Do antidepressants or analgesics have an effect on behavioral and psychological symptoms associated with dementia?

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SBU Enquiry Service

Responds to queries received from Swedish healthcare and social service providers, or governmental organisations. Queries have a limited scope and the process is designed to enable a more rapid response, typically within two to three months. Reports are based on systematic reviews, that are identified through structured searches and critically appraised for risk of bias.

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Published: Report no: ut202609  Registration no: SBU 2026/48

Question

What effect do antidepressants and analgesics (specifically paracetamol and medications for neuropathic pain) have on behavioural and psychological symptoms of dementia?

PICO

  • Population: People with a diagnosis of dementia (Alzheimer’s disease, vascular dementia, frontotemporal dementia, Lewy body dementia, Parkinson’s disease dementia, alcohol-related dementia, mixed dementia, dementia NOS, mild cognitive impairment)
  • Intervention: Antidepressants or analgesics (in the form of paracetamol or neuropathic pain medications)
  • Comparison: Placebo, other active treatment, or no treatment
  • Outcome: Prevalence or severity of behavioural and psychological symptoms

Method

A systematic literature search was performed using the following databases: Medline (Ovid), Scopus, and Embase.

Two authors independently assessed the abstracts of all identified studies.

Risk of bias in relevant systematic reviews was assessed using an assessment tool based on AMSTAR and RoB NMA.

Identified literature

Three relevant systematic reviews with low to moderate risk of bias were identified [1-3]. Because the three included systematic reviews overlap in terms of research question and included studies, we do not present results from the systematic review by Seitz and colleagues [3]. The results and conclusions are presented in Table 1. In 30 relevant systematic reviews, the risk of bias was considered to be high, therefore the results and conclusions are not reported [4-33].

Table 1 Systematic reviews with low/moderate risk of bias.
CI = confidence interval; OR = odds ratio; RCT = randomized controlled trial; SMD = standardized mean difference; SSRI = selective serotonin reuptake inhibitors
Included studies Population, Intervention, Control Outcome and Results
Hsu et al, 2021 [1]
Efficacy of serotonergic antidepressant treatment for the neuropsychiatric symptoms and agitation in dementia: A systematic review and meta-analysis
14 RCT

Setting:
Asia: 2 studies
Europe: 5 studies
North America: 7 studies		 Population:
Patients diagnosed with dementia according to the
Diagnostic and Statistical Manual of Mental Disorders (DSM) and
the National Institute of Neurological and Communicative Disorders
and Stroke and the Alzheimer’s disease and Related Disorders Association, including Alzheimer’s disease (NINCDS-ADRDA), frontotemporal dementia,
and vascular dementia.

Intervention:
Serotonergic antidepressants as monotherapy or in combination with other treatments (e.g., anti-dementia medications) 

Control:
Placebo		 Overall neuropsychiatric symptom (NPS)
Serotonergic antidepressants (12 studies, n=1276):
Serotonergic antidepressants were associated with a statistically significant reduction in overall NPS compared with placebo
SMD: −0.49 (95% CI, −0.74 to −0.24) 

SSRIs (9 studies, n=1109):
The subgroup SSRIs were associated with a statistically significant reduction in overall NPS compared with placebo
SMD: –0.49 (95% CI, −0.78 to −0.20) 

Agitation
Serotonergic antidepressants (9 studies, n=749):
Serotonergic antidepressants were associated with a statistically significant reduction in agitation compared with placebo
SMD: −0.49 (95% CI, −0.43 to −0.14) 

SSRIs (6 studies, n=605):
The subgroup SSRIs were associated with a statistically significant reduction in agitation compared with placebo
SMD: –0.49 (95% CI, −0.78 to −0.20) 

Depressive symptoms
Serotonergic antidepressants (8 studies, n=938):
Serotonergic antidepressants were associated with a statistically significant reduction in depressive symptoms compared with placebo
SMD: –0.32 (95% CI, −0.49 to −0.15) 

SSRIs (6 studies):
The subgroup SSRIs were associated with a statistically significant reduction in depressive symptoms compared with placebo
SMD: –0.29 (95% CI, −0.48 to −0.09) 

Note: This is a short summary. Please see the review [1], for a complete list of results and analyses.
Authors' conclusion:
”The current meta-analysis of 14 RCTs involving a total of 1347 participants with dementia found that serotonergic antidepressants may effectively alleviate overall NPS, agitation, depressive symptoms, care burden, and improve cognition. However, the effect sizes range from very small to small and interpretation of results should be cautious. Even though, the present study provides additional evidence for the possible role of serotonergic antidepressants in managing overall NPS, agitation, and depressive symptoms in patients with dementia”
Kongpakwattana et al, 2018 [2]
Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis
36 RCTs included in network meta-analysis 

Setting:
Asia: 6 studies
Europe: 12 studies
North America: 17 studies
Australia/Oceania: 1		 Population:
Patients diagnosed with dementia based on standardized criteria who developed agitation 

Intervention:
Pharmacological treatment		 Agitation
8-week response rates 

Citalopram (n=147) vs placebo:
No statistically significant difference
OR: 2.13 (95% CI, 0.92 to 4.93) 

Fluoxetine (n=6) vs placebo:
No statistically significant difference 
OR: 0.93 (95% CI, 0.03 to 31.84) 

Fluvoxamine (n=28) vs placebo:
No statistically significant difference
OR:2.65 (95% CI, 0.98 to 7.13) 

Sertraline (n=137) vs placebo
No statistically significant difference:
OR: 1.31 (95% CI, 0.73 to 2.36) 

SSRIs (n=318) vs placebo:
Sensitivity analysis: SSRIs were associated with a statistically significant reduction in agitation
OR: 1.61 (95% CI, 1.02 to 2.53) 

Treatment acceptability
Citalopram (n=147) vs placebo:
No statistically significant difference
OR: 0.86 (95% CI, 0.42 to 1.77) 

Fluoxetine (n=6) vs placebo:
No statistically significant difference
OR: 0.19 (95% CI, 0.01 to 4.37) 

Fluvoxamine (n=28) vs placebo:
No statistically significant difference
OR: 2.34 (95% CI, 0.40 to 13.71) 

Sertraline (n=137) vs placebo:
No statistically significant difference
OR: 0.90 (95% CI, 0.42 to 1.96) 

Note: This is a short summary. Please see the review [2], for a complete list of results and analyses.
Authors' conclusion:
”SSRIs only showed significantly superior efficacy to placebo when considered as a class in the sensitivity analysis, suggesting that SSRIs have the potential to be more efficacious than placebo but current available evidence is insufficient to recommend one SSRI over another.”

References

  1. Hsu TW, Stubbs B, Liang CS, Chen TY, Yeh TC, Pan CC, et al. Efficacy of serotonergic antidepressant treatment for the neuropsychiatric symptoms and agitation in dementia: A systematic review and meta-analysis. Ageing Res Rev. 2021;69:101362. Available from: https://doi.org/10.1016/j.arr.2021.101362
  2. Kongpakwattana K, Sawangjit R, Tawankanjanachot I, Bell JS, Hilmer SN, Chaiyakunapruk N. Pharmacological treatments for alleviating agitation in dementia: a systematic review and network meta-analysis. Br J Clin Pharmacol. 2018;84(7):1445–56. Available from: https://doi.org/10.1111/bcp.13604
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  19. Martinon-Torres G, Fioravanti M, Grimley EJ. Trazodone for agitation in dementia. Cochrane Database Syst Rev. 2004(4):CD004990. Available from: https://doi.org/10.1002/14651858.CD004990
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Search strategies

Medline via OvidSP 25 March 26

Title: Analgesics and antidepressants for symptoms of BPSD
/ = Term from the MeSH controlled vocabulary; .sh = Term from the MeSH controlled vocabulary; exp = Term from MeSH including terms found below this term in the MeSH hierarchy; .ti,ab = Title or abstract; .tw = Title or abstract; .kf = Keywords; .kw = Keywords, exact; .bt = Book title. NLM Bookshelf; .pt = Publication type; .ja = Journal abbreviation; .af = All fields; adjn = Adjacent. Proximity operator retrieving adjacent words, adj3 retrieves records with search terms within two terms from each other; * or $ = Truncation; “ “ = Citation Marks; searches for an exact phrase
Search terms Items found
Population: Persons with dementia
1. Exp Dementia/ 237 687
2. (Dement* OR Mild Cognitive Impairment OR MCI OR Alzheimer* OR Lewy body OR frontotemporal diseas* OR Major Neurocognitive Disorder).ti,ab,kf. 360 865
3. ((vascular OR frontotemporal OR parkinson* OR alcohol OR mixed) adj4 (dement*)).ti,ab,kf. 29 468
4. 1 OR 2 OR 3 403 181
Intervention: Analgesics or antidepressants
5. Exp Analgesics/ 628 272
6. Anticonvulsants/ 59 630
7. (Analgesic* OR anticonvulsant* OR analgetic* OR paracetamol OR acetaminophen OR pregabalin OR gabapentin OR lyrica OR neurontin).ti,ab,kf. 177 090
8. (pain adj4 (treatment OR management OR relief)).ti,ab,kf. 149 901
9. 5 OR 6 OR 7 OR 8 853 763
10. Exp Antidepressive Agents/ 169 521
11. Selective Serotonin Reuptake Inhibitors/ 22 281
12. “Serotonin and Noradrenaline Reuptake Inhibitors”/ 679
13. (ssri OR snri OR antidepr* OR selective serotonin reuptake inhibitor* OR “serotonin and noradrenalin reuptake inhibitor*” OR citalopram OR escitalopram OR sertraline OR duloxetine OR venlafaxine).ti,ab,kf. 106 944
14. 10 OR 11 OR 12 OR 13 217 796
15. 9 OR 14 1 041 946
Study types: systematic reviews and meta-analysis
16. (Systematic Review/ or Meta-Analysis/ or Cochrane Database Syst Rev.ja. or (((systematic or realist or integrative or mixed method* or umbrella) adj4 (review)) or "meta analys*" or metaanalys*).ti,bt,ab.) not (editorial/ or letter/ or case reports/) 606 252
Combined sets:
17. 4 AND 15 AND 16 395
Final result
18.   395

Scopus via scopus.com 25 March 26

Title: Analgesics and antidepressants for symptoms of BPSD
Search terms Items found
TITLE-ABS-KEY = Title, abstract or keywords (including indexed keywords and author keywords); ALL = All fields; W/n = Within. Proximity operator retrieving terms within n words from each other; PRE/n = Precedes by. Proximity operator, the first term in the search must precede the second by n words; LIMIT-TO (X) = Includes only results of specified type, e.g., publication type or time range; DOCTYPE = Publication type; “re” = review; “le” = letter; “ed” = editorial; “ch” = book chapter; “cp” = conference proceedings; * = Truncation; “ “ = Citation Marks; searches for an exact phrase  
Population: Persons with dementia
1. TITLE-ABS-KEY (Dement* OR "Mild Cognitive Impairment" OR MCI OR Alzheimer* OR “lewy body” OR “frontotemporal disease” OR “Major Neurocognitive Disorder”) 550 575  
2. TITLE-ABS-KEY ((vascular OR frontotemporal OR parkinson* OR alcohol OR mixed) W/3 dement*) 42 921  
3. 1 OR 2 550 575  
Intervention: Analgesics or antidepressants
4. TITLE-ABS-KEY (analgesic* OR anticonvulsant* OR analgetic* OR paracetamol OR acetaminophen OR pregabalin OR gabapentin OR lyrica OR neurontin) 497 671  
5. TITLE-ABS-KEY ((pain) W/3 (treatment OR management OR relief)) 204 209  
6. 4 OR 5 633 355  
7. TITLE-ABS-KEY (ssri OR snri OR antidepr* OR “selective serotonin reuptake inhibitor*” OR “serotonin and noradrenalin reuptake inhibitor*” OR citalopram OR escitalopram OR sertraline OR duloxetine OR venlafaxine) 251 033  
8. 6 OR 7 844 853  
Study types: systematic reviews and meta-analysis
9. TITLE-ABS-KEY (((systematic OR realist OR integrative OR “mixed method*” or umbrella) W/3 review) OR "meta analy*" OR metaanaly*) AND (EXCLUDE (DOCTYPE, “le”) OR EXCLUDE (DOCTYPE, “ed”) OR EXCLUDE (DOCTYPE, “ch”) OR EXCLUDE (DOCTYPE, “cp”)) 912 758  
Combined sets:
10. 3 AND 8 AND 9 1192  
Final result
11.   1192  

Embase via Elsevier 25 March 26

Title: Analgesics and antidepressants for symptoms of BPSD
/de = Term from the EMTREE controlled vocabulary; /exp = Term from the EMTREE controlled vocabulary, including all narrower terms in the hierarchy; ti = Title; ab = Abstract; kw = Author keywords; it = Publication type; NEAR/n = Near. Proximity operator retrieving terms within n words from each other; * = Truncation; ‘ ‘ = Citation Marks; searches for an exact phrase
Search terms Items found
Population: Persons with dementia
1. 'Dementia'/exp OR 'mild cognitive impairment'/exp AND [embase]/lim 506 098
2. ('Dement*':ti,ab,kw OR 'Mild Cognitive Impairment':ti,ab,kw OR 'MCI':ti,ab,kw OR 'Alzheimer*':ti,ab,kw OR 'Lewy body':ti,ab,kw OR 'frontotemporal diseas*':ti,ab,kw OR 'Major Neurocognitive Disorde':ti,ab,kw) AND [embase]/lim 450 327
3. (('vascular' OR 'frontotemporal' OR 'parkinson*' OR 'alcohol' OR 'mixed') NEAR/3 ('dement*')):ti,ab,kw AND [embase]/lim 37 901
4. 1 OR 2 OR 3 591 847
Intervention: Analgesics or antidepressants
5. 'analgesic agent'/exp OR 'anticonvulsive agent'/exp OR 'paracetamol'/exp OR 'pregabalin'/exp OR 'gabapentin'/exp OR 'analgesia'/exp AND [embase]/lim 1 751 388
6. (('pain') NEAR/4 ('treatment' OR 'management' OR 'relief')):ti,ab,kw AND [embase]/lim 186 584
7. 5 OR 6 1 814 755
8. 'antidepressant agent'/exp OR 'serotonin uptake inhibitor'/exp OR 'serotonin noradrenalin reuptake inhibitor'/exp AND [embase]/lim 646 780
9. ('ssri' OR 'snri' OR 'antidepr*' OR 'selective serotonin reuptake inhibitor*' OR 'serotonin and noradrenalin reuptake inhibitors' OR 'citalopram' OR 'escitalopram' OR 'sertraline' OR 'duloxetine' OR 'venlafaxine'):ti,ab,kw AND [embase]/lim 147 624
10. 8 OR 9 666 316
11. 7 OR 10 2 156 638
Study types: systematic reviews and meta-analysis
12. ('systematic review'/de OR 'meta analysis'/de OR [cochrane review]/lim OR (((systematic NEAR/4 review) OR 'meta analys*' OR metaanalys*):ti,ab)) NOT ('case report'/de OR 'editorial'/it OR 'letter'/it OR 'note'/it) 878 047
Combined sets:
13. 4 AND 11 AND 12 2147
Final result
14.   2147
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