1. Lithium: Clinical Uses and Pharmacokinetics
Flavio Guzman, MD

2. Indications

3. Lithium indications FDA-approved: Evidence of effectiveness:
Bipolar disorder: manic episodes
Bipolar disorder: maintenance treatment
Evidence of effectiveness:
Bipolar depression
Unipolar depression (as adjunctive)

4. Lithium in mania Pros: More efficacious than placebo
FDA-approved for mania
Lithium monotherapy: first line option
Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3),

5. Lithium in mania Cons: Mixed mania: poor response
Relatively slow onset of action
Clinical improvement usually seen after days of treatment
Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3),

6. Lithium in mania
Lithium is often used in combination with an antipsychotic or benzodiazepine
Lithium + AP: better in combination than monotherapy of either agent
Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3),

7. Lithium in bipolar depression
Evidence: small RCTs
6-8 weeks to take effect
Clinical guidelines (APA, NICE):
Lithium monotherapy: recommended first line
Consider adding:
SGA
Antidepressant
Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3),

8. Lithium as maintenance treatment
Effective in prophylaxis of:
Manic episodes
Depressive episodes
Effective in prophylaxis of:
Suicidal behavior
Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3),

9. Lithium as maintenance treatment
Effect in preventing mania is more pronounced than for depression
Abrupt cessation:
Recurrence of symptoms
Taper lithium slowly (monthly 300 mg) decrements
Geddes, J. R.,et al (2004). Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials. American Journal of Psychiatry, 161(2),
Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3),

10. Lithium as maintenance treatment
Patients with rapid cycling generally do less well than patient with less frequent episodes
Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3),

11. Lithium for bipolar disorder: summary
Efficacious for:
Mania
Bipolar depression
Prophylaxis (maintenance)
Reduces suicidal behavior

12. Lithium for unipolar depressionAD
AD + Lithium
Lithium augmentation: first line for treatment-resistant depression
Depression not responding to AD
Gitlin, M. Unipolar depression in adults: Treatment with lithium. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed August 2014)

13. Lithium for unipolar depressionAD
AD + Lithium
Most trials involved tricyclics
Further research needed on the role of role of lithium in combination with other antidepressants
Depression not responding to AD
Gitlin, M. Unipolar depression in adults: Treatment with lithium. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed August 2014)

14. Lithium for unipolar depressionAD
AD + Lithium
Limited data suggests lithium is comparable to T3 or a second antidepressant
Depression not responding to AD
Gitlin, M. Unipolar depression in adults: Treatment with lithium. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed August 2014)

15. Lithium for unipolar depressionAD
AD + Lithium
Lithium augmentation may reduce the risk of completed suicide in patients with unipolar depression
Gitlin, M. Unipolar depression in adults: Treatment with lithium. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed August 2014)

16. Lithium for aggression
Effective for aggressive behavior
Mental retardation
Prison populations
Schatzberg, AF, Nemeroff CB. Essentials of Clinical Psychopharmacology 3rd ed.American Psychiatric Publishing, 2013

17. Lithium for schizoaffective disorder
Not approved by the FDA
Of value in combination with antipsychotics
Useful when affective component is prominent

18. Pharmacokinetics

19. Lithium Pharmacokinetics
Absorbed from the GI tract
Peak plasma concentration
1-2 hours with standard preparations
4 – 5 hours with slow and controlled release formulations
No metabolites
No protein binding
Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3),

20. Lithium Pharmacokinetics
Excreted almost entirely by the kidneys
Assess renal function
Elimination half-life:
18-24 hours
Sensitive to glomerular filtration rate
Steady state concentrations achieved within 4-5 days
Malhi, G. S., Tanious, M., Das, P., & Berk, M. (2012). The science and practice of lithium therapy. Australian and New Zealand journal of psychiatry,46(3),

21. End of presentation