BONUS DIGITAL CONTENT

Medicine by the Numbers

A Collaboration of TheNNT.com and AFP

Interventions for Treatment

of Poststroke Depression
Kento Sonoda, MD, AAHIVS, and Mako Wakabayashi, MD

Details for This Review

Study Population:​5,831 patients with THE NUMBERS
depression and a history of stroke
Benefits Harms
Efficacy End Points:​ Remission of 1 in 6 had remission of depression at 1 in 11 experienced neurologic
depression at the end of treatment;​ the end of pharmacologic treatment, adverse events from pharmacologic
inadequate response to treatment (less compared with placebo treatment, compared with placebo
than 50% reduction in scale scores at 1 in 3 in the pharmacologic treatment 1 in 8 experienced gastrointestinal
the end of treatment) group had reduced risk of inadequate adverse events from pharmacologic
treatment response, compared with treatment, compared with placebo
placebo group
Harm End Points:​ Adverse events
1 in 7 had remission of depression
from therapy such as death, neurologic
from psychological therapy, compared
events, and gastrointestinal effects with usual care or attention control
1 in 7 had remission of depression
Narrative:​ Approximately one-third of from noninvasive brain stimulation
stroke survivors experience depression plus pharmacologic treatment, com-
within five years of the stroke.1,2 Post- pared with pharmacologic treatment
stroke depression is associated with plus sham stimulation or usual care
increased mortality and can negatively
impact activities of daily living and
cognitive function.3-5 Given the U.S. Preventive Services Task ranged from 52 to 78 years. The period between stroke diag-
Force recommendation for routine depression screening in nosis and depression intervention varied from within one
adults, family physicians are well positioned to identify and week to more than one year. In this review, stroke included
treat poststroke depression in the ambulatory setting.6 The cerebral infarction, intracerebral hemorrhage, and uncertain
main treatment options for poststroke depression include pathologic subtypes. The primary outcomes were remission
pharmacologic therapy, noninvasive brain stimulation, and of depression at the end of treatment (using the Diagnostic
psychological interventions. and Statistical Manual of Mental Disorders, 5th ed, criteria
A 2023 Cochrane review evaluated multiple treatment for depression or similar standard diagnostic criteria), inad-
modalities for poststroke depression.7 The review included equate response to treatment (less than a 50% reduction in
65 randomized controlled trials (RCTs), with 5,831 par- scale scores at the end of treatment), and adverse events.
ticipants who had a history of stroke and a diagnosis of Very low-certainty evidence showed that, compared with
depression on recruitment. The studied interventions were placebo, pharmacologic interventions are more likely to
pharmacologic therapy (18 trials achieve remission of depression after
with 1,829 participants;​12 trials a treatment course of varying dura-
studied selective serotonin reuptake The NNT Group Rating System tion (risk ratio [RR] = 0.70;​95% CI,
inhibitors, and two trials studied 0.55 to 0.88;​absolute risk difference
tricyclic antidepressants), noninva- Green Benefits greater than harms [ARD] = 17.9%;​number needed to
sive brain stimulation (eight trials Yellow Unclear benefits treat [NNT] = 6;​eight RCTs with
with 516 participants), psycholog- 1,025 participants) and have a lower
ical interventions (22 trials with Red No benefits likelihood of inadequate depression
1,764 participants), or a combina- Black Harms greater than benefits treatment response (RR = 0.48;​95%
tion (three trials with 278 partici- CI, 0.32 to 0.70;​ARD = 37.7%;​NNT
pants). The mean age of participants = 3;​six RCTs with 511 participants).

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 MEDICINE BY THE NUMBERS
Very low-certainty evidence suggested that,
compared with usual care or attention control,
psychological therapy is more likely to achieve
remission of depression (RR = 0.77;​95% CI, 0.62
to 0.95;​ARD = 16.2%;​NNT = 7;​six trials with 521
participants). The combination of pharmacologic
therapy plus noninvasive brain stimulation is
more likely to achieve remission of depression vs.
pharmacologic therapy plus sham stimulation or
usual care (RR = 0.77;​95% CI, 0.64 to 0.91;​ARD
= 14.7%;​NNT = 7;​three RCTs with 392 partici-
pants;​ low-certainty evidence).
Very low-certainty evidence demonstrated that,
compared with placebo, the pharmacologic treat-
ment group had more neurologic adverse events
(RR = 1.55;​95% CI, 1.12 to 2.15;​ARD = 8.5%;​
number needed to harm [NNH] = 11) and gas-
trointestinal adverse events (RR = 1.62;​95% CI,
1.19 to 2.19;​ARD = 11.2%;​NNH = 8), although
pharmacologic treatment did not increase mor-
tality rates. The analysis found no difference in
adverse events for patients treated with noninva-
sive brain stimulation, psychological therapy, or
a combination of these, compared with placebo
or usual care.
Caveats:​ The Cochrane review had several lim-
itations. Many trials excluded participants with
communication problems, cognitive impair-
ment, concomitant traumatic brain injuries, or
psychiatric conditions, which can be common
among stroke survivors, limiting generalizabil-
ity. Depression treatment guidelines from the
U.S. Department of Veterans Affairs and U.S.
Department of Defense recommend that patients
take antidepressants for at least six months before
an adequate treatment assessment can be per-
formed.8 Because most trials included a shorter
pharmacologic treatment period, this review may
have inadequately assessed the effectiveness of
antidepressants. Many trials showed substantial
heterogeneity (I2 = 50% to 89%) and had high risk
of bias in multiple domains (e.g., allocation con-
cealment [selection bias], blinding [performance
bias], and incomplete outcome data [attrition
bias]). Diagnostic criteria for depression were also
inconsistent among trials.
November 2023 ◆ Volume 108, Number 5 www.aafp.org/afp
Conclusion:​ Although the results are promis-
ing for pharmacologic and psychological ther-
apies and for the combination of noninvasive
brain stimulation plus pharmacologic therapies,
we assigned a color recommendation of yellow
(unclear benefits) for the treatment of poststroke
depression based on a high potential for bias,
significant heterogeneity, and limited generaliz-
ability. Further research with longer duration of
antidepressant therapy is needed to properly eval-
uate the balance of benefits and risks. Additional
studies are also needed to investigate the effect of
treatment in stroke survivors with communica-
tion barriers, traumatic brain injury, or concomi-
tant psychiatric disorders.
Copyright © 2023 MD Aware, LLC (theNNT.com).
Used with permission.
This series is coordinated by Christopher W. Bunt,
MD, assistant medical editor, and the NNT Group.
A collection of Medicine by the Numbers published
in AFP is available at https://​w ww.aafp.org/afp/mbtn.
Author disclosure:​No relevant financial relationships.
References
1. Hackett ML, Pickles K. Part I:​frequency of depression after
stroke:​an updated systematic review and meta-analysis of
observational studies. Int J Stroke. 2014;​9(8):​1017-1025.
2. Dong L, Williams LS, Brown DL, et al. Prevalence and
course of depression during the first year after mild to
moderate stroke. J Am Heart Assoc. 2021;​10(13):​e020494.
3. Cai W, Mueller C, Li YJ, et al. Post stroke depression and
risk of stroke recurrence and mortality:​a systematic review
and meta-analysis. Ageing Res Rev. 2019;​50:​102-109.
4. Ezema CI, Akusoba PC, Nweke MC, et al. Influence of
post-stroke depression on functional independence in
activities of daily living. Ethiop J Health Sci. 2019;​29(1):​
841-846.
5. Shin M, Sohn MK, Lee J, et al. Post-stroke depression and
cognitive aging:​a multicenter, prospective cohort study.
J Pers Med. 2022;​1 2(3):​389.
6. Barry MJ, Nicholson WK, Silverstein M, et al. Screening
for depression and suicide risk in adults:​US Preventive
Services Task Force recommendation statement. JAMA.
2023;​329(23):​2057-2067.
7. Allida SM, Hsieh CF, Cox KL, et al. Pharmacological, non-
invasive brain stimulation and psychological interventions,
and their combination, for treating depression after stroke.
Cochrane Database Syst Rev. 2023;​( 7):​CD003437.
8. U.S. Department of Veterans Affairs;​U.S. Department
of Defense. VA/DoD clinical practice guideline. Man-
agement of major depressive disorder. February 2022.
Accessed August 21, 2023. https://​w ww.healthquality.
va.gov/guidelines/​MH/mdd/ ■
American Family Physician 449C