CHAPTER 26 LITHIUM

Introduction
1970: FDA approved in treating acute mania
Inexpensive + Effective: highly cost-effective
Pharmacological Profile
Minimal protein bound
Renal eliminated
Pharmacokinetics
Absorbed from GI, excreted through Renal in 24hrs
Peak in 1-2hrs(rapid) or 4-5hrs(sustained)
Steady state achieved in 4-5days

Indications and Efficacy

Bipolar disorder
Unipolar depression
Suicide: Is lithium protective?

Lithium in Bipolar Disorder(1)

Acute Mania
Lithium VS antipsychotics
Chlorpromazine > Li with Li less side effects (Prien 1972)
Haloperidol / halo + Li > Lithium alone (Garfinkel 1980)
Li = haloperidol = risperidone (Segal 1998)
Antipsychotics work faster but higher risks for weight gain and other metab

olic effects
Lithium VS anticonvulsants
Carbamazapine = Li (Small 1991)
Valp = Li, 48% achieve response in 3wks (Bowden 1994)
Li = Valp = Carbamazepine (Emilien 1996)
Anticonvulsants better tolerated than Lithium
Patients with EEG abnormalities: Valp > Li
Co-occurrence with depression: poor response to Li, better to Valp

Lithium in Bipolar Disorder(2)

Bipolar Depression
Li is 1st line treatment (79% had complete/partial response) (Goodwin
1990)
Li recommended as monotherapy for mild to moderate bipolar depre
ssion (expert consensus in 2004)
Rapid Cycling
Rapid cyclers do poorly with most, Li does improve burden of illness
Li less effective in prevention
>1 year of Li: higher % of well time, less severity and duration of epis

odes

Lithium in Bipolar Disorder(3)

Prophylaxis and Maintenance
Effective in long-term use(>1 yr) in decreasing frequency of mood epi
sodes (Tondo 2001)
Only 24% free of mood episodes (Kulhara 1999)
Patients received valproate remained in treatment significantly longer
than did those received lithium. (Bowden 2000)
BALANCE: Li + Valp > Valp
,
Li > Valp
Dose: QDHS > BID (higher brain-to-serum ratio)

Lithium in Unipolar Depression

Lithium augmentation found significant improvement in 56

% - 96% (5 controlled trials)

15.9% who did not experience remission with citalopram a
nd another medication trial experienced remission after ad
dition of Lithium. (STAR*D)

Lithium in Suicidal Protection

Lower mortality than bipolar population, did not have high

er suicide rate than general population. (Schou 1998)

Risks of completed and attempted suicides were 8.6-fold
higher in patients w/o Li.

Use in Special Populations(1)

Children and Adolescents
More efficacious than placebo for bipolar disorder, but not for major
depression
The Elderly
More patients > 55 y/o improved with Li than Valp
Therapeutic range is similar (>0.8mmol/L)
Increase Li level: Volume depletion, NSAIDs, thiazide
HD: Li given only after dialysis, need not given daily
Neuroprotective, decrease oxidative damage, prevention of neuroc

ognitive decline, Alzheimers dz

Use in Special Populations(2)

Pregnant/Lactating Women
Lithium is not a high-risk teratogen
Although Ebsteins anomaly higher with Li, 0.05%-0.1%
The risk is < than neural tube defect of anticonvulsants

71% recurrence risk when discontinued mood stabilizer Tx during p

regnancy
11 times shorter of the time to recurrence if mood stabilizer was dis
continued abruptly, not gradually
1.6 times higher in women using mood stabilizer other than Li
Rates of relapse increased sharply during postpartum period pro
phylactic Tx
Found in breast milk and infant serum(0.090.3mEg/L)
increase in baby TSH, BUN, Cr, w/o evident long-term effects

Side Effects and Toxicology(1)

Renal & Thyroid function: twice during the first 6 months, t

hen once every 6 months.

Most disturbing: cognitive & weight gain
Self-reported noncompliance: cognition and coordination
Neurotoxicity, delirium, encephalopathy
especially combine with typical antipsychotics
Potentially irreversible

Side Effects and Toxicology(2)

Tremor
Tremor may decrease with time, severe tremor indicate toxicity
Elimination of caffeine may worsen tremor
Thyroid function
14.9% female, 3.4% male developed hypothyroidism (Kirov 1998)
Female OR > 50 y/o were more likely

Side Effects and Toxicology(3)

Renal Complications
Tubular dysfunction
20% - 40% Nephrogenic diabetes insipidus
CKD (10-20 years of lithium administration)
Cardiac Changes
Sinus bradycardia, sinus node dysfunction
AV block, T-wave change

Drug-Drug Interactions(1)
Lithium and Anticonvulsants
Lithium + valproate: sedation, tremor, weight gain
Lithium + carbamazepine: neurotoxicity
Lithium + CCB: Neurotoxicity
Lithium and Antipsychotics
Neurotoxicity & TD can occur
Low dose antipsychotics, Li level < 1.0mEq/L
Lithium + clozapine: DKA, NMS
Lithium + risperidone: fever, leukocytosis, increase CPK, delirium
Lithium + Gabapentin: safe
Lithium + BZDs: safe

Drug-Drug Interactions(2)
Lithium + serotonergic antidepressants: serotonin syndro

me
Lithium + nonpsychotropic medications
NSAIDs, thiazide, ACEI