lilly, Lundbeck and Wyeth. None of the companies have a financial interest in this research.

scholarly journals Delaying clozapine: how long is too long?

2020 ◽  
Vol 33 (2) ◽  
pp. e100172
Author(s):  
Tom Varghese M ◽  
KS Jyothi ◽  
KS Shaji ◽  
Lekshmi Rita Venugopal
Keyword(s):  
Correlation Coefficient ◽  
Symptom Score ◽  
Negative Symptom ◽  
Antipsychotic Treatment ◽  
Treatment Resistant ◽  
Duration Of Treatment ◽  
Clozapine Therapy ◽  
Syndrome Scale ◽  
The Mean ◽  
Negative Syndrome

BackgroundAlthough clozapine is the most effective drug for treatment-resistant schizophrenia, its use remains restricted in clinical practice in India. The delay in initiating treatment with clozapine and its impact on disease outcome needs evaluation.AimTo identify the implications of delaying clozapine initiation in clinical outcomes among people with treatment-resistant schizophrenia.MethodsSubjects with treatment-resistant schizophrenia, stabilised on clozapine monotherapy, were recruited from the outpatient clinic of a general hospital psychiatry unit offering tertiary care services in Thrissur district, Kerala, India. A retrospective cohort design was employed, and information on duration of illness, total duration of treatment and duration of treatment with clozapine was collected. Present symptom status was measured using the Positive and Negative Syndrome Scale. Factors associated with higher symptom scores were analysed using an independent sample t test, Spearman correlation and multiple linear regression.ResultsForty subjects stabilised on long-term clozapine therapy formed the study sample. The mean dose of clozapine used in the study population was 200 mg. The mean duration of antipsychotic treatment before starting clozapine was 89.3 months (7.4 years). The duration of treatment before starting clozapine was found to have a significant positive association with the total Positive and Negative Syndrome Scale score (correlation coefficient 0.40; p=0.01) and negative symptom score (correlation coefficient 0.33; p=0.04). The multiple regression analysis adjusting for covariates showed that the duration of treatment before starting clozapine was an independent factor associated with a higher negative symptom score in the Positive and Negative Syndrome Scale (slope β=0.05; p=0.02; R2=0.27).ConclusionPoor treatment outcomes in treatment-resistant schizophrenia could be secondary to a delay in initiating clozapine therapy.

A New Model of Electrically Evoked Pain and Hyperalgesia in Human Skin

2001 ◽  
Vol 95 (2) ◽  
pp. 395-402 ◽  
Author(s):  
Wolfgang Koppert ◽  
Sara K. Dern ◽  
Reinhard Sittl ◽  
Sven Albrecht ◽  
Jürgen Schüttler ◽  
...  
Keyword(s):  
Time Course ◽  
Rating Scale ◽  
High Current Density ◽  
Experimental Pain ◽  
Numeric Rating Scale ◽  
Human Model ◽  
High Temporal Resolution ◽  
Double Blind ◽  
New Model ◽  
Analgesic Effects

Background The authors used the analgesics alfentanil, S(+)-ketamine, and systemic lidocaine to examine a new human model of experimental pain and hyperalgesia. Methods Transcutaneous electrical stimulation at a high current density (5 Hz, 67.5+/-6.6 mA) was used to provoke acute pain (numeric rating scale, 5 of 10), stable areas of secondary mechanical hyperalgesia to pin prick (43.6+/-32.1 cm2), and light touch (27.5+/-16.2 cm2) for 2 h. Alfentanil, S(+)-ketamine, and lidocaine were applied for 20 min in a double-blind, placebo-controlled, crossover design in 12 subjects using target controlled infusions. Results In the placebo session, pain ratings and areas of hyperalgesia were stable during the stimulation period, which facilitated the assessment of analgesic effects. Alfentanil effectively inhibited electrically evoked pain and reduced pin prick hyperalgesia and allodynia during its infusion. S(+)-ketamine-induced inhibition of secondary hyperalgesia was more pronounced and lasted for the whole experimental protocol. Therapeutic levels of systemic lidocaine showed only marginal analgesic effects, but lasting antihyperalgesic effects. Conclusions A new model of electrically induced pain and hyperalgesia was established, which enabled assessment of the time course of analgesic and antihyperalgesic effects with high temporal resolution and minimum tissue damage and which was further validated by use of common intravenous anesthetics.

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