Table 2.

Signal output from the signal-detection workshop focusing on patient reports

Signal	Description	Total reports in combinations lista	Total patient reports in combinations list
Amitriptyline–dry eyes	New possible ADR: “Dry eyes” was not found to be listed as an ADR in either SmPCs or PILs, although amitriptyline has an anticholinergic effect and dry eyes is an established anticholinergic reaction. The ADR would probably not appear surprising to HCPs, but the missing information would give pts no clue this could be a reaction caused by the drug	38	20
Desloratadine–depression	New possible ADR: Depression is not labelled for desloratadine. The reports, with a median time to onset of 3 days, most pts recovering after withdrawal of desloratadine, and several reported positive re-challenges constitutes a strong signal for depression caused by desloratadine	16	9
Desogestrel–panic attack, suicidal ideation, self-injurious behavior	New possible ADR: Altered and depressed mood are listed adverse reactions in the product labelling. However, the more severe terms panic attack, suicidal behavior, and suicidal ideation are not. In most reports, desogestrel was the only suspected drug, and a large proportion of the reports documented that pts improved upon withdrawal of the drug. The cases were further strengthened by the pts’ stories and send a signal to prescribers to be aware of possible relations to more severe psychiatric disorders for desogestrel	49	43
Levothyroxine–panic attack	New possible ADR: Panic attacks may be viewed as expected adverse effects of levothyroxine therapeutic overdoses considering the known ADRs, which include palpitations, tremor, and sometimes anxiety. However, the risk of panic attacks seems not to be explicitly mentioned in PILs, and pts and doctors may not associate this severe experience with the listed ADRs	34	21
Pregabalin–color vision distortion	New possible ADR: Although changes in color vision can have other causes, the relationship with pregabalin is strengthened by the fact that changes in color vision is a known ADR of drugs (vigabatrin and tiagabine) that exert their effects in ways similar to that of pregabalin. The reports in VigiBase support a causal relationship; time to onset seems quick and changes in color vision seem to occur within hours to days of starting the drug. The ADR also seems to be reversible	10	6
Noscapine–chest pain, stomach pain, headache	New aspect of an already known ADR: Noscapine was highlighted for reports of headache, stomach ache, and chest pain, sometimes with severe or intense pain, reported mainly from five countries. This was adequately labelled in three countries, labelled for one of the ADRs in one country and not labelled at all in the last country	84	47
SGLT-2 inhibitors–genital pruritus	New aspect of an already known ADR: Genital pruritus is a well-known and well characterized ADR for SGLT-2 inhibitors. The pt narratives in these reports revealed this event could be described as “severe” and with additional consequences, sometimes leading to discontinuation of the drug, which might not be known to all prescribers and which is not reflected in the PIL	48	25
Systemic hormonal contraceptives–loss of libido	New aspect of an already known ADR: Most of the PILs for systemic hormonal contraceptives mentioned “decreased libido” or “changes in libido.” However, a complete loss of libido as reported and described by pts in the reports in VigiBase was highlighted by the narratives as unexpected and with impact on quality of life for the pts	47	37

ADR adverse drug reaction, HCP healthcare provider, PIL patient information leaflet, pt(s) patient(s), SGLT-2 sodium glucose-linked transporters subtype 2, SmPC summary of product characteristics

^a Total number of reports is the number of reports originally shown in the drug–event combinations list. Some of the signals included additional terms or drugs in the in-depth clinical review, increasing the total number of reports included in the final signal