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

Lithium + Antidepressant Treatment

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.

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.

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

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

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.

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.

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

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 0.4-0.6 mmol/L

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 0.4-0.6 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. 2013 Oct 31;151(1):209-19.

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 0.4-0.6 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. 2013 Oct 31;151(1):209-19.

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.

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.

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

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

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.

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

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

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