ANTIDEPRESSANTS - BRIEF HISTORY AND OVERVIEW

I am credentialed to prescribe these medications.

Important discoveries in medicine have often been made seemingly by accident, when an alert investigator happened to notice something unrelated to what they were studying and decided to pursue it to see where it might lead. The discovery of penicillin by Sir Alexander Fleming is a classic example. Fleming noticed that a Petri dish containing a bacterial grown that had been left open and contaminated by an airborne mold showed no bacterial growth around the mold. Curious about this unexpected phenomenon, he purified and identified the mold(penicillium chrysogenum), conducted further experiments, and proved its antibacterial properties.

Antidepressant medications were discovered in the early 1950s by doctors treating tuberculosis with a new antibiotic called iproniazid. Some patients treated with this drug exhibited side effects including improved mood, appetite, sleep and energy that were far out of proportion to improvement in their health condition. Iproniazid was quickly identified as a mood elevating agent and used in other chronic and debilitating illnesses to treat depressive symptoms. Although its dangerous side effects soon curtailed such usage, investigation quickly began on its mechanism of action and other, safer drugs were soon discovered and used in psychiatry to treat cases of serious depression.

Prior to the discovery of the antidepressant effects of iproniazid the only effective treatment for serious depression was electroconvulsive(ECT) therapy. (This was also discovered by accident, when doctors noticed that depressed epileptic patients showed a striking improvement in mood following naturally occurring seizures. This observation led to the hypothesis that perhaps an artificial induced seizure in a depressed non-epileptic might also improve mood, something that proved to be the case.) Thus the development of the class of medications known as antidepressants was a major breakthrough in the treatment of depression.

The first widely used antidepressants were called tricyclics because of their three ring molecular structure. Tofranil(imipramine) and Elavil(amitriptyline) were among the most widely used ones. Though they are still sometimes used today to treat depression they have largely been replaced by newer and safer medications with far fewer side effects. The real importance of Prozac when it was introduced in the mid-1980s was not that it was much more effective in treating depression but that it was simpler and safer to use and much side effects than the tricyclics, a relatively small quantity of which could be and often was lethal when taken in
overdose.

Many antidepressants have been introduced since the original discovery, but all are believed to work in the same basic way, by correcting deficiencies of certain brain neurotransmitters such as serotonin, norepinephrine and dopamine. This “chemical imbalance” model of depression is undoubtedly oversimplified. New approaches to the causes and treatment of depression are now being developed and it is likely that within a few years entirely different and more effective medications will be available.

Although controversy as to the actual effectiveness of antidepressants versus placebos in treating depression has dogged their use from the very beginning -and continues in some quarters to this day- few clinicians who have treated depressed patients, or patients with depression who have responded to these medications, will have any doubt that in some but unfortunately not all cases they can seem to work wonders. Because there are many different kinds of depression stemming from a variety of poorly understood causes, antidepressants are not magic pills or cure-alls. When they work, they often work very nicely. When they do not work, they just do not work. In many if not most cases the only way to tell if they will help in a particular case is to try one(or more) and see. Studies are underway to develop more reliable predictors of response.

The category name “antidepressants’ is somewhat misleading, since these medications can also sometimes be useful in treating certain anxiety, obsessive-compulsive and eating disorders.

Antidepressants are not pep pills or stimulants. They do not enhance mood in people who are not depressed. They have no “street value” as recreational drugs and are not liable to abuse. Though sudden decrease or discontinuation can sometimes cause transient discomfort, they do not cause physical dependence or addiction the way other drugs such as alcohol, opiates, and benzodiazepines do.

Psychiatric diagnoses and treatments invariably provoke philosophical, moral and political debates, and depression and antidepressants are no exception. Concerns about over-diagnosis and overprescription are common and in many cases have some validity. Non-psychiatric medical practitioners prescribe the vast majority of antidepressants today and there can be little question that many patients are receiving these medications for symptoms and conditions they are not effective. On the other hand, the argument has been made that in this specific situation, overdiagnosis and treatment of depression with antidepressants has the advantage of minimizing under-diagnosis and treatment of severe life-altering and sometimes life-ending depressive mental illness. Be\er, it has been claimed, to cast a wide net than to throw a too narrow one that could deprive some people of help that is desperately needed and frequently highly effective. Critics of this view point to what they say are serious and even dangerous side effects of antidepressants. All medications can have side effects, occasionally serious ones. Antidepressants are no exception - but considering the vast numbers of patients treated with these agents, the actual incidence of serious or life-threatening side effects is remarkably small compared to other widely used pharmaceuticals.

Suggested resources for further information:
https://medlineplus.gov/antidepressants.html
https://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20046273
https://en.wikipedia.org/wiki/Antidepressant