A review of ssri-induced indifference
Download 203.85 Kb.
|
Quality of the evidenceThe following is an evaluation of the quality of the evidence based on study type. Randomized Control Trials The RCTs are of poor quality and no conclusions can be drawn. However, they present some interest in their various methodologies in measuring emotional blunting or apathy. The first of the five (5) RCTs by Raskin et al.7 was a multicenter, double-blind study investigating whether switching from a SSRI to a Serotonin Norepinephrine Reuptake Inhibitor (“SNRI”) (duloxetine) compared with switching to another SSRI (escitalopram) improved apathy symptoms. These were patients who had been treated with a SSRI for depression but continued to have apathy (Apathy Evaluation Scale > 30). Following eight (8) weeks of treatment, both the Duloxetine group and the Escitalopram group significantly improved from baseline, with no significant difference including the subgroup that had received Escitalopram before the study. There was no placebo arm and as the authors noted, the expectation of recovery may have confounded the findings. The second by Corruble et.al8 was a 24-week double blind trial comparing twenty-five (25) patients started on agomelatine versus twenty patients (20) on Escitalopram having completed the Oxford Questionnaire on the Emotional Side-Effects of Antidepressants. It was an ancillary study to a larger study of three hundred and twenty-four (324) patients and suffered from significant limitations that made the study of poor quality most notably the cherry picking of favorable outcome measures from the multi-item Oxford Questionnaire and favorable weekly intervals, and the lack of an intention to treat despite the large drop-out rates (two hundred and thirty-nine (239) completed the study from an initial randomized population of three hundred and twenty-four (324)). The third RCT by Gaillard et al.9 tested healthy volunteers randomized to Agomelatine, Escitalopram and placebo, and measured outcomes with a probabilistic learning task (the subjects played a game of picking rewarding/punishing complex electronic symbols while resisting misleading feedback). The authors concluded that although the Agomelatine group showed significantly higher accuracy compared to the Escitalopram group (82% and 81% vs 74%), the early difference vanished after eight (8) weeks. Although interesting as a study that attempted to measure motivation with a performance test, there was little detail about the statistical significance of the results, and minimLdiscussion about the validity of the performance test as a measure of motivation, making it difficult to derive any comprehensive conclusion from this study. The fourth RCT by Furlan et. al.10 studied healthy volunteers after randomizing to Paroxetine, Sertraline and placebo groups. Outcome measures were poorly recorded in a mood diary, and an admittedly conservative finding that SSRIs were not associated with affective toxicity was made. One novel study was by McCabe et al. 2010 where forty-five (45) healthy volunteers were randomized to receive seven (7) days of oral treatment with Citalopram (20mg/day n=15), Reboxetine (4mg twice daily n=15) or placebo (n=15) in a double-blind study. The study was designed to compare brain responses to reward-related (chocolate delivered via a tube) and aversive stimuli (strawberry drink rated as intensely unpleasant) across the three groups by fMRI and subjective pleasure/displeasure ratings. Both sight (visual of the chocolate and moldy strawberry) and taste stimuli were measured. The findings were: the Citalopram group, in response to both sight and taste of chocolate showed less activation in the areas known to play a role in reward such as the ventral striatum (Z 4.64 for reboxetine> citalopram) p value 0.07) and ventral medial orbitofrontal cortex (3.44 p value 0.01). The Reboxetine group had enhanced activation compared to the placebo group. Similarly, the Citalopram group showed less activation in the areas known to play a role in processing aversive stimuli of both sight and taste of moldy strawberry (placebo>citalopram Z score 4.22 p<0.001) while the Reboxetine group also had less activation compared to placebo for the aversive stimuli (Z score 4.39 p 0.05) The authors conclude that although the participants on Citalopram showed no subjective sense of impaired reward, the corresponding neural response was substantially diminished in comparison to the subjects on Reboxetine or placebo. They acknowledge the limitations of the short study period of seven (7) days. fMRI outcome findings in research present multiple comparison problem, and though the authors attempt to state in their methodology section that they have adjusted for this problem, it is not discussed further in their limitations section, thereby, making it difficult to accept this novel result. In a non-randomized control study Aydemir et al.21 took forty (40) patients with major depression and twenty patients (20) with various anxiety disorders, and commenced them on either a SSRI or SNRI according to clinical indications. The Apathy Evaluation Scale was applied(?) before treatment and at six (6) weeks during treatment(?). Apathy scores increased from a mean of 20.5 at baseline to 25 after antidepressant treatment and the authors concluded that this study proved apathy was associated with SSRIs but not SNRIs. However, it is a poor-quality study, with only five (5) patients put on SNRI in the control population, and the authors had treated the study as a cohort study instead. There were multiple comparisons of outcomes (mean, median) without comment on effect sizes. In summary, no conclusions can be drawn from the RCTs as their study designs and analysis are of poor quality. Download 203.85 Kb. Share with your friends:
|