Emotional Blunting, Cognitive Impairment, Bone Fractures, and Bleeding as Possible Side Effects of Long-Term Use of SSRIs

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are amongst the most prescribed drugs worldwide not only for psychiatric conditions, but also for medical purposes. Converging data gathered throughout the decades following their development would indicate that SSRIs have a broader side effect profile than previously assumed. Therefore, the aim of the present paper was to to review available literature highlighting less common side effects emerging with their long-term use. This systematic review, carried out according to PRISMA guidelines, was performed through searching electronic databases of PubMed, Google Scholar, Cochrane Library, Embase, MEDLINE, PsycINFO and Scopus. The keyword used was "SSRIs" combined with the following: "Side effects", or "Emotional blunting or flattening", or "Cognition", or "Neuroimaging", or "Bone", "or "Platelet aggregation", or "Bleeding". The most common side effects, besides the classical ones described in the literature are represented by decreased emotional response to both adversive and pleasurable events, some cognitive impairments, bone fractures and prolonged overall bleeding time. After analyzing critically the available findings, it should be noted that only the so-called "emotional blunting" is supported by converging data, while results on cognitive impairment are extremely controversial, given some evidence showing that SSRIs may improve cognition. Similarly, no agreement exists on the detrimental effects of SSRIs on bone metabolism and coagulation.Large, prospective and long-term studies are needed to clarify the possible impact of SSRIs on emotions, cognitive functions, bone fractures and coagulation, as well to detect other possible still neglected side effects.