CANMAT recognizes that the level and quality of evidence vary widely with indication and type of treatment, that the majority of RCTs (and, hence, the meta-analyses based on them) may not reflect ...real-world clinical practice, and that there are very few predictors of treatment response for an individual patient. ...there are few absolute or first-choice treatments. Declaration of Conflicting Interests The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RWL has received honoraria for ad hoc speaking or advising/ consulting, or received research funds from the Asia-Pacific Economic Cooperation, AstraZeneca, Brain Canada, Bristol-Myers Squibb, Canadian Institutes of Health Research, Canadian Depression Research and Intervention Network, Canadian Network for Mood and Anxiety Treatments, Canadian Psychiatric Association, Coast Capital Savings, Johnson & Johnson, Lundbeck, Lundbeck Institute, Medscape, Pfizer, St. Jude Medical, Takeda, University Health Network Foundation, and Vancouver Coastal Health Research Institute.
The objective of the Genomics Used to Improve DEpression Decisions (GUIDED) trial was to evaluate the utility of pharmacogenomic testing to improve outcomes among patients with major depressive ...disorder (MDD) who had not responded to at least 1 prior medication trial. The objective of the present analysis was to assess outcomes for the subset of patients expected to benefit from combinatorial pharmacogenomic testing because they were taking medications with predicted gene-drug interactions.
Participants (enrolled from April 14, 2014, to February 10, 2017) had an inadequate response to at least 1 psychotropic medication in the current episode of MDD. Patients were randomized to treatment as usual (TAU) or the guided-care arm, in which clinicians had access to a combinatorial pharmacogenomic test report to inform medication selection. Patients and raters were blinded to study arm through week 8. The following outcomes were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17): symptom improvement (percent change in HDRS-17 score), response (≥ 50% decrease in HDRS-17 score), and remission (HDRS-17 score ≤ 7). In the GUIDED trial, the primary endpoint of symptom improvement did not reach significance in the intent-to-treat cohort (P = .069). Here, a post hoc analysis of patients who were taking medications subject to gene-drug interactions at baseline as predicted by combinatorial pharmacogenomic testing (N = 912) is presented.
Among participants taking medications subject to gene-drug interactions at baseline, outcomes at week 8 were significantly improved for those in the guided-care arm compared to TAU (symptom improvement: 27.1% versus 22.1%, P = .029; response: 27.0% versus 19.0%, P = .008; remission: 18.2% versus 10.7%, P = .003). When patients who switched medications were assessed, all outcomes were significantly improved in the guided-care arm compared to TAU (P = .011 for symptom improvement, P = .011 for response, P = .008 for remission).
By identifying and focusing on the patients with predicted gene-drug interactions, use of a combinatorial pharmacogenomic test significantly improved outcomes among patients with MDD who had at least 1 prior medication failure.
ClinicalTrials.gov identifier: NCT02109939.
Objective
Serotonergic psychedelics are re-emerging as potential novel treatments for several psychiatric disorders including major depressive disorder. The Canadian Network for Mood and Anxiety ...Treatments (CANMAT) convened a task force to review the evidence and provide a consensus recommendation for the clinical use of psychedelic treatments for major depressive disorder.
Methods
A systematic review was conducted to identify contemporary clinical trials of serotonergic psychedelics for the treatment of major depressive disorder and cancer-related depression. Studies published between January 1990 and July 2021 were identified using combinations of search terms, inspection of bibliographies and review of other psychedelic reviews and consensus statements. The levels of evidence for efficacy were graded according to the Canadian Network for Mood and Anxiety Treatments criteria.
Results
Only psilocybin and ayahuasca have contemporary clinical trials evaluating antidepressant effects. Two pilot studies showed preliminary positive effects of single-dose ayahuasca for treatment-resistant depression (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy and safety to an active comparator (escitalopram with supportive psychotherapy) in major depressive disorder, with additional randomized controlled trials showing efficacy specifically in cancer-related depression (Level 3 evidence). There was only one open-label trial of psilocybin in treatment-resistant unipolar depression (Level 4 evidence). Small sample sizes and functional unblinding were major limitations in all studies. Adverse events associated with psychedelics, including psychological (e.g., psychotomimetic effects) and physical (e.g., nausea, emesis and headaches) effects, were generally transient.
Conclusions
There is currently only low-level evidence to support the efficacy and safety of psychedelics for major depressive disorder. In Canada, as of 2022, psilocybin remains an experimental option that is only available through clinical trials or the special access program. As such, Canadian Network for Mood and Anxiety Treatments considers psilocybin an experimental treatment and recommends its use primarily within clinical trials, or, less commonly, through the special access program in rare, special circumstances.
•Higher baseline depression scores predicted recurrence even in euthymic patients.•Comorbid alcohol use disorder predicted longer times to remission.•Comorbid anxiety disorder predicted a shorter ...time to recurrence.•Depression as the first episode predicted longer delays in correct diagnosis.•Younger age at onset predicted longer delays in the diagnosis of bipolar disorder.
The HOPE-BD was a naturalistic study established to follow individuals in Canada seeking treatment for bipolar disorder (BD). The study aimed to examine the course of BD and describe how clinical and sociodemographic factors are associated with outcomes.
Individuals with BD had their clinical data recorded at enrolment and were naturalistically treated. Participant were followed for up to four years, and visits occurred at least once every three months. We investigated the longitudinal outcomes with logistic, Cox, and quantile regressions.
Among the 354 participants, 57.3% had BD type I. Depression as first episode, younger ages at onset and older ages of the first professional help predicted longer delays in correct diagnosis. Among the symptomatic patients at baseline, the median time to remission was 10.9 months. Comorbid alcohol use disorder and the severity of baseline depressive symptoms predicted longer times to remission. Among the euthymic participants, the median time to recurrence was 14.5 months. History of anxiety disorder and younger ages at onset predicted shorter times to recurrence. Baseline depression scores predicted recurrence in euthymic patients.
We did not investigate the predictors of each polarity. Our findings may not apply to individuals followed in non-specialised outpatient services.
Our study reinforces the necessity of early diagnosis and interventions, as well as the importance of treating depressive symptoms and comorbidities.
•The treatment of major depression still relies on trial and error for treatment selection.•Novel artificial intelligence models may assist with treatment selection.•These models must be tested to ...ensure clinicians and patients find them useful and acceptable.•Here we describe a mixed methods simulation center study of an AI tool and its perceived utility.•The tool seems to integrate well into practice and may help enrich clinician-patient interactions.
Aifred is a clinical decision support system (CDSS) that uses artificial intelligence to assist physicians in selecting treatments for major depressive disorder (MDD) by providing probabilities of remission for different treatment options based on patient characteristics. We evaluated the utility of the CDSS as perceived by physicians participating in simulated clinical interactions. Twenty physicians who were either staff or residents in psychiatry or family medicine completed a study in which they had three 10-minute clinical interactions with standardized patients portraying mild, moderate, and severe episodes of MDD. During these scenarios, physicians were given access to the CDSS, which they could use in their treatment decisions. The perceived utility of the CDSS was assessed through self-report questionnaires, scenario observations, and interviews. 60% of physicians perceived the CDSS to be a useful tool in their treatment-selection process, with family physicians perceiving the greatest utility. Moreover, 50% of physicians would use the tool for all patients with depression, with an additional 35% noting that they would reserve the tool for more severe or treatment-resistant patients. Furthermore, clinicians found the tool to be useful in discussing treatment options with patients. The efficacy of this CDSS and its potential to improve treatment outcomes must be further evaluated in clinical trials.
To determine the objective neurocognitive effects of (1) single-dose ketamine, (2) repeated-dose ketamine, (3) ketamine adjunct to electroconvulsive therapy (ECT), and (4) ketamine as the anesthetic ...for ECT in major depressive disorder (MDD) and depression in bipolar disorder (BD).
Cochrane, MEDLINE, Embase, and PsycINFO databases were searched on March 19, 2020 (updated July 2, 2020), using the terms terms
and
and their synonyms. Clinical trial registries (search date May 4, 2020) and reference sections of included articles were also searched. There was no restriction on language or year of publication.
Of 4,035 identified articles, 17 met inclusion criteria. Controlled and open-label studies of adults who received at least 1 ketamine treatment for a current major depressive episode, as part of MDD or BD, were included. Only studies measuring cognition using at least 1 validated, objective neurocognitive assessment were eligible.
Results are presented using a narrative review format. Data regarding change in cognitive performance from baseline to end-of-treatment and/or differences in cognition between ketamine and control groups were extracted.
There were no negative effects of single- or repeated-dose intravenous ketamine up to 2 weeks post-treatment in MDD. Limited data were available for BD populations, as well as on other routes of ketamine administration.
Data to definitively answer the question of whether ketamine has substantive or persistent cognitive effects are insufficient; thus, larger controlled trials measuring cognition as the primary outcome are needed. Future research should focus on different routes of ketamine administration, ketamine enantiomers, and BD populations.
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