Treating Depression in Acute Stage: Biochemical and Clinical Aspects

  • O. J. Rafaelsen
  • A. Gjerris
Conference paper
Part of the Psychopharmacology Series book series (PSYCHOPHARM, volume 5)

Abstract

The treatment of depression has advanced dramatically over the last 50 years: electroconvulsion, monoamine oxidase inhibitors (MAOIs), cyclic antidepressants — in chronological order. The amine theories have been giving guidance in the development of new antidepressant drugs and have thus been important in the selectivity of drugs acting, for example, primarily on 5-hydroxytryptamine (5-HT) reuptake. Drugs like citalopram, fluoxetine, fluvoxamine, and paroxetine are very selective in their 5-HT reuptake inhibition, so that in clinical practice they can be tested for the specific importance of this system in depression.

Research on cerebrospinal fluid (CSF) has for many years been restricted to amine metabolites, but we have now been able to measure the parent neurotransmitters, thanks to international cooperation. CSF adrenaline was low, noradrenaline normal, and serotonin and dopamine increased in untreated depression. This calls for major revision of the amine theories.

In addition, our animal studies have shown marked increase in CSF adrenaline after MAOIs, and long-term effect of citalopram on CSF noradrenaline. This indicates the need for enlargement of the number of transmitters in the elucidation of the biology of depression and its treatment, and that interactive counterregulations may lessen the initial selectivity of antidepressant drugs.

Keywords

Depression Dopamine Dementia Schizophrenia Serotonin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ågren H (1980) Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid. II. Suicide. Psychiatry Res 3: 225–236Google Scholar
  2. Åsberg M, Bertilsson L, Martensson B, Scalia-Tomba G-P, Thorén, Träskman-Bendtz L (1984) CSF monoamine metabolites in melancholia. Acta Psychiatr Scand 69: 201–219PubMedCrossRefGoogle Scholar
  3. Berger PA, King R, Lemoine P, Mefford IN, Barchas JD (1984) Cerebrospinal fluid epinephrine concentrations: discrimination of subtypes of depression and schizophrenia. Pharmacol Bull 20: 412–415Google Scholar
  4. Christensen NJ, Vestergaard P, Sørensen T, Rafaelsen OJ (1980) Cerebrospinal fluid adrenaline and noradrenaline in depressed patients. Acta Psychiatr Scand 61: 178–185PubMedCrossRefGoogle Scholar
  5. Gjerris A, Barry DI, Christensen NJ, Rafaelsen OJ (1984) Brain and cerebrospinal fluid epinephrine in isocarboxazide and zimeldine-treated rats. In: Usdin E, Carlsson A, Dahlström A, Engel J (eds) Catecholamines, part C: Neuropharmacology and central nervous system - therapeutic aspects. Liss, New York, pp 139–142Google Scholar
  6. Gjerris A, Werdelin L, Gjerris F, Sørensen PS, Rafaelsen OJ, Alling C (1987 a) CSF-amine metabolites in depression, dementia and in controls. Acta Psychiatr Scand 75: 619–628PubMedCrossRefGoogle Scholar
  7. Gjerris A, Rafaelsen OJ, Christensen NJ (1987 b) CSF-adrenaline — low in “somatizing depression”. Acta Psychiatr Scand 75: 516–520PubMedCrossRefGoogle Scholar
  8. Gjerris A, Sørensen AS, Rafaelsen OJ, Werdelin L, Alling C, Linnoila M (1987c) 5-HT and 5-HIAA in cerebrospinal fluid in depression. J Affective Disord 12: 13–22CrossRefGoogle Scholar
  9. Gjerris A, Werdelin L, Rafaelsen OJ, Alling C, Christensen NJ (1987d) CSF dopamine increased in depression: CSF dopamine, noradrenaline and their metabolites in depressend patients and in controls. J Affective Disord 13: 279–286CrossRefGoogle Scholar
  10. King RJ, Mefford IN, Wang C, Murchinson A, Caligari EJ, Berger PA (1986) CSF dopamine levels correlated with extraversion in depressed patients. Psychiatry Res 305–310Google Scholar
  11. Koslow SH, Maas JW, Bowden CL, Davis JM, Hanin I, Javaid J (1983) CSF and urinary biogenic amines and metabolites in depression and mania. Arch Gen Psychiatry 40: 999–1010PubMedCrossRefGoogle Scholar
  12. Mendlewicz J, Pinder RM, Stulemeijer SM, van Dorth R (1982) Monoamine metabolites in cerebrospinal fluid of depressed patients during treatment with mianserin or amitriptyline. J Affective Disord 4: 219–226CrossRefGoogle Scholar
  13. Post RM, Goodwin FK (1974) Effects of amitriptyline and imipramine on amine metabolites in the cerebrospinal fluid of depressed patients. Arch Gen Psychiatry 30: 234–239PubMedCrossRefGoogle Scholar
  14. Post RM, Lake CR, Jimerson DC, Bunney WE, Wood JH, Ziegler MG, Goodwin FK (1978) Cerebrospinal fluid norepinephrine in affective illness. Am J Psychiatry 135: 907–912PubMedGoogle Scholar
  15. Post RM, Ballenger JC, Goodwin FK (1980) Cerebrospinal fluid studies of neurotransmitter function in manic and depressive illness. In: Wood JH (ed) Neurobiology of cerebrospinal fluid 1. Plenum, New York, pp 685–717Google Scholar
  16. Potter WZ, Scheinen M, Golden RW, Rudorfor MW, Cowdry RW, Calil HM, Ross RW, Linnoila M (1985) Selective antidepressants and cerebrospinal fluid. Arch Gen Psychiatry 42: 1171–1177PubMedCrossRefGoogle Scholar
  17. Träskmann L, Åsberg M, Bertilsson L, Sjöstrand L (1981) Monoamine metabolites in CSF and suicidal behavior. Arch Gen Psychiatry 38: 631–636CrossRefGoogle Scholar
  18. van Praag HM (1982) Depression, suicide and the metabolism of serotonin in the brain. J Affective Disord 4: 275–290CrossRefGoogle Scholar
  19. Vestergaard P, Sørensen T, Hoppe E, Rafaelsen OJ, Yates CM, Nicolaou N (1978) Biogenic amine metabolites in cerebrospinal fluid of patients with affective disorders. Acta Psychiatr Scand 58: 88–95PubMedCrossRefGoogle Scholar
  20. Ziegler MG, Wood JH, Lake CR, Kopin IJ (1977) Norepinephrine and 3-methoxy-4-hydroxy-phenyl glycol gradients in human cerebrospinal fluid. Am J Psychiatry 134: 565–568PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • O. J. Rafaelsen
    • 1
  • A. Gjerris
    • 1
  1. 1.Department of PsychiatryRigshospitaletCopenhagenDenmark

Personalised recommendations