Biochemical mechanisms of action of antidepressants
Authors:
Zdeněk Fišar; Jana Hroudová; Jiří Raboch
Authors‘ workplace:
Univerzita Karlova v Praze, 1. lékařská fakulta, Psychiatrická klinika VFN
Published in:
Čas. Lék. čes. 2011; 150: 531-540
Category:
Review Article
Overview
The findings regarding direct, early and long-term biochemical effects of antidepressants are summarized in this review. Mechanisms of action of other drugs showing antidepressant activity are mentioned as well as alternative possibilities of adjuvants. Psychotropic drugs used in the therapy of mood disorders show neurotrophic or neuroprotective effects after long-term treatment. Thus, next to adenylate cyclase, guanylate cyclase, phosphoinositide and calcium systems, attention has been paid to tyrosine kinase pathway and Wnt pathway. Knowledge about biological markers of mood disorders and predictors of efficiency of pharmacotherapy is included also in relation to importance, potentialities and perspectives in the development of new antidepressants.
Key words:
antidepressant, neurotransmitter, depression, receptor, transporter, neuroplasticity.
Sources
1. Simon GE, et al. Is the lifetime risk of depression actually increasing? J Clin Epidemiol 1995; 48(9): 1109–1118.
2. Kessler RC, et al. Lifetime prevalence and age-of-onset distributions of mental disorders in the World Health Organization’s World Mental Health Survey Initiative. World Psychiatry 2007; 6: 168–176.
3. Murray CJL, Lopez AD. Alternative visions of the future: projecting mortality and disability, 1990–2020. In: Murray CJL, et al. The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Cambridge, Mass: Harvard School of Public Health on behalf of the WHO and the World Bank 1996; 325–395.
4. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997; 349(9064): 1498–1504.
5. Mathers CD, Lopez AD, Murray ChJL. The Burden of Disease and Mortality by Condition: Data, Methods, and Results for 2001. In: Lopez AD, et al. Global Burden of Disease and Risk Factors. Disease Control Priorities Project. Washington (DC): World Bank 2006; 45–93.
6. WHO. Depression. World Health Organization (WHO), Geneva 2011, http://www.who.int/mental_health/management/depre ssion/definition/en/
7. McEwen BS, et al. The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation. Mol Psychiatry 2010; 15(3): 237–249.
8. Fishback JA, et al. Sigma receptors: potential targets for a new class of antidepressant drug. Pharmacol Ther 2010; 127(3): 271–282.
9. Popoli M. Agomelatine: innovative pharmacological approach in depression. CNS Drugs 2009; 23(Suppl 2): 27–34.
10. Švestka J, et al. Agomelatin – antidepresivum s novým mechanizmem působení. Psychiatrie 2010; 14(2): 98–108.
11. Millan MJ, et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J Pharmacol Exp Ther 2003; 306(3): 954–964.
12. Bourin M, et al. Antidepressant-like activity of S 20098 (agomelatine) in the forced swimming test in rodents: involvement of melatonin and serotonin receptors. J Psychiatry Neurosci 2004; 29(2): 126–133.
13. Anttila SA, et al. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev 2001; 7(3): 249–264.
14. Hamik A, et al. Analysis of tandospirone (SM-3997) interactions with neurotransmitter receptor binding sites. Biol Psychiatry 1990; 28(2): 99–109.
15. Bartoszyk GD, et al. EMD 68843, a serotonin reuptake inhibitor with selective presynaptic 5-HT1A receptor agonistic properties. Eur J Pharmacol 1997; 322(2–3): 147–153.
16. Tatsumi M, et al. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol 1997; 340(2–3): 249–258.
17. Fisar Z, et al. Inhibition of monoamine oxidase activity by antidepressants and mood stabilizers. Neuro Endocrinol Lett 2010; 31(5): 645–656.
18. Richelson E. Pharmacology of antidepressants. Mayo Clin Proc 2001; 76(5): 511–527.
19. Fišar Z, et al. Serotonergní účinky antidepresiv. Česká a slovenská psychiatrie 2011; 107: (2): 115–120.
20. Richelson E. Interactions of antidepressants with neurotransmitter transporters and receptors and their clinical relevance. J Clin Psychiatry 2003; 64(Suppl 13): 5–12.
21. Nikolaus S, et al. In vivo imaging of synaptic function in the central nervous system: II. Mental and affective disorders. Behav Brain Res 2009; 204(1): 32–66.
22. Duman RS. Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression. Dialogues Clin Neurosci 2009; 11(3): 239–255.
23. Maes M, et al. The inflammatory & neurodegenerative (I & ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis 2009; 24(1): 27–53.
24. Nikisch G. Involvement and role of antidepressant drugs of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor function. Neuro Endocrinol Lett 2009; 30(1): 11–16.
25. Bunney JN, et al. Circadian abnormalities, molecular clock genes and chronobiological treatments in depression. Br Med Bull 2008; 86: 23–32.
26. Schulz P, et al. Neurobiology of circadian systems. CNS Drugs 2009; 23(Suppl 2): 3–13.
27. Mendlewicz J. Disruption of the circadian timing systems: molecular mechanisms in mood disorders. CNS Drugs 2009; 23(Suppl 2): 15–26.
28. Savitz J, et al. 5-HT1A receptor function in major depressive disorder. Prog Neurobiol 2009; 88(1): 17–31.
29. Blier P, et al. Current advances and trends in the treatment of depression. Trends Pharmacol Sci 1994; 15(7): 220–226.
30. Blier P, et al. Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive-compulsive disorder responses. Biol Psychiatry 1998; 44(5): 313–323.
31. Blier P, et al. Is there a role for 5-HT1A agonists in the treatment of depression? Biol Psychiatry 2003; 53(3): 193–203.
32. Meyer JH. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci 2007; 32(2): 86–102.
33. Stahl SM. Mechanism of action of trazodone: a multifunctional drug. CNS Spectr 2009; 14(10): 536–546.
34. Blier P. The pharmacology of putative early-onset antidepressant strategies. Eur Neuropsychopharmacol 2003; 13(2): 57–66.
35. Smith DF, et al. Molecular tools for assessing human depression by positron emission tomography. Eur Neuropsychopharmacol 2009; 19(9): 611–628.
36. Sargent PA, et al. Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry 2000; 57(2): 174–180.
37. Bhagwagar Z, et al. Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635. Mol Psychiatry 2004; 9(4): 386–392.
38. Drevets WC, et al. Serotonin-1A receptor imaging in recurrent depression: replication and literature review. Nucl Med Biol 2007; 34(7): 865–877.
39. Sargent PA, et al. 5-HT1A receptor binding in euthymic bipolar patients using positron emission tomography with [carbonyl-11C]WAY-100635. J Affect Disord 2010; 123(1-3): 77–80.
40. Parsey RV, et al. Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study. Biol Psychiatry 2006; 59(2): 106–113.
41. Moses-Kolko EL, et al. Measurement of 5-HT1A receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [11C]WAY-100635. Synapse 2007; 61(7): 523–530.
42. Praschak-Rieder N, et al. Tryptophan depletion and serotonin loss in selective serotonin reuptake inhibitor-treated depression: an [18F] MPPF positron emission tomography study. Biol Psychiatry 2004; 56(8): 587–591.
43. Meyer JH, et al. Brain monoamine oxidase A binding in major depressive disorder: relationship to selective serotonin reuptake inhibitor treatment, recovery, and recurrence. Arch Gen Psychiatry 2009; 66(12): 1304–1312.
44. Selvaraj S, et al. Diminished brain 5-HT transporter binding in major depression: a positron emission tomography study with [11C]DASB. Psychopharmacology (Berl) 2011; 213(2–3): 555–562.
45. Meyer JH, et al. Elevated monoamine oxidase a levels in the brain: an explanation for the monoamine imbalance of major depression. Arch Gen Psychiatry 2006; 63(11): 1209–1216.
46. Praschak-Rieder N, et al. Seasonal variation in human brain serotonin transporter binding. Arch Gen Psychiatry 2008; 65(9): 1072–1078.
47. Yang S, et al. Sigma receptor agonists provide neuroprotection in vitro by preserving bcl-2. Anesth Analg 2007; 104(5): 1179–1184.
48. Fišar Z, et al. Intracellular signalling pathways and mood disorders. Folia Biol (Praha) 2010; 56(4): 135–148.
49. Heiberg IL, et al. Reduction of cGMP and nitric oxide has antidepressant-like effects in the forced swimming test in rats. Behav Brain Res 2002; 134(1–2): 479–484.
50. Paul IA, et al. Glutamate and depression: clinical and preclinical studies. Ann NY Acad Sci 2003; 1003: 250–272.
51. Gould TD, et al. Targeting signal transduction pathways in the treatment of mood disorders: recent insights into the relevance of the Wnt pathway. CNS Neurol Disord Drug Targets 2007; 6(3): 193–204.
52. Chen G, et al. The extracellular signal-regulated kinase pathway: an emerging promising target for mood stabilizers. Curr Opin Psychiatry 2006; 19(3): 313–323.
53. Rapoport SI, et al. Bipolar disorder and mechanisms of action of mood stabilizers. Brain Res Rev 2009; 61(2): 185–209.
54. Machado-Vieira R, et al. Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol Ther 2009; 123(2): 143–150.
55. Madaan V, et al. Neuropeptides: relevance in treatment of depression and anxiety disorders. Drug News Perspect 2009; 22(6): 319–324.
56. Flores BH, et al. Clinical and biological effects of mifepristone treatment for psychotic depression. Neuropsychopharmacology 2006; 31(3): 628–636.
57. Kehne JH. The CRF1 receptor, a novel target for the treatment of depression, anxiety, and stress-related disorders. CNS Neurol Disord Drug Targets 2007; 6(3): 163–182.
58. Linde K. St. John’s wort – an overview. Forsch Komplementmed 2009; 16(3): 146–155.
59. Ernst E, et al. Adverse effects profile of the herbal antidepressant St. John’s wort (Hypericum perforatum L.). Eur J Clin Pharmacol 1998; 54(8): 589–594.
60. Akhondzadeh Basti A, et al. Comparison of petal of Crocus sativus L. and fluoxetine in the treatment of depressed outpatients: a pilot double-blind randomized trial. Prog Neuropsychopharmacol Biol Psychiatry 2007; 31(2): 439–442.
61. Akhondzadeh S, et al. A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer’s disease. Psychopharmacology (Berl) 2010; 207(4): 637–643.
62. Kulkarni SK, et al. Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders. Phytother Res 2010; 24(3): 317–324.
63. Seol GH, et al. Antidepressant-like effect of Salvia sclarea is explained by modulation of dopamine activities in rats. J Ethnopharmacol 2010; 130(1): 187–190.
64. Setzer WN. Essential oils and anxiolytic aromatherapy. Nat Prod Commun 2009; 4(9): 1305–1316.
65. Delgado PL, et al. Tryptophan-depletion challenge in depressed patients treated with desipramine or fluoxetine: implications for the role of serotonin in the mechanism of antidepressant action. Biol Psychiatry 1999; 46(2): 212–220.
66. Sontrop J, et al. ω-3 polyunsaturated fatty acids and depression: a review of the evidence and a methodological critique. Prev Med 2006; 42(1): 4–13.
67. Nemets H, et al. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry 2006; 163(6): 1098–1100.
68. Freeman MP. Omega-3 fatty acids in major depressive disorder. J Clin Psychiatry 2009; 70(Suppl 5): 7–11.
69. Appleton KM, et al. Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr 2010; 91(3): 757–770.
70. Hibbeln JR, et al. Plasma total cholesterol concentrations do not predict cerebrospinal fluid neurotransmitter metabolites: implications for the biophysical role of highly unsaturated fatty acids. Am J Clin Nutr 2000; 71(1 Suppl): 331S–338S.
71. Horrobin DF, et al. Depression and bipolar disorder: relationships to impaired fatty acid and phospholipid metabolism and to diabetes, cardiovascular disease, immunological abnormalities, cancer, ageing and osteoporosis. Possible candidate genes. Prostaglandins Leukot Essent Fatty Acids 1999; 60(4): 217–234.
72. Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006; 97(6): 1634–1658.
73. Cumurcu BE, et al. Total antioxidant capacity and total oxidant status in patients with major depression: impact of antidepressant treatment. Psychiatry Clin Neurosci 2009; 63(5): 639–645.
74. Gałecki P, et al. Lipid peroxidation and antioxidant protection in patients during acute depressive episodes and in remission after fluoxetine treatment. Pharmacol Rep 2009; 61(3): 436–447.
75. BolaĖos JP, et al. Mitochondria and reactive oxygen and nitrogen species in neurological disorders and stroke: Therapeutic implications. Adv Drug Deliv Rev 2009; 61(14): 1299–1315.
76. Valko M, et al. Metals, toxicity and oxidative stress. Curr Med Chem 2005; 12(10): 1161–1208.
77. Gutteridge JM, et al. Antioxidants: Molecules, medicines, and myths. Biochem Biophys Res Commun 2010; 393(4): 561–564.
78. Raboch J. Kognitivní funkce, stárnutí a stravovací návyky. Čes a slov psychiat 2010; 106(2): 81–86.
79. Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev 2008; 13(3): 216–226.
80. Tanti A, et al. Open questions in current models of antidepressant action. Br J Pharmacol 2010; 159(6): 1187–1200.
81. Diazgranados N, et al. A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry 2010; 67(8): 793–802.
82. Kennaway DJ. Clock genes at the heart of depression. J Psychopharmacol 2010; 24(8): 5–14.
83. Halene TB, et al. PDE inhibitors in psychiatry – future options for dementia, depression and schizophrenia? Drug Discov Today 2007; 12(19-20): 870–878.
84. Cashman JR, et al. Dual inhibitors of phosphodiesterase-4 and serotonin reuptake. J Med Chem 2009; 52(6): 1530–1539.
85. Stahl SM. Multifunctional drugs: a novel concept for psychopharmacology. CNS Spectr 2009; 14(2): 71–73.
86. Fišar Z, et al. Depression, antidepressants, and peripheral blood components. Neuro Endocrinol Lett 2008; 29(1): 17–28.
Labels
Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental HygienistArticle was published in
Journal of Czech Physicians
Most read in this issue
- Biochemical mechanisms of action of antidepressants
- Hypophosphatasia – biochemical and clinical manifestations, molecular enetic principles
- Conflict of Interest: The World Medical Association Statement
- Post-traumatic panniculitis (decubitus ulcer?) of the breast – a clinical case