Pharmacological, psychological, and non-invasive brain stimulation interventions for treating depression after stroke (Review)

Abstract

Background
Depression is an important morbidity associated with stroke that impacts on recovery yet is often undetected or inadequately treated.

Objectives
To evaluate the benefits and harms of pharmacological intervention, non-invasive brain stimulation, psychological therapy, or combinations of these to treat depression after
stroke.

Search methods
This is a living systematic review. We search for new evidence every two months and update the review when we identify relevant new evidence. Please refer to the Cochrane
Database of Systematic Reviews for the current status of this review. We searched the Specialised Registers of Cochrane Stroke, and Cochrane Depression Anxiety and Neurosis, CENTRAL, MEDLINE, Embase, five other databases, two clinical trials registers, reference lists and conference proceedings (February 2022). We contacted
study authors.

Selection criteria
Randomised controlled trials comparing (1) pharmacological interventions with placebo; (2) non-invasive brain stimulation with sham stimulation or usual care; (3) psychological
therapy with usual care or attention control; (4) pharmacological intervention and psychological therapy with pharmacological intervention and usual care or attention control; (5) pharmacological intervention and noninvasive brain stimulation with pharmacological intervention and sham stimulation or usual care; (6) pharmacological intervention and
psychological therapy with placebo and psychological therapy; (7) pharmacological intervention and non-invasive brain stimulation with placebo plus non-invasive brain stimulation; (8) non-invasive brain stimulation and psychological therapy versus non-invasive brain stimulation plus usual care or attention control; and (9) non-invasive brain stimulation and psychological therapy versus sham brain stimulation or usual care plus psychological therapy, with the intention of treating depression after stroke.

Data collection and analysis
Two authors independently selected studies, assessed risk of bias, and extracted data from included studies. We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data, and risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I² statistic and certainty of the evidence according to GRADE.

Main results
We included 65 trials (72 comparisons) with 5831 participants. Data were available for (1) 20 comparisons; (2) 9 comparisons; (3) 25 comparisons; (4) 3 comparisons; (5) 14 comparisons; and (6) 1 comparison. We found no trials for comparisons 7 to 9.
Comparison 1- Pharmacological interventions: Very low-certainty evidence from eight trials suggest pharmacological interventions decreased the number of people meeting the study criteria for depression (RR 0.70, 95% CI 0.55 to 0.88; p= 0.002; 8 RCTs; 1025 participants) at end of treatment and very low-certainty evidence from six trials suggest that pharmacological interventions decreased the number of people with inadequate response to treatment(RR 0.47, 95% CI 0.32 to 0.70; p= 0.0002; 6 RCTs; 511 participants) compared to placebo. More adverse events related to the central nervous system (CNS; RR 1.55, 95% CI 1.12 to 2.15; p=0.008; 5 RCTs; 488 participants; very low-certainty evidence) and gastrointestinal system (RR 1.62, 95% CI 1.19 to 2.19; p= 0.002; 4 RCTs; 473 participants; very low-certainty evidence) were noted in the pharmacological intervention than in the placebo group.
Comparison 2- Non-invasive brain stimulation: Very-low certainty evidence from two trials show that non-invasive brain stimulation had little to no effect on the number of people
meeting the study criteria for depression (RR 0.67, 95% CI 0.39 to 1.14; p= 0.14; 2 RCTs; 130 participants) and the number of people with inadequate response to treatment (RR 0.84, 95% CI 0.52, 1.37; p= 0.49; 2 RCTs; 130 participants) compared to sham stimulation. Non-invasive brain stimulation resulted in no deaths.
Comparison 3- Psychological therapy: Very low-certainty evidence from six trials suggest that psychological therapy decreased the number of people meeting the study
criteria for depression at end of treatment (RR 0.77, 95% CI 0.62 to 0.95; p= 0.01; 521 participants) compared to usual care/attention control. No trials of psychological therapy reported on the outcome inadequate response to treatment. No differences in the number of deaths or adverse events were found in the psychological therapy group compared to the usual care/attention control group.
Comparison 4- Pharmacological interventions with psychological therapy: No trials of this combination reported on the primary outcomes. Combination therapy resulted in no deaths.
Comparison 5- Pharmacological interventions with non-invasive brain stimulation: Non-invasive brain stimulation with pharmacological intervention reduced the number of people meeting study criteria for depression at end of treatment (RR 0.77, 95% CI 0.64 to 0.91; p= 0.002; 3 RCTs; 392 participants; low certainty evidence) but not the number of people with inadequate response to treatment (RR 0.95, 95% CI 0.69 to 1.30; p= 0.75; 3 RCTs; 392 participants; very-low certainty evidence) compared to pharmacological therapy alone. Very-low certainty evidence from five trials suggest no difference in deaths between this combination therapy (RR 1.06, 95% CI 0.27 to 4.16; p= 0.93; 487 participants) compared to pharmacological therapy intervention and sham stimulation or usual care.
Comparison 6- Non-invasive brain stimulation with psychological therapy: No trials of this combination reported on the primary outcomes.