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Schizophrenia modafinil

Michael J Minzenberg, Jong H Yoon, Steffan K Soosman, Cameron S Carter
Candidate pro-cognitive drugs for schizophrenia targeting several neurochemical systems have consistently failed to demonstrate robust efficacy. It remains untested whether concurrent antipsychotic medications exert pharmacodynamic interactions that mitigate pro-cognitive action in patients. We used functional MRI (fMRI) in a randomized, double-blind, placebo-controlled within-subject crossover test of single-dose modafinil effects in 27 medicated schizophrenia patients, interrogating brainstem regions where catecholamine systems arise to innervate the cortex, to link cellular and systems-level models of cognitive control...
March 6, 2018: Translational Psychiatry
Zhiyong Ding, Jordan W Brown, Lynne E Rueter, Eric G Mohler
RATIONALE: A novel rodent continuous performance test (CPT) was developed as one of the goals of the NEWMEDS (Novel Methods leading to New Medications in Depression and Schizophrenia) consortium to improve its translatability to the CPT test used in human subjects. OBJECTIVES: The objective of the study is to investigate the effects of attention and cognition enhancing drugs in rodent CPT. METHODS: A single cohort of rats were trained to asymptotic performance in the test...
April 2018: Psychopharmacology
Daniel Neto, Carla Spínola, Joaquim Gago
Schizophrenia is a severe mental disorder characterised by positive and negative symptoms. Negative symptoms are difficult to treat and there is no specific treatment. In small trials, modafinil has been studied in association with antipsychotic treatment. We present three cases of its use; two have developed positive symptoms and one developed renal impairment. Further studies are needed to assess its usefulness in schizophrenia and safety in this group of patients.
June 5, 2017: BMJ Case Reports
J Lees, P G Michalopoulou, S W Lewis, S Preston, C Bamford, T Collier, A Kalpakidou, T Wykes, R Emsley, G Pandina, S Kapur, R J Drake
BACKGROUND: Cognitive deficits in schizophrenia have major functional impacts. Modafinil is a cognitive enhancer whose effect in healthy volunteers is well-described, but whose effects on the cognitive deficits of schizophrenia appear to be inconsistent. Two possible reasons for this are that cognitive test batteries vary in their sensitivity, or that the phase of illness may be important, with patients early in their illness responding better. METHODS: A double-blind, randomised, placebo-controlled single-dose crossover study of modafinil 200 mg examined this with two cognitive batteries [MATRICS Consensus Cognitive Battery (MCCB) and Cambridge Neuropsychological Test Automated Battery (CANTAB)] in 46 participants with under 3 years' duration of DSM-IV schizophrenia, on stable antipsychotic medication...
October 2017: Psychological Medicine
Y Dauvilliers, C Gaig, L Barateau, F Graus, A Iranzo, R Lopez, J Santamaria
Frequency and mechanisms underlying the association between narcolepsy type 1 (NT1) and psychosis remain unclear with potential role for a common immune pathway. We estimated the frequency of psychosis and its characteristics in NT1 at two European sleep centers (France, n = 381; Spain, n = 161) and measured IgG autoantibodies that recognize the GluN1 subunit of the NMDAR in 9 patients with NT1 with psychosis, and 25 NT1 patients without psychosis. Ten NT1 patients (6 in France, 4 in Spain) were diagnosed with comorbid psychosis, a frequency of 1...
May 4, 2016: Scientific Reports
Chittaranjan Andrade
Modafinil or armodafinil (ar/mod) augmentation of antipsychotic medication in schizophrenia patients may be considered with a view to reduce negative symptoms associated with the illness or excessive daytime drowsiness due to any cause. The available data suggest that there is no role for ar/mod in reducing negative symptom burden. A recent pharmacokinetic (PK) study suggested that armodafinil (250 mg/d) reduces key PK parameters of risperidone by about 50%, and key PK parameters of 9-hydroxyrisperidone (paliperidone) by about 20%-30%, probably through induction of CYP3A4...
December 2015: Journal of Clinical Psychiatry
Saeed Shoja Shafti, Sasan Akbari
OBJECTIVES: Negative symptoms are a significant barrier to successful functional outcome and recovery in individuals with schizophrenia, and their management is not easy. Prior tryouts with antidepressants and some cognitive enhancers were not really encouraging, and experiments with modafinil had mixed and indecisive results. The objective of the present study was to assess modafinil's efficacy on subjective and objective aspects of negative symptoms of schizophrenia. METHODS: This study was an 8-week randomized, placebo-controlled trial of modafinil, as an adjective to haloperidol, in treatment of 50 schizophrenic patients...
February 2016: Journal of Clinical Psychopharmacology
Brian E Cade, Daniel J Gottlieb, Diane S Lauderdale, David A Bennett, Aron S Buchman, Sarah G Buxbaum, Philip L De Jager, Daniel S Evans, Tibor Fülöp, Sina A Gharib, W Craig Johnson, Hyun Kim, Emma K Larkin, Seung Ku Lee, Andrew S Lim, Naresh M Punjabi, Chol Shin, Katie L Stone, Gregory J Tranah, Jia Weng, Kristine Yaffe, Phyllis C Zee, Sanjay R Patel, Xiaofeng Zhu, Susan Redline, Richa Saxena
Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample. Meta-analyses were conducted of genetic associations with self-reported, habitual sleep duration from seven Candidate Gene Association Resource (CARe) cohorts of over 25 000 individuals of African, Asian, European and Hispanic American ancestry. All individuals were genotyped for ∼50 000 SNPs from 2000 candidate heart, lung, blood and sleep genes...
January 1, 2016: Human Molecular Genetics
Mona Darwish, Mary Bond, Ronghua Yang, Edward T Hellriegel, Philmore Robertson
BACKGROUND AND OBJECTIVE: Patients with bipolar I disorder and schizophrenia have an increased risk of obstructive sleep apnea. The effects of armodafinil, a weak cytochrome P450 (CYP) 3A4 inducer, on pharmacokinetics and safety of risperidone, an atypical antipsychotic used to treat major psychiatric illness, were investigated. METHODS: Healthy subjects received 2 mg risperidone alone and after armodafinil pretreatment (titrated to 250 mg/day). Pharmacokinetic parameters were derived from plasma concentrations of risperidone and its active metabolite, 9-hydroxyrisperidone (formed via CYP2D6 and CYP3A4), collected before and over 4 days after risperidone administration, and from steady-state plasma concentrations of armodafinil and its circulating metabolites, R-modafinil acid and modafinil sulfone...
November 2015: Clinical Drug Investigation
Michael J Minzenberg, Jong H Yoon, Yaoan Cheng, Cameron S Carter
Control-related cognitive processes such as rule selection and maintenance are associated with cortical oscillations in the gamma range, and modulated by catecholamine neurotransmission. Control-related gamma power is impaired in schizophrenia, and an understudied treatment target. It remains unknown whether pro-catecholamine pharmacological agents augment control-related gamma oscillations in schizophrenia. We tested the effects of 4-week fixed-dose daily adjunctive modafinil (MOD) 200 mg, in a randomized double-blind, placebo-controlled, parallel-groups design...
April 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Evangelia M Tsapakis, Trisevgeni Dimopoulou, Frank I Tarazi
Overwhelming research evidence suggests that the negative symptoms of schizophrenia (NSS) contribute more to impaired quality of life and poor functioning than positive symptoms, and that NSS, including affective flattening, alogia and avolition are present in at least one-fifth of patients diagnosed with schizophrenia. Despite this, management of NSS continues to be a major clinical unmet need as treatment with current antipsychotic medication seems to reach at best modest efficacy. A critical review of the current pharmacological, non-pharmacological and psychosocial treatments available for NSS is presented here, using data retrieved from the MEDLINE/PUBMED, the Cochrane Database of Systematic Reviews and the ClinicalTrials...
September 2015: Pharmacology & Therapeutics
Alexandra Patin, René Hurlemann
Social cognition is a major problem underlying deficiencies in interpersonal relationships in several psychiatric populations. And yet there is currently no gold standard for pharmacological treatment of psychiatric illness that directly targets these social cognitive areas. This chapter serves to illustrate some of the most innovative attempts at pharmacological modulation of social cognition in psychiatric illnesses including schizophrenia, borderline personality disorder, autism spectrum disorders, antisocial personality disorder and psychopathy, social anxiety disorder, and posttraumatic stress disorder...
2015: Handbook of Experimental Pharmacology
Panayiota G Michalopoulou, Shôn W Lewis, Richard J Drake, Abraham Reichenberg, Richard Emsley, Anastasia K Kalpakidou, Jane Lees, Tracey Bobin, James K Gilleen, Gahan Pandina, Eve Applegate, Til Wykes, Shitij Kapur
Several efforts to develop pharmacological treatments with a beneficial effect on cognition in schizophrenia are underway, while cognitive remediation has shown modest effects on cognitive performance. Our goal was to test if pharmacological augmentation of cognitive training would result in enhancement of training-induced learning. We chose modafinil as the pharmacological augmenting agent, as it is known to have beneficial effects on learning and cognition. 49 participants with chronic schizophrenia were enroled in a double-blind, placebo-controlled study across two sites and were randomised to either modafinil (200mg/day) or placebo...
August 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Yasmin Walters, Mark Agius
One of the major symptoms of schizophrenia is cognitive deficits. Despite this, these impairments still lack an effective treatment. It was hoped that atypical antipsychotics would treat these symptoms better than their first generation counterparts, but unfortunately the likes of quetiapine and clozapine did not do so. Asenapine and lurasidone, two newer atypicals, have shown promise, as have agents that interact with the glutamate system. Another approach has been to add agents such as modafinil. More research is needed to consolidate the findings of these studies...
November 2014: Psychiatria Danubina
Bernardo Dell'Osso, Cristina Dobrea, Laura Cremaschi, Chiara Arici, A Carlo Altamura
Medications promoting wakefulness are currently used in psychopharmacology in different contexts and with different objectives. In particular, they may be used for the treatment of syndromes that primarily show significant impairment in alertness/wakefulness (e.g., excessive sleepiness and other sleep disorders) as well as for the symptomatic treatment of different neuropsychiatric disorders that, in turn, are not exclusively characterized by sleep-wake disturbances (like mood disorders, for instance). In addition, several psychotropic compounds, including some antipsychotics, mood stabilizers, antidepressants, and anxiolytics have well-established sedating side effects that may go beyond the therapeutic target and require the symptomatic use of wake-promoting agents...
December 2014: Current Psychiatry Reports
Chittaranjan Andrade, Steve Kisely, Ingrid Monteiro, Sanjay Rao
We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of modafinil or armodafinil (ar/mod) augmentation in schizophrenia. We searched PubMed, clinical trial registries, reference lists, and other sources for parallel group, placebo-controlled RCTs. Our primary outcome variable was the effect of ar/mod on negative symptom outcomes. Eight RCTs (pooled N = 372; median duration, 8 weeks) met our selection criteria. Ar/mod (200 mg/day) significantly attenuated negative symptom ratings (6 RCTs; N = 322; standardized mean difference [SMD], -0...
January 2015: Journal of Psychiatric Research
Michael J Minzenberg, Jong H Yoon, Yaoan Cheng, Cameron S Carter
Control-related cognitive processes such as rule selection are associated with cortical oscillations in the theta, alpha and, beta ranges, and modulated by catecholamine neurotransmission. Thus, a potential strategy for improving cognitive control deficits in schizophrenia would be to use pro-catecholamine pharmacological agents to augment these control-related oscillations. In a double-blind, placebo-controlled (within-subjects) study, we tested the effects of adjunctive single-dose modafinil 200 mg on rule-related 4-30 Hz oscillations in 23 stable schizophrenia patients, using EEG during cognitive control task performance...
December 2014: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Eugenia Sinita, David Coghill
Psychostimulants play a central role in the management of ADHD. Here we review the evidence pertaining to the use of methylphenidate, dexamphetamine and related amphetamine salts, the prodrug lisdexamfetamine and modafinil for the management of comorbid ADHD and non-ADHD indications. There is a growing consensus that stimulant medications are helpful at improving the emotional dysregulation and lability, and oppositional and conduct symptoms that are often associated with ADHD. There is some evidence that psychostimulants may improve outcomes in those with treatment resistant depression, reduce negative symptoms and improve cognitive performance in schizophrenia, and that methylphenidate may reduce binge eating in those with bulimia nervosa...
December 2014: Neuropharmacology
Rick E Bernardi, Rainer Spanagel
Clock genes have been implicated in several disorders, such as schizophrenia, bipolar disorder, autism spectrum disorders, and drug dependence. However, few studies to date have examined the role of clock genes in fear-related behaviors. The authors used mice with the ClockΔ19 mutation to assess the involvement of this gene in contextual fear conditioning. Male wild-type (WT) and ClockΔ19 mutant mice underwent a single session of contextual fear conditioning (12 min, 4 unsignaled shocks), followed by daily 12-min retention trials...
August 2014: Behavioral Neuroscience
Philipp A Csomor, Katrin H Preller, Mark A Geyer, Erich Studerus, Theodor Huber, Franz X Vollenweider
Despite advances in the treatment of schizophrenia spectrum disorders with atypical antipsychotics (AAPs), there is still need for compounds with improved efficacy/side-effect ratios. Evidence from challenge studies suggests that the assessment of gating functions in humans and rodents with naturally low-gating levels might be a useful model to screen for novel compounds with antipsychotic properties. To further evaluate and extend this translational approach, three AAPs were examined. Compounds without antipsychotic properties served as negative control treatments...
September 2014: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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