Short-term and long-term treatment in depressive syndromes: focus on antidepressants tolerability

Objective Long-term treatment with antidepressants prevents relapses and recurrences of major depressive disorders and favours functional recovery. However, antidepressant side effects other than affect patient's health, may limit treatment adherence and social functioning. Most studies concerning antidepressant treatment have focused on short-term tolerability, less attention has been devoted to side effects that are reported during long-term. Method Medline databases were searched for existing studies on side effects and tolerability of long-term antidepressant treatment. Manual search on significant book chapters and reviews on the same topic has been also performed. Results Among old generation antidepressants, MAOI are today utilized only seldom in resistant cases, because of their potentially lethal interactions and scarce manageability. Cardiotoxicity and lethality in overdose limit the use of TCA, even if there is evidence of good tolerability of these compounds in long-term treatment of highly recurrent major depressives. New antidepressants, SSRIs and SNRIs, show a relatively favourable short-term as well as long-term tolerability compared with older drugs (e.g. TCA and IMAO). Common long-term side effects with SSRI are weight gain, sexual dysfunction, sleep disturbances, fatigue, apathy and cognitive impairment (e.g. working memory dysfunction). SNRI presents a similar profile but seems to be better tolerated than SSRI as concern weight gain and cognitive disturbances. Conclusion In order to rationalize long-term treatment of depression, further research on long-term antidepressants side effects and tolerability is necessary.