New CANMAT Guidelines for Depression and Bipolar Disorder

Chairperson: Roumen V Milev, MD, PhD

Milev explained the objectives of this session as follows: participants should be able, the end of the session, to “1) Recognize the CANMAT role in developingevidence-based clinical guidelines; 2) Identify the newaspects of the guidelines for treatment of major depressivedisorder; and 3) Identify the new aspects of the guidelinesfor treatment of bipolar disorder.”

The“Canadian Network for Mood and Anxiety Treatment(CANMAT) was formed in 1995 and established itselfas a leading research and educational organization,” Milev began. “In2009, the update for the second edition of CANMATand International Society for Bipolar Disorders (ISBD)collaborative update of CANMAT guidelines for themanagement of patients with Bipolar Disorder: Update2009 took place. Also,the second edition of the CANMAT clinical guidelines for themanagement of Major Depressive Disorder in adults waspublished.” The chairperson then explained that the following presenters would focus on these latest two sets and explain how clinical practice can incorporate evidence-based psychiatry.

CANMAT Clinical Guidelines for Mood & Anxiety Disorders — History and Development

Sidney H. Kennedy, MD

Providing some background, Kennedy explained that “in 2001, CANMAT, a not-for-profit scientific and educational organization, published the first Canadian guidelines for the management of major depressive disorder (MDD) and bipolar disorder,” with revisions starting with meetings among the CANMAT working committee in 2008 and having culminated into the published depression and bipolar guidelines.”

The current depression guidelines are comprised of five sections: 1) Classification, burden and principles of management; 2) Psychotherapy alone or in combination with antidepressant medication; 3) Pharmacotherapy; 4) Neurostimulation therapies; and 5) Complementary and alternative medicine treatments.

To create the guidelines, explained Kennedy, “systematic literature searches were conducted to identify relevant studies between January 1, 2000 to December 31, 2008. Level 1 evidence requires at least 2 randomized controlled trials with adequate samples sizes, placebo control, and/or a meta-analysis with narrow confidence intervals. Levels of evidence for recommendations are based on criteria from the 2001 guidelines, but now also include consensus opinions about quantitative reviews. In addition, recommendations are graded depending on a treatment’s balance of efficacy, tolerability, and clinical support.

“The guidelines are comprehensive in the varieties of treatments assessed, although there are more data available for psychotherapeutic and pharmacologic interventions in comparison to complementary and alternative treatments,” he continued. “For this reason, first-line psychotherapy or pharmacotherapy recommendations usually should be considered before neurostimulation or complementary therapies. These guidelines, if applied correctly, have the potential to add considerable value to the management of depression in primary and tertiary care.”

CANMAT Clinical Guidelines for Management of Adults with Major Depressive Disorder

Raymond Lam, MD

Significant progress has been made in the management of major depressive disorder since the first Canadian guidelines were published in 2001, noted Lane, “including the advent of larger-scaleeffectiveness trials to bridge the gap between pristine trialsand daily clinical practice.”

Focusing on highlights from the 2009 major update of the CANMAT depression guidelines, Lane explained that the update occurred following a “systematic literature search that identified relevant studies with an emphasis on meta-analyses.” Levels of evidence were specified for recommendations, which were then graded according to line of treatment, “where first-line treatment represents a balance of efficacy, tolerability, and clinical support (referring to application of CANMAT expert opinion to ensure that interventions are realistic and applicable for clinical practice),” he added.

The five sections of the guidelines following the major update include focuses on:

• prevalence, burden, and principles of management.
• “traditional” psychotherapies (eg, CBT, IPT), emerging treatments (eg, mindfulness-based approaches) and novel methods of delivery (eg, Internet-delivered CBT).
• comparative efficacy and tolerability among first-line antidepressants, add-on/adjunctive strategies to manage patients with incomplete response, and sequencing of pharmacotherapy
• neurostimulation therapies (ECT, VNS, rTMS and DBS)
• evidence and cautions for complementary and alternative medicine treatments

“There is good evidence to support efficacy of many treatments for MDD, but still limited information about the comparative efficacy of treatments and their optimal sequencing, especially in real-world clinical populations,” Lane concluded. “Although the evidence base is the foundation for treatment selection, treatment choice must still be tailored for an individual patient.”

CANMAT Guidelines for Management of Bipolar Depression

Lakshmi Yatham, MBBS

“Although there is international consensuson guidelines for management of acute mania andprophylaxis of bipolar disorder, there continues to bewider disagreements about guidelines for managing bipolardepression,” stated Yatham.

Focusing on the guidelines developed by the CANMAT along with experts from the International Society for Bipolar Disorders, Yatham explained that the strength of evidence for each treatment included in the guidelines “was ranked in categories ranging from category 1 to 4, with category 1 being the best evidence as indicated by data from replicated, double-blind, placebo-controlled trials. The evidence was then translated by the group to clinical recommendations, ranging from first-line to not-recommended categories.” The recommendations took into account the evidence for efficacy, support for efficacy from clinical practice, and safety considerations, he added.

Although controversy surrounded the use of antidepressants and lamotrigine, the group used the above criteria to reach a consensus that “there is sufficient evidence to recommend lithium, lamotrigine, and quetiapine monotherapy, olanzapine plus SSRI, and lithium or divalproex plus SSRI/bupropion as first-line options.” The speaker recognizes that these recommendations are “in contrast to other guidelines which do not recommend antidepressants and lamotrigine as first line treatments.”

Finally, Yatham stated that new data support adjunctive modafinil as a second-line option for bipolar depression, with current evidence suggesting that aripiprazole should not be used as monotherapy.