Refractory Depression

Refractory depression can be defined as a major depressive disorder in which depression has not reacted to treatment, such as the use of various antidepressants with no effect. Refractory Depression, also known as treatment-resistant depression, is a challenging condition affecting some individuals struggling with both addiction and depression. It is not uncommon for people seeking help at rehabs or addiction treatment centers to also have a history of depression. In fact, research suggests that substance abuse and depression often coexist, leading to a more complex recovery process. However, if you are among those with refractory depression, navigating this path may be even more difficult.

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Historically, the concept of refractory depression has been recognised for many years. Addiction recovery professionals discovered that a significant number of people battling addiction also experienced persistent depression symptoms that seemed resistant to conventional treatment approaches. Over time, this led to the recognition and acknowledgment of refractory depression as a distinct and unique condition.

The challenge with refractory depression lies in finding effective treatment strategies. Since traditional therapies might not suffice, alternative interventions may be explored. These can include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or even experimental psychoactive substances. These approaches aim to address the underlying causes of the depression, potentially offering relief when other methods have failed.

Refractory depression affecting about 30% of those diagnosed with major depressive disorder (MDD) who have tried medications, remains a challenging condition. MDD itself impacts 5% to 17% of people at some point in their lives. Symptoms of refractory depression closely resemble those of MDD, including severe symptoms, longer-lasting depressive episodes, anhedonia and a higher number of lifetime depressive episodes. It may also co-occur with anxiety and suicidal ideation.

The exact cause of refractory depression remains unknown but it likely involves various factors, including chronic stress’s impact on the hypothalamic-pituitary-adrenal (HPA) axis. Those with refractory depression often have physical health conditions like autoimmune diseases, thyroid disease, heart disease or cerebrovascular disease.

Diagnosing refractory depression typically involves healthcare providers assessing patients who haven’t shown improvement after trying at least two first-line antidepressant medications. These first-line medications include SSRIs, SNRIs, bupropion and mirtazapine. Treatment options for refractory depression may include adjusting current medications, adding different types of antidepressants, psychotherapy or referral to a psychiatrist.

FDA-approved treatments for refractory depression include medications like aripiprazole, brexpiprazole, quetiapine, olanzapine and esketamine nasal spray. Non-medication options encompass electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS), lithium, MAOIs, pramipexole, vagus nerve stimulation (VNS) and ongoing research into psilocybin.

These treatments may come with more side effects than first-line antidepressants and their effectiveness can vary. While prevention of refractory depression isn’t guaranteed due to its multilayered origins, managing chronic stress through exercise, quality sleep, relaxation activities, goal-setting, mindfulness and support from loved ones can help.

Individuals with refractory depression can complement medical treatment by engaging in regular exercise, maintaining good sleep hygiene, adhering to a healthy diet, avoiding alcohol and nonmedical drugs and nurturing relationships. It’s important to maintain regular appointments with healthcare providers to monitor progress and address any side effects or worsening symptoms during treatment.

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    Founded in 2008, WeDoRecover has evolved from an advisory service for addiction treatment into a comprehensive provider of care, following its 2019 merger with Changes Addiction Rehab in Johannesburg. Specialising in connecting patients to top-tier addiction treatment centers in the UK, South Africa and Thailand, WeDoRecover supports individuals globally, including those from the United Arab Emirates and Europe. Accepting both South African medical aid and international health insurance our organisation facilitates access to high-quality treatment for substance and alcohol use disorders, offering individualised care that addresses the physical, mental and social needs of patients.



    Our team, led by Gareth Carter, offers empathetic and professional support, guiding you through every step of the treatment process. Whether you're in South Africa or abroad, our acceptance of various insurance plans makes quality care accessible, providing a platform for lasting recovery and a healthier future.


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    Rehab care is a good option if you are at risk of experiencing strong withdrawal symptoms when you try stop a substance. This option would also be recommended if you have experienced recurrent relapses or if you have tried a less-intensive treatment without success.

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