Addressing the Unmet Need in the Treatment of Poststroke Anxiety, Depression, and Apathy: A Systematic Review of Potential Therapeutic Options

Abstract

Half of stroke patients experience depression, anxiety, and/or apathy, adversely impacting poststroke recovery. Yet management of these remains suboptimal. To identify the broad spectrum of therapeutic modalities investigated for post-stroke mood disorders, and their characteristics, administration regimens, and clinical outcomes. A structured, PRISMA-guided literature review identified studies exploring preventative or treatment options. Seventy-one identified studies (N = 5748 patients) comprised 62 clinical trials, 4 case reports, and 4 protocols or published abstracts. Most focused on depression; relatively few addressed anxiety and/or apathy. Overall, the efficacy of most treatments remains unclear due to the diversity and small size of studies (mostly pilot studies) precluding comparison. Preventative modalities such as nortriptyline (6 studies) reduced the incidence of depression, noting high rates of effectiveness in smaller studies (92.3%, study N = 48) patients. For the treatment of diagnosed mood disorders (58 studies), conventional pharmacotherapies (e.g., fluoxetine) were most effective, reducing depression, anxiety and/or apathy in up to 95.8% of patients (study N = 60). Physiological interventions (e.g., repetitive Transcranial Magnetic Stimulation, rTMS) variably reduced depression/anxiety severity (in 20.8%–93.3% of patients) whilst complementary therapies (e.g., acupuncture) reduced depression/anxiety severity in 60.0%–92.4% of patients (study N = 60). Combination therapies (e.g., fluoxetine plus acupuncture or rTMS plus Deanixt) significantly reduced depression severity in 93.3% of patients (study N = 60). Within the limited evidence in poststroke mood disorders, conventional pharmacotherapies appear most effective for both prevention and treatment, whilst nonpharmacological strategies and CAMs show potential. No treatment can be fully recommended without more robust trials.