Possible serotonergic mechanisms underlying the antidepressant and anti-obsessive–compulsive disorder responses

Considerable evidence is now available to support the pivotal role of the serotonin (5-HT) system is exerting the antidepressant response in humans. Different type of antidepressant treatments enhance 5-HT neurotransmission via different pre- or postsynaptic mechanisms. The time course for the occurrence of these adaptive changes in the brain of laboratory animals is consistent with the delayed onset of the antidepressant response in humans. The drugs effective in obsessive-compulsive disorder (OCD) also enhance 5-HT neurotransmission in brain regions involved in mediating OCD symptoms but with a more prolonged delay, consistently with the larger time necessary to obtain therapeutic effect in OCD than in depression. The elucidation of these mechanisms of action lead to the development of new pharmacologic strategies to potentiate the therapeutic effect of the drugs currently available and the identification of novel targets to accelerate and further improve treatment response in depression and OCD.

[1]  P. Blier,et al.  In Vivo Electrophysiological Characterization of 5-HT Receptors in the Guinea Pig Head of Caudate Nucleus and Orbitofrontal Cortex , 1997, Neuropharmacology.

[2]  C. de Montigny,et al.  Effect of Pindolol on the Function of Pre- and Postsynaptic 5-HT1A Receptors: In Vivo Microdialysis and Electrophysiological Studies in the Rat Brain , 1996, Neuropsychopharmacology.

[3]  C. McDougle,et al.  Limited therapeutic effect of addition of buspirone in fluvoxamine-refractory obsessive-compulsive disorder. , 1993, The American journal of psychiatry.

[4]  W. Goodman,et al.  Efficacy of fluvoxamine in obsessive-compulsive disorder. A double-blind comparison with placebo. , 1989, Archives of general psychiatry.

[5]  D. Murphy,et al.  A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder. , 1992, Journal of clinical psychopharmacology.

[6]  L. Wilkinson,et al.  Extracellular serotonin levels change with behavioral state but not with pyrogen-induced hyperthermia , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  C. Montigny Electroconvulsive shock treatments enhance responsiveness of forebrain neurons to serotonin. , 1984 .

[8]  C. de Montigny,et al.  Modification of 5‐HT neuron properties by sustained administration of the 5‐HT1A agonist gepirone: Electrophysiological studies in the rat brain , 1987, Synapse.

[9]  J. Sweeney,et al.  A controlled study of the antidepressant efficacy and side effects of (-)-deprenyl. A selective monoamine oxidase inhibitor. , 1989, Archives of general psychiatry.

[10]  M Briley,et al.  Serotonin autoreceptor subsensitivity and antidepressant activity. , 1990, European journal of pharmacology.

[11]  C. Wilcox,et al.  A double-blind trial of low- and high-dose ranges of gepirone-ER compared with placebo in the treatment of depressed outpatients. , 1996, Psychopharmacology bulletin.

[12]  P. Delgado,et al.  Hallucinogen-induced relief of obsessions and compulsions. , 1997, The American journal of psychiatry.

[13]  M Diksic,et al.  Differences between males and females in rates of serotonin synthesis in human brain. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[14]  G. Aghajanian,et al.  Serotonin function and the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. , 1990, Archives of general psychiatry.

[15]  A. Anand,et al.  Effect of pindolol in hastening response to fluoxetine in the treatment of major depression: a double-blind, placebo-controlled trial. , 1997, The American journal of psychiatry.

[16]  C. McDougle,et al.  Addition of desipramine to serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder. , 1997, The American journal of psychiatry.

[17]  P. Blier,et al.  Modulation of 5‐HT release in the guinea‐pig brain following long‐term administration of antidepressant drugs , 1994, British journal of pharmacology.

[18]  M. Jenike Obsessive compulsive disorder. , 1983, Comprehensive psychiatry.

[19]  M. Tome,et al.  Paroxetine and pindolol: a randomized trial of serotonergic autoreceptor blockade in the reduction of antidepressant latency , 1997, International clinical psychopharmacology.

[20]  C. S. Mellor,et al.  Female hypersexuality treated with cyproterone acetate. , 1988, The American journal of psychiatry.

[21]  M. Jenike Obsessive-compulsive disorder: efficacy of specific treatments as assessed by controlled trials. , 1993, Psychopharmacology bulletin.

[22]  K. Hanes Serotonin, psilocybin, and body dysmorphic disorder: a case report. , 1996, Journal of clinical psychopharmacology.

[23]  M. Liebowitz,et al.  Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder. , 1995, Archives of general psychiatry.

[24]  P. Blier,et al.  Alteration of Serotonin Release in the Guinea Pig Orbito-Frontal Cortex by Selective Serotonin Reuptake Inhibitors , 1995, Neuropsychopharmacology.

[25]  C. McDougle,et al.  The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. , 1993, Journal of clinical psychopharmacology.

[26]  C. Montigny,et al.  5-HT1D Receptors Regulate 5-HT Release in the Rat Raphe Nuclei , 1995, Neuropsychopharmacology.

[27]  E. Smeraldi,et al.  5HT‐2 receptor and fluvoxamine effect in obsessive‐compulsive disorder , 1992 .

[28]  C. Montigny,et al.  Serotoninergic but not noradrenergic neurons in rat central nervous system adapt to long-term treatment with monoamine oxidase inhibitors , 1985, Neuroscience.

[29]  T. Insel,et al.  Toward a neuroanatomy of obsessive-compulsive disorder. , 1992, Archives of general psychiatry.

[30]  J. Rapoport,et al.  A double-blind desipramine substitution during long-term clomipramine treatment in children and adolescents with obsessive-compulsive disorder. , 1991, Archives of general psychiatry.

[31]  V. Pérez,et al.  Randomised, double-blind, placebo-controlled trial of pindolol in combination with fluoxetine antidepressant treatment , 1997, The Lancet.

[32]  C. de Montigny,et al.  Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: I. Effect of spiperone. , 1993, The Journal of pharmacology and experimental therapeutics.

[33]  G. W. Price,et al.  The role of 5-HT(1B/1D) receptors in the modulation of 5-hydroxytryptamine levels in the frontal cortex of the conscious guinea pig. , 1997, European journal of pharmacology.

[34]  V. Pérez,et al.  Pindolol induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors. , 1994, Archives of general psychiatry.

[35]  A. Mørk,et al.  Altered protein phosphorylation in the rat brain following chronic lithium and carbamazepine treatments , 1997, European Neuropsychopharmacology.

[36]  C. Montigny,et al.  Presynaptic and postsynaptic modifications of the serotonin system by long-term administration of antidepressant treatments. An in vivo electrophysiologic study in the rat. , 1991, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[37]  C. Montigny Lithium addition in treatment-resistant depression. , 1994 .

[38]  R. Mccall,et al.  Chronic antidepressant treatment enhances alpha-adrenergic and serotonergic responses in the facial nucleus. , 1980, Life sciences.

[39]  E. Smeraldi,et al.  How long should pindolol be associated with paroxetine to improve the antidepressant response? , 1997, Journal of clinical psychopharmacology.

[40]  R. Mccall,et al.  Serotonergic facilitation of facial motoneuron excitation , 1979, Brain Research.

[41]  L. Fabre,et al.  Clinical Effects of the 5‐HT1A Partial Agonists in Depression: A Composite Analysis of Buspirone in the Treatment of Depression , 1990, Journal of clinical psychopharmacology.

[42]  R. Salomon,et al.  Clinical and biochemical effects of catecholamine depletion on antidepressant-induced remission of depression. , 1996, Archives of general psychiatry.

[43]  C. de Montigny,et al.  Short‐term lithium treatment enhances responsiveness of postsynaptic 5‐HT1A receptors without altering 5‐HT autoreceptor sensitivity: An electrophysiological study in the rat brain , 1987, Synapse.

[44]  D. Middlemiss,et al.  Effects of selective h5-HT1B (SB-216641) and h5-HT1D (BRL-15572) receptor ligands on guinea-pig and human 5-HT auto- and heteroreceptors , 1997, Naunyn-Schmiedeberg's Archives of Pharmacology.

[45]  G. Aghajanian,et al.  Tricyclic antidepressants: long-term treatment increases responsivity of rat forebrain neurons to serotonin. , 1978, Science.

[46]  J. Hyttel,et al.  Citalopram — Pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity , 1982, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[47]  A. Rush,et al.  A multicenter investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder. , 1994, Archives of general psychiatry.

[48]  D. Charney,et al.  Serotonin function and mechanism of action of antidepressant treatment. Effects of amitriptyline and desipramine. , 1984, Archives of general psychiatry.

[49]  C. Montigny,et al.  Current advances and trends in the treatment of depression. , 1994, Trends in pharmacological sciences.

[50]  C. Montigny,et al.  Desensitization of the neuronal 5-HT carrier following its long-term blockade , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[51]  P. Blier,et al.  Effect of long-term administration of antidepressant treatments on serotonin release in brain regions involved in obsessive–compulsive disorder , 1999, Biological Psychiatry.

[52]  T. Insel,et al.  Clomipramine in obsessive-compulsive disorder. Further evidence for a serotonergic mechanism of action. , 1989, Archives of general psychiatry.

[53]  J. Deveaugh-Geiss,et al.  Clomipramine in obsessive-compulsive disorder , 1990, Biological Psychiatry.

[54]  C. Montigny,et al.  Selective Activation of Postsynaptic 5-HT1A Receptors Induces Rapid Antidepressant Response , 1997, Neuropsychopharmacology.

[55]  P. Blier,et al.  Effectiveness of pindolol with selected antidepressant drugs in the treatment of major depression. , 1995, Journal of clinical psychopharmacology.