Nortriptyline for treatment-resistant depression.
BACKGROUND
Up to 30% of patients with major depression fail to respond to an antidepressant trial, with most taking a selective serotonin reuptake inhibitor (SSRI) as initial treatment. While the tricyclic antidepressants might be effective for SSRI nonresponders, they have been relegated to third- and fourth-line treatment. This study assesses the efficacy of nortriptyline for patients with treatment-resistant major depression.


METHODS
92 patients with treatment-resistant DSM-III-R major depression, with resistance defined by at least 1, but no more than 5, well-documented adequate trials of antidepressants during the current episode, were treated openly with nortriptyline for 6 weeks. Patients were titrated up to full target doses of nortriptyline within 1 week, with target blood levels of 100 ng/mL. Response was defined as a 50% or greater decrease of baseline 17-item Hamilton Rating Scale for Depression score. We performed an intent-to-treat analysis with the last observation carried forward.


RESULTS
Approximately 40% of patients were responders (N = 39) and 12% were remitters (N = 11) after 6 weeks of nortriptyline. Over a third of patients were unable to complete the trial.


CONCLUSIONS
Nortriptyline was effective for over a third of patients with treatment-resistant depression, and nortriptyline should be considered as potential treatment if patients fail to respond to other antidepressants.
Nierenberg
Andrew A
AA
Depression Clinical and Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, USA. anierenberg@partners.org
Papakostas
George I
GI
Petersen
Timothy
T
Kelly
Karen E
KE
Iacoviello
Brian M
BM
Worthington
John J
JJ
Tedlow
Joyce
J
Alpert
Jonathan E
JE
Fava
Maurizio
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009661:Nortriptyline / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012189:Retrospective Studies; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D009661:Nortriptyline; D017367:Selective Serotonin Reuptake Inhibitors