The effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone as augmentation agents in treatment-resistant major depressive disorder.
BACKGROUND
Many questions remain regarding the use of atypical neuroleptics as antidepressant augmentation agents. To date, there have been no reports in the literature regarding the effectiveness of these drugs when trials of one or more of them have failed previously as antidepressant augmentation.


METHODS
This retrospective chart review was conducted to determine the effectiveness of olanzapine, risperidone, quetiapine, and ziprasidone when given in a fee-for-service setting as anti-depressant augmentation agents to patients with treatment-resistant, nonpsychotic major depressive disorder (DSM-IV). Prospective (Global Assessment of Functioning [GAF]) along with retrospective (Clinical Global Impressions-Improvement [CGI-I] and -Severity of Illness scales) ratings were completed for each patient. Analyses were conducted in an attempt to identify factors that appeared to correlate with response, including order of administration and Thase-Rush staging of treatment resistance.


RESULTS
In this study of 76 medication trials in 49 patients, the overall response rate based on the CGI-I ratings was 65% (32/49). Individual rates of response were 57% (21/37) for olanzapine, 50% (7/14) for risperidone, 33% (6/18) for quetiapine, and 10% (1/10) for ziprasidone. None of the differences between neuroleptics in rates of response were significant. The difference between baseline and final GAF scores was statistically significant only in the olanzapine (p <.001) and risperidone (p =.047) groups. Rates of discontinuation did not vary significantly between agents, though trends were present. Crossover trials from one atypical neuroleptic to another in the event of nonresponse appeared to be effective.


CONCLUSIONS
Although limited by its design, this study suggests atypical neuroleptic augmentation of antidepressants may be a viable option in treatment-resistant major depressive disorder.
Department of Psychiatry, Louisiana State University Health Sciences Center, New Orleans 70112, USA. jbarbe@lsuhsc.edu
James G
JG
Barbee
Erich J
EJ
Conrad
Nowal J
NJ
Jamhour
D000928:Antidepressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008499:Medical Records; D000077152:Olanzapine; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D012107:Research Design; D012189:Retrospective Studies; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; C092292:ziprasidone; D018967:Risperidone; D000077152:Olanzapine