Lithium Reduces Risk of Suicide and Recurrent Episodes of Bipolar and Major Depressive Disorders

Patients treated for bipolar or major depressive disorder were less likely to have recurrent episodes of illness, suicidal ideation, or to attempt suicide in the 1-year after the addition of lithium than in the year before, in a within-subject, naturalistic outpatient study.¹

"The present findings indicate that including lithium in the long-term treatment of mood disorder patients was strongly associated with reduced risk of clinical recurrence, suicidal ideation and suicide attempts in patients diagnosed with either [bipolar disorder] or [major depressive disorder], as well as longer times to these outcomes," reported lead author Maurizio Pompili, MD, PhD, Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Centre, Sant'Andrea Hospital, Sapienza University of Rome, and colleagues.

The investigators recruited 296 adult psychiatric outpatients (162 women, 134 men, mean age 44.1 ± 12.8 years) in treatment at the Psychiatric Unit of Sant'Andrea Hospital in Rome for either bipolar disorder (BD, n=171) or major depressive disorder (MDD, n=125) without comorbid neurological conditions. Their mean age of illness onset was 30.8 ± 11.2 years

At study entry, in the year prior to the addition of lithium treatment, 125 patients (42.2%) reported current suicidal ideation (31% of those with BD, 57.6% of those with MDD). Overall, 51 (17.2%) had attempted suicide within 6 months (13.5% of those with BD and 22.4% of those with MDD).There were 296 observations with 97 adverse clinical events (32.8%), also described as clinical recurrence, (censoring rate of 67.2%).

Treatment regimens at study entry included antipsychotics (78.0%), mood stabilizing antiepileptics (78.0%), benzodiazepines (57.4%) and antidepressants (36.5%). At the start of lithium treatment, the daily nadir lithium concentration averaged 0.71 (SD ± 0.26) mEq/L, with a mean (±SD) daily oral dose of 605 ± 262mg lithium carbonate.

The primary outcomes in the first year of lithium treatment compared to the year before were clinical recurrence, suicide attempt and suicidal ideation. The investigators applied a paired-sample analysis to ascertain statistically and clinically significant reduction in the proportion of patients with these adverse outcomes and discern whether change in outcomes after lithium treatment differed between patients with BD or MDD.

Lithium Improves Course of BD and MDD

Pompili and colleagues reported a substantial reduction in each primary outcome measure in the year following the addition of lithium. Of 295 observations, there were 31 adverse clinical events (or recurrences), a reduction to 10.5% from 32.8% in the year prior to lithium treatment (89.5% censoring rate). The estimated mean survival time until clinical event/recurrence in the year before lithium treatment was 10.3 (95% CI: 9.92–10.6) months, which was increased modestly but statistically highly significantly to 11.4 (11.2–1.6) months with lithium.

There was no statistically significant difference in the reduction after lithium between patients with BP or MDD, which suggests, the investigators indicate, "similar benefits of lithium treatment with both diagnostic groups."

In comparison with 143 events of suicidal ideation in 296 observations overall (48.3% [42.7–54.0]) prior to lithium, there were 30 (10.1% [7.10–14.0]) after lithium (censoring rate of 88.8%).Latency to new suicidal ideation increased after lithium from 9.29 (8.91–9.68) months to 11.4 (11.2–11.6) months.

In patients with MDD, the risk of new suicidal ideation decreased with lithium administration, from 64.8% (56.2–72.8) to 13.6% (8.40–20.4), and from 36.3% (29.3–43.6) to 7.6% (4.11–12.6) with BD. There was a similar increase in latency to new suicidal ideation after lithium for patients with MDD or BD.

Suicide attempts overall were similarly reduced in the year of lithium treatment from the prior year, with 13 events in 296 observations (4.39%) (censoring rate of 95.6%) compared to 85 suicidal events (28.7%) (censoring rate of 71.3%) without lithium.Suicide attempt rates in patients with MDD were reduced from 38.4% (30.2–47.1) to 6.40% (3.10–10.7), and from 21.6% (16.0–28.3) to 2.90% (1.10–6.30) in those with BD.

The investigators characterize the overall reduction in suicide ideation events from 48.3% to 10.1% as "a highly significant, 4.78-fold overall decrease with lithium added"; the 6.54-fold overall reduction in suicide attempts from 28.7% to 6.4% was noted as a "major beneficial effect" of lithium.

Is Lithium Uniquely Antisuicidal?

Pompili and coinvestigator Ross Baldessarini, MD, Department of Psychiatry, Harvard Medical School, Boston, MA, discussed with Psychiatric Times whether lithium has antisuicidal effects, or if that effect emerges with the mood stabilization and therapeutic synergy that improves affective symptoms.

They noted that there is evidence for a greater suicide-risk reducing effect of lithium than other psychiatric medications, and that this effect may not require substantial improvement in affective symptoms. Suicide risk is a multifactorial phenomenon, they pointed out, with a given diagnosis being a significant, but not exclusive, contributing factor to the risk.²

"Lithium seems to attenuate some of the features often associated with suicide risk, such as irritable, volatile, suicidal states, probably acting on molecular mechanisms that regulate such phenotypes," Pompili posited.

"What we care about in suicide risk is the degree of a peculiar construct called mental pain, the drama occurring in the suicidal mind when the individual sees no way out. In this regard, some features that constitute mental pain, I believe, can be attenuated by lithium," Pompili said.

Dr Bender reports on medical innovations and advances in practice and edits presentations for news and professional education publications. He previously taught and mentored pharmacy and medical students, and he provided and managed pharmacy care and drug information services.

References

1. Pompili M, Bernardelli I, Sarubbi S, et al. New episodes and suicidal risks in bipolar and major depressive disorder patients during versus before long-term treatment with lithium. Acta Psychiatr Scand. 2025: 152:290-298.

2. Favril L, Yu R, Uyar A, et al. Risk factors for suicide in adults: systematic review and meta-analysis of psychological autopsy studies. Evid Based Ment Health. 2022;25(4):148-155.