The discovery of insulin represents an authentic breakthrough, characterized, at the same time, by contrasts, controversies and disputes among scholars, as well as by great disappointments, failures and hopes. It is the story of famous, almost famous and little known people, of serendipities, discoveries and re-discoveries. The discovery of insulin has been a milestone and has truly revolutionized both the therapy and the prognosis of the diabetes, one of the diseases most studied in the history of medicine, whose first mentions trace back to a collection of ancient Egyptian, Indian and Chinese textbooks. As stated by Colwell, the introduction of insulin has heralded the end of the so-called “pre-insulin era” or “frustration era”, paving the way for a new era and clinical advancements. The current review offers a broad, comprehensive overview of main steps culminating into insulin discovery, including recent advancements such as personalized and individualized insulin therapy.

Idiopathic Parkinson's disease (IPD) is characterized by motor signs such as akinesia, rigidity, and often tremor at rest. In addition to these symptoms, depression is a common finding affecting 40% of patients with IPD. This study evaluates the effect of the selective serotonin reuptake inhibitor, citalopram, on motor and nonmotor symptoms of depressed and nondepressed patients with IPD. Forty-six nondemented patients with IPD (24 men, 22 women; mean age 64 +/- 5.3 years; mean +/- SD disease duration, 6.4 +/- 3.2 years; mean +/- SD Hoehn-Yahr stage, 2.8 +/- 1.2) were included in the study. Patients were divided in two subgroups: depressed (n = 18) and nondepressed (n = 28). Citalopram was added in an unblinded manner, starting with 10 mg/d, and, after a week, increased up to 20 mg/d in the depressed subgroup (n = 18) and in half of the nondepressed subgroup (n = 14). Parkinsonian and depressive symptoms were evaluated before and after 1 and 4 months of treatment. Statistical evaluation was made by analysis of variance for repeated measures. Citalopram did not worsen motor performance in IPD, but improved bradykinesia and finger taps after 1 month and 4 months of treatment both in patients with and without depression (p < 0.05 versus baseline). A clear improvement in mood was also observed in 15 of 16 patients with depression. Although case reports indicate that citalopram can potentially worsen the motor symptoms in patients with PD, to date this effect has not been confirmed. Many of the symptoms, typically associated with depression, can be observed in nondepressed patients with IPD, because signs thought to represent depression can be produced by Parkinson's disease. In this study, we observed that when combined with levodopa, citalopram induces an improvement of motor performance, in particular of subscores 23 and 31 of Unified Parkinson's Disease Rating Scale both in depressed and in nondepressed patients with IPD.

Citalopram or other SSRIs and reboxetine may be of first choice treatment in PSD because of their good efficacy and lack of severe side effects. In addition, PSD patients should be classified according to their clinical profile (similarly to patients affected by primary depression) for the selection of SSRIs or reboxetine as drugs of choice in particular subgroups of patients.

Clinical history, symptoms, signs, response to therapy, and brain imaging help to differentiate PD and VP as two clinical entities with different clinical, prognostic and therapeutic implications, even if the coexistence of PD and a cerebral vascular disease in elderly patients is not infrequent and can make the diagnosis difficult.

Antidepressants are used to treat chronic daily headache disorders such as migraine and chronic tension-type headache (TTH), which are often associated with depression and anxiety. Here, we studied the efficacy and tolerability of amitriptyline and citalopram, given alone or in combination, in patients with ‘triple’ comorbidity of depression, TTH, and migraine. Eighty-eight patients were enrolled in the study and randomly divided into two groups. The first group received amitriptyline and the second citalopram for 16 weeks. Patients were assessed at weeks 0, 4, 8, and 16. The two drugs were equally efficacious in relieving depressive symptoms, although amitriptyline was more efficacious than citalopram in reducing migraine and TTH attacks. Patients who did not respond to monotherapy (<30% of improvement in the clinical scores) were treated with a combination of the two drugs for 16 additional weeks. In these selected patients, the combined treatment produced a substantial improvement in depression, migraine and TTH without producing major side effects such as those commonly related to the ‘serotonergic’ syndrome. The results indicate that a combined therapy with amitriptyline and citalopram may be particularly beneficial for patients with TTH, migraine and comorbid depression that do not respond to monotherapy.