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Next, let’s look at the CANMAT/ISBD Treatment Guidelines for Acute Bipolar Mania. This is pretty simple, and there’s nothing hugely or shockingly new here except that in this set of guidelines, the authors organized their recommendations hierarchically. This means that each of the listings amongst the medications that are listed as “first line,” the order in which they are listed tells us something about what the authors regard as hierarchical levels of evidence for efficacy and combined tolerability as well. So, they’re offering us more in the way of “First try this, then try that, then try that” than previously.
What was the rank ordering of medications for the treatment of acute bipolar mania? I hope you will not be surprised, but perhaps you will be, that lithium comes in as the top in this hierarchical ordering of first-line agents for the treatment of mania. Second is quetiapine, and third is divalproex. These are followed by a collection of second-generation antipsychotics; in order, they are asenapine, aripiprazole, paliperidone, risperidone, and cariprazine. That’s the rank ordering of medication strategies for acute bipolar mania, and the top 3 are lithium, quetiapine, and divalproex. Again, these are hierarchically organized based on not just evidence for efficacy but also tolerability, meaning safety and probability of side effects and severity of side effects.
However, the CANMAT/ISBD recommendations also point out that combination therapy is actually preferred as a starting arrangement for the treatment of acute mania. They note that, in general, combination therapy has shown in several clinical trials to have about a 20% greater response rate versus monotherapy with lithium or divalproex. So, in general, one would start with the combination of an antipsychotic plus lithium or divalproex, and they list 3 particular antipsychotics for use in that fashion in the order of quetiapine, aripiprazole, risperidone, or asenapine. All of those combination therapies are with lithium or divalproex, and that is preferred over monotherapy because of the greater response rate. However, they clearly leave open the use of clinical judgment that, in some cases, particularly less-severe patient presentations, one might start with monotherapy. And in that case, monotherapies (in order) are lithium, quetiapine, and divalproex. The combinations are lithium or divalproex combined with (in order) quetiapine, aripiprazole, or risperidone, followed by asenapine.
In summary, we have here specific guidelines from CANMAT/ISBD for pharmacotherapy for bipolar mania. For combination therapy—which, in general, is the starting point—those agents are lithium or divalproex combined with either quetiapine, aripiprazole, risperidone, or asenapine, in that order. Monotherapy is in the following order: lithium, quetiapine, and divalproex.
Abstract
Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 Guidelines for the Management of Patients With Bipolar Disorder
Lakshmi N Yatham, Sidney H Kennedy, Sagar V Parikh, Ayal Schaffer, David J Bond, Benicio N Frey, Verinder Sharma, Benjamin I Goldstein, Soham Rej, Serge Beaulieu, Martin Alda, Glenda MacQueen, Roumen V Milev, Arun Ravindran, Claire O’Donovan, Diane McIntosh, Raymond W Lam, Gustavo Vazquez, Flavio Kapczinski, Roger S McIntyre, Jan Kozicky, Shigenobu Kanba, Beny Lafer, Trisha Suppes, Joseph R Calabrese, Eduard Vieta, Gin Malhi, Robert M Post, and Michael Berk
The Canadian Network for Mood and Anxiety Treatments (CANMAT) previously published treatment guidelines for bipolar disorder in 2005, along with international commentaries and subsequent updates in 2007, 2009, and 2013. The last two updates were published in collaboration with the International Society for Bipolar Disorders (ISBD). These 2018 CANMAT and ISBD Bipolar Treatment Guidelines represent the significant advances in the field since the last full edition was published in 2005, including updates to diagnosis and management as well as new research into pharmacological and psychological treatments. These advances have been translated into clear and easy to use recommendations for first, second, and third‐ line treatments, with consideration given to levels of evidence for efficacy, clinical support based on experience, and consensus ratings of safety, tolerability, and treatment‐emergent switch risk. New to these guidelines, hierarchical rankings were created for first and second‐ line treatments recommended for acute mania, acute depression, and maintenance treatment in bipolar I disorder. Created by considering the impact of each treatment across all phases of illness, this hierarchy will further assist clinicians in making evidence‐based treatment decisions. Lithium, quetiapine, divalproex, asenapine, aripiprazole, paliperidone, risperidone, and cariprazine alone or in combination are recommended as first‐line treatments for acute mania. First‐line options for bipolar I depression include quetiapine, lurasidone plus lithium or divalproex, lithium, lamotrigine, lurasidone, or adjunctive lamotrigine. While medications that have been shown to be effective for the acute phase should generally be continued for the maintenance phase in bipolar I disorder, there are some exceptions (such as with antidepressants); and available data suggest that lithium, quetiapine, divalproex, lamotrigine, asenapine, and aripiprazole monotherapy or combination treatments should be considered first‐line for those initiating or switching treatment during the maintenance phase. In addition to addressing issues in bipolar I disorder, these guidelines also provide an overview of, and recommendations for, clinical management of bipolar II disorder, as well as advice on specific populations, such as women at various stages of the reproductive cycle, children and adolescents, and older adults. There are also discussions on the impact of specific psychiatric and medical comorbidities such as substance use, anxiety, and metabolic disorders. Finally, an overview of issues related to safety and monitoring is provided. The CANMAT and ISBD groups hope that these guidelines become a valuable tool for practitioners across the globe.
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Reference
Yatham, L. N., Kennedy, S. H., Parikh, S. V., Schaffer, A., Bond, D. J., Frey, B. N., Sharma, V., Goldstein, B. I., Rej, S., Beaulieu, S., Alda, M., MacQueen, G., Milev, R. V., Ravindran, A., O’Donovan, C., McIntosh, D., Lam, R. W., Vazquez, G., Kapczinski, F., McIntyre, R. S., … Berk, M. (2018). Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disorders, 20(2), 97–170.
