“The medication doesn’t work anymore,” is a sentence I often hear. But why would your medication stop working? Is it even possible?

The answer is yes. Bacteria can get resistant against antibiotics and when we become addicted to something like painkillers, sleeping tablets, or alcohol, our body develops a tolerance for these and you find yourself in a situation where you require more in order  to obtain the same effect.

But what about antidepressants?

It is well known fact that depression can be a recurrent illness and that many individuals will experience more than one depressive episode during their lifetime. Some people may initially respond well to antidepressant treatment, but then, over time, their depressive symptoms can return – even while still on treatment! This can be a very scary period for a patient.

Poop-out and tachyphylaxis are terms used to describe loss of antidepressant response after initial benefit, but both descriptors are problematic. Poop-out may offend some individuals as it sounds not “serious”, while tachyphylaxis is a pharmacological term describing rapid or acute reduction in response to a drug after administration. The better term to describe this recurrence of depressive symptoms despite sustained treatment with an antidepressant that did initially work is “depressive recurrence on antidepressant treatment” (DRAT) or “breakthrough” depression. Some studies report DRAT to occur in approximately 10% of patients at 6 months and 20% at 2 years, while others report that up to 30% of individuals using antidepressants will experience breakthrough or recurring symptoms during the course of one year.

On consulting “Dr Google”, I realised just how dangerous he can be! I was amazed at all the unscientific and unfounded explanations given for the development of DRAT. I found false statements claiming antidepressants are burning out your brain, burning out your adrenal glands, damaging your hormones, addictive, while psychiatrists are playing antidepressant roulette. More worrisome is blanket statements and potentially dangerous advise such as to allow your nervous system / genetic homeostasis to reset itself, you likely need to spend a significant portion of time off of medication and to stay of medication and give your body time to recover which would put you in a more favourable position than creating further neurochemical chaos. Warning: please NEVER do this without consulting with your psychiatrist! We DO have our patients’ best interests at heart!


What causes DRAT?

We do not fully understand the reasons for DRAT. Although some patients may indeed develop tachyphylaxis (i.e. the brain receptors become less sensitive or responsive to the effect of the medication) or tolerance (i.e. a higher dose of medication is needed to obtain the same effect), most cases of DRAT are due to other reasons such as:

  • Poor compliance. Patients often forget or skip doses of medication – especially when they are feeling better. When you have a fractured leg and the doctor puts on a cast, the pain is often rapidly reduced! However, just because the pain is less, you do not take off the cast – you wear it for six weeks for the bone to regrow and heal. Our brains are similar, just more intricate. Your medication is the “cast” – you need to “wear” it daily – until you are healed (which can be a period of at least 6 months to a year) even if you are noticing signs of improvement.
  • Worsening of the depression. Patients may have initially suffered from a mild or moderate depressive episode which responded well to the medication. Many reasons, either biological, or situational, can worsen the depression, which would then need a higher dose of the medication.
  • Added stressors. A bit of stress and stress hormone (cortisol) is good – it gives us drive and motivation. However, too much stress (either in intensity, frequency, or chronicity) can cause stress hormone to “burn” some of the good neurotransmitters in your brain – thereby causing worsening or a recurrence of depression.
  • Misdiagnosis or missed diagnosis. When a patient presents with a depressed episode in the absence of a previous hypomanic/manic (“high”) episode, a psychiatrist will diagnose unipolar depression. However, the patient may still in future develop a “high” – which may be induced by the antidepressant, or just in the natural course of the illness. These individuals, as well as individuals with additional (“comorbid”) illnesses such as substance abuse or anxiety disorders, often do not respond as well to antidepressants only.
  • Poor lifestyle choices. More than 50 percent of people with mood disorders have alcohol or other substance use problems. This creates havoc in the brain. Many substances are depressogenic (i.e. it causes symptoms of depression). Substances also interferes with the metabolism of medication rendering it inefficacious.  Always limit the intake of alcohol, painkillers, and “calmers”, and avoid other drugs completely. It is also important to get enough sleep and to follow a regular sleeping pattern. Up to 80% of patients with chronic sleep deprivation becomes depressed! A healthy diet and regular (5 times a week) exercise are crucial for your mental well-being.
  • Ageing. When you age, your metabolism changes, affecting how you absorb drugs. You might also start taking other medications that interfere with the absorption process of medication (e.g. anti-acid medication). You are also more likely to suffer from other medical disorders.
  • Medical disorders and medication side-effects. Many medical conditions (e.g. hypothyroidism, multiple sclerosis, diabetes, hypertension, Parkinson’s disease, acne and vitamin D deficiency) and their treatments (e.g. cortisone, methotrexate, isotretinoin, some beta-blockers and certain painkillers) can trigger or worsen depression.

Scientific research has proven antidepressants to be effective and efficacious which is why they are accepted as being a first-line treatment option for depression. Antidepressants can improve the quality of your life! However, it is not a given that you will never experience DRAT, or even a recurrence of depression. However, you can take personal responsibility and join in a team effort with your psychiatrist to regain, maintain, and preserve your mental health.


How do we manage DRAT?

  • Do not lose hope! DRAT can be successfully managed!
  • Your health is your responsibility. Ensure that you are fully compliant with your treatment, and make healthy lifestyle choices and changes today.
  • Consult your psychiatrist. It is important that your psychiatrist does a full reassessment of your symptoms, your medication, and other causes of DRAT.
  • Medication changes. Available medication strategies to address DRAT are similar to those used for any depressed patient who has relapsed or is difficult to treat, and should be individualised for the specific clinical circumstances of each patient. Common strategies are to increase the dose of the current medication, combining or augmenting medication (your psychiatrist may decide to add another antidepressant, or to add another type of drug such as a mood stabiliser), or to switch medication.
  • Drug “holidays”. This is not a common strategy as the risk of being without medication for a period of 2 to 4 weeks, especially in the case of suicidality may be more than to adjust the current medication strategy. A more judicious approach would be to decrease the current dose of medication. Although it may seem somewhat counter-intuitive, depressive symptoms may improve in some patients when the dosage is simply reduced. This approach is based on the possibility that certain antidepressants may have a “therapeutic window” whereby below a certain dose or above a certain dose, it may be less effective, or that side-effects above a certain dose overshadows the therapeutic benefit of the medication.
  • Holistic care. The treatment of depression does not only consist of medication. Psychotherapy to address underlying issues, distorted thought processes, and to assist with the development of coping skills and resilience are very important to support one’s treatment. It’s vital that one addresses the stressors and triggers. It doesn’t help to buy new shoes, if the actual problem is the thorn in your foot that needs to be removed… Lastly, as mentioned: avoid substances, sleep enough, follow a healthy and balanced diet, and exercise!