Can pharmacological, psychological, and brain stimulation treatments reduce depression prevalence or depressive symptoms after stroke?

Depression is difficult to recognize and assess in stroke survivors, mainly because some cognitive sequelae of stroke may interfere with the administration and scoring of validated tools for the diagnosis and assessment of major depression and other depressive illnesses. 

Whether depression after stroke is more related to some specific brain lesion rather than to the patient’s psychological response to this adverse life event is still a highly controverted issue. However, mood disorders occur in up to half of stroke survivors, and about one-third of them are reported to have depression persisting during the first year or longer after stroke onset. 

Depression may influence recovery and functional, cognitive and physical outcomes, including the increased burden on caregivers, but many people with stroke do not receive screening and/or treatment for it. This may also depend on the current uncertainty as to the balance of benefits and risks of therapies in this specific setting. 

Recommended treatment options mainly fall into three broad interventions: pharmacological, psychological and brain stimulation treatments, which were investigated in a recent 2020 Cochrane Review, updated in 2004 and 2008. 

How are these interventions believed to act? 

Pharmacological interventions are thought to alter the synaptic transmission process within the brain to increase neurotransmission. 

Electrical or magnetic non-invasive brain stimulation are believed to alter chemical pathways in the brain that are responsible for depression by inducing intracerebral current flow to increase or decrease neuronal excitability and/or to activate nerve cells in the specific area being stimulated. 

Psychological therapy is designed to treat depression by different approaches, and generally implies the therapist talking the patient into identifying and attempting to change dysfunctional thinking, emotional, behavioural, and relationship patterns.

The authors aimed to establish whether one or more of the considered interventions, alone or combined, can be associated with reduced prevalence of stroke-related diagnosable depression after treatment (suggesting remission) and/or reduced levels of depressive symptoms, improved physical and neurological function and health-related quality of life, and reduced dependency after stroke; they also searched evidence on the safety of and adherence to such interventions. 

This review included 49 trials with 3,342 participants. 

The results suggest that it is uncertain if pharmacological or psychological therapies can reduce the prevalence of depression (very low-certainty evidence). Very low-certainty evidence is also reported for all the considered interventions, either alone or combining a pharmacological treatment with either of the other two interventions, to reduce depressive symptoms; as for non-invasive brain stimulation, this evidence is related to repetitive transcranial magnetic stimulation (rTMS) only. On the other hand, an association was found between pharmacological intervention and adverse events involving the central nervous system and gastrointestinal tract. 

Thus, the authors conclude that current evidence “tentatively supports the use of prescription antidepressants or psychological therapy to treat depression,” but, in the case of antidepressants, an increased risk of harm requires care in their use. Most studies presented relevant methodological limitations. In particular, the wide range of the length of time between stroke onset and entry into the trial between studies; the reduced time frame for treatment duration and follow-up; and the frequent exclusion of persons with communication problems, cognitive loss, or previous psychiatric illness; strongly limit the generalizability of these findings. Thus, further research is much needed to provide higher quality of evidence on these interventions for treating depression in “real world” stroke survivors.

Commented by Francesca Cecchi