The Over-protraction of Antidepressant Treatments

Year 2018:

The situation in Spain is very similar to what is happening in USA, where more than 15 million people, about 5% of population, take antidepressant drugs for five or more consecutive years. This figure has doubled since 2010; and tripled since 2000. This increase has been influenced by the “loss of innocence” which for many Americans the 9/11 terrorist attack in 2001 signified.

Moreover, 25 million Americans take antidepressant drugs for more than two consecutive years, 60% more than in 2010.

Another “loss of innocence” was the so-called “interruption syndrome” which can explain why many people are unable to abandon their antidepressant treatment. The Drug Regulatory Bodies by-passed this problem when “new” drugs were authorised. Many “serotonin re-uptake inhibitors” emerged as a lucrative proposition in the pharmaceutical market. These “new” antidepressants had fewer side effects compared to the former antidepressants (“tricyclic”) and therefore, they were prescribed far more than necessary (1), becoming a kind of ” pill of bliss”. The opportunistic publication of the psychiatrist Peter Kramer’s book “Listen to Prozac”, contributed to the extensive prescription this type of drugs. In turn, serotonin (a neurotransmitter metabolically derived from the amino acid tryptophan) became the “marvellous” molecule which regulates the patient’s mood, and whose synaptic concentration had to be raised for it to be able to counteract a whole host of “melancholic” states.

It is true that these medications have helped millions of people all around the world to overcome depression and anxiety. These drugs are fundamental in the “armoury” of modern psychiatry. However, the problem of over-protracted treatments remains unsolved.

Initially, these drugs were approved based on pre-clinical studies – phase III clinical trials – for limited periods of time; approximately two months. Estimated pre-clinical studies of its long-term effects were not carried out, even though there are now millions of “addicts”, who find it practically impossible to give up their treatments.

The problem of the massive use of antidepressants affects practically all echelons of society. In the United Kingdom, antidepressant prescriptions have doubled over the last decade (2).

This also happens in Spain, and in the antipodes. In New Zealand, the consumption of antidepressants is at an all-time high. In the Oceanic country, a pioneer in its concern about the side effects of drugs, three quarters of users report that withdrawal symptoms are their main problem when trying to discontinue an antidepressant treatment.

At present, there is no contrasted protocol or clinical guidelines that can be utilized by doctors and patients in order to facilitate the abandonment of prolonged treatment with antidepressants. The strategy is improvised on the basis of “trial and error”, but there are many failings with this system, and patients and doctors choose to continue the treatment which worsens the problem.

Originally, antidepressants were considered a short-term treatment for episodic mood alterations. There was a certain clinical consensus not to maintain the treatments for more than nine consecutive months.

However, some studies suggested that the establishment of a steady or stable dose (3) could prevent relapses in some patients. The pharmaceutical industry manifested an unjustifiable interest in these studies as they induced the prolongation of the treatment, and therefore an increase in sales. However, the clinical trials only lasted for two years.

However, under the pressure of both the pharmaceutical industry and patients, many doctors succumbed to the comfortable continued prescription of these drugs, especially because of the “absence” of significant side effects. Thus, a growing body of patients being given over-protracted treatment with antidepressants was created.

In normal circumstances, the patient goes to his family physician and, after a brief visit, leaves the surgery with a prescription for antidepressants. This situation is comfortable for the prescribing physician who is thus able to make up for his lack of time for an exhaustive anamnesis, as well as for the patient, who thinks he can settle his problems with just a daily “pill”. In many situations, a placebo would suffice. However, everyone seems to gain by this state of affairs: the doctor, the patient, and the pharmaceutical industry! The treatment becomes protracted, without anyone warning about the future risks when the patient wants to abandon the therapy.

One dimension of the problem can be inferred from the following data: in the United States, during the 1999-2000 biennium, 13.4 million were taking antidepressants; while in the 2013-2014 biennium, their number was 34.4 million (data from the National Health and Nutrition Examination Survey) (4).

Women over 45 years of age are the main users of antidepressant drugs. However, its use is increasing notably in young adults (less than 45 years old), as well as in social minorities, even among Oriental people, for whom depression has pejorative connotations (5), and who are reluctant to accept its diagnosis.

Women of over 45 years of age represent 20% of the population of developed countries, but take up 41% of antidepressant use, 11% higher than in the year 2000. In addition, this population group represents 58% of all people who use antidepressant medication for prolonged periods which, makes it very difficult for many to abandon their treatments.

The tendency towards the over-prolongation of antidepressant treatments is, therefore, an unquestionable fact.

However, there are people who feel better when their treatment with antidepressants is protracted, and therefore, in these cases, it is not considered good practice to try to stop the treatment. The question is whether we are prescribing to prevent setbacks, or to help people overcome an adverse clinical profile.

Antidepressants are not harmless drugs. In the best of possible situations, the prolonged use of antidepressants causes an attenuation of emotions, loss of libido, erectile dysfunction and, eventually, weight gain. Many patients experience the concern about these side effects that leads them to doubt that they are recovering, or will ever recover at all.

Many patients who take antidepressant medication for years demonstrate that it is impossible for them to discontinue their treatment. In a recent survey, of the 250 people (6) who were taking antidepressants protractedly, half said they had withdrawal symptoms which they described as “severe”.

In another study involving 180 prolonged users of antidepressants (7), 130 were declared “addicted” or unable to abandon their treatments when different strategies to gradually reduce their dosage are employed.

More and more patients report that they were not informed of the possible difficulty of discontinuing their treatment.

The manufacturers of antidepressants have finally recognized that many patients have serious difficulties to abandon their medication without suffering the “interruption syndrome” (they prefer to avoid the expression “withdrawal syndrome”, which might be more appropriate). The only option available is the “trial and error” test when reducing dependence on these drugs.

This issue is not new. During the 1990s many psychiatrists recognized “interruption (or “abstinence”) syndrome” as one of the main problems with the then relatively novel “serotonin re-uptake inhibitors”. In fact, at a conference held in Phoenix (Arizona, United States) sponsored by Eli Lilly (which markets Prozac® – Fluoxetine – the first drug in the group of «inhibitors of serotonin re-uptake», and now another blockbuster, Cymbalta ® – Duloxetine), the symptoms associated with the interruption of prolonged treatments with these medications, such as balance disorders, insomnia, anxiety (sometimes extreme) and other more idiosyncratic reactions were reported.

Bibliography

Zaragoza (Spain), July, 2nd 2018

López-Tricas, J.M. MD

Hospital Pharmacist

Zaragoza (Spain)

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