Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy.
ABSTRACT In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field.
The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included Levels of Evidence and expert clinical support. This section on "Pharmacotherapy" is one of 5 guideline articles.
Despite emerging data on efficacy and tolerability differences amongst newer antidepressants, variability in patient response precludes identification of specific first choice medications for all patients. All second-generation antidepressants have Level 1 evidence to support efficacy and tolerability and most are considered first-line treatments for MDD. First-generation tricyclic and monoamine oxidase inhibitor antidepressants are not the focus of these guidelines but generally are considered second- or third-line treatments. For inadequate or incomplete response, there is Level 1 evidence for switching strategies and for add-on strategies including lithium and atypical antipsychotics.
Most of the evidence is based on trials for registration and may not reflect real-world effectiveness.
Second-generation antidepressants are safe, effective and well tolerated treatments for MDD in adults. Evidence-based switching and add-on strategies can be used to optimize response in MDD that is inadequately responsive to monotherapy.
- SourceAvailable from: Gustavo Vazquez[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: Long-term symptomatic status in persons with major depressive and bipolar disorders treated clinically is not well established, although mood disorders are leading causes of disability worldwide. AIMS: To pool data on long-term morbidity, by type and as a proportion of time-at-risk, based on published studies and previously unreported data. METHODS: We carried out systematic, computerized literature searches for information on percentage of time in specific morbid states in persons treated clinically and diagnosed with recurrent major depressive or bipolar I or II disorders, and incorporated new data from one of our centers. RESULTS: We analyzed data from 25 samples involving 2479 unipolar depressive and 3936 bipolar disorder subjects (total N=6415) treated clinically for 9.4 years. Proportions of time ill were surprisingly and similarly high across diagnoses: unipolar depressive (46.0%), bipolar I (43.7%), and bipolar II (43.2%) disorders, and morbidity was predominantly depressive: unipolar (100%), bipolar-II (81.2%), bipolar-I (69.6%). Percent-time-ill did not differ between UP and BD subjects, but declined significantly with longer exposure times. CONCLUSIONS: The findings indicate that depressive components of all major affective disorders accounted for 86% of the 43-46% of time in affective morbidity that occurred despite availability of effective treatments. These results encourage redoubled efforts to improve treatments for depression and adherence to their long-term useJournal of Affective Disorders 03/2015; 3(178):71-78. DOI:10.1016/j.jad.2015.02.011. · 3.71 Impact Factor
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ABSTRACT: Context The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150-225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD). Method In a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n= 55), active rTMS combined with placebo venlafaxine (n= 60) or sham rTMS combined with active venlafaxine (n= 55). The patients received once daily sessions of active or sham 1Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 ± 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS-17 score < 8. Results We reported a similar significant antidepressant effect in the 3 groups (p< 10-6), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; p= 0.59). Conclusion Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 minutes) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD.Brain Stimulation 11/2014; 7(6). DOI:10.1016/j.brs.2014.07.040 · 5.43 Impact Factor
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ABSTRACT: This randomized, placebo-controlled study evaluated the efficacy and safety of a fixed dose (3mg/day) and flexible dose (3-15mg/day) schedule of aripiprazole as augmentation therapy in Japanese patients with inadequate response to antidepressant therapy (ADT). During an 8-week prospective treatment phase, patients experiencing a major depressive episode received clinicians' choice of ADT. Subjects with inadequate response to ADT were randomized to receive adjunctive treatment with placebo (n=195), fixed dose aripiprazole (n=197) or flexible dose aripiprazole (n=194) for 6 weeks. The primary efficacy endpoint was mean change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from the end of prospective treatment (baseline) to the end of randomized treatment. More than 90% of patients in all treatment groups completed the 6-week double-blind treatment phase. Mean MADRS total score was improved to a significantly greater extent with fixed dose aripiprazole and flexible dose aripiprazole (-10.5 and -9.6, respectively) than with placebo (-7.4). Aripiprazole was well tolerated. The incidence of akathisia observed in the flexible dose group may relate to a higher prevalence of the CYP2D6(*)10 allele in Asian populations. Six weeks of adjunctive treatment is insufficient to draw conclusions about the long-term benefits of aripiprazole. Exclusion of patients with established medical comorbidities does not reflect real-world practice. Aripiprazole augmentation at a fixed or flexible dose was superior to ADT alone and was reasonably well tolerated in Japanese patients with inadequate response to ADT. ClinicalTrials.gov identifier NCT00876343.Journal of Affective Disorders 08/2013; 151(3). DOI:10.1016/j.jad.2013.07.035 · 3.71 Impact Factor