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NIHR Signal Antidepressants do not help treat depression in people living with dementia

Published on 8 January 2019

doi: 10.3310/signal-000705

Antidepressants do not reduce symptoms of depression in people with dementia compared with placebo (dummy pills). Measured 6 to 13 weeks after starting the treatment, there is little or no difference in participants’ symptoms, but an increased chance of unwanted side effects. The review did not identify enough data to determine if antidepressants have an effect in the longer-term.

This Cochrane review included randomised controlled trials of any antidepressant drugs compared to placebo. Participants were aged 75 years on average, with mild or moderate dementia. The quality of the included trials was mixed, with not enough information reported to fully assess the risk of bias, though the main result is reliable.

This review supports the NICE guideline, which recommends that antidepressants are not routinely offered to people with dementia and depression, but that psychological treatments are considered instead.

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Why was this study needed?

Dementia is a condition that includes memory loss, reasoning and communication difficulties, and changes in personality. It is progressive, so symptoms usually get worse. The most common types of dementia are Alzheimer’s disease and vascular dementia.

The number of people with dementia is increasing as people live longer. In December 2017, GP registers in the UK showed more than 450,000 people had a formal diagnosis of dementia. The total for all forms of diagnosed and undiagnosed dementia may be higher, as the Alzheimer's Society estimates there are currently around 850,000 people in the UK with dementia.

People with dementia often also have mood changes. While diagnosing depression in people with dementia can be difficult, studies have shown that 10-20% of people with Alzheimer’s disease have clinical depression. Antidepressants are often prescribed for people with dementia and depression, but it isn’t clear how effective they are in the presence of dementia. Many of the trials are small. This study aimed to combine results from appropriate trials to give a better picture of the likely effects of treatment.

What did this study do?

This Cochrane review found ten randomised controlled trials comparing antidepressants with placebo in 1,592 people diagnosed with dementia and depression using accepted criteria. Eight trials were included in the meta-analyses.

A variety of antidepressants were used. The trials used different outcome measures to assess changes in depression symptoms. Most of the trials lasted between 6 and 12 weeks; one continued for 39 weeks.

Only one trial took place in the UK, using community mental health teams. Other studies were conducted in outpatient clinics in the US, Brazil and Argentina. One study, in Austria, was carried out among inpatients and nursing home residents.

The trials were all double-blind, so neither the clinicians nor the participants knew which drug they were taking, which increases the reliability of the results. There was some uncertainty about the assessment of clinical recovery or remission, but any flaws would be unlikely to explain a lack of effect.

What did it find?

  • There was little or no difference in depression scores between the antidepressant and placebo groups after 6 to 13 weeks (standardised mean difference [SMD] -0.10, 95% confidence interval [CI] -0.26 to 0.06; 8 studies, 614 participants, high-quality evidence).
  • According to the Cornell Scale for Depression in Dementia (range 0 to 38), there was also no difference between groups after six to nine months (mean difference 0.59 points, 95% CI -1.12 to 2.30; 2 studies, 357 participants, moderate-quality evidence).
  • More people (about one in five) taking antidepressants recovered from depression (the remission rate) by 6 to 13 weeks (antidepressant 40%, placebo 21.7%; odds ratio [OR] 2.57 (95% CI 1.44 to 4.59; 4 studies, 240 participants, moderate-quality evidence). However, only one trial continued to 24 weeks, and so it is unclear whether antidepressants have an effect on long-term remission.
  • Antidepressants had no effect on people’s ability to carry out daily living tasks at 6 to 13 weeks (SMD -0.05, 95% CI -0.36 to 0.25; 4 studies, 173 participants, high-quality evidence).
  • People taking antidepressants were more likely to suffer at least one adverse event than those on placebo treatment (antidepressant 49.2%, placebo 38.4%; OR 1.55, 95% CI 1.21 to 1.98; 3 studies, 1,073 participants).

What does current guidance say on this issue?

The NICE guideline published in June 2018 on the assessment and management of dementia has a section on managing non-cognitive symptoms. It suggests considering psychological treatments for people with mild to moderate dementia who have mild to moderate depression. It says that antidepressants should not be routinely offered unless they are indicated for a pre-existing severe mental health problem.

What are the implications?

This updated Cochrane review supports the advice that antidepressants should not be prescribed to treat depression in people living with dementia.

The previous version only included four studies, with a total of 137 participants. The additional six trials, with more participants, have strengthened the message and confidence in the finding. As the largest systematic review to date, it supports NICE guidance.

There wasn’t enough evidence to draw conclusions about any individual antidepressant, or about different types of dementia. There was also little evidence about the longer-term effects of antidepressants. Future research could focus on these areas to address any doubts about the applicability of this finding.

Citation and Funding

Dudas R, Malouf R, McCleery J and Dening T. Antidepressants for treating depression in dementia. Cochrane Database Syst Rev. 2018;(8):CD003944. 

Cochrane UK and the Cochrane Dementia and Cognitive Impairment group are supported by NIHR infrastructure funding.

Bibliography

NHS website. Living well with dementia. London: Department of Health and Social Care; 2018.

NICE. Dementia: assessment, management and support for people living with dementia and their carers. NG97. London: National Institute for Health and Care Excellence; 2018.

NICE. Depression in adults: recognition and management. CG90. London: National Institute for Health and Care Excellence; 2009, updated 2018.

Why was this study needed?

Dementia is a condition that includes memory loss, reasoning and communication difficulties, and changes in personality. It is progressive, so symptoms usually get worse. The most common types of dementia are Alzheimer’s disease and vascular dementia.

The number of people with dementia is increasing as people live longer. In December 2017, GP registers in the UK showed more than 450,000 people had a formal diagnosis of dementia. The total for all forms of diagnosed and undiagnosed dementia may be higher, as the Alzheimer's Society estimates there are currently around 850,000 people in the UK with dementia.

People with dementia often also have mood changes. While diagnosing depression in people with dementia can be difficult, studies have shown that 10-20% of people with Alzheimer’s disease have clinical depression. Antidepressants are often prescribed for people with dementia and depression, but it isn’t clear how effective they are in the presence of dementia. Many of the trials are small. This study aimed to combine results from appropriate trials to give a better picture of the likely effects of treatment.

What did this study do?

This Cochrane review found ten randomised controlled trials comparing antidepressants with placebo in 1,592 people diagnosed with dementia and depression using accepted criteria. Eight trials were included in the meta-analyses.

A variety of antidepressants were used. The trials used different outcome measures to assess changes in depression symptoms. Most of the trials lasted between 6 and 12 weeks; one continued for 39 weeks.

Only one trial took place in the UK, using community mental health teams. Other studies were conducted in outpatient clinics in the US, Brazil and Argentina. One study, in Austria, was carried out among inpatients and nursing home residents.

The trials were all double-blind, so neither the clinicians nor the participants knew which drug they were taking, which increases the reliability of the results. There was some uncertainty about the assessment of clinical recovery or remission, but any flaws would be unlikely to explain a lack of effect.

What did it find?

  • There was little or no difference in depression scores between the antidepressant and placebo groups after 6 to 13 weeks (standardised mean difference [SMD] -0.10, 95% confidence interval [CI] -0.26 to 0.06; 8 studies, 614 participants, high-quality evidence).
  • According to the Cornell Scale for Depression in Dementia (range 0 to 38), there was also no difference between groups after six to nine months (mean difference 0.59 points, 95% CI -1.12 to 2.30; 2 studies, 357 participants, moderate-quality evidence).
  • More people (about one in five) taking antidepressants recovered from depression (the remission rate) by 6 to 13 weeks (antidepressant 40%, placebo 21.7%; odds ratio [OR] 2.57 (95% CI 1.44 to 4.59; 4 studies, 240 participants, moderate-quality evidence). However, only one trial continued to 24 weeks, and so it is unclear whether antidepressants have an effect on long-term remission.
  • Antidepressants had no effect on people’s ability to carry out daily living tasks at 6 to 13 weeks (SMD -0.05, 95% CI -0.36 to 0.25; 4 studies, 173 participants, high-quality evidence).
  • People taking antidepressants were more likely to suffer at least one adverse event than those on placebo treatment (antidepressant 49.2%, placebo 38.4%; OR 1.55, 95% CI 1.21 to 1.98; 3 studies, 1,073 participants).

What does current guidance say on this issue?

The NICE guideline published in June 2018 on the assessment and management of dementia has a section on managing non-cognitive symptoms. It suggests considering psychological treatments for people with mild to moderate dementia who have mild to moderate depression. It says that antidepressants should not be routinely offered unless they are indicated for a pre-existing severe mental health problem.

What are the implications?

This updated Cochrane review supports the advice that antidepressants should not be prescribed to treat depression in people living with dementia.

The previous version only included four studies, with a total of 137 participants. The additional six trials, with more participants, have strengthened the message and confidence in the finding. As the largest systematic review to date, it supports NICE guidance.

There wasn’t enough evidence to draw conclusions about any individual antidepressant, or about different types of dementia. There was also little evidence about the longer-term effects of antidepressants. Future research could focus on these areas to address any doubts about the applicability of this finding.

Citation and Funding

Dudas R, Malouf R, McCleery J and Dening T. Antidepressants for treating depression in dementia. Cochrane Database Syst Rev. 2018;(8):CD003944. 

Cochrane UK and the Cochrane Dementia and Cognitive Impairment group are supported by NIHR infrastructure funding.

Bibliography

NHS website. Living well with dementia. London: Department of Health and Social Care; 2018.

NICE. Dementia: assessment, management and support for people living with dementia and their carers. NG97. London: National Institute for Health and Care Excellence; 2018.

NICE. Depression in adults: recognition and management. CG90. London: National Institute for Health and Care Excellence; 2009, updated 2018.

Antidepressants for treating depression in dementia

Published on 1 September 2018

Dudas, R.,Malouf, R.,McCleery, J.,Dening, T.

Cochrane Database Syst Rev Volume 8 , 2018

BACKGROUND: The use of antidepressants in dementia accompanied by depressive symptoms is widespread, but their clinical efficacy is uncertain. This review updates an earlier version, first published in 2002. OBJECTIVES: To determine the efficacy and safety of any type of antidepressant for patients who have been diagnosed as having dementia of any type and depression as defined by recognised criteria. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's Specialised Register, on 16 August 2017. ALOIS contains information on trials retrieved from databases and from a number of trial registers and grey literature sources. SELECTION CRITERIA: We included all relevant double-blind, randomised trials comparing any antidepressant drug with placebo, for patients diagnosed as having dementia and depression. DATA COLLECTION AND ANALYSIS: Two review authors selected studies for inclusion and extracted data independently. We assessed risk of bias in the included studies using the Cochrane 'Risk of bias' tool. Where clinically appropriate, we pooled data for treatment periods up to three months and from three to nine months. We used GRADE methods to assess the overall quality of the evidence. MAIN RESULTS: We included ten studies with a total of 1592 patients. Eight included studies reported sufficiently detailed results to enter into analyses related to antidepressant efficacy. We split one study which included two different antidepressants and therefore had nine groups of patients treated with antidepressants compared with nine groups receiving placebo treatment. Information needed to make 'Risk of bias' judgements was often missing.We found high-quality evidence of little or no difference in scores on depression symptom rating scales between the antidepressant and placebo treated groups after 6 to 13 weeks (standardised mean difference (SMD) -0.10, 95% confidence interval (CI) -0.26 to 0.06; 614 participants; 8 studies). There was probably also little or no difference between groups after six to nine months (mean difference (MD) 0.59 point, 95% CI -1.12 to 2.3, 357 participants; 2 studies; moderate-quality evidence). The evidence on response rates at 12 weeks was of low quality, and imprecision in the result meant we were uncertain of any effect of antidepressants (antidepressant: 49.1%, placebo: 37.7%; odds ratio (OR) 1.71, 95% CI 0.80 to 3.67; 116 participants; 3 studies). However, the remission rate was probably higher in the antidepressant group than the placebo group (antidepressant: 40%, placebo: 21.7%; OR 2.57, 95% CI 1.44 to 4.59; 240 participants; 4 studies; moderate-quality evidence). The largest of these studies continued for another 12 weeks, but because of imprecision of the result we could not be sure of any effect of antidepressants on remission rates after 24 weeks. There was evidence of no effect of antidepressants on performance of activities of daily living at weeks 6 to 13 (SMD -0.05, 95% CI -0.36 to 0.25; 173 participants; 4 studies; high-quality evidence) and probably also little or no effect on cognition (MD 0.33 point on the Mini-Mental State Examination, 95% CI -1.31 to 1.96; 194 participants; 6 studies; moderate-quality evidence).Participants on antidepressants were probably more likely to drop out of treatment than those on placebo over 6 to 13 weeks (OR 1.51, 95% CI 1.07 to 2.14; 836 participants; 9 studies). The meta-analysis of the number of participants suffering at least one adverse event showed a significant difference in favour of placebo (antidepressant: 49.2%, placebo: 38.4%; OR 1.55, 95% CI 1.21 to 1.98, 1073 participants; 3 studies), as did the analyses for participants suffering one event of dry mouth (antidepressant: 19.6%, placebo: 13.3%; OR 1.80, 95% CI 1.23 to 2.63, 1044 participants; 5 studies), and one event of dizziness (antidepressant: 19.2%, placebo: 12.5%; OR 2.00, 95% CI 1.34 to 2.98, 1044 participants; 5 studies). Heterogeneity in the way adverse events were reported in studies presented a major difficulty for meta-analysis, but there was some evidence that antidepressant treatment causes more adverse effects than placebo treatment does. AUTHORS' CONCLUSIONS: The available evidence is of variable quality and does not provide strong support for the efficacy of antidepressants for treating depression in dementia, especially beyond 12 weeks. On the only measure of efficacy for which we had high-quality evidence (depression rating scale scores), antidepressants showed little or no effect. The evidence on remission rates favoured antidepressants but was of moderate quality, so future research may find a different result. There was insufficient evidence to draw conclusions about individual antidepressant drugs or about subtypes of dementia or depression. There is some evidence that antidepressant treatment may cause adverse events.

Expert commentary

Depression is very common in people with dementia, and there have been concerns about the balance between the possible benefits and risks of treatment with antidepressants.

Dudas and colleagues updated the previous Cochrane review from 2002 and included ten studies with 1,592 patients. Of these, eight studies had sufficient data for further analysis. The quality of the evidence varied considerably. There was little to suggest that antidepressants were effective in reducing depression in people with dementia although they did give higher rates of adverse events. As the remission rate seemed higher in the antidepressant group compared to the placebo group, they also suggested future research may show a different result.

From a clinical perspective, this excellent review will discourage prescribers from using antidepressants to treat depression in dementia, while still holding out a glimmer of hope that they might be found to be helpful in future studies.

Professor Martin Orrell, Director, Institute of Mental Health; Head, Division of Psychiatry and Applied Psychology, University of Nottingham

The commentator declares no conflicting interests

Expert commentary

The evidence summarised in this review indicates that antidepressants have little or no effect on depressive symptoms in people with dementia, though they may increase the likelihood of remission.

The authors suggest we need more research to elucidate how people with dementia who have depression of different severities respond to antidepressants. In current NICE guidelines, antidepressants are only recommended first line for treatment of more severe depression in populations without dementia.

The pharmacological evidence base for current treatments for depression in people with dementia is weak. We need more trials, of new pharmacological treatments and non-pharmacological approaches to treating depression in people living with dementia; and further research to understand whether existing treatments might be more appropriately targeted, for example at those with more severe depressive illnesses.

Claudia Cooper, Professor of Psychiatry of Older Age, UCL

The commentator declares no conflicting interests