1. Prescribing lithium safely: side effects
Flavio Guzman, MD

2. Overview

3. Side effects: classification
Lithium toxicity
Long-term
Short-term (Acute)

4. Acute side effects

5. Acute side effects
Within the first 5 days of starting lithium treatment
Some of them are dose-related
Transitory nature
Ferrier, I. N., S. P. Tyrer, and A. J. Bell. "Lithium therapy." Advances in Psychiatric Treatment 1.4 (1995):

6. Acute side effects Gastrointestinal: Metallic taste CNS:
Abdominal discomfort
Diarrhea
Nausea
Metallic taste
CNS:
Fine tremor
Cognitive dulling
Dysarthria
Janicak, P. Bipolar disorder in adults and lithium: Pharmacology, administration, and side effects.In: UpToDate, Keck, P , UpToDate, Waltham, MA

7. Acute renal side effects
Renal: difficulty concentrating urine
Lithium inhibits the effects of ADH
ADH promotes the expression of aquaporin channels
McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817),

8. H20
H20
H20
H20
H20

9. H20
H20
H20
H20
H20
H20

10. Acute renal side effects
Thirst
Polydipsia
Polyuria

11. Acute renal side effects
Thirst
Polydipsia
Polyuria
Reversible
Complications avoided by maintaining an adequate fluid and salt intake
Janicak, P. Bipolar disorder in adults and lithium: Pharmacology, administration, and side effects.In: UpToDate, Keck, P , UpToDate, Waltham, MA

12. Acute side effects: clinical considerations
Dose related:
Nausea
Tremor
Cognitive dulling
May diminish
Dose reduction
Dividing the daily dose
Janicak, P. Bipolar disorder in adults and lithium: Pharmacology, administration, and side effects.In: UpToDate, Keck, P , UpToDate, Waltham, MA

13. Long-term effects

14. Renal: GFR, urine concentration
Long-term effects
Renal: GFR, urine concentration
Hypothyroidism
Hyperparathyroidism
Weight gain
Other:
Cardiac (ECG changes)
Dermatologic

15. Renal effects of lithium
Glomerular filtration rate is impaired with lithium therapy
Impairment is not clinically significant in most patients
McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817),

16. Renal effects of lithium
Risk of end-stage renal failure
Increased, but absolute risk is very low
Risk of end-stage renal failure
Healthy controls
Bipolar patients on lithium
0.2 %
0.53 %
McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817),

17. Renal effects of lithium
In most patients the trajectory of decrease of GFR is similar to that associated with ageing
Diabetes more common in bipolar patients
McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817),

18. Hypothyroidism 8 - 19% of patients on lithium Especially in:
Women
Elderly
Most patients are asymptomatic: biochemical diagnosis
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),

19. Thyroid 4 potential negative effects on thyroid function:
Inhibition of iodine uptake
Inhibition of iodotyrosine coupling
Alteration in thyroglobulin structure
Inhibition of thyroxine secretion
4 potential negative effects on thyroid function:
McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817),

20. Thyroid - UTD T3 I- T4

21. Thyroid - UTD T3 I- T4

22. Parathyroid – Primary hyperparathyroidism
Frequent finding
Lithium: absolute risk 10%
General population 0.1%
PTH
Ca++
McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817),

23. Thyroid and Parathyroid
Thyroid and parathyroid abnormalities occur in about 25% of patients receiving lithium therapy
Guidelines for bipolar disorder make no mention of monitoring of calcium.
McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817),

24. Weight gain
Long-term treatment with lithium results in noticeable weight gain
Reported by 5% or more of patients
Important cause of nonadherence
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),

25. Weight gain
Increase of 1-2 kg over the first 12 weeks of treatment is common
In some patients this increase may continue
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),

26. Weight gain Important to anticipate weight gain:
Preventive lifestyle changes: diet and exercise
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),

27. Weight gain – Factors Stimulation of hypothalamic center
Hypothyroidism
Increased thirst
Insulin-like properties
Weight gain
McKnight, R. F., Adida, M., Budge, K., Stockton, S., Goodwin, G. M., & Geddes, J. R. (2012). Lithium toxicity profile: a systematic review and meta-analysis. The Lancet, 379(9817),

28. Fine Tremor Relatively common It occurs at therapeutic levels
Common cause of treatment discontinuation
Image credit: University of Miami
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),

29. Flapping or coarse tremor
Fine Tremor
Fine tremor
Flapping or coarse tremor
Image credit: University of Miami
Malhi

30. Cardiac effects ECG changes QTc interval prolongation
Increased PR interval duration
Diffuse T-wave inversion
Synus bradycardia
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),

31. Cardiac effects
Most changes are reversible (disappear when lithium is withdrawn)
Rarely may precipitate clinically significant arrhythmias
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),

32. Dermatologic side effects
Acne
Psoriasis
Exacerbation of pre-existing psoriasis
Induction of new lesions
Kim, Grace K., and James Q. Del Rosso. "Drug-provoked psoriasis: is it drug induced or drug aggravated?: understanding pathophysiology and clinical relevance." The Journal of clinical and aesthetic dermatology 3.1 (2010): 32.

33. End of presentation