Ketamine vs SSRI: A Holistic Approach to Depression

Licensed clinical social worker with experience in therapy for over 20 years; Experience as a therapist and clinical director in public mental health, private practice, and in various treatment centers.

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Ketamine vs SSRI: A Holistic Approach to Depression

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Understanding Depression

Understanding depression is essential when comparing treatment options like ketamine and SSRIs (Selective Serotonin Reuptake Inhibitors). Depression is not just a transient feeling of sadness; it’s a complex persistent mental health disorder that significantly impacts a person’s mood, thoughts, physical health, and daily functioning. 

What Are the Types and Symptoms of Depression?

Depression manifests in various forms, each with its unique characteristics and symptoms. Understanding the different types of depression can help in recognizing the condition and seeking appropriate treatment. Here are the main types of depression:

1. Major Depressive Disorder (MDD) and Minor Depressive Disorder

Major Depressive Disorder, also known as clinical depression, is characterized by persistent and intense feelings of sadness or despair which must cause significant distress or impairment, according to the DSM IV or V [1]. Individuals with MDD experience 5 or more symptoms summarized below. Minor Depressive Disorder is similar but with 2-4 symptoms.

It can manifest in various forms:

  • Persistent Sadness or Hopelessness: While it’s normal to experience a wide range of emotions, persistent feelings of sadness, hopelessness, or emptiness are red flags. If these feelings last for more than two weeks, it could indicate depression.
  • Changes in Behavior and Interests: Pay attention if you suddenly lose interest in activities you used to enjoy, withdraw from social interactions, or have a significant change in eating or sleeping patterns.
  • Physical Symptoms: Depression can manifest physically through constant fatigue, unexplained aches and pains, or changes in appetite or weight.
  • Emotional Outbursts: Look for signs of uncharacteristic irritability, anger, or frustration, which can all be indicators of underlying depression.
  • Self-destructive Behavior: Any talk of suicide, self-harm, or engaging in risky or harmful activities should be taken very seriously, as these can be signs of deep psychological distress.
  • No manic or hypomanic behavior

2. Persistent Depressive Disorder (Dysthymia)

Persistent Depressive Disorder, or dysthymia, involves a chronic state of depression where symptoms last for at least two years for adults or one year for children and adolescents. While the symptoms are not as severe as in major depressive disorder, their long-lasting nature can significantly impact a person’s quality of life.

3. Bipolar Disorder

Bipolar disorder is characterized by mood swings that range from depressive lows to manic highs. The depressive phases of bipolar disorder can resemble those of major depressive disorder but are interspersed with periods of high energy, euphoria, or irritability.

4. Seasonal Affective Disorder (SAD)

Seasonal Affective Disorder is a type of depression that typically occurs during the winter months when there is less natural sunlight. It is more common in countries far from the equator. Symptoms might include oversleeping, appetite changes, weight gain, and a heavy, leaden feeling in the arms or legs.

5. Postpartum Depression

Postpartum depression is a significant type that affects women after giving birth. It goes beyond the “baby blues,” with mothers experiencing severe mood swings, exhaustion, and a sense of detachment from their baby.

6. Atypical Depression

Atypical depression refers to a subtype of major depressive disorder. Individuals with this type experience a temporary mood lift in response to positive events, alongside other symptoms like weight gain, increased appetite, excessive sleep, and a heavy feeling in the limbs.

Recognizing the diversity in depressive disorders is key for diagnosis and treatment. Each type of depression has its specific traits and may require different treatment approaches, emphasizing the need for personalized mental health care.

What Causes Depression?

The causes of depression are multifaceted, involving a combination of genetic, biological, environmental, and psychological factors. While the exact mechanism is not entirely understood, it’s believed that a significant aspect of depression is the imbalance of neurotransmitters in the brain, chemicals that help regulate mood. Traditional views have focused on the ‘monoamine hypothesis,’ which suggests that a deficiency in certain neurotransmitters like serotonin, norepinephrine, and dopamine contributes to depression.

What Are SSRIs?

SSRIs, which include medications like fluoxetine (Prozac), sertraline (Zoloft), and citalopram (Celexa), are the most commonly prescribed antidepressants. They work by blocking the reuptake of serotonin in the brain, increasing its availability, and are generally recommended as a first-line treatment for depression. SSRIs are favored for their relative safety, fewer side effects compared to older antidepressants, and their effectiveness in treating a broad range of depressive disorders.

How Does Ketamine Help With Depression?

Ketamine, a medication traditionally used for anesthesia in humans and animals, emerged as a novel off-label (unapproved use of an FDA approved drug) treatment for depression, particularly in cases where other treatments have failed. A version of ketamine (esketamine) finally received FDA approval in 2019, following years of research and clinical trials [2]. Subanesthetic doses of ketamine are administered.

Ketamine is categorized as a dissociative anesthetic, which means a sense of disconnection from the usual self and ordinary reality. Most people using the light approved doses will most likely experience mild anesthetic, antidepressant, anxiolytic (anxiety reducing), and, potentially, psychedelic effects. It is best administered together with appropriate psychotherapy.

Unlike SSRIs, which can take weeks to show effects, ketamine can produce rapid antidepressant effects, sometimes within hours or days [3]. It is believed to work through a different mechanism than SSRIs, primarily affecting the glutamate system, another crucial neurotransmitter pathway involved in mood regulation.

The distinction between ketamine and SSRIs highlights the complexity of depression and the necessity of personalized treatment approaches. While SSRIs are effective for many, they don’t work for everyone (about 50%) and can have side effects that vary from person to person. But they have been proven effective in many cases of Treatment Resistant Depression (TRD) which affects millions, of whom 80% will relapse. Ketamine offers an alternative for those who have not benefited from traditional treatments, though its long-term effects and optimal usage protocols are still under research.

In summary, understanding the multifaceted nature of depression is crucial in evaluating and choosing between treatments like ketamine and SSRIs. The decision should be tailored to the individual, considering the specific symptoms, underlying causes, response to previous treatments, and the balance between benefits and potential side effects. 

This holistic approach acknowledges the complexity of depression and the need for comprehensive treatment strategies that address both the biological and psychosocial aspects of the disorder.

Who Is a Good Candidate for Ketamine Therapy?

Ketamine therapy, particularly for mental health conditions, has gained attention in recent years as an innovative and rapid treatment option. However, it’s not suitable for everyone, and the decision to use ketamine therapy should always be guided by a healthcare professional. Here are some general considerations to determine who might be a good candidate for ketamine therapy:

  1. Treatment-Resistant Depression: Patients who have not responded to conventional antidepressants or other treatments for depression might benefit from ketamine. It’s particularly considered for those with severe, treatment-resistant depression.
  1. Acute Suicidal Ideation: Because of its rapid-acting nature, ketamine has been studied in the context of reducing acute suicidal thoughts in individuals with mood disorders.
  1. Other Mood Disorders: Besides depression, ketamine might be beneficial for individuals with certain other mood disorders, such as anxiety or bipolar disorder, especially if other treatments have not been effective.
  1. Chronic Pain Syndromes: Ketamine is sometimes used for chronic pain management, particularly for conditions where pain is difficult to control with standard treatments.
  1. Proper Medical Supervision: A good candidate is someone who can undergo ketamine therapy under the guidance and supervision of a qualified healthcare provider, ensuring that the treatment is administered safely and effectively.
  1. No Contraindicating Health Conditions: Patients should not have health conditions that could make ketamine dangerous for them. For instance, individuals with certain cardiovascular conditions, uncontrolled hypertension, or a history of substance abuse may not be suitable candidates.
  1. Informed Consent: A good candidate is someone who has been fully informed about the potential benefits and risks of ketamine therapy and agrees to proceed with a clear understanding of the treatment process.

It’s crucial for anyone considering ketamine therapy to have a thorough evaluation by a healthcare provider to discuss their medical history, mental health history, and other treatment options before deciding on ketamine therapy. This ensures that the treatment is appropriate for their specific condition and circumstances.

 How Do SSRIs Help People With Depression?

Selective Serotonin Reuptake Inhibitors (SSRIs) are a class of drugs commonly used to treat depression, and they work by impacting chemical signals in the brain. For years they have been the gold standard used by medical professionals Here’s a more detailed look at how SSRIs help people with depression:

  • Serotonin Modulation: SSRIs primarily function by increasing the level of serotonin, a neurotransmitter, in the brain. Serotonin is sometimes called the “feel-good” neurotransmitter because it contributes to feelings of well-being and happiness.
  • Blocking Reuptake: Normally, once serotonin is released into the synaptic space (the gap between neurons), it is reabsorbed by the releasing neuron in a process known as reuptake. SSRIs work by blocking this reuptake process.
  • Increased Serotonin Levels: By preventing the reuptake of serotonin, SSRIs increase the amount of serotonin available in the synaptic space. This allows it to bind to and stimulate the receptor sites on the receiving neuron for a longer time, enhancing the transmission of serotonin signals.
  • Neurotransmitter Balance: The increased presence of serotonin in the synaptic space helps to correct the neurotransmitter imbalances that are often associated with depression. While the exact cause of depression is multifaceted and not fully understood, it’s believed that an imbalance in neurotransmitters plays a significant role.
  • Adaptive Changes: SSRIs don’t usually lead to immediate improvements in symptoms. Over time (typically 4-12 weeks), the increased availability of serotonin promotes various adaptive changes in the brain. These changes can include the alteration of receptor densities and the enhancement of neuroplasticity, which can improve mood and cognitive functions.
  • Reduced Symptoms: By facilitating these changes, SSRIs can help alleviate the symptoms of depression, such as sadness, lack of interest in activities, and disturbances in sleep and appetite. They can also improve concentration, increase energy, and decrease anxiety.
  • Individual Responses: It’s important to note that individuals respond differently to SSRIs. What works well for one person may not work as effectively for another, and some people may experience side effects that make a particular SSRI unsuitable for them.

While SSRIs are commonly used and can be highly effective, they are just one part of a comprehensive treatment plan for depression that may also include other medications, therapy, lifestyle changes, and support.

Who Gets Prescribed With Antidepressants?

Antidepressants are typically prescribed to individuals who have been diagnosed with mood disorders or other conditions where these medications can be beneficial. Here’s a more detailed overview of who might be prescribed antidepressants:

  • Individuals with Major Depressive Disorder (MDD): This is the primary group for whom antidepressants are prescribed. People with MDD experience persistent and intense feelings of sadness and despair that affect their daily functioning.
  • People with Anxiety Disorders: Antidepressants, especially SSRIs and SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), are commonly used to treat various anxiety disorders, including generalized anxiety disorder, panic disorder, and social anxiety disorder.
  • Patients with Obsessive-Compulsive Disorder (OCD): Some antidepressants, particularly those that affect serotonin levels, are effective in treating OCD symptoms.
  • Individuals with Bipolar Disorder: While the primary treatment for bipolar disorder is mood stabilizers, antidepressants may be used cautiously in conjunction with these medications to manage depressive episodes.
  • People with Chronic Pain Conditions: Certain antidepressants, particularly tricyclic antidepressants, can be effective in managing chronic pain conditions, even in the absence of depression.
  • Patients with Eating Disorders: Antidepressants might be prescribed to individuals with conditions like bulimia nervosa or binge-eating disorder to help manage symptoms.
  • Those with Post-Traumatic Stress Disorder (PTSD): Antidepressants can be part of the treatment regimen for PTSD to help manage symptoms such as anxiety, flashbacks, and depression.
  • Individuals with Premenstrual Dysphoric Disorder (PMDD): SSRIs can be effective in treating the severe mood-related symptoms of PMDD.

It’s crucial to note that the decision to prescribe antidepressants is typically made after a thorough evaluation by a healthcare provider, who considers the individual’s specific symptoms, medical history, other medications, and overall health. The goal is to ensure that the benefits of the medication outweigh any potential risks or side effects. 

Furthermore, antidepressants are often more effective when combined with therapy, lifestyle changes, and other supportive measures.

Is Ketamine Therapy Safe to Take While on Antidepressants?

The combination of ketamine therapy with antidepressants needs to be approached with caution and under close supervision by a healthcare professional. Here’s a general overview of the considerations and potential interactions:

Selective Serotonin Reuptake Inhibitors (SSRIs): Generally, ketamine can be used alongside SSRIs. Many patients who undergo ketamine therapy are already on SSRIs due to treatment-resistant depression. However, individual responses can vary, necessitating close monitoring.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): Like SSRIs, SNRIs can typically be used concurrently with ketamine. The healthcare provider will monitor the patient’s response to the combination to adjust treatment as necessary.

Tricyclic Antidepressants (TCAs): Because TCAs impact a wide range of neurotransmitters, it’s crucial to monitor interactions closely if combined with ketamine therapy.

Monoamine Oxidase Inhibitors (MAOIs): Combining MAOIs with ketamine could potentially lead to hypertensive issues or other adverse effects. This combination is usually avoided or approached with extreme caution.

Mood Stabilizers and Antipsychotics: If a patient is on mood stabilizers or antipsychotics, the healthcare provider will need to evaluate the risks and benefits of introducing ketamine therapy.

Risk of Serotonin Syndrome: While rare, there’s a theoretical risk of serotonin syndrome when combining ketamine with medications that increase serotonin levels. This condition is serious and requires immediate medical attention.

Personalized Assessment: Before starting ketamine therapy, it’s crucial for healthcare providers to review the patient’s current medications, medical history, and overall health to assess the safety and potential for drug interactions.

Clinical Supervision: If a patient on antidepressants begins ketamine therapy, it should be done under strict medical supervision. The healthcare provider will monitor for side effects, interactions, and the overall effectiveness of the treatment.

In summary, while ketamine therapy can often be safely combined with antidepressants, it requires a personalized approach and should only be conducted under the guidance of a healthcare professional who can closely monitor the patient’s response and adjust treatment as necessary.

How To Use Ketamine Therapy to Improve Your Mental Health

Using ketamine therapy to improve mental health involves a carefully managed medical process, typically reserved for individuals who have not adequately responded to conventional treatments. Here’s a structured approach on how to use ketamine therapy:

1. Consultation with a Healthcare Professional

  • Initial Assessment: Consult a psychiatrist or mental health professional experienced in ketamine therapy. They will evaluate your medical history, current mental health condition, and treatment history.
  • Eligibility Determination: The professional will determine if you’re a suitable candidate for ketamine therapy, considering your health history and any potential contraindications.

2. Understanding the Treatment

  • Educate Yourself: Learn about the process, potential benefits, risks, and what to expect during and after therapy.
  • Informed Consent: Ensure you understand all aspects of the therapy and provide informed consent before proceeding.

3. Undergoing Ketamine Therapy

  • Medical Setting: Ketamine therapy should be administered in a controlled medical setting under the supervision of qualified healthcare providers.
  • Administration: Subanesthetic doses of ketamine can be administered intravenously, intramuscularly, or nasally, depending on the protocol used by your healthcare provider.
  • Monitoring: During the treatment, healthcare professionals will monitor your vital signs and overall well-being to ensure safety.

4. Post-Therapy Care

  • Observation: Post-treatment, you’ll be observed until the immediate effects of the drug wear off, ensuring you’re safe to leave the healthcare facility.
  • Transportation: Arrange for someone to drive you home after the treatment, as you should not operate vehicles or heavy machinery until fully recovered from the immediate effects.

5. Integrating Psychotherapy into Overall Care

  • Therapeutic Integration: Consider integrating psychotherapy sessions alongside ketamine treatments to maximize benefits and address underlying issues.
  • Follow-Up: Regular follow-up appointments with your healthcare provider are crucial to assess the therapy’s effectiveness and make any necessary adjustments.

6. Monitoring and Adjusting Treatment

  • Assessment: Continuous monitoring of your mental health condition is vital to evaluate the effectiveness of the treatment and make necessary adjustments.
  • Long-term Plan: Work with your healthcare provider to develop a long-term treatment plan, which may include additional ketamine sessions or other therapeutic interventions.

7. Lifestyle and Support

  • Support System: Engage with a support system, such as family, friends, or support groups, which can provide emotional support throughout your treatment.
  • Holistic Approaches: Complement the therapy with lifestyle changes, like regular exercise, a balanced diet, and mindfulness practices, to support overall mental health.

Using ketamine therapy for mental health is a significant step that should be approached with thorough preparation and professional guidance to ensure safety and effectiveness. Always follow the advice of your healthcare provider and keep them informed about your experiences throughout the treatment process.

Making An Informed Decision

Making an informed decision about undergoing ketamine therapy involves understanding the potential benefits, risks, and the overall process. Here’s a structured guide to help you make an informed choice:

Step 1: Gather Information

  • Understand the Therapy: Research ketamine therapy, how it works, its uses, and its mechanism of action in treating mental health conditions.
  • Evidence and Studies: Look into the latest research and clinical studies on the effectiveness and safety of ketamine therapy for your specific condition.

Step 2: Medical Consultation

  • Healthcare Provider: Consult with a mental health professional or a medical doctor who has experience with ketamine therapy. They can provide personalized information based on your medical history and condition.
  • Assessment: Get a thorough assessment to determine if you are a suitable candidate for ketamine therapy. This includes discussing your treatment history, current health status, and any potential contraindications.

Step 3: Understand the Risks and Benefits

  • Benefits: Discuss the potential benefits of ketamine therapy for your condition, including the expected outcomes and the duration of the effects.
  • Risks: Understand the possible side effects and risks associated with ketamine therapy, including both short-term and long-term implications.

Step 4: Practical Considerations

  • Treatment Plan: Understand the specifics of the treatment plan, including the number of sessions, the form of ketamine administration, and the duration of the treatment.
  • Cost: Consider the cost of therapy, as ketamine treatments are not always covered by insurance, and assess how it fits within your financial means.

Step 5: Support and Integration

  • Support System: Think about your support system and how they can assist you during the treatment process. This includes transportation to and from sessions, as well as emotional support.
  • Integration: Consider how you will integrate the therapy into your overall treatment plan, including combining it with psychotherapy, lifestyle changes, or other treatments.

Step 6: Seek Second Opinions

  • Professional Opinions: It can be beneficial to seek second opinions from other healthcare professionals to get a broader perspective on the suitability and potential effectiveness of ketamine therapy for you.

Step 7: Reflect and Decide

  • Personal Reflection: Take the time to reflect on all the information you have gathered. Weigh the pros and cons in the context of your personal health, goals, and values.
  • Decision: Make an informed decision, ensuring that it aligns with your overall treatment goals and health objectives.

Step 8: Continuous Evaluation

  • Monitor Progress: If you decide to proceed with ketamine therapy, continuously evaluate its impact on your condition with your healthcare provider.
  • Adjustments: Be open to making adjustments to your treatment plan based on your response to the therapy.

By thoroughly researching, consulting healthcare professionals, and considering your personal circumstances and health goals, you can make a well-informed decision about pursuing ketamine therapy for mental health improvement.

Corner Canyon Can Help With Ketamine-Assisted Psychotherapy

At Corner Canyon Health Centers, if a client is clinically and medically approved, we offer a 6 week course of ketamine shots, administered intramuscularly in a quiet private room and supervised by medical personnel. This is followed by a therapy session with the primary therapist. Subsequent group and individual therapy sessions throughout the week also capitalize on the increased neuroplasticity of the brain to achieve greater therapeutic gains than possible otherwise.

If you or a loved one would like to participate in this closely supervised treatment, reach out to us to discuss or book an appointment.


[1] Table 1. Diagnostic criteria for primary DSM-IV depression disorders in children and adolescents. 2009. Screening for Child and Adolescent Depression In Primary Care Settings: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Evidence Syntheses, No. 69. Williams SB, O’Connor E, Eder M, et al. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Apr

[2] Cracking the Ketamine Code

[3] Mandal S. et al. 2019. Efficacy of ketamine therapy in the treatment of depression.Indian J Psychiatry. 2019 Sep-Oct; 61(5): 480–485. Doi: 10.4103/psychiatry.IndianJPsychiatry_484_18

Licensed clinical social worker with experience in therapy for over 20 years; Experience as a therapist and clinical director in public mental health, private practice, and in various treatment centers.

Liz Lund, MPA

Liz is originally from lush green Washington State. She is a life enthusiast and a huge fan of people. Liz has always loved learning why people are the way they are. She moved to UT in 2013 and completed her bachelors degree in Psychology in 2016. After college Liz worked at a residential treatment center and found that she was not only passionate about people, but also administration. Liz is recently finished her MPA in April 2022. Liz loves serving people and is excited and looking forward to learning about; and from our clients here at Corner Canyon.
When Liz is not busy working she love being outdoors, eating ice cream, taking naps, and spending time with her precious baby girl and sweet husband.