1. Copyright Notice
This presentation is copyrighted by the Psychopharmacology Institute.
Subscribers can download it and use it for professional use.
The contents of the presentation may be modified, but the Psychopharmacology Institute logo must remain visible in all slides.

2. Use of Mood Stabilizers in Treatment-Resistant Depression
Prof. Philip Cowen
Professor of Psychopharmacology
Department of Psychiatry
University of Oxford, UK

3. Lithium + Antidepressant Treatment

4. Lithium + Antidepressant Treatment
Small number of patients assessed:
Less than 250
Evidence base: less than with atypicals
Nelson JC, Baumann P, Delucchi K, Joffe R, Katona C (2014). A systematic review and meta-analysis of lithium augmentation in tricyclic and second generation antidepressants in major depression. Journal of Affective Disorders 156, 269–75.

5. Lithium + Antidepressant Treatment
Small number of patients assessed:
Less than 250
Evidence base: less than with atypicals
Less popular treatment
Need for blood tests and continual monitoring
Nelson JC, Baumann P, Delucchi K, Joffe R, Katona C (2014). A systematic review and meta-analysis of lithium augmentation in tricyclic and second generation antidepressants in major depression. Journal of Affective Disorders 156, 269–75.

6. Lithium + Antidepressant Treatment
Small number of patients assessed:
Less than 250
Evidence base: less than with atypicals
Less popular treatment
Need for blood tests and continual monitoring
Patients:
“It’s a dangerous drug”
“It’s used to treat very severe mental illness”
Reluctance to take it

7. Lithium + Antidepressant Treatment
Meta-analyses
Effective treatment
NNT: 4-5

8. Lithium + Antidepressant Treatment
Meta-analyses
Effective treatment
NNT: 4-5
Suicidal behavior
Cipriani A, Hawton K, Stockton S, Geddes JR (2013). Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. British Medical Journal 346, f3646.

9. Lithium + Antidepressant Treatment
Meta-analyses
Effective treatment
NNT: 4-5
Suicidal behavior
Lowers risk of suicide and suicidal behavior
Cipriani A, Hawton K, Stockton S, Geddes JR (2013). Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. British Medical Journal 346, f3646.

10. Lithium + Antidepressant Treatment
Meta-analyses
Effective treatment
NNT: 4-5
Suicidal behavior
Lowers risk of suicide and suicidal behavior
Dosing and plasma levels

11. Lithium + Antidepressant Treatment
Meta-analyses
Effective treatment
NNT: 4-5
Suicidal behavior
Lowers risk of suicide and suicidal behavior
Dosing and plasma levels
Lower doses than in bipolar disorder
mmol/L

12. Lithium + Antidepressant Treatment
Meta-analyses
Effective treatment
NNT: 4-5
Suicidal behavior
Lowers risk of suicide and suicidal behavior
Dosing and plasma levels
Lower doses than in bipolar disorder
mmol/L
Lithium vs QTP:
Best results at plasma levels of 0.6 mmol/L and above
Bauer M, Dell'Osso L, Kasper S, Pitchot W, Vansvik ED, Köhler J, Jørgensen L, Montgomery SA. Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder. Journal of affective disorders Oct 31;151(1):

13. Lithium + Antidepressant Treatment
Meta-analyses
Effective treatment
NNT: 4-5
Suicidal behavior
Lowers risk of suicide and suicidal behavior
Dosing and plasma levels
Lower doses than in bipolar disorder
mmol/L
Lithium vs QTP:
Best results at plasma levels of 0.6 mmol/L and above
Effectiveness vs side effects
Bauer M, Dell'Osso L, Kasper S, Pitchot W, Vansvik ED, Köhler J, Jørgensen L, Montgomery SA. Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder. Journal of affective disorders Oct 31;151(1):

15. Bipolar depression (BD I and BD II): evidence of efficacy
Lamotrigine
Bipolar depression (BD I and BD II): evidence of efficacy
Vázquez GH, Tondo L, Undurraga J, et al (2014) Pharmacological treatment of bipolar depression. Advances in Psychiatric Treatment, 20: 193–201.

16. Lamotrigine Bipolar depression (BD I and BD II): evidence of efficacy
Unipolar depression: not very helpful
Barbee JG, Thompson TR, Jamhour NJ, et al (2011) A double-blind placebo-controlled trial of lamotrigine as an antidepressant augmentation agent in treatment-refractory unipolar depression. Journal of Clinical Psychiatry, 72: 1405–12.

17. Unipolar or Bipolar Depression?
Some TRD patients: bipolar spectrum features

18. Unipolar or Bipolar Depression?
Not hypomanic or manic according to DSM criteria
Brief spells of hypomania
Family history of bipolar disorder
Subthreshold criteria for hypomania
Some TRD patients: bipolar spectrum features

19. Unipolar or Bipolar Depression?
MDQ (Mood Disorder Questionnaire): helpful in differential diagnosis
Not hypomanic or manic according to DSM criteria
Brief spells of hypomania
Family history of bipolar disorder
Subthreshold criteria for hypomania
Some TRD patients: bipolar spectrum features
Francesca MM, Efisia LM, Alessandra GM, Marianna A, Giovanni CM. Misdiagnosed hypomanic symptoms in patients with treatment-resistant major depressive disorder in Italy: results from the improve study. Clinical practice and epidemiology in mental health: CP & EMH. 2014;10:42.

20. Unipolar or Bipolar Depression?
Some TRD patients: bipolar spectrum features
Not hypomanic or manic according to DSM criteria
Brief spells of hypomania
Family history of bipolar disorder
Subthreshold criteria for hypomania
MDQ (Mood Disorder Questionnaire): helpful in differential diagnosis
Unclear if they should be treated as bipolar depression

21. Unipolar or Bipolar Depression?
Unclear if they should be treated as bipolar depression
Lamotrigine or quetiapine if they don’t respond?
MDQ (Mood Disorder Questionnaire): helpful in differential diagnosis
Not hypomanic or manic according to DSM criteria
Brief spells of hypomania
Family history of bipolar disorder
Subthreshold criteria for hypomania
Some TRD patients: bipolar spectrum features

22. Next Presentation- Use of Stimulants and Dopamine Agonists: Methylphenidate, Amphetamines and Pramipexole