Tricyclics on Steroids?

Long before Me Too was a social movement, ‘me too’ drugs were a feature of the pharmaceutical industry. Broadly, they came in two types.

One is a variation of the original chemical by the manufacturer – as patents expire, so competitors can move in with generic versions. But by ‘tweaking’ the formula, a new patent will protect their market for many years to come. This approach has been tried by the makers of salbutamol, the bronchodilator, with very limited success, as the original formula is (largely) safe and effective, allowing a generic version to be more attractive to doctors and patients alike than switching to a new drug at a higher price with few (if any) benefits.

The other type of ‘me too’ drug is one that emphasises the difference between it and the original, while not necessarily being significantly different at all. Most fall by the wayside, but some show fewer side effects, or greater effectiveness. Or simply succeed by better marketing (the H2 blocker cimetidine, for example, lost most of the huge and growing market to ranitidine, which could be given twice a day, rather than three times, and also benefitted from Glaxo’s unbeatable marketing machine).

In the 1960s, the antidepressants of choice were the tricyclics, led by imipramine (tofranil) and amitryptilene (Tryptizol), and these soon attracted a multitude of imitators, most of which were no better (and often worse) than the leading drugs, and few survived into the 1970s. One of those that did survive was desipramine (Pertofran). While it never threatened the then-supremacy of Tofranil (imipramine), Pertofran’s longer half-life meant less frequent dosage, which probably helped.

The manufacturers noted that Pertofran’s biochemical action could – theoretically at least – shorten the delay in clinical benefit: Tricyclics, generally, didn’t show much benefit for the first three to five weeks of use, perhaps Pertofran could show improvement in two weeks?

I think it’s fair to say that the very few studies that actually compared Tofranil and Pertofran failed to show any significant advantage, but undeterred, they tried a new approach. Perhaps if it was given by injection, they’d get the required result?

I saw it used once: a man with ‘smiling depression’ – though a pretty bland, mirthless smile - turned out to have delusions of being responsible for most, if not all, of the troubles of the world. He was ‘specialed’ 24 hours a day as a suicide risk, and ECT was suggested as an emergency measure. But Pertofran was chosen instead. For the first few days, no change. Then I had a weekend off, and returned to find him giggling. It seemed so wrong. It was as if Hollywood had replaced the leading actor part way though the movie. But he settled down, his delusions faded, and he was discharged after three weeks or so.

There were no community psychiatric nurses back then, but the Charge Nurse, rightly concerned about the fast recovery, telephoned his home a couple of weeks later. Apparently he had repainted the house, almost completely, but had now ‘settled down’.

I never heard any more about that man, but I'm told that Pertofran by injection continued to be used on admission wards for at least a couple of years. But it didn't stay the course, and with the benefit of 50 years of hindsight, I think it may have been a matter of expense. Our man was given 24 hourly observation for several days during the treatment, as it was recognised even then, that rapid recovery could be a suicide risk: modern antidepressants still make headlines when they lead to suicide; with the improvement in motor activity produced by the drugs often preceding an improvement in mood, suicidal patients have the energy to act on their feelings.

This is another ‘research’ treatment for which I can find no published studies.