Lithium's Emerging Role in The Treatment of Refractory Major Depressive Episodes: Augmentation of Antidepressants
Lithium's Emerging Role in The Treatment of Refractory Major Depressive Episodes: Augmentation of Antidepressants
Lithium's Emerging Role in The Treatment of Refractory Major Depressive Episodes: Augmentation of Antidepressants
DOI: 10.1159/000314308
Study Subjects Antidepressant Lithium dosage (serum level) and Fixed effects: Response criteria;
duration odds ratioa (95% CI) response rates
Heninger et al. 14 UP, 1 BP various TCAs lithium carbonate 900–1,200 mg/day 23.57 (1.00–556.08) decrease of 2 or more
[47], 1983 12 F, 3 M and tetracyclics (0.5–1.1 mEq/l) points on SCRS;
mean age 50 years 12 days lithium: 62.5%
placebo: 0%
Kantor et al. 7 UP various TCAs lithium carbonate 900 mg/day 3.00 (0.09–102.05) ≥40% decrease in
[10], 1986 sex nr 48 h HAM-D score;
mean age nr lithium: 25%
placebo: 0%
Zusky et al. 16 UP various TCAs lithium carbonate 300 mg/day first 1.80 (0.21–15.41) final HAM-D score ≤7;
[11], 1988 13 F, 3 M and MAOIs week, 900 mg/day second week lithium: 38%
mean age 45 years 14 days placebo: 25%
Schöpf et al. 18 UP, 9 BP various lithium carbonate 600–800 mg/day 27.00 (1.35–541.57) ≥50% decrease in HAM-D;
[30], 1989 19 F, 8 M antidepressants (0.6–0.8 mEq/l) lithium: 50%
mean age 54 years 7 days placebo: 0%
Browne et al. 14 UP, 3 BP various TCAs lithium carbonate 900 mg/day 3.00 (0.35–25.87) ≥50% decrease in HAM-D;
[12], 1990 10 F, 7 M and tetracyclics 48 h lithium: 43%
mean age 42 years placebo: 20%
Stein and 34 UP various TCAs lithium carbonate 250 mg/day or 0.50 (0.08–3.19) ≥50% decrease in HAM-D;
Bernadt 27 F, 7 M 750 mg/day lithium (250 mg): 18%
[13], 1993 mean age 47 years 21 days lithium (750 mg): 44%
placebo: 22%
Joffe et al. 33 UP various TCAs lithium carbonate 900 mg/day 4.88 (1.01–23.57) ≥50% decrease in HAM-D;
[21], 1993 18 F, 15 M (>0.55 mEq/l) lithium: 52%
mean age 37 years 14 days placebo: 18.7%
Katona et al. 61, polarity nr SSRI and TCA lithium 800 mg/day (0.6–1 mmol/l) 3.21 (1.09–9.48) ≥50% decrease in HAM-D;
[48], 1995 35 F, 26 M 42 days lithium: 53%
mean age 40 years placebo: 25%
Baumann et al. 23 UP, 1 BP SSRI lithium carbonate 800 mg/day 9.00 (1.27–63.89) ≥50% decrease in HAM-D;
[49], 1996 17 F, 7 M (citalopram) (0.5–0.8 mmol/l) lithium: 58%
mean age 41 years 7 days placebo: 14%
Nierenberg et al. 35 UP TCA lithium carbonate 900 mg/day 0.58 (0.08–4.01) ≥50% decrease in HAM-D;
[14], 2003 16 F, 19 M (nortriptyline) lithium: 12.5%
mean age 38 years placebo: 20%
UP = Unipolar; BP = bipolar; F = female; M = male; nr = not reported; MAOI = monoamine oxidase inhibitor; TCA = tricyclic antidepressant; HAM-
D = Hamilton Depression Rating Scale; SCRS = Short Clinical Rating Scale; CI = confidence interval.
a
All studies: odds ratio 3.11 (1.80–5.37); data from meta-analysis.
Since the first meta-analysis [16], only 1 placebo-con- view, arguments for a true augmentation effect derive
trolled study has been published [14]. As noted on the from a controlled clinical trial showing that the antide-
original meta-analysis published in 1999 [16], a new neg- pressant effects of lithium addition were significantly
ative study would have to include more than 2,500 pa- higher in amitriptyline-pretreated depression patients,
tients per group to change the results of this pooling. compared with placebo-pretreated patients, who showed
However, it remains to be examined whether the response no improvement after a 3-week treatment [17]. In sum-
to lithium augmentation represents true augmentation mary, a randomized, double-blind study is warranted
resulting from synergistic effects or whether the response which investigates the effects of lithium alone and com-
is simply owing to the antidepressant effect of lithium it- pares them with the effects of lithium in combination
self. Experimental studies supporting the former possi- with an antidepressant.
bility will be reviewed below. From the clinical point of