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11: Lithium

Risk Management and Treatment » Pharmacologic Treatments
11: Lithium

We suggest offering lithium alone (among patients with bipolar disorder) or in combination with another psychotropic agent (among patients with unipolar depression or bipolar disorder) to decrease the risk of death by suicide in patients with mood disorders.

Strength:

Weak for

Category:

ReviewedNew-replaced

Grades and Definitions

Strong for
or "We recommend offering this option …"
Weak for
or "We suggest offering this option …"
No recommendation
or "There is insufficient evidence …"
Weak against
or "We suggest not offering this option …"
Strong against
or "We recommend against offering this option …"

Categories and Definitions

Evidence Reviewed* Recommendation Category* Definition*
Reviewed New-added New recommendation following review of the evidence
New-replaced Recommendation from previous CPG that has been carried over to the updated CPG that has been changed following review of the evidence
Not changed Recommendation from previous CPG that has been carried forward to the updated CPG where the evidence has been reviewed but the recommendation is not changed
Amended Recommendation from the previous CPG that has been carried forward to the updated CPG where the evidence has been reviewed and a minor amendment has been made
Deleted Recommendation from the previous CPG that has been removed based on review of the evidence
Not reviewed Not changed Recommendation from previous CPG that has been carried forward to the updated CPG, but for which the evidence has not been reviewed
Amended Recommendation from the previous CPG that has been carried forward to the updated CPG where the evidence has not been reviewed and a minor amendment has been made
Deleted Recommendation from the previous CPG that has been removed because it was deemed out of scope for the updated CPG
*Adapted from the NICE guideline manual (2012): The guidelines manual. London: National Institute for Health and Care Excellence;2012. and Martinez Garcia L, McFarlane E, Barnes S, Sanabria AJ, Alonso-Coello P, Alderson P. Updated recommendations: An assessment of NICE clinical guidelines. Implement Sci. 2014;9:72.

Recommendation Resources

Although there is competing evidence in relation to lithium's anti-suicidal properties, several cohort studies and systematic reviews suggest that lithium maintenance is associated with reduced suicidal behaviors and deaths. Lithium has a narrow therapeutic window, and a variety of potential side effects which may complicate treatment adherence. Lithium can be lethal in overdose, and so it is vital that prescribers attend to that risk and limit the amount of lithium dispersed when indicated. Options to reduce risk of toxicity in overdose include dispensing smaller quantities, safe medication storage options, or even having a caregiver or family member store the medication. If suicide plans, or prior attempts, involve overdose, providers should consider alternatives to lithium for treatment.

Training Resources

This section includes links to training resources about offering lithium to decrease the risk of death to suicide in patients with bipolar disorder or unipolar depression:

Considerations informing individualized risk-benefit analysis regarding lithium for suicide prevention (Wortzel et al., 2022)
 
Does the patient have psychiatric conditions in addition to mood disorder, or applicable medical conditions?

Evidence suggests that Lithium's potential anti-suicide benefits may be diminished in the setting of additional mental health conditions, such as substance use disorders, personality disorders, or PTSD. Various medical conditions (e.g., kidney disease, thyroid disease, TBI) may compromise the safety, efficacy, and/or tolerability of lithium.

Is the patient at acute risk for suicide? Is there a history of suicide attempts involving overdose?

Though evidence suggests that lithium may be able to mitigate chronic risk in some cases (i.e., patients with mood disorders maintained at therapeutic levels for extended periods), it is unlikely to significantly impact acute risk, or a suicide crisis in progress. In that setting, the provision of a potential lethal means for suicide is dangerous, especially in the setting of prior suicide attempts via overdose. The weak evidence that lithium might mitigate suicide risk will seldom overcome histories of repeated suicide attempts via overdose when conducting risk-benefit analysis (i.e., justify the provision of a potentially lethal means), especially when other treatment options exist.

Does the patient have the capacity/willingness to sustain long-term treatment adherence with lithium and the associated monitoring?

Many patients struggle with sustained treatment adherence, to include those at risk for suicide. Absent the ability/willingness to sustain long-term treatment at therapeutic levels, and the required associated monitoring, lithium's potential anti-suicidal benefits are unlikely to be realized.

Has a therapeutic relationship been established, and what is the strength of the relationship?

The sustained treatment and monitoring required to realize anti-suicidal benefits from lithium seem far more feasible in the context of an established and strong therapeutic relationship. That relationship may also serve to diminish or address issues relating to the provision of a potential lethal means for suicide.

Are there other viable treatment options that are favorable in terms of efficacy, safety, and feasibility?

Lithium's anti-suicidal effects are less clear when compared to other psychotropic medications (as opposed to placebo), many of which may carry the potential for analogous benefits while being more safe, tolerable, and feasible.

Return to Resource Options

Webinars

This section includes links to webinars that are recommended about offering lithium to decrease the risk of death to suicide in patients with bipolar disorder or unipolar depression:

CPG Webinar Lithium for Suicide — a Therapeutic Risk Management Informed Approach Presented by Dr. Hal Wortzel
Return to Resource Options

Articles

This section includes links to recommended articles about offering lithium to decrease the risk of death to suicide in patients with bipolar disorder or unipolar depression:

Baldessarini, R. J., Tondo, L., Davis, P., Pompili, M., Goodwin, F. K., & Hennen, J. (2006). Decreased risk of suicides and attempts during long-term lithium treatment: a meta-analytic review. Bipolar disorders, 8(5 Pt 2), 625-639. https://doi.org/10.1111/j.1399-5618.2006.00344.x
Cipriani, A., Hawton, K., Stockton, S., & Geddes, J. R. (2013). Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis.. BMJ (Clinical research ed.), 346, f3646. https://doi.org/10.1136/bmj.f3646
Cipriani, A., Pretty, H., Hawton, K., & Geddes, J. R. (2005). Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. The American journal of psychiatry, 162(10), 1805-1819. https://doi.org/10.1176/appi.ajp.162.10.1805
Ernst, C. L., & Goldberg, J. F. (2004). Antisuicide properties of psychotropic drugs: a critical review. Harvard review of psychiatry, 12(1), 14-41. https://doi.org/10.1080/10673220490425924
Goodwin, F. K., Fireman, B., Simon, G. E., Hunkeler, E. M., Lee, J., & Revicki, D. (2003). Suicide risk in bipolar disorder during treatment with lithium and divalproex. JAMA, 290(11), 1467-1473. http://doi:10.1001/jamapsychiatry.2021.3170
Katz I.R., Rogers M.P., Lew R., et al. (2022). Lithium Treatment in the Prevention of Repeat Suicide-Related Outcomes in Veterans With Major Depression or Bipolar Disorder: A Randomized Clinical Trial. JAMA Psychiatry, 79(1), 24-32. https://doi.org/10.1001/jama.290.11.1467
Müller-Oerlinghausen, B., Felber, W., Berghöfer, A., Lauterbach, E., & Ahrens, B. (2005). The impact of lithium long-term medication on suicidal behavior and mortality of bipolar patients. Archives of suicide research : official journal of the International Academy for Suicide Research, 9(3), 307-319. https://doi.org/10.1080/13811110590929550
Nabi, Z., Stansfeld, J., Plöderl, M., Wood, L., & Moncrieff, J. (2022). Effects of lithium on suicide and suicidal behaviour: a systematic review and meta-analysis of randomised trials. Epidemiology and psychiatric sciences, 31, e65. https://doi.org/10.1017/S204579602200049X
Oquendo, M. A., Galfalvy, H. C., Currier, D., Grunebaum, M. F., Sher, L., Sullivan, G. M., Burke, A. K., Harkavy-Friedman, J., Sublette, M. E., Parsey, R. V., & Mann, J. J. (2011). Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior. The American journal of psychiatry, 168(10), 1050-1056. https://doi.org/10.1176/appi.ajp.2011.11010163