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Re: Which antidepressants are 'less' activating?

Posted by Mtom on August 6, 2021, at 18:20:09

In reply to Re: Which antidepressants are 'less' activating? SLS, posted by linkadge on August 6, 2021, at 14:16:29

Thank you for your comments so far. In particular those who commented research shows TCAS are not inferior to SSRIs and may be superior for efficacy. I am trying to find research so if anyone happens to have links, would be great.

There was an extensive meta-analysis published in 2018 which ranked Amitriptyline as the most efficacious antidepressant, followed by Mirtazapine although the number of studies included for these two were low in comparison to the number for several of the more popular SSRIs and others and received some criticism based on this and other biases. However in terms of acceptability and drop out rate, this study showed Amitriptyline tied for 6th with Paroxetine out of 21, and Mirtazapine ranked 11th.

Almost all papers describe a significantly higher drop out rate for TCAs versus most SSRIs due to adverse effects. These are attributed to the fact that they are not selective (vs Selective SRIs and Selective NRIs) so they impact more body systems. Id say that every article or research paper Ive read mentions higher side effects with TCAs.

In addition, a large concern noted in most articles re: TCAs is the greater risk of potentially fatal heart arrythmias and possibly seizures. Also concerns about potentially fatal overdoses.

For example a 2016 article states A substantial body of evidence indicates that the cardiovascular safety profile of newer generation antidepressants is significantly improved compared to the TCAs.

Although interestingly, I just found a paper published in April of this year 2021 Antidepressants and Risk of Sudden Cardiac Death: A Network Meta-Analysis and Systematic Review that found through a meta-analysis that TCAs were actually associated with fewer cardiovascular events. This is contrary to all other articles Ive read on TCAs. They cited a number of limitations to their study, and also noted that CV events previously seen with TCAs may have involved higher doses plus Doctors now regularly monitor patients on TCAs and discontinue should warning signs appear.

One study which did not favour efficacy of TCAs: A 2014 meta-analysis of 5 studies in young people aged 7 to 25 found SSRIs produced a significantly greater response compared to TCAs.

Most studies cite multiple limitations (such as low numbers of participants, varying methodologies and sometimes publication bias). Theres not a lot of interest in, or maybe more importantly funding for, "large" post-marketing studies of these medications, especially extensive comparisons between the many different types. And articles indicate that Doctors now generally avoid TCAs based on adverse effects (and a perception that newer ADs are better, which may apparently be baseless). And many also reach such different conclusions that it makes your head spin.




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