Placebo-controlled trial of lithium augmentation of fluoxetine and lofepramine.
BACKGROUND
This study was designed to establish whether (as suggested in a number of open and relatively small controlled trials) lithium augmentation is more effective than continued antidepressant alone, where response to a standard course of antidepressant treatment has been absent or partial.


METHODS
Lithium or placebo was added on a double-blind basis for six weeks to the drug regime of 62 patients with major depressive illness (in both hospital and primary care settings) who had failed to respond to a controlled trial of fluoxetine or lofepramine. Response was defined as a final Hamilton Depression Rating Scale (HDRS) score of < 10.


RESULTS
Response was seen more frequently in patients taking lithium (15/29) than in those remaining on antidepressant alone (8/32; P < 0.05). Rapid response to lithium augmentation (LA) was not consistently observed in this cohort. Mean HDRS scores after six weeks were significantly lower (P < 0.01) in the lithium group after excluding those who had not achieved significant exposure to lithium (arbitrarily defined as two or more lithium levels > or = 0.4 mmol/l). No differences in the efficacy of LA were apparent between fluoxetine and lofepramine.


CONCLUSIONS
Our results confirm that LA is a useful strategy in the treatment of antidepressant-resistant depression. Partial response was, however, frequently observed with continued antidepressant treatment alone, and the superiority of LA appears to depend on achieving adequate serum lithium levels.
Katona
C L
CL
Department of Psychiatry, University College London Medical School.
Abou-Saleh
M T
MT
Harrison
D A
DA
Nairac
B A
BA
Edwards
D R
DR
Lock
T
T
Burns
R A
RA
Robertson
M M
MM
D000293:Adolescent; D000328:Adult; D000368:Aged; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D016651:Lithium Carbonate / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008127:Lofepramine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged
D005473:Fluoxetine; D016651:Lithium Carbonate; D008127:Lofepramine