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Oxford University Press 2001 Printed in Great Britain Treatments for late life depression in primary care—
a systematic review
Ulrich Freudenstein, Carol Jaggera, Antony Arthura and
Norbert Donner-Banzhoffb
Freudenstein U, Jagger C, Arthur A and Donner-Banzhoff N. Treatments for late life depression
in primary care—a systematic review. Family Practice 2001; 18: 321–327.
Background. Depression is common among older people. It is associated with increased
mortality and use of health services. We could identify no prior systematic review of treatment
for depression in either primary care attenders or population samples of older people.
Objectives. The aim of this study was to carry out a systematic review of trials of treatments
for depression of patients over 60 years of age in primary care or population samples.
Methods. We searched Medline, Embase, Cinahl, the Cochrane Library, Psyclit, BIDS—Social
Science and BIDS—Science Citation Indices for trials of drug treatment, interpersonal psycho-
therapy, cognitive behavioural psychotherapy, counselling and social interventions for late life
depression in English, French or German published between 1980 and June 1999.
Results. Of the studies identified, only two were of patients over 60 years of age and met all
inclusion criteria for content and quality. Three further studies that were not restricted to but
included patients over the age of 60 years also fulfilled our criteria. We found no studies of psycho-
logical therapies for depression in older people. With few exceptions, studies were limited to older
people who reached a diagnostic threshold and excluded those with ‘subcase level depression'.
Conclusion. There is little evidence of effectiveness for a variety of treatment approaches
for depression in older people in primary care, particularly in those with less severe depression.
As older people take more medication, making contra-indications to the use of antidepressant
drugs more likely, there is a pressing need for studies of the efficacy of non-pharmacological
interventions in primary care settings.
Keywords. Aged, depression, drug therapy, primary health care, psychotherapy.
evidence exists concerning the management of depres-sion in other settings,8 yet a review of international studies Major depression is associated with subjective well- (mostly conducted in Britain and the USA) suggests that being, increased mortality1,2 and, more importantly only 10% of depressed older people are referred to for health care providers, increased health service psychiatric services.9 This latter group are likely to differ utilization.3–5 The weighted average prevalence of major substantially from depressed primary care attenders by depression in older people was 1.8% in an international being more severely depressed.10,11 systematic review, although estimates as high as 35% We have sought, therefore, to identify studies of treat- have been reported.6 ments for depression in older people in primary care in Little is known about the effectiveness of treatments order to summarize the current state of knowledge and for depressed older people in primary care.7 More to provide guidance for future studies in this area.
Received 31 August 2000; Accepted 8 January 2001.
Regional Office, NHS Executive South West, 22 ChesterfieldRoad, Bristol BS6 5DL, aDepartment of Epidemiology and Sources and type of studies and treatments included Public Health, University of Leicester, 22–28 Princess Road We searched the electronic databases Medline, Embase, West, Leicester LE1 6TP, UK and bDepartment of Primary Cinahl, the Cochrane Library, Psyclit, BIDS—Social Care, Rehabilitation and Preventive Medicine, University ofMarburg, Blitzweg 16, D-35033 Marburg, Germany.
Science Citation Index and BIDS—Science Citation Family Practice—an international journal Index, and the references of studies we identified as well symptoms. Information about included and excluded as those of other reviews of antidepressant treatment.
studies is presented in Tables 1 and 2, respectively.
Controlled clinical trials, randomized controlled trials, We found no studies of psychological treatment, nor ‘controlled before and after studies' and ‘interrupted did we find any high quality studies of drug treatment in time series' studies were included if they were published the studies restricted to older people. Studies of drug between 1980 and June 1999 and the language of pub- treatment that we did find were short (4–8 weeks) and lication was English, French or German. We sought trials excluded many patients with other illnesses, thus making of cognitive and/or behavioural therapy,12 interpersonal any assessment of how treatment would perform under psychotherapy,13,14 ‘counselling', social support and drug health service conditions (effectiveness) rather than ideal circumstances (efficacy) virtually impossible.
In addition, subjects had to be recruited from a sample Exclusions commonly used in studies of antidepres- of the general population or from primary care attenders.
sants in older people are summarized in Table 3 to show Studies were included if all subjects were over the age of the limited generalizability of drug trial results.
60 years. However, studies that were not elderly specific Given the extent of the evidence, only limited con- but included some subjects over the age of 60 were clusions are possible. A flexible approach to the treat- sought and analysed separately. Initial selection on all ment of depression in older people led by a community the above criteria was made by one of the authors.
psychiatric team can lead to the considerable improve-ment of 40–50% of those treated. Routine treatment Methodological quality criteria for inclusion in primary care only achieved 25–30% improvement.
All included studies had to comply with the quality The difference was probably largely due to the greater criteria for intervention studies published by the number of patients on antidepressant drug treatment in Cochrane Effective Practice and Organisation of Care the intervention groups.
Group.15 The criteria pertinent to the retrieved studies A total of eight studies that were not primarily of older were: relevant and interpretable data, concealed allocation people, but did include patients over the age of 60 years, of subjects, follow-up of at least 80–100% of randomized met all selection criteria. All were randomized controlled patients, a baseline measurement, a reliable primary trials of antidepressant drugs. Three of them also met outcome measure, protection against contamination, all methodological quality criteria and were therefore and blinded assessment of primary outcomes or use of an included in the review. None of the eight studies objective outcome measure. This review was, however, investigated the effectiveness of psychotherapy.
not carried out by members of the Cochrane Effective The studies are also shown not because they allow Practice and Organisation of Care Review Group but specific conclusions to be drawn for the overall effective- employed some of its methods.
ness of antidepressant treatment in older people but Two reviewers, trained in the use of the quality because they provide a fuller impression of the treat- criteria, read each study independently (and blind to ments used with older people even when they were not the other's appraisal). They summarized the presented the focus of the study. Only one excluded study analysed data and categorized the compliance of studies with results for subjects over 65 years separately. A meta- the quality criteria (done, not clear, not done or do not analysis of results was therefore impossible.
know). They then compared their findings and discussed We did not analyse effect sizes in more detail because differences. Agreement on the accuracy of the factual of this lack of separate analysis and the lack of com- information, the quality and the decision to include or parability of patient groups between the two trials of exclude a study were made by consensus between the two older people alone.
reviewers. In general, studies were excluded if one of the In contrast to trials of psychiatric team care, the drug quality criteria was classified as ‘not done'. However, trials of antidepressant drugs with less representative the actual method of randomization often was not stated.
participants and of younger patients achieved higher We therefore included studies that stated randomization rates of improvement (54–81%). The most likely without providing further detail.
explanation would be the exclusion of patients withsignificant co-morbidity. It is also worth noting that 47%of patients treated with placebo improved over 6 months in the study of Malt et al.,16 probably reflecting thespontaneous improvement of some patients over the Seven studies of patients over the age of 60 years met all relatively long observation period as well as the placebo selection criteria. All were randomized controlled trials.
Only two of them also met all methodological quality We cannot say on the basis of our review whether criteria and were therefore included in the review. Both serotonin re-uptake inhibitors (SSRIs) should be used in investigated the effectiveness of psychiatric team care preference to older antidepressants in the elderly. The for patients with depressive symptoms or depression found high quality studies of community mental health team among a population sample screened for depressive care did not provide a breakdown of specific treatments Treatments for late life depression , 27% in the control , twice as many patients , 25% in control group , 75% in control group , 76% in control group ver 60 years of age 43% of patients in the intervention group much improved on SHOR in intervention group received 58% much improved in intervention antidepressant use 4 times higher in intervention group 81% much improved in intervention only study where intention to treat analysis and treatment success for those who completed treatment were done and reported, clinical improvement was 10% higher for completers in both intervention and 61% much improved in intervention 78% much improved in intervention h included some patients o 22 (age range 21–73) 20% during placebo.
T structured interview opulation, exclusion criteria P (if different from summary in text) Participants in a community survey (average age 76), depressed mood assessed by short care screening instrument, all were included in the trial. Only 56% of screen positives were depressed according to GMS- No exclusion criteria stated.
All recipients of homecare in an area (average age 80.4) who scored self-care questionnaire if in psychiatric care Primary care attenders (age range 21–70) depression diagnosed by GP Primary care attenders (age range 18–79) depression diagnosed by GP In addition to the common exclusions also excluded those whose MADRS score decreased by 25% prior to randomization Primary care attenders (age range 18–79) depression diagnosed by GP In addition to the common exclusions also excluded those whose MADRS score treatment prior to randomization ver the age of 60 years and studies whic psychological and drug treatment as Citalopram (34 mg) sertraline (83.5 mg) Sertraline (144.6 mg) mianserin (78 mg) Citalopram (20 mg) fluoxetine (20 mg) Included studies meeting all selection and quality criteria of patients o Proportion improved represents either those with a 50% drop in scores on a depression screening tool or a move from case to non Studies of patients aged 60 years and Family Practice—an international journal , not clear at which Reason for exclusion 80% follow-up of subjects 80% follow-up of subjects 80% of patients in final analysis 80% of patients followed-up ver the age of 60 years and reason for exclusion rial not designed to study efficac rial not designed to study efficac Clinical information not relevant, control drug given in subtherapeutic dose one of the intervention drugs not now recommended for depression, control drug not used for depression at all relevant clinical information could not be derived from data provided , those who responded to placebo retrospectively point in the analysis exclusion took place not stated who first identified patients for inclusion into trial and how Clinical Global Impression Scale (physician opinion) used to report patient improvement, not reported patient symptom score change—not clinically relevant Not defined who identified patients for inclusion and how severity of depression assessed, used unreferenced outcome measure Did not provide clinically relevant information , provide clinically relevant information Primary care attenders (average age 72), judged as depressed by GP and scoring above a specified level on HAM-D Primary care attenders and other volunteers (age range 65–89) depressed by semi-structured interview Primary care attenders aged over 60 Primary care attenders (average age 72) not stated how and by whom depression Primary care attenders (age range 65–88), not stated how and by whom depression Attenders of community-based general GPs (age range 19–75) Primary care attenders (age range 18–82) Primary care attenders (age range 36–89), not stated by whom and how depression Primary care attenders (age range 18–79), depression diagnosed by GP Primary care attenders (age range 18–72), depression diagnosed by GP and ver the age of 60 years and those including some patients o continued longer razodone SR (150 mg) Paroxetine (20 mg) amitriptyline (100 mg) Buspirone (36 mg) imipramine (80 mg) Flupenthixol (0.75 mg) amitriptyline (37.5 mg) nortriptyline (1.5/30 mg max. dose) promazine (150 mg max. dose) Flupenthixol (0.8 mg) amitriptyline S/R 40 mg Lorazepam (4.93 mg) alprazolam (2.08 mg) amitriptyline (102 mg) Fluvoxamine (140 mg) lorazepam (2.96 mg) Lofepramine (105 mg) amitriptyline (75 mg) nortriptyline (1.5/30 mg) fluphenazine (1.5 mg) nortriptyline (30 mg) trazodone (150 mg) Excluded studies meeting all selection but not all quality criteria of patients o Studies of patients aged 60 years and Treatments for late life depression Common exclusion criteria for trials of antidepressant drugs in older people (based on the reviewed trials) Parkinson's disease; prostatism; recent myocardial infarct; impaired renal or liver function; cancer; epilepsy; unspecified braindisorder; glaucoma Depression requiring admission; depression requiring ECT; patient suicidal; manic depressive disorder; other mental illness;alcohol or drug misuse (either current or in previous year) Current treatment with other psycho-active drug; treatment with tranquillisers or antidepressants currently or in the recentpast used. Of the studies including some patients over the age Older people take more medication on a regular basis,27 of 60, only that of Malt16 compared a tetracyclic anti- thus increasing the likelihood of drug interactions and depressant (mianserin) with an SSRI (sertraline) and making contra-indications to the use of antidepressant placebo. Total drop-out from active treatment was 29% drugs more likely. The need for other forms of treatment for the tetracyclic, 26% for the SSRI and 5% for placebo.
therefore becomes more pressing in this age group.
In contrast, Ekselius et al.17 compared two SSRIs in a Improvements on placebo that were apparent in slightly younger population with only about half the Malt's generally younger study population16 may be less drop-out rates (10 and 15%). Subject selection rather common in older people. A systematic review found that than the nature of the drug may be the cause of the after 1 year, only 33% of patients were well compared differences between studies of similar size and the same with 21% who had died and another 33% who were still depressed.28 Because of the protracted nature of late lifedepression, studies need to treat or at least follow-upparticipants for at least 6 months.
Studies to date that have compared SSRIs and older antidepressants have been efficacy studies. We still need The aim of this review was to evaluate critically the studies showing us how newer antidepressant drugs would current evidence for treatment of depression in older perform specifically for older patients with minimal people. We found a lack of good quality studies in this exclusions. Such studies might take the same flexible area as well as a concentration on treatment of severe approach as Waterreus' and Banerjee's studies29,30 depression with no allowance made for prior duration, but use exclusively SSRIs in one group and older anti- previous episodes or additional morbidity.
depressants in the other group.
The focus on severe depression is understandable Cognitive and behavioural psychotherapy can improve as researchers have reliable methods to identify severe severe depression in depressed psychiatric in- and out- depression. However, depressive symptoms below that patients. Interpersonal psychotherapy has been tested level are much harder to classify meaningfully. They could successfully in maintenance treatment of recurrent represent the early or late stages of severe depression, severe depression.31–34 Cognitive behavioural therapy reactions to upsetting life events or the response to has also been shown to be effective when delivered to adverse social circumstances. They could also be the psychiatric out-patients as an outreach service.35 Con- effect of physical disease such as stroke. Older primary sequently, if psychotherapy was given to primary care care patients with depressive symptoms also have more patients, it should only be offered to those with major physical illness than their non-depressed peers.18 As in depression. This will require some formal psychiatric major depression, the treating physician has to decide whether to consider depressive symptoms as a disorder Counselling was included in our review because it is in their own right or as the symptom of another illness.19 widely available in UK primary care. It does not describe A previous history of depression particularly before any specific psychotherapeutic approach but individual the age of 65 increases the likelihood of recurrence.20 approaches to helping clients by counsellors with differ- Age alone after adjustment for other known risk factors ent backgrounds and with or without formal qualifications.36 does not appear to make depression more likely.21 In A recent review of the effectiveness of counselling for contrast, it has been debated whether older people are major depression in adults under the age of 65 concluded less depressed than younger age groups.22,23 However, that counselling was not effective in the treatment of major it is clear that the inability to fulfil social roles resulting depression on current evidence37 and did not recommend from physical disabilities is a major risk factor for its use for that purpose. However, it is also tremendously depression in older people.24–26 Ironically, this risk factor popular with the general public in Britain, with 90% may be the reason why older people often are excluded of a representative sample considering it as effective from trials of potentially effective interventions for for depression and only 60% thinking the same about Family Practice—an international journal The benefits of all forms of treatment are much less clear for patients with milder forms of depressionwhose weighted average prevalence in the community is This work was funded by research and development 9.8%.6 It is also found more commonly in primary care.
grant RBH 97XX3 from the Regional Office of the NHS Only a third of adults under 65 years treated by primary Executive Trent.
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