Table 1.
Randomized controlled trials—not specifically focusing on suicidality or mortality
| Year/country | Author | Diagnoses | Medication/type of study | Number of patients | Duration | Results |
|---|---|---|---|---|---|---|
| 1971/UK | Coppen et al. | Unipolar | Li | 65 | 2 years | 3 died (Plac) from causes not related to affective disorders |
| Bipolar | Placebo | Li (n = 28) | ||||
| Plac (n = 37) | ||||||
| Randomly assigned | Unipolar Li (n = 11) Unipolar Plac (n = 17) Bipolar Li (n = 15) Bipolar Plac (n = 22) | |||||
| 1973/USA | Prient et al. (a) | Unipolar | Li | 122 | 2 years, observation period started after patient discharge | 1 suicide (Plac), 4 deaths due to other causes not related to affective disorder |
| Bipolar | Imipramine | Li (n = 45) Imipramine (n = 38) Plac (n = 39) | ||||
| Placebo | ||||||
| Randomly assigned | Bipolar (n = 44) | |||||
| Unipolar (n = 78) | ||||||
| 1973/USA | Prien et al. (b) | Bipolar | Li | 205 | 2 years | 1 suicide (Plac) |
| Placebo | Li (n = 101) | 2 deaths due to other causes | ||||
| Plac (n = 104) | ||||||
| Randomly assigned | ||||||
| 1989/USA | Dorus et al. | Depressed vs. non-depressed alcoholics | Li compliant | 457 | 52 weeks | 1 death from all causes (Plac), no death (Li) |
| (n = 82) | Depressed (n = 171 ≥ 108 study completers) | |||||
| Placebo compliant (n = 82) | ||||||
| Non-depressed (n = 286 ≥ 172 study completers) | ||||||
| Double-blind, placebo-controlled trial | ||||||
| 1996/Germany | Greil et al. | Unipolar depression | Li | 81 | 2.5 years | 1 suicide (amitriptyline) 0 suicide (Li) |
| Amitriptyline | Li (n = 40) | |||||
| Prospective randomized multicenter trial | Amitriptyline (n = 41) | |||||
| 1997/Germany | Greil et al. (a) | Bipolar disorder | Li | 144 | 2.5 years | 0 suicide or SA (Li) |
| CBZ | Li (n = 74) | 1 suicide, 1 SA (CBZ) | ||||
| CBZ (n = 70) | ||||||
| Prospective randomized multicenter trial | ||||||
| 1997/Germany | Greil et al. (b) | Schizoaffective disorder | Li | 90 | 2.5 years | 0 suicide or SA (Li) |
| CBZ | Li (n = 43) | 0 suicide, 4 SA (CBZ) | ||||
| CBZ (n = 47) | ||||||
| Prospective randomized multicenter trial | ||||||
| 2000/UK | Coppen et al. | Unipolar | Li | 103 | Study population was recruited in 1977 | 10 patients died during the study, expected number of deaths was 18.31 and no deaths from suicide |
| Bipolar | Placebo | Unipolar (n = 67) Bipolar (n = 30) Schizoaffective (n = 6) | ||||
| Schizoaffective | Randomly assigned | |||||
| 2000/Germany | Bauer et al. | Refractory depression | AD + Li | 30 | 4.5 months | 1 suicide (Plac) |
| AD + placebo | AD + Li (n = 14) | |||||
| AD + Plac (n = 15) | ||||||
| Randomized, double-blind, placebo-controlled trial | ||||||
| 2002/UK | Wilkinson et al. | Unipolar depression | AD + Li | 49 | 2 years | 4 deaths from unrelated causes (2 Li, 2 Plac) |
| AD + placebo | AD + Li (n = 25) | |||||
| AD + Plac (n = 24) | ||||||
| Randomized, double-blind, controlled trial | Elderly patients (>65) | |||||
| 2003/Europe, Canada, USA | Calabrese et al. | Bipolar I | Li | 966 | 8–16 weeks open label, 18 months | 6 deaths: 4 suicides, 2 of the suicides during open-label study, 1 suicide after discontinuation from open-label study |
| Placebo | Li (n = 121) | |||||
| LTG | Plac (n = 121) | |||||
| LTG (n = 221) | ||||||
| Randomized, double-blind, placebo-controlled trial | ||||||
| 0 suicide (Li), 1 suicide (LTG) | ||||||
| 11 SA (10 open label, 1 in Plac) | ||||||
| 2005/USA | Findling et al. | Bipolar I, II | Li | 60 | Phase 1: up to 20 weeks | 0 suicide, 0 SA in both groups |
| VLP | Li (n = 30) | |||||
| VLP (n = 30) | Phase 2: 76 weeks | |||||
| Randomized, double-blind, controlled trial | Pediatric (5–17 years) | |||||
| 2005/USA, Africa, Australia, Canada, Europe | Tohen et al. | Bipolar I | Li | 431 | Open label with Li + OLZ 6–12 weeks, 52 weeks double-blind phase monotherapy | 1 suicide (Li) during open-label phase, 2 died (Li) during double-blind phase (1 suicide, 1 accident) |
| OLZ | Li (n = 214) | |||||
| OLZ (n = 217) | ||||||
| Randomized, double-blind, controlled trial | ||||||
| 2007/Netherlands | Kok et al. | Treatment resistant depression | Augmentation with Li | 29 | 6 weeks + 2 years follow-up | 2 deaths (Li), 3 deaths (phenelzine) |
| Li (n = 15) | ||||||
| Augmentation with phenelzine | Phenelzine (n = 14) | |||||
| Elderly (>60 years) | ||||||
| Open, randomized controlled trial | ||||||
| 2008/Germany | Lauterbach et al. | Depressive disorders | Li | 167 | 12 months | 0 suicide (Li) |
| Placebo | Li (n = 84) | 3 suicides (Plac) | ||||
| Plac (n = 83) | 7 SA (Li) | |||||
| Randomized, double-blind, placebo-controlled trial | 7 SA (Plac) | |||||
| 2010/UK, France, USA, Italy | Geddes et al. | Bipolar I | Li | 330 | 24 months | 2 deaths from all causes (Li), 3 deaths from all causes (VLP), 1 death from all causes (Li + VLP) |
| VLP | Li (n = 110) | |||||
| Li + VLP | VLP (n = 110) | |||||
| Li + VLP (n = 110) | ||||||
| Randomized, open-label trial | ||||||
| 2010/Denmark, Sweden | Licht et al. | Bipolar I | Li | 155 | 52 weeks | 1 suicide (Li) |
| LTG | Li (n = 78) | 1 SA (LTG) | ||||
| LTG (n = 77) | ||||||
| Open, randomized trial | ||||||
| 2011/USA | Oquendo et al. | Bipolar disorder | Li | 98 | 2.5 years | 0 suicide |
| VLP | Li (n = 49) | 6 SA (Li), 8 SA (VLP) | ||||
| Randomized, double-blind controlled trial | VLP (n = 49) | 45 suicidal events (16 Li, 18 VLP) | ||||
| 2011/Asia, Europe, Central and South America, USA | Weisler et al. | Bipolar I | Li | 2438 (open label) | Open label 4–24 weeks, double-blind up to 104 weeks | 3 deaths (Quet): 2 due to other causes, 1 suicide/accidental gunshot, similar overall incidence of suicidal behavior/ideation in the Quet (n = 3), Li (n = 3), and Plac (n = 8) groups |
| Quetiapin | 1226 (double-blind) | |||||
| Placebo | Li (n = 364) | |||||
| Quet (n = 404) | ||||||
| Randomized, placebo-controlled trial | Plac (n = 404) | |||||
| 2011/USA | Khan et al. | Depressive disorders | Cit + Li | 80 | 4 weeks | Subgroup of the patients assigned to citalopram and lithium had significantly higher Sheehan Suicidality Tracking Scale (S-STS) remission rates compared to patients assigned to citalopram and placebo |
| Cit + Placebo | Cit + Li (n = 40) | |||||
| Cit + Plac (n = 40) | ||||||
| Randomized, double-blind trial |
SA suicide attempt, Li lithium, Plac placebo, Cit citalopram, Quet quetiapine, VLP valproate, LTG lamotrigine, CBZ carbamazepine