Treatment-resistant depression is a term used in
psychiatry
Psychiatry is the medical specialty devoted to the diagnosis, prevention, and treatment of mental disorders. These include various maladaptations related to mood, behaviour, cognition, and perceptions. See glossary of psychiatry.
Initial p ...
to describe people with
major depressive disorder
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
(MDD) who do not respond adequately to a course of appropriate
antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...
medication within a certain time. Definitions of treatment-resistant depression vary, and they do not include a resistance to
psychological therapies
Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome prob ...
. Inadequate response has most commonly been defined as less than 50% reduction in
depressive symptoms
Depression is a mental state of low mood and aversion to activity, which affects more than 280 million people of all ages (about 3.5% of the global population). Classified medically as a mental and behavioral disorder, the experience of ...
) following treatment with at least one antidepressant medication, although definitions vary widely.
Some factors that contribute to inadequate treatment are: a history of repeated or severe
adverse childhood experiences Adverse childhood experiences (ACEs) encompass various forms of physical and emotional abuse, neglect, and household dysfunction experienced in childhood. The harms of ACEs can be long-lasting, affecting people even in their adulthood. ACEs have be ...
, early
discontinuation of treatment, insufficient dosage of medication, patient noncompliance,
misdiagnosis, cognitive impairment, low income and other socio-economic variables, and concurrent medical conditions, including comorbid
psychiatric disorders
A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitt ...
.
Cases of treatment-resistant depression may also be referred to by which medications people with treatment-resistant depression are resistant to (e.g.:
SSRI
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs increase the extracellul ...
-resistant).
In treatment-resistant depression adding further treatments such as
psychotherapy
Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome pro ...
,
lithium
Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense soli ...
, or
aripiprazole
Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressiv ...
is weakly supported as of 2019.
Risk factors
Comorbid psychiatric disorders
Comorbid
In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary ...
psychiatric disorders commonly go undetected in the treatment of
depression. If left untreated, the symptoms of these disorders can interfere with both evaluation and treatment.
Anxiety disorder
Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause phy ...
s are one of the most common disorder types associated with treatment-resistant depression. The two disorders commonly co-exist, and have some similar symptoms. Some studies have shown that patients with both MDD and
panic disorder
Panic disorder is a mental and behavioral disorder, specifically an anxiety disorder characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, short ...
are the most likely to be nonresponsive to treatment.
Substance abuse
Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...
may also be a predictor of treatment-resistant depression. It may cause depressed patients to be noncompliant in their treatment, and the effects of certain substances can worsen the effects of depression.
Other psychiatric disorders that may predict treatment-resistant depression include
attention deficit hyperactivity disorder
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
,
personality disorder
Personality disorders (PD) are a class of mental disorders characterized by enduring maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the individual's cultu ...
s,
obsessive compulsive disorder
Obsession may refer to:
Psychology
* Celebrity worship syndrome, obsessive addictive disorder to a celebrity's personal and professional life
* Fixation (psychology), a persistent attachment to an object or idea
* Idée fixe (psychology), a pr ...
, and
eating disorder
An eating disorder is a mental disorder defined by abnormal eating behaviors that negatively affect a person's physical or mental health. Only one eating disorder can be diagnosed at a given time. Types of eating disorders include binge eating d ...
s.
Comorbid medical disorders
Some people who are diagnosed with treatment-resistant depression may have an underlying undiagnosed health condition that is causing or contributing to their depression.
Endocrine disorders
Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology.
Types of disease
Broadly speaking, endocrine disorders may be subdivided into three groups:
# Endocrin ...
like
hypothyroidism
Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as ...
,
Cushing's disease
Cushing's disease is one cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary (secondary hypercortisolism). This is most often as a result of a pituitary adenoma (spe ...
, and
Addison's disease
Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrena ...
are among the most commonly identified as contributing to
depression. Others include
diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
,
coronary artery disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pl ...
,
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
,
HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
, and
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
.
Another factor is that medications used to treat comorbid medical disorders may lessen the effectiveness of
antidepressants
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
or cause
depression symptoms
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introd ...
.
Features of depression
People with depression who also display psychotic symptoms such as
delusions
A delusion is a false fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or som ...
or
hallucinations
A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...
are more likely to be treatment resistant. Another depressive feature that has been associated with poor response to treatment is longer duration of
depressive episodes.
Finally, people with more
severe depression
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...
and those who are
suicidal
Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and subs ...
are more likely to be nonresponsive to
antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...
treatment.
Treatment
There are three basic categories of drug treatment that can be used when a medication course is found to be ineffective. One option is to switch the patient to a different
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...
. Another option is to add a medication to the patient’s current treatment. This can include
combination therapy
Combination therapy or polytherapy is therapy that uses more than one medication or modality. Typically, the term refers to using multiple therapies to treat a ''single'' disease, and often all the therapies are pharmaceutical (although it can al ...
: the combination of two different types of
antidepressants
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
, or
augmentation therapy: the addition of a non-antidepressant medication that may increase the effectiveness of the
antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...
.
Medication
Antidepressants
=Dose increase
=
Increasing the dosage of an
antidepressant
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common Side effect, side-effects of antidepressants include Xerostomia, dry mouth, weig ...
is a common strategy to treat
depression that does not respond after adequate treatment duration. Practitioners who use this strategy will usually increase the dose until the person reports intolerable
side effects
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequenc ...
, symptoms are eliminated, or the dose is increased to the limit of what is considered safe.
=Switching antidepressants
=
Studies have shown a wide variability in the effectiveness of switching
antidepressants
Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...
, with anywhere from 25–70% of people responding to a different antidepressant. There is support for the effectiveness of switching people to a different
SSRI
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs increase the extracellul ...
; 50% of people that were non-responsive after taking one SSRI were responsive after taking a second type. Switching people with treatment-resistant depression to a different class of antidepressants may also be effective. People who are non-responsive after taking an SSRI may respond to
moclobemide or
tricyclic antidepressants
Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants, which is important for the management of depression. They are second-line drugs next to SSRIs. TCAs were discovered in the early 1950s and wer ...
,
bupropion
Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the case ...
or an
MAOI
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especi ...
.
However, the more antidepressants an individual had already tried, the less likely they were to benefit from a new antidepressant trial.
Some off label antidepressants are low dose
ketamine
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...
and highly serotonergic
catecholamines
A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol (benzene with two hydroxyl side groups next to each other) and a side-chain amine.
Catechol can be either a free molecule or a substi ...
(including very controlled use of
MDMA
3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...
in the treatment of
PTSD
Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats on a ...
and crippling
depression/
anxiety
Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
). For lethargic syndromes,
dysthymia
Dysthymia ( ), also known as persistent depressive disorder (PDD), is a mental and behavioral disorder, specifically a disorder primarily of mood, consisting of similar cognitive and physical problems as major depressive disorder, but with lon ...
, or caffeine-resistant amotivation, a dopaminergic stimulant such as
methlyphenidate, or even
dextroamphetamine
Dextroamphetamine is a central nervous system (CNS) stimulant and an amphetamine enantiomer that is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used as an athletic performance and ...
or
methamphetamine
Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...
can be helpful.
Primarily dopaminergic or norepinephrine releasing stimulants, in low doses, have been used especially in the past, or in conjunction with a multidisciplinary therapy approach, although more targeted and "mild" agents, including
modafinil
Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant medication used to treat sleepiness due to narcolepsy, shift work sleep disorder, and obstructive sleep apnea. While it has seen off-label ...
and
atomoxetine
Atomoxetine, sold under the brand name Strattera, among others, is a medication used to treat attention deficit hyperactivity disorder (ADHD). It may be used alone or along with psychostimulants. It is also used as a cognitive enhancer to impro ...
are considered first line for both childhood and adult
lethargy
Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
and inattention disorders, due to their virtually nonexistent abuse potential (limited to one or two cases per 10 000), and higher selectivity, safety, and thus slightly broader therapeutic index. When depression is related or co-morbid to an inattention disorder, often
ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
, then both can be carefully managed with the same first line stimulant medication, typically both
methylphenidate
Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, ...
and
lisdexamfetamine
Lisdexamfetamine, sold under the brand name Vyvanse among others, is a stimulant medication that is mainly used to treat attention deficit hyperactivity disorder (ADHD) in people over the age of five as well as moderate-to-severe binge eating ...
.
Other medications
Medications that have been shown to be effective in people with treatment-resistant depression include
lithium
Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense soli ...
,
triiodothyronine
Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.
Production of T3 and its prohormone thyroxine ( ...
,
benzodiazepine
Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...
s,
atypical antipsychotic
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...
s, and
stimulant
Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
s. Adding lithium may be effective for people taking some types of antidepressants; it does not appear to be effective in patients taking
SSRIs
Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions.
SSRIs increase the extracellul ...
. Triiodothyroxine (T3) is a type of
thyroid hormone
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
and has been associated with improvement in mood and depression symptoms. Benzodiazepines may improve treatment-resistant depression by decreasing the adverse side effects caused by some antidepressants and therefore increasing patient compliance.
Since the entry of
olanzapine
Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is ta ...
into
psychopharmacology
Psychopharmacology (from Greek grc, ψῡχή, psȳkhē, breath, life, soul, label=none; grc, φάρμακον, pharmakon, drug, label=none; and grc, -λογία, -logia, label=none) is the scientific study of the effects drugs have on m ...
, many
psychiatrists
A psychiatrist is a physician who specializes in psychiatry, the branch of medicine devoted to the diagnosis, prevention, study, and treatment of mental disorders. Psychiatrists are physicians and evaluate patients to determine whether their sy ...
have been adding low dose
olanzapine
Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is ta ...
to antidepressants and other
atypical antipsychotics
The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as major tranquilizers and ne ...
such as
aripiprazole
Aripiprazole, sold under the brand names Abilify and Aristada among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder. Other uses include as an add-on treatment in major depressiv ...
and
quetiapine
Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its ...
. Eli Lilly, the company that sells both olanzapine and fluoxetine individually, has also released a combination formulation which contains olanzapine and fluoxetine in a single capsule. Some low to moderate quality evidence points to success in the short term (8–12 weeks) using
mianserin
Mianserin, sold under the brand name Tolvon among others, is an atypical antidepressant that is used primarily in the treatment of depression in Europe and elsewhere in the world. It is a tetracyclic antidepressant (TeCA). Mianserin is closely ...
(or antipsychotics
cariprazine
Cariprazine, sold under the brand names Vraylar and Reagila among others, is an on oral atypical antipsychotic originated by Gedeon Richter, which is used in the treatment of schizophrenia, bipolar mania, and bipolar depression. It acts prim ...
,
olanzapine
Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is ta ...
,
quetiapine
Quetiapine, sold under the brand name Seroquel among others, is an atypical antipsychotic medication used for the treatment of schizophrenia, bipolar disorder, and major depressive disorder. Despite being widely used as a sleep aid due to its ...
or
ziprasidone
Ziprasidone, sold under the brand name Geodon among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It may be used by mouth and by injection into a muscle (IM). The IM form may be used for acute agitation ...
) to augment antidepressant medications.
These have shown promise in treating refractory depression but come with serious side effects. Stimulants such as
amphetamines
Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting, one or more hydrogen atoms in the amphetamine core structure with sub ...
and
methylphenidate
Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, ...
have also been tested with positive results but have potential for
abuse
Abuse is the improper usage or treatment of a thing, often to unfairly or improperly gain benefit. Abuse can come in many forms, such as: physical or verbal maltreatment, injury, assault, violation, rape, unjust practices, crimes, or other t ...
. However, stimulants have been shown to be effective for the unyielding depressed combined lacking
addictive personality
An addictive personality refers to a hypothesized set of personality traits that make an individual predisposed to developing addictions. This hypothesis states that there may be common personality traits observable in people suffering from addicti ...
traits or
heart problems
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, ...
.
Ketamine
Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppresses ne ...
has been tested as a rapid-acting antidepressant for treatment-resistant depression in
bipolar disorder
Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
, and
major depressive disorder
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
.
Spravato, a nasal spray form of
esketamine
Esketamine, also known as (S)-ketamine or S(+)-ketamine, is the ''S''(+) enantiomer of ketamine, is a dissociative hallucinogen drug used as a general anesthetic and as an antidepressant for treatment of depression. It is sold under the brand ...
, was approved by the
FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
in 2019 for use in treatment-resistant depression when combined with an oral antidepressant.
=Research
=
A 2016
placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
randomized controlled trial
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical te ...
evaluated the
rapid antidepressant effects of the psychedelic
ayahuasca
AyahuascaPronounced as in the UK and in the US. Also occasionally known in English as ''ayaguasca'' (Spanish-derived), ''aioasca'' (Brazilian Portuguese-derived), or as ''yagé'', pronounced or . Etymologically, all forms but ''yagé'' descen ...
in treatment-resistant depression with positive outcome.
Physical psychiatric treatments
Electroconvulsive therapy
Electroconvulsive therapy
Electroconvulsive therapy (ECT) is a psychiatry, psychiatric treatment where a generalized seizure (without muscular convulsions) is electrically induced to manage refractory mental disorders.Rudorfer, MV, Henry, ME, Sackeim, HA (2003)"Electroco ...
is generally only considered as a treatment option in severe cases of treatment-resistant depression. It is used when medication has repeatedly failed to improve symptoms, and usually when the patient’s symptoms are so severe that they have been hospitalized. Electroconvulsive therapy has been found to reduce thoughts of
suicide
Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and s ...
and relieve depressive symptoms. It is associated with an increase in
glial cell line derived neurotrophic factor.
rTMS
rTMS (
repetitive transcranial magnetic stimulation
Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse ge ...
) is gradually becoming recognised as a valuable therapeutic option in treatment-resistant depression. A number of randomised placebo-controlled trials have compared real versus sham rTMS. These trials have consistently demonstrated the efficacy of this treatment against major depression. There have also been a number of
meta-analyses
A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...
of
RCTs
The Railway Correspondence and Travel Society (RCTS) is a national society founded in Cheltenham, England in 1928 to bring together those interested in rail transport and locomotives.
Since 1929 the Society has published a regular journal ''The ...
confirming the efficacy of rTMS in treatment-resistant major depression, as well as naturalistic studies showing its effectiveness in "real world" clinical settings.
dTMS
dTMS (
deep transcranial magnetic stimulation
Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse ge ...
) is a continuation of the same idea as rTMS, but with the hope that deeper stimulation of subcortical areas of the brain leads to increased effect.
A 2015
systematic review
A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
and
health technology assessment
Health technology assessment (HTA) is a multidisciplinary process that uses systematic and explicit methods to evaluate the properties and effects of a health technology. Health technology is conceived as any intervention (test, device, medici ...
found lacking evidence in order to recommend the method over either ECT or rTMS because so few studies had been published.
Psychotherapy
There is sparse evidence on the effectiveness of
psychotherapy
Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome pro ...
in cases of treatment-resistant depression.
However, a review of the literature suggests that it may be an effective treatment option.
Psychotherapy may be effective in people with treatment-resistant depression because it can help relieve
stress
Stress may refer to:
Science and medicine
* Stress (biology), an organism's response to a stressor such as an environmental condition
* Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
that may contribute to depressive symptoms.
A
Cochrane systematic review
A systematic review is a Literature review, scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from publ ...
has shown that psychological therapies (including
cognitive behavioural therapy
Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (su ...
, dialectal behavioural therapy,
interpersonal therapy and intensive short-term dynamic psychotherapy) added to usual care (with antidepressants) can be beneficial for depressive symptoms and for response and
remission rates over the short term (up to six months) for patients with treatment-resistant depression. Medium‐ (7–12 months) and long‐term (longer than 12 months) effects seem similarly beneficial. Psychological therapies added to usual care (antidepressants) seem as acceptable as usual care alone.
Outcomes
Treatment-resistant depression is associated with more instances of
relapse
In internal medicine, relapse or recidivism is a recurrence of a past (typically medical) condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or r ...
than depression that is responsive to treatment. One study showed that as many as 80% of people with treatment-resistant depression who needed more than one course of treatment relapsed within a year. Treatment-resistant depression has also been associated with lower long-term quality of life.
larify: were patients in these studies being treated for treatment-resistant depression specifically, or were they merely given treatment as usual for depression in general?
Another study saw just 8 of 124 patients in remission after two years of standard depression treatment.
References
External links
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Major depressive disorder
Drug resistance