Modulation of brain and serum glutamatergic concentrations following a switch from conventional neuroleptics to olanzapine

• Published in: Biological psychiatry (1969) Vol. 51; no. 6; pp. 493 - 497
• Main Authors: GOFF, Donald C, HENNEN, John, IN KYOON LYOO, GUOCHUAN TSAI, WALD, Lawrence L, EVINS, A. Eden, YURGELUN-TODD, Deborah A, RENSHAW, Perry F
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Science 15.03.2002
• Subjects: Adult; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Benzodiazepines; Biological and medical sciences; Chronic Disease; Creatine - metabolism; Female; Glutamic Acid - metabolism; Gyrus Cinguli - drug effects; Gyrus Cinguli - metabolism; Humans; Magnetic Resonance Spectroscopy; Male; Medical sciences; Middle Aged; Neuropharmacology; Olanzapine; Pharmacology. Drug treatments; Pirenzepine - administration & dosage; Pirenzepine - adverse effects; Pirenzepine - analogs & derivatives; Psychiatric Status Rating Scales; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Reference Values; Schizophrenia - blood; Schizophrenia - diagnosis; Schizophrenia - drug therapy; Treatment Outcome; Olanzapine; Neuroleptic; Psychotropic; Dopamine receptor; Dopamine antagonist; Serotonin antagonist; Central nervous system; NMR spectrometry; Clozapine; Concentration; Serotonine receptor; Glutamate; Drug conversion; Cingulate cortex; Negative symptom; Modulation; Serum; Antagonist; Brain (vertebrata)
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/s0006-3223(01)01321-x

Recent evidence suggests that effects upon glutamatergic transmission may contribute to the therapeutic action of certain atypical antipsychotic agents. Glutamate concentrations were measured in serum and were estimated (Glx/Cr) in cingulate cortex by proton magnetic resonance spectroscopy (MRS) in schizophrenia patients while they were being treated with conventional neuroleptics and then 8 weeks after switching to olanzapine. Serum glutamate concentrations were obtained from 11 subjects, and MRS estimates of Glx/Cr were available from 10 subjects at both time points. Serum glutamate concentrations significantly increased after the switch from conventional agents to olanzapine; brain glutamate (Glx/Cr) did not change significantly; however, brain glutamate (Glx/Cr) concentrations increased significantly in patients who exhibited an improvement in negative symptoms with olanzapine compared with patients with no change or worsening of negative symptoms. Comparisons performed following the switch from conventional agents to olanzapine are consistent with previous studies of clozapine and provide additional preliminary evidence supporting the hypothesis that effects on excitatory amino acid activity may contribute to olanzapine's efficacy for treating negative symptoms.