title: Effect of a single dose of citalopram on amygdala response to emotional faces Modafinil for clozapine-treated schizophrenia patients: a double-blind, placebo-controlled pilot trial. Effects of modafinil on cognitive functions in first episode psychosis Does Modafinil Enhance Cognitive Performance in Young Volunteers Who Are Not Sleep-Deprived? Cognitive enhancing effects of modafinil in healthy volunteers Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Modafinil Improves Cognition and Attentional Set Shifting in Patients with Chronic Schizophrenia Effect of Modafinil on Learning and Task-Related Brain Activity in Methamphetamine-Dependent and Healthy Individuals The Effect of Citalopram Pretreatment on Neuronal Responses to Neuropsychological Tasks in Normal Volunteers: An fMRI Study Cognitive performance following modafinil versus placebo in sleep-deprived emergency physicians: a double-blind randomized crossover study. Effects of Modafinil on Wakefulness and Executive Function in Patients With Narcolepsy Experiencing Late-Day Sleepiness A randomized, double-blind, placebo-controlled trial of modafinil for negative symptoms in schizophrenia. Modulatory Effects of Modafinil on Neural Circuits Regulating Emotion and Cognition Modafinil-induced hippocampal activation in narcolepsy Modafinil for excessive sleepiness associated with chronic shift work sleep disorder: effects on patient functioning and health-related quality of life. Modafinil Attenuates Disruptions in Cognitive Performance During Simulated Night-Shift Work Is emotion processing a predictor of functional outcome in schizophrenia? Modafinil modulates anterior cingulate function in chronic schizophrenia. A placebo-controlled study of the modafinil added to risperidone in chronic schizophrenia Modafinil improves alertness, vigilance, and executive function during simulated night shifts. The effects of caffeine, dextroamphetamine, and modafinil on humor appreciation during sleep deprivation. Effect of modafinil on fatigue, mood, and health-related quality of life in patients with narcolepsy Modafinil and unconstrained motor activity in schizophrenia: double-blind crossover placebo-controlled trial. Maintaining alertness and performance during sleep deprivation: modafinil versus caffeine Acute modafinil effects on attention and inhibitory control in methamphetamine-dependent humans. Benefits of adjunct modafinil in an open-label, pilot study in patients with schizophrenia Modafinil affects mood, but not cognitive function, in healthy young volunteers. The Effects of Modafinil, Caffeine, and Dextroamphetamine on Judgments of Simple Versus Complex Emotional Expressions Following Sleep Deprivation Cerebral blood flow changes in man by wake-promoting drug, modafinil: a randomized double blind study. Effect of Pharmacological Enhancement on the Cognitive and Clinical Psychomotor Performance of Sleep-Deprived Doctors: A Randomized Controlled Trial Effects of modafinil in children with attention-deficit/hyperactivity disorder: an open-label study. Modafinil in children with attention-deficit hyperactivity disorder. Randomized controlled trial of effect of prescription of clozapine versus other second-generation antipsychotic drugs in resistant schizophrenia. Double-blind, placebo-controlled study of modafinil for fatigue and cognition in schizophrenia patients treated with psychotropic medications. A Randomized, Double-Blind, Crossover Trial of Modafinil on Mood A randomized, double-blind, placebo-controlled study of modafinil film-coated tablets in children and adolescents with attention-deficit/hyperactivity disorder. Modafinil activates cortical and subcortical sites in the sleep-deprived state. A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression. Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder Effects of Modafinil on Emotional Processing in First Episode Psychosis
abstract: Background Selective serotonin reuptake inhibitors ( SSRIs ) are typically thought to have a delay of several weeks in the onset of their clinical effects . However , recent reports suggest they may have a much earlier therapeutic onset . A reduction in amygdala responsivity has been implicated in the therapeutic action of SSRIs . Aims To investigate the effect of a single dose of an SSRI on the amygdala response to emotional faces . Method Twenty-six healthy volunteers were r and omised to receive a single oral dose of citalopram ( 20 mg ) or placebo . Effects on the processing of facial expressions were assessed 3 h later using functional magnetic resonance imaging . Results Volunteers treated with citalopram displayed a significantly reduced amygdala response to fearful facial expressions compared with placebo . Conclusions Such an immediate effect of an SSRI on amygdala responses to threat supports the idea that antidepressants have an earlier onset of therapeutically relevant effects than conventionally thought BACKGROUND Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine . Clozapine-induced sedation can worsen cognition and impair social and occupational functioning . OBJECTIVES To evaluate the efficacy , tolerability , and safety of modafinil for negative symptoms , cognition , and wakefulness/fatigue in DSM-IV-diagnosed schizophrenia patients treated with clozapine . METHOD A double-blind , placebo-controlled , flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007 , adding modafinil up to 300 mg/d to stabilized schizophrenia out patients receiving clozapine .  Psychopathology , cognition , and wakefulness/fatigue were assessed with st and ard rating scales . RESULTS Thirty-five patients were r and omly assigned to treatment with study drug and included in the analysis . Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo . Modafinil was well tolerated and did not worsen psychosis . CONCLUSIONS Results of this pilot trial do not support routine use of modafinil to treat negative symptoms , cognitive deficits , or wakefulness/fatigue in patients on clozapine . However , given our limited power to detect a treatment effect and the clear possibility of a type II error , larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00573417 Rationale Cognitive impairments are important determinants of functional outcome in psychosis , which are inadequately treated by antipsychotic medication . Modafinil is a wake-promoting drug that has been shown to improve attention , memory and executive function in the healthy population and in patients with schizophrenia . Objectives We aim ed to establish modafinil ’s role in the adjunctive treatment of cognitive impairments in the first episode of psychosis , a time when symptoms may be more malleable than at chronic stages of the disease . Methods Forty patients with a first episode of psychosis participated in a r and omised , double-blind , placebo-controlled crossover design study assessing the effects of a single dose of 200 mg modafinil on measures of executive functioning , memory , learning , impulsivity and attention . Results Modafinil improved verbal working memory ( d = 0.24 , p = 0.04 ) , spatial working memory errors ( d = 0.30 , p = 0.0004 ) and strategy use ( d = 0.23 , p = 0.03 ) . It also reduced discrimination errors in a task testing impulsivity . Modafinil showed no effect on impulsivity measures , sustained attention , attentional set-shifting , learning or fluency . Conclusions Modafinil selectively enhances working memory in first episode psychosis patients , which could have downstream effects on patients ’ social and occupational functioning Abstract : In a double-blind , parallel groups study , 60 healthy student volunteers ( 29 men and 31 women , aged 19 - 22 years ) were r and omly allocated to receive placebo , 100 or 200 mg modafinil . Two hours later , in the early evening , they completed an extensive cognitive battery . The 3 groups did not differ in self-ratings of sleepiness or tiredness before the testing session , and there were no treatment-associated changes in these or in mood ratings during the tests . Modafinil was without effect in several tests of reaction time and attention , but the 200-mg group was faster at simple color naming of dots and performed better than placebo in the Rapid Visual Information Processing test of sustained attention . Modafinil was without effect on spatial working memory , but the 100-mg group performed better in the backward part of the digit span test . Modafinil was without effect on verbal short-term memory ( story recall ) , but 100 mg improved digit span forward , and both doses improved pattern recognition , although this was accompanied by a slowing of response latency in the 200-mg group . There were no significant effects of modafinil compared with placebo in tests of long-term memory , executive function , visuospatial and constructional ability , or category fluency . These results suggest that the benefits of modafinil are not clearly dose-related , and those from 100 mg are limited to the span of immediate verbal recall and short-term visual recognition memory , which is insufficient for it to be considered as a cognitive enhancer in non-sleep-deprived individuals Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder OBJECTIVE Antidepressants that inhibit the reuptake of serotonin ( SSRIs ) or norepinephrine ( SNRIs ) are effective in the treatment of disorders such as depression and anxiety . Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders , but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information . The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers . METHOD Forty-two male and female volunteers were r and omly assigned to 7 days of double-blind intervention with the SSRI citalopram ( 20 mg/day ) , the SNRI reboxetine ( 8 mg/day ) , or placebo . On the final day , facial expression recognition , emotion-potentiated startle response , and memory for affect-laden words were assessed . Question naires monitoring mood , hostility , and anxiety were given before and after treatment . RESULTS In the facial expression recognition task , citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear . Citalopram also abolished the increased startle response found in the context of negative affective images . Both antidepressants increased the relative recall of positive ( versus negative ) emotional material . These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety . However , reboxetine decreased subjective ratings of hostility and elevated energy . CONCLUSIONS Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers , reducing the processing of negative relative to positive emotional material . Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders . They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression Modafinil , a novel cognitive enhancer , selectively improves neuropsychological task performance in healthy volunteers and adult patients with attention deficit hyperactivity disorder ( ADHD ) . It has been argued that persistent cognitive deficits in patients with schizophrenia are responsible for the failure of many patients to rehabilitate socially even when psychotic symptoms are in remission . The present study examined the potential of modafinil as a cognitive enhancer in schizophrenia . Twenty chronic patients with a diagnosis of schizophrenia were entered into a double-blind , r and omized , placebo-controlled crossover study using a 200 mg dose of modafinil . Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD . Improvement was seen on short-term verbal memory span , with trends towards improved visual memory and spatial planning . This was accompanied by slowed response latency on the spatial planning task . No effect on stop-signal performance was seen . Importantly , significant improvement in attentional set shifting was seen , despite no effect of modafinil on this task being seen in healthy volunteers or ADHD patients . Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia , particularly because of its beneficial effects on attentional set shifting Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function . Therefore , medications that improve cognition in these subjects may improve the success of therapy for their addiction , especially when cognitive behavioral therapies are used . Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers . We therefore conducted a r and omized , double-blind , placebo-controlled , cross-over study , using functional magnetic resonance imaging , to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent , MA-dependent , and healthy control participants .  Modafinil ( 200 mg ) and placebo were administered orally ( one single dose each ) , in counterbalanced fashion , 2 h before each of two testing sessions . Under placebo conditions , MA-dependent participants showed worse learning performance than control participants . Modafinil boosted learning in MA-dependent participants , bringing them to the same performance level as control subjects ; the control group did not show changes in performance with modafinil . After controlling for performance differences , MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants . The findings suggest that modafinil improves learning in MA-dependent participants , possibly by enhancing neural function in regions important for learning and cognitive control . These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence Changes in serotonin neurotransmission have also been implicated in the etiology and treatment of impulse control disorders , depression , and anxiety . We have investigated the effect of enhancing serotonin function on fundamental brain processes that we have proposed are abnormal in these disorders . In all , 12 male volunteers received  citalopram  ( 7.5 mg intravenously ) and placebo pretreatment in a single-blind crossover design before undertaking Go/No-go , Loss/No-loss , and covert ( aversive ) face emotion recognition tasks during functional magnetic resonance imaging ( fMRI ) . Blood oxygenation level dependent responses were analyzed using Statistical Parametric Mapping ( SPM2 ) . The tasks activated prefrontal and subcortical regions generally consistent with literature with lateral orbitofrontal cortex ( BA47 ) common to the three tasks . Citalopram pretreatment enhanced the right BA47 responses to the No-go condition , but attenuated this response to aversive faces . Attenuations were seen following citalopram in the medial orbitofrontal ( BA11 ) responses to the No-go and No-loss ( ie relative reward compared with Loss ) conditions . The right amygdala response to aversive faces was attenuated by citalopram . These results support the involvement of serotonin in modulating basic processes involved in psychiatric disorders but argue for a process-specific , rather than general effect . The technique of combining drug challenge with fMRI ( pharmacoMRI ) has promise for investigating human psychiatric disorders OBJECTIVES Modafinil has recently been approved for the treatment of shift work sleep disorder , making it potentially available for shift-working emergency physicians . The authors ' objectives were to determine whether modafinil improved cognitive performance of emergency physicians following overnight shifts and to record symptoms and subjective evaluations of the effect of modafinil on the participants . METHODS This was a r and omized , double-blind , placebo-controlled crossover study that followed CONSORT guidelines . Participants were assigned to one of two study groups , with study sessions occurring at least seven weeks apart , and received either modafinil or placebo depending on their r and om allocation . Testing after night shifts included a coding task and an AX version of the Continuous Performance Task , both of which test cognitive function . Participants also completed visual analog scales for three subjective outcomes , and symptoms were elicited . RESULTS Modafinil facilitated performance on long interstimulus-interval AX trials ( F [ 1 , 23 ] = 6.65 , p = 0.1 ) and marginally reduced errors on AY trials in the Continuous Performance Task ( F [ 1 , 23 ] = 3.59 , p = 0.07 ) , suggesting facilitation of sustained attention , cognitive control , and working memory . Additionally , modafinil , compared with placebo , facilitated performance on the coding task at the first session . Subjective data from visual analog scales confirmed that modafinil increased perceived alertness during the simulated patient care sessions but worsened sleep onset when opportunities for sleep arose . CONCLUSIONS Modafinil increased certain aspects of cognitive function and subjectively improved participants ' ability to attend post-night-shift didactic sessions but made it more difficult for participants to fall asleep when opportunities for sleep arose Objectives : A modafinil daily dosing strategy promotes wakefulness in narcolepsy patients experiencing excessive daytime sleepiness ; however , some patients may continue to experience late-day sleepiness . Excessive sleepiness in narcolepsy is associated with cognitive impairment . Modafinil has improved executive function in other models of excessive sleepiness . This study evaluated the effects of once-daily vs. split doses of modafinil on wakefulness and of combined doses on executive function in narcolepsy patients experiencing late-day sleepiness despite satisfactory modafinil treatment earlier in the day . Methods : After a 2-week washout , 24 patients received 3 weeks of double-blind treatment with modafinil 400-mg once daily ( 7 AM ) plus placebo ( noon ) or modafinil 600-mg split dose ( 400 mg , 7 AM ; 200 mg , noon ) . Assessment s included a Maintenance of Wakefulness Test ( MWT ) for individual regimens and the Wisconsin Card Sort Test ( WCST ) for treatments combined . Results : Modafinil 600-mg split dose was significantly more effective than modafinil 400-mg once daily in improving late-day MWT scores ( 5 PM–7 PM ; P < 0.05 ) . Significant mean ( ± SEM ) reductions from baseline of 8.2 ± 2.7 in the total number of errors and 5.9 ± 1.9 in total percent of errors ( P < 0.05 , both ) were demonstrated for modafinil on the WCST . Modafinil was well tolerated ; adverse events included headache ( n = 1 ) , emotional lability ( n = 1 ) , bronchitis ( n = 1 ) , and accidental injury ( n = 2 ) , with no reports of insomnia . Conclusions : For patients with residual late-day sleepiness associated with narcolepsy , an additional 200-mg dose of modafinil taken at midday was effective in sustaining wakefulness throughout the entire waking day . Treatment with modafinil also significantly improved executive function OBJECTIVE Negative symptoms are core features of schizophrenia that are functionally debilitating , associated with poor outcomes , and resistant to existing pharmacotherapies . We performed a r and omized , double-blind , placebo-controlled study of modafinil , a medication approved for the treatment of excessive daytime sleepiness , to explore its efficacy as an adjunctive therapy for negative symptoms in schizophrenia . METHOD Twenty subjects with DSM-IV schizophrenia or schizoaffective disorder were r and omly assigned to double-blind treatment with modafinil or placebo for 8 weeks . The study ran from March 2002 through March 2006 . Outcome measures included the Scale for the Assessment of Negative Symptoms ( SANS ) , Brief Psychiatric Rating Scale ( BPRS ) , Clinical Global Impressions ( CGI ) scale , Quality of Life Interview , neurocognitive assessment s ( California Verbal Learning Test , De grade d Performance-Continuous Performance Test , Trail-Making Test B ) , and somatic measures ( sleep , weight , side effects ) . RESULTS Modafinil treatment was associated with a greater rate ( CGI-Improvement [ CGI-I ] score < or = 3 , 7/10 vs. 1/10 ) and degree ( mean CGI-I score , 3.2 vs. 4.1 ) of global improvement at study endpoint compared with placebo . However , modafinil did not significantly improve global negative symptoms as measured by the total SANS or SANS individual global items . Modafinil did not significantly worsen psycho-pathology ( according to the BPRS ) , compared with placebo , and was well tolerated . CONCLUSIONS Although no effect on negative symptoms was found , adjunctive therapy with modafinil may result in global improvements in patients with schizophrenia who have prominent negative symptoms Modafinil differs from other arousal-enhancing agents in chemical structure , neurochemical profile , and behavioral effects . Most functional neuroimaging studies to date examined the effect of modafinil only on information processing underlying executive cognition , but cognitive enhancers in general have been shown to have pronounced effects on emotional behavior , too . We examined the effect of modafinil on neural circuits underlying affective processing and cognitive functions . Healthy volunteers were enrolled in this double-blinded placebo-controlled trial ( 100 mg/day for 7 days ) . They underwent BOLD fMRI while performing an emotion information-processing task that activates the amygdala and two prefrontally dependent cognitive tasks — a working memory ( WM ) task and a variable attentional control ( VAC ) task . A clinical assessment that included measurement of blood pressure , heart rate , the Hamilton anxiety scale , and the profile of mood state ( POMS ) question naire was also performed on each test day . BOLD fMRI revealed significantly decreased amygdala reactivity to fearful stimuli on modafinil compared with the placebo condition . During executive cognition tasks , a WM task and a VAC task , modafinil reduced BOLD signal in the prefrontal cortex and anterior cingulate . Although not statistically significant , there were trends for reduced anxiety , for decreased fatigue-inertia and increased vigor-activity , as well as decreased anger-hostility on modafinil . Modafinil in low doses has a unique physiologic profile compared with stimulant drugs : it enhances the efficiency of prefrontal cortical cognitive information processing , while dampening reactivity to threatening stimuli in the amygdala , a brain region implicated in anxiety This study was undertaken to investigate regional metabolic abnormalities and to determine the effects of modafinil in narcoleptics on cerebral glucose metabolism using [ (18)F ] fluorodeoxyglucose positron emission tomography ( FDG PET ) .  Eight narcoleptic patients participated in the study . Two [ (18)F ] FDG PET scans were obtained before and after 2 weeks of modafinil treatment . To identify the effect of modafinil on regional cerebral abnormalities in narcoleptics , pre- and post-treatment PET scans were compared using paired t-statistics with voxel-wised manner . In narcolepsy patients , significant decreases in cerebral glucose metabolism were observed in the midbrain and upper pons , bilateral hypothalamus , posterior thalamus , hippocampus and right parahippocampus as compared with healthy subjects . After treatment , a significant increase in glucose metabolism in the left hippocampus was found in comparison with pre-treatment scan . This study demonstrated that modafinil activates the hippocampus which receives the afferents from hypothalamus , the center of sleep-wake rhythm OBJECTIVE We evaluated the effects of modafinil , a wake-promoting agent , on patient functioning , health-related quality of life , and nighttime and daytime sleep in patients with excessive sleepiness associated with shift work sleep disorder ( SWSD ) . METHOD A 12-week , r and omized , double-blind , placebo-controlled study was performed at 31 centers in the United States between February 2001 and March 2002 . Adults ( N = 278 ) with excessive sleepiness associated with chronic SWSD ( International Classification of Sleep Disorders criteria ) were r and omly assigned to receive modafinil 200 or 300 mg or placebo , 30 to 60 minutes before each night shift . Effects on patient functioning and quality of life were assessed using the Functional Outcomes of Sleep Question naire ( FOSQ ) and the 36-item Short Form Health Survey ( SF-36 ) , respectively . Daily patient diaries were used as a sleep log . RESULTS Modafinil 300 mg significantly improved mean FOSQ total score relative to placebo ( 2.3-point increase from baseline vs. 1.6 for placebo ; p < .05 ) . Both doses of modafinil significantly improved mean SF-36 mental component scores relative to placebo ( mean changes from baseline of 3.2 , 3.7 , and 0.7 points in the modafinil 300-mg , modafinil 200-mg , and placebo groups , respectively ; p < .05 for each comparison vs. placebo ) . Modafinil did not adversely affect sleep when sleep was desired or caffeine use . Modafinil was well tolerated . Headache ( 21.5 % ) and nausea ( 12.4 % ) were the most common adverse events in modafinil-treated patients . Differences between modafinil and placebo for vital sign measurements , physical examination findings , or electrocardiography results were not clinical ly meaningful . CONCLUSIONS Modafinil significantly improves functioning and quality of life in patients with SWSD . Modafinil is an effective treatment for excessive sleepiness associated with SWSD Common complaints among shift workers are sleep disruptions and increased sleepiness while working , which may contribute to shift workers being more susceptible to diminished performance and work-related accidents . The purpose of this double-blind , within-participant study was to examine the effects of the alerting agent modafinil on cognitive/psychomotor performance , mood , and measures of sleep during simulated shift work . In all , 11 participants completed this 23-day residential laboratory study . They received a single oral modafinil dose ( 0 , 200 , 400 mg ) 1 h after waking for three consecutive days under two shift conditions : day shift and night shift . Shifts alternated three times during the study , and shift conditions were separated by an ‘ off ’ day . When participants received placebo , cognitive performance and subjective ratings of mood were disrupted during the night shift , relative to the day shift . Objective and subjective measures of sleep were also disrupted , but to a lesser extent . Modafinil reversed disruptions in cognitive performance and mood during the night shift . While modafinil produced few effects on sleep measures during the night shift , the largest dose produced several sleep alterations during the day shift . These data demonstrate that abrupt shift changes produced cognitive performance impairments and mood disruptions during night shift work . Therapeutic doses of modafinil attenuated night-shift-associated disruptions , but the larger dose produced some sleep impairments when administered during day-shift work Deficits in the ability to perceive facial and vocal emotion expression are common in schizophrenia . However , relatively little is known about how such deficits might affect functional outcomes . This prospect i ve study examined cross-sectional and longitudinal relationships between perception of emotion and aspects of psychosocial functioning , including family relationships , social relationships , work functioning , and independent living/self-care in 94 clinical ly stabilized schizophrenia out patients from five community-based rehabilitation programs .  Emotion perception ( facial emotion , voice emotion , and affect perception ) and psychosocial outcome ( Strauss and Carpenter Outcome Scale and Role Functioning Scale ) were assessed at baseline and after 12 months of psychosocial rehabilitation . Significant associations were found between perception of emotion and work functioning/independent living both cross-sectionally and prospect ively over the 12 months . Causal explanatory models suggested that perception of emotion might cause work functioning/independent living outcome over 1 year . The results remained significant when conceptual disorganization was statistically controlled . We did not find differences between men and women in the correlations between emotion perception and work functioning/independent living . Associations between social functioning/family relationships and perception of emotion were not significant . These findings suggest that emotion processing is a key determinant of work functioning/independent living for individuals with serious mental illness BACKGROUND Schizophrenia is associated with widespread cognitive deficits that have an impact on social function . Modafinil promotes wakefulness and is reported to enhance cognition . AIMS To study the acute effects of modafinil administration upon brain activity and cognitive performance in people with chronic schizophrenia . METHOD In a r and omised double-blind placebo-controlled crossover design , 19 patients received either modafinil ( 100 mg ) or placebo prior to undertaking a working memory task with functional magnetic resonance imaging . RESULTS Seventeen patients completed the study and another underwent acute relapse 4 days post-drug . Modafinil administration was associated with significantly greater activation in the anterior cingulate cortex during the working memory task . The anterior cingulate cortex signal correlated with cognitive performance , although only a subset of patients exhibited ' enhancement ' . CONCLUSIONS Modafinil modulates anterior cingulate cortex function in chronic schizophrenia but its beneficial cognitive effects may be restricted to a subset of patients requiring further characterisation RationalIn recent years , evidence suggests that modafinil may be useful for certain symptom domains of schizophrenia , especially for the negative and cognitive symptoms . However , the results are not consistent . Objective This study was design ed to investigate the effect of modafinil added to risperidone in patients with chronic schizophrenia in a double blind and r and omized clinical trial . Methods Participants were in patients males ( 35 ) and females ( 11 ) , ages 20–49 years at two teaching psychiatric hospital in Iran . All patients were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia . Patients were allocated in a r and om fashion 23 patients to risperidone 6 mg/day plus modafinil 200 mg/day and 23 patients to risperidone 6 mg/day plus placebo . The principal measure of outcome was the positive and negative syndrome scale ( PANSS ) . Patients were assessed by a psychiatrist at baseline and after 2 , 4 , 6 and 8 weeks after the start of medication . Results The modafinil group had significantly greater improvement in the negative symptoms as well as PANSS total scores over the 8-week trial . Therapy with 200 mg/day of modafinil was well tolerated and no clinical ly important side effects were observed . Conclusion The present study indicates modafinil as a potential adjunctive treatment strategy for treatment of schizophrenia particularly the negative symptoms . Nevertheless , results of larger-controlled trials are needed before recommendation for broad clinical application can be made . This trial is registered with the Iranian Clinical Trials Registry ( I RCT 138903131556N16 ) STUDY OBJECTIVES To assess the effect of 200 mg of modafinil compared to placebo on alertness , neurobehavioral performance , and executive function during 4 consecutive simulated night shifts . DESIGN Double-blind , r and omized , parallel groups . SETTING Sleep research facility . PARTICIPANTS 32 male and female volunteers between the ages of 18 and 55 years . INTERVENTIONS 200 mg of modafinil or placebo given nightly on the 4 consecutive simulated night shifts . MEASUREMENTS AND RESULTS Subjects were r and omly assigned to 1 of the 2 treatment conditions , following medical , psychiatric , and polysomnographic screening . On 4 consecutive nights , subjects took study drug at 2200 , and then from about 2300 to 0730 participated in a simulated night shift that included the Maintenance of Wakefulness Test , Psychomotor Vigilance Test , Digit Symbol Substitution Test , measures of subjective alertness , and multiple executive-function measures . At 0800 , daytime sleep periods were recorded polysomnographically for 6 to 8 hours . Alertness -- as measured by the MWT , vigilance and reaction time as indexed by Psychomotor Vigilance Test lapses , and slowest 10 % of reaction times-- and 3 executive-function tasks showed significant enhancement with modafinil versus placebo .  Subjective sleepiness at night and some performance measures did not show consistent treatment differences . Daytime sleep showed minimal differences between conditions . CONCLUSIONS The physiologic sleepiness and neurobehavioral deficits that occurred during the hours of a typical night shift were clearly attenuated by modafinil . Modafinil also had beneficial effects on some measures of executive function STUDY OBJECTIVES Sleep loss consistently impairs performance on measures of alertness , vigilance , and response speed , but its effects on higher-order executive functions are not well delineated . Similarly , whereas deficits in arousal and vigilance can be temporarily countered by the use of several different stimulant medications , it is not clear how these compounds affect complex cognitive processes in sleep-deprived individuals . DESIGN We evaluated the effects of double-blind administration of 3 stimulant medications or placebo on the ability to appreciate humor in visual ( cartoons ) or verbal ( headlines ) stimuli presented on a computer screen following 49.5 hours of sleep deprivation . SETTING In-residence sleep-laboratory facility at the Walter Reed Army Institute of Research . PARTICIPANTS Fifty-four healthy adults ( 29 men , 24 women ) , ranging in age from 18 to 36 years . INTERVENTIONS Each participant was r and omly assigned to 1 of 3 stimulant medication groups , including caffeine , 600 mg , n = 12 ; modafinil , 400 mg , n = 11 ; dextroamphetamine , 20 mg , n = 16 ; or placebo , n = 14 . MEASUREMENTS AND RESULTS Humor appreciation for cartoon stimuli was enhanced by modafinil relative to both placebo and caffeine , but there was no effect of any stimulant medication on the appreciation of verbal humor during sleep loss . In contrast , all 3 stimulants improved psychomotor response speed , whereas only caffeine and dextroamphetamine improved ratings of subjective sleepiness . CONCLUSIONS Findings suggest that , despite similar alerting and vigilance-promoting effects , these 3 compounds have significantly different effects on those highly complex cognitive abilities mediated by the pre-frontal cortex Introduction In addition to excessive sleepiness , patients with narcolepsy often have significant fatigue , depressed mood , and decreased quality of life . Objective To determine whether treatment with modafinil for excessive sleepiness improves fatigue , mood , and health-related quality of life ( HRQOL ) in patients with narcolepsy . Material s and methods Out patients with narcolepsy underwent a 14-day washout of psychostimulants and then were enrolled in this 6-week , open-label , multicenter study . Patients received modafinil starting at 200 mg once daily for week 1 , and then 200 or 400 mg daily for weeks 2 through 6 . Efficacy was evaluated using the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) and the Profile of Mood States ( POMS ) . Safety was assessed by monitoring adverse events ( AE ) . Results At baseline , 151 patients had moderate to severe excessive sleepiness ( mean Epworth Sleepiness Scale score=17.8±4.4 ) . Most patients ( ≥70 % of 123 who completed the study ) received 400 mg modafinil once daily during weeks 2 through 6 . Modafinil significantly improved HRQOL , based on SF-36 measures of mental and physical component summary scores and subdomain scores of role-physical , social functioning , and vitality ( each P<0.001 ) . Modafinil treatment was also associated with significantly reduced fatigue and significantly improved vigor and cognition as assessed by the POMS ( each P<0.001 ) from weeks 1 through 6 . The most frequent AE with modafinil treatment were headache , nausea , and insomnia ; most AE were mild or moderate in nature . Only seven patients ( 5 % ) withdrew from the study because of AE . Conclusion In narcolepsy patients who were switched from psychostimulants , modafinil therapy improved HRQOL and subjective feelings of vigor and cognitive functioning and reduced fatigue Avolition affects quality of life in chronic schizophrenia . We investigated the effect of modafinil upon unconstrained motor activity in 18 male patients . In a r and omised crossover design study , wrist-worn actigraphic monitors were used to objective ly record motor activity  over a 20 h period . Patients ' total activity was significantly greater when given the drug . These data suggest that modafinil increases quantifiable motor behaviour in schizophrenia and may have an impact on avolition Abstract . Rationale : The performance and alertness effects of modafinil were evaluated to determine whether modafinil should replace caffeine for restoring performance and alertness during total sleep deprivation in otherwise healthy adults . Objectives : Study objectives were to determine ( a ) the relative efficacy of three doses of modafinil versus an active control dose of caffeine 600 mg ; ( b ) whether modafinil effects are dose-dependent ; and ( c ) the extent to which both agents maintain performance and alertness during the circadian trough . Methods : Fifty healthy young adults remained awake for 54.5 h ( from 6:30 a.m. day 1 to 1:00 p.m. on day 3 ) and performance and alertness tests were administered bi-hourly from 8:00 a.m. day 1 until 10:00 p.m. day 2 . At 11:55 p.m. on day 2 ( after 41.5 h awake ) , subjects received double blind administration of one of five drug doses : placebo ; modafinil 100 , 200 , or 400 mg ; or caffeine 600 mg ( n=10 per group ) , followed by hourly testing from midnight through 12:00 p.m. on day 3 . Results : Performance and alertness were significantly improved by modafinil 200 and 400 mg relative to placebo , and effects were comparable to those obtained with caffeine 600 mg . Although a trend toward better performance at higher modafinil doses suggested a dose-dependent effect , differences between modafinil doses were not significant . Performance enhancing effects were especially salient during the circadian nadir ( 6:00 a.m. through 10:00 a.m. ) . Few instances of adverse subjective side effects ( nausea , heart pounding ) were reported . Conclusions : Like caffeine , modafinil maintained performance and alertness during the early morning hours , when the combined effects of sleep loss and the circadian trough of performance and alertness trough were manifest . Thus , equivalent performance- and alertness-enhancing effects were obtained with drugs possessing different mechanisms of action . However , modafinil does not appear to offer advantages over caffeine ( which is more readily available and less expensive ) for improving performance and alertness during sleep loss in otherwise normal , healthy adults OBJECTIVE Individuals who are methamphetamine dependent exhibit higher rates of cognitive dysfunction than healthy people who do not use methamphetamine  , and this dysfunction may have a negative effect on the success of behavioral treatments for the disorder . Therefore , a medication that improves cognition , such as modafinil ( Provigil ) , may serve as a useful adjunct to behavioral treatments for methamphetamine dependence . Although cognitive-enhancing effects of modafinil have been reported in several population s , little is known about the effects of modafinil in methamphetamine-dependent individuals . We thus sought to evaluate the effects of modafinil on the cognitive performance of methamphetamine-dependent and healthy individuals . METHOD Seventeen healthy subjects and 24 methamphetamine- dependent subjects participated in this r and omized , double-blind , placebo-controlled , crossover study . Effects of modafinil ( 200 mg , single oral dose ) were assessed on participants ' performance on tests of inhibitory control , working memory , and processing speed/attention . RESULTS Across subjects , modafinil improved performance on a test of sustained attention , with no significant improvement on any other cognitive tests . However , within the methamphetamine-dependent group only , participants with a high baseline frequency of methamphetamine use demonstrated a greater effect of modafinil on tests of inhibitory control and processing speed than those participants with low baseline use of methamphetamine . CONCLUSIONS Although modafinil produced limited effects across all participants , methamphetamine-dependent participants with a high baseline use of methamphetamine demonstrated significant cognitive improvement on modafinil relative to those with low baseline methamphetamine use . These results add to the findings from a clinical trial that suggested that modafinil may be particularly useful in methamphetamine-dependent subjects who use the drug frequently Patients with schizophrenia experience cognitive impairments associated with hypofunctioning of the frontal cortex . Modafinil , a novel wake-promoting agent , works through the sleep – wake centers of the brain to activate the cortex . This 4-week , open-label , pilot study evaluated adjunct modafinil in patients with schizophrenia or schizoaffective disorder . Eleven patients received once-daily oral doses of modafinil ( 100 mg/day , days 1–14 ; 100 or 200 mg/day , days 15–28 ) in addition to antipsychotic therapy . Modafinil significantly improved patients ' global functioning as assessed by a blinded clinician ( week 2 , P = 0.026 ; week 4 , P = 0.012 ) and the investigator ( week 3 , P = 0.035 ) . Modafinil significantly improved overall clinical condition , with 64 % and 82 % of patients rated as clinical ly improved at week 4 by a blinded clinician and the investigator respectively . Eighty-nine percent of patients considered themselves to be clinical ly improved . Modafinil significantly improved fatigue ( P = 0.025 , week 3 ) and tended to improve cognitive functioning scores . Control of positive symptoms was well maintained . Treatment-emergent adverse events included dry mouth ( n = 2 ) and hallucinations ( n = 2 ) . One patient discontinued the study because of hallucinations that were considered to be possibly related to inadequate antipsychotic therapy . Although preliminary , these results suggest modafinil may be an effective and well-tolerated adjunct treatment that improves global functioning and clinical condition , and reduces fatigue in patients with schizophrenia or schizoaffective disorder . Additional controlled studies are warranted Modafinil is a selective wakefulness-promoting agent with beneficial effects in narcolepsy and conditions of sleep deprivation . In a double-blind study we examined its effects in 30 healthy , non sleep-deprived students ( 19 men and 11 women , aged 19 - 23 years ) , who were r and omly allocated to placebo , 100 or 200 mg modafinil and 3 h later completed 100 mm visual analogue scales relating to mood and bodily symptoms , before and after an extensive battery of cognitive tests ( pen and paper and CANTAB ) . There were no significant differences between the three treatment groups on any of the cognitive tests used in this study . There was a significant post-treatment change in the factor measuring ' somatic anxiety ' and in individual ratings of ' shaking ' , ' palpitations ' , ' dizziness ' , ' restlessness ' , ' muscular tension ' , ' physical tiredness ' and ' irritability ' , which was mainly due to significantly higher ratings of somatic anxiety in the 100 mg group compared with the other two groups . Further changes in mood were revealed after the stress of cognitive testing , with the 100 mg group showing greater increases in the ' psychological anxiety ' and the ' aggressive mood ' factors ( as measured from the Bond and Lader scales ) Cognitive abilities such as vigilance , attention , memory , and executive functioning can be de grade d significantly following extended periods of wakefulness . Although much evidence suggests that sleep-loss induced deficits in alertness and vigilance can be reversed or mitigated by stimulants such as caffeine , it is not clear how these compounds may affect other higher level cognitive processes such as emotional perception and judgment . Following 47 h of sleep deprivation , the study examined the effect of three stimulant medications ( modafinil 400 mg , dextroamphetamine 20 mg , caffeine 600 mg ) or placebo on the ability of 54 healthy participants to discriminate and label simple emotional expressions versus complex affect blends ( created by morphing photographs of two different affective facial expressions ) . For simple affective faces , neither sleep loss nor stimulant medications made any difference on the accuracy of judgments . In contrast , for complex emotion blends , all three stimulant medications significantly improved the ability to discriminate subtle aspects of emotion correctly relative to placebo , but did not differ from one another . These findings suggest that all three stimulant medications are effective at restoring some aspects of subtle affective perception To investigate the effects of a wake-promoting drug , modafinil on regional cerebral blood flow ( rCBF ) in healthy volunteers , we performed (99m)Tc-ethylcysteinate dimer single photon emission computed tomography ( SPECT ) before and after modafinil or placebo administration . Twenty-one healthy subjects received single doses of 400 mg modafinil or placebo in a double blind r and omized crossover study design . Administrations of modafinil or placebo in a subject were separated by a 2-week washout . Brain SPECT was performed twice before and 3 h after modafinil or placebo administration . For statistical parametric mapping analysis , all SPECT images were spatially normalized to the st and ard SPECT template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel . The paired t-test was used to compare pre- versus post-modafinil and pre- versus post-placebo SPECT images . Differences in rCBF between post-modafinil and post-placebo conditions were also tested . Modafinil decreased Epworth and Stanford sleepiness scales whereas placebo did not . The post-modafinil condition was associated with increased rCBF in bilateral thalami and dorsal pons , whereas the post-placebo condition showed increased rCBF in a smaller area of the dorsal pons when compared with the drug naïve baseline condition . Compared with the post-placebo condition , the post-modafinil condition showed higher rCBF in bilateral frontopolar , orbitofrontal , superior frontal , middle frontal gyri , short insular gyri , left cingulate gyrus , left middle/inferior temporal gyri , left parahippocampal gyrus , and left pons . In healthy volunteers , modafinil increased wakefulness and rCBF in the arousal-related systems and in brain areas related to emotion and executive function Objectives : To investigate the effect of modafinil 200 mg on the performance of a cohort of healthy male doctors after 1 night of supervised sleep deprivation . Summary Background Data : Sleep-deprived and fatigued doctors pose a safety risk to themselves and their patients . Yet , because of the around-the-clock nature of medical practice , doctors frequently care for patients after periods of extended wakefulness or during circadian troughs . Studies suggest that a group of substances may be capable of safely and effectively reversing the effects of fatigue . However , little work has been done to investigate their role within our profession . Methods : We conducted a parallel , double-blind , r and omized , and placebo-controlled study to investigate the effect of pharmacological enhancement on performance doctors . Thirty-nine healthy male resident doctors received either lactose placebo ( n = 19 ) or modafinil 200 mg ( n = 20 ) after 1 night of sleep deprivation . A selection of CANTAB neuropsychological tests was used to assess higher cognitive function . Clinical psychomotor performance was assessed using the Minimally Invasive Surgical Trainer Virtual Reality . Assessment s were carried out between 6.00 AM and approximately 8.00 AM . Results : Modafinil improved performance on tests of higher cognitive function ; participants in the modafinil group worked more efficiently when solving working memory ( F 1,38 = 5.24 , P = 0.028 ) and planning ( F 1,38 = 4.34 , P = 0.04 ) problems , were less-impulsive decision makers ( F 1,37 = 6.76 , P = 0.01 ) , and were more able to flexibly redirect their attention ( F 1,38 = 4.64 , P = 0.038 ) . In contrast , no improvement was seen in tests of clinical psychomotor performance . Conclusions : Our results suggest that fatigued doctors might benefit from pharmacological enhancement in situations that require efficient information processing , flexible thinking , and decision making under time pressure . However , no improvement is likely to be seen in the performance of basic procedural tasks OBJECTIVE To examine the effect of once-daily dosing of modafinil , a stimulant that has a long duration of action , on clinical features of attention-deficit/hyperactivity disorder ( ADHD ) in children . METHOD An open-label design was used to compare the Conners Parent and Teacher Rating Scale-Revised ( L ) ( CPRS , CTRS ) , the ADHD Rating Scale-IV , and the Test of Variables of Attention ( TOVA ) , without and with medication , in children with ADHD . Eleven children with ADHD , ranging in age from 5 to 15 years , took modafinil for an average of 4.6 weeks . RESULTS Average TOVA ADHD scores improved by 2.43 SD ( p = .0009 ) . CTRS and CPRS ADHD index T scores improved by an average of 14.1 ( p = .0009 ) and 17.7 points ( p = .001 ) , respectively . The mean ADHD Rating Scale-IV scores improved from the 88th percentile to the 75th percentile ( p = .047 ) . One subject withdrew from the study because of an adverse event that was resolved completely with medication withdrawal . Other side effects were mild and responded to dose adjustment . No subjects required more than one dose per day . CONCLUSIONS Modafinil may be a useful once-daily treatment for children with ADHD . Further study using a double-blind , placebo-controlled design is needed Previous clinical evidence suggested that modafinil may improve clinical features of  children with attention-deficit hyperactivity disorder .  To test this hypothesis , a r and omized , double-blind , placebo-controlled study design was used . Of 24 children initially r and omized into the study , 11 control subjects and 11 treatment patients completed the study , with evaluation before medication and after 5 to 6 weeks . The average Test of Variables of Attention attention-deficit hyperactivity disorder z score improved by 2.53 S.D.s for the modafinil group compared with a decline of 1.02 for control patients ( P < or = 0.02 ) . Conners Rating Scales ADHD total t scores for the modafinil group improved from 76.6 to 68.2 compared with improvement from 77.7 to 76.0 for control subjects ( P = 0.04 ) . Ten of 11 treatment patients were reported as " significantly " improved , whereas eight of 11 control subjects were reported as manifesting " no " or " slight " improvement ( P < 0.001 ) . Adverse effects were few and manageable , with no anorexia . Modafinil may be a useful treatment for children with ADHD , particularly when anorexia limits use of stimulants There is good evidence that clozapine is more efficacious than first-generation antipsychotic drugs in resistant schizophrenia .  It is less clear if clozapine is more effective than the other second-generation antipsychotic ( SGA ) drugs . A noncommercially funded , pragmatic , open , multisite , r and omized controlled trial was conducted in the United Kingdom National Health Service ( NHS ) . Participants were 136 people aged 18 - 65 with DSM-IV schizophrenia and related disorders whose medication was being changed because of poor clinical response to 2 or more previous antipsychotic drugs . Participants were r and omly allocated to clozapine or to one of the class of other SGA drugs ( risperidone , olanzapine , quetiapine , amisulpride ) as selected by the managing clinician . Outcomes were assessed blind to treatment allocation . One-year assessment s were carried out in 87 % of the sample . The intent to treat comparison showed no statistically significant advantage for commencing clozapine in Quality of Life score ( 3.63 points ; CI : 0.46 - 7.71 ; p = .08 ) but did show an advantage in Positive and Negative Syndrome Scale ( PANSS ) total score that was statistically significant ( -4.93 points ; CI : -8.82 to -1.05 ; p = .013 ) during follow-up . Clozapine showed a trend toward having fewer total extrapyramidal side effects . At 12 weeks participants who were receiving clozapine reported that their mental health was significantly better compared with those receiving other SGA drugs . In conclusion , in people with schizophrenia with poor treatment response to 2 or more antipsychotic drugs , there is an advantage to commencing clozapine rather than other SGA drugs in terms of symptom improvement over 1 year OBJECTIVE To assess the effects of modafinil on fatigue , symptoms , attention , working memory , and executive functioning in schizophrenia patients treated with psychotropic medications . METHOD Twenty-four patients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder ( 10 men and 14 women ) were r and omly assigned to modafinil up to 200 mg a day ( N = 13 ) or placebo ( N = 11 ) as an adjunct therapy in an 8-week , double-blind , placebo-controlled study . Data were collected from May 18 , 2001 to September 11 , 2003 . RESULTS Four subjects terminated the study early , including one because of worsening of psychosis during the first week taking modafinil . In the modafinil ( N = 10 ) and placebo ( N = 10 ) groups , fatigue improved significantly over time ( p < .01 ) , but there were no differences between groups on changes in fatigue , positive and negative symptoms , or cognition . CONCLUSION Fatigue improved in both groups , and there were no differences between groups on changes in fatigue , symptoms , attention , working memory , or executive functioning . Lack of differences between groups may be due to small sample size or possible regression to the mean in the placebo group Modafinil , a medication for the excessive sleepiness associated with narcolepsy , has been hypothesized to improve not just alertness but mood as well . The purpose of this study was to determine how treatment with modafinil affects mood in healthy volunteers . Normal healthy volunteers ( n = 12 , 10 men and 2 women ; 30 - 44 years ) underwent a 3-day , counterbalanced , r and omized , crossover , inpatient trial of modafinil ( 400 mg daily ) versus placebo with 4-day washout period between 2 treatments . Mood was assessed daily using both the Positive and Negative Affect Schedule and a general mood scale , which consisted of 10 bipolar adjective ratings based on a severity scale ranging from 1 to 10 . Modafinil increased general mood and Negative Affect scales relative to placebo and had a significant effect on Positive Affect scales . These results suggest that modafinil may have general mood-elevating effects accompanied by increased negative affect ( anxiety ) . The findings may have implication s for clinical practice , in particular for the adjunctive use of modafinil in treatment-resistant depression OBJECTIVE To evaluate the efficacy and tolerability of modafinil in children and adolescents , ages 7 to 17 , with attention-deficit/hyperactivity disorder ( ADHD ) . METHOD In this 9-week , double-blind , flexible-dose study , patients were r and omized to  once-daily modafinil ( 170 - 425 mg ) or placebo . Assessment s included ADHD Rating Scale-IV ( ADHD-RS-IV ) School and Home Versions and Clinical Global Impression of Improvement ( CGI-I ) scale . RESULTS Two hundred patients were r and omized . Modafinil produced significant reductions in ADHD-RS-IV total scores at school ( n = 128 ; mean change + /- SD : -17.5 + /- 13.1 points ) compared with placebo ( n = 66 ; -9.7 + /- 10.3 points ; p < .0001 ) . Similarly , modafinil reduced ADHD-RS-IV total scores at home compared with placebo ( -17.6 + /- 13.3 versus -7.5 + /- 11.8 points ; p < .0001 ) . Fifty-two percent of patients r and omized to modafinil and 18 % of those r and omized to placebo met pre study criteria for responder on the CGI-I ( p < .0001 ) . R and omization to modafinil was associated with significantly more insomnia , headache , decreased appetite , and weight loss than r and omization to placebo , but discontinuation attributed to adverse events did not differ statistically between treatment groups ( modafinil , 5 % ; placebo , 6 % ) . CONCLUSION Modafinil was well tolerated and reduced ADHD symptoms at school and home compared with placebo UNLABELLED SUBJECT OBJECTIVES : To assess the effect of the wake-promoting drug modafinil on working memory and brain activation in the executive network , following a single night of sleep deprivation . DESIGN R and omized , placebo-controlled , 4-arm , double-blind evaluation of a single 200-mg dose of modafinil on working memory ( 1- , 2- , and 3-back)-related functional brain activation and performance following overnight sleep deprivation . SETTING General Clinical Research Center , Biomedical Imaging Center . SUBJECTS Eight medication-free men , aged 21 to 35 years . INTERVENTIONS Overnight sleep deprivation , single-dose 200-mg modafinil , functional magnetic resonance imaging MEASUREMENTS AND RESULTS Brain activation patterns and regional signal intensity based on the blood-oxygen level-dependent signal were assessed . The following reaction times were used as measures of performance : ( 1 ) attention in the scanner before functional scanning , ( 2 ) " back " responses during the active-task block , and ( 3 ) attention during the baseline task block . Contrast of activation maps among conditions revealed sleep-deprivation and drug effects , and their interactions . Performance in the deprived state was enhanced by modafinil only at an intermediate ( 2-back ) level of task difficulty and was associated with the recruitment of increased cortical activation volumes . Strong and consistent individual differences in performance were noted on the working memory tasks . CONCLUSIONS Modafinil effectively counters the adverse effects of overnight sleep deprivation on working memory but only when task difficulty is moderate , recruiting extensive areas in the executive network to do so . Interindividual differences in working-memory performance are stable trait characteristics OBJECTIVE Modafinil is approved by the U.S. Food and Drug Administration for improving wakefulness in patients with excessive sleepiness associated with narcolepsy , obstructive sleep apnea , and shift-work sleep disorder . This study was conducted to evaluate the efficacy and safety of adjunctive modafinil in bipolar depression , which is often characterized by excessive sleepiness and fatigue . METHOD Eighty-five patients with bipolar depression that was inadequately responsive to a mood stabilizer with or without concomitant antidepressant therapy were r and omly assigned to receive adjunctive modafinil ( N=41 ) or placebo ( N=44 ) for 6 weeks . The primary outcome measure was baseline-to-endpoint change in score on the Inventory of Depressive Symptoms -- Clinician Rated ( IDS ) . RESULTS The baseline-to-endpoint change in IDS score was significantly greater in the modafinil group ( mean dose , 177 mg/day ) compared with the placebo group . Improvement in depressive symptoms was significantly greater in the modafinil group by week 2 , and this greater improvement was maintained at weeks 4 , 5 , and 6 . Both the response and remission rates were significantly higher in the modafinil group ( 44 % and 39 % ) compared with the placebo group ( 23 % and 18 % ) . During the 6-week study period , there was no difference between groups in treatment-emergent hypomania or mania ( six patients in the modafinil group and five in the placebo group ) or hospitalization for mania ( one in each group ) . CONCLUSIONS These data suggest that adjunctive modafinil at doses of 100 - 200 mg a day may improve depressive symptoms in patients with bipolar disorder BACKGROUND Modafinil , a novel cognitive enhancer , has a clinical profile similar to conventional stimulants such as methylpheni date , despite a seemingly different mechanism of action . Modafinil selectively improves neuropsychological task performance in healthy volunteers , possibly through improved inhibitory control . We examined whether modafinil induced similar improvements in adults with attention-deficit/hyperactivity disorder . METHODS Twenty patients with a DSM-IV diagnosis of attention-deficit/hyperactivity disorder were entered into a double-blind , r and omized , placebo-controlled crossover study using a single 200 mg dose of modafinil . RESULTS Modafinil produced a similar pattern of cognitive enhancement to that observed in healthy adults , with improvements on tests of short-term memory span , visual memory , spatial planning , and stop-signal motor inhibition . On several measures , increased accuracy was accompanied by slowed response latency . This alteration in the speed-accuracy trade-off may indicate that modafinil increases the ability to " reflect " on problems coupled with decreased impulsive responding . Improvements were also seen in sustained attention , which was unaffected in healthy subjects . CONCLUSIONS If these benefits are shown to be maintained with chronic administration , modafinil may have potential as an important therapy for attention-deficit/hyperactivity disorder with a similar effect to stimulants such as methylpheni date in improving stop-signal response inhibition but without the side effects commonly experienced with amphetamine-like drugs BACKGROUND Emotional impairments are important determinants of functional outcome in psychosis , and current treatments are not particularly effective . Modafinil is a wake-promoting drug that has been shown to improve emotion discrimination in healthy individuals and attention and executive function in schizophrenia . We aim ed to establish whether modafinil might have a role in the adjuvant treatment of emotional impairments in the first episode of psychosis , when therapeutic endeavor is arguably most vital . METHODS Forty patients with a first episode of psychosis participated in a r and omized , double-blind , placebo-controlled crossover design study testing the effects of a single dose of 200 mg modafinil on neuropsychological performance . Emotional functions were evaluated with the  emotional face recognition test  , the  affective go-no go task  , and the  reward and punishment learning test . Visual analogue scales were used throughout the study to assess subjective mood changes . RESULTS Modafinil significantly improved the recognition of sad facial expressions ( z = 2.98 , p = .003 ) . In contrast , there was no effect of modafinil on subjective mood ratings , on tasks measuring emotional sensitivity to reward or punishment , or on interference of emotional valence on cognitive function , as measured by the affective go-no go task . CONCLUSIONS Modafinil improves the analysis of emotional face expressions . This might enhance social function in people with a first episode of psychosis
target: A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions , with pro-mnemonic effects and problem solving improvements .
  The systematic review on the neurochemical modulation of the modafinil suggests that its mnemonic enhancing properties might be the result of glutamatergic and dopaminergic increased neuronal activation in the hippocampus and in the prefrontal cortex respectively .
  Other neurotransmitters were also activated by modafinil in various limbic brain areas , suggesting that the drug acts on these brain regions to influence emotional responses .
background: Modafinil is a central nervous system wake promoting agent used for the treatment of excessive daytime sleeping .
  Its vigilance promoting properties and low abuse potential has intrigued the scientific community and has led to use it as a cognitive enhancer , before its neural functions were understood .
  Here , we review the effects of modafinil in human cognition and emotion and its specific actions on symptoms in patients with schizophrenia and whether these are consistently effective throughout the literature .
  We also performed a systematic review on the effects of modafinil on neurotransmitter signalling in different areas of the brain in order to better underst and the neuromechanisms of its cognitive and emotional enhancing properties .