Edited by: Francesca Assogna, Santa Lucia Foundation (IRCCS), Italy
Reviewed by: Nerisa Banaj, Santa Lucia Foundation (IRCCS), Italy; Luca Cravello, ASST Rhodense, Italy
*Correspondence: Luis Agüera-Ortiz,
This article was submitted to Aging Psychiatry, a section of the journal Frontiers in Psychiatry
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Present knowledge about depression in the elderly is still scarce and often controversial, despite its high frequency and impact. This article reports the results and most relevant conclusions of a Delphi-based consensus on geriatric depression promoted by the Spanish Psychogeriatric Association.
A 78-item questionnaire was developed by 7 highly specialized geriatric psychiatrists and was evaluated using the Modified Delphi technique in two rounds answered by 35 psychiatrists with an extensive expertise in geriatric depression. The topics and number of questions (in brackets) covered were: concepts, clinical aspects, and risk factors (12); screening and diagnosis (7); psychotic depression (17); depression and dementia (5); antidepressant drug treatment (18); non-pharmacological biological treatments (5); psychotherapeutic treatments (4); comorbidity and preventive aspects (6); professional training needed (4). In addition, the expert panel’s opinion on the antidepressants of choice in 21 common comorbid conditions and on different strategies to approach treatment-resistant cases in terms of both efficacy and safety was assessed.
After the two rounds of the Delphi process, consensus was reached for 59 (75.6%) of the 78 items. Detailed recommendations are included in the text. Considering pharmacological treatments, agomelatine was the most widely mentioned drug to be recommended in terms of safety in comorbid conditions. Desvenlafaxine, sertraline, and vortioxetine, were the most frequently recommended antidepressants in comorbid conditions in general. Combining parameters of efficacy and safety, experts recommended the following steps to address cases of treatment resistance: 1. Escalation to the maximum tolerated dose; 2. Change of antidepressant; 3. Combination with another antidepressant; 4. Potentiation with an antipsychotic or with lamotrigine; 5. Potentiation with lithium; 6. Potentiation with dopamine agonists or methylphenidate
Consensus was reached for a high number of items as well as for the management of depression in the context of comorbid conditions and in resistant cases. In the current absence of sufficient evidence-based information, our results can be used to inform medical doctors about clinical recommendations that might reduce uncertainty in the diagnosis and treatment of elderly patients with depressive disorders.
Depression in the elderly can be considered a real public health problem, because of its frequency, its clinical implications, and the great suffering that it causes (
The irrefutable epidemiological data pertaining to the increase in the proportion of elderly population and the high prevalence of depression in such age group have led to a growing demand for care that requires efficient, evidence-based responses (
However, until recent decades, neither primary care physicians nor specialists have given this disease due consideration, and this is reflected in the scarce literature on the topic. While professionals demand information, what can be found in the specialized literature, be it articles, books or clinical practice guidelines, does not frequently meet their expectations.
Significant advances have been made regarding the neurobiology of depression in older people, from many points of view, from basic science (
One way to remedy this situation is to draw up clinical practice guides and build expert consensuses. In recent years, the number of guides addressing geriatric depression therapy has slightly increased. However, the scarcity of documents that approach depression in the elderly from a broader perspective that goes beyond treatment is still remarkable (
The Spanish Psychogeriatric Association drew up a first consensus document on geriatric depression that was presented in 2011 (
The common goal of both projects was and is to reach consensus on a proposal for professional criteria and clinical recommendations to reduce uncertainty in the diagnosis and treatment of elderly patients with depressive disorders. As with the first edition of the Consensus, the latest version of the Delphi method, an agreement of expert’s technique that is reliable and has a long tradition of use in biomedicine has been used.
The main purpose of this project was to explore the opinion of a panel of experts in psychogeriatrics and reach sufficient professional consensus based on a battery of criteria and recommendations regarding depression management in elderly patients in the light of the available scientific knowledge and the panel’s clinical expertise.
The study consists of three parts: an actual consensus on different issues regarding the management of depression in the elderly, using the Delphi method; and two specific analyses that follow two different approaches, one addressing the choice of the most adequate antidepressant drug according to existing comorbidities and another on strategies for cases of inadequate response to antidepressant therapy.
This article reports the results and most relevant conclusions of the study, hoping that they might be of practical interest not only for specialists in psychiatry, but also for other professionals that care for the elderly, such as geriatricians, primary care physicians, physicians working at nursing homes, neurologists or psychologists, beyond the territorial context where it was carried out.
The first part of the consensus document is a study using the Delphi method. Such technique is based on the answers to a questionnaire previously drawn up by a scientific committee of experts or “core” provided to a group of experts in the same area, known as panellists, that is assessed more than once. The purpose of the series of questionnaires is to reduce variability in answers as far as possible.
The expert committee for this consensus consisted of seven leading members of the Spanish Psychogeriatric Association, and the panel of experts was made up of 35 psychiatrists with clinical expertise and specific professional recognition in the approach of depression in elderly patients, selected in accordance with the criteria of the expert committee following a
The scientific committee drew up a series of items for the survey, designed in the form of statements (positive and negative). A first list of these statements was built using in part those of the first edition of the consensus and many other new ones. In some instances, questions that achieved a good degree of agreement in the first edition were not repeated in the second in order to keep a manageable total number that could be adequately answered by the experts. The items included in the final questionnaire were the product of a process of consensus achieved through email exchanges among the members and a face-to-face meeting.
The final version of the survey contains 78 items structured into nine topic areas. The items by topic area were:
Topic area | Number of items |
---|---|
1.- Concepts, clinical aspects, and risk factors | 12 |
2.- Screening and diagnosis | 7 |
3.- Psychotic depression | 17 |
4.- Depression and dementia | 5 |
5.- Antidepressant drug treatment | 18 |
6.- Non-pharmacological biological treatments (fundamentally ECT) | 5 |
7.- Psychotherapeutic treatments | 4 |
8.- Comorbidity and preventive aspects | 6 |
9.- Professional training to address depression in the elderly | 4 |
TOTAL | 78 |
The two rounds of the Delphi process were performed in the first trimester of 2018. Once the Delphi method had been applied, results were organized and discussed by the core of experts, checking them against the existing scientific literature.
All the results and conclusions have been published in an extensive monograph that is available on the website of the Spanish Psychogeriatric Association (
The Delphi method is a structured technique for a process of group communication by members who are generally geographically scattered, and is effective in allowing a group of individuals, as a whole, to address a complex problem. The forecasting capacity of the Delphi method is based on the systematic use of an intuitive opinion expressed by a group of experts (
The modified Delphi method (
Statements (items) were assessed using a single ordinal nine-point Likert type scale, according to the UCLA-Rand Corporation format that is currently used for healthcare technology assessment (
1-3: I
4-6: I
7-9: I
The phases of the Delphi study are shown in
Phases of the Delphi study.
For each item of the questionnaire, the mean of the panelists’ scores and the confidence interval for the average at a 95% confidence level were calculated.
Interpretation according to statistical estimators was performed using the following explicit criteria for achieved or failed consensus:
The higher the average (closer to 9) for each item, the stronger the group’s agreement with the statement expressed by the item.
The lower the average (closer to 1) for each item, the stronger the group’s disagreement with the statement expressed by the item.
The lower the confidence interval, the greater the unanimity in the group’s agreement or disagreement opinions.
If the confidence interval encompasses the value 5 (“neither agree nor disagree”), the group does not reach unanimous consensus in either direction. In such case, a description of the causes for such lack of consensus in any direction of the side values will be described (there are either markedly different opinions among panelists, or most of the group claims to have no definitive criterion on the item).
The analysis of group opinion and the type of consensus reached on each of the questions posed was conducted using the position of the median of group scores (score zone: [1-3] [4-6] [7-9]) and the “level of agreement” reached by the respondents, according to the following criteria:
Item consensus was established when the panel showed “
Conversely, when the scores of one third or more of the panelists fell within the [1-3] zone and those of another third within the [7-9] zone, “discrepancy” in criterion was established. The remaining items that obtained neither consistency nor discrepancy were considered of “indeterminate” level of consensus.
All the items on which the group did not reach clear consensus in favor or against the issue (unclear items, those where disagreement can be observed and those where consensus was indeterminate) were proposed for reconsideration by the panelists in the second round of the Delphi. Items on which there was high dispersion of opinions among the respondents, with interquartile ratings ≥ 4 points (from p25 to p75) were also subjected to reassessment.
In between both rounds, panelists were informed of the detailed distribution of the group’s answers to the first survey (using bar graphs), and they were provided with the comments and explanations contributed by each participant. After reviewing such information, they were asked for a new personal assessment of the items on which no consensus had been reached in the first round.
The findings are presented using a color code that accounts for the final positioning of group opinion on each of the assessed items (a clinical criterion or recommendation):
Representation of findings is done as follows:
Preferences regarding the use of different antidepressants in patients with various medical comorbidities that are frequent in older adults were subjected to the consensus process and collected during the first round of the Delphi study. All the modern antidepressants available in Spain at the time of the fieldwork were included. Regarding the oldest drugs, monoamine oxidase inhibitors were not included, and of the tricyclics, only nortriptyline -which is possibly the most widely supported tricyclic choice for use in the elderly population- was assessed.
The observations in this section mostly refer to the safety of antidepressants in the presence of each of the listed situations and not to the efficacy of the drug under such circumstances, except in the generic case of chronic pain patients.
The comorbidity situations proposed were as follows:
Ischemic cardiomyopathy/infarction
Arrhythmias
Hypertension
Anticoagulated patient
Diabetes
Dyslipidemia
Obesity
Appetite and weight loss
Significant constipation
Risk of gastrointestinal bleeding
Risk of hyponatremia
Drowsiness
Falls
Alcohol abuse
Sexual dysfunction
Glaucoma
Risk of epileptic seizures
Stroke
Parkinson’s disease and extrapyramidal disorders
Cognitive impairment, dementia, Alzheimer’s disease
Pain disorders
For each of these situations, the expert was asked to choose among the following options:
Drug
Drug
Drug that
Drug that is a
Drug
No opinion about it
To facilitate interpretation, answers have been arranged according to the following criteria for each of the given comorbidity situations:
Selected as drug of choice by ≥ 6 panelists Selected as contraindicated drug by < 6 panelists |
|
Selected by ≥ 6 panelists Selected as contraindicated drug by < 6 panelists |
|
Selected as contraindicated drug by ≥ 6 panelists |
The last part of the consensus involved assessing the different strategies to approach cases where depression was resistant or where adequate response to the originally prescribed antidepressant treatment was not achieved, in terms of efficacy and of safety separately. This information was collected during the first round of the Delphi study.
Experts were provided with a list of 9 possible strategies to rank in order of preference. We opted for a fairly open definition of inadequate response or resistance to treatment. Experts were asked to order the 9 options in the form of progressive steps in case the previous one failed, in an attempt to reflect routine clinical practice.
Such 9 strategies were as follows:
Escalation to maximum dosage
Change to an antidepressant from a different group
Change to an antidepressant of the same group
Combination with another antidepressant
Potentiation with lithium
Potentiation with an antipsychotic drug
Potentiation with lamotrigine
Potentiation with a dopamine agonist
Potentiation with methylphenidate
Each of these options was to be assessed on a 1 to 9 scale, where 1 = first to use; and 9 = last to use. Besides, they were asked to rank the different options in order of safety on another 1 to 9 scale, where 1 = safest; and 9 = least safe. Results were analyzed by summarizing the number of votes.
After the two rounds of the Delphi process, consensus was reached for 59 (75.6%) of the 78 items that made up the survey. Such percentage comprises the 47 (60.2%) items where there was consensus in accepting the statement proposed and the 12 (15.4%) items where there was consensus in rejecting it. No consensus was reached on 19 items (24.4%).
The number and percentage of items (in brackets) for which a consensus was reached in each section were as follows:
Concepts, clinical aspects, and risk factors: Consensus in 11 (92%) out of 12 items. Screening and diagnosis: Consensus in 6 (85,7%) out of 7 items. Psychotic depression: Consensus in 10 (59%) out of 17 items. Depression and dementia: Consensus in all 5 (100%) items. Antidepressant drug treatment: Consensus in 11 (61%) out of 18 items. Non-pharmacological biological treatments (fundamentally ECT): Consensus in 4 (80%) out of 5 items. Psychotherapeutic therapies: Consensus in 2 (50%) out of 4 items. Comorbidity and preventive aspects Consensus in all 6 (100%) items. Professional training to address depression in the elderly: Consensus in all 4 (100%) items.
Degree of consensus for the items grouped into sections.
Section | Total items | Items that reached consensus (%) | Items that did not reach consensus (%) | ||
---|---|---|---|---|---|
Items with agreement consensus (%) | Items with disagreement` consensus (%) | ||||
Concepts, clinical aspects and risk factors | 12 | ||||
11 (92%) | 0 (0%) | ||||
Screening and diagnosis | 7 | ||||
5 (71,4%) | 1 (14,3%) | ||||
Psychotic depression | 17 | ||||
6 (35%) | 4 (24%) | ||||
Depression and dementia | 5 | ||||
4 (80%) | 1 (20%) | ||||
Antidepressant drug treatment | 18 | ||||
9 (50%) | 2 (11%) | ||||
Non-pharmacological biological treatment (fundamentally ECT) | 5 | ||||
2 (40%) | 2 (40%) | ||||
Psychotherapeutic therapies | 4 | ||||
2 (50%) | 0 (0%) | ||||
Comorbidity and preventive aspects | 6 | ||||
5 (83%) | 1 (17%) | ||||
Professional training to address depression in the elderly | 4 | ||||
3 (75%) | 1 (25%) | ||||
Total | 78 | ||||
47 (60.2%) | 12 (15.4%) |
Global results: Degree of consensus.
The degree of consensus on the different items grouped into nine topic areas is shown in
Topic area 1—Concepts, clinical aspects, and risk factors.
Consensus Disagreement | No consensus | Consensus Agreement | |
---|---|---|---|
1.1. Late-onset depression (first episode in old age rather than in adulthood) is a clinically useful concept in psychiatry. |
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1.2. Vascular depression is a clinically useful concept in psychiatry. |
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1.3. Depressive pseudodementia is a clinically useful concept in psychiatry. |
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1.4. Depression in the elderly, as compared to adults, is more specifically associated with higher levels of anxiety. |
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1.5. Depression in the elderly, as compared to adults, is more specifically associated with higher levels of hypochondriac symptomatology. |
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1.6. Depression in the elderly, as compared to adults, is more specifically associated with less likelihood to express sadness. |
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1.7. Depression in the elderly, as compared to adults, is more specifically associated with higher levels of suicidal ideation. |
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1.8. Depression in the elderly, as compared to adults, is more specifically associated with greater impact on daily life. |
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1.9. Frailty states in the transition from autonomy to dependence entail a significant risk factor for depression in old age. |
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1.10. Disclosure of a dementia diagnosis is a significant risk factor for depression in old age. |
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1.11. Severe physical diseases in older adults are a higher risk factor for suicide in men than in women. |
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1.12. Non-depressed older adults with thoughts of death require clinical care. |
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Topic area 2—Screening and diagnosis.
Consensus disagreement | No consensus | Consensus agreement | |
---|---|---|---|
2.1. The diagnostic criteria of standard nosologies (ICD 11, DSM5) are adequate to diagnose and classify depressive disorders in the elderly. |
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2.2. Specific diagnostic criteria for depressive disorders in the elderly population are necessary. |
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2.3. Teleassistance services should include some type of screening system for depression. |
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2.4. ALL elderly patients living in nursing homes should be systematically screened for depression. |
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2.5. ALL elderly patients should be systematically screened for depression in Primary Care. |
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2.6. Any diagnostic process in late-onset depression |
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2.7. Any diagnostic process in late-onset depression should include neuroimaging testing. |
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Topic area 3—Psychotic depression.
Consensus disagreement | No consensus | Consensus agreement | |
---|---|---|---|
3.1. Negativistic/oppositional behaviors in depressed older adults point towards the presence of psychotic depression. |
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3.2. The onset of psychotic symptoms in depressed older adults involves a higher risk for evolving into dementia. |
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3.3. The onset of psychotic symptoms in depressed older adults involves a greater risk for suicide. |
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3.4. ECT is the first therapeutic option to treat psychotic depression in the elderly. |
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3.5. Combined treatment with antidepressants and antipsychotics is the first therapeutic option to treat psychotic depression in the elderly. |
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3.6. ECT should ONLY be used to treat psychotic depression in older adults when there is lack of response to pharmacological treatment. |
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3.7. In psychotic depression in the elderly, dual-action antidepressants are preferable to SSRIs. |
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3.8. When pharmacological treatment fails, ECT is the best option to treat psychotic depression in the elderly. |
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3.9. In non-life-threatening psychotic depression in the elderly that does not respond to pharmacological treatment, ECT should be prescribed no later than 6 weeks. |
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3.10. In non-life-threatening psychotic depression in the elderly that does not respond to pharmacological treatment, ECT should be prescribed no later than 12 weeks. |
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3.11. In non-life-threatening psychotic depression in the elderly that does not respond to pharmacological treatment, ECT should be prescribed no later than 24 weeks. |
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3.12. After good response to ECT in the acute phase, pharmacological treatment combined with continuation/maintenance ECT is the treatment of choice to prevent early relapse and recurrence. |
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3.13. After good response to ECT in the acute phase, pharmacological-only continuation/maintenance treatment is the treatment of choice to prevent early relapse and recurrence. |
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3.14. After good response to ECT in the acute phase, continuation/maintenance ECT therapy-only is the treatment of choice to prevent early relapse and recurrence. |
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3.15. After good response to ECT in the acute phase, the addition of lithium to the combined antidepressant-antipsychotic drug therapy is the treatment of choice to prevent early relapse and recurrence. |
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3.16. During continuation/maintenance treatment of psychotic depression, the antipsychotic should be maintained as long as the antidepressant. |
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3.17. In psychotic depression in the elderly, pharmacological treatment should be maintained indefinitely even if there has only been one episode. |
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Topic area 4—Depression and dementia.
Consensus disagreement | No consensus | Consensus agreement | |
---|---|---|---|
4.1. The criteria to diagnose depression in dementia/major neurocognitive disorder are well defined and clinically useful. |
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4.2. It is necessary to establish differentiated depression criteria for the different diseases or clinical conditions that may involve dementia/major neurocognitive disorder (for example, Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, etc.). |
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4.3. It is necessary to establish differentiated depression criteria for the different phases of dementia/major neurocognitive disorder. |
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4.4. Antidepressant drugs are effective in the treatment of depression in dementia. |
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4.5. Psychological therapies are effective in the treatment of depression in dementia. |
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Topic area 5—Antidepressant drug treatment.
Consensus disagreement | No consensus | Consensus agreement | |
---|---|---|---|
5.1. Subclinical depression requires pharmacological treatment. |
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5.2. When prescribing antidepressants for elderly patients, laboratory tests should be carried out at the beginning of treatment. |
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5.3. When prescribing an antidepressant for an elderly patient, an EKG should be performed at the beginning of treatment. |
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5.4. In general, SSRIs antidepressants are first choice treatment drugs for depression in the elderly. |
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5.5. In general, dual-action antidepressants are first choice drugs for depression in the elderly. |
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5.6. Dual-action antidepressants achieve higher levels of effectiveness in the treatment of depression in the elderly as compared to SSRIs. |
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5.7. Dietary supplements (Omega 3, DHA…) are effective in improving depression in the elderly. |
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5.8. Antidepressants have a slower onset of action in the elderly than in younger adults. |
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5.9. The introduction of antidepressants increases the risk for suicide in depressed elderly patients at the beginning of treatment. |
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5.10. The elderly tolerate dual-action antidepressants better than SSRIs. |
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5.11. Sexual dysfunction caused by antidepressants is a problem for elderly patients. |
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5.12. After a depressive episode in an elderly patient, treatment at effective doses should be maintained for 6 months. |
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5.13. After a depressive episode in an older adult, treatment at effective doses should be maintained for 1 year. |
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5.14. After a depressive episode in an older adult, treatment at effective doses should be maintained for 2 years. |
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5.15. After a depressive episode in an older adult, treatment at effective doses should be maintained for 3 to 4 years. |
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5.16. In depression in elderly patients, indefinite pharmacological therapy should be stablished after the first episode. |
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5.17. In depression in elderly patients, indefinite pharmacological therapy should be stablished after the second episode. |
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5.18. In depression in elderly patients, indefinite pharmacological therapy should be stablished after the third episode. |
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Topic area 6—Non-pharmacological biological treatments (fundamentally ECT).
Consensus disagreement | No consensus | Consensus agreement | |
---|---|---|---|
6.1. ECT is indicated for vascular depression. |
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6.2. ECT is indicated for depression in elderly patients with dementia. |
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6.3. Bilateral ECT should only be used when unilateral ECT yields unsatisfactory results. |
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6.4. Cognitive effects associated with ECT significantly limit its indication for depression in elderly patients. |
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6.5. Transcranial magnetic stimulation should be regarded as a therapeutic option for resistant depression in elderly patients. |
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Topic area 7—Psychotherapeutic treatments.
Consensus disagreement | No consensus | Consensus agreement | |
---|---|---|---|
7.1. The efficacy of psychotherapy in geriatric depression is at least equal to that of pharmacological treatments. |
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7.2. Psychotherapy is less effective in the elderly than in adults. |
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7.3. In geriatric depression, the presence of cognitive impairment/mild dementia does not limit the use of psychotherapy. |
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7.4. Psychotherapy is effective in the treatment of subclinical geriatric depression. |
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Topic area 8—Comorbidity and preventive aspects.
Consensus disagreement | No consensus | Consensus agreement | |
---|---|---|---|
8.1. In cases of late-onset depression it is necessary to consider the subsequent development of a neurodegenerative disorder (dementia, Parkinson’s disease, etc.). |
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8.2. In cases of late-onset depression it is necessary to consider the subsequent development of a major medical condition (cancer, cardiopathies, etc.). |
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8.3. Elderly patients living in nursing homes have access to the same therapies (antidepressant treatment, psychotherapies, ECT, etc.) as those living in the community. |
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8.4. Teleassistance services are useful to reduce the risk for suicide in the elderly. |
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8.5. Physical exercise has a significant protective effect against depression in old age. |
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8.6. Interventions aimed at reducing social isolation are significant and effective strategies in the prevention of depression in the elderly. |
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Topic area 9—Professional training to address depression in the elderly.
Consensus disagreement | No consensus | Consensus agreement | |
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9.1. The training received by residents in psychiatry is currently insufficient to competently address depressive disorders in older adults. |
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9.2. Psychiatrists require specific training to competently address depressive disorders in older adults. |
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9.3. Detection of depression in older adults is currently noticeably below optimal and desirable levels. |
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9.4. Because of its complexity, depression on older adults should be mainly treated by specialists in psychiatry. |
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Individual drug recommendations for different comorbidity situations.
Recommended | Reasonable option | To be avoided | |
---|---|---|---|
Ischemic cardiomyopathy/infarction | Sertraline, agomelatine | Desvenlafaxine, venlafaxine, fluvoxamine, vortioxetine, mirtazapine | Citalopram/escitalopram, reboxetine, nortriptyline |
Arrhythmias | Sertraline, agomelatine | Desvenlafaxine, fluoxetine, fluvoxamine, vortioxetine, mirtazapine | Citalopram/escitalopram, bupropion, reboxetine, nortriptyline |
Hypertension | Sertraline, agomelatine | Citalopram/escitalopram, fluoxetine, fluvoxamine, paroxetine, vortioxetine, mirtazapine | Venlafaxine |
Anticoagulated patient | Desvenlafaxine, venlafaxine, duloxetine, sertraline, citalopram/escitalopram, mirtazapine, bupropion, agomelatine, vortioxetine | ||
Diabetes | Desvenlafaxine, venlafaxine, duloxetine, fluoxetine, sertraline, citalopram/escitalopram, agomelatine, vortioxetine, bupropion, reboxetine | ||
Dyslipidemia | Fluoxetine, sertraline, citalopram/escitalopram, duloxetine, bupropion, vortioxetine, agomelatine | ||
Obesity | Fluoxetine, bupropion, agomelatine | Desvenlafaxine, venlafaxine, duloxetine, citalopram/escitalopram, fluvoxamine, sertraline, vortioxetine, reboxetine | Mirtazapine |
Appetite and weight loss | Mirtazapine | Desvenlafaxine, venlafaxine, duloxetine, paroxetine, sertraline, citalopram/escitalopram, nortriptyline | Fluoxetine |
Significant constipation | Fluoxetine, fluvoxamine, sertraline, citalopram/escitalopram, bupropion, agomelatine, vortioxetine | ||
Risk of gastrointestinal bleeding | Desvenlafaxine, venlafaxine, mirtazapine, bupropion, nortriptyline | Fluoxetine, citalopram/escitalopram | |
Risk of hyponatremia | Desvenlafaxine, venlafaxine, duloxetine, mirtazapine, bupropion, agomelatine, vortioxetine | Fluoxetine, citalopram/escitalopram | |
Drowsiness | Bupropion | Desvenlafaxine, venlafaxine, fluoxetine, sertraline, citalopram/escitalopram, reboxetine, agomelatine, vortioxetine | Mirtazapine |
Falls | Desvenlafaxine, venlafaxine, duloxetine, fluoxetine, sertraline, citalopram/escitalopram, bupropion, vortioxetine | Nortriptyline | |
Alcohol abuse | Desvenlafaxine, venlafaxine, duloxetine, fluoxetine, paroxetine, Sertraline, citalopram/escitalopram, mirtazapine, bupropion, vortioxetine | ||
Sexual dysfunction | Agomelatine, bupropion, mirtazapine | Reboxetine, vortioxetine | Fluoxetine, paroxetine |
Glaucoma | Desvenlafaxine, sertraline, citalopram/escitalopram, bupropion, agomelatine, vortioxetine, tianeptine | nortriptyline, venlafaxine | |
Risk of epileptic seizures | Mirtazapine | Nortriptyline, bupropion | |
Stroke | Desvenlafaxine, sertraline, citalopram/escitalopram, agomelatine, vortioxetine, mirtazapine | ||
Parkinson’s disease and extrapyramidal disorders | Bupropion | Desvenlafaxine, venlafaxine, duloxetine, sertraline, agomelatine, vortioxetine, mirtazapine, tianeptine | |
Cognitive impairment, dementia, Alzheimer’s disease | Desvenlafaxine, venlafaxine, duloxetine, sertraline, citalopram/escitalopram, bupropion, agomelatine, vortioxetine, mirtazapine | Nortriptyline | |
Pain disorders | Duloxetine, desvenlafaxine, venlafaxine | Nortriptyline |
Priority strategy for efficacy in treatment-resistant depression.
Priority strategy for safety in treatment-resistant depression.
The discussion of results is approached using a question-answer format, since this makes understanding and grouping into homogeneous areas easier.
A basic question is to consider whether geriatric depression as an entity is sufficiently defined in itself and in relation to that of the adult. Furthermore, it is important to discern which are the relevant aspects for the diagnostic process.
The panel of experts defended the importance of the clinical differences between depression in old age and depression in younger adults, specifically stressing a possible increase in anxiety, hypochondriac symptoms, suicidal ideation, and functional impact in the elderly, alongside with less likeliness to express sadness.
It should be noted that whether there are differences or not in symptomatology—somatic, cognitive, emotional—between depression in the elderly and in young individuals has been discussed at length (
There is major consensus on considering that the criteria of current nosology to diagnose and classify depression in the latest stages of life are insufficient. According to our experts, the particularities of the clinical expression of depression in older adults, its evolution (which is associated with a greater risk for becoming chronic and with higher relapse rates) and its high comorbidity with other somatic and brain pathologies (
The practically unanimous recommendation of our experts, which is consistent with that found in the scientific literature (
It is not possible to infer from the previous statements that experts regard depression in the elderly as a different clinical entity from that in adults, but rather that they recommend greater alertness when gathering the clinical singularities in the diagnostic algorithm.
A favorable agreement on the clinical usefulness of the concepts of “late-onset depression” and “vascular depression” was reached, although there is not enough empirical evidence of them yet. In the first case, interest is associated with a tendency to the onset of more prominent cognitive symptoms, brain lesions – for example, of a vascular nature – and a higher risk for developing dementia in cases of late onset (
On the other hand, there is no consensus on the clinical usefulness of the concept of “depressive pseudodementia”, a traditional term that refers to the onset of symptoms involving such prominent cognitive and functional impairment that they imitate the presence of a dementia disorder, but that are really caused by a case of depression and are therefore approachable using the appropriate antidepressant treatment. The classical controversies around the usefulness of the concept are reflected in the dispersion of answers obtained in this consensus. In any case, it must be noted that the term has plainly fallen into disuse in scientific literature.
The request for laboratory testing throughout the process of diagnosing geriatric depression has been a subject of discussion. According to our experts, the high comorbidity that is often present in these patients, many of them sufferers of multiple pathologies and also polymedicated, makes it necessary to carry out laboratory tests. Their opinion, however, is less unanimous as to the routine use of neuroimaging tests, despite their importance in the differential diagnosis of dementia cases (
It is suspected that a substantial percentage of cases of depression in the elderly are not adequately identified, which would preclude appropriate care. A specific diagnostic category for geriatric depression would probably allow better identification of the process. To develop, implement and maintain an efficient detection process seems to be the first step towards a successful therapeutic approach.
We have gathered the opinion of experts on the suitability of using screening strategies at different levels (primary care, nursing homes for the elderly or through teleassistance services) for all senior patients. Most answers expressed agreement with the use of such strategies for the detection of these processes. However, there was a percentage (around 10%) who did not believe in the appropriateness of systematic screening for depression in elderly patients in primary care, an opinion that is in contrast with the efforts that are being made to assign initial treatment in depression cases in the first levels of care, regardless of the population group that is affected (
Three interesting questions referred to risk factors were added to those concerning diagnosis:
There was consensus that the presence of physical conditions is a more significant risk factor for suicide in men than in women.
There was consensus among the experts that the presence of thoughts of death in older adults who are apparently not depressed requires clinical care and assessment. This is because ideas of death in the elderly are associated with significant psychological distress, even in people who are not diagnosed with depression, and can be a symptom of subclinical depression or even a risk factor for suicide (
As well as regarding the path from autonomy to dependence as a risk factor for depression in older adults, disclosure of a diagnosis of dementia was signaled by the experts as a significant risk factor for depression in this population. Nevertheless, it should be noted that there is growing evidence suggesting that the diagnosis of dementia can be safely communicated if done so in an appropriate way (
Psychotic depression (PD) is to date one of the most controversial clinical syndromes in the specific psychopathology of older adults, especially in aspects regarding its clinical presentation, therapeutics, and prognosis, and this consensus devotes a high number of questions to it.
At the psychopathological level, PD in general has been regarded by certain authors as a separate nosological entity. Psychotic symptoms are considered a criterion of endogeneity and a manifestation more commonly found in old age (
There is sound scientific evidence of the risk for developing dementia associated with the cases of depression and psychosis in older adults (
Most studies in PD in general note the superiority of electroconvulsive therapy (ECT) over combined antidepressant/antipsychotic (AD/AP) pharmacological therapy, and of the latter over pharmacological antidepressant monotherapy. There are scarce comparative studies on both therapeutic options. Current guidelines for the pharmacological treatment of depression in the elderly recommend the use of atypical antipsychotics, SSRI antidepressants, and dual-action antidepressants (
There is a high level of agreement among the experts consulted on the use of combined therapy with antipsychotics and antidepressants as the first therapeutic option in psychotic depression in the elderly. Likewise, there is broad consensus among them on the preference of using dual-action antidepressants over other pharmacological antidepressant options, and they also agree that ECT is the best therapeutic option when pharmacological treatment fails, although there is group disagreement as to its exclusive use in such circumstances. In the same line, there is no agreement among our experts on ECT being the first therapeutic option for PD in the elderly, so that its prescription remains subject to individual needs and to the risk-benefit balance of each case. After starting combined pharmacological treatment, and in absence of vital risk, no consensus is reached by the experts on the time required to assess refractoriness to pharmacological treatment prior to prescribing ECT, although the panel strongly disagrees with prescribing ECT beyond 24 weeks from the described situation, thus it should be used earlier.
Psychotic depression in the elderly is associated with high rates of relapse and/or recurrence, sometimes early in time (
The group of experts reaches minimum group agreement on the recommendation of using maintenance ECT alongside combined AD/AP pharmacological maintenance therapy as the treatment of choice if ECT was needed, against therapeutic options such as pharmacological monotherapy or only maintenance ECT to prevent mid/long-term relapse and recurrence. The opinion of our experts is consistent with the results on long-term effectiveness that certain authors describe in the literature (
Adding lithium for maintenance treatment has been suggested as effective to prevent recurrence in recurrent depressive disorder with psychotic symptoms after its remission using ECT during the index episode (
There is a complex relationship between dementia and depression. This topic was extensively addressed in the first edition of this consensus (
Depression and dementia are very frequent disorders in the elderly population, and there is evidence that they share some common neurobiological mechanisms. Likewise, it seems well established that depression throughout life is a risk factor for dementia, and that late-onset depression can sometimes be a prodrome for a dementia syndrome (
It should be emphasized that our experts’ answers show a high level of consensus on the questions regarding this issue. There is a clear consensus on the disagreement with the accuracy in the definition and usefulness of the current criteria for diagnosing depression in dementia/major neurocognitive disorder. The experts support the need to establish distinct criteria for depression in the different diseases or entities that might involve dementia/major neurocognitive disorder such as, for example, Alzheimer’s or Parkinson’s disease and also for the different severity phases of dementia, since their clinical expression may vary widely depending on the degree of impairment (
As regards to therapeutic interventions, the experts agree that both antidepressant drugs and psychological therapy can be effective in treating depression in dementia, although evidence in this area is still scarce and disparate (
The main therapeutic approach in geriatric depression consists on the use of antidepressant drugs, which is the most common first-line treatment. Despite the clinical importance of an adequate therapeutic approach to this condition, studies in this population group and the evidence they provide are still insufficient. Thus, evidence-based therapeutic recommendations in adult populations are often extrapolated to this age group, which might not be appropriate. Given its importance, this is the part that accounts for the highest number of questions of those addressed in this consensus.
The experts consulted failed to reach an agreement on this issue, with a bimodal distribution where two clearly dichotomic opinions can be observed: one of the groups of panelists is against the use of antidepressant drugs, while the other chooses to use pharmacological treatment in subclinical depression.
The experts were in favor of preforming laboratory tests and an electrocardiogram prior to choosing the appropriate antidepressant treatment. Their opinion is consistent with that found in the scientific literature regarding the advisable procedures before beginning treatment in geriatric depression (
SSRI antidepressants were regarded as the first choice in the treatment of geriatric depression. More than half of the experts extended first-line treatment to dual-action antidepressants, although no statistical consensus was reached in this issue. By contrast, in the former edition of this consensus there was consensus that dual-action drugs are also first choice drugs (
The experts have agreed that dual-action antidepressants are more effective than SSRI in geriatric depression. This is in contrast with the fact that, as mentioned before, no agreement is reached on dual-action antidepressants being first-line drugs. This could be more of a reflection of clinical habits or economic criteria than of an application of the available clinical evidence although the latter is not unanimous (
In conclusion, although in the opinion of our experts SSRIs can be considered as first-choice agents, dual-action drugs are preferred in terms of efficacy.
There was no consensus in favor or against this issue among the psychiatrists consulted, whose answers mainly reflect their lack of experience with these agents. While there are publications that support the use of dietary supplements in depressed elderly population (
There was consensus among the experts consulted on the presence of increased antidepressant response latency in older adults. This usually entails the need for a longer period to assess efficacy.
This is a controversial issue regardless of age. Although there was a certain trend in favor of this assertion, experts did not reach consensus, providing very heterogeneous answers.
No consensus was reached on the issue of different tolerability between dual-action antidepressants and SSRI. On the other hand, there was unanimous consensus that antidepressant drug-induced sexual dysfunction also happens and is a problem among the elderly population.
In the absence of scientific evidence on the issue, the scientific committee deemed it appropriate to ask the experts several questions about the right length of time for maintenance treatment and when it should be prolonged indefinitely.
It was agreed that one year would be a suitable length of time for maintenance therapy after an isolated episode, and there was disagreement on maintaining this treatment up to three or four years. Indefinite treatment was rejected for a first depressive episode, and the experts consulted agreed on recommending indefinite pharmacological treatment from the second depressive episode onwards.
As mentioned, the answers to this question, grouped according to the relevant condition, are gathered in
Desvenlafaxine and sertraline, followed by vortioxetine, are the antidepressants that appear most frequently as recommended or good alternatives.
Treatment-resistant depression is a significant concern among clinicians who care for depressed elderly patients. An international survey of 585 psychiatrists revealed that treatment-resistant depression could amount to between a quarter to a half of their workload, geriatric depression accounting for between 10 and 25% of this load (
Panelists were provided with a list of possible strategies to use in the event of unsatisfactory response to a first prescribed antidepressant treatment, chosen among the most commonly mentioned in the literature (
Regarding the efficacy of the different options provided, the most widely supported first instance strategy was the escalation of the antidepressant to the maximum dose. This recommendation differs partly from the common procedure of using low doses in elderly patients and suggests increasing the dose to the maximum tolerated in cases of inadequate therapeutic response.
The second and third most supported strategies after this are changing to an antidepressant of a different group and changing to one belonging to the same group, respectively. It is estimated that these are the most common alternatives in any branch of medicine.
The answers suggested for cases when these strategies fail are of special interest. The combination of antidepressants in elderly patients with inadequate response is highly supported by the experts, followed by two possible potentiation actions using an antipsychotic or using lamotrigine, both of them with similar levels of support. Far below is lithium potentiation, and the potentiation with dopaminergic agents or methylphenidate comes last.
This information must be combined with that referred to safety aspects. The strategy that was indicated as the safest was the same that was chosen as the first alternative: dose escalation. This means that escalation to maximum dosage with modern antidepressants is believed to be not only effective, but also safe. Changing to an antidepressant of a different group or combining antidepressants is the next stated, with a similar degree of safety. On the following level, considered less safe, is improvement using an antipsychotic, lithium or lamotrigine -all three of them believed to be very similar in terms of safety-, and next, changing to an antidepressant of the same group. Improvement using dopamine agonists or methylphenidate are viewed as the least safe alternatives, which could perhaps reflect that experts do not have much experience with these agents.
In short, according to their efficacy and safety, the panel of experts recommends the following steps in order of preference for cases of resistance or insufficient response to antidepressant treatment:
1. Escalation to the maximum tolerated dose
2. Change of antidepressant
3. Combination with another antidepressant
4. Potentiation with an antipsychotic or with lamotrigine
5. Potentiation with lithium
6. Potentiation with dopamine agonists or methylphenidate
There is currently broad agreement about the effectiveness of Electroconvulsive Therapy (ECT) in aged patients (
The incidence of side effects is low, and there are hardly any absolute contraindications, so that it is safe and especially indicated in the elderly (
The most common response was yes. Although the concept of vascular depression is still partially questioned, the answers could be directed towards the effectivity of ECT when vascular factors are clearly involved in cases of depression in older adults (
Here, most of the consensus group also answered affirmatively. Despite the fact that one of the potential side effects of ECT is secondary cognitive impairment, this is not considered decisive to discourage its use in severe depressive episodes suffered by patients with cognitive impairment or dementia. It is not uncommon for patients with dementia to experience regressive behaviors, such as active food intake refusal or other severe behavioral disturbances, such as agitation or aggression (
Most of the group disagrees with this assertion. There is evidence, and controversy, regarding the greater effectiveness of using bilateral over unilateral ECT in cases of severe depression (
Group consensus is again reached against this assertion. ECT-related cognitive effects are frequent within all age ranges and are one of the common reasons for complaint among patients. Moreover, there are a series of concurrent factors in the elderly that are associated with greater cognitive side-effects: older age (
Transcranial magnetic stimulation (rTMS) consists in magnetic stimuli applied in a rhythmic and repeated way, with different frequency ranges. It has proven effective to treat depression and, also, chronic pain, stroke, Parkinson’s disease, schizophrenia, and obsessive-compulsive disorder among others (
The experts took no position for or against the statement, probably for a lack of direct experience or the absence of conclusive data on its effectiveness.
There is not yet much consensus among experts on the issue of psychotherapy in older adults, perhaps due in part to the heterogeneity of the studies available and the difficulty to compare them.
The efficacy of psychological treatments for depression in older adults is already sufficiently supported in the literature. Meta-analytic studies involving randomized controlled trials (
All of the above endorses the fact that the elderly can benefit from psychotherapeutic treatments, when available. But, despite their acknowledged efficacy, their use on this segment of the population is still rare. This seems due to the scarce availability in healthcare services of these treatments for the elderly and to the prejudices of professionals who are generally reluctant to carry out these interventions (
While old age in itself is not an obstacle to psychotherapy (
Psychological treatments might be more relevant in the elderly, since aged patients with depression are more vulnerable to the side effects and pharmacological interactions of drugs. (
Our study shows general consensus in favor of psychotherapy’s efficacy in treating subclinical geriatric depression. The studies reviewed that included patients suffering from minor depression or dysthymia provided evidence of psychotherapy’s greater effect.
Research in the area suggests that psychotherapies are effective even in the presence of cognitive impairment (
Even though 45.7% of the experts consulted believe that psychotherapy is not as effective as pharmacological treatment in the elderly, the opinion is not homogeneous enough to achieve consensus.
Among the studies that exclusively compare psychotherapeutic treatment with treatment combining psychotherapy and pharmacotherapy (
Research confirms the vulnerability of depressed individuals to physical diseases in general. In 2004, the World Health Organization included comorbidity between depression and chronic physical illness among its ten world public health concerns.
The association between depression and medical conditions is bidirectional, being especially relevant in old age. While such relationship has been extensively studied, and although there is an increase in the number of studies where depression is regarded as a result of chronic conditions (
In our study, there is outstanding consensus with regard to the comorbidity of geriatric depression. More than 90% of the experts agreed that the presence of late-onset depression makes it necessary to consider the eventual onset of a neurodegenerative disorder (e.g. dementia or Parkinson’s disease) or of serious medical conditions such as cancer or heart disease (77% of the group of experts).
There are robust data supporting that the presence of depression in the elderly population is associated with greater social isolation. Loneliness and social isolation are linked with higher rates of morbimortality, especially from mental disorders or cardiovascular disease (
In our study, the experts surveyed show maximum consensus on the assertion that interventions aimed at reducing social isolation are a significant strategy that is effective in the prevention of depression in older adults.
Sustained physical activity is associated with increased longevity and better maintenance of physical and mental functions (
In our study, there is broad and consistent consensus among the experts on the significance of physical exercise as a protecting factor against depression in old age.
According to the reviews on interventions to reduce suicide in the elderly population, the most effective were multifaceted depression detection and management programs in primary care, therapeutic approaches (pharmacotherapy and psychotherapy), community programs, and telephone counseling for vulnerable older adults (
Our experts agree that teleassistance services are useful in reducing the risk for suicide in older adults.
There was also consensus in our study that elderly people living in geriatric nursing homes do not have access to the same treatments (antidepressants, psychotherapy, ECT, etc.) as those living in the community. It seems evident that therapeutic resources vary widely according to place of residence and type of geriatric institution, which has an impact on both care and prevention.
Addressing depression in elderly patients poses significant challenges for professionals. Its clinical characteristics could partly explain why it is an infradiagnosed disease. Clinical comorbidity (
The mostly negative answer to this question reflects the opinion that the training in geriatric psychiatry that is provided during the training of psychiatrists is insufficient. A survey reported that in Spain, around 60% of the psychiatry residents lack any type of specific training in psychogeriatrics, despite awareness (87.7%) of it being an especially relevant area of training. Psychiatry residents’ supervisors believe (61.9%) that the former are not provided with adequate training and consider (81%) that this should be a compulsory subject (
The most common answer is yes. The detection of affective disorders in the elderly presents complexities that can only be addressed if psychiatrists have the adequate skills. Thus, low rates of identification of depressive symptomatology have been documented among psychiatrists (
While there are certain nuances, it is acknowledged that psychiatrists are the right specialists for the diagnosis and therapeutic management of depression in older adults, especially in the most severe cases, although many depressive episodes are currently addressed in primary care. The difficulties experienced by general practitioners in detecting geriatric depression have to do among other causes, with patients’ reasons for consulting—being the most common physical ailments (
In summary, a broad degree of consensus was achieved, reaching two thirds of the questions raised.
Clinical differences between depression in the elderly and in younger adults and the need for these differences to appear in current classification systems (including the concepts of late-onset and vascular depression) were highlighted. Specific criteria for depression in the context of dementia are also needed. Routine laboratory tests but not neuroimaging is recommended in the regular clinical assessment of geriatric depression.
The presence of late-onset depression makes it necessary to consider the subsequent onset of a neurodegenerative disorder such as dementia or Parkinson’s disease or of serious medical conditions such as cancer or heart disease.
The onset of psychotic symptoms in geriatric depression confers an increased risk for evolution into dementia and is also related to a higher risk for suicide. Combined therapy with antipsychotics and antidepressants is considered the first therapeutic option in psychotic depression in the elderly. ECT is the best therapeutic option when pharmacological treatment fails.
The experts were in favor of preforming laboratory tests and an electrocardiogram prior to choosing the appropriate pharmacological antidepressant treatment. Although SSRI antidepressants were regarded as the first choice, dual-action antidepressants were considered more effective than SSRI in geriatric depression.
Experts consulted agreed on the presence of an increased antidepressant response latency in older adults. Once response is achieved, one year is deemed necessary for maintenance therapy after an isolated episode in old age and recommendations are made for indefinite pharmacological treatment from the second depressive episode onwards.
In terms of pharmacological treatments, agomelatine was the most widely mentioned drug recommended in comorbid conditions in terms of safety. Desvenlafaxine, sertraline, and vortioxetine, were the most frequently recommended antidepressants in comorbid conditions in general.
Combining parameters of efficacy and safety, experts recommended to follow some gradual steps to address cases of treatment resistance. These are: 1. Escalation to the maximum tolerated dose; 2. Change of antidepressant; 3. Combination with another antidepressant; 4. Potentiation with an antipsychotic or with lamotrigine; 5. Potentiation with lithium; 6. Potentiation with a dopamine agonist or methylphenidate.
There is broad agreement about the effectiveness of ECT in elderly patients especially in cases of severe depression or in the presence of a significant physical condition. ECT can also be recommended in vascular depression and in severely depressed patients with dementia.
Although it might be less effective than in adults, the experts recommend the use of psychotherapy for clinical and subclinical geriatric depression even in the presence of mild cognitive impairment or mild dementia. Interventions aimed at reducing social isolation and promoting physical exercise are strategies that can be effective in the prevention of depression in older adults.
Psychiatrists are considered the adequate specialists for the diagnosis and therapeutic management of depression in older adults, especially in severe cases. Thus, all psychiatry medical residents should receive a specific training in geriatric psychiatry in general and in geriatric depression in particular
We hope that this consensus can contribute to reduce uncertainty in the diagnosis and treatment of elderly patients with depressive disorders, but further formal research is needed to shed light on the still unclear and controversial aspects of this disease
The datasets generated for this study are available on request to the corresponding author.
Ethical approval and written, informed consent was not required according to local legislation and national guidelines.
All the authors contributed equally to the study design and manuscript preparation. LA-O coordinated the expert group.
The Spanish Psychogeriatric Association received economic support from Pfizer Spain for the technical aspects of this study (Delphi analysis). Pfizer was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
LA-O has received honoraria by Exeltis, Janssen, Lundbeck, Neuraxfarm, Otsuka, Servier and Pfizer. MM-C has received honoraria by Pfizer, Servier, and Lundbeck. MR-P has received honoraria by Janssen, Ludnbeck, Neuraxpharm, Otsuka, and Pfizer. MS-P has received honoraria by Exeltis, Lundbeck, Otsuka, Pfizer, and Servier.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Dr. Manuel Franco MD, PhD, President of the Spanish Psychogeriatric Association provided all kind of support for the development of the manuscript. Dr. Fernando Caballero MD, PhD provided technical support for the Delphi technique and analysis. Julia Sevilla Llewellyn-Jones PhD revised the manuscript for the quality of the English language.
The Supplementary Material for this article can be found online at: