Mood stabilizers: WPA update

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New updates in the concept and clinical usage of "mood stabilizers" based on the new report of WPA section on pharmacopsychiatry, June 2012.
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  • *Any pharmacologic agent with evidence of efficacy in at least one area of bipolar disorder management (acute depression, acute hypomania, acute mania/mixed, or maintenance) and no evidence suggesting that it is associated with increased risk of mood switching or cycle acceleration.†Any drug that meets the definition of PMS, with its primary therapeutic activity being one-directional—either effectively treating depression or hypomania/mania/mixed episodes.††Any drug that meets the definition of PMS, with its primary therapeutic activity being two-directional—both effectively treating depression and hypomania, mania, or mixed episodes. A bidirectional PMS has not demonstrated full maintenance efficacy.§Any drug that meets the definition of PMS, with its primary therapeutic activity being maintenance efficacy. An intermediate PMS has no established acute efficacy. ¶Any drug that meets the definition of PMS and has unidirectional or bidirectional mood stabilizing properties and only partial maintenance efficacy. Alternatively, maintenance efficacy plus unidirectionalefficacy.
  • Randomized, placebo-controlled trials have demonstrated the efficacy of all five second-generation atypical antipsychotics (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole) and led to their US FDA approval for the management of acute bipolar mania with or without psychotic features. With the exception of quetiapine, they are all approved for mixed states in bipolar disorder.
  • cycle acceleration“switching”“protected” antidepressants
  • Bullet combos for bipolar depression. Experts diverge in their opinions of how to treat bipolardepression, particularly when it comes to antidepressants. Some believe that even when combination treatment i*required, it should never involve use of an antidepressant (Boston bipolar brew), while others recommendcautious addition of an antidepressant to one or more mood stabilizers (California careful cocktail). For patientswho develop symptoms of activation during treatment with an antidepressant for unipolar depression, someexperts suggest adding an atypical antipsychotic rather than discontinuing the antidepressant (Tennessee moodshine). Another school of thought (Buckeye bipolar bullets) focuses on lamotrigine as the primary treatment forbipolar depression, with augmentation of other mood stabilizers (as opposed to antidepressants) whenlamotriginemonotherapy is not enough. Lamotrigine may be considered a "stealth treatment," as it must betitrated slowly and can have a long latency of onset of action. Reasonable augmenting agents would include anatypical antipsychotic, particularly quetiapine (lami-quel). Quetiapine itself is an established monotherapy forbipolar depression and can be combined with many other agents as well (quel-kit). Another potential agent toadd to lamotrigine, quetiapine, or lamotrigine and quetiapine is modafinil, particularly for patients with daytimesleepiness (modafinil combo). If none of these combinations produce a good response, one may consider addingan antidepressant to lamotrigine/quetiapine (reluctant combo).
  • Atypical combos. Any combination containing the partial dopamine agonist aripiprazole may bereferred to as an "able stabilizer," while any combination containing the serotonin dopamine antagonistziprasidone may be collectively termed a "Walt Disney." These include ziprasidone plus lithium (zipa-li),ziprasidone plus lamotrigine (zipa-la), ziprasidone plus Depakote (zipa-do), and ziprasidone plus lithium,lamotrigine, and Depakote (zipa-li-do-la). California sunshine is a powerful combination for bipolar depressionwith full-dose ziprasidone and full-dose lithium as well as augmentation with either transdermalselegiline orhigh-dose venlafaxine.
  • Mood stabilizers: WPA update

    1. 1. Class A Class BStahl M: Stahls essential psychopharmacology : ncuroscientific basis and practical applications. 3rd ed,2008. Cambridge University Press Mood stabilizers: update Cairo, June 2012 2
    2. 2. Mania DepressionAcute Lithium Lithium ECT ECT Carbamazepine Olanzapine Divalproex Quetiapine Chlorpromazine Valproate Haloperidol Lamotrigine (practical difficulty) Risperidone Olanzapine Quetiapine Ziprasidone Aripiprazole Clonazepam Verapamil ClonidineMaitenance Lithium Lithium ECT ECT(Prophylaxis) Carbamazepine Lamotrigine Valproate Olanzapine Lamotrigine Quetiapine Olanzapine Aripiprazole Nimodipine Mood stabilizers: update Cairo, June 2012 3
    3. 3. Muzina D, et al: Mood Stabilizers. In: Tasman A, et al (eds): Psychiatry, 3rd ed, 2008. John Wiley & Sons, Ltd. Mood stabilizers: update Cairo, June 2012 4
    4. 4. Mood stabilizers: update Cairo, June 2012 5
    5. 5.  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.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. Mood stabilizers: update Cairo, June 2012 6
    6. 6. Mania DepressionAcute •Haloperidol → lithium - Lamotrigine + Lithium •Carbamazepine → lithium -Olanzapine (or •Phenytoin → haloperidol olanzapine and fluoxetine, •Divalproex → neuroleptic OFC) → lithium, •Olanzapine → lithium or anticonvulsants and/or divalproex neuroleptics •Risperidone or haloperidol -Pramipexole → lithium or → lithium or divalproex divalproex (BPD-II) •Quetiapine → lithium or - divalproexMaitenance - Imipramine → lithium(Prophylaxis) - 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 Cairo, June 2012 7
    7. 7. Stahl M: Stahls essential psychopharmacology : ncuroscientific basis and practical applications. 3rd ed, 2008. Cambridge University Press Mood stabilizers: update Cairo, June 2012 8
    8. 8. Stahl M: Stahls essential psychopharmacology : ncuroscientific basis and practical applications. 3rd ed, 2008. Cambridge University Press Mood stabilizers: update Cairo, June 2012 9
    9. 9. Stahl M: Stahls essential psychopharmacology : ncuroscientific basis and practical applications. 3rd ed, 2008. Cambridge University Press Mood stabilizers: update Cairo, June 2012 10
    10. 10. Stahl M: Stahls essential psychopharmacology : ncuroscientific basis and practical applications. 3rd ed, 2008. Cambridge University Press Mood stabilizers: update Cairo, June 2012 11
    11. 11. Stahl M: Stahls essential psychopharmacology : ncuroscientific basis and practical applications. 3rd ed, 2008. Cambridge University Press Mood stabilizers: update Cairo, June 2012 12
    12. 12. Stahl M: Stahls essential psychopharmacology : ncuroscientific basis and practical applications. 3rd ed, 2008. Cambridge University Press Mood stabilizers: update Cairo, June 2012 13
    13. 13.  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 RCBDMuzina D, et al: Mood Stabilizers. In: Tasman A, et al (eds): Psychiatry, 3rd ed, 2008. John Wiley & Sons, Ltd. Mood stabilizers: update Cairo, June 2012 14
    14. 14.  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.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. Mood stabilizers: update Cairo, June 2012 15
    15. 15. Stahl M: Stahls essential psychopharmacology : ncuroscientific basis and practical applications. 3rd ed, 2008. Cambridge University Press Mood stabilizers: update Cairo, June 2012 16
    16. 16.  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 depressionAmann 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. Mood stabilizers: update Cairo, June 2012 17

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