Background Patients with sickle cell disease, who must manage serious and unpredictable complications related to their disease, particularly chronic pain, suffer from numerous psychosocial problems such as depression, anxiety, stress, and disruption of interpersonal relationships; these problems often lead to fatigue and poor quality of life. Objectives This study aimed to determine the effectiveness of self-management programs targeting pain, fatigue, depression, anxiety, and stress in sickle cell patients. Patients and Methods This was a quasi-experimental study; participants were 53 patients with sickle cell disease who were referred to the Thalassemia Clinic of Ahvaz Shafa Hospital. Participants were recruited by census in 2013. Participants received a self-management program that was implemented in five sessions over 12 weeks. Levels of fatigue, depression, anxiety, and stress were assessed before and 24 weeks after the intervention; pain was assessed during the intervention and at a 24 week post-intervention follow-up using the fatigue severity scale (FSS), DASS21, and a pain record. Descriptive statistics, Fisher’s exact test, Chi-square, independent t-tests, paired t-tests, repeated measures tests and correlations were used to analyze the data. Results Scores for fatigue, anxiety, depression, and stress after the intervention were significantly decreased compared to before the intervention (P < 0.001). Repeated measures testing showed that mean scores for frequency and duration of pain decreased significantly during the 12 weeks of intervention, as well as during the 24 weeks of follow-up (P < 0.001). Conclusions The results suggest the effectiveness of self-management programs on the reduction of pain, fatigue, anxiety, depression, and stress in sickle cell patients. Therefore, self-management programs are advisable in order to empower patients and assist their management of health-related problems
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