This publication is intended for information purposes only, and is not intended to be interpreted or used as a standard of medical practice. Best efforts were used to ensure that the information in this publication is accurate; however, the publisher and every person involved in the creation of this publication disclaim any warranty as to the accuracy, completeness, or currency of the contents of this publication. This publication is distributed with the understanding that neither the publisher nor any person involved in the creation of this publication is rendering professional advice. Physicians and other readers must determine the appropriate clinical care for each individual patient on the basis of all the clinical data available for the individual case. The publisher and every person involved in the creation of this publication disclaim any liability arising from contract, negligence, or any other cause of action, to any party, for the publication contents or any consequences arising from its use. The CCSMH gratefully acknowledges support from AIRD & BERLIS LLP for their guidance on Copyright issues and for the review and creation of the disclaimer statement. Funding for the CCSMH Guideline Initiative was originally provided by the Public Health Agency of Canada, Population Health Fund. Guideline updates were made possible through a CIHR-Institute of Aging Betty Havens Award for Knowledge Translation in Aging. The CCSMH gratefully acknowledges the financial contribution of both funders for their ongoing support and continued commitment to the area of seniors' mental health. In addition, special thanks to the original and update Guideline Group members who dedicated countless number of hours and engaged in the creation of the original and updated guidelines and recommendations.# Introduction
T he proportion of Canadians who are seniors is expected to increase dramatically. Currently older adults (i.e., those aged  65) account for 18% of our country's population (Statistics Canada, 2020). Approximately 20% of those aged 65 and older are living with a mental illness. Although this figure is consistent with the prevalence of mental illness in other age groups, it does not capture the high prevalence rates seen within health and social institutions. For example, it has been reported that 80-90% of nursing home residents live with some form of mental illness and/or cognitive impairment (Seitz et al., 2010;Rovner et al., 1990). Late-life depression is common but often under-diagnosed and undertreated contributing to significant functional impairment and reduced quality of life. The Canadian Coalition for Seniors' Mental Health (CCSMH) National Guideline Project was originally created to support the development of evidence-based recommendations in 4 key areas of seniors' mental health, including depression.
The CCSMH first published national interdisciplinary best practice guidelines on the assessment and treatment of depression in older adults in 2006. Since then a number of clinical trials have been conducted that called for reinforcement or modification of the recommendations made in the initial guidelines. In 2018, CCSMH initiated an update of the guidelines. A team of interdisciplinary health care professionals from across Canada examined the latest peer-reviewed journal articles published since 2006.
In Section 3 (page 6), all new recommendations and recommendations with major modifications are described, with explanations. Some additional recommendation updates with relatively minor changes are only described in Section 4, which compares the original 2006 recommendations to the 2021 recommendations. New or modified recommendations are listed in the right-hand column. Readers are encouraged to review Sections 3 and 4.

# Methods
A systematic search for peer-reviewed scholarly articles was performed in 5 databases including Medline, Embase, HealthStar, Cochrane, and PsychINFO from the beginning of the end date of the literature review from the previous version of the guideline-July 2006-through December 2018. The searches included and were restricted to English papers only and search terms used were the same as for the 2006 Guidelines.
Multiple phases of title and abstract review were conducted by one of the authors to identify 344 full-text articles from an initial yield of 1560 articles from database searches; those were further categorized based on types of study such as controlled trials (especially randomized), meta-analyses, reviews (especially systematic), and practice guidelines or expert committee reports potentially relevant to the subject area. Subsequently, additional relevant articles of which the members were aware were included.
A working group was assembled (listed on page 2) and participated in the evidence review followed by development of updated recommendations. Individual working group members focused on specific areas and wrote summaries with proposed recommendation updates. The working group met several times to discuss proposed changes, any gaps or controversies with proposed updated recommendations, and consensus was obtained. The proposed updates were presented at the Canadian Academy of Geriatric Psychiatry (CAGP)-CCSMH virtual conference in October 2020, providing an opportunity for feedback from our peers.
The overall grouping of the 2006 recommendations is retained with the addition of a few new categories. The strength of each recommendation was assessed using the same system utilized in the 2006 Guidelines (i.e., Shekelle et al., 1999) Categories of Evidence and Strength of Recommendations) summarized on the next page. (Shekelle et al., 1999) (Shekelle et al., 1999) Evidence from meta-analysis of randomized controlled trials Ia Evidence from at least 1 randomized controlled trial Ib Evidence from at least 1 controlled study without randomization IIa

# CATEGORIES OF EVIDENCE FOR CAUSAL RELATIONSHIPS AND TREATMENT

# STRENGTH OF RECOMMENDATION
Evidence from at least 1 other type of quasi-experimental study IIb
Evidence from non-experimental descriptive studies, such as comparative studies, correlation studies, and case-control studies

# III
Evidence from expert committees reports or opinions and/or clinical experience of respected authorities IV

# Directly based on category I evidence A
Directly based on category II evidence or extrapolated recommendation from category I evidence B
Directly based on category III evidence or extrapolated recommendation from category I or II evidence C Directly based on category IV evidence or extrapolated recommendation from category I, II, or III evidence D
The strength of the recommendations, ranging from A to D (see below), is based on the entire body of evidence (i.e., all studies relevant to the issue) and the expert opinion of the Guideline Development Group regarding the available evidence. For example, a strength level of D has been given to evidence extrapolated from literature on younger population groups or considered a good practice point by the Guideline Development Group.
It is important to interpret the rating for the strength of recommendation (A to D) as a synthesis of all the underlying evidence and not as a strict indication of the relevant importance of the recommendation for clinical practice or quality of care. Some recommendations with little empirical support, resulting in a lower rating for strength on this scale, are in fact critical components of the assessment and treatment of depression.
T he updated Guidelines include a greater emphasis on depression prevention. Historically, healthcare systems have under-funded prevention approaches, especially in the mental health arena. Although research on prevention is in its infancy, prevention may be an alternative strategy to further reduce the disease burden of depression, which has been described as a global public health priority (Reynolds et al., 2012). Universal prevention focuses on the general public or a whole population group regardless of risk status. Selective prevention targets individuals or subgroups that are at higher risk of developing mental disorders than average individuals or subgroups. Indicated prevention focuses on individuals who are identified as having prodromal symptoms or biological markers of mental disorders, but who do not yet meet the diagnostic criteria for a full-blown diagnosis. The recommendations below primarily focus on universal and selective prevention. Of note, there is not enough evidence to recommend the use of antidepressants for people at high risk, although 1 small study suggested a reduced risk in individuals who had suffered a stroke (Robinson et al., 2008 Studies of interventions for social isolation, loneliness, and depression among older adults have been conducted globally. For example, Chiang et al. (2010) investigated the effects of weekly reminiscence therapy sessions on older adults living in long-term care homes. This intervention significantly decreased feelings of loneliness and depressive symptoms among participants. Similarly, a randomized controlled trial (RCT) conducted by Westerhof et al. (2017) aimed to understand the effectiveness of an autobiographical memory discussion intervention among older adults living in residential care. Participants with clinically relevant depressive symptoms had a significant reduction in symptoms during and post-intervention. In addition, loneliness significantly decreased among intervention participants. Tse et al. (2014) investigated the effectiveness of a weekly physical exercise program on nursing home residents. The findings showed significant improvements in both loneliness and depression.
There are several published systematic reviews of social isolation and/or loneliness and/or depression interventions. Quan et al. (2019)  The definition of social prescribing comes from Friedli and Watson (2004). Ways to Wellness, an organization located in the United Kingdom, examined the effects of social prescribing in an urban setting amongst middle-aged and older adults with chronic and multiple long-term conditions (Moffatt et al., 2017). Individuals were referred to a 'Link Worker' who identified meaningful health and wellness community and voluntary services and resources. Service users reported positive changes including reduced social isolation and improved mental health after 6 months. Age United Kingdom (UK) conducted a Social Prescribing Pilot Project that investigated the effectiveness of general practitioners referring older adults aged 55 years and older who had mild to moderate depression or who experienced loneliness or social isolation to the social prescribing service. Older adults who participated in this study demonstrated a significant improvement in their emotional well-being. The Alliance for Healthier Communities in Ontario, Canada (2020) conducted an 18-month mixed methods pilot study on the effectiveness of social prescribing across 11 community health centres. In the Rx: Community -Social Prescribing in Ontario study, approximately half of participants were between the ages of 61-80 years. The most frequent reasons for referral were: (a) anxiety, (b) depression, (c) social isolation, and (d) mental health symptoms. Clients reported a significant improvement in mental well-being, reduced loneliness, and increased sense of belonging and connectedness. It should be noted that Bickerdike et al. (2017) suggested that more research was required in order to support the widespread use of this approach.

# NEW: PREVENTION
A stepped-care approach (e.g., watchful waiting, cognitive behavioural therapy  bibliotherapy, problem-solving therapy, and referral to primary care for antidepressant medication) can reduce the incidence of depressive and anxiety disorders in community-dwelling older adults with subthreshold depression or anxiety. 
A stepped-care approach has been shown to reduce the incidence of depressive and anxiety disorders in communitydwelling older adults with subthreshold depression or anxiety. Van't Veer-Tazelaar et al. (2009) studied the following steps: a watchful waiting approach, CBT-based bibliotherapy, CBTbased problem-solving treatment, and referral to primary care for medication, if required. The intervention group had a 50% reduction in incidence of major depressive disorder or anxiety disorder over a 12-month period compared to usual care.
Other promising approaches to preventing depression in older adults with subthreshold depression include the use of lay counsellors in middle and low-income countries (Dias et al., 2019) and the use of problem-solving therapy (Reynolds et al., 2014).

# NEW: PREVENTION
Higher levels of physical activity are consistently associated with lower odds of developing future depression. This finding is consistent across all age groups including older adults. Clinicians should encourage patients with low levels of physical activity to become more active. Tools are available for clinicians to assist patients in setting health-related goals (e.g., Fountain of Health).
Schuch et al. carried out a meta-analysis of 49 studies of physical activity (2018). Compared with people with low levels of physical activity, those with high levels had significantly lower odds of developing depression. Furthermore, physical activity had a protective effect against the emergence of depression across all age groups including older adults.
Protective effects against depression (major depression or symptoms) were found across geographical regions, with adjusted odds ratios ranging from 0.65 to 0.84 in Asia, Europe, North America, and Oceania.
The Canadian Program entitled Fountain of Health provides clinicians and the public with tools to support behaviour change, aimed at improving lifestyle behaviours including exercise (Gough et al., 2019;Cassidy et al., 2020;www.fountainofhealth.ca).

# NEW: PREVENTION
Clinicians should utilize the instilling of hope and positive thinking as important therapeutic tools in the prevention of depression and in helping individuals with depressive symptoms or disorders.
The therapeutic value of hope to health, healing, wellbeing, and quality of life has been well described (Moore 2005;Wilson et al., 2010). There is increasing interest in understanding the role of hope in healing, goal-setting, coping with illness, and as an approach to combat hopelessness. When confronted with illness or loss people are highly vulnerable. Clinicians should consider the important role of instilling authentic hope and positive thinking in their interactions with patients and families in all healthcare settings. There have been a limited number of studies focused on assessing the impact of interventions specifically designed to increase hope with variable results (Kwon et al., 2015;Cheavens at al., 2006;Wilson et al., 2010). A review of 9 studies, utilizing such interventions by nurses in patients coping with cancer, concluded that it is possible to increase hope in this group (Li et al., 2018). Moore (2005) suggests that nurses are in key positions to have conversations with their clients/patients about hope and about strategies to find renewed hope in any situation. She notes that others have stressed the importance of honouring hope as a complex and multidimensional component of people's experiences through illness and suffering (Bland & Darlington, 2002). Although more research is necessary to understand optimal interventions, we would encourage all healthcare staff to reflect on how best to incorporate the instilling of hope into their practices. In 2006 it was recommended that ECT should be considered if adequate trials of antidepressants combined with psychotherapy have been ineffective or if the health of the patient is deteriorating rapidly due to depression. The modification above underlines the need to consider ECT in a number of different circumstances, including its potential use as a first-line treatment in some patients who are at risk of poor outcomes. Its use for continuation/maintenance treatment for some patients is also noted.
We have added repetitive transcranial magnetic stimulation (rTMS) as an additional option for patients with major depressive disorder (MDD) who have failed to respond to at least 1 adequate trial of antidepressant (see page 11). In the 2006 Guidelines it was recommended that if there is no specific contraindication to its use, patients with psychotic depression should be offered treatment with ECT when available. Alternatively, a combination of antidepressant plus antipsychotic medication was recommended. We now recommend that combined pharmacotherapy can also be considered first line. The Study of the Pharmacotherapy of Psychotic Depression (STOP-PD) trial investigated the effectiveness of combined antipsychotic medications with antidepressants (Meyers et al., 2009). The trial found higher remission rates after 12 weeks of treatment with olanzapine combined with sertraline (41.9%) as compared to olanzapine with placebo (23.9%). This was the case for patients both less than 60 and greater than 60 years of age. A 2016 meta-analysis identified 8 RCTs of exercise interventions in adults aged 60 and older with depression. Adjusting for publication bias resulted in a large effect size of exercise on depressive symptoms with aerobic exercise combined with strength training, but not either alone. Benefit was also found with group-based interventions, which were of moderate but not vigorous intensity (Schuch et al., 2016). A review of previous meta-analyses examined the effects of exercise on late-life depression (symptoms or disorder) in adults older than 60 years. Three meta-analyses met eligibility criteria. A total of 1487 participants from diverse settings with ages ranging from 63.5-77.5 years were included. Depressive symptoms were significantly reduced by exercise, and the authors conclude it is a safe and effective treatment that should be incorporated into the standard care of older adults with depression (Catalan-Matamoros et al., 2016).

# NEW: PSYCHOTHERAPIES AND PSYCHOSOCIAL INTERVENTIONS

# MODIFIED: PSYCHOTHERAPIES AND PSYCHOSOCIAL INTERVENTIONS

# Psychotherapies with the most evidence for effectiveness in older adults include: cognitive behaviour therapies (CBT; individual and group) and problem-solving therapy (PST). PST can be provided to older adults with cognitive impairment and executive dysfunction; CBT and PST have also shown benefit for older adults with depression and medical comorbidity. 
Psychotherapies and psychosocial treatments should be made available to older adults with depression (symptoms and disorder) in diverse settings (community, hospital, long-term care) across all regions of Canada.

# There is also evidence to support behaviour therapy, behavioural activation, reminiscence, and other psychotherapies including psychodynamic psychotherapy and interpersonal psychotherapy (IPT). 
Internet-delivered therapies may be comparable to face-to-face treatment, and may improve access to services for individuals in under-serviced areas and those with mobility issues.
We emphasize the vital need for psychotherapies and psychosocial treatments to be made available for older adults with depression in diverse settings in all regions of the country.
Although many forms of psychotherapy have demonstrated benefits for older adults with depression, we note that the most evidence for effectiveness is for CBT (individual and group) and PST. Numerous meta-analyses support CBT as an effective treatment for late-life depression (Cuijpers et al., 2006;Pinquart et al., 2007;Peng et al., 2009) when provided in both individual and group formats. Some of these meta-analyses also found evidence in support of other psychotherapies such as reminiscence therapy. Emerging studies also suggest CBT is an effective intervention for depressed older adults with medical comorbidities such as chronic pain (Ehde et al., 2014) and heart failure (Jeyanantham et al., 2017). Meta-analyses of psychotherapeutic interventions also support the effectiveness of PST for late-life depression showing moderate to high effect sizes (Cuipjers et al., 2016Kirkham et al., 2016, including among frail older adults (Jonsson et al., 2016).
Internet-delivered cognitive behavioural therapy (iCBT) has been piloted with depressed older adults with favourable results (Titov et al., 2015). Such interventions can improve access to psychotherapy, especially for older adults in underserviced areas, and/or those who face mobility challenges. One RCT comparing online or iCBT to usual care among depressed older adults with knee osteoarthritis showed benefit compared to usual care (O' Moore et al., 2018). This approach is highly relevant during the expansion of virtual care related to the COVID-19 pandemic.

# MODIFIED: SELECTING AN ANTIDEPRESSANT/MONITORING FOR SIDE EFFECTS AND DRUG INTERACTIONS

# It is recommended that clinicians consider sertraline or duloxetine as first-line medications for an acute episode of major depression in older adults. Alternatives include escitalopram and citalopram based on the low possibility of drug interactions but concern about QTc interval may limit dosage to sub-therapeutic levels. 
In addition, we suggest clinicians should choose an antidepressant with lowest risk of anticholinergic side effects and drug-drug interactions, as well as being relatively safe in the case of cardiovascular comorbidity. Patients need to be closely monitored for medication compliance, substance use, suicidal ideation, and development of drug toxicity.
Because of concerns about QTc prolongation with citalopram and escitalopram, and incorporating level of evidence, we are recommending sertraline or duloxetine as first-line medications for an acute episode of major depression in older adults. Citalopram and escitalopram remain useful options.
There are a variety of other appropriate antidepressants for older adults such as venlafaxine, bupropion, and mirtazapine.
In addition vortioxetine is a relatively new antidepressant, which has shown benefit for older adults, including some evidence of improvement in depression-related cognitive dysfunction (McIntyre et al., 2014;Nomikos et al., 2017;McIntyre et al., 2016). In most cases, fluoxetine is not recommended due to its long biological half-life, paroxetine is not recommended due to higher anticholinergic effects, and first generation monoamine oxidase inhibitors are not recommended due to higher risk of serious drug-drug and drug-food interactions. Tricyclic antidepressants should only be considered as third-line agents with due consideration of their potentially serious side effects.
A number of systematic reviews and meta-analyses have been conducted since the last iteration of these guidelines. Overall, the meta-analyses have found that antidepressants are efficacious for geriatric depression. A systematic review and meta-analysis of non-tricyclic "second generation" antidepressants found that these antidepressants were superior to placebo for MDD in adults over 60 years of age. The mean pooled response rates for antidepressant and placebo were 44.4% and 34.7%, respectively. The therapeutic effects were found to be modest and vary according to study and medication (Nelson et al., 2008). Of interest, it was found that longer trials of 10-12 weeks were needed for older adult to achieve a response. A meta-analysis of 51 double-blind RCTs of anti depressants in older patients found that all classes of antidepressant (tricyclic antidepressants , selective serotonin reuptake inhibitors , and other antidepressants) were superior to placebo to achieve response, with less robust findings for remission. There were no differences in remission or response rates between classes of antidepressants. The numbers needed to treat (NNT) were 14.4 and 6.7 for response and remission, respectively (Kok et al., 2012). The efficacy of duloxetine was supported by a systematic review and metaanalysis of 12 trials of antidepressants for geriatric major depression, with less convincing outcomes for SSRIs . The 2006 Guidelines recommended weekly visits after starting an antidepressant. Although ideal, this has been deemed often unrealistic (e.g., in primary care and in many mental health ambulatory settings). A brief check-in by phone may be helpful for some patients who are experiencing side effects and may encourage patients to continue taking the medication as the initial side effects frequently diminish.

# MODIFIED: TITRATION AND DURATION OF THERAPY (INADEQUATE RESPONSE)
When significant improvement has occurred but recovery is not complete after an adequate trial, the clinician should consider:
- a further 4 weeks of monotherapy or consider augmentation with another antidepressant or lithium or an antipsychotic (e.g., aripiprazole) or specific psychotherapy (e.g., IPT, CBT, PST).
- a switch to another antidepressant (same or another class) after discussing with the patient the potential risk of losing any significant improvements made with the first treatment.
- augmentation with lithium remains a viable option but needs to be used carefully due to the risk of lithium toxicity; the clinician must be aware of how to monitor the patient on lithium over time through investigations.

# NOTE: 2006 recommendation did not include augmentation with an antipsychotic.
The atypical antipsychotic aripiprazole has been investigated for treatment-refractory depression with promising results. A post hoc examination of 3 RCTs for patients 18-67 years of age demonstrated that augmentation with aripiprazole was superior to placebo in reducing depression and achieving remission in the 61-67 year-old subgroup (Steffens et al., 2011).
A subsequent randomized, placebo-controlled trial of aripiprazole for older adults (average age 66) who did not respond to venlafaxine found that augmentation with aripiprazole (average daily dose 7 mg) resulted in remission significantly more often than placebo (44% vs 29%) (Lenze et al., 2015). The NNT to achieve remission with aripiprazole augmentation was 6. Extended-release quetiapine has demonstrated efficacy as monotherapy for geriatric depression (Katila et al., 2013). It must be noted that atypical antipsychotic medications have significant potential side effects such as tardive dyskinesia, akathisia, extrapyramidal side effects, and prolongation of QTc, and there may be an increased risk of death and stroke, based on the dementia literature.
In attempting to achieve optimal outcomes, some experts favour an approach that utilizes a treatment algorithm. One Canadian example of this approach was described by Mulsant et al. (2014). In this algorithm, the first-line antidepressant was escitalopram, with sertraline and duloxetine as alternatives.
For non-responders, duloxetine is the preferred second-line antidepressant, with venlafaxine and desvenlafaxine as alternatives. Duloxetine was favoured partly due to the impact on the management of several pain syndromes that are quite common in older adults. If the patient fails an SSRI and a serotonin and norepinephrine reuptake inhibitor (SNRI); i.e., no response despite an adequate trial at a therapeutic dose) the next step is the use of the TCA nortriptyline, with bupropion as an alternative. For those patients who achieve a partial response to a first-or second-line antidepressant (SSRI or SNRI), the algorithm recommends augmentation with either lithium or an atypical antipsychotic. An alternative is combining the SSRI or SNRI with mirtazapine or bupropion.

# MODIFIED: MONITORING FOR SIDE EFFECTS AND DRUG INTERACTIONS (SODIUM)
When prescribing SSRI or SNRI antidepressants to older adults, the prescriber should screen for a history of hyponatremia before prescribing, as part of the consent process and then consider getting a sodium level prior to starting the antidepressant if there is a history of hyponatremia. The 2006 Guidelines recommended that a sodium level be done after 1 month, especially if the patient was taking a medication known to cause hyponatremia. Reports suggest that hyponatremia often occurs with the first 2 weeks of treatment (Leth-Mller et al., 2016;Lien, 2018).
A review of 21 studies and over 100 case reports revealed a relatively higher risk of hyponatremia with SSRIs and venlafaxine, particularly when combined with patient risk factors for hyponatremia (De Picker et al., 2014). The risks associated with mirtazapine were lower. A recent commentary compared 4 population-based studies, revealing that SSRIs and SNRIs are most likely to cause hyponatremia in older adults, with TCAs and mirtazapine having lower risk. There are case reports for bupropion possibly causing hyponatremia as well (Lien, 2018). rTMS is a brain stimulation method that uses magnetic field pulses, rather than an electrical current, and does not induce a seizure. The procedure requires a stimulator and coil to produce an electromagnetic field. A typical treatment course is 5 days per week for between 4-6 weeks. In general, the treatment has a favourable adverse effect profile with common side effects including scalp discomfort and transient headache.
There are no cognitive adverse effects reported with rTMS. In 2008, the FDA approved rTMS as a treatment for depression for patients not responding to at least 1 antidepressant medication with a maximum age of 69 (Manepalli et al., 2014).
Despite the relatively large number of rTMS studies completed to date, there is a paucity of studies evaluating the efficacy of rTMS in treatment-resistant late-life depression specifically. A number of older reports have suggested that older age is a negative predictor of response to rTMS (Figiel et al., 1998;Fregni et al., 2006;Manes et al., 2001;Mosimann et al., 2002). However, these studies were limited in several important ways: short treatment courses and suboptimal stimulation parameters, particularly with respect to the stimulation intensity needed to overcome the prefrontal atrophy that occurs with advancing age. The proposed mechanism for these negative findings is likely related to the increased scalp-tocortex distance in the elderly (Figiel et al. 1998). Imaging studies (Mosimann et al., 2004;Kozel et al., 2000) and a small uncontrolled clinical pilot study (Nahas et al., 2004) have suggested a correlation between antidepressant effect of rTMS and scalp-to-cortex distance. Nahas et al. (2004) used an open design in which they adjusted stimulus intensity based on the distance of the scalp to the cortex and used magnetic resonance imaging (MRI) co-registration to target the dorsolateral prefrontal cortex (DLPFC), in 18 older subjects. The average intensity required was 114%; significantly higher than the intensity used in other treatment trials at the time. Interestingly, a more recent RCT in an elderly sample with depression and cerebrovascular damage found unilateral rTMS at 110% stimulation intensity resulted in a significant, but modest 27.3% remission rate (Jorge et al., 2008).
The rTMS field has moved to using 120% of the motor threshold intensity across the age range of subjects and as a result, meta-analyses of more recent DLPFC rTMS have not found that older age is a negative predictor of response (Berlim et al., 2014;Gross et al., 2007). Some preliminary data suggest that older adults may respond better to a sequential bilateral form of rTMS where low frequency (i.e., 1 Hz) right-sided stimulation is immediately followed by high frequency (i.e., 10 Hz) left-sided stimulation, using 120% stimulation intensity (Blumberger et al., 2012;Blumberger et al., 2016;Trevizol et al.,2019). Other data suggest that older adults may respond better with a coil that generates a larger induced electrical field than the standard figure of 8 coils (Levkovitz et al., 2009). A controlled trial in older adults aged 60-80 demonstrated that deep rTMS led to a statistically significant higher remission rate compared to sham (Kaster et al., 2018).
Further study of rTMS in older adults is warranted given that optimal treatment parameters have demonstrated more promising results than earlier studies. Controlled studies across the age spectrum of older adults (i.e., over age 70) are needed to confirm efficacy and tolerability in this subgroup of older adults. Older adults may be particularly able to benefit from rTMS as daily schedules may be more conducive to the 5 days weekly treatment schedule. rTMS has good patient acceptability due to the favourable adverse effect profile, in particular the lack of cognitive side effects. There is some recent evidence that pharmacogenetic testing might improve outcomes among older adults with MDD who had failed a trial of at least 1 antidepressant.
In a controlled trial of 206 adults (aged 65 or older) participants receiving care guided by pharmacogenetic testing showed significantly improved response and rates of remission compared to usual care (Forester et al., 2020). However, this testing is not widely available and is expensive. We do not recommend its use in routine practice, although some patients who are intolerant of several antidepressants may benefit from a pharmacogenetic test. A number of meta-analyses and systematic reviews have investigated the efficacy of antidepressants for depression associated with dementia. The initial Cochrane review in 2002 was negative (Bains et al., 2002). This was followed by a positive meta-analysis of 5 studies, which showed a NNT of 5 to achieve remission (Thompson et al., 2007). Subsequently, 4 more meta-analyses, including another Cochrane review in 2018, were negative (Nelson et al., 2011, Sepehry et al., 2012, Orgeta et al., 2017, Dudas et al., 2018. We would still suggest that antidepressant medication could be offered if symptoms are severe and persistent.

# NEW: SPECIAL POPULATIONS: PARKINSON'S DISEASE
We recommend SSRIs as first line for the treatment of depression in patients with Parkinson's disease with SNRIs as an alternative.

# CBT can also be considered. 
The 2006 Guidelines did not make a recommendation for patients with depression associated with Parkinson's disease. A meta-analysis of 20 RCTs compared pharmacologic, behavioural, or rTMS with a placebo/other drugs or methods. There were 13 medication trials, 9 of 13 were placebo-controlled and most were studies involving antidepressants. Two studies examined dopamine agonists and 1 study examined memantine. Antidepressant medications were found to be efficacious, specifically SSRIs and SNRIs. Non-antidepressant medications (e.g., dopamine agonists) did not have positive results. CBT was also beneficial (Bomasang-Layno et al., 2015). Another metaanalysis assessed the efficacy of antidepressants for depression in Parkinson's disease compared to placebo or a control group. This involved 20 studies and of those, 12 were randomized, placebo-controlled trials, while the others were either comparative studies or antidepressant versus no treatment. The results demonstrated efficacy for SSRIs, MAOIs, and TCAs when compared with placebo. The antidepressants were well-tolerated overall (Mills et al., 2018). Given equal efficacy among antidepressants, we recommend SSRIs or SNRIs, as they are generally better tolerated than older antidepressants such as TCAs. Several meta-analyses have demonstrated that a variety of antidepressants are superior to placebo in PSD (Xu et al., 2016;Deng et al. 2017;Qin et al., 2018). We favour SSRIs as first line based on overall risk of side effects, although they are associated with an increased risk of bleeding when combined with non-steroidal anti-inflammatory medication (Shin 2015).
Methylphenidate may be efficacious based on 1 placebocontrolled RCT (Grade et al., 1998).

# NEW: MODELS OF CARE (COLLABORATIVE, INTERPROFESSIONAL MODELS)
Core elements of evidence-based models for treating late-life depression in primary care include improved patient education, and incorporating interprofessional staff as depression care managers who routinely assess and follow patients clinically, utilizing a stepped-care approach. Treatment prescriptions are provided by a primary care physician or nurse practitioner, with as needed psychiatric consultation. An individualized plan of care should be developed using a collaborative approach.
Interventions that integrate mental health services into primary care have increased the number of patients who are treated for depression and the quality of that treatment. The most effective models involve systematic depression screening and monitoring, interprofessional teams that include primary care providers and mental health specialists, a depression care manager to work directly with patients over time, and the use of guideline-based depression treatment (Bruce & Sirey, 2018). Three major studies have demonstrated the effectiveness of integrated approaches (PRISM-E, IMPACT, and PROSPECT) in the care of older adults. Thota et al., (2012) carried out an extensive review and meta-analysis of collaborative care to improve the management of depressive disorders across multiple patient populations. The results from their metaanalyses suggest robust evidence of effectiveness of collaborative care in improving depression symptoms, adherence to treatment; response to treatment, remission of symptoms, recovery from symptoms, quality of life/functional status, and satisfaction with care for patients diagnosed with depression.

# NEW: MODELS OF CARE (VIRTUAL CARE)
To optimize access to clinical services, " The use of telepsychiatry for care of older adults has been shown to be feasible and effective (Conn et al., 2013;Ramos-Rios et al., 2012). A systematic review of studies demonstrated that telehealth care is feasible and well-accepted in the areas of inpatient and nursing home consultation, cognitive testing, dementia diagnosis and treatment of depression in integrated and collaborative care models and psychotherapy (Gentry et al., 2019). However, the use of telepsychiatry in Canada has been quite limited prior to the COVID-19 pandemic. Since then the use of virtual care approaches has dramatically increased across multiple areas of healthcare. Older adults are often at a disadvantage with many having limited capacity to utilize newer technologies.
As such we strongly advocate for senior-friendly virtual care options with appropriate equipment and support. Health care providers should be familiar with the physical, psychological, and social risk factors for depressive disorders in older adults and include a screening for depression for their clients/ patients who present with some of these risk factors.

# Unchanged
We recommend targeted screening of those elderly at higher risk for depression due to the following situations:
- Recently bereaved with unusual symptoms (e.g., active suicidal ideation, guilt not related to the deceased, psychomotor retardation, mood congruent delusions, marked functional impairment after 2 months of the loss, reaction that seems out of proportion with the loss) Essentially unchanged, but note that the exclusion of major depression in the first 2 months after the loss and in bereavement was removed in Diagnostic and Statistical Manual of Mental Disorders, 5 th Edition (DSM-V). We recommend initial treatment with supportive psychosocial interventions or psychotherapy. If symptoms become severe enough to meet DSM-IV diagnostic criteria for a depressive disorder or persist after resolution of the stressor, more specific therapies in keeping with the revised diagnosis should be considered (e.g., medication, more intensive/ specific psychotherapy).

# Recommendations: Screening and Assessment -Screening and Screening Tools
No change except for new version of DSM (DSM-5).

# TREATMENT OPTIONS FOR TYPE AND SEVERITY OF DEPRESSION (CONT'D)
Recommendations Patients with severe unipolar depression should be offered a combination of antidepressants and concurrent psychotherapy when appropriate services are available and there is no contra-indication to either treatment.

# Unchanged
ECT should be considered if adequate trials of antidepressants combined with psychotherapy have been ineffective or if the health of the patient is deteriorating rapidly due to depression.
Electroconvulsive therapy (ECT) should be considered in the treatment of older patients with severe unipolar depression who have previously had a good response to a course of ECT and/or failed to respond to 1 or more adequate antidepressant trials plus psychotherapy, especially if their health is deteriorating rapidly due to depression. ECT is a firstline treatment in older, depressed patients who are at high risk of poor outcomes-those with suicidal ideation or intent, severe physical illness, or with psychotic features.
ECT can also be useful for continuation/maintenance therapy of older patients who are partially responsive, treatment resistant, or treatment intolerant with pharmacotherapy during the acute phase of treatment.
Recommendation: Treatment: Major Depressive Disorder, Single or Recurrent Episodes -Severe with Psychotic Features

# RECOMMENDATIONS 2021 NEW OR UPDATED RECOMMENDATIONS
If there is no specific contraindication to its use, patients with psychotic depression should be offered treatment with ECT when available. Alternatively, a combination of antidepressant plus antipsychotic medication should be used. If this combination is not effective (e.g., poorly tolerated, no improvement in at least some of the symptoms within 4-8 weeks of treatment, or lack of remission despite optimisation of dose and duration of treatment over more than 8-12 weeks), ECT needs to be offered. ECT should also be considered if severe health consequences (e.g., suicide, metabolic derangement) are imminent because pharmacological treatment has been poorly tolerated or would be too slow to provide needed improvements.
Recently, more placebo-controlled clinical trials reported safe and effective use of combined antidepressant and antipsychotic drugs in MDD with psychotic features, so we recommend that clinicians use their judgement based on severity and patient's physical conditions to try combination pharmacotherapy first. ECT should be considered after 4-8 weeks if combination therapy fails, is poorly tolerated, or if patient develops severe health consequences. Change of terminology from depression with co-morbid substance abuse to depression with co-morbid substance use disorder.

# TREATMENT OPTIONS FOR TYPE AND SEVERITY OF DEPRESSION (CONT'D)
Recommendation Change of terminology from depression with co-morbid substance abuse to depression with co-morbid substance use disorder. Psychotherapies and/or psychosocial treatments should be made available to older adults with depression (symptoms or disorder) in all settings (community, hospital, long-term care).

# Recommendations: Pharmacogenetic Testing
Evidence-based psychotherapies recommended for geriatric depressions include: behaviour therapy; cognitive-behaviour therapy; problem-solving therapy; brief dynamic therapy; interpersonal therapy; and reminiscence therapy.
Psychotherapies with the most evidence for effectiveness in older adults include: cognitive behavioural therapy (CBT)individual and group, and problem-solving therapy (PST). PST can be provided to older adults with cognitive impairment and executive dysfunction; CBT and PST have also been studied in older adults with medical comorbidity.
There is also evidence to support behaviour therapy, behavioural activation, reminiscence, and other psychotherapies including psychodynamic psychotherapy and interpersonal therapy.
Internet-delivered therapies may be comparable to face-toface treatment, and may improve access to services for individuals in under-serviced areas and those with mobility issues. When choosing agents from a specific class, clinicians should select those found to be safer with the elderly (e.g., selecting drugs with the lowest anti-cholinergic properties amongst available antidepressants).
We suggest clinicians choose an antidepressant with the lowest risk of anticholinergic side effects and drug-drug interactions as well as being relatively safe in the case of cardiovascular comorbidity. Patients need to be closely monitored for medication compliance, substance use, suicidal ideation, and development of drug toxicity.
We recommend that physicians and pharmacists consult up-to-date drug interaction data bases when a new antidepressant is prescribed to patients taking multiple medications. We recommend checking sodium blood levels after one month of treatment with SSRIs, especially with patients taking other medications that can cause hyponatremia (e.g., diuretics).
We recommend checking sodium levels before switching to another agent due to poor response or tolerance or when patients display symptoms of hyponatremia (e.g., fatigue, malaise, delirium).
When prescribing SSRI or SNRI antidepressants to older adults, the prescriber should screen for a history of hyponatremia before prescribing, as part of the consent process and then consider getting a sodium level prior to starting the antidepressant if there is a history of hyponatremia. Before considering a change in medication, it is important to ensure an adequate trial. Change should be made if: there is no improvement in symptoms after at least 4 weeks at the maximum tolerated or recommended dose; there is insufficient improvement after 8 weeks at the maximum tolerated or recommended dose.

# Unchanged
When significant improvement has occurred but recovery is not complete after an adequate trial, the clinician should consider:
- a further 4 weeks of treatment with or without augmentation with another antidepressant or lithium or specific psychotherapy (e.g., IPT, CBT, PST); - a switch to another antidepressant (same or another class) after discussing with the patient the potential risk of losing any significant improvements made with the first treatment.
When significant improvement has occurred but recovery is not complete after an adequate trial, the clinician should consider:
- a further 4 weeks of monotherapy or consider augmentation with another antidepressant or lithium or an antipsychotic (e.g., aripiprazole) or specific psychotherapy (e.g., IPT, CBT, PST). - a switch to another antidepressant (same or another class) after discussing with the patient the potential risk of losing any significant improvements made with the first treatment. - augmentation with lithium remains a viable option, but needs to be used carefully due to the risk of lithium toxicity. The clinician must be aware of how to monitor the patient on lithium over time through investigations.
When switching agents, it is generally safe to reduce the current medication while starting low doses of the alternate agent. Specific drug interaction profiles need to be checked for both drugs involved during this overlap since antidepressants commonly interact with each other.

# Unchanged
Augmentation strategies require supervision by experienced physicians.

# Unchanged
Given its long half-life and risk of interaction with many of the drugs prescribed for the elderly, we do not recommend the use of fluoxetine as first-line treatment despite its documented efficacy.
Fluoxetine is not recommended due to long biological halflife, paroxetine is not recommended due to higher anticholinergic effects, and first generation MAOIs are not recommended due to higher risk of serious drug-drug or drug-food interactions.
Antidepressants, especially SSRIs, should not be abruptly discontinued but should be tapered off over a 7 to10 day period when possible. In LTC homes, the response to antidepressant therapy should be evaluated monthly after initial improvement and at quarterly care conferences, as well as at the annual assessment after remission of symptoms.
A decision to continue or discontinue the antidepressant therapy should be based on:
- whether the depression has been treated long enough to allow sustained remission of symptoms (e.g., now one year of full remission); or - whether the treatment is still tolerated well in the context of their health problems; and - the risks of discontinuation (i.e., return of original depressive symptoms) are less than those associated with continuation of medication. 

# Unchanged
Health care professionals should provide older depressed adults with education regarding the nature of depression, its biological, psychological and social aspects, effective coping strategies, and lifestyle changes that will assist their recovery, while being mindful of the individual's stresses and strengths.

# Unchanged
Families of depressed older adults should be provided with information regarding the signs and symptoms of depression, attitudes and behaviours of the depressed person and their own reaction to them, and depression coping strategies, as well as available treatment options and the benefits of treatment. 

# Unchanged
The choice of mood stabilizer should be based on prior response to treatment, type of illness (e.g., rapid-cycling or not), medical contraindications to the use of specific mood stabilizers (i.e., side effects that could worsen pre-existing medical problems), and potential interactions with other drugs required by the patient.

# Unchanged
All mood stabilizers require monitoring over time for possible short-term and longer-term adverse events.
All mood stabilizers require monitoring over time for possible short-term and longer-term adverse events. Using lithium requires the patient, family, and healthcare team to understand the factors that may increase lithium levels leading to potential toxicity. Lithium can cause hypothyroidism, hypercalcemia through hyperparathyroidism, and renal dysfunction. The clinician must regularly monitor the patient on lithium, including laboratory investigations. There is limited evidence to recommend antidepressant therapy for mild or moderate depression associated with dementia. Behavioural interventions may be utilized as a firstline intervention and antidepressant medication could be offered if symptoms are severe and persistent, understanding that efficacy is not well established and that side effects could occur.
In selecting pharmacological treatment for depression with dementia, clinicians should select drugs that have low anticholinergic properties, such as citalopram and escitalopram, sertraline, moclobemide, venlafaxine, or bupropion.
As noted above, we recommend duloxetine and sertraline as first-line antidepressants, while recognizing that other antidepressants are also appropriate. Limiting exposure to anticholinergic properties remains an important consideration in patients with both dementia and depression.

# SPECIAL POPULATIONS (CONT'D)
Recommendations: Special Populations: Dementia

# RECOMMENDATIONS 2021 NEW OR UPDATED RECOMMENDATIONS
Psychosocial treatment should be part of the treatment of depression co-existing with dementia. This treatment should be flexible to account for the decline in functioning as well as multifaceted to provide help with the diversity of problems facing the patient and caregiver. It should be delivered by clinicians sensitized to the vulnerabilities and frailties of older adults with dementia. This treatment should include helping caregivers deal with the disease in a skill-oriented manner.

# Unchanged
For patients who have psychotic depression and dementia, a combination of antidepressant and antipsychotic medication is usually the first choice, although ECT may be used if medications are ineffective or rapid response is required to maintain safety. 

# MODELS OF CARE
Recommendations: Models of Care

# RECOMMENDATIONS 2021 NEW OR UPDATED RECOMMENDATIONS
Health care professionals and organizations should implement a model of care that addresses the physical/ functional as well as the psychosocial needs of older depressed adults.
Given the complex care needs of older adults, these are most likely to require interdisciplinary involvement in care, whether in primary care or specialized mental health settings.

# Unchanged
Health care professionals and organizations should implement a model of care that promotes continuity of care as older adults appear to respond better to consistent primary care providers.

# Unchanged
New:
Core elements of evidence-based models for treating late-life depression in primary care include: improved patient education, incorporating interprofessional staff as depression care managers who routinely assess and follow patients clinically, utilizing a stepped-care approach. Treatment prescriptions are provided by a primary care physician or nurse practitioner, with as needed psychiatric consultation.
An individualized plan of care should be developed using a collaborative approach.