Text version
Finally, for our review of the CANMAT/ISBD Treatment Guidelines for 2018, let’s look at the recommendations for acute bipolar depression.
First, they have another sensitive discussion of diagnosis emphasizing the importance of recognizing bipolar depression and distinguishing it from unipolar depression and acknowledging the difficulty of doing so. In that context, I think it’s interesting that they have given us a paragraph citing the “numerous features that increase the likelihood of a diagnosis of bipolar disorder in depressed individuals.” You’ll hear this litany of features often and are probably familiar with most of them. I’ll read them again because I think it’s important to hear them from this group and recognize the prominence that is being given to these diagnostic features. They include: Earlier age of illness onset that’s before age 25, brief highly or current depressive episodes, a family history of bipolar disorder, depression with psychotic features, and the atypical features. Atypical features are relatively weak and would be hypersomnia, hyperphagia, and leaden paralysis. But a few left on this list that are important are postpartum depression or psychosis and then finally antidepressant-induced irritability or manic symptoms or rapid cycling. All of those increase the likelihood of a diagnosis of bipolar disorder in depressed individuals. It is important to include those in our diagnostic assessment when someone presents with depression.
The guidelines for medication treatment of acute bipolar depression are hierarchically organized so that the order in which they appear is reflective of the group’s belief about how they ought to be used. The top 4 on their list are quetiapine, lurasidone used adjunctively with either lithium or divalproex, lithium, and lamotrigine. Lurasidone is not being used alone. It’s not listed as monotherapy but rather as a combined treatment with lithium or divalproex. Again, that list is: quetiapine, adjunctive lurasidone, lithium, and lamotrigine. They offer a thoughtful discussion of why lithium and lamotrigine made this list even though their evidence quality is not as good as for the others. If you have any doubts about that ranking, I’d refer you to that paragraph on page 117 of the hard-copy publication. (It appears on a different page in the PDF.)
It is also important to recognize that some agents are specifically not recommended. The authors follow up with a table of studies that have negative evidence—not just a lack of evidence but *negative evidence—*and that includes, notably, antidepressant monotherapy. For bipolar I depression, antidepressant monotherapy is specifically not recommended. Likewise, amongst approaches not recommended is lamotrigine combined with folic acid. As you may know, this is based on a single study. We need more data on this, but for the moment, it appears that folic acid may interfere with lamotrigine’s efficacy, so the combination is specifically not recommended.
Finally, there’s a whole separate section on bipolar II, where their recommendations are crafted independently of the recommendations for bipolar I. The most important recommendation that emerges specifically for bipolar II is that antidepressants are controversial. There’s a specific page in the document that describes this controversy and how they handled it. The bottom line there is, they recommend that antidepressants be used only in the context of a “pure depression,” meaning not mixed—no manic symptoms admixed with the depression symptoms. In that case, after the 4 first-line options I mentioned earlier, second-line options of bupropion and sertraline are the top choices if you’re going to use an antidepressant in that very narrow context of bipolar II pure depression.
In summary, we have these new treatment guidelines from the CANMAT/ISBD, who are reliable authorities on the subject. And in the case of bipolar depression, first-line options are quetiapine, adjunctive lurasidone, lithium, or lamotrigine followed by combinations of those agents in the first line. Antidepressants fall to second line only in the context of pure depression and only in bipolar II, not in bipolar I.
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.
Download PDF and other files
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.
