The August issue of Psychotherapy and Psychosomatics published a review conducted by André F. Carvalho and colleagues regarding the literature around the long-term use of newer generation antidepressant drugs (ADs) and their side effects. Their investigation, which focused on data obtained from populations diagnosed with Major Depressive Disorder (MDD), found that there were a number of safety issues and potentially serious adverse events, which occurred as a consequence of using ADs.
“ADs, particularly following long-term use, may increase the risk of experiencing additional psychopathological (e.g. treatment-emergent affective switches and paradoxical symptoms), or medical (e.g. obesity and bleeding) problems that do not necessarily subside after discontinuation of the drug, and that may modify responsiveness to subsequent treatments,” they write, citing a previous article written by one of the co-authors.
MDD is considered a major public health issue and antidepressants have been found to be the most frequently prescribed medications in the U.S. among certain age groups. A projection study conducted by the World Health Organization has predicted that unipolar depressive disorders will be one of the top three leading causes of “burden of disease” by 2030. As newer drugs are developed, these are typically considered “safer” than the tricyclic agents (TCAs) that were first used for the treatment of MDD.
“It is a common belief that newer generation antidepressants (and particularly SSRIs) have fewer side effects than TCAs. This assumption only pertains to the safety of ADs in overdose. On the contrary, the long-term use of SSRIs and SNRIs is likely to yield important side effects…”
Despite recent research efforts, evidence regarding the safety and efficacy of these newer drugs remains fraught with controversial results.
The authors evaluated the literature on newer generation antidepressants including serotonin and noradrenaline reuptake inhibitors, bupropion, mirtazapine, trazodone, agomelatine, vilazodone, levomilnacipran, and vortioxetine. In their review of adverse events related to these drugs, they included data obtained from observational studies, randomized controlled trials, previous reviews, and case reports.
Main adverse reactions related to the use of these ADs include:
- Gastrointestinal issues
- Hepatoxicity and hypersensitivity reactions
- Weight gain and metabolic disturbances
- Genitourinary issues
- Sexual dysfunction
- Osteoporosis and risk of fractures
- Central nervous system issues
- Sleep disturbances
- Affective disturbances
- Ophthalmic manifestations
- Risk during pregnancy and lactation
- Risk of malignancies
Results from the review showed that while some side effects were transient, others could persist even after treatment discontinuation. Iatrogenic comorbidity then becomes another concern with the use of ADs and could impact future treatments.
The authors conclude stating “the findings of this review suggest that long-term treatment with new generation ADs should be avoided if alternative treatments are available.” Thus physicians should critically examine their decision to prescribe these drugs, weighing the risks, as well as the likelihood of efficacy and responsiveness.
Carvalho, A. F., Sharma, M. S., Brunoni, A. R., Vieta, E., & Fava, G. A. (2016). The safety, tolerability and risks associated with the use of newer generation antidepressant drugs: A critical review of the literature. Psychotherapy and Psychosomatics, 85(5), 270-288. (Abstract)