Nicergoline

Dementia and cognitive impairment in older people

• The Fioravanti and Flicker 2001 Cochrane review included 14 trials. Patients were older people with mild to moderate cognitive and behavioral impairment of various causes, diagnosed with criteria of the time. On the SCAG behavior scale (814 patients) nicergoline beat placebo by 5.18 points out of 133, MMSE scores were 2.86 points better at 12 months (261 patients), ADAS-Cog in Alzheimer's disease did not differ significantly (342 patients), and the odds of improvement on clinical global impression were 3.33 times higher (921 patients). The reviewers found some evidence of positive effects but too few Alzheimer's patients for a definitive answer (PMID: 11687175).
• In Herrmann 1997, a 6-month double-blind trial in 136 people with mild to moderate multi-infarct dementia, nicergoline 30 mg twice daily beat placebo on both primary endpoints, the SCAG and the MMSE (p<0.01), with a similar number of adverse events (PMID: 8997547).
• Saletu 1995 was an 8-week double-blind trial in 112 residents of retirement homes with Alzheimer-type or multi-infarct dementia. The primary endpoint, clinical global impression, favored nicergoline in both groups; responders were 16 of 24 against 8 of 24 in the Alzheimer group and 17 of 24 against 7 of 26 in the multi-infarct group, and MMSE, SCAG, EEG and P300 measures also changed in nicergoline's favor (PMID: 7604138).
• In Nappi 1997, a 12-month double-blind trial in 108 outpatients at five Italian centres, SCAG scores improved and MMSE scores were maintained with nicergoline compared with placebo, and global evaluations by physicians and patients favored nicergoline (p<0.001) (PMID: 27519492).
• The EMA summarized two Alzheimer's disease trials. In a US single-centre trial of 149 patients over 6 months, the global impression of change favored nicergoline but ADAS-Cog did not differ; in a European trial of 346 patients, ADAS-Cog was 1.55 points better at 6 months while the global impression of change did not differ (EMA assessment report EMA/750632/2013).
• In the EMA's 2013 review, the CHMP noted that none of these studies was designed for the indication it reviewed, that the data were weakened by publication bias and by changes in diagnostic criteria, and its scientific advisory group found that the cognitive indication was no longer used in clinical practice (EMA assessment report EMA/750632/2013).
• Bes 1999 was a 24-month double-blind pilot in 72 older people with hypertension and white matter changes but no dementia. People on nicergoline declined less or improved more on several memory and attention tests than people on placebo (PMID: 10210912).
• In a Japanese study of 33 people with Alzheimer's disease and depression or apathy (Takemoto 2020), the 9 patients given nicergoline showed no significant change in depression or apathy scores over 3 months (PMID: 32568205).

Healthy volunteers

• Saletu 1990 was a double-blind, placebo-controlled study in 16 healthy volunteers. During 23 minutes of breathing air with 9.8 percent oxygen, mental performance fell 43 percent after placebo and 29, 24 and 31 percent after single doses of 10, 30 and 60 mg nicergoline, and the difference from placebo was significant for the 30 mg dose (p<0.01) (PMID: 2127674).

Swallowing problems

• In a randomized Japanese study of 50 stroke patients (Nishiyama 2010), serum substance P rose after 4 weeks of nicergoline (p=0.021) but not without it (PMID: 20029189).
• Nakashima 2011 randomized 60 older people in Japan with dysphagia and previous pneumonia to nicergoline or imidapril. The proportion with better swallowing and the rate of recurrent pneumonia did not differ significantly between nicergoline and the blood pressure drug imidapril (PMID: 21694649).
• Imsub 2026, an open-label pilot in Thailand, compared 26 patients against 66 historical controls. Swallowing screen scores were higher and choking less frequent with nicergoline, and the authors called for randomized trials (PMID: 42355896). ClinicalTrials.gov lists a completed phase 3 dose comparison in dysphagia at the same Bangkok hospital, with no posted results (ClinicalTrials.gov NCT05551182).

Circulation, eye and migraine indications

For the peripheral circulation, eye and migraine indications, the EMA found the evidence too weak for any conclusion: no data for intermittent claudication, mostly old non-randomized studies in peripheral arterial disease, open studies without a placebo group in eye disease, and two open studies of 40 and 17 patients in migraine (EMA assessment report EMA/750632/2013).

Fibrosis

A French case series covering 1985 to 1995 described eight people who developed lung or pleural changes during long-term treatment at regular doses with ergot drugs, four of them on nicergoline; six had thickening of the pleura (the lining of the lungs) with or without fluid, all eight improved slowly after the drug was stopped, with slight residual pleural thickening in five of the six. The authors concluded that nicergoline and dihydroergotamine can cause chronic pleural thickening or effusion that slowly improves after withdrawal (PMID: 8793465). In its 2013 review the EMA counted 30 reports of fibrotic events with nicergoline, mostly in the lungs (pulmonary fibrosis 9, interstitial lung disease 6, pleural effusion 6, pleural fibrosis 5); in 21 of them a link to nicergoline could not be excluded, and these occurred after 5 months to 30 years of treatment in people aged 59 to 90, at the recommended daily dose where recorded (EMA assessment report EMA/750632/2013). Ten of the lung cases without another explanation improved 3 to 10 months after nicergoline was stopped, and one patient died after a diagnosis of pulmonary fibrosis suspected to be linked to nicergoline and amiodarone (EMA assessment report EMA/750632/2013). The EMA judged nicergoline to be associated with a risk of fibrotic reactions and noted probable under-reporting, because fibrosis develops slowly and is diagnosed late (EMA assessment report EMA/750632/2013).

Ergotism

No report in the manufacturer's safety database used the term ergotism with nicergoline, but 90 of 390 spontaneous reports collected over 40 years contained terms that can indicate ergotism, such as tingling, ischaemia, cold sensation, gangrene and vasospasm, and the EMA concluded that ergotism could not be ruled out (EMA assessment report EMA/750632/2013).

Pregnancy

PubMed searches on 27 October 2026 found no study of nicergoline in human pregnancy; the published pregnancy studies were rat studies of diabetic pregnancy (PMID: 2140805, PMID: 1969751).