Off-label Uses of Selective Serotonin Reuptake Inhibitors (SSRIs)

Abstract

: Psychiatric drugs have primacy for off-label prescribing. Among those, selective serotonin reuptake inhibitors (SSRIs) are extremely versatile and, therefore, widely prescribed. Moreover, they are commonly considered as having a better safety profile compared to other antidepressants. For these reasons, when it comes to off-label prescribing, SSRIs rank among the top positions. In this review, we present the state of the art of off-label applications of selective serotonin reuptake inhibitors, ranging from migraine prophylaxis to SARS-CoV-2 antiviral properties. Research on SSRIs provided significant evidence in the treatment of premature ejaculation, both with the on-label dapoxetine 30 mg and the off-label paroxetine 20 mg. However, other than serotoninergic syndrome, serious conditions like increased bleeding rates, hyponatremia, hepatoxicity, and post-SSRIs sexual dysfunctions, are consistently more prominent when using such compounds. These insidious side effects might be frequently underestimated during common clinical practice, especially by non-psychiatrists. For this reason, some points must be addressed when using SSRIs. Among these, a psychiatric evaluation before every administration that falls outside the regulatory agencies-approved guidelines has to be considered mandatory. For these reasons, we aim with the present article to identify the risks of inappropriate uses and to advocate the need to actively boost research encouraging future clinical trials on this topic.

The association of depression and anxiety with treatment outcomes in patients with rheumatoid arthritis – a pooled analysis of five randomised controlled trials

“…This may be partly due to the propensity for clinicians to use antidepressants, predominately SSRIs, as an established treatment in alternative psychological conditions or for use in off-label conditions where there is a limited evidence base. 58 – 60 …”

The upregulation of tryptophan hydroxylase‐2 expression is important for premature ejaculation treatment with the selective serotonin reuptake inhibitor

“…14 What's more, dapoxetine can take effect in a short time and obviously extend IELT in men with PE. 36 In this study, dapoxetine had significant effects on the ejaculatory behavior of rapid rats. The frequency of ejaculation in rapid rats with acute administration of dapoxetine was decreased, while the ejaculation latency was significantly prolonged.…”

“…Unlike classical SSRIs, dapoxetine is absorbed and removed rapidly in the body 14 . What's more, dapoxetine can take effect in a short time and obviously extend IELT in men with PE 36 . In this study, dapoxetine had significant effects on the ejaculatory behavior of rapid rats.…”

The network meta‐analysis of “on‐demand” and “daily” use of paroxetine in treating men with premature ejaculation from randomized controlled trials

“…Nowadays, the preferred treatment for PE is SSRIs (Sathianathen et al, 2021). Paroxetine is the common SSRIs and can significantly increase the content of 5‐hydroxytryptamine (5‐HT) in postsynaptic membrane receptors, thereby playing a key role in delaying ejaculation (Jannini et al, 2021). Although it was not FDA approved for use in PE, the comparison of paroxetine with other regimens has been investigated in a number of high‐quality randomized controlled trials (RCTs) and showed comparable therapeutic effects (Gameel et al, 2013; Hamidi‐Madani et al, 2018; Salonia et al, 2002).…”