Pharmacological Approaches in Amyotrophic Lateral Sclerosis: A Systematic Review of Clinical Trials on Efficacy, Survival, and Safety Profiles

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that results in the deterioration of neuromuscular connections, with no effective treatment currently available. The present study aimed to synthesize clinical trial data regarding pharmacological approaches in amyotrophic lateral sclerosis, focusing on the impact of various drugs on the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), patient survival, and safety profiles. A systematic review was conducted following the PRISMA 2020 guidelines (PROSPERO ID: CRD42023373675). The inclusion criteria consisted of clinical trials published in Portuguese, Spanish, or English, with participants diagnosed solely with amyotrophic lateral sclerosis and no other comorbidities. The exclusion criteria were systematic reviews, meta-analyses, and studies involving patients with additional health conditions. A total of 616 articles were identified through databases such as PubMed®, Cochrane Library®, ScienceDirect®, and Clinical Trials®. After applying selection filters, 37 articles met the inclusion criteria. Data from these studies were extracted into a table, detailing authors, publication year, sample size, clinical trial phase, and endpoints, including ALSFRS-R scores, survival rates, and adverse events. Regarding survival, Edaravone demonstrated a significant survival benefit, with active treatment groups living longer than placebo groups. Other promising treatments, such as Sodium Phenylbutyrate and Taurursodiol, reduced mortality and hospitalizations, offering hope for improving patient outcomes. Tofersen also showed a survival increase, indicating substantial clinical potential. Safety profiles revealed common adverse effects, including headaches, dizziness, gastrointestinal issues, and increased fall risks, primarily affecting the nervous and digestive systems. These findings highlight the importance of careful risk–benefit evaluation in ALS treatment. Although the results indicate positive therapeutic developments, further trials are essential to confirm the long-term safety and efficacy of these treatments.