Advertisement

Drug washout issues in studies of cerebral metabolism by positron emission tomography in psychiatric patients

  • J.-L. Martinot
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 37)

Summary

Many studies of brain glucose utilization by positron emission tomography attempt to describe the modifications of the brain activity during psychiatric diseases. A major difficulty in such studies is the necessity to assess patients free of pharmacological treatment, in order to relate the measured changes in glucose utilization to the pathopsychology, and not to a drug effect. In this paper are reviewed the arguments from the literature allowing to estimate the drug washout time for considering the patients as drug-free. The review is focussed on the known effects of the psychotrops on brain glucose utilization. This time is approximatively six months for the neuroleptics given orally, one month for antidepressants, and five and a half half-lives for benzodiazepines. Alternative research strategies for avoiding a long drug washout are mentioned, and ethical limitations are considered.

Keywords

Positron Emission Tomography Psychotropic Drug Glucose Utilization Cerebral Metabolism Brain Glucose 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ableitner A, Herz A (1987) Influence of meprobamate and phenobarbital upon local cerebral glucose utilization: parallelism with effects of the anxiolytic diazepam. Brain Res 403: 82–88PubMedCrossRefGoogle Scholar
  2. Ableitner A, Wüster M, Herz A (1985) Specific changes in local cerebral glucose utilization in the rat brain induced by acute and chronic diazepam. Brain Res 359: 49–56PubMedCrossRefGoogle Scholar
  3. Baxter LR, Phelps ME, Mazziotta JC, Schwartz JM, Gerner RH, Selin CE, Sumida RM (1985) Cerebral metabolic rates for glucose in mood disorders. Arch Gen Psychiatry 42: 441–447PubMedCrossRefGoogle Scholar
  4. Baxter LR, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE (1987) Local cerebral metabolic rates in nondepressed patients with obsessive-compulsive disorder: a comparison with rates in unipolar depression and normal controls. Arch Gen Psychiatry 44: 211–218PubMedCrossRefGoogle Scholar
  5. Baxter LR, Schartz JM, Phelps ME, Mazziotta JC, Guze BH, Selin CE, Gerner RH, Sumida RM (1989) Reduction of prefrontal cortex glucose metabolism common to three types of depression. Arch Gen Psychiatry 46: 243–250PubMedCrossRefGoogle Scholar
  6. Benkelfat C, Nordahl TE, Semple W, King C, Murphy DL, Cohen RM (1990) Local cerebral glucose metabolic rates in obsessive compulsive disorder. Patients treated with clomipramine. Arch Gen Psychiatry 47: 840–848Google Scholar
  7. Boulenger JP (1986) Caractéristiques pharmacocinétiques des benzodiazépines. Act Méd Inter-Psychiatrie 36: 913–914Google Scholar
  8. Brodie JD, Christman DR, Corona JF, Fowler JS, Volkow ND, Wolf AP, Wolkin A (1984) Patterns of metabolic activity in the treatment of schizophrenia. Ann Neurol 15: 166–169CrossRefGoogle Scholar
  9. Buchsbaum MS, Wu J, Haier R, Hazlett E, Ball R, Katz M, Sokolski K, Lagunas-Solar M, Langer D (1987) Positron emission tomography assessment of effects of benzodiazepines on regional glucose metabolic rate in patients with anxiety disorder. Life Sci 40: 2393–2400PubMedCrossRefGoogle Scholar
  10. Campbell A, Baldessarini RJ, Teicher MH, Kola NS (1985) Prolonged antidopaminergic action of single doses of butyrophenones in the rat. Psychopharmacology 87: 161–166PubMedCrossRefGoogle Scholar
  11. Charney DS, Heninger GR, Sternberg DE, Landis H (1982) Abrupt discontinuation of tricyclic antidepressant drugs: evidence for noradrenergic hyperactivity. Br J Psychiatry 141: 377–386PubMedCrossRefGoogle Scholar
  12. DeLisi LE, Holcomb HH, Cohen RM, Pickar D, Carpenter W, Morihisa JM, King AC, Kessler R, Buchsbaum MS (1985) Positron emission tomography in schizophrenic patients with and without neuroleptic medication. J Cereb Blood Flow Metab 5: 201–206PubMedCrossRefGoogle Scholar
  13. Faucon Biguet N, Buda M, Lamouroux A, Samolyk D, Mallet J (1986) Time course of the changes of TH mRNA in rat brain and adrenal medulla after a single injection of reserpine. EMBO J 5: 287–291PubMedGoogle Scholar
  14. Foster N, van der Speck AFL, Aldrich MS, Berent S, Hichwa RH, Sackellares JC, Gilman S, Agranoff BW (1987) The effect of diazepam sedation on cerebral glucose metabolism in Alzheimer’s disease as measured using positron emission tomography. J Cereb Blood Flow Metab 7: 415–420PubMedCrossRefGoogle Scholar
  15. Garnett ES, Nahmias C, Cleghorn G (1985) Pattern of local cerebral glucose metab-olism in untreated schizophrenics. J Cereb Blood Flow Metab 5 [Suppl] 1: 179–180 Gur RE, Resnick SM, Gur RC, Alavi A, Caroff S, Kushner M, Reivich M (1987)Google Scholar
  16. Regional brain function in schizophrenia. Arch Gen Psychiatry 44: 126–129 Hubbard JW, Ganes D, Midha KK (1987) Prolonged pharmacological activity of neuroleptic drugs. Arch Gen Psychiatry 44: 99–100Google Scholar
  17. Ingvar DH, Franzén G (1974) Abnormalities of cerebral blood flow distribution in patients with chronic schizophrenia. Acta Psychiatr Scand 50: 425–462PubMedCrossRefGoogle Scholar
  18. Kornhuber J, Riederer P, Reynolds GP, Beckmann H, Jellinger K, Gabriel E (1989) 3H-spiperone binding in post mortem brains from schizophrenic patients: relationship to neuroleptic drug treatment, abnormal movements, and positive symptoms. J Neural Transm 75: 1–10Google Scholar
  19. Kraus RP, Hux M, Grof P (1987) Psychotropic drug withdrawal and the dexamethasone suppression test. Am J Psychiatry 144: 82–85PubMedGoogle Scholar
  20. McCulloch J, Savaki HE, Sokoloff L (1982) Distribution of effects of haloperidol on energy metabolism in the rat brain. Brain Res 243: 81–90PubMedCrossRefGoogle Scholar
  21. Martinot JL, Allilaire JF, Mazoyer BM, Hantouche E, Huret JD, Legaut-Demare F, Deslauriers AG, Hardy P, Pappata S, Baron JC, Syrota A (1990) Obsessive-compulsive disorder: a clinical, neuropsychological and positron emission tomography study. Acta Psychiatr Scand 82: 233–242PubMedCrossRefGoogle Scholar
  22. Martinot JL, Hardy P, Feline A, Huret JD, Mazoyer B, Attar-Levy D, Pappata S, Syrota A (1990a) Left prefrontal glucose hypometabolism in the depressed state: a confirmation. Am J Psychiatry 147: 1313–1317PubMedGoogle Scholar
  23. Palacios JM, Wiederhold KH (1985) Dopamine D2 receptor agents, but not dopamine D1, modify brain glucose metabolism. Brain Res 327: 390–394PubMedCrossRefGoogle Scholar
  24. Pizzolato G, Soncrant TI’, Rapoport S (1984) Haloperidol and cerebral metabolism in the conscious rat: relation to pharmacokinetics. J Neurochem 43: 724–732PubMedCrossRefGoogle Scholar
  25. Pizzolato G, Soncrant TT, Larson DM, Rapoport SI (1985) Reduced metabolic response of the rat brain to haloperidol after chronic treatment. Brain Res 335: 1–9CrossRefGoogle Scholar
  26. Pizzolato G, Soncrant TI’, Larson DM, Rapoport SI (1987) Stimulatory effect of the D2 antagonist sulpiride on glucose utilization in dopaminergic regions of rat brain. J Neurochem 49: 631–638PubMedCrossRefGoogle Scholar
  27. Poirier MF, Galzin AH, Lôo H, Pimoule C, Segonzac A, Benkelfat C, Sechter D, Zarifian E, Schoemaker H, Langer SZ (1987) Changes in [3H]5-HT uptake and [3H]imipramine binding in platelets after chlorimipramine in healthy volunteers. Comparison with maprotiline and amineptine. Biol Psychiatry 22: 287–302Google Scholar
  28. Ross SB, Aberg-Wistedt A (1983) Inhibitors of serotonin and noradrenalin uptake in human plasma after withdrawal of zimelidine and clomipramine treatment. Psychopharmacology 79: 298–303PubMedCrossRefGoogle Scholar
  29. Sari A, Fukuda Y, Sakabe T, Maekawa T, Toshizo I (1975) Effects of psychotropic drugs on canine cerebral metabolism and circulation related to EEG. Diazepam, clomipramine, and chlorpromazine. J Neurol Neurosurg Psychiatry 38: 838–844Google Scholar
  30. Volkow ND, Brodie JD, Wolf A, Angrist B, Russel J, Cancro R (1986) Brain metabolism in patients with schizophrenia before and after acute neuroleptic administration. J Neurol Neurosurg Psychiatry 49: 1199–1202PubMedCrossRefGoogle Scholar
  31. Wik G, Wiesel FA, Sjögren I, Blomqvist G, Greitz T, Stone-Elander S (1989) Effects of sulpiride and chlorpromazine on regional cerebral glucose metabolism in schizophrenic patients as determined by positron emission tomography. Psycho-pharmacology 97: 309–318Google Scholar
  32. Wistedt B, Jorgensen A, Wiles D (1982) A depot neuroleptic withdrawal study. Plasma concentration of fluphenazine and flupenthixol and relapse frequency. Psycho-pharmacology 78: 301–304Google Scholar
  33. Wolkin A, Jaeger J, Brodie JD, Wolf AP, Fowler J, Rotrosen J, Gomez-Mont F, Cancro R (1985) Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography. Am J Psychiatry 142: 564–571PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • J.-L. Martinot
    • 1
    • 2
  1. 1.Service Hospitalier Frédéric Joliot, CEA, Orsay, and Service de psychiatrieHôpital A. ChenevierCréteilFrance
  2. 2.Psychiatric DepartmentAlbert Chenevier HospitalCréteilFrance

Personalised recommendations