An open pilot study of nefazodone in depression with anger attacks: relationship between clinical response and receptor binding

• Published in: Psychiatry research Vol. 116; no. 3; pp. 151 - 161
• Main Authors: Mischoulon, David, Dougherty, Darin D, Bottonari, Kathryn A, Gresham, Robert L, Sonawalla, Shamsah B, Fischman, Alan J, Fava, Maurizio
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 30.12.2002; Elsevier
• Subjects: Adult; Anger; Antidepressant; Antidepressive Agents, Second-Generation - pharmacokinetics; Antidepressive Agents, Second-Generation - therapeutic use; Binding Sites; Biological and medical sciences; Brain - metabolism; Depression - diagnosis; Depression - drug therapy; Dopamine; Female; Humans; Male; Medical sciences; Neuroimaging; Neuropharmacology; Pharmacology. Drug treatments; Pilot Projects; Piperazines; Positron emission tomography (PET); Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptor; Receptors, Dopamine - metabolism; Receptors, Serotonin - metabolism; Serotonin; Severity of Illness Index; Surveys and Questionnaires; Thalamus - metabolism; Tomography, Emission-Computed; Triazoles - pharmacokinetics; Triazoles - therapeutic use; Neuroimaging; Antidepressant; Positron emission tomography (PET); Dopamine; Serotonin; Receptor; Radionuclide study; Affect affectivity; Psychotropic; Nefazodone; Central nervous system; Antidepressant agent; Antagonist; Mechanism of action; Mood disorder; Anger; Human; Serotonin antagonist; Treatment efficiency; D1 Dopamine receptor; Depression; 5-HT2 Serotonine receptor; Symptomatology; Chemotherapy; Biological fixation; Treatment; Follow up study; Predictive factor; Subtype; Comparative study; Aggressiveness; Brain (vertebrata); Positron; Emission tomography
• ISSN: 0925-4927; 0165-1781; 1872-7506
• DOI: 10.1016/S0925-4927(02)00082-3

Nefazodone has been widely used as an antidepressant, but it has not been tested for depression with anger attacks. In an open study, we administered nefazodone (maximum 600 mg/day) for 12 weeks to 16 outpatients who had major depression with anger attacks. Assessment instruments comprised the Structured Clinical Interview for DSM-IV (SCID), Anger Attacks Questionnaire (AAQ), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinician Global Impression Scale (CGI), Symptom Questionnaire (SQ), Modified Overt Aggression Scale (MOAS), and MOAS-Self-Rated. Three subjects underwent positron emission tomography (PET) with [ 18F]-setoperone for 5-HT2 binding potential (BP) and [ 11C]-SCH-23,390 for D1 BP, both at baseline and after 6 weeks of treatment. Eight subjects underwent PET with [ 18F]-setoperone and with [ 11C]-SCH-23,390 at baseline only. In an examination of whether D1 and 5HT2 (data available in six subjects) receptor BP predicted treatment response, we found significant decreases in the HAM-D-17, CGI-S, weighted MOAS, MOAS verbal scale, OAS Self-Rated verbal, SQ Depression and Anger/Hostility scales after nefazodone; 50% responded to nefazodone (defined as ≥50% decrease in HAM-D-17 score), and 44% reported disappearance of anger attacks. A statistically significant percentage decrease in 5HT2 BP was observed for the right mesial frontal and left parietal regions after 6 weeks of treatment. No significant change was observed in D1 BP in any region. Although CGI-I scores correlated significantly with D1 BP in the left thalamic region, the correlation was not significant after Bonferroni correction. The effectiveness of nefazodone for depression with anger attacks may be related to widespread changes in 5HT2 receptor BP.