Side-effect profile of fluoxetine in comparison with other SSRIs, tricyclic and newer antidepressants: a meta-analysis of clinical trial data.
BACKGROUND
In the last ten years, SSRIs have increasingly replaced TCAs as comparators of newer antidepressants (ADs), because of their better tolerability profile. In particular, fluoxetine has become a reference drug for the treatment of depression, but the occurrence of individual side effects in depressed subjects treated with fluoxetine and each comparator AD have not been systematically investigated.


METHODS
This meta-analysis investigated the frequency of side effects induced by fluoxetine or alternative ADs and compared the occurrence of individual side effects in depressed subjects. All randomised clinical trials (RCTs) comparing fluoxetine with any other AD drug in patients with major depression were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Controlled Trials Register. Two reviewers independently extracted information.


RESULTS
Significantly less percentage of patients treated with fluoxetine experienced any side effects in comparison with TCAs (50.9 % vs 60.3 %, 29 RCTs; RR = 0.84, p = 0.003), but not in comparison with other SSRIs (59.4 % vs 59.3 %, 15 RCTs; RR = 1.00, p = 0.902). In addition, fluoxetine was better tolerated in comparison with TCAs and related ADs (RR 0.61, 95 % CI 0.52, 0.71), but not in comparison with other SSRIs. Regard to individual side effects, activating (insomnia, agitation, tremor and anxiety) and gastrointestinal adverse events (nausea, vomiting, diarrhoea, weight loss and anorexia) were significantly more frequent in fluoxetine-treated patients, whereas cholinergic side effects were significantly less frequent.


CONCLUSIONS
Fluoxetine compared to other ADs had more activating and gastrointestinal adverse effects, which often require additional pharmacotherapy or other managements strategies, leading to discontinuation and non-compliance and increasing the costs. This information is relevant to base on evidence the prescription of ADs in everyday clinical practice.
Brambilla
P
P
Department of Pathology and Experimental Medicine, Section of Psychiatry, University of Udine, Udine, Italy. paolo.bambilla@uniud.it
Cipriani
A
A
Hotopf
M
M
Barbui
C
C
D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects* / Q000145:classification / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy*; D004361:Drug Tolerance; D005473:Fluoxetine / Q000009:adverse effects* / Q000627:therapeutic use; D041981:Gastrointestinal Tract / Q000187:drug effects; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000145:classification / Q000627:therapeutic use
D000929:Antidepressive Agents, Tricyclic; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors