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Breakthrough Depression : Exploring Psychedelic-Assisted Therapies for Lasting Relief

    1. Introduction

      1. What is Breakthrough Depression

        Breakthrough Depression refers to a state in which depressive symptoms persist or worsen despite an individual taking antidepressant medications that were previously effective. The symptoms affect daily functioning, mood, and overall quality of life.

        Breakthrough signifies the failure of the current treatment regimen to effectively manage symptoms of depression.

        It may be difficult for doctors to manage breakthrough depression.(1) This may get distressing and frustrating for the person with depression as well.

      2. Rise in Psychedelic-Assisted Therapies

        Psychedelic therapies have gained attention and recognition in recent years for the treatment of mental conditions. There are several factors that can be a reason behind the rise: 

        • A resurgence of scientific interest in studying the therapeutic effects of psychedelic substances. Research shows promising results in using psychedelics like psilocybin, MDMA, and LSD for various mental health conditions including depression, anxiety, post-traumatic stress disorder, and addiction.(8)
        • A gradual shift in societal attitudes towards psychedelics. The change in cultural acceptance has created a more receptive environment for researching and implementing psychedelic-assisted therapies.
        • Prevalence of treatment-resistant mental health conditions such as depression and PTSD. Traditional treatments have limitations and most individuals do not experience adequate relief.
        • Individuals undergone psychedelic-assisted therapies and experienced transformative outcomes have a significant role in driving awareness and advocating for wider access.
        • Psychedelic therapies draw on both ancient indigenous practices and modern psychedelic frameworks. This provides a holistic and culturally sensitive context for utilizing psychedelics.
    2. Understanding Breakthrough Depression

      1. Causes of Breakthrough Depression

        There are several factors that may affect breakthrough depression: 

        • Non-adherence of the individual to the treatment. Missing doses or stopping the medication altogether can undermine the therapeutic effects. This can increase the risk of depression relapse.
        • Worsening of depression may lessen the effectiveness of medication.
        • Sometimes individuals may perceive improvement in symptoms after taking medication they believe to be beneficial.
        • Underlying health conditions or unique neurobiology in some individuals. This may make them less responsive to certain antidepressant medications.

        Research suggests breakthrough depression is more common with selective serotonin reuptake inhibitors (SSRI) than selective-serotonin and noradrenalin reuptake inhibitors (SSNRI) and tricyclic antidepressants.(2)

      2. Signs and Symptoms of Breakthrough Depression

        Breakthrough depression can be debilitating and can have a significant impact on the individual’s emotional well-being, daily function, and quality of life.

        The symptoms include:(3)

        • Intense and pervasive feelings of sadness, hopelessness, and emptiness. The mood disturbance is present for most of the day, every day, and even despite ongoing treatment.
        • Inability to experience pleasure or interest in previously enjoyed activities.
        • Cognitive difficulties include problems with concentration, memory, decision-making, and overall cognitive progress.
        • Insomnia or hypersomnia. A person may find it difficult to fall asleep, stay asleep, or may experience sleepiness during the day.
        • Decreased appetite causing weight loss.
        • Decreased energy even with adequate rest and sleep. A person can get physically and mentally exhausted.
        • Psychomotor agitation is characterized by restlessness, fidgeting, and inability to sit still. Some may experience psychomotor retardation and movement through processes slow down significantly.
        • Individuals may experience recurrent thoughts of death, contemplate suicide or engage in self-harming behavior.
      3. Prevalence and Impact of Breakthrough Depression on Individual

        Breakthrough depression can affect individuals in various aspects of their lives, some of which include: 

        • It impairs an individual’s ability to function effectively
        • Lead to social withdrawal, isolation, and difficulties in maintaining relationships
        • Diminishes quality of life and reduces the sense of well-being
        • Association with co-occurring mental health conditions
        • There may be an increases risk of suicidal thoughts and behavior
        • Lead to frustration and disappointment in individuals who have tried multiple treatments approaches
      4. Current Treatment Approaches and Limitations

        The current treatment approach for breakthrough depression involves a combination of psychotherapy and pharmacotherapy. The effectiveness of treatment approaches may vary from person to person. 

        • Psychotherapy: Different types of psychotherapy include cognitive behavior therapy, interpersonal therapy, and psychodynamic therapy. These are commonly used in the treatment of depression. These therapies help individuals identify and modify negative thought patterns, improve coping skills, address interpersonal difficulties, and gain insight into the underlying causes of their depression.
        • Pharmacotherapy: Antidepressants such as selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors are prescribed frequently for depression.
    3. Overview of Psychedelic therapies

      1. What are Psychedelic therapies

        Psychedelic therapies involve incorporating psychedelic substances such as psilocybin, MDMA, LSD, and ayahuasca in psychological healing, personal growth, and transformative experiences.

      2. Types of Psychedelic Therapies

        There are several types of psychedelic therapies that have emerged or are currently being explored. 

        • Psilocybin-Assisted Therapy: This involves using psilocybin (an active compound in certain species of mushrooms) in conjunction with therapeutic support. Psilocybin has shown promising results in the treatment of depression, anxiety, and addiction.
        • MDMA-Assisted Therapy: MDMA is commonly known as ecstasy and is used to facilitate deep emotional healing and promote empathy. The substance creates a heightened introspection, trust, and emotional openness, allowing individuals to explore and address trauma, anxiety, and relationship issues.
        • LSD-Assisted Therapy: LSD (Lysergic acid diethylamide) is a powerful psychedelic substance. It aims to facilitate deep introspection, emotional processing, and self-discovery.
        • Ayahuasca-Assisted Therapy: Ayahuasca is a plant-based psychedelic brew, traditionally used by indigenous cultures for spiritual and healing purposes. Ayahuasca-assisted therapies are used in ceremonial rituals led by healers and shamans. These promote self-reflection, emotional healing, and spiritual exploration.
        • Ketamine-Assisted Therapy: Ketamine is a dissociative anesthetic and a potential therapeutic tool for treatment-resistant depression. This treatment is accompanied by supportive therapy and helps individuals process their experiences and integrate insights.
        • Ibogaine-Assisted Therapy: Ibogaine is derived from the iboga plant and is a potential treatment for substance use disorders. It is believed to facilitate introspection, provide insight into the underlying cause of addiction, and support recovery.

        All these therapies should only be conducted under the supervision of trained professionals and in a controlled environment.

    4. Overview of Current Research on Psychedelic-Assisted Therapies for Depression

      Psychedelic-assisted therapies have garnered significant attention in recent years for the treatment of breakthrough depression. Studies have been conducted to look for the efficacy, safety, and therapeutic potential of psychedelic therapy in addressing depression.

      Studies conducted to assess the use of psilocybin-assisted therapy for depression.(4, 5) The result showed a significant reduction in symptoms of depression, improvement in mood, and increased quality of life. Its effect was observed to stay for several weeks to months after treatment.

      MDMA-assisted therapies have been primarily studied in the context of post-traumatic stress disorder, but have shown potential for treating depression by promoting emotional openness, empathy, and trust.(6) More depression-focused studies are needed to understand its effectiveness fully.

      Ketamine-assisted therapy has been researched extensively for treatment-resistant depression.(7, 8) It acts on the glutamate system of the brain, leading to synaptic changes that can alleviate depressive symptoms.

      Other psychedelics such as LSD, ayahuasca, and ibogaine have shown preliminary evidence of antidepressant effects, but more research is needed to determine their efficacy.(910)

Future Direction and Challenges of Psychedelic-Assisted Therapies

Psychedelic-assisted therapies are seen to be quite promising for the treatment of various mental health conditions including breakthrough depression. The research in the field continues to evolve to make it even more promising. Addressing future direction and changes requires collaboration among researchers, clinicians, policymakers, and the public.

Standardized treatment protocol for psychedelic-assisted therapies is essential to ensure consistency and safety across different therapeutic contexts.

More research is needed to assess the long-term safety profile of these treatments. Understanding of the risks and benefits over extended periods can help inform guidelines for follow-up care and treatment optimization.

Future research is needed to deepen the understanding of the mechanism of action underlying the therapeutic effects of psychedelics-assisted therapies.

Psychedelic-assisted therapies have the potential to revolutionize mental healthcare and provide new avenues of treatment for individuals with depression and other mental health conditions.


Breakthrough depression is characterized by persistent symptoms despite conventional treatment and may require innovative approaches to improve the quality of life.

Psychedelic-assisted therapies as a treatment for breakthrough depression offer a promising avenue for significant challenges associated with this mental health condition.

By addressing challenges and further research, psychedelic-assisted therapies have the potential to revolutionize the treatment for breakthrough depression. It is important that these therapies should be conducted under the guidance of trained professionals in a safe and controlled environment.

An ongoing exploration of psychedelic-assisted therapies provides hope for individuals with breakthrough depression and offers a possibility for finding relief and rediscovering a sense of well-being.

Team PainAssist
Team PainAssist
Written, Edited or Reviewed By: Team PainAssist, Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:July 10, 2023

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