Management of depression may involve a number of different therapies: medications, behavior therapy, and medical devices. Major depressive disorder, often referred to simply as "depression", is diagnosed more frequently in developed countries, where up to 20% of the population is affected at some stage of their lives. According to WHO (World Health Organization), depression is currently fourth among the top 10 leading causes of the global burden of disease; it is predicted that by the year 2020, depression will be ranked second.
Though psychiatric medication is the most frequently prescribed therapy for major depression, psychotherapy 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, or "active intervention
controls". 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 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
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.
As the most studied form of psychotherapy for depression, cognitive behavioral therapy
(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.
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, and significantly worse than the antidepressant fluoxetine. 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 for depression is sometimes referred to as behavioral activation. Studies exist showing behavioral activation to be superior to CBT. In addition, behavioral activation appears to take less time and lead to longer lasting change.
Acceptance and commitment therapy
(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
(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.
Interpersonal psychotherapy
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 structured course with a set
number of weekly sessions (often 12) as in the case of CBT; however, the
focus is on relationships with others. Therapy can be used to help a
person develop or improve interpersonal skills in order to allow him or her to communicate more effectively and reduce stress.
Psychoanalysis, a school of thought founded by Sigmund Freud 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, 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.
Medication
Isoniazid, the first compound called antidepressant
To find the most effective pharmaceutical drug
treatment, the dosages of medications must often be adjusted, different
combinations of antidepressants tried, or antidepressants changed.
Response rates to the first agent administered may be as low as 50%.
It may take anywhere from three to eight weeks after the start of
medication before its therapeutic effects can be fully discovered.
Patients are generally advised not to stop taking an antidepressant
suddenly and to continue its use for at least four months to prevent the
chance of recurrence.
Selective serotonin reuptake inhibitors (SSRIs), such as sertraline (Zoloft, Lustral), escitalopram (Lexapro, Cipralex), fluoxetine (Prozac), paroxetine (Seroxat), and citalopram,
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 (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 (NaSSA) antidepressant mirtazapine (Zispin, Remeron) can be used in such cases. Cognitive Behavioral Therapy for Insomnia can also help to alleviate the insomnia without additional medication. Venlafaxine (Effexor) 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.
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 is lacking.
Tricyclic antidepressants
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, in particular, appears to be more effective. A different class of antidepressants, the monoamine oxidase inhibitors,
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.
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:
‘funded by a pharmaceutical company (Servier) and two of its authors are
employees of that company’, which may bias the results. The study
authors’ note: "emotional blunting is reported by nearly half of
depressed patients on antidepressants and that it appears to be common
to all monoaminergic antidepressants not only SSRIs". Additionally, they
note: "The OQuESA scores are highly correlated with the HAD depression
score; emotional blunting cannot be described simply as a side-effect of
antidepressant, but also as a symptom of depression...More emotional
blunting is associated with a poorer quality of remission..."
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. 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. Addition of atypical antipsychotics
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. There is some evidence for the addition of a thyroid hormone, triiodothyronine, in patients with normal thyroid function. Stephen M. Stahl, renowned academician in psychopharmacology, has stated resorting to a dynamic psychostimulant, in particular, d-amphetamine is the "classical augmentation strategy for treatment-refractory depression". However, the use of stimulants in cases of treatment-resistant depression is relatively controversial.
Efficacy of medication and psychotherapy
Antidepressants are statistically superior to placebo but their overall effect is low-to-moderate. In that respect they often did not exceed the National Institute for Health and Clinical Excellence
criteria for a "clinically significant" effect. In particular, the
effect size was very small for moderate depression but increased with
severity, reaching "clinical 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 dysthymia.
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 60.6% with medication alone and
the 43.2% with CBT alone. Similarly, TORDIA showed a 54.8% improvement with CBT and drugs versus a 40.5% with drug therapy alone.
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
Ketamine
Research on the antidepressant effects of ketamine
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
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.
Creatine
The amino acid creatine, commonly used as a supplement to improve the performance of bodybuilders,
has been studied for its potential antidepressant properties. A
double-blinded, placebo-controlled trial focusing on women with major
depressive disorder found that daily creatine supplementation adjunctive
to escitalopram was more effective than escitalopram alone.
Studies on mice have found that the antidepressant effects of creatine
can be blocked by drugs that act against dopamine receptors, suggesting
that the drug acts on dopamine pathways.
Dopamine receptor agonist
Some
research suggests dopamine receptor agonist may be effective in
treating depression, however studies are few and results are preliminary
SAMe
S-Adenosyl methionine (SAMe) is available as a prescription antidepressant in Europe and an over-the-counter dietary supplement
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 amino acid tryptophan is converted into 5-hydroxytryptophan (5-HTP) which is subsequently converted into the neurotransmitter serotonin.
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
in North America, but requires a prescription in Europe. 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 associated with tryptophan use, the use of tryptophan and 5-HTP is not highly recommended or thought to be clinically useful.
Inositol
Inositol, an alcohol sugar found in fruits, beans grains and nuts may have antidepressant effects in high doses. Inositol may exert its effects by altering intracellular signaling.
Medical devices
A
variety of medical devices are in use or under consideration for
treatment of depression including devices which offer electroconvulsive
therapy, vagus nerve stimulation, repetitive transcranial magnetic stimulation, and cranial electrotherapy stimulation. Use of such devices in the United States requires approval by the U.S. Food and Drug Administration
(FDA) after field trials. In 2010 a 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
Electroconvulsive therapy (ECT) is a standard psychiatric treatment in which seizures are electrically induced in patients to provide relief from psychiatric illnesses. ECT is used with informed consent as a last line of intervention for major depressive disorder.
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. 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 is no
longer suffering 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 effect mostly in the frontal lobes, and longer term via neurotrophic effects primarily in the medial temporal lobe.
Deep brain stimulation
The support for the use of deep brain stimulation in treatment-resistant depression 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. It is available in Australia.
Repetitive transcranial magnetic stimulation
Transcranial magnetic stimulation (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. 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 major depressive disorder in 2008 and as of 2014 clinical evidence supports this use. 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.
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 with alternating current is safe and effective for treating depression.
Other treatments
Bright light therapy
Bright light therapy is sometimes used to treat depression, especially in its seasonal form.
A meta-analysis of bright light therapy commissioned by the American Psychiatric Association
found a significant reduction in depression symptom severity associated
with bright light treatment. Benefit was found for both seasonal affective disorder
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.
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
The 2013 Cochrane Collaboration review on physical exercise
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 methologically 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 (BDNF) in mediating some of the neurobiological effects of physical exercise was noted in one review which hypothesized that increased BDNF signaling is responsible for the antidepressant effect.
A review of clinical evidence and guidelines for the management of depression with exercise therapy was published in June 2015. It noted that the available evidence on the effectiveness of exercise therapy for depression suffers from some limitations; nonetheless, it stated that there is clear evidence of efficacy in the reduction of depressive symptoms.
The review also noted that patient characteristics, the type of
depressive disorders, and the nature of the exercise program all affect
the antidepressant properties of exercise therapy.
Meditation
Mindfulness meditation
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 resulted in a noticeable improvement in depressive symptoms, with still greater improvement after 16 to 51 sessions.
St John's wort
A 2008 Cochrane Collaboration meta-analysis 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 side effects
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
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, a brain chemical targeted by antidepressants. St. John’s wort can also limit the effectiveness of many prescription medicines."
Sleep
Depression is sometimes associated with insomnia
- (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 is important to help break this vicious circle. It would include measures such as regular sleep routines, avoidance of stimulants such as caffeine and management of sleeping disorders such as sleep apnea.
Smoking cessation
Quitting smoking cigarettes is associated with reduced depression and anxiety, with the effect "equal or larger than" those of antidepressant treatments.
Total/partial sleep deprivation
Sleep deprivation
(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, light therapy, antidepressant drugs, and lithium have been found to potentially stabilize sleep deprivation treatment effects.
Essential Fatty Acids
A 2015 Cochrane Collaboration review found insufficient evidence with which to determine if omega-3 fatty acid has any effect on depression. A 2016 review found that if trials with formulations containing mostly eicosapentaenoic acid (EPA) are separated from trials using formulations containing docosahexaenoic acid (DHA), it appeared that EPA may have an effect while DHA may not, but there was insufficient evidence to be sure.
Shared
care, when primary and specialty physicians have joint management of an
individual's health care, has been shown to alleviate depression
outcomes.
