Table 3.

Maintenance of Augmentation Medications following Remission

Study	Class^	N	Mean Age (y)	Diagnosis	Initial agents; duration	Aug/Comb agent (n)	Measure	Findings	Comments
Reynolds et al., 1996 (51)	II	39	62	DSM-IV, unipolar, nonpsychotic, no dementia;*	Ongoing trial of maint for LLD; received adjunctive medication if HRSD-17 >10 after 8wks nortriptyline at 80–120 ng/mL	- Li (0.5–0.8 meq/L) (16) - perphen (4mg/d) (8) - Li + perphen (12) - Li→parox (2) - parox alone (1)	HRSD-17 - Response ≤10 × 3wks - Relapse reappearance HRSD≥17	Acute-phase responders: - 25/39 (64.1%) aug - 99/119 (83.2%) non-aug Cont-phase relapsers∷ - 13/25 (52.0%) aug relapse - 6/99 (6.1%) non-aug relapse	Comparing Li to perphenazine, no difference in rate of response, relapse, or sustained remission
Hardy et al., 1997 (49)	I	12	76	DSM-III-R unipolar w/o depressive symptoms ≥1y on Li aug;*	Responders to Li augmentation after ≥6mos TCA monotherapy and symptom-free for ≥1y while being maintained on Li augmentation	Lithium withdrawn from half at rate < 150mg/d/wk in double-blind, PBO-controlled fashion (level 0.4 mEq/L)	Recurrence: - hospitalization - change AD dose/type - MADRS > 15 and/or +10 from baseline - GDRS > 20	- 2/4 on Li had recurrence, both after significant stressors (spouse death, CVA causing dementia) - 2/5 on placebo had recurrence with long delay in response to Li re-initiation (7-week and 92-week)	- placebo group w/fewer side effects (esp urinary symptoms, neurotoxicity)
Fahy et al., 2001 (50)	III	21	78	Unipolar MDE “deemed to be clinically well”;*	AD class not specified Time “well” not defined	Lithium tapered over 2–12 weeks Did not include: - patients known to have relapsed in the past not included;	Relapse “a re-emergence of depressive symptoms at any time”	11/21 (52.4%) relapsed	-11/21 relapsed (52.4%) - relapsers had been on Li longer (2.5y v. 1.4, p=0.007) - no clear predictors of relapse
Alexopoulos et al., 2008 (52)	II	63	63	DSM-IV, unipolar, +/− psychosis, MMSE > 23;*	Citalopram monotherapy (20–40mg/d) × 4–6 wks; continued to augmentation only if <50% rdxn HRSD	Phase 2: C (avg 40.0mg/d) + risperidone (0.25–1mg/d, avg 0.8mg/d) × 4–6wks; Phase 3: Those who met criteria for remission then continued on C+R or C+PBO (dbl-blind)	Remission: - HRSD-17≤7 - CGI 1 or 2 Relapse: - CGI 6 or 7 - HRSD ≥16 - discontinuation - deliberate self-injury or suicidal intent	Time to and rate of Relapse: - R: 105d, 18/32 (56%) - PBO: 57d, 20/31 (65%) - p for time to relapse 0.069

^*Mean MMSE not provided

^{^}Class I: randomized, controlled trials; Class II: well-designed observation studies with concurrent controls such as cohort or case-control; Class III: expert opinion, case series, case report, and studies with historical controls