CGPR: Tell us about using lithium in older adults.
Dr. Gitlin: In older adults, natural declines in renal function, medical comorbidities, and different pharmacodynamic sensitivities change how we target blood levels, interpret side effects, and weigh risk-benefit ratios over a realistic time horizon. The core principles remain the same as in younger adults, but there’s more “noise” from aging physiology and coexisting illnesses that we need to parse carefully when prescribing lithium in older adults.

CGPR: What’s your preferred lithium formulation in this demographic?
Dr. Gitlin: I default to immediate-release (IR) lithium carbonate, dosed once daily. Extended-release’s main advantage is less nausea, which is helpful early on in sensitive patients, but it often causes more diarrhea. Critically, renal risk appears more tied to trough exposure than peak, so once-daily IR yields the lowest 24-hour trough (about 23 hours after dosing), which may be gentler on the renal tubules. By contrast, BID dosing keeps troughs higher. If nausea necessitates divided doses early, I’ll still aim to consolidate to once daily as tolerability improves. 

CGPR: Does dosing time (morning vs night) matter for renal protection?
Dr. Gitlin: Not as far as we know. Most people take lithium at night to facilitate a 12-hour post-dose level the next morning without hunting for a lab at 8 pm. The kidney-sparing logic is about once-daily dosing to lower troughs, not about morning versus evening. Choose a consistent time that allows reliable, 12-hour post-dose level checks and supports adherence. 

CGPR: What’s your first step when considering lithium in an older adult with declining kidney function?
Dr. Gitlin: I anchor decisions to eGFR and age-matched norms, not serum creatinine alone. Many adults age 70+ have an eGFR ≤ 60 mL/min/1.73m², which can reflect normal aging as well as comorbid conditions like hypertension, diabetes, and cardiovascular disease. Before attributing decline solely to lithium, I assess those contributors and their cumulative effects. Then, I recenter the conversation around risk-benefit ratios in the context of mood stability, history of relapse, and lithium’s unique preventive effects, particularly against mania and suicidality, while acknowledging renal risk. We discuss the options together: continuing lithium at the lowest effective dose with close monitoring, or tapering gradually after having added other mood stabilizer(s). This is where shared decision-making starts, grounded in numbers (serial eGFRs, lithium levels) and the patient’s lived experience on and off lithium. 

“I aim for the lowest effective serum level, often 0.4–0.6 (and as low as 0.35–0.4 in some), rarely exceeding 0.7 after age 60. Older adults are more sensitive to a given level.”

Michael Gitlin, MD 

CGPR: What maintenance lithium levels do you target in older adults, and why?
Dr. Gitlin: Across ages, lithium maintenance targets have shifted downward from 0.8–1.0 mEq/L toward 0.6–0.7 because higher levels correlate with greater eGFR decline. Older adults differ in two ways: They often require lower doses to reach a given level due to reduced renal clearance, and they’re more sensitive to a given level. Some feel well and stay stable at levels as low as 0.35–0.4, while levels around 0.6 can produce disproportionate side effects. Age-related changes in the sodium-lithium pump and increased blood-brain barrier permeability may increase brain and intracellular lithium despite “therapeutic” serum levels, helping explain why lower lithium levels are often effective and better tolerated in late life. 

CGPR: What side effects push you to adjust levels in older adults?
Dr. Gitlin: Watch for disproportionate neurocognitive and neurologic effects: tremor, ataxia, confusion, and overall “feeling unwell” at levels that a younger adult might tolerate. These often resolve when you lower the morning level to 0.4–0.6 or even 0.35–0.4 (for once-daily bedtime regimens), provided mood stability holds. Also minimize dehydration risks and aggressively prevent toxicity episodes, as even transient toxic levels are associated with later eGFR decline. In short, err on the side of finding the lowest effective level and let the patient’s tolerability guide you. 

CGPR: How often should you monitor lithium levels and labs in older adults? 
Dr. Gitlin: In younger patients, annual monitoring is usually sufficient. In older adults, I increase monitoring to every 3–6 months as eGFR drifts from the 70s into the 50s and tighten further if the trajectory steepens or comorbidities add risk I distinguish screening (when eGFR is comfortably ≥ 60–70 and stable) from active monitoring (when I’m tracking a concerning trend), and I explain this distinction to patients. I explain that we begin with routine check-ins, but if kidney function changes, we move to closer follow-up to protect renal health while keeping mood stable. I routinely monitor calcium and TSH, and I recheck lithium levels after any dose adjustment, medication change, or intercurrent illness that could affect kidney function or volume status (Editor’s note: Expert consensus also recommends obtaining a baseline ECG in patients with cardiac risk factors (Sampogna G et al, Int J Bipolar Disord 2025;13(1):21)). I allow adequate time for steady state before checking levels: While lithium generally equilibrates in about five days for younger adults, the half-life is often longer in older adults, so I usually wait about seven days.

CGPR: Why is eGFR preferred over creatinine when monitoring kidney function?
Dr. Gitlin: eGFR is far more useful than creatinine for routine care. Serum creatinine alone can be misleading because it’s confounded by muscle mass, which declines with age. An older adult can have a “normal” creatinine despite significant kidney impairment. eGFR integrates age, sex, and creatinine into a more clinically meaningful estimate of filtration capacity. It’s a more reliable indicator of renal function and is sufficiently accurate for psychiatric decision-making. 

CGPR: How do you decide when to adjust dose, consult nephrology, or consider stopping lithium if eGFR falls?
Dr. Gitlin: If eGFR is ≥ 60 at any age, I don’t worry and continue standard monitoring. In older adults with eGFR in the 50s, I discuss risks and benefits, increase the monitoring cadence, and often seek nephrology input, especially as values approach 50. Below 50, the risk-benefit conversation becomes more urgent. Renal outcomes after lithium discontinuation appear to depend on baseline kidney function. Stopping lithium often slows eGFR decline and may allow partial stabilization, but once kidney disease is more advanced (particularly once eGFR falls into the 30s), progression can continue despite discontinuation, suggesting a threshold of irreversibility we want to avoid (Hoekstra R et al, Bipolar Disord 2022;24(6):667–670). 

CGPR: At what point do you consider advanced renal testing or kidney biopsy?
Dr. Gitlin: I reserve those decisions for nephrology. A nephrologist may consider advanced renal studies or biopsies when the diagnosis is unclear or when there’s suspicion of another etiology of renal function decline besides lithium. While a biopsy can show lithium’s characteristic pattern of chronic interstitial nephritis, it carries procedural risks and rarely changes management in routine psychiatric care. In most cases, our role is to recognize concerning trends in eGFR and collaborate with nephrology early. 

CGPR: How do you counsel about drug interactions that raise lithium levels, like NSAIDs, thiazides, or ACE inhibitors?
Dr. Gitlin: Keep it simple and pragmatic. Intermittent NSAID use for a day or two rarely matters when the lithium level sits in the low therapeutic range, but daily use can raise levels roughly 25%–30%. Thiazide diuretics reliably raise levels by about a third. ACE inhibitors and ARBs can also raise levels. If the patient begins regular use of an interacting drug, check a lithium level and adjust. The relationship between dose and level is reasonably linear, so if a change raises the level by a third, a one-third dose reduction will usually recenter it. Teach patients to flag new meds and dehydration risks early. 

CGPR: How do you manage a patient who only remains stable at higher lithium levels (like 1.0) but has borderline renal function?
Dr. Gitlin: This is where true informed consent and meticulous monitoring matter. If every attempt to lower to ≤ 0.7 leads to relapse, I’ll maintain the higher level while increasing the frequency of eGFR and toxicity checks, documenting the discussion and clinical rationale. A plausible explanation is that there’s a subset of older adults in whom the lithium pump works much better. At their level of 1.0, they might not have as much intracellular lithium—but we don’t measure intracellular lithium. When talking with patients and caregivers, I explain it this way: “You seem to need a bit more lithium in your blood for it to work, but that also means we need to watch your kidneys more closely.” Regardless, I would proceed with eyes open: Avoid dehydration, promptly address intercurrent illness, and prevent toxicity episodes, which themselves accelerate renal decline. If eGFR trends below 50 despite these precautions, I’d reopen the discontinuation discussion. 

CGPR: How do you distinguish lithium-related CKD from age-related CKD in practice?
Dr. Gitlin: Most of the time you don’t, at least not with certainty. We judge by pattern and pace: A long, low-level eGFR decline that tracks with higher lithium levels and toxicity episodes suggests lithium contribution, especially without strong competing renal risks. Definitive differentiation requires biopsy, which occasionally shows lithium’s chronic interstitial nephritis pattern with tubular scarring and relatively preserved glomeruli. However, that’s a nephrology decision and not routine. 

CGPR: When do you draw a hard line and recommend discontinuation?
Dr. Gitlin: I become distinctly uncomfortable once eGFR drops below 50, and I’ve at times refused to continue lithium when renal risk felt unacceptable, even when the patient wished to stay on it. Longitudinal experience following patients to dialysis or transplant sensitizes you to the stakes. Some colleagues are more permissive, but population-level data suggest that lithium treatment is associated with an increased risk of stage 3 CKD, and my clinical experience aligns with that signal (Shine B et al, Lancet 2015;386(9992):461–468). Practically, you look at the trajectory plus risk factors, patient values, and alternative stabilization options. Below 50, those strands often converge on tapering. 

CGPR: If you decide to stop lithium based on kidney function, how fast should you taper?
Dr. Gitlin: Never stop abruptly unless there’s acute toxicity. Add the replacement mood stabilizer first, titrate to a therapeutic dose, and then taper lithium over at least one to three months. The best data we have show that sudden discontinuation (≤ 2 weeks) carries a higher relapse risk than slower tapers (Baldessarini RJ et al, Bipolar Disord 2022;24(7):720–725). There’s also a risk of discontinuation rebound mania. Because lithium-related renal change accrues over years, there’s no renal advantage to rushing; prioritize mood stability during the transition.

CGPR: What is your preferred medication to start if tapering off lithium due to renal concerns?
Dr. Gitlin: Lamotrigine is my strong first choice for bipolar II or depression-predominant illness. It’s better at preventing lows than highs, generally well tolerated after the initial titration, and has minimal effects on weight, cognition, and daytime energy. The risk of serious immunologic rash, including Stevens–Johnson syndrome, is real but rare and largely confined to the first two months; beyond that, lamotrigine is one of the easiest mood stabilizers to live with. That said, lamotrigine is not an antimanic agent. When mania or hypomania is the primary concern, I typically start with a cautiously dosed antipsychotic in older adults, given its faster onset, and reserve valproate as a later option. I don’t assume valproate is renal-protective by default: Observational data suggest that lithium at trough levels < 1.0 mEq/L and valproate carry similar long-term CKD risk (Bosi A et al, JAMA Netw Open 2023;6(7):e2322056).

CGPR: What’s your view on lithium orotate and microdosing in older adults with kidney disease?
Dr. Gitlin: Lithium orotate is sold over the counter in tiny doses with claims of better brain penetration, but we don’t measure brain lithium; we measure serum levels. For mood stabilization, sub-detectable serum levels leave us flying blind, and I don’t recommend substituting orotate for therapeutic lithium in bipolar disorder. Separately, emerging data suggest very-low-dose lithium might be neuroprotective, potentially slowing progression from mild cognitive impairment to dementia (Haussmann R et al, Neurosci Lett 2021;760:136044). There’s also early literature that trace lithium may be associated with lower suicide rates in addition to reduced dementia rates (Terao T et al, Pharmaceuticals (Basel) 2024;17(11):1486).

CGPR: Summarize your core, kidney-conscious lithium playbook for older adults.
Dr. Gitlin: Start IR lithium carbonate once daily; aim for the lowest effective serum level, often 0.4–0.6 (and as low as 0.35–0.4 in some), rarely exceeding 0.7 after age 60. Monitor eGFR, TSH, calcium, and lithium levels with a cadence tied to the renal trajectory; escalate to nephrology as eGFR approaches 50 or declines rapidly. Avoid dehydration and minimize interacting drugs; if a regular interactor is needed, recheck levels and adjust. Treat toxicity episodes as renal risk events. If discontinuation is warranted, add the replacement first and taper lithium over one to three months. Above all, ground decisions in numbers and function, and keep the conversation centered on the patient’s mood stability and life goals.

CGPR: Thank you for your time, Dr. Gitlin.