PBrain stroke is a syndrome characterized by the onset of a neurological disorder for at least 24 hours. This syndrome is a reflection of central nervous system involvement and is the result of a cerebrovascular disorder. Stroke consists of two types of ischemic and hemorrhagic. The ischemic type is more common and occurs due to local thrombosis of the cerebrovascular or embolization following thrombosis in distant places such as cardiovascular system (1). This syndrome is associated with a high mortality and is known to be the third leading cause of death (2). In Iran, after heart disease and cancers, brain stroke is the third leading cause of death in people over 45 years of age (2, 3). Brain stroke is more common in men, increases with age, and about two-thirds of cases occur in people over age of 65.
Factors that increase the risk of stroke include hypertension, hypercholesterolemia, smoking, alcohol and contraceptive pills (3). During the last decades, anti-hypertensive treatment has reduced the incidence of cerebrovascular accidents. Several factors affect the prognosis of patients after a brain stroke, and the most important of these factors is the severity of the neurological disorder caused by stroke (4). Age of patient, cause of stroke, and comorbidity also affect on prognosis. In general, less than 80% of patients with brain stroke survive for at least one month and the proportion of a 10-year survival after stroke is 35% (5).
Psychological problems are also common during the post-stroke period which can be directly related to central nervous system disease and damage or in the event of a loss of efficacy and severe damage to self-confidence and a person's sense of being healthy (5). Mood problems and especially depression are of the most common diseases which occurs in people with brain stroke (6). Depression occurs at varying degrees in these patients and in addition to causing a number of problems related to the nature of the depression itself, it can lead to poor performance, poor quality of life, and reduced patient collaboration in the treatment and rehabilitation process (7, 8). Lack of cooperation in the process of treatment and rehabilitation causes other problems, including death and exacerbation and stabilization of disabilities (9).
Several studies have reported that fluoxetine, nortriptyline and sertraline compared with placebo were effective for treatment and prophylaxis of post-stroke depression and improvement of daily activities during follow-up time (10-12). Recently, a protocol for a systematic review of sertraline RCTs for patients with post-stroke depression has been published, the results of which are not yet available (13). This study was conducted to evaluate the effect of sertraline compared to nortriptyline on the quality of life and prophylaxis of depression in post-stroke patients.
 

Characteristics of stroke patients treated with sertraline (n=28) and nortriptyline (n=27) are shown in Table 1. The mean age of the patients in sertraline and nortriptyline groups were 61.68±5.43 and 63.56±5.13, respectively (P=0.194). No significant differences were observed for other variables between two groups.

Table 1. Characteristics of stroke patients in two treatment groups

     ^*Chi-Square test, ^**Fisher’s Exact test.
 

The score for all dimensions of quality of life were indicated in table 2. The mean scores for energy level, social isolation, pain, physical ability, sleep and emotional response decreased significantly during 6 months for both groups (P<0.001 for all dimensions, Table 2). However, the effect of sertraline was not different from nortriptyline for energy level (P=0.466), social isolation (P=0.877), pain (P=0.449), physical ability (P=0.801), sleep (P=0.241), and emotional response (P=0.721) (Table 2). 

Table 2. Scores for the dimensions of quality of life by treatment and time

M±SE=Mean± Standard Error, *Repeated Measures between-subjects, **Repeated Measures within-subjects (Sphericity/Huynh-Feldt)
 

The mean score of quality of life at study entry was 293.8 and decreased to 244.0 and 176.7 at the second and the six month, respectively, in the sertraline group and the mean score of quality of life at study entry was 343.5 and declined to 246.2 and 186.8 at the second and the six month, respectively, in the nortriptyline group (Figure 2, P<0.001).  The effect of sertraline was not different from nortriptyline on the total score of quality of life (F=0.277, df=1, P=0.601) and the partial eta-squared was 0.005. The interaction between treatment group and time was also not significant (F=1.954, df=2, P=0.147).

 
Figure 2. Quality of Life in Stroke Patients by treatment and time

Pairwise comparisons of the mean scores for total quality of life between study entry and second month, study entry and six month, second and six month with Bonferroni test were statistically significant (P<0.001 for all). Pairwise comparisons of the mean score of energy level in these occasions were statistically significant (P<0.001, P<0.001 and P=0.034, respectively). The mean score of social isolation between study entry and six month, second and six month were statistically different (P=0.007, P=0.001, respectively). However, the mean score of social isolation at study entry was not different from its mean score at the second month (P=0.574). Pairwise comparisons of the mean score of pain and emotional response between study entry and second month, study entry and six month, second and six month were statistically significant (P<0.001 for both in all occasions). The mean score of physical ability in these occasions were significantly different (P<0.033, P<0.001 and P<0.001, respectively). The mean score of sleep between study entry and second month, study entry and six month were significantly different (P<0.001 for both). However, the mean score of sleep at the second month was not different from its mean score at the six month (P=0.054).
At the end of study, 35.7% of patients in the sertraline group and 33.3% in the nortriptyline group had no depression. The proportions of moderate or severe depression were 17.9% in the sertraline group and 37.0% in the nortriptyline group, respectively (P=0.24, Table 3). The mean score of depression in the sertraline group was 20.64±11.79 and in the nortriptyline group was 22.89±16.18 (P=0.56) at the end of study. The only adverse event was dry mouth that reported by two patients in the nortriptyline group.

     ^**Chi-Square test

Discussion

This study was conducted on patients with the first episode of brain stroke who were between 50 and 70 years old. During the first two weeks after stroke, these patients were screened for depression using BDI (II) questionnaire by a psychiatrist and those without depression were randomized into two groups. Patients in these two groups were treated with sertraline and nortriptyline, respectively. During follow-up and at the end of study, quality of life and depression were assessed in the patients.
At the end of study, 35.7% of patients in the sertraline group and 33.3% in the nortriptyline group had no depression and the proportion of mild depression in the intervention group was 46.4% and in the other group was 29.6%. The proportion of moderate to severe depression in the sertraline group was 17.9% and in the nortriptyline group was 37.0% (P=0.24). This finding showed that the effect of sertraline and nortriptyline for prevention of depression in this study was similar. The result of our study was contradicted with the finding of Robinson et al. They compared nortriptyline and fluoxetine with placebo in the treatment of post-stroke depression and reported that nortriptyline had a significantly higher response rate than fluoxetine or placebo in treating poststroke depression (10). However, this study was different from ours in several ways. One was the comparison of nortriptyline with fluoxetine, the second was the treatment of depressed people, and the third was that the dose of nortriptyline used for patients that was higher than our study, starting at 25 mg/day and increased to 100 mg/day. These can justify the difference between our results and theirs.  
Some prospective studies have also looked at the natural history of depression after stroke. Ayis et al. in a study performed on patients from the South London Stroke Register between 1998 and 2013, reported that 15.51% of patients were free of depression symptoms when screened for depression symptoms at 3 months after stroke (15). Hornsten et al. also stated that 57.2% of patients with a history of stroke were not depressed with taking antidepressants (16). This proportion for our population in both groups, at the end of study, was 35% which could be due to the prevention effects of medication.
Consequences of stroke such as depending on others for daily activities and disruption of their social life have a negative impact on the quality of life (QoL) of patients. In this study, the effect of sertraline and nortriptyline on the quality of life was compared during six months. The results showed that the mean score of quality of life and its dimensions at the second, fourth and six month significantly declined for both groups (P<0.001) given that a lower score indicates a better quality of life. Therefore, both sertraline and nortriptyline played a significant role for improving all aspects of quality of life during follow-up. However, the effect of sertraline on total quality of life was not significantly different from nortriptyline (P=0.601) and the partial eta-squared was 0.005 that only 0.5% of quality of life variations are due to the effect of the intervention. Bilge et al., in a study showed that citalopram antidepressant therapy has been effective in improving the function and quality of life of these patients (17). Mikami et al. reported patients who received fluoxetine or nortriptyline had significantly greater improvement and recovery from disability compared to patients who received placebo (p = 0.002). They also suggested that antidepressants may facilitate the neural mechanisms of recovery in patients with stroke (11). Robinson et al. in a study compared nortriptyline and fluoxetine with placebo in the recovery from physical and cognitive impairments after stroke. They reported that nortriptyline had a significantly higher response rate than fluoxetine or placebo in improving anxiety symptoms, and in improving recovery of activities of daily living (10). Mead et al. in a systematic review have concluded that the administration of specific inhibitors of serotonin increases the quality of life in stroke patients (18). Ghorashizadeh et al. conducted a study on stroke patients and compared the effect of sertraline with placebo on reducing disabilities. Those who received sertraline in comparison with controls had a lower level of depression and higher quality of life during a 9-month follow up (14). In a recent meta-analysis, Feng et al. reported that sertraline is safe and effective in the treatment and prevention of poststroke depression (12). The results of these two recent studies on the effect of sertraline on depression and quality of life are in accordance with ours. However, we evaluated the effect of sertraline in comparison with nortriptyline on depression and quality of life and observed that both sertraline and nortriptyline were effective.
One of limitations in our study was lack of a control group without treatment because quality of life in post-stroke patients without medication also improves over time. The small sample size in our study may have limited our statistical power to find a significant difference between two groups in terms of moderate to severe depression.

 

Conclusion

The results of this study indicate that, both sertraline and nortriptyline played a significant role for improving all aspects of quality of life during follow-up, however, the effect of sertraline on quality of life was not significantly different from nortriptyline. In addition, the effect of sertraline and nortriptyline for prevention of depression was similar. Therefore, in patients suffering from brain stroke, the administration of sertraline or nortriptyline could be beneficial and improve their recovery.

 

Acknowledgements

We acknowledge the Social Determinants of Health Research Center and Deputy of Research and Technology at Zanjan University of Medical Sciences.

 

Conflicts of Interest

The authors declare that they have no conflict of interests.