Mood stabilizers: WPA update

Mood stabilizers: updateAhmed el-Aghoury

Specialist psychiatrist at Abbassia HospitalEgyptian & Arab Board certified

Cairo, June 2012

Mood stabilizers: update 2

WHAT IS A M

OOD STABILIZER? Stahl M: Stahl's essential psychopharmacology : ncuroscientific basis and practical applications. 3rd ed, 2008. Cambridge University Press

Cairo, June 2012

Class A

Class B


Mood Stabilizers: The “2 × 2” DefinitionBauer M: Mood Disorders: Bipolar (Manic–Depressive) Disorders. In: Tasman A, et al (eds): Psychiatry, 3rd ed, 2008. John Wiley & Sons, Ltd.

Mania DepressionAcute Lithium

ECTCarbamazepineDivalproexChlorpromazineHaloperidol RisperidoneOlanzapineQuetiapineZiprasidoneAripiprazoleClonazepamVerapamilClonidine

LithiumECTOlanzapineQuetiapineValproateLamotrigine (practical difficulty)

Maitenance(Prophylaxis)

LithiumECTCarbamazepineValproateLamotrigineOlanzapineAripiprazoleNimodipine

LithiumECTLamotrigineOlanzapineQuetiapine

Cairo, June 2012


Redefining Mood Stabilizers: Partial Mood Stabilizers (PMS)

Cairo, June 2012

Muzina D, et al: Mood Stabilizers. In: Tasman A, et al (eds): Psychiatry, 3rd ed, 2008. John Wiley & Sons, Ltd.


Approved Medications in the US for Bipolar DisorderMuzina D, et al: Mood Stabilizers. In: Tasman A, et al (eds): Psychiatry, 3rd ed, 2008. John Wiley & Sons, Ltd.

Cairo, June 2012


WPA Report, 2012 Lithium, first and second generation antipsychotics and valproate

and carbamazepine are efficacious in the treatment of acute mania. Quetiapine and the olanzapine-fluoxetine combination are

efficacious for treating bipolar depression The combination with best data in acute bipolar depression is

lithium plus lamotrigine. Lamotrigine is efficacious in the prevention of depression, and it

remains to be clarified whether it is also efficacious for mania. Antidepressants should only be used in combination with an

antimanic agent, because they can induce switching to mania / hypomania / mixed states/rapid cycling when utilized as monotherapy.

Lithium, olanzapine, quetiapine and aripiprazole are efficacious during the maintenance phase.

Electroconvulsive therapy is an option for refractory patients.

Cairo, June 2012

Fountoulakis KN, et al: Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry. Eur Arch Psychiatry Clin Neurosci. 2012 Jun;262 Suppl 1:1-48. PubMed PMID: 22622948.


Combination strategiesBauer M: Mood Disorders: Bipolar (Manic–Depressive) Disorders. In: Tasman A, et al (eds): Psychiatry, 3rd ed, 2008. John Wiley & Sons, Ltd.

Cairo, June 2012

Mania DepressionAcute •Haloperidol → lithium

•Carbamazepine → lithium •Phenytoin → haloperidol •Divalproex → neuroleptic •Olanzapine → lithium or divalproex •Risperidone or haloperidol → lithium or divalproex•Quetiapine → lithium or divalproex

- Lamotrigine + Lithium-Olanzapine (or olanzapine and fluoxetine, OFC) → lithium, anticonvulsants and/or neuroleptics-Pramipexole → lithium or divalproex (BPD-II)-

Maitenance(Prophylaxis)

- Imipramine → lithium- High-dose thyroxine → treatment as usual (in rapid cycling)- Divalproex → lithium- Magnesium → verapamil.- Omega-3 fatty acids → treatment as usual- Gabapentin → lithium or divalproex or Carbamazepine

Mood stabilizers: update 8Cairo, June 2012

Stahl M: Stahl's essential psychopharmacology : ncuroscientific basis and practical applications. 3rd ed, 2008. Cambridge University Press












Mood Stabilizers for Rapid Cycling Bipolar Disorder (RCBD)

Frequently (≥ 4 / y) RECURRING & REFRACTORY depressive episodes appear to be a “hallmark” of RCBD and may be exacerbated (cycle induction or acceleration) by antidepressant use. Up to 15 % of BP pts, esp in females (80%)

Lithium, divalproex, lamotrigine, and the atypical antipsychotics are the current mainstays of treatment.

Combination strategies are most often necessary. Thyroid hormone augmentation may also be of

great benefit for some patients with RCBDCairo, June 2012

Muzina D, et al: Mood Stabilizers. In: Tasman A, et al (eds): Psychiatry, 3rd ed, 2008. John Wiley & Sons, Ltd.


AEDs are Mood stabilizers? CBZ & VPA: best evidence, monotherapy / in combination

esp Mania, both acute and maitenance LMT & PHT: evolving evidence, but in combination Others: poor evidence Current evidence supports the use of divalproex

and lamotrigine in the treatment of acute bipolar depression

Anticonvulsants are not a class when treating mania. While valproate and carbamazepine are significantly more effective than placebo, gabapentin, topiramate, and lamotrigine are not.

Cairo, June 2012

Reinares M, et al: A systematic review on the role of anticonvulsants in the treatment of acute bipolar depression. Int J Neuropsychopharmacol. 2012 May 10:1-12. PubMed PMID: 22575611.Rosa AR, et al. Is anticonvulsant treatment of mania a class effect? Data from randomized clinical trials. CNS Neurosci Ther. 2011 Jun;17(3):167-77. Epub 2009 Dec 15. Review. PubMed PMID: 20015083.


Anti-Kindling

Cairo, June 2012



Lamotrigine as a mood stabilizer

Approved for BP maitenance therapy esp BP depression (FDA)

LMT + Li: acute BP depression (WPA) Add-on LMT: maitenance (WPA) NO grounds for recommending its use

in manic or mixed states, in rapidly-cycling bipolar I or in unipolar depression

Cairo, June 2012

Amann B, et al. Lamotrigine: when and where does it act in affective disorders? A systematic review. J Psychopharmacol. 2011 Oct;25(10):1289-94. Epub 2010 Sep 7. Review. PubMed PMID: 20823080.

Health & Medicine

Mood stabilizers: WPA update