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The effects of modafinil on mood and cognition in Huntington’s disease

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Abstract

Rationale

The wake-promoting agent modafinil selectively improves neuropsychological task performance in healthy volunteers, in adults with attention deficit hyperactivity disorder (ADHD) and in schizophrenia. We examined whether modafinil induced similar effects in individuals with Huntington’s disease (HD).

Materials and methods

Twenty patients with genetically proven, mild HD participated in a double-blind, randomised, placebo-controlled cross-over study using a single 200 mg dose of modafinil. Patients undertook a battery of neuropsychological tests including measures of cognition and mood.

Results

Modafinil increased alertness as indexed by visual analogue scales. Modafinil did not elicit any significant improvements in cognitive function or mood. Modafinil had a deleterious effect on visual recognition and working memory.

Conclusions

Two hundred milligrams acute modafinil administration did improve alertness but did not improve cognition or mood in patients with mild HD. A multiple dose, chronic administration study is needed before the potential clinical utility of modafinil in HD is discounted.

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References

  • Alexander GE, DeLong MR, Strick PL (1986) Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 9:357–381

    Article  PubMed  CAS  Google Scholar 

  • Anderson KE, Marshall FJ (2005) Behavioral symptoms associated with Huntington’s disease. Adv Neurol 96:197–208 Review

    PubMed  Google Scholar 

  • Aron AR, Dowson JH, Sahakian BJ, Robbins TW (2003) Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder. Biol Psychiatry 54(12):1465–1468

    Article  PubMed  CAS  Google Scholar 

  • Bechara A, Tranel D, Damasio AR (2002) The somatic marker hypothesis and decision-making. In: Grafman J (ed) Handbook of neuropsychology, vol. 7. 2nd edn. Elsevier Science BV, Amsterdam, pp 117–143

    Google Scholar 

  • Beck AT, Steer RA (1987) Beck depression inventory manual. Psychological Corporation, San Antonio, TX

    Google Scholar 

  • Bond A, Lader M (1974) The use of analogue scales in rating subjective feelings. Br J Med Psychol 47:211–218

    Google Scholar 

  • Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C, Richardson JA, Williams SC, Xiong Y, Kisanuki Y, Fitch TE, Nakazato M, Hammer RE, Saper CB, Yanagisawa M (1999) Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell 98(4):437–451

    Article  PubMed  CAS  Google Scholar 

  • Ciarmiello A, Cannella M, Lastoria S, Simonelli M, Frati L, Rubinsztein DC, Squitieri F (2006) Brain white-matter volume loss and glucose hypometabolism precede the clinical symptoms of Huntington’s disease. J Nucl Med 47(2):215–222

    PubMed  CAS  Google Scholar 

  • Deroche-Gamonet V, Darnaudery M, Bruins-Slot L, Piat F, Le Moal M, Piazza PV (2002) Study of the addictive potential of modafinil in naïve and cocaine-experienced rats. Psychopharmacology 161(4):387–395

    Article  PubMed  CAS  Google Scholar 

  • Downes JJ, Roberts AC, Sahakian BJ, Evenden JL, Morris RG, Robbins TW (1987) Impaired extra-dimensional shift performance in medicated and unmedicated Parkinson’s disease: evidence for a specific attentional dysfunction. Neuropsychologia 27(11–12):1329–1343

    Google Scholar 

  • Elliott R, Sahakian BJ, Matthews K, Bannerjea A, Rimmer J, Robbins TW (1997) Effects of methylphenidate on spatial working memory and planning in healthy young adults. Psychopharmacology 131(2):196–206

    Article  PubMed  CAS  Google Scholar 

  • Evenden J (1999) The pharmacology of impulsive behaviour in rats V: the effects of drugs on responding under a discrimination task using unreliable visual stimuli. Psychopharmacology 143(2):111–122

    Article  PubMed  CAS  Google Scholar 

  • Ferraro L, Antonelli T, O’Connor WT, Tanganelli S, Rambert FA, Fuxe K (1997) Modafinil: an antinarcoleptic drug with a different neurochemical profile to damphetamine and dopamine uptake blockers. Biol Psychiatry 42:1181–1183

    Article  PubMed  CAS  Google Scholar 

  • Ho AK, Sahakian BJ, Brown RG, Barker RA, Hodges JR, Ane MN, Snowden J, Thompson J, Esmonde T, Gentry R, Moore JW, Bodner T, NEST-HD Consortium (2003) Profile of cognitive progression in early Huntington’s disease. Neurology 61(12):1702–1706

    PubMed  CAS  Google Scholar 

  • Huntington Study Group (1996) The unified Huntington’s disease rating scale: reliability and consistency. Mov Disord 11:136–142

    Article  Google Scholar 

  • Ishizuka T, Sakamoto Y, Sakurai T, Yamatodani A (2003) Modafinil increases histamine release in the anterior hypothalamus of rats. Neurosci Lett 339(2):143–146

    Article  PubMed  CAS  Google Scholar 

  • Lawrence AD, Hodges JR, Rosser AE, Kershaw A, ffrench-Constant C, Rubinsztein DC, Robbins TW, Sahakian BJ (1998a) Evidence for specific cognitive deficits in preclinical Huntington’s disease. Brain 121(Pt 7):1329–1341

    Article  PubMed  Google Scholar 

  • Lawrence AD, Weeks RA, Brooks DJ, Andrews TC, Watkins LH, Harding AE, Robbins TW, Sahakian BJ (1998b) The relationship between striatal dopamine receptor binding and cognitive performance in Huntington’s disease. Brain 121(Pt7):1343–1355

    Article  PubMed  Google Scholar 

  • Logan GD (1994) On the ability to inhibit thought and action. In: Dagenbach D, Carr TH (eds) Inhibitory processes in attention, memory and language. Academic, San Diego, pp 189–239

    Google Scholar 

  • Marin RS (1996) Apathy, concept, syndrome, neural mechanisms and treatment. Clinical Neuropsychiatry 1(4):303–314

    Google Scholar 

  • Marin RS, Biedrzycki RC, Firinciogullari S (1991) Reliability and validity of the apathy evaluation scale. Psychiatry Res 38(2):143–162

    Article  PubMed  CAS  Google Scholar 

  • Mehta MA, Sahakian BJ, McKenna PJ, Robbins TW (1999) Systemic sulpiride in young adult volunteers simulates the profile of cognitive deficits in Parkinson’s disease. Psychopharmacology (Berl) 146:162–174

    Article  CAS  Google Scholar 

  • Morton AJ, Wood NI, Hastings MH, Hurelbrink C, Barker RA, Maywood ES (2005) Disintegration of the sleep–wake cycle and circadian timing in Huntington’s disease. J Neurosci 25(1):157–163

    Article  PubMed  CAS  Google Scholar 

  • Murphy FC, Sahakian BJ, Rubinsztein JS, Michael A, Rogers RD, Robbins TW, Paykel ES (1999) Emotional bias and inhibitory control processes in mania and depression. Psychol Med 29:1307–1321

    Article  PubMed  CAS  Google Scholar 

  • Nelson H (1982) National adult reading test manual. Windsor NFER-Nelson, UK

    Google Scholar 

  • Owen AM, Downes JJ, Sahakian BJ, Polkey CE, Robbins TW (1990) Planning and spatial working memory following frontal lobe lesions in man. Neuropsychologia 28:1021–1034

    Article  PubMed  CAS  Google Scholar 

  • Owen AM, Sahakian BJ, Semple J, Polkey CE, Robbins TW (1995) Visuo-spatial short term recognition memory and learning after temporal lobe excisions, frontal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia 33:1–24

    Article  PubMed  CAS  Google Scholar 

  • Pavese N, Andrews TC, Brooks DH, Ho AK, Rosser AE, Barker RA, Robbins TW, Sahakian BJ, Dunnett SB, Piccini P (2003) Progressive striatal and cortical dopamine receptor dysfunction in Huntington’s disease: a PET study. Brain 126(pt5):1127–1135

    Article  PubMed  Google Scholar 

  • Petersen A, Gil J, Maat-Schieman ML, Bjorkqvist M, Tanila H, Araujo IM, Smith R, Popovic N, Wierup N, Norlen P, Li JY, Roos RA, Sundler F, Mulder H, Brundin P (2005) Orexin loss in Huntington’s disease. Hum Mol Genet 14(1):39–47

    Article  PubMed  CAS  Google Scholar 

  • Rosas HD, Tuch DS, Hevelone ND, Zaleta AK, Vangel M, Hersch SM, Salat DH (2006) Diffusion tensor imaging in presymptomatic and early Huntington’s disease: selective white matter pathology and its relationship to clinical measures. Mov Disord 21(9):1317–1325

    Article  PubMed  Google Scholar 

  • Scammel TE, Estabrooke IV, McCarthy MT, Chemelli RM, Yanagisawa M, Miller MS, Saper CB (2000) Hypothalamic arousal regions are activated during modafinil-induced wakefulness. J Neurosci 20(22):8620–8628

    Google Scholar 

  • Taylor FB, Russo J (2000) Efficacy of modafinil compared to dextoamphetamine for the treatment of attention deficit hyperactivity disorder in adults. J Child Adolesc Psychopharmacol 10(4):311–320 Winter

    Article  PubMed  CAS  Google Scholar 

  • Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ (2003a) Cognitive enhancing effects of modafinil in healthy volunteers. Psychopharmacology 165(3):260–269

    PubMed  CAS  Google Scholar 

  • Turner DC, Robbins TW, Clark L, Aron AR, Dowson J, Sahakian BJ (2003b) Relative lack of cognitive effects of methylphenidate in elderly male volunteers. Psychopharmacology (Berl) 168(4):455–464

    Article  CAS  Google Scholar 

  • Turner DC, Clark L, Dowson J, Robbins TW, Sahakian BJ (2004a) Modafinil improves cognition and response inhibition in adult attention-deficit-hyperactivity disorder. Biol Psychiatry 55(10):1031–1040

    Article  PubMed  CAS  Google Scholar 

  • Turner DC, Clark L, Pomarol-Clotet E, McKenna P, Robbins TW, Sahakian BJ (2004b) Modafinil improves cognition and attentional set shifting in patients with chronic schizophrenia. Neuropsychopharmacology 29(7):1363–1373

    Article  PubMed  CAS  Google Scholar 

  • Watson D, Clark LA, Tellegen A (1988) Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 54:1063–1070

    Article  PubMed  CAS  Google Scholar 

  • Wechsler D (1981) Wechsler adult intelligence scale—revised. The Psychological Corporation, New York

    Google Scholar 

  • Werheid K, Hoppe C, Thöne A, Müller U, Müngersdorf M, Von Cramon DY (2002) The adaptive digit ordering test: clinical application, reliability and validity of a verbal working memory test. Arch Clin Neuropsychol 17:547–565

    Article  PubMed  Google Scholar 

  • Willie JT, Renthal W, Chemelli RM, Miller MS, Scammell TE, Yanagisawa M, Sinton CM (2005) Modafinil more effectively induces wakefulness in orexin-null mice than in wild-type littermates. Neuroscience 130(4):983–995

    Article  PubMed  CAS  Google Scholar 

  • Wisor JP, Eriksson KS (2005) Dopaminergic–adrenergic interactions in the wake promoting mechanism of modafinil. Neuroscience 132(4):1027–1034

    Article  PubMed  CAS  Google Scholar 

  • Wisor JP, Nishino S, Sora I, Uhl GH, Mignot E, Edgar DM (2001) Dopaninergic role in stimulant-induced wakefulness. J Neurosci 21(5):1787–1794

    PubMed  CAS  Google Scholar 

  • Wong YN, King SP, Laughton WB, McCormick GC, Grebow PE (1998) Single-dose pharmacokinetics of modafinil and methylphenidate given alone or in combination in healthy male volunteers. J Clin Pharmacol 38:276–282

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank the patients for participating in this study, which was funded by a grant from the High Q Foundation; grant (CHDI, Inc.) awarded to BJS, ADB, RAB and TWR. This project was completed in association with the MRC/Wellcome Trust-funded Behavioural and Clinical Neuroscience Institute. TWR and BJS consult for Cambridge Cognition Ltd. ADB is now employed by Cambridge Cognition Ltd.

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Authors and Affiliations

  1. Department of Psychiatry, School of Clinical Medicine, University of Cambridge, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2QQ, UK

    Andrew D. Blackwell & Barbara J. Sahakian

  2. Cambridge Centre for Brain Repair, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge, CB2 2PY, UK

    Nicole S. Paterson & Roger A. Barker

  3. Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge, CB2 3EB, UK

    Trevor W. Robbins

Authors
  1. Andrew D. Blackwell
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  2. Nicole S. Paterson
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  3. Roger A. Barker
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  4. Trevor W. Robbins
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  5. Barbara J. Sahakian
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Corresponding author

Correspondence to Barbara J. Sahakian.

Appendix 1—state apathy evaluation

Appendix 1—state apathy evaluation

Table 4 How do you feel right now (at this minute)?
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Blackwell, A.D., Paterson, N.S., Barker, R.A. et al. The effects of modafinil on mood and cognition in Huntington’s disease. Psychopharmacology 199, 29–36 (2008). https://doi.org/10.1007/s00213-008-1068-0

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  • DOI: https://doi.org/10.1007/s00213-008-1068-0

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