Lithium: Clinical Uses and Pharmacokinetics Flavio Guzman, MD

Indications

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

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), 192-211.

Lithium in mania Cons: Mixed mania: poor response Relatively slow onset of action Clinical improvement usually seen after 6- 10 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), 192-211.

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), 192-211.

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), 192-211.

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), 192-211.

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), 217-222. 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), 192-211.

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), 192-211.

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

Lithium for unipolar depression AD 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)

Lithium for unipolar depression AD 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)

Lithium for unipolar depression AD 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)

Lithium for unipolar depression AD 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)

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

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

Pharmacokinetics

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), 192-211.

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), 192-211.

End of presentation