Over a period of years, between 10 and 20 per cent of patients diagnosed with major depressive disorder who are taking medication at a maintenance dose will have a relapse. This is despite the fact that they are stating that they are taking their medication as normal. The process typically happens gradually, although it may be that there is a certain ‘turning point’ when the patient recognises that their symptoms are no longer adequately controlled. It is possible that this happens because the effects of the medication wear off – something known as antidepressant tachyphylaxis, but little evidence supports this. Yes, tachyphylaxis is a problem when patients are prescribed opioid painkillers and certain blood pressure medications, but not when they are taking SSRIs.
If you look carefully at the cohort of individuals who say that their medication is less effective after many years on the same dose, there is no correlating reduction in side effects. Although their depression is breaking through, they report no relief from known side effects such as lowered libido and delayed orgasm. In my view, if the drug was losing its effectiveness because the body was becoming resistant to the chemicals, then all the effects would start to wane, including the side effects.
It is also interesting to see that most people on long-term antidepressant medications are on the same dose for many years. There is no evidence that people need a higher and higher level of the drug to get the same effects as you would expect if the body became resistant over time.
There is, however, plenty of evidence to suggest that people who have been taken antidepressants for a long time may not always take the correct dose at the right time and even forget their medication. A three-year study in the US looking at a cohort of people who said that their medication was becoming ineffective, found that around half of the people who relapsed had drug plasma levels which were consistent with non-compliance.
Despite the fact there is no evidence that antidepressant tachyphylaxis does exist, there is also no evidence that it doesn’t. There are very few long-term studies looking at this issue because manufacturers and pharmaceutical companies are only required by European Medicine Association regulations to show that antidepressant products work for a period of a year after commencing a drug regime. If more compelling evidence comes to light, it might be time to take a fresh look at this puzzling condition.