Therapeutic drug monitoring of lithium involves monitoring lithium levels in patients taking lithium carbonate to treat conditions like bipolar disorder. Key points: - Lithium is most commonly used as a mood stabilizer to treat manic episodes of bipolar disorder. - Therapeutic lithium levels range from 0.6 to 1.25 mEq/L, with levels of 0.9 to 1.1 mEq/L favored for treating acute mania. - Factors like diuretics, dehydration, and medications can impact lithium levels, so monitoring is important to avoid toxicity from levels above 1.5 mEq/L or below therapeutic ranges. - Blood

1. THERAPEUTIC DRUG MONITORING
OF LITHIUM

2. Therapeutic drug monitoring (TDM) Definition
Therapeutic drug monitoring (TDM) is defined as the management of a
patient’s drug regimen based on the serum, plasma, or whole blood
concentration of a drug.
Therapeutic Drug Monitoring - an overview | ScienceDirect Topics

3. FUNCTION
1) Selection of drug
2) Designing of dosage regimen
3) Evaluation of patients response
4) Determining the need for measuring serum drug concentration
5) Assay of drug
6) Performing pharmacokinetic evaluation of drug levels
7) Readjustment of dosage regimen
8) Monitoring serum drug concentration
9) Recommending special requirements

4. GENERAL INTRODUCTION
• Lithium is a psychiatric medication that is used to treat patients with bipolar
disorder (antimanic agent)
• Most commonly prescribed as lithium carbonate
• When other treatments are not effective, lithium is also used for:
1. Major depression
2. Schizophrenia
3. Mood disorders (bipolar disorder being the most important one)
https://www.nhs.uk/medicines/lithium/

5. USES
• Lithium affects the flow of sodium through nerve and muscle cells in the
body. Sodium affects excitation or mania.
• Lithium a mood stabilizer that is a used to treat or control the manic
episodes of bipolar disorder (manic depression). Manic symptoms include
hyperactivity, rushed speech, poor judgment, reduced need for sleep,
aggression, and anger.
• In Bipolar disorder - Lithium is the most effective mood stabilizer. Good
against depression and mania.
• In Unipolar Depression - Used in combination with antidepressants.
https://www.ncbi.nlm.nih.gov/books/NBK519062/

6. USES
• In Suicide and aggressivity - Reduces the risk of suicide and aggressivity
Lithium also helps to prevent or lessen the intensity of manic episodes.
• Other conditions – Hyperthyroidism, Hematologic conditions, Seborrheic
dermatitis, Herpes simplex
• Neuroprotective effects - Could prevent dementia
• Other mental health conditions – Schizophrenia.
https://www.ncbi.nlm.nih.gov/books/NBK519062/

7. MECHANISM OF ACTION
• Drug → inhibits 2 SIGNAL TRANDUCTION PATHWAYS
• Pathways inhibited include:
a. Intracellular inositol → reduced inositol signaling
b. GSK-3 (Glycogen synthase kinase)
• GSK-3:-
Component of various intracellular signaling pathways.
Promotes signaling of:
a. Insulin/ insulin-dependent growth factor
b. BDNF (Brain-derived neurotrophic factor)

8. MECHANISM OF ACTION
• Lithium → inhibits GSK-3→ reduces phosphorylation (breakdown) of
BETA CATENIN→ increases concentration of beta-catenin → shows
the following effects (via transcription of proteins):
a. Modulates energy metabolism
b. Provides neuroprotection
c. Increases neuroplasticity
1. https://pubmed.ncbi.nlm.nih.gov/23371914/#:~:text=At%20a%20neuronal%20level%2C%20lithium,by%20way%20of%20compensatory%20changes

9. COMMON BRANDS
• India :
Carbolith® [Tab]
LicabⓇ [Tab]
Lalithium® [Tab]
Elcab (300mg)
Genlith® [Tab]
Lalithium-XR (400mg)
Lithoset (400mg)
Intalith® [Tab]
Alkalith Cr® [Tab]
https://www.medindia.net/drug-price/lithium.htm

10. DOSAGE FORMS
• Lithium preparations:
Lithium carbonate capsules: 150, 300, 600 mg
Lithium carbonate tablets: 300 mg
Lithium carbonate controlled-release tablets: 450 mg
Lithium carbonate slow-release tablets: 300 mg
Lithium citrate syrup : 8 mEq/5 mL
https://www.medindia.net/drug-price/lithium.htm

11. DOSAGE RANGE
Eskalith (Lithium) [Prescribing Information] Research Triangle Park, NC: GSK, Inc. Accessed November 2014

12. Pharmacokinetic profile
• Half life- 18-24hrs
• Lithium is readily absorbed with peak plasma levels occurring 2-4
hours after a single oral dose of lithium carbonate
• Lithium is distributed rapidly in liver, kidney, muscle, bone and brain.
• Elimination is predominantly 95% via kidneys and is influenced by
sodium balance.
• Depletion of sodium can precipitate lithium toxicity
Ward ME, Musa MN, Bailey L. Clinical pharmacokinetics of lithium. J Clin Pharmacol. 1994 Apr;34(4):280-5. doi: 10.1002/j.1552-4604.1994.tb01994.x. PMID: 8006194.

13. Dose dependent effects
The plasma concentration-response relationship derived on the basis of
the 12-hour standardized lithium level:
• <0.4 mmol/L: little therapeutic effect
• 0.4-1.0 mmol/L: optimum range for prophylaxis
• 0.8-1.2 mmol/L: Optimum range for acute mania
• 1.2-1.5 mmol/L: Causes renal impairment
• 1.5-3.0 mmol/L: Causes renal impairment, ataxia, weakness, drowsiness,
thirst, diarrhea
• >3.0 mmol/L: Causes confusion, spasticity, dehydration, convulsions,
coma, death (>3.5 mmol/L: Medical emergency)
Ward ME, Musa MN, Bailey L. Clinical pharmacokinetics of lithium. J Clin Pharmacol. 1994 Apr;34(4):280-5. doi: 10.1002/j.1552-4604.1994.tb01994.x. PMID: 8006194.

14. FACTORS AFFECTING SERUM DRUG CONCENTRATION OF LITHIUM
• Diuretics, dehydration, febrile illness, or gastrointestinal loss can lead
to elevated lithium levels in the serum
• The following medications may decrease the levels and effect of
lithium: Caffeine, Sodium chloride.
• A medication used to treat breathing problems called theophylline
Ward ME, Musa MN, Bailey L. Clinical pharmacokinetics of lithium. J Clin Pharmacol. 1994 Apr;34(4):280-5. doi: 10.1002/j.1552-4604.1994.tb01994.x. PMID: 8006194.

15. Ward ME, Musa MN, Bailey L. Clinical pharmacokinetics of lithium. J Clin Pharmacol. 1994 Apr;34(4):280-5. doi: 10.1002/j.1552-4604.1994.tb01994.x. PMID: 8006194.

16. https://www.slideshare.net/ramesh_2417/tdm-of-psychiatric-drugs

17. DRUG INTERACTIONS
• Diuretics - Diuretic induced sodium loss may reduce the renal clearance of
lithium and cause lithium toxicity.
• NSAIDS - NSAIDs may increase lithium levels in the body.
• ACE Inhibitors - Medications for high blood pressure can increase lithium
levels in the body.
• Calcium Channel Blockers - Increased risk of neurotoxicity in the form of
ataxia, tremors, nausea, vomiting, diarrhea.

18. CONTRAINDICATIONS
• Cardiovascular disease, significant high risk of lithium toxicity -
treatment is required, monitoring in a hospital setting is necessary
• Use of diuretics
• Dehydration
• Renal disease
• Sodium depletion

19. ADVERSE EFFECTS
Dose-related
Therapeutic levels
nausea, diarrhea, polyuria, polydipsia, cognitive impairment, fine hand
tremor, muscle weakness.
Signs of toxicity
coarse hand tremor, persistent nausea, diarrhea, slurred speech,
confusion, seizures, increased deep tendon reflexes.
Non dose-related
Irregular pulse, hypotension, coma nephrogenic diabetes insipidus,
goiter, hypothyroidism, hypercalcemia, weight gain, macropapular or
acneiform reactions, benign leukocytosis

20. SERUM LEVEL MONITORING
• Concentrations considered to be effective and acceptable safe are
between 0.6 and 1.25 mEq per liter.
• The range of 0.9 to 1.1 mEq per liter is favored for treatment of
acutely manic or hypomanic patients.
• Somewhat lower values (0.6 to 0.75 mEq per liter) are considered
adequate and are safer for long-term use for prevention of recurrent
manic-depressive illness.
• The recommended concentration usually is attained by doses of 900
to 1500 mg of lithium carbonate per day in outpatients and 1200 to
2400 mg per day in hospitalized manic patients.
https://www.slideshare.net/BasilWilson7/lithium-87865698

21. APPROPRIATE SAMPLING TIME
• Blood samples should be drawn 12 hours after the evening dose,
because this will allow for distribution and represent the slowest
excretion rate.
• In general, lithium concentration should be determined 3-7 days after
therapy has started.
• In acute mania, initial 12 hour lithium concentration is monitored
once or twice weekly until the desired therapeutic concentration
achieved.

22. THANK YOU