Escitalopram and Language Intervention for Subacute Aphasia

In this project, the investigators will investigate the effects of a selective serotonin reuptake inhibitor (SSRI), escitalopram, on augmenting language therapy effectiveness, as measured by naming untrained pictures and describing pictures, in individuals with aphasia in the acute and subacute post stroke period (i.e., within three months post stroke). There has been no previous randomized controlled trial (RCT) to evaluate the effect of daily SSRI in the first three months after stroke on improvement of language in people undergoing aphasia treatment. It is plausible that SSRIs, which elevate synaptic serotonin, might enhance recovery by augmenting synaptic plasticity.

The investigators propose to conduct a Phase 2 multi-center, randomized, double blind, placebo-controlled trial of escitalopram for augmenting language intervention in subacute stroke. The investigators hypothesize that daily escitalopram for 90 days after stroke results in greater improvement (compared to placebo) in naming untrained pictures, as well as greater increase in content of picture description and greater improvement in morphosyntactic production, when combined with speech and language treatment (SALT). A second aim is to evaluate the mechanisms of language recovery in individuals who receive active medical treatment and those who receive placebo, using resting state functional magnetic resonance imaging (rsfMRI) and genetic testing. The investigators hypothesize that greater improvement in language is associated with increased connectivity within the left hemisphere language network on rsfMRI in participants who receive escitalopram than in those who receive placebo, independently of improvement in depression. The investigators also hypothesize that the effects are greatest in individuals with val/val allele of brain-derived neurotrophic factor (BDNF) - (consistent with previous studies showing a greater response to treatment and greater neuroplasticity in people with the val/val allele than those with one or more met alleles.

Inclusion criteria

• Participants must have sustained an acute ischemic left hemisphere stroke.
• Participants must be fluent speakers of English by self-report.
• Participants must be capable of giving informed consent or indicating a legally authorized representative to provide informed consent.
• Participants must be age 18 or older.
• Participants must be within 5 days of onset of stroke.
• Participants must be pre-morbidly right-handed by self-report.
• Participants must have an aphasia diagnosis as confirmed by the Western Aphasia Battery-Revised (Aphasia Quotient < 93.8).

Exclusion criteria

• Previous neurological disease affecting the brain including previous symptomatic stroke
• Diagnosis of schizophrenia, autism, or other psychiatric or neurological condition that affects naming/language
• A history of additional risk factors for torsades de pointes (TdP; e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• Current severe depression, defined as a score of > 15 on the Patient Health Questionnaire (PHQ-9)
• Uncorrected visual loss or hearing loss by self-report
• Use of any medication approved by the FDA for treatment of depression at the time of stroke onset
• Concomitant use of any monoamine oxidase inhibitors (MAOIs) or pimozide, or other drugs that prolong the QT/QTc interval, triptans (and other 5-Hydroxytryptamine Receptor Agonists), or other contraindications to escitalopram that may be identified.
• A QTc greater than 450 milliseconds on electrocardiogram or evidence of hyponatremia (Na < 130) at baseline
• Pregnancy at the time of stroke or planning to become pregnant during the study term.