Wednesday, 13.12.2017

Comments by Ervin Varga

Ervin Varga’s comment on Ildiko Miklya’s essay on The History of Selegiline (Miklya Collection)

When I try to relate my memories about the birth of deprenyl, I have to remind myself that I worked as Associate Professor in Budapest at the Semmelweis University Psychiatric Clinic. I was trained and conditioned to be a clinician with a narrow focus on my patients. I was both a neurologist and a psychiatrist, but I was neither biochemist nor pharmacologist. My exclusive interest was diagnostic evaluation and treatment of patients under my care.

In the 1960s, Hungary was a communist country. We had limited access to literature or exchange with western colleagues. But since the discoveries of the phenothiazines and tricyclic antidepressants in the 1950s, we became involved in drug trials. They were unsophisticated clinical trials, especially Phase 1 studies with unknown substances, reviewed only by pharmacologists without clinical experience.

At the same time, we had complete freedom with little involvement with drug companies or ethics committees. We were not restrained by cost issues, because there were no grants.  Healthcare in Hungary in those days was free. Doing research, we were on our own. Depression was the target of our research. Tricyclic antidepressants were fine for many patients, but it took time until they improved and the severity of their depression simply did not permit us to wait. So, we went for ECT. The chairman of my Department was Professor Gyula Nyirö, who with Meduna introduced convulsive treatment in the 1930s. It was still the treatment of choice in severe delusional cases or when we were concerned about suicide. There was need for a faster acting antidepressant, since ECT was not applicable to frail patients with involutional depression. We still did not use muscle relaxants with anesthesia. 

I remember my discussion with Joseph Knoll, my old friend and classmate, about the available choices. That was the time when endorphin became the vogue and opiates promised the route to developing the ultimate antidepressant. Knoll did not believe this, and went on the catecholamine path.

He wanted me to examine a group of new substances, phenylethylamines, which he combined with  pargyline  (all I knew was that this was a sedative antihypertensive drug).

The combination of a stimulant with a sedative reminded me of the once famous Brom Caffeine tablets.

Sometime in 1964, Knoll started to send me experimental samples. First, I took such tablets myself for 1-2 days, and since it seemed harmless, I gave it to patients. If I remember, I gave 5 mg tablets and when no change was noticed, I increased the dose  to 15 mg/day, but for no longer than another 5-6 days. When still no improvement was noticeable, I stopped the experimental drug and continued either with Tofranil or ECT. This went on with 5 different patients, one after the other, without any result until the 6th patient showed marked improvement after only 4 days. It was as dramatic as an ECT treatment. I called Knoll, told him the last sample was an antidepressant.

The rest is well described by Dr. Miklya.

 

Ervin Varga

August 7, 2014