Management of depression is the treatment of depression that may involve a number of different therapies: medications,

behavior therapy Behaviour therapy or behavioural psychotherapy is a broad term referring to clinical psychotherapy that uses techniques derived from behaviourism and/or cognitive psychology. It looks at specific, learned behaviours and how the environment, or ...

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 ...

, and

medical device A medical device is any device intended to be used for medical purposes. Significant potential for hazards are inherent when using a device for medical purposes and thus medical devices must be proved safe and effective with reasonable assura ...

s. Depression is a symptom of some physical diseases; a

side effect 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, consequence ...

of some drugs and medical treatments; and a symptom of some

mood disorders A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the '' Diagnostic and St ...

such as

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 ...

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 l ...

. Physical causes are ruled out with a clinical assessment of depression that measures vitamins, minerals, electrolytes, and hormones. Though

psychiatric medication A psychiatric or psychotropic medication is a psychoactive drug taken to exert an effect on the chemical makeup of the brain and nervous system. Thus, these medications are used to treat mental illnesses. These medications are typically made of ...

is the most frequently prescribed therapy for major depression,

may be effective, either alone or in combination with medication. Combining psychotherapy and antidepressants may provide a "slight advantage", but antidepressants alone or psychotherapy alone are not significantly different from other treatments, like "active intervention controls". ( e.g., sham acupuncture) Given an accurate diagnosis of major depressive disorder, in general the type of treatment (psychotherapy and/or antidepressants, alternate or other treatments, or active intervention) is "less important than getting depressed patients involved in an active therapeutic program." Psychotherapy is the treatment of choice in those under the age of 18, with medication offered only in conjunction with the former and generally not as a first line agent. The possibility of depression, substance misuse or other mental health problems in the parents should be considered and, if present and if it may help the child, the parent should be treated in parallel with the child.

Psychotherapy and behavior therapy

There are a number of different psychotherapies for depression which are provided to individuals or groups by psychotherapists, psychiatrists, psychologists, clinical social workers, counselors or psychiatric nurses. With more chronic forms of depression, the most effective treatment is often considered to be a combination of medication and psychotherapy. Psychotherapy is the treatment of choice in people under 18. A meta-analysis examined the effectiveness of psychotherapy for depression across ages from younger than 13 years to older than 75 years. It summarizes results from 366 trials included 36,702 patients. It found that the best results were for young adults, with an average

effect size In statistics, an effect size is a value measuring the strength of the relationship between two variables in a population, or a sample-based estimate of that quantity. It can refer to the value of a statistic calculated from a sample of data, the ...

of ''g''=.98 ( 95% ''CI'', 0.79-1.16). The effects were smallest for young children (<13 years), ''g'' = .35 (95% ''CI'', 0.15-0.55), and second largest in the oldest group, ''g'' = .97 (95% ''CI'', 0.42-1.52). The study was not able to compare the different types of therapy to each other. Most of the studies with children used therapies originally developed with adults, which may have reduced the effectiveness. The greater benefits with young adults might be due to a large number of studies including college students, who might have an easier time learning therapy skills and techniques. Most of the studies in children were done in the US, whereas in older age groups, more balanced numbers of studies came from Europe and other parts of the world as well. As the most studied form of psychotherapy for depression, ''

cognitive behavioral 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 (suc ...

'' (CBT) is thought to work by teaching clients to learn a set of cognitive and behavioral skills, which they can employ on their own. Earlier research suggested that cognitive behavioral therapy was not as effective as antidepressant medication in the treatment of depression; however, more recent research suggests that it can perform as well as antidepressants in treating patients with moderate to severe depression. Beck's treatment manual, ''Cognitive therapy of depression'', has undergone the most research and accumulated the most evidence for its use. However, a number of other CBT manuals also have evidence to support their effectiveness with depression. The effect of psychotherapy on patient and clinician rated improvement as well as on revision rates have declined steadily from the 1970s. A systematic review of data comparing low-intensity CBT (such as guided self-help by means of written materials and limited professional support, and website-based interventions) with usual care found that patients who initially had more severe depression benefited from low-intensity interventions at least as much as less-depressed patients. For the treatment of adolescent depression, one published study found that CBT without medication performed no better than a

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 ...

, and significantly worse than the antidepressant

fluoxetine Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive diso ...

. However, the same article reported that CBT and fluoxetine outperformed treatment with only fluoxetine. Combining fluoxetine with CBT appeared to bring no additional benefit in two different studies or, at the most, only marginal benefit, in a fourth study.

Behavior therapy Behaviour therapy or behavioural psychotherapy is a broad term referring to clinical psychotherapy that uses techniques derived from behaviourism and/or cognitive psychology. It looks at specific, learned behaviours and how the environment, or ...

for depression is sometimes referred to as behavioral activation. In addition, behavioral activation appears to take less time and lead to longer lasting change. Two well-researched treatment manuals include ''Social skills training for depression'' and ''Behavioral activation treatment for depression''. Emotionally focused therapy, founded by Sue Johnson and Les Greenberg in 1985, treats depression by identifying and processing underlying emotions. The treatment manual, ''Facilitating emotional change'', outlines treatment techniques.

Acceptance and commitment therapy Acceptance and commitment therapy (ACT, typically pronounced as the word "act") is a form of psychotherapy, as well as a branch of clinical behavior analysis. It is an empirically based psychological intervention that uses acceptance and mind ...

(ACT), a mindfulness form of CBT, which has its roots in behavior analysis, also demonstrates that it is effective in treating depression, and can be more helpful than traditional CBT, especially where depression is accompanied by anxiety and where it is resistant to traditional CBT. A review of four studies on the effectiveness of

mindfulness-based cognitive therapy Mindfulness-based cognitive therapy (MBCT) is an approach to psychotherapy that uses cognitive behavioral therapy (CBT) methods in collaboration with mindfulness meditative practices and similar psychological strategies. The origins to its concept ...

(MBCT), a recently developed class-based program designed to prevent relapse, suggests that MBCT may have an additive effect when provided with the usual care in patients who have had three or more depressive episodes, although the usual care did not include antidepressant treatment or any psychotherapy, and the improvement observed may have reflected non-specific or placebo effects. Of note, although ''Mindfulness-based cognitive therapy for depression'' prevented relapse of future depressive episodes, there is no research on whether it can cause the remission of a current depressive episode. ''

Interpersonal psychotherapy Interpersonal psychotherapy (IPT) is a brief, attachment-focused psychotherapy that centers on resolving interpersonal problems and symptomatic recovery. It is an empirically supported treatment (EST) that follows a highly structured and time-limite ...

'' (IPT) focuses on the social and interpersonal triggers that may cause depression. There is evidence that it is an effective treatment for depression. Here, the therapy takes a fairly structured course (often 12 sessions, as in the original research versions) as in the case with CBT; however, the focus is on relationships with others. Unlike family therapy, IPT is an individual format, so it is possible to work on interpersonal themes even if other family members do not come to the session. Therapy can be used to help a person develop or improve

interpersonal skills A social skill is any competence facilitating interaction and communication with others where social rules and relations are created, communicated, and changed in verbal and nonverbal ways. The process of learning these skills is called so ...

in order to allow him or her to communicate more effectively and reduce stress. In a meta-analysis of 16 studies and 4,356 patients, the average improvement in depressive symptoms was an

of ''d'' = 0.63 (95% ''CI'', 0.36 to 0.90). IPT combined with pharmacotherapy was more effective in preventing relapse than pharmacotherapy alone, number needed to treat = 7.63. ''

Psychoanalysis PsychoanalysisFrom Greek: + . is a set of theories and therapeutic techniques"What is psychoanalysis? Of course, one is supposed to answer that it is many things — a theory, a research method, a therapy, a body of knowledge. In what might ...

'', a school of thought founded by

Sigmund Freud Sigmund Freud ( , ; born Sigismund Schlomo Freud; 6 May 1856 – 23 September 1939) was an Austrian neurologist and the founder of psychoanalysis, a clinical method for evaluating and treating pathologies explained as originating in conflicts i ...

that emphasizes the resolution of unconscious mental conflicts, is used by its practitioners to treat clients presenting with major depression. A more widely practiced technique, called ''

psychodynamic psychotherapy Psychodynamic psychotherapy or psychoanalytic psychotherapy is a form of psychological therapy. Its primary focus is to reveal the unconscious content of a client's psyche in an effort to alleviate psychic tension, which is inner conflict wi ...

'', is loosely based on psychoanalysis and has an additional social and interpersonal focus. In a meta-analysis of three controlled trials, psychodynamic psychotherapy was found to be as effective as medication for mild to moderate depression.

Shared care

Shared decision making is an approach whereby patients and clinicians freely share important evidence when tasked with decision making and where patients are guided to consider the best available options to make an informed decision. The principles are well documented, but there is a gap in that it's hard to apply them in routine clinical practice. The steps have been simplified into five steps. The first step is seeking patient participation in that the health practitioner is tasked with communicating existing choices and therefore inviting them to the decision-making process. The next step involves assisting the patient to explore and compare the treatment options by a critical analysis of the risks and benefits. The third step involves the assessment of the patient's values and what they prefer taking to account what is of paramount urgency to the patient. Step 4 involves decision making where the patient and the practitioner make a conclusive decision on the best option and arrange for subsequent follow up meetings. Finally, the fifth step involves the analysis of the patient's decision'. Five steps for you and your patients to work together to make the best possible health care decisions. The step involves monitoring of the degree of implementation, overcoming of barriers of decision implantation consequently the decisions need to be revisited and optimized thus ensuring the decision has a positive impact on health outcomes. Its success relies on the ability of the health practitioner to create a good interpersonal relationship with the patient. (Stone, 2017) Depression is a major problem globally, affecting an estimated 4.4 percent of the world population in 2017, roughly equivalent to 300 million people. The depression is multifactorial and has been on the increase due to societal pressure, genetic association and increase in use of drugs (Zhang et al. 2016). incorporation of nursing in management of depression may seem important in that nursing hold a pivotal role in health care delivery where they are they are the health practitioners that have been trained to be versatile from clinical to psychological care Their incorporation shared decision making in treating depression may be important as nurses are known to have the best interpersonal relationship with the patients thus a better collaborative model can be achieved due to this fact (Williams et al. 2016). With this in mind, the nurses may serve to administer drugs in management, prepare and maintain the patient's records, interaction with other care staff to achieve optimum care, and organizing therapy sessions (Lu et al. 2019). Kathleen Walsh, 2017, recognizes that Dr. Velligan stated that SDM is of importance in demonstrating patient preferences in decision making when there is no clear approach to treatment. In addition, numerous tools can be used to make the decision making the process easier these include the Controlled Preferences Scale that informs clinicians on how to actively involve patients. She further gives the suggestion that providers need to embrace shared decision making by making sure the patients participate actively in their management thus enabling the success of the model.

Medication

To find the most effective

pharmaceutical drug 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 ...

treatment, the dosages of medications must often be adjusted, different combinations of antidepressants tried, or antidepressants changed.

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors 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 ...

(SSRIs), such as

sertraline Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The efficacy of sertraline for depression is similar to that of other antidepressants, and the diffe ...

(Zoloft, Lustral),

escitalopram Escitalopram, sold under the brand names Lexapro and Cipralex, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. Escitalopram is mainly used to treat major depressive disorder and generalized anxiet ...

(Lexapro, Cipralex),

(Prozac), paroxetine (Seroxat), and

citalopram Citalopram, sold under the brand name Celexa among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive compulsive disorder, panic disorder, and so ...

, are the primary medications considered, due to their relatively mild side effects and broad effect on the symptoms of depression and anxiety, as well as reduced risk in overdose, compared to their older tricyclic alternatives. Those who do not respond to the first SSRI tried can be switched to another. If sexual dysfunction is present prior to the onset of depression, SSRIs should be avoided. Another popular option is to switch to the atypical antidepressant

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 cas ...

(Wellbutrin) or to add bupropion to the existing therapy; this strategy is possibly more effective. It is not uncommon for SSRIs to cause or worsen insomnia; the sedating

noradrenergic and specific serotonergic antidepressant Noradrenergic and specific serotonergic antidepressants (NaSSAs) are a class of psychiatric drugs used primarily as antidepressants. They act by antagonizing the α2-adrenergic receptor and certain serotonin receptors such as 5-HT2A and 5-HT2 ...

(NaSSA) antidepressant

mirtazapine Mirtazapine, sold under the brand name Remeron amongst others, is an atypical antidepressant, and as such is used primarily to treat depression. Its effects may take up to four weeks, but can also manifest as early as one to two weeks. It is o ...

(Zispin, Remeron) can be used in such cases. For children and adolescents with moderate-to-severe depressive disorder, fluoxetine seems to be the best treatment (either with or without

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 (suc ...

) but more research is needed to be certain. Sertraline, escitalopram, duloxetine might also help in reducing symptoms. In the UK fluoxetine is the only antidepressant recommended for people under the age of 18, though, if a child or adolescent patient is intolerant to fluoxetine, another SSRI may be considered. Evidence of effectiveness of SSRIs in those with depression complicated by

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

is lacking.

Norepinephrine dopamine reuptake inhibitor

Some norepinephrine–dopamine reuptake inhibitors can be used as antidepressants.

Norepinephrine reuptake inhibitor

Norepinephrine reuptake inhibitors (NRIs) can be used as antidepressants.

Serotonin norepinephrine reuptake inhibitor

Venlafaxine Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin-norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, panic ...

(Effexor) from the SNRI class may be moderately more effective than SSRIs; however, it is not recommended as a first-line treatment because of the higher rate of side effects, and its use is specifically discouraged in children and adolescents.

Tricyclic antidepressant

Tricyclic antidepressant 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 ...

s (TCAs) have more side effects than SSRIs (but less sexual dysfunctions) and are usually reserved for the treatment of inpatients, for whom the tricyclic antidepressant

amitriptyline Amitriptyline, sold under the brand name Elavil among others, is a tricyclic antidepressant primarily used to treat cyclic vomiting syndrome (CVS), major depressive disorder and a variety of pain syndromes from neuropathic pain to fibromyalgi ...

, in particular, appears to be more effective.

Monoamine oxidase inhibitor

Monoamine oxidase inhibitor 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, esp ...

s, have historically been plagued by questionable efficacy (although early studies used dosages now considered too low) and life-threatening adverse effects. They are still used only rarely, although newer agents of this class ( RIMA), with a better side effect profile, have been developed. In older patients TCAs and SSRIs are of the same efficacy. However, there are differences between TCA related antidepressants and classical TCAs in terms of side effect profiles and withdrawal when compared to SSRIs. There is evidence a prominent side-effect of antidepressants, emotional blunting, is confused with a symptom of depression itself. The cited study, according to Professor Linda Gask was:

NMDA antagonists

Ketamine

Research on the antidepressant effects of

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 suppress ...

infusions at subanaesthetic doses has consistently shown rapid (4 to 72 hours) responses from single doses, with substantial improvement in mood in the majority of patients and

remission Remission often refers to: *Forgiveness Remission may also refer to: Healthcare and science *Remission (medicine), the state of absence of disease activity in patients with a chronic illness, with the possibility of return of disease activity *R ...

in some. However, these effects are often short-lived, and attempts to prolong the antidepressant effect with repeated doses and extended ("maintenance") treatment have resulted in only modest success. A nasal spray formulation of esketamine, sold under the brand name Spravato, gained FDA approval in 2019 for the treatment of treatment-resistant depression when combined with an oral antidepressant.

Zinc

A 2012 cross-sectional study found an association between zinc deficiency and depressive symptoms among women, but not men, and a 2013 meta-analysis of 17 observational studies found that blood zinc concentrations were lower in depressed subjects than in control subjects. A 2012 meta-analysis found that zinc supplementation as an adjunct to antidepressant drug treatment significantly lowered depressive symptom scores of depressed patients. The potential mechanisms underlying the association between low serum zinc and depression remain unclear, but may involve the regulation of neurotransmitter, endocrine and neurogenesis pathways. Zinc supplementation has been reported to improve symptoms of

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-inap ...

and depression. A 2013 review found that zinc supplementation may be an effective treatment in major depression.

Acetyl-l-carnitine

Acetylcarnitine levels were lower in depressed patients than controls and in rats it causes rapid antidepressant effects through epigenetic mechanisms. A systematic review and meta-analysis of 12 randomized controlled trials found "supplementation significantly decreases depressive symptoms compared with placebo/no intervention, while offering a comparable effect with that of established antidepressant agents with fewer adverse effects."

Augmentation

Physicians often add a medication with a different mode of action to bolster the effect of an antidepressant in cases of treatment resistance; a 2002 large community study of 244,859 depressed Veterans Administration patients found that 22% had received a second agent, most commonly a second antidepressant. Stephen M. Stahl, renowned academician in psychopharmacology, has stated resorting to a dynamic

psychostimulant 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 ...

, in particular,

d-amphetamine 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 ...

is the "''classical augmentation strategy'' for treatment-refractory depression". However, the use of stimulants in cases of treatment-resistant depression is relatively controversial. It is also possible to use a benzodiazepine as to improve sleep without impairing the antidepressant response specially in patients presenting symptoms of insomnia and disturbed sleep. A randomized controlled trial found that the use of eszopiclone with fluoxetine resulted in a better remission rate. Addition of

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 when the patient has not responded to an antidepressant is also known to increase the effectiveness of antidepressant drugs, albeit at the cost of more frequent and potentially serious side effects.

Lithium

Lithium has been used to augment antidepressant therapy in those who have failed to respond to antidepressants alone. Furthermore, lithium dramatically decreases the suicide risk in recurrent depression. According to the results of the STAR-D experiment, the remission rate of lithium for treatment-resistant depression is about 15.9%.

Thyroid hormones

There is some evidence for the addition of a thyroid hormone,

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 thyrox ...

, in patients with normal thyroid function. For TRD patients, T3 has been studied in the STAR-D study with having a remission rate of 24.7%. T4 is also being studied for this purpose and found remission rates of 21.5% - 64.7% for TRD patients.

Regulatory status, efficacy and tolerability of adjunctive treatments in depression

Efficacy of medication and psychotherapy

Antidepressants are statistically superior to

but their overall effect is low-to-moderate. In that respect they often did not exceed the

National Institute for Health and Clinical Excellence The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care in England that publishes guidelines in four areas: * the use of health technologies withi ...

criteria for a "clinically significant" effect. In particular, the effect size was very small for moderate depression but increased with severity, reaching "

clinical significance In medicine and psychology, clinical significance is the practical importance of a treatment effect—whether it has a real genuine, palpable, noticeable effect on daily life. Types of significance Statistical significance Statistical significance ...

" for very severe depression. These results were consistent with the earlier clinical studies in which only patients with severe depression benefited from either psychotherapy or treatment with an antidepressant, imipramine, more than from the placebo treatment. Despite obtaining similar results, the authors argued about their interpretation. One author concluded that there "seems little evidence to support the prescription of antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed to provide benefit." The other author agreed that "antidepressant 'glass' is far from full" but disagreed "that it is completely empty". He pointed out that the first-line alternative to medication is psychotherapy, which does not have superior efficacy. Antidepressants in general are as effective as psychotherapy for major depression, and this conclusion holds true for both severe and mild forms of MDD. In contrast, medication gives better results for

. The subgroup of SSRIs may be slightly more efficacious than psychotherapy. On the other hand, significantly more patients drop off from the antidepressant treatment than from psychotherapy, likely because of the side effects of antidepressants. Successful psychotherapy appears to prevent the recurrence of depression even after it has been terminated or replaced by occasional "booster" sessions. The same degree of prevention can be achieved by continuing antidepressant treatment. Two studies suggest that the combination of psychotherapy and medication is the most effective way to treat depression in adolescents. Both TADS (Treatment of Adolescents with Depression Study) and TORDIA (Treatment of Resistant Depression in Adolescents) showed very similar results. TADS resulted in 71% of their teen subjects having "much" or "very much" improvement in mood over the 61% with medication alone and 43% with CBT alone. Similarly, TORDIA showed a 55% improvement with CBT and drugs versus a 41% with drug therapy alone. However, a more recent meta-analysis of 34 trials of 14 drugs used with children and adolescents found that only fluoxetine produced significant benefit compared to placebo, with a medium-sized effect (standardize mean difference = .5).

Treatment resistance

The risk factors for treatment resistant depression are: the duration of the episode of depression, severity of the episode, if bipolar, lack of improvement in symptoms within the first couple of treatment weeks, anxious or avoidant and borderline comorbidity and old age. Treatment resistant depression is best handled with a combination of conventional antidepressant together with atypical antipsychotics. Another approach is to try different antidepressants. It's inconclusive which approach is superior. Treatment resistant depression can be misdiagnosed if subtherapeutic doses of antidepressants is the case, patient nonadherence, intolerable adverse effects or their thyroid disease or other conditions is misdiagnosed as depression.

Experimental treatments

Ayahuasca

Research into ayahuasca has been recommended, given there is limited early evidence of potential

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 ...

and

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...

effects.

Chromium

Clinical and experimental studies have reported antidepressant activity of

chromium Chromium is a chemical element with the symbol Cr and atomic number 24. It is the first element in group 6. It is a steely-grey, lustrous, hard, and brittle transition metal. Chromium metal is valued for its high corrosion resistance and hard ...

particularly in

atypical depression Atypical depression is defined in the '' DSM IV'' as depression that shares many of the typical symptoms of major depressive disorder or dysthymia but is characterized by improved mood in response to positive events. In contrast to those with ...

, characterized by increased appetite and carbohydrate craving.

Creatine

The

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

creatine Creatine ( or ) is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. It exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate ( ...

, commonly used as a supplement to improve the performance of

bodybuilders Bodybuilding is the use of progressive resistance exercise to control and develop one's muscles (muscle building) by muscle hypertrophy for aesthetic purposes. It is distinct from similar activities such as powerlifting because it focuses o ...

, has been studied for its potential antidepressant properties. A review found that creatine "has the potential to improve these disruptions f brain metabolismin some patients, and early clinical trials indicate that it may have efficacy as an antidepressant agent." Studies on mice have found that the antidepressant effects of creatine can be blocked by dopamine receptor antagonists such as

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...

, suggesting that the drug acts on dopamine pathways.

Magnesium

A meta-analysis has found an association between

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ...

intake and depression. Magnesium was lower in serum of depressed patients than controls. A 2018 review found that Mg²⁺ supplementation (range 225–4000 mg) and number of weeks of treatment (range 1–12) were not related to changes in mood disorder.

Essential Fatty Acids

There is insufficient evidence to determine that

omega-3 fatty acid Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...

has any effect on depression. A 2016 review found that if trials with formulations containing mostly

eicosapentaenoic acid Eicosapentaenoic acid (EPA; also icosapentaenoic acid) is an omega-3 fatty acid. In physiological literature, it is given the name 20:5(n-3). It also has the trivial name timnodonic acid. In chemical structure, EPA is a carboxylic acid with a 20-c ...

(EPA) are separated from trials using formulations containing

docosahexaenoic acid Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-lin ...

(DHA), it appeared that EPA may have an effect while DHA may not, but there was insufficient evidence to be sure. A 2020 meta-analysis showed that a high dose of omega-3 polyunsaturated fatty acid (>2g/day) used as an adjuvent improved depressive symptoms.

Dopamine receptor agonist

Some research suggests dopamine receptor agonists, most commonly pramipexole, may be effective in treating depression. Studies are few and results are preliminary, however.

N-Acetylcysteine

A systematic review and meta-analysis of 5 studies found that N-acetylcysteine reduces depressive symptoms more than placebo and has good tolerability. N-acetylecysteine may exert its benefits by replenishing the chief cellular antioxidant,

glutathione Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, pe ...

, thus modulating glutamatergic, neurotropic and inflammatory pathways.

Psilocybin

Psilocybin Psilocybin ( , ) is a naturally occurring psychedelic prodrug compound produced by more than 200 species of fungi. The most potent are members of the genus ''Psilocybe'', such as '' P. azurescens'', '' P. semilanceata'', and '' P.&nbs ...

has been shown in several studies to improve symptoms in people with treatment-resistant depression. In 2018 and 2019, the FDA designated psilocybin as a "

breakthrough therapy Breakthrough therapy is a United States Food and Drug Administration designation that expedites drug development that was created by Congress under Section 902 of the 9 July 2012 Food and Drug Administration Safety and Innovation Act. The FDA's " ...

" for drug-resistant depression and major depressive disorder.

St John's wort

A 2008

Cochrane Collaboration Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...

meta-analysis 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 m ...

concluded that "The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer

s than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation." The United States

National Center for Complementary and Integrative Health The National Center for Complementary and Integrative Health (NCCIH) is a United States government agency which explores complementary and alternative medicine (CAM). It was initially created in 1991 as the Office of Alternative Medicine (OAM), ...

advice is that "St. John's wort may help some types of depression, similar to treatment with standard prescription antidepressants, but the evidence is not definitive." and warns that "Combining St. John's wort with certain antidepressants can lead to a potentially life-threatening increase of

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...

, a brain chemical targeted by antidepressants. St. John's wort can also limit the effectiveness of many prescription medicines."

Rhodiola rosea

A 2011 review reported Rhodiola rosea "is an adaptogen plant that can be especially helpful in treating asthenic or lethargic depression, and may be combined with conventional antidepressants to alleviate some of their common side effects."

Saffron

A 2013 meta-analysis found that

saffron Saffron () is a spice derived from the flower of ''Crocus sativus'', commonly known as the "saffron crocus". The vivid crimson stigma (botany), stigma and stigma (botany)#style, styles, called threads, are collected and dried for use mainly ...

supplementation significantly reduced depression symptoms compared to placebo, and both saffron supplementation and the antidepressant groups were similarly effective in reducing depression symptoms. A 2015 meta-analysis supported the "efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior." Therapeutic doses of saffron exhibits no significant toxicity in both clinical and experimental investigations.

SAMe

S-Adenosyl methionine ''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...

(SAMe) is available as a prescription antidepressant in

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...

and an over-the-counter

dietary supplement A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...

in the US. Evidence from 16 clinical trials with a small number of subjects, reviewed in 1994 and 1996 suggested it to be more effective than placebo and as effective as standard antidepressant medication for the treatment of major depression.

Tryptophan and 5-HTP

The

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

is converted into

5-hydroxytryptophan 5-Hydroxytryptophan (5-HTP), also known as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin. Uses 5-HTP is sold over the cou ...

(5-HTP) which is subsequently converted into the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...

. Since serotonin deficiency has been recognized as a possible cause of depression, it has been suggested that consumption of tryptophan or 5-HTP may therefore improve depression symptoms by increasing the level of serotonin in the brain. 5-HTP and tryptophan are sold

over the counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

in North America, but requires a prescription in Europe. The use of 5-HTP instead of tryptophan bypasses the conversion of tryptophan into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin, and 5-HTP easily crosses the blood–brain barrier unlike tryptophan, which requires a transporter. Small studies have been performed using 5-HTP and tryptophan as adjunctive therapy in addition to standard treatment for depression. While some studies had positive results, they were criticized for having methodological flaws, and a more recent study did not find sustained benefit from their use. The safety of these medications has not been well studied. Due to the lack of high quality studies, preliminary nature of studies showing effectiveness, the lack of adequate study on their safety, and reports of

Eosinophilia–myalgia syndrome Eosinophilia–myalgia syndrome is a rare, sometimes fatal neurological condition linked to the ingestion of the dietary supplement L-tryptophan. The risk of developing EMS increases with larger doses of tryptophan and increasing age. Some resea ...

from contaminated tryptophan in 1989 and 1990, the use of tryptophan and 5-HTP is not highly recommended or thought to be clinically useful.

Medical devices

A variety of medical devices are in use or under consideration for treatment of depression including devices that offer electroconvulsive therapy, vagus nerve stimulation,

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 gener ...

, and

cranial electrotherapy stimulation Cranial electrotherapy stimulation (CES) is a form of neurostimulation that delivers a small, pulsed, alternating current via electrodes on the head. CES is used with the intention of treating a variety of conditions such as anxiety, depression a ...

. The use of such devices in the United States requires approval by the U.S.

Food and Drug Administration 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 ...

(FDA) after field trials. In 2010 an FDA advisory panel considered the question of how such field trials should be managed. Factors considered were whether drugs had been effective, how many different drugs had been tried, and what tolerance for suicides should be in field trials.

Electroconvulsive therapy

In 2004, a meta-analytic review paper found in terms of efficacy, "a significant superiority of ECT in all comparisons: ECT versus simulated ECT, ECT versus

, ECT versus antidepressants in general, ECT versus tricyclics and ECT versus

monoamine oxidase inhibitor 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, esp ...

s."

Electroconvulsive therapy Electroconvulsive therapy (ECT) is a psychiatric treatment where a generalized seizure (without muscular convulsions) is electrically induced to manage refractory mental disorders.Rudorfer, MV, Henry, ME, Sackeim, HA (2003)"Electroconvulsive th ...

(ECT) is a standard

psychiatric 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 psy ...

treatment in which

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

s are electrically induced in patients to provide relief from psychiatric illnesses. ECT is used with

informed consent Informed consent is a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treat ...

as a last line of intervention for major depressive disorder. Among the elderly, who often experience depression, the efficacy of ECT is difficult to determine due to the lack of trials comparing ECT to other treatments. A round of ECT is effective for about 50% of people with treatment-resistant major depressive disorder, whether it is unipolar or bipolar. Follow-up treatment is still poorly studied, but about half of people who respond relapse with twelve months. Aside from effects in the brain, the general physical risks of ECT are similar to those of brief

general anesthesia General anaesthesia (UK) or general anesthesia (US) is a medically induced loss of consciousness that renders the patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general ...

. Immediately following treatment, the most common adverse effects are confusion and memory loss. ECT is considered one of the least harmful treatment options available for severely depressed pregnant women. A usual course of ECT involves multiple administrations, typically given two or three times per week until the patient no longer has symptoms ECT is administered under anesthetic with a muscle relaxant. Electroconvulsive therapy can differ in its application in three ways: electrode placement, frequency of treatments, and the electrical waveform of the stimulus. These three forms of application have significant differences in both adverse side effects and symptom remission. After treatment, drug therapy is usually continued, and some patients receive maintenance ECT. ECT appears to work in the short term via an

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

effect mostly in the

frontal lobes The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove betwe ...

, and longer term via

neurotrophic Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and differentiation of both developing and mature neurons. Most NTFs exert their tro ...

effects primarily in the

medial temporal lobe The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe is involved in p ...

Deep brain stimulation

The support for the use of

deep brain stimulation Deep brain stimulation (DBS) is a neurosurgical procedure involving the placement of a medical device called a neurostimulator, which sends electrical impulses, through implanted electrodes, to specific targets in the brain (the brain nucleus ...

treatment-resistant depression Treatment-resistant depression is a term used in psychiatry to describe people with major depressive disorder (MDD) who do not respond adequately to a course of appropriate antidepressant medication within a certain time. Definitions of treatment- ...

comes from a handful of case studies, and this treatment is still in a very early investigational stage. In this technique electrodes are implanted in a specific region of the brain, which is then continuously stimulated. A March 2010 systematic review found that "about half the patients did show dramatic improvement" and that adverse events were "generally trivial" given the younger psychiatric patient population than with movements disorders. Deep brain stimulation is available on an experimental basis only in the United States; no systems are approved by the FDA for this use.

Repetitive transcranial magnetic stimulation

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 gener ...

(TMS) or deep transcranial magnetic stimulation is a noninvasive method used to stimulate small regions of the brain. During a TMS procedure, a magnetic field generator, or "coil" is placed near the head of the person receiving the treatment. The coil produces small electric currents in the region of the brain just under the coil via

electromagnetic induction Electromagnetic or magnetic induction is the production of an electromotive force (emf) across an electrical conductor in a changing magnetic field. Michael Faraday is generally credited with the discovery of induction in 1831, and James Cle ...

. The coil is connected to a pulse generator, or stimulator, that delivers electric current to the coil. TMS was approved by the FDA for treatment-resistant

in 2008 and as of 2014 clinical evidence supports this use.
(6) The American Psychiatric Association, the Canadian Network for Mood and Anxiety Disorders, and the Royal Australia and New Zealand College of Psychiatrists have endorsed rTMS for trMDD. The response rate is about 29% for TRD patients. Remission rate is about 20%.

Vagus nerve stimulation

Vagus nerve stimulation (VNS) uses an implanted electrode and generator to deliver electrical pulses to the vagus nerve, one of the primary nerves emanating from the brain. It is an approved therapy for treatment-resistant depression in the EU and US and is sometimes used as an adjunct to existing antidepressant treatment. The support for this method comes mainly from open-label trials, which indicate that several months may be required to see a benefit. The only large double-blind trial conducted lasted only 10 weeks and yielded inconclusive results; VNS failed to show superiority over a sham treatment on the primary efficacy outcome, but the results were more favorable for one of the secondary outcomes. The authors concluded "This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression."

Cranial electrotherapy stimulation

A 2014 Cochrane review found insufficient evidence to determine whether or not

Cranial electrotherapy stimulation Cranial electrotherapy stimulation (CES) is a form of neurostimulation that delivers a small, pulsed, alternating current via electrodes on the head. CES is used with the intention of treating a variety of conditions such as anxiety, depression a ...

with alternating current is safe and effective for treating depression.

Transcranial direct current stimulation

A 2016 meta-analysis of transcranial direct current stimulation (tDCS) reported some efficacy of tDCS in the treatment of acute depressive disorder with moderate effect size, and low efficacy in treatment-resistant depression, and that use of 2 mA current strength over 20 min per day over a short time span can be considered safe.

Other treatments

Herbal remedies

Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder. Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults. Overall results showed that saffron possessed better efficacy in the improvement of depressive symptoms when compared with placebo, whereas saffron was as effective as synthetic antidepressants

Bright light therapy

A meta-analysis of bright

light therapy Light therapy, also called phototherapy or bright light therapy is intentional daily exposure to direct sunlight or similar-intensity artificial light in order to treat medical disorders, especially seasonal affective disorder (SAD) and circad ...

commissioned by the

American Psychiatric Association The American Psychiatric Association (APA) is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world. It has more than 37,000 members are invo ...

found a significant reduction in depression symptom severity associated with bright light treatment. Benefit was found for both

seasonal affective disorder Seasonal affective disorder (SAD) is a mood disorder subset, in which people who have normal mental health throughout most of the year exhibit depressive symptoms at the same time each year. Common symptoms include sleeping too much, having li ...

and for nonseasonal depression, with effect sizes similar to those for conventional antidepressants. For non-seasonal depression, adding light therapy to the standard antidepressant treatment was not effective. A meta-analysis of light therapy for non-seasonal depression conducted by Cochrane Collaboration, studied a different set of trials, where light was used mostly in combination with antidepressants or

wake therapy Wake therapy, a specific application of intentional sleep deprivation, encompasses many sleep-restricting paradigms that aim to address mood disorders with a form of non-pharmacological therapy. Wake therapy was first popularized in 1966 and 1 ...

. A moderate statistically significant effect of light therapy was found, with response significantly better than control treatment in high-quality studies, in studies that applied morning light treatment, and with patients who respond to total or partial sleep deprivation. Both analyses noted poor quality of most studies and their small size, and urged caution in the interpretation of their results. The short 1–2 weeks duration of most trials makes it unclear whether the effect of light therapy could be sustained in the longer term.

Exercise

Soccer football informal in Manipur India cropped

The 2013 Cochrane Collaboration review on

physical exercise Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic s ...

for depression noted that, based upon limited evidence, it is moderately more effective than a control intervention and comparable to psychological or antidepressant drug therapies. Smaller effects were seen in more methodologically rigorous studies. Three subsequent 2014 systematic reviews that included the Cochrane review in their analysis concluded with similar findings: one indicated that physical exercise is effective as an adjunct treatment with antidepressant medication; the other two indicated that physical exercise has marked antidepressant effects and recommended the inclusion of physical activity as an adjunct treatment for mild–moderate depression and mental illness in general. These studies also found smaller effect sizes in more methodologically rigorous studies. All four systematic reviews called for more research in order to determine the efficacy or optimal exercise intensity, duration, and modality. The evidence for

brain-derived neurotrophic factor Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canon ...

(BDNF) in mediating some of the

neurobiological effects of physical exercise The neurobiological effects of physical exercise are numerous and involve a wide range of interrelated effects on brain structure, brain function, and cognition. A large body of research in humans has demonstrated that consistent aerobic exerc ...

was noted in one review which hypothesized that increased BDNF signaling is responsible for the antidepressant effect. A

of 15 studies published in 2022 suggested a curvilinear dose-response relationship between exercise and depression risk, with low levels of exercise showing the best dose-response.

Meditation

Mindfulness Mindfulness is the practice of purposely bringing one's attention to the present-moment experience without evaluation, a skill one develops through meditation or other training. Mindfulness derives from ''sati'', a significant element of Hind ...

meditation Meditation is a practice in which an individual uses a technique – such as mindfulness, or focusing the mind on a particular object, thought, or activity – to train attention and awareness, and achieve a mentally clear and emotionally calm ...

programs may help improve symptoms of depression, but they are no better than active treatments such as medication, exercise, and other behavioral therapies.

Music therapy

A 2009 review found that 3 to 10 sessions of

music therapy Music therapy, an allied health profession, "is the clinical and evidence-based use of music interventions to accomplish individualized goals within a therapeutic relationship by a credentialed professional who has completed an approved music t ...

(when added to standard care) resulted in a noticeable improvement in depressive symptoms, with still greater improvement after 16 to 51 sessions. A 2017 cochrane systematic review found that music therapy added to the usual treatment of depression gives better outcome than the usual treatment alone: "The effect size translates to a difference of 9.8 points on the HAM-D". It also found that there is no significant difference between active and receptive music therapy comparing depression outcome. It is also important to note that music therapy is not associated with more or fewer adverse events than treatment as usual.

Sleep

Depression is sometimes associated with

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

- (difficulty in falling asleep, early waking, or waking in the middle of the night). The combination of these two results, depression and insomnia, will only worsen the situation. Hence, good

sleep hygiene Sleep hygiene is a behavioral and environmental practice developed in the late 1970s as a method to help people with mild to moderate insomnia. Clinicians assess the sleep hygiene of people with insomnia and other conditions, such as depression, ...

is important to help break this vicious circle. It would include measures such as regular sleep routines, avoidance of

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 such as

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class. It is mainly recreational drug use, used recreationally as a Nootropic, cognitive enhancer, increasing alertness and attentional perfor ...

and management of sleeping disorders such as

sleep apnea Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many tim ...

Smoking cessation

Quitting

smoking Smoking is a practice in which a substance is burned and the resulting smoke is typically breathed in to be tasted and absorbed into the bloodstream. Most commonly, the substance used is the dried leaves of the tobacco plant, which have b ...

cigarette A cigarette is a narrow cylinder containing a combustible material, typically tobacco, that is rolled into thin paper for smoking. The cigarette is ignited at one end, causing it to smolder; the resulting smoke is orally inhaled via the opp ...

s is associated with reduced depression and

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 ...

, with the effect "equal or larger than" those of antidepressant treatments.

Total/partial sleep deprivation

Sleep deprivation Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either chronic or acute and may vary ...

(skipping a night's sleep) has been found to improve symptoms of depression in 40% - 60% of patients. Partial sleep deprivation in the second half of the night may be as effective as an all night sleep deprivation session. Improvement may last for weeks, though the majority (50%-80%) relapse after recovery sleep. Shifting or reduction of sleep time,

, antidepressant drugs, and lithium have been found to potentially stabilize sleep deprivation treatment effects.

Shared Care

Shared care, when primary and specialty physicians have joint management of an individual's health care, has been shown to alleviate depression outcomes.

Research

Trials are investigating whether

botulinum toxin Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neurom ...

, when used to make a person appear to frown less, stops negative feedback from the face and affects depression.

may have a beneficial role in the treatment of depression. A 2019 meta-analysis found that

hypnotherapy Hypnotherapy is a type of mind–body intervention in which hypnosis is used to create a state of focused attention and increased suggestibility in the treatment of a medical or psychological disorder or concern. Popularized by 17th and 18th c ...

may be an effective way of alleviating the symptoms of depression. No model of depression in animals that fully explains the mechanism of depression has been found .

References

External links

*{{Commons category-inline, Treatment of depression Treatment of bipolar disorder