Does Ketamine Work for Depression?

Individuals who use ketamine for depression may experience a feeling of relaxation.

Ketamine for Depression

There are many studies citing the treatment efficacy of ketamine for depression in a variety of uses and contexts. To understand how using ketamine for depression works and helps, one must first look at an overview of treatment methods for Depressive disorders, identify the ‘gold standards’ in treatments for depression, and then understand and evaluate ketamine for depression.

Treatment Methods for Depressive Disorders

There are many methods of treating Depressive disorders. Treatment plans may vary per diagnosed individual. For instance, two individuals with the same diagnosis may have different treatment plans, as the disorder can affect the two individuals in different ways. A treatment plan can include a single method or a combination of methods of treatment.

Gautam et. al’s (2017) study states that managing depression requires both a comprehensive assessment and a proper establishment of diagnosis. The study states that formulating a treatment plan begins with establishing a diagnosis in a patient with Depressive features. After this comes the assessment of the patient’s severity of illness, risk of harm, comorbid or dependence on substance use, personality factors, treatment history, and levels of functioning or work dysfunction. The patient must be given a physical examination, and a mental status examination. The patient’s beliefs of the cause of his illness and beliefs of the treatment will be assessed as well, along with an assessment for social support, stigma, and coping. After the patient has been fully assessed decisions about the treatment setting will be made, which consider which course of action will provide the best treatment for the patient. The patient may then be treated with pharmacological management by giving him the most appropriate antidepressants. The patient may also be treated with electroconvulsive therapy for certain cases. The patient may also receive non-pharmacological treatment through psychoeducation and psychotherapeutic intervention.

Gautam et. al’s (2017) study states that in the formulation of the treatment plan, patients and their caregivers may be consulted on decisions regarding treatment settings, medications, and psychological treatments to be used, in order to formulate a treatment plan that is practical, feasible, and flexible. In order to ensure good outcomes, there must be a good alliance between the patient and the psychiatrist. There must be compliance with the treatment as well. Any sign of a patient’s relapse must be addressed early, in order to decrease the chances of a full-blown relapse or any further complications.

Gold Standard Treatments for Depressive Disorders

There are many treatment methods used for Depressive disorders. Here is a non-definitive list of some treatment methods, which discuss the gold standard treatment for every treatment method.

Case Management

An individual’s case manager is a primary care provider who helps assess, plan, and implement strategies for the individual’s recovery. Hopper (2015)’s study defines good case management as one that lasts 6 to 12 months, monitors medication, assesses the improvement of depression symptoms, assesses and responds to crisis, provides education, takes responsibility for follow-ups, and takes actions when the individual does not meet the expectations of prescribed care. Individuals who had case managers showed an improvement in documenting and monitoring PHQ9 scores, and an improvement in response rates and remission rates when compared to usual care. Improved suicide assessment, potential for intervention and access to care had observed improvements as well.

Complementary and Alternative Medicine (CAM)

CAM covers all treatment methods not associated with standard care which can be used in place of, or in addition to standard care. Nahas and Sheikh’s (2011) study on CAM for treating major depressive disorder discuss how using St. John’s wort and regularly exercising were effective treatments. Gelenberg et. al’s (2010) work states that CAM’s effectiveness relies on the therapist’s skill. However when used alone, CAM’s antidepressant efficacy is limited or absent.

Here is a list of some CAM treatment methods:

  • St. John’s Wort
  • S-adenosyl methionine
  • Omega-3 fatty acids
  • Folate
  • Light therapy
  • Acupuncture

Electroconvulsive Therapy (ECT)

Gelenberg et. al’s (2010) work states that among any form of antidepressant treatment, electroconvulsive therapy has the highest rates of response and remission, with a greater proportion of patients with major depressive disorder who respond to ECT than the proportion of patients who respond to medication. ECT should be considered for cases of severe major depressive disorder that is not responsive to psychotherapeutic and/or pharmacological interventions.

Hospitalization

Individuals are sometimes hospitalized so that they may be closely monitored, accurately diagnosed, or have their medications adjusted as needed. Individuals who need hospitalization for depression are those that have severe cases of depression or treatment-resistant depression.

Medication

Pharmacotherapy refers to therapy which uses pharmaceutical drugs. Medications help individuals manage their symptoms of depression. Gautam et. al’s (2017) study states that antidepressants in general have shown efficiency in managing depression. As an initial treatment, antidepressants can be used for patients who have mild, moderate, or severe depressive episodes. In general, Selective Serotonin Reuptake Inhibitors (SSRIs) are used as the first line of antidepressants, because of SSRIs side effect and safety profile. Other antidepressants may also be used. Gelenberg et. al’s (2010) work states that the selection of a medication may depend on the cost, and the patient’s tolerability, safety, preference, and history of prior medication treatment.

Here is a list of groups of medication used for Depressive disorders:

  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • tricyclic antidepressants (TCAs)
  • Serotonin-norepinephrine Reuptake Inhibitors (SNRIs)
  • Monoamine Oxidase Inhibitors (MAOIs)
  • other medications such as bupropion, nefazodone, trazodone, and mirtazapine

Peer Support

Individuals can receive help from others who have the same experiences as them.

Psychotherapy

Psychotherapy improves an individual’s well-being through exploring his thoughts, feelings, and behaviors. Psychotherapeutic interventions may be considered for patients with mild to moderate depressive disorder. Gelenberg et. al’s (2010) work states that psychotherapy’s effectiveness relies on the skill and training of the therapist.

Here is a list of some psychotherapeutic interventions:

  • Cognitive Behavioral Therapy (CBT)
  • Interpersonal Therapy (IPT)
  • Supportive psychotherapy
  • Behavioral Therapy (BT)
  • Marital Therapy (MT)
  • Family Therapy
  • Brief Psychodynamic Therapy

Psychoeducation

Gautam et. al’s (2017) study states that education about depression may be given to the patient and his family.

Support Groups

Individuals in support groups share their goal of recovering with members who guide each other.

Ketamine for Depression

What is Ketamine?

Ketamine is a dissociative anesthetic, a schedule III drug that blocks sensory perception. Niciu et. al’s (2014) work defines ketamine as a N-methyl-D-aspartate (NMDA) receptor antagonist. This simply means that ketamine is a drug that can block or reduce a biological response by binding and blocking a receptor.

Ketamine comes in the form of a clear liquid, or in the form of a white powder. While ketamine is legally produced and used for anesthetic purposes, ketamine can be abused for its hallucinogenic properties.

Niciu et. al’s (2014) work states that ketamine can be taken in the following ways:

  • intravenously
  • intramuscularly
  • intranasally
  • sublingually
  • rectally
  • orally
  • topically

Individuals who use ketamine for depression may experience a feeling of relaxation. Low doses of ketamine for depression can relieve some symptoms. However, using ketamine for depression may cause some side effects.

Here is a list of side effects of ketamine:

  • amnesia
  • bluish lips, skin, or fingernails
  • blurred vision
  • changes in heartbeat speed or irregularities in heartbeat
  • chest pain
  • cloudy or bloody urine
  • confusion
  • convulsions
  • delusions
  • difficulty breathing
  • difficulty thinking
  • difficulty swallowing
  • difficulty urinating
  • dizziness
  • fainting
  • fatigue
  • frequent urination
  • hives, itching, or rashes
  • inability to control eye movement
  • increased pressure in brain or eyes
  • loss of appetite
  • mild sedation
  • nausea
  • nervousness or restlessness
  • paleness
  • puffy eyelids, lips or tongue
  • slurred speech
  • sweating

Where Has Ketamine for Depression Worked?

In Murrough et. al’s (2013) two-site randomized controlled trial, patients with treatment-resistant major depression experiencing a depressive episode were randomly assigned in two groups, where one group would take a single intravenous infusion of ketamine for depression, and the other group took midazolam as a placebo for depression. Ketamine was shown to have rapid antidepressant effects, a result consistent with findings from other studies in their literature review.

Niciu et. al’s (2014) work supports Murrough et. al’s work, stating that ketamine has rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bipolar depression.

Why Does Ketamine for Depression Work?

Niciu et. al’s (2014) work states that treatment for major depressive disorder and bipolar depression has focused on monoamine modulation. While current medications used for treating Depressive disorders have a good profile, there have been many recent studies which find that these first-line antidepressants and combinations of antidepressants can be ineffective for many patients. Monoaminergenic antidepressants also take weeks or months to achieve their maximum efficacy, which can place a big burden on both individuals and the health-care system. These studies found a need for rapid-acting antidepressants with alternative mechanisms of action.

Unlike current medications used, ketamine works on different neurotransmitters and receptors, which helps patients with treatment-resistant depression experience relief from some of their symptoms. Currently, experts recommend using ketamine for depression with other depressants. Experts recommend using ketamine for depression for short-term treatment, while other antidepressants are still taking effect.

Limitations of Ketamine for Depression

While there are studies which show positive effects of ketamine for depression, there are still limitations. Serafini et. al’s (2014) study states that the long-term efficacy of ketamine for depression has not been investigated by studies yet. Tanner (2018)’s work states that there needs to be more work on ketamine for depression’s long-term effectiveness and safety.

Thielking’s (2018) work states that there needs to be more work on optimal dosage of ketamine for depression, work on how to maintain the effects of ketamine on depression, and more work on the best kind of care to go with other treatment methods.

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