Comparative efficacy and safety of selective serotonin reuptake inhibitors in the short- and medium-term treatment of major depressive disorders

Abstract

The efficacy and safety of the selective serotonin reuptake inhibitors (SSRIs) have been compared with those of the tri- and tetra-cyclic antidepressants in a large number of studies. Traditional drugs such as amitriptyline, imipramine, maprotiline, mianserin, dothiepin, and nortriptyline have all shown efficacy on a par with the SSRIs. With regard to the safety profile, however, the differences are substantial. The side effects of the older antidepressants are well know, ranging from the tolerable dry mouth and blurred vision, to orthostatic hypotension and weight increase, to potentially fatal cardiovascular effects. The SSRIs have a much more tolerable side effect profile, with nausea and dry mouth being the most frequent side effects. Because of lower toxicity, the therapeutic index of the SSRIs is wider than that of the older antidepressants. This also reduces the risk of a fatal outcome in case of overdose, which is a major advantage in a patient population at high suicide risk. So far, only a few studies have compared the relatively new SSRIs with each other. The efficacy and toxicity of the drugs seem to be the same. With regard to the tolerability and potential for interactions with other drugs, differences have been suggested. Thus citalopram has shown efficacy on a par with fluvoxamine. However, the incidence of treatment-emergent gastrointestinal symptoms tend to be higher in patients receiving fluvoxamine. That fluvoxamine may induce a few more side effects has also been suggested in a comparative study of paroxetine and fluvoxamine showing no difference in efficacy. However, it has been suggested that fluvoxamine induces fewer incidences of sexual dysfunction than paroxetine and sertraline. In conclusion, major differences have been shown between SSRIs and older antidepressants with regard to tolerability and safety. Only a few studies have compared the SSRIs, and so far only minor differences have been seen. However, as individual SSRIs do have different chemical configurations, important differences in, for example, the potential for interaction with other drugs may be revealed.

Key Words:

• Efficacy
• Selective serotonin reuptake inhibitors
• Tolerability
• Toxicity