Modafinil combined with cognitive training: pharmacological augmentation of cognitive training in schizophrenia.
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. All participants engaged in a cognitive training program for 10 consecutive weekdays. The primary outcome measure was the performance on the trained tasks and secondary outcome measures included MATRICS cognitive battery, proxy measures of everyday functioning and symptom measures. 84% of the participants completed all study visits. Both groups showed significant improvement in the performance of the trained tasks suggesting potential for further learning. Modafinil did not induce differential enhancement on the performance of the trained tasks or any differential enhancement of the neuropsychological and functional measures compared to placebo. Modafinil showed no significant effects on symptom severity. Our study demonstrated that combining pharmacological compounds with cognitive training is acceptable to patients and can be implemented in large double-blind randomised controlled trials. The lack of differential enhancement of training-induced learning raises questions, such as choice and optimal dose of drug, cognitive domains to be trained, type of cognitive training, intervention duration and chronicity of illness that require systematic investigation in future studies.
Section on Schizophrenia, Imaging and Therapeutics, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, PO Box 053, 16 De Crespigny Park, London SE5 8AF, UK. Electronic address: panayiota.michalopoulou@kcl.ac.uk.
Panayiota G
PG
Michalopoulou
Institute of Brain, Behaviour and Mental Health, University of Manchester, UK.
Shôn W
SW
Lewis
Institute of Brain, Behaviour and Mental Health, University of Manchester, UK.
Richard J
RJ
Drake
Icahn School of Medicine, Mount Sinai, New York, USA; Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, UK.
Abraham
A
Reichenberg
Institute of Population Health, University of Manchester, UK.
Richard
R
Emsley
Section on Schizophrenia, Imaging and Therapeutics, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, PO Box 053, 16 De Crespigny Park, London SE5 8AF, UK.
Anastasia K
AK
Kalpakidou
Institute of Brain, Behaviour and Mental Health, University of Manchester, UK.
Jane
J
Lees
Section on Schizophrenia, Imaging and Therapeutics, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, PO Box 053, 16 De Crespigny Park, London SE5 8AF, UK.
Tracey
T
Bobin
Section on Schizophrenia, Imaging and Therapeutics, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, PO Box 053, 16 De Crespigny Park, London SE5 8AF, UK.
James K
JK
Gilleen
Janssen Research & Development, LLC, USA.
Gahan
G
Pandina
Institute of Brain, Behaviour and Mental Health, University of Manchester, UK.
Eve
E
Applegate
Department of Psychology, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, UK.
Til
T
Wykes
Section on Schizophrenia, Imaging and Therapeutics, Institute of Psychiatry, Psychology and Neuroscience, King׳s College London, PO Box 053, 16 De Crespigny Park, London SE5 8AF, UK.
Shitij
S
Kapur
D000328:Adult; D001559:Benzhydryl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D002908:Chronic Disease; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D000077408:Modafinil; D011569:Psychiatric Status Rating Scales; D011619:Psychotropic Drugs / Q000009:adverse effects / Q000627:therapeutic use*; D012559:Schizophrenia / Q000628:therapy*; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D016896:Treatment Outcome
D001559:Benzhydryl Compounds; D011619:Psychotropic Drugs; D000077408:Modafinil
Clinical trial; Cognitive impairment associated with schizophrenia (CIAS); Cognitive remediation; Cognitive-enhancing drugs; Combination of cognitive-enhancing drugs with cognitive training; Modafinil