Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers (original) (raw)

Abstract

1. The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double-blind, placebo-controlled, randomised crossover study. 2. Twenty-five healthy volunteers sequentially took 40 mg day-1 simvastatin, 40 mg day-1 pravastatin or placebo for 4 weeks, separated by a 4-6 week washout phase. 3. CNS measures included EEG evoked potentials, power spectral analysis, Leeds Sleep Questionnaire, Hospital Anxiety Depression (HAD) Scale, and Digit Symbol Substitution Test (DSST); biochemical measures included plasma cholesterol, liver enzymes (gamma-GT, AST, ALT) and creatine kinase. 4. Mean cholesterol concentrations with both drugs were significantly lower than with placebo, and the cholesterol-lowering effect was greater with simvastatin. There were no significant differences between treatment in EEG evoked potentials, HAD Scale, or DSST scores. On the sleep measure, subjects reported significantly greater difficulty in getting to sleep while on simvastatin than on pravastatin, but neither score differed from placebo. No significant correlations were observed between sleep ratings and either plasma cholesterol concentrations or EEG evoked potentials. 5. The study showed that, while both drugs reduced plasma cholesterol concentrations, neither exerted significant effects, compared with placebo, on EEG evoked potentials, mood, sleep, or cognitive performance after 4 weeks of chronic administration in healthy volunteers.

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Selected References

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  1. Ashton H., Golding J. F., Marsh V. R., Thompson J. W., Hassanyeh F., Tyrer S. P. Cortical evoked potentials and clinical rating scales as measures of depressive illness. Psychol Med. 1988 May;18(2):305–317. doi: 10.1017/s0033291700007856. [DOI] [PubMed] [Google Scholar]
  2. Ashton H., Millman J. E., Telford R., Thompson J. W. The effect of caffeine, nitrazepam and cigarette smoking on the contingent negative variation in man. Electroencephalogr Clin Neurophysiol. 1974 Jul;37(1):59–71. doi: 10.1016/0013-4694(74)90245-4. [DOI] [PubMed] [Google Scholar]
  3. BECK A. T., WARD C. H., MENDELSON M., MOCK J., ERBAUGH J. An inventory for measuring depression. Arch Gen Psychiatry. 1961 Jun;4:561–571. doi: 10.1001/archpsyc.1961.01710120031004. [DOI] [PubMed] [Google Scholar]
  4. Barth J. D., Kruisbrink O. A., Van Dijk A. L. Inhibitors of hydroxymethylglutaryl coenzyme A reductase for treating hypercholesterolaemia. BMJ. 1990 Sep 29;301(6753):669–669. doi: 10.1136/bmj.301.6753.669-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Black D. M., Lamkin G., Olivera E. H., Laskarzewski P. M., Stein E. A. Sleep disturbance and HMG CoA reductase inhibitors. JAMA. 1990 Sep 5;264(9):1105–1105. doi: 10.1001/jama.1990.03450090041020. [DOI] [PubMed] [Google Scholar]
  6. Chen Z., Peto R., Collins R., MacMahon S., Lu J., Li W. Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. BMJ. 1991 Aug 3;303(6797):276–282. doi: 10.1136/bmj.303.6797.276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Duits N., Bos F. M. Depressive symptoms and cholesterol-lowering drugs. Lancet. 1993 Jan 9;341(8837):114–114. doi: 10.1016/0140-6736(93)92591-g. [DOI] [PubMed] [Google Scholar]
  8. Eckernäs S. A., Roos B. E., Kvidal P., Eriksson L. O., Block G. A., Neafus R. P., Haigh J. R. The effects of simvastatin and pravastatin on objective and subjective measures of nocturnal sleep: a comparison of two structurally different HMG CoA reductase inhibitors in patients with primary moderate hypercholesterolaemia. Br J Clin Pharmacol. 1993 Mar;35(3):284–289. [PMC free article] [PubMed] [Google Scholar]
  9. Engelberg H. Low serum cholesterol and suicide. Lancet. 1992 Mar 21;339(8795):727–729. doi: 10.1016/0140-6736(92)90609-7. [DOI] [PubMed] [Google Scholar]
  10. Fowkes F. G., Leng G. C., Donnan P. T., Deary I. J., Riemersma R. A., Housley E. Serum cholesterol, triglycerides, and aggression in the general population. Lancet. 1992 Oct 24;340(8826):995–998. doi: 10.1016/0140-6736(92)93009-c. [DOI] [PubMed] [Google Scholar]
  11. Golding J. F., Ashton H., Marsh R., Thompson J. W. Transcutaneous electrical nerve stimulation produces variable changes in somatosensory evoked potentials, sensory perception and pain threshold: clinical implications for pain relief. J Neurol Neurosurg Psychiatry. 1986 Dec;49(12):1397–1406. doi: 10.1136/jnnp.49.12.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kassler-Taub K., Woodward T., Markowitz J. S. Depressive symptoms and pravastatin. Lancet. 1993 Feb 6;341(8841):371–372. doi: 10.1016/0140-6736(93)90171-c. [DOI] [PubMed] [Google Scholar]
  13. Lechleitner M., Hoppichler F., Konwalinka G., Patsch J. R., Braunsteiner H. Depressive symptoms in hypercholesterolaemic patients treated with pravastatin. Lancet. 1992 Oct 10;340(8824):910–910. doi: 10.1016/0140-6736(92)93318-h. [DOI] [PubMed] [Google Scholar]
  14. Lindberg G., Råstam L., Gullberg B., Eklund G. A. Low serum cholesterol concentration and short term mortality from injuries in men and women. BMJ. 1992 Aug 1;305(6848):277–279. doi: 10.1136/bmj.305.6848.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Morgan R. E., Palinkas L. A., Barrett-Connor E. L., Wingard D. L. Plasma cholesterol and depressive symptoms in older men. Lancet. 1993 Jan 9;341(8837):75–79. doi: 10.1016/0140-6736(93)92556-9. [DOI] [PubMed] [Google Scholar]
  16. Muldoon M. F., Manuck S. B., Matthews K. A. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. BMJ. 1990 Aug 11;301(6747):309–314. doi: 10.1136/bmj.301.6747.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Neaton J. D., Blackburn H., Jacobs D., Kuller L., Lee D. J., Sherwin R., Shih J., Stamler J., Wentworth D. Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992 Jul;152(7):1490–1500. [PubMed] [Google Scholar]
  18. Shagass C., Roemer R. A., Straumanis J. J., Josiassen R. C. Combinations of evoked potential amplitude measurements in relation to psychiatric diagnosis. Biol Psychiatry. 1985 Jul;20(7):701–722. doi: 10.1016/0006-3223(85)90150-7. [DOI] [PubMed] [Google Scholar]
  19. Wysowski D. K., Gross T. P. Deaths due to accidents and violence in two recent trials of cholesterol-lowering drugs. Arch Intern Med. 1990 Oct;150(10):2169–2172. [PubMed] [Google Scholar]
  20. Zigmond A. S., Snaith R. P. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x. [DOI] [PubMed] [Google Scholar]