Abstract
Abstract 
 At any moment, the continuous usage of medications can accompanied by DNA damage and the accumulation of such damages can cause serious consequences. Antidepressants are long-term used drugs and the incidence of their genotoxic impacts cannot be excluded. Therefore, this work was designed to investigate the possible genotoxic effects of the commonly used antidepressants (fluoxetine and amitriptyline) in adult male rats.
 Detection of DNA damage in individual cells was assessed by comet and micronucleus assays in three different cell populations i.e. liver, testis and bone marrow tissues of 24 swiss albino adult male rats. The animals were randomly allocated into three groups of 8 rats each: Group I - rats orally-administered distilled water via gavage tube for four weeks as a negative control. Group II - rats orally-treated with fluoxetine hydrochloride solution (7.2mg/kg/day) via gavage tube for four weeks. Group III - rats orally-treated with amitriptyline hydrochloride solution (27mg/kg/day) via gavage tube for four weeks.
 The results showed that both drugs (Group II and Group III) induced the same extent of DNA damage, as evidenced by a significantly higher DNA fragmentation in liver and testis tissues with increased frequencies of micronuclei formation in bone marrow tissues as compared with the negative control (Group I).
 These findings indicates that both Fluoxetine and Amitriptyline have genotoxic potentials and can induce the same extent of cytogenetic damage in rats. Special precautions and medical supervision should be taken in consideration with their uses.
Highlights
Depression and anxiety disorders are common growing problems in public health (1)
Substantial international studies on antidepressants prescribing patterns, showed that fluoxetine and amitriptyline are two of the most commonly prescribed antidepressants belonging to selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) groups, respectively (6, 7)
The present study demonstrated that amitriptyline (Group 3) exerted a pronounced DNA damage in testicular tissues compared to the negative control (Group 1) rats, as represented by comet scores in (Table 1) and (Figure 1)
Summary
Depression and anxiety disorders are common growing problems in public health (1). Depression affects approximately 350 million people worldwide; constituting a major portion of mental health disorders (2). Substantial international studies on antidepressants prescribing patterns, showed that fluoxetine and amitriptyline are two of the most commonly prescribed antidepressants belonging to selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) groups, respectively (6 , 7). Fluoxetine is a widely-marketed (SSRI) commonly used for treatment of major depressive disorder, obsessive compulsive disorder, panic disorder, bulimia nervosa and premenstrual dysphoric disorder (8). In spite of being an important antidepressant, fluoxetine may induce several unwanted effects, including anxiety, sexual dysfunction, insomnia, and GI problems (10). While amitriptyline is a (TCA), used in the treatment of several psychiatric disorders, including major depression, obsessive compulsive, panic attacks, generalized anxiety, post-traumatic stress and bulimia, in addition to its different off-label uses, including migraine prevention, neuropathic pain management, fibromyalgia, and enuresis (11). Some of the side effects for amitriptyline include anticholinergic effects such as constipation, dizziness, dry mouth, blurred vision and urinary retention, besides weight gain, sexual dysfunction, orthostatic hypotension and cardiotoxicity (13)(14)
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