Modafinil as an Adjunctive Treatment of Sedation, Negative Symptoms, and Cognition in Schizophrenia

Saavedra-Velez, Carlos; Yusim, Anna; Anbarasan, Deepti; Lindenmayer, Jean-Pierre

doi:10.4088/jcp.07r03982

Cited by 54 publications

(30 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For these reasons, this group of medications has not been systematically studied in these two disorders that essentially or commonly need antipsychotics. Most studies of stimulants in schizophrenia have used modafinil or armodafinil [110][111][112][113][114][115]. The most recent meta-analysis of randomized trials (pooled N = 372; median duration 8 weeks) concluded that modafinil or armodanifil (200 mg/d) had a significant effect on improvement of negative symptoms with small effect sizes.…”

Section: Using Stimulant and Stimulant-like Agentsmentioning

confidence: 99%

Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management

et al. 2016

View full text Add to dashboard Cite

Somnolence is a common side effect of antipsychotics. To assess the incidence of this side effect, we performed a MEDLINE search for randomized, double-blinded, placebo- or active-controlled studies of adult patients treated with antipsychotics for schizophrenia, mania, bipolar depression, or bipolar disorder. We extracted rates of somnolence from original publications and pooled them based on the dose of each antipsychotic in the same psychiatric condition, then estimated the absolute risk increase (ARI) and the number needed to harm (NNH) of an antipsychotic relative to placebo or an active comparator in the same psychiatric condition. According to the ARI in acute schizophrenia, bipolar mania, and bipolar depression, antipsychotics can be classified as high somnolence (clozapine), moderate somnolence (olanzapine, perphenazine, quetiapine, risperidone, ziprasidone), and low somnolence (aripiprazole, asenapine, haloperidol, lurasidone, paliperidone, cariprazine). The risk of somnolence with blonanserin, brexpiprazole, chlorpromazine, iloperidone, sertindole, and zotepine needs further investigation. The rates of somnolence were positively correlated to dose and duration for some antipsychotics, but not for others. Many factors, including antipsychotic per se, the method used to measure somnolence, patient population, study design, and dosing schedule, might affect the incidence of antipsychotic-induced somnolence. The mechanisms of antipsychotic-induced somnolence are likely multifactorial, although the blockade of histamine 1 receptors and α1 receptors may play a major role. The management of antipsychotic-induced somnolence should include sleep hygiene education, choosing an antipsychotic with a lower risk for somnolence, starting at a lower dose with a slower titration based on psychiatric diagnoses, adjusting doses when necessary, and minimizing concurrent somnolence-prone agents. Since most cases of somnolence were mild to moderate, allowing tolerance to develop over at least 4 weeks is reasonable before discontinuing an antipsychotic.

show abstract

Section: Using Stimulant and Stimulant-like Agentsmentioning

confidence: 99%

Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management

et al. 2016

View full text Add to dashboard Cite

show abstract

“…28,29 Recently, the psychostimulant modafinil has been reported to improve cognitive deficits in schizophrenic patients. [30][31][32][33] This presents us with the opportunity to validate the subchronic PCP model as a translational model of the cognitive and cerebral metabolic deficits in schizophrenia. Here we test the ability of modafinil to reverse PCPinduced deficits in cognitive flexibility and overt alterations in cerebral metabolism.…”

Section: Introductionmentioning

confidence: 99%

Modafinil Reverses Phencyclidine-Induced Deficits in Cognitive Flexibility, Cerebral Metabolism, and Functional Brain Connectivity

Dawson

Thompson

McVie

et al. 2010

Schizophrenia Bulletin

View full text Add to dashboard Cite

Objective: In the present study, we employ mathematical modeling (partial least squares regression, PLSR) to elucidate the functional connectivity signatures of discrete brain regions in order to identify the functional networks subserving PCP-induced disruption of distinct cognitive functions and their restoration by the procognitive drug modafinil. Methods: We examine the functional connectivity signatures of discrete brain regions that show overt alterations in metabolism, as measured by semiquantitative 2-deoxyglucose autoradiography, in an animal model (subchronic phencyclidine [PCP] treatment), which shows cognitive inflexibility with relevance to the cognitive deficits seen in schizophrenia. Results: We identify the specific components of functional connectivity that contribute to the rescue of this cognitive inflexibility and to the restoration of overt cerebral metabolism by modafinil. We demonstrate that modafinil reversed both the PCP-induced deficit in the ability to switch attentional set and the PCP-induced hypometabolism in the prefrontal (anterior prelimbic) and retrosplenial cortices. Furthermore, modafinil selectively enhanced metabolism in the medial prelimbic cortex. The functional connectivity signatures of these regions identified a unifying functional subsystem underlying the influence of modafinil on cerebral metabolism and cognitive flexibility that included the nucleus accumbens core and locus coeruleus. In addition, these functional connectivity signatures identified coupling events specific to each brain region, which relate to known anatomical connectivity. Conclusions: These data support clinical evidence that modafinil may alleviate cognitive deficits in schizophrenia and also demonstrate the benefit of applying PLSR modeling to characterize functional brain networks in translational models relevant to central nervous system dysfunction.

show abstract

“…Second, modafinil is a weak psychostimulant that could in principle directly provoke psychosis. Fortunately, the available empirical evidence suggests at most a small risk of provoking psychosis in non-psychotic (Davies et al, 2013) or schizophrenia (Saavedra-Velez et al, 2009) patients. In addition, antipsychotics have variable but significant DA receptor antagonism, and many have significant anti-adrenergic effects as well (Minzenberg and Yoon, 2011).…”

Section: Discussionmentioning

confidence: 99%

Sustained Modafinil Treatment Effects on Control-Related Gamma Oscillatory Power in Schizophrenia

Minzenberg

Yoon

Cheng

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

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. Twenty-seven stable schizophrenia patients performed a cognitive control task during EEG, at baseline and after 4 weeks of treatment. EEG data underwent time-frequency decomposition with Morlet wavelets to determine power of 4-80 Hz oscillations. The modafinil group (n = 14), relative to placebo group (n = 13), exhibited enhanced oscillatory power associated with high-control rule selection in the gamma range after treatment, with additional effects during rule maintenance in gamma and sub-gamma ranges. MOD-treated patients who exhibited improved task performance with treatment also showed greater treatmentrelated delay period gamma compared with MOD-treated patients without improved performance. This is the first evidence in schizophrenia of augmentation of cognition-related gamma oscillations by an FDA-approved agent with therapeutic potential. Gamma oscillations represent a novel treatment target in this disorder, and modulation of catecholamine signaling may represent a viable strategy at this target.

show abstract

Modafinil as an Adjunctive Treatment of Sedation, Negative Symptoms, and Cognition in Schizophrenia

Cited by 54 publications

References 0 publications

Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management

Antipsychotic Drug-Induced Somnolence: Incidence, Mechanisms, and Management

Modafinil Reverses Phencyclidine-Induced Deficits in Cognitive Flexibility, Cerebral Metabolism, and Functional Brain Connectivity

Sustained Modafinil Treatment Effects on Control-Related Gamma Oscillatory Power in Schizophrenia

Contact Info

Product

Resources

About