If you or someone you know is suffering from drug-resistant depression, taking anti-depressant medication that gradually stops working or doesn’t work at all can be quite discouraging. Healthcare providers struggle to address this dilemma, with research indicating that only 60% of individuals with depression respond to antidepressant therapy. Furthermore, 10% to 30% of those who do not respond demonstrate drug-resistant symptoms along with additional issues such as impaired occupational and social function, suicidal thoughts, the deterioration of physical health, and an increased need for healthcare services.
Drug-resistant depression is defined as having an unsatisfactory or poor response to at least two trials of the recommended duration and dosage of two different types of antidepressants. This situation currently affects about 4 million Americans. If you are currently experiencing this situation, you may be wondering why your anti-depressant medication is not working. Let’s take a closer look at some of the reasons why this may be happening.
Depression is not a Uniform Condition
People are affected in different ways by depression and this is demonstrated through the irregular manner in which people respond to treatment. For instance, older individuals may be less responsive to antidepressant medication than middle-aged individuals, and younger women generally benefit less from tricyclic antidepressants (TCAs) than women who are prescribed monoamine oxidase inhibitors (MAOIs).
Furthermore, clinical research has investigated the effectiveness of MAOIs such as tranylcypromine (Parnate) in people with depression who failed to experience benefits from selective serotonin reuptake inhibitors(SSRI) treatment. The response rate for the MAOI therapy was found to be between 12% to 45.5%. Several of the individuals who switched to the MAOI discontinued taking the medication due to its side effects.
There are a number of risk factors that increase the likelihood of drug-resistant depression, some of which include: drug interactions, age, gender, drug or alcohol abuse, or concurrent medical or psychiatric conditions.
Antidepressants are Linked to Tolerance
Another common problem with this form of treatment is that people gradually develop a tolerance for the medication they are taking. Indeed, it has been reported that anti-depression medication typically loses its effectiveness after about 6 months, which is usually during the maintenance phase.One multi-center study even showed that for 289 individuals with recurrent depression who were treated with TCA, SSRIs, or other antidepressants, 21% of the participants discontinued the treatment, 36% were categorized as partial or non-responders, and remission was only observed for 43% of the participants. This means that it is often hard for a healthcare professional to know what type of anti-depression medication an individual may respond to. Subsequently, the trial and error method of treatment generally leads to low response rates.
Antidepressants Disrupt The Activity of Certain Chemicals in the Brain
MAOIs and SSRIs increase the levels of a chemical in the brain called serotonin. Low levels of serotonin are associated with depression, and although these two types of antidepressants increase serotonin levels, they slow down the activity of nerve cells in the brain that typically absorb serotonin. This delays the therapeutic process and leads to a poor response or no benefit at all for some people. The use of antipsychotics for drug-resistant depression has also demonstrated poor outcomes.
More specifically, a number of studies have shown that aripiprazole treatment for people with drug-resistant depression has response rates of about 47% to 70% and relapse rates of approximately 29% to 53%, but all of the studies reported significant incidences of treatment discontinuation due to aripiprazole-induced side effects such as akathisia (uncontrollable movement). Additional research confirmed that certain antidepressants, mood stabilizers, and antipsychotics may negatively affect the nervous system and even damage nerve cells, thereby rendering them both ineffective and potentially dangerous for some people.
Certain Genes Contribute to Drug-Resistance
Researchers have found that certain genes may increase the probability of experiencing drug resistance. For instance, one study explains that a specific gene mutation of a protein called cyclic adenosine monophosphate response element binding (CREB1) may be linked to drug resistance in people with depression.
Furthermore, a mutation in the gene that leads to the production of the tryptophan enzyme may also contribute to antidepressant resistance. This particular enzyme promotes the production of serotonin, but for people with major, severe, or drug-resistant depression, the gene mutation causes lowers levels of the tryptophan enzyme and this is linked to an unsatisfactory response to antidepressants.
Overall, there are a number of reasons that antidepressants don’t work for most people with depression and it is difficult for healthcare providers to accurately determine what type or dosage of medication may target your depression effectively. Therefore, if you have been prescribed one or more antidepressants or a combination of different types of medication and they are not working, you may benefit from non-pharmaceutical forms of treatment such as deep transcranial magnetic stimulation (dTMS).