depression treatment

Psilocybin

A Revolution in the Depression Treatment

Definition of Depression

Depression is a common mood disorder that affects approximately 5% of adults worldwide. This disorder leads to a continuous feeling of sadness, loss of interest in daily activities, and a decrease in motivation. It can occur due to problems in school, work, or personal life, and can lead to further difficulties in various areas. Contrary to popular belief, depression is different from normal mood and emotional changes related to everyday life and can severely impact all aspects of life, including relationships with family, friends, and society, to the extent that it may even result in suicide in severe cases. Individuals can conceal the symptoms of depression to the point where they appear happy, healthy, and normal, making it challenging to diagnose and provide appropriate treatment. Depression can affect anyone, although individuals who have experienced abuse, loss of loved ones, or other stress-inducing events are more susceptible to developing depression. It is estimated that around 7% of the global population experiences a major depressive disorder annually. However, these numbers are not very precise as many individuals suffering from depression do not seek medical help. The prevalence of depression is three times higher in individuals aged 18 to 29 compared to those over 60 years old. Additionally, women are 1.5 to 3 times more likely to experience depression than men during adolescence.

Symptoms of Depression and Diagnostic Criteria

The diagnostic stage is one of the most important steps as it determines the approach and treatment plan. The examination of depression symptoms begins by assessing changes in sleep patterns, appetite, and energy levels. At least five of the following criteria are necessary for a clinical diagnosis (one of the symptoms must be either a depressed mood or loss of interest or pleasure):
  1. Sleep disturbances
  2. Loss of interest or pleasure
  3. Feelings of guilt or worthlessness
  4. Fatigue and disrupted energy levels
  5. Impaired concentration and attention
  6. Changes in appetite and weight
  7. Depressed mood
  8. Disturbances in sexual desire
Among these, all patients with depression should be evaluated for suicidal risk. Any suicide risk should be promptly addressed, which may involve hospitalization or close and frequent monitoring. After assessing the aforementioned criteria, the physician also studies the patient’s medical, family, and social background to make an appropriate evaluation for selecting the treatment plan. Common features in all depressive disorders include feelings of sadness, emptiness, or irritable mood accompanied by physical symptoms such as fatigue and low energy levels, decreased pain tolerance such as lower back pain and other muscular pains, visual problems or decreased vision, stomach pain and digestive problems, and disruptions‌‌ in bowel movements, significantly impacting an individual’s functioning. Depending on the severity and intensity of symptoms, as well as the impact of the condition on a person’s functioning, a depressive episode can be classified as mild, moderate, or severe.‌

Causes of Depression

Depressive disorder is a multifactorial illness influenced by various genetic and environmental factors. First-degree relatives of individuals with depression are approximately three times more likely to develop depression compared to the general population. However, depression can occur in individuals with no family history of depression.

Patients with neurodegenerative diseases (particularly Alzheimer’s and Parkinson’s disease), stroke, multiple sclerosis (MS), seizure disorders, cancer, and chronic pain are at risk of developing depression.

In general, daily life events and individual concerns act as triggers for depression. Stressful events such as the death or loss of a loved one, lack or reduction of social support, financial problems, cognitive conflicts, and interpersonal difficulties are examples of stress-inducing factors that can lead to depression.

Depression Pathophysiology

Researchers assess the physiological changes within the body to understand the effects of illness on an individual’s functioning and to develop better treatments for various physical and mental disorders. Current evidence indicates a complex interaction between neurotransmitters and receptors. The majority of serotonergic, noradrenergic, and dopaminergic neurons are located in the midbrain and brainstem, transmitting messages to extensive areas of the brain. Clinical and preclinical experiments demonstrate a disruption in serotonin (5-HT) activity within the central nervous system as a significant factor in the development of depression. Other involved neurotransmitters in depression include norepinephrine (NE), dopamine (DA), glutamate, and brain-derived neurotrophic factor (BDNF).

Almost any compound that inhibits the reuptake of monoamines and leads to an increase in their concentration in the synaptic cleft has clinical utility as an antidepressant. The antidepressant effects of these neurotransmitter systems have given rise to the most relevant pharmacological theory of depression, known as the monoamine deficiency hypothesis. Research findings indicate that these medications not only increase the availability of neurotransmitter reuptake but also regulate neurotransmitter receptors, intracellular signaling, and gene expression over time.

Management and Treatment Approaches for Depression

There are several effective methods for treating depression. Psychotherapy, including cognitive-behavioral therapy and interpersonal therapy, is one of these approaches. Its goal is to address the thoughts and beliefs that unconsciously contribute to the development of depression. Another treatment approach for individuals suffering from depression is the use of antidepressant medications prescribed by a psychiatrist. However, the use of antidepressant drugs may have side effects, and long-term usage can pose risks to an individual’s health. Combination therapy, which involves a combination of psychotherapy and medication, is another method of coping with depression. It has consistently shown a significant improvement in symptoms, increased quality of life, and better adaptation to the treatment process compared to monotherapy. In severe cases where a patient does not respond to medication and psychotherapy or has suicidal thoughts, various forms of electroconvulsive therapy may be employed.

Different therapeutic approaches for depressive disorders have been satisfactory at various levels. However, due to numerous parameters such as the complexity of the disease’s mechanism of action, that involvement of various physiological factors, and the influence of life circumstances on an individual’s mental state, the response to treatments may vary. A medication used for treating depression in one individual may not be effective for another person, even with the same level of depression. Furthermore, despite the progress made in our understanding of the pathophysiology of depression, no specific mechanism can explain all aspects of this condition. Therefore, it is essential and unavoidable to investigate and utilize new approaches for treating depression.

Despite the existence of known and effective treatments for various psychological disorders, over 75% of people in low- and middle-income countries do not receive any form of treatment. Even in developed countries, due to misconceptions, nearly 60% of individuals with depression do not seek medical help. Many individuals feel that being afflicted by mental health disorders is socially unacceptable and may jeopardize their personal and professional lives. This perception can be perceived as a potential risk, particularly in cases of severe depression.

Psilocybin and Depression Treatment

Psilocybin is a psychoactive compound found in certain species of mushrooms, known as psilocybin mushrooms. In novel therapeutic approaches, this medication is combined with supportive psychotherapy to help individuals explore the root causes of their mental health issues and address them. Various studies in recent years have shown that psilocybin eliminates the damaging and distressing thought patterns characteristic of depression by enhancing the connectivity between different regions of the brain. According to multiple research findings, treatment with psilocybin can lead to faster, more comprehensive, and more sustainable antidepressant effects, especially in treatment-resistant individuals. Some of these effects have persisted for at least one year in some patients, while the treatment durability of other medications is much shorter and more subject to relapse.

Some countries have approved or are currently examining the use of psilocybin treatment for depression and other mental health disorders. For instance, the Food and Drug Administration (FDA) in the United States has approved psilocybin treatment as a successful intervention for severe depression. Canada utilizes psilocybin therapy for untreatable patients, and the Netherlands allows the use of truffles containing psilocybin for therapeutic purposes. Certain cities in the United States, such as Denver, Oakland, and Santa Cruz, have decriminalized the use of psilocybin mushrooms. The Therapeutic Goods Administration (TGA) in Australia has approved the prescription of psilocybin for treatment-resistant depression starting from July 2023, making Australia one of the first countries to officially recognize this substance as a medication.

In general, the exploration of depression’s multifaceted nature has shed light on its prevalence, causes, diagnostic methods, and treatment options. As we examine the complexities of this mental disorder, the potential of psilocybin as a novel therapeutic approach is encouraging. Recent approvals in various countries have opened up new horizons for individuals struggling with depression. However, it is crucial to use psilocybin for treatment under proper medical supervision and in compliance with legal guidelines. While we have a clear path for further research to fully understand the long-term effects and applications of psilocybin, evidence indicates that this substance, as an alternative treatment, can effectively address various forms of depression with just two stable doses of 25 mg per 70 kg.