Practical Guide to Long-Term Pharmacotherapy in Bipolar Disorder: An Updated Synthesis of Current Clinical Guidelines

Transcription

1 SECOND-GENERATION ANTIPSYCHOTICS IN BIPOLAR DISORDER Practical Guide to Long-Term Pharmacotherapy in Bipolar Disorder: An Updated Synthesis of Current s Flavio Guzman, MD Editor Psychopharmacology Institute About this guide: This guide reviews key data for the safe and effective prescription of drugs in the long-term treatment of bipolar disorder. All drugs are presented using the same format: evidence of efficacy, disadvantages and place in clinical guidelines. For some drugs we have included an additional section titled comments. Remember that clinical guidelines have their limitations and they are not a replacement for clinical judgment..1

2 An Updated Synthesis of Current s The guidelines summarized are the following: : Group: World Federation of Societies of Biological Psychiatry Guideline title:the World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2012 on the long-term treatment of bipolar disorder Year updated: 2012 : Group: Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) Guideline title: Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013 Year updated: 2013 : Group: National Institute for Health and Care Excellence (NICE) Guideline title: Bipolar disorder: the assessment and management of bipolar disorder in adults, children and young people in primary and secondary care Year updated: 2014 : Group: British Association for Psychopharmacology Guideline title: Evidence-based guidelines for treating bipolar disorder: Revised third edition recommendations from the British Association for Psychopharmacology Year updated:

3 An Updated Synthesis of Current s Table of contents 03. Table of contents 04. Before You Read the Evidence: A Warning About Enriched Study Designs 05. A Summary of Drugs Used to Prevent Mood Episodes 05. Lithium 06. Lamotrigine 07. Valproate 08. Olanzapine 09. Quetiapine 10. Risperidone LAI 11. Aripiprazole 12. Ziprasidone 13. Carbamazepine 14. References.3

4 An Updated Synthesis of Current s Before You Read the Evidence: A Warning About Enriched Study Designs When interpreting the evidence derived from maintenance studies there is something important to consider: clinical trials often use enriched patient samples. There are two types of maintenance study designs: prophylaxis and relapse prevention [1]. Prophylaxis design: All comers are included in the study. Any patient who is euthymic, no matter how that person got well, is eligible to be randomized to drug versus placebo or control. Relapse prevention design: Only those patients who acutely respond to the drug being studied are then eligible to enter the maintenance phase, which is when the study begins. Those who responded to the drug are then randomized to stay on the drug or be switched to placebo or control. Most maintenance trials studying second-generation antipsychotics enroll individuals who have recently recovered from mania (relapse prevention). This enriched enrolled population has a greater proclivity toward manic recurrence than depressive recurrence. Only quetiapine and lamotrigine have been studied for individuals recovering from a depressive episode..4

5 An Updated Synthesis of Current s A Summary of Drugs Used to Prevent Mood Episodes Lithium Lithium is considered the gold standard for long-term maintenance therapy in bipolar disorder [2] It is the only mood stabilizer effective at reducing the risk of suicide [3] Monotherapy is ideal but often not adequate, and lithium can often be successfully combined with other adjunctive drugs such as lamotrigine or quetiapine [4] Several lines of evidence suggest that the benefit with lithium is greater for the prevention of manic episodes than it is for preventing depressive symptomatology[5] Tolerability There is a high risk of recurrence on abrupt cessation [6] Place in s Recommendation grade of 1 (best grade). First-line treatment. First-line treatment. quis enim. First-line Donec treatment. pede justo, Comments Patients should not be deprived of lithium without a specific reason Side effects and risks are manageable if both the physician and the patient are well informed For patients who do not respond sufficiently to lithium, have contraindications or non-tolerable side effects, other mood stabilizers should be used Once-daily dosing at bedtime is better for treatment adherence (twice daily dosing gives sustained higher minimum concentrations, this has been linked to more pathological renal changes on biopsy).5

6 An Updated Synthesis of Current s Lamotrigine Lamotrigine is most effective as a bipolar maintenance agent in patients who experience depressivedominant bipolar disorder [7] May be appropriate for non-classic cases with mixed features or rapid cycling [8] Slow titration (6 weeks) needed to decrease the risk of Stevens-Johnson syndrome Dose adjustment necessary if used in combination with valproate or carbamazepine Place in s Recommendation grade of 1 (best grade), for patients tolerating lamotrigine where the predominant treatment goal is to prevent depressive recurrences or any episode. First-line treatment (limited efficacy in preventing mania). No specific mention to lamotrigine in long-term treatment. - Consider adding lamotrigine in depression-predominant bipolar disorder if lithium alone is ineffective. - Consider lamotrigine as monotherapy in bipolar II disorder when depression is the major burden..6

7 An Updated Synthesis of Current s Valproate While valproate has reported empirical efficacy, only a few trials support its long-term use A recent review suggested that valproate may have superior tolerability compared to lithium for some patients [9] About the BALANCE study [10]: Results Lithium was superior to valproate. The combination of lithium and valproate was more effective than valproate monotherapy in preventing depressive recurrences. Comments This study had a methodological limitation: an open design The results show the importance of combination treatment in some patients Should be avoided during pregnancy due to teratogenicity risk Should not usually be considered for women of child-bearing potential [11] Place in s Recommendation grade of 3 (1 is the best), limited positive evidence from controlled studies. First-line treatment. - No longer recommended as first-line treatment. - The updated guidelines recommend valproate as second-line treatment if lithium is poorly tolerated or unsuitable. If lithium alone is ineffective, consider combination treatment with valproate. If lithium is poorly tolerated or unsuitable, consider valproate among other options..7

8 An Updated Synthesis of Current s Olanzapine Meta-analysis of five RCTs by Cipriani and cols [12] : Results: Olanzapine was effective as adjunct to lithium or valproate in preventing manic, but not composite outcomes of all mood episodes Comments: Olanzapine may prevent further manic episodes only in patients who have responded to olanzapine in an acute manic or mixed episode and who had not previously responded to lithium or valproate Risk of metabolic side effects: weight gain, increased risk of type II diabetes, increased cholesterol and triglycerides Place in s Recommendation grade of 2 (the best grade is 1). This grade means there is full evidence from controlled studies, but a moderate risk-benefit ratio. First-line treatment, mainly for the prevention of mania. Recommended if lithium is poorly tolerated or is not suitable. No specific recommendation for olanzapine. If lithium is poorly tolerated or unsuitable, consider other options: dopamine antagonists/partial agonists. Comments Good evidence of efficacy, but there are significant concerns about long-term side effects.8

9 An Updated Synthesis of Current s Quetiapine Quetiapine has shown efficacy in randomized controlled trials as monotherapy and adjunctive therapy [13] It is efficacious for preventing manic and depressive relapses [14] Short-term studies suggest it may be a good option for patients with mixed features, rapid cycling and sleep deficits [15] Risk of metabolic side effects Place in s Recommendation grade of 1. Evidence base for quetiapine is quite outstanding. Recommended as first-line monotherapy and as adjunctive therapy with lithium or divalproex. Consider quetiapine if it has been effective during an episode of mania or bipolar depression and if lithium is poorly tolerated or not suitable. If lithium alone is ineffective, consider combination treatment with quetiapine (recommended for depression predominant bipolar disorder). Comments Metabolic concerns warrant careful monitoring Efficacy shown for preventing manic and depressive episodes.9

10 An Updated Synthesis of Current s Risperidone LAI Risperidone long-acting injection has been shown to improve outcomes and reduce the risk of manic recurrence [15] Similar to olanzapine, risperidone was more efficacious in preventing mania relapses than depression, however, it was found to be less effective in preventing overall relapse compared to olanzapine [16] Metabolic side effects Hyperprolactinemia Place in s Recommendation grade of 2 (the best grade is 1). First-line treatment both as monotherapy and as adjunct to lithium or valproate. No specific mention. Consider long-acting formulations if prophylaxis against recurrence of mania is required and adherence to oral medication is erratic or injection preferred..10

11 An Updated Synthesis of Current s Aripiprazole Aripiprazole is efficacious as monotherapy and as adjunctive treatment [17] Evidence from randomized trials suggests aripiprazole is more effective at preventing manic and mixed episodes than depressive episodes [18] Risk of akathisia Place in s - Recommendation grade of 1. However, this applies only to patients with an index episode of mania and acute response to aripiprazole. - For all other groups of patients, long-term use is not supported by solid evidence, but should not be excluded in specific clinical scenarios such as: non-response, tolerability or safety problems with other long-term treatments. First-line treatment as monotherapy and as adjunctive therapy with lithium or valproate. No specific mention. - Dopamine antagonists/partial agonists may be appropriate for the long-term management of bipolar patients especially where non-mood-congruent psychotic features are prominent. - Dopamine antagonists/partial agonists may be useful in difficultto-treat cases of rapid cycling..11

12 An Updated Synthesis of Current s Ziprasidone There is evidence from one randomized controlled trial supporting the use of ziprasidone as adjunctive maintenance treatment [19] Use as monotherapy is not supported by evidence. As is the case with other SGAs (olanzapine, risperidone LAI and aripiprazole) ziprasidone is efficacious for the prevention of mania but not for the prevention of depressive episodes. Place in s Recommendation grade 3 (the best grade is 1). This grade is based on Category B evidence (limited positive evidence from controlled studies). - Recommended as first-line treatment as adjunctive therapy with lithium or valproate. - Not recommended as monotherapy. No specific recommendation. No specific recommendation..12

13 An Updated Synthesis of Current s Carbamazepine Effectiveness in clinical practice is not as robust as other first-line treatments such as lithium [20] There is evidence suggesting greater efficacy in patients with bipolar II disorder compared to those with bipolar I disorder. However, these data are derived from post-hoc analyses and are limited by small sample size [21] Clinical usefulness is limited by tolerability and drug interaction potential Place in s Recommendation grade of 3 (the best grade is 1). This grade is based on Category B evidence (limited positive evidence from controlled studies). Second-line treatment both as monotherapy and as adjunctive with lithium or valproate. No specific recommendation. Less effective than lithium, has little if any effect on relapse to depression and is liable to interfere with the metabolism of other drugs..13

14 An Updated Synthesis of Current s References 1. Ghaemi, S. N. (2009). A clinician s guide to statistics and epidemiology in mental health: Measuring truth and uncertainty. Cambridge, UK: Cambridge University Press. 2. 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), Cipriani, A., Hawton, K., Stockton, S., & Geddes, J. R. (2013). Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. 4. Malhi, G. S., Adams, D., Lampe, L., Paton, M., O Connor, N., Newton, L. A., & Berk, M. (2009). Clinical practice recommendations for bipolar disorder. Acta Psychiatrica Scandinavica,119(s439), Yildiz, A. (n.d.). (2015).The bipolar book: History, neurobiology, and treatment. (1st ed.). New York, N.Y.: Oxford University Press. 6. Suppes, T., Baldessarini, R. J., Faedda, G. L., & Tohen, M. (1991). Risk of recurrence following discontinuation of lithium treatment in bipolar disorder. Archives of General Psychiatry, 48(12), Malhi, G. S., McAulay, C., Das, P., & Fritz, K. (2015). Maintaining mood stability in bipolar disorder: a clinical perspective on pharmacotherapy. Evidence Based Mental Health,18(1), Chou, Y. H., Chu, P. C., Wu, S. W., Lee, J. C., Lee, Y. H., Sun, I. W., & Yen, Y. C. (2015). A Systemic Review and Experts Consensus for Long-acting Injectable Antipsychotics in Bipolar Disorder. Clinical Psychopharmacology and Neuroscience, 13(2), Yatham, L. N., Fountoulakis, K. N., Rahman, Z., Ammerman, D., Fyans, P., Marler, S. V., & Carlson, B. X. (2013). Efficacy of aripiprazole versus placebo as adjuncts to lithium or valproate in relapse prevention of manic or mixed episodes in bipolar I patients stratified by index manic or mixed episode. Journal of affective disorders,147(1), Vieta, E., & Valentí, M. (2013). Pharmacological management of bipolar depression: acute treatment, maintenance, and prophylaxis. CNS drugs, 27(7), Bowden, C. L., Vieta, E., Ice, K. S., Schwartz, J. H., Wang, P. P., & Versave, M. (2010). Ziprasidone plus a mood stabilizer in subjects with bipolar I disorder: a 6-month, randomized, placebo-controlled, double-blind trial. The Journal of clinical psychiatry, 71(2), Yildiz, A. (n.d.). (2015).The bipolar book: History, neurobiology, and treatment. (1st ed.). New York, N.Y.: Oxford University Press. 21. Chen, C. H., & Lin, S. K. (2012). Carbamazepine treatment of bipolar disorder: a retrospective evaluation of naturalistic long-term outcomes.bmc psychiatry, 12(1), Gitlin, M., & Frye, M. A. (2012). Maintenance therapies in bipolar disorders. Bipolar disorders,14(s2), Cipriani, A., Barbui, C., Rendell, J., & Geddes, J. R. (2014). Clinical and regulatory implications of active run-in phases in long-term studies for bipolar disorder. Acta Psychiatrica Scandinavica,129(5), BALANCE investigators. (2010). Lithium plus valproate combination therapy versus monotherapy for relapse prevention in bipolar I disorder (BALANCE): a randomised openlabel trial. The Lancet, 375(9712), Goodwin, G. O., & Consensus Group of the British Association for Psychopharmacology. (2016). Evidence-based guidelines for treating bipolar disorder: revised second edition recommendations from the British Association for Psychopharmacology. Journal of Psychopharmacology. 12. Cipriani, A., Rendell, J., & Geddes, J. R. (2009). Olanzapine in the long-term treatment of bipolar disorder: a systematic review and meta-analysis.journal of psychopharmacology. 13. Chiesa, A., Chierzi, F., De Ronchi, D., & Serretti, A. (2012). Quetiapine for bipolar depression: a systematic review and meta-analysis. International clinical psychopharmacology, 27(2), Weisler, R. H., Nolen, W. A., Neijber, A., Hellqvist, Å., & Paulsson, B. (2011). Continuation of quetiapine versus switching to placebo or lithium for maintenance treatment of bipolar I disorder (Trial 144: a randomized controlled study). The Journal of clinical psychiatry, 72(11), Vieta, E., & Valentí, M. (2013). Pharmacological management of bipolar depression: acute treatment, maintenance, and prophylaxis. CNS drugs, 27(7),