Comparison of medication, psychotherapy and ECT for the treatment of depression in children and adolescents in the U.S.
Childhood and adolescent depression is an ever-increasing health concern in the U.S. Adolescence, in particular, is a vulnerable time for this condition due to the many biological, cognitive and social-environmental changes that occur during this phase of life. Furthermore, depression in adolescence is a strong predictor of recurrent depression in adulthood and long-term functional impairment.
Three treatment approaches – psychotherapy, pharmacotherapy and electrical convulsive therapy (ECT) – were investigated to determine each treatment’s success and reliability when used to treat child and adolescent depression. It was concluded that one approach, ECT, while highly effective was underutilized and that a combined treatment plan might be most appropriate for this disorder.
Keywords and Definitions:
Allopathic medicine or mainstream medical uses pharmacologically active agents or physical interventions to treat or suppress symptoms or pathophysiologic processes of diseases or conditions.
Cognitive behavioral therapy (CBT), developed by the psychiatrist, Aaron Beck, in the 1960s, is a short-term, goal-oriented psychotherapy method. It can be considered a combination of traditional psychotherapy and behavioral therapy. It is based on the theory that much of how a person feels is determined by his personal way of thinking.
Dialectical behavior therapy (DBT) is a specific type of cognitive-behavioral psychotherapy developed by psychologist Marsha Linehan in the 1980s to help treat chronically suicidal individuals diagnosed with borderline personality disorder (BPD) more effectively. It has been used for the treatment of other kinds of mental health disorders.
Electroconvulsive therapy (ECT) is a procedure, done under general anesthesia, in which small electric currents are passed through the brain, intentionally triggering a brief seizure. ECT seems to cause changes in brain chemistry that can quickly reverse symptoms of certain mental illnesses. It often works when other treatments are unsuccessful.
Fluoxetine: (trade name: Prozac – Eli Lilly and Company) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder and several other psychological conditions.
Interpersonal therapy (IPT) is a brief, attachment-focused form of psychotherapy that centers on resolving interpersonal problems and symptomatic recovery. It is an empirically supported treatment (EST) that focuses on a patient’s relationships with his peers and family members and the way he sees himself. Interpersonal psychotherapy is a highly structured and time-limited approach that is intended to be completed in a 12-16 week period.
Monoamine-oxidase inhibitor (MAOI), first introduced in the 1950s, is a class of drugs designed for depression that inhibit the activity of the monoamine oxidase enzyme family. MAOI antidepressants prevent the breakdown of neurotransmitters, noradrenaline (norepinephrine) and serotonin, as it is theorized that an altered balance of serotonin and other neurotransmitters such as noradrenaline has a role in causing depression. This class of drugs can take up to three weeks to build up their effective chemical levels.
Selective serotonin reuptake inhibitor (SSRI) class of antidepressant drugs. See Fluoxetine – Prozac.
Tricyclic antidepressants (TCAs) are chemical compounds used primarily as antidepressants, discovered in the early 1950s and used primarily as antidepressant medication. They were named based on their chemical structure, which contains three rings of atoms.
There is a prevalence of major depressive disorder (MDD) being diagnosed in children and adolescents in the U.S. Despite the challenges in recognizing and properly diagnosing this condition, Clark reported that at least 2.8% of children under the age of 13 years and 5.6% of adolescents (ages 13 to 18) in the U.S. have experienced major depressive disorder. Numerous risk factors for childhood and adolescent depression have been recognized. Biological factors include low birth weight, gender, existing medical conditions and a family history of depression. Children between the ages of 3 to 5 diagnosed with certain health conditions, including diabetes mellitus or asthma were likely to have a major depressive episode. There can be environmental factors such as an instable home environment or deficient parenting skills that fail to provide adequate nurturing for the child or adolescent. Children of the age of 5 years who were considered “hostile” by their teachers were found to be at greater risk of depression Psychological, emotional and learning components can also contribute to depression in this young population. As these factors are often intertwined, it becomes a greater challenge for health care providers to separate and identify these underlying components. (Clark et al, 2012)
In particular, adolescence is a vulnerable time due to biological, cognitive and social-environmental changes that become major risk factors. Clark et al report that while younger children with depression were more likely to have somatic symptoms, restlessness, separation anxiety, phobias, and hallucinations, adolescents were more likely to be unable to experience pleasure (anhedonia) as well as suffered from boredom, hopelessness, hypersomnia, weight change, alcohol or drug use, and suicide attempts. Zack found that more than half of all adolescents have reported experiencing depressed mood with 8% to 10% of this group showing clinically diagnosable symptoms. (Zach et al, 2012)
The Centers for Disease Control and Prevention indicated approximately four children out of every 500,000 below the age of 12 commit suicide each year. Even more alarming is the fact that this number has doubled since 1979. Suicide is the 14th leading cause of death for children. The suicide rate rises among adolescents aged 10 to 14 (1.3 per 100,000) and spikes among teenagers between the ages of 15 to 19 years (7.67 per 100,000). (Beam, 2010)
Depression is expensive in terms of personal lives, emotional and social well-being and academic learning as well as an economic burden to the individual and society. Zack stated that “depression in adolescence is a strong predictor of recurrent depression in adulthood and long-term functional impairment, and it confers a 10-fold increase in risk for suicidal behavior.” (Zach et al, 2012)
A study by Greenberg and colleagues (2015) examined costs associated with MDD, using data spanning from 2005, when the country’s finances and job markets were robust, to 2010, following the U.S. economic downturn. A total economic burden of MDD was estimated to be $210.5 billion per year. This demonstrated a 21.5% increase from $173.2 billion per year in 2005. Nearly half (48%-50%) of these costs are attributed to the workplace, including absenteeism and reduced productivity while at work. Approximately 45%-47% of the costs were direct medical costs (e.g., outpatient and inpatient medical services, pharmacy costs), which are shared by employers, employees, and society and 5% of the total cost was related to suicide. (Greenberg et al, 2015) (Kuhl, 2015)
Clark also found that approximately 60% of adolescents with depression have recurrences of depression throughout their adulthood, yet while the prevalence of adolescent depression was high, it was significantly under-diagnosed and therefore often untreated. Adolescent-onset depression was associated with many future adulthood problems including abuse and neglect, substance abuse, poor work performance and disruptions in social, employment and family settings. (Clark, 2012)
DoSomething.org, a global movement of 5.5 million young people focused on making positive change in the lives of young people provides these general facts about suicide:
- Nearly 30,000 Americans commit suicide every year.
- In the U.S., suicide rates are highest during the spring.
- Approximately 1 in 65,000 children (ages 10 – 14) commit suicide each year
- Suicide is the 3rd leading cause of death for 15 to 24-year-olds and 2nd for 24 to 35-year-olds.
- On average, 1 person commits suicide every 16.2 minutes.
- Each suicide intimately affects at least 6 other people.
It is therefore critical that health care providers accurately diagnose depression in children and adolescents and select the best medical care to provide rapid and effective relief. This treatment plan must consider various factors including the severity of depression, suicidality, developmental stage of the patient, and all environmental and social factors.
Use of Psychotherapy
Psychotherapy seems like a natural treatment for major depressive disorder, which is a “psychological” disorder. Both the American Psychiatric Association and the American Academy of Child and Adolescent Psychiatry recommend psychotherapy as a component in the treatment plan for children and adolescents suffering with depression.
A number of researchers supported this position. Zach reported that psychotherapy for depression was as effective as medication in many cases of depression and recommended its use as a primary treatment for mild to moderately depressed youths. Ryan’s research concluded that two types of psychotherapy, cognitive-behavioral therapy and interpersonal therapy, showed some effectiveness in the treatment of depression in children and adolescents. (Zach et al, 2012) (Ryan, 2005)
Clark point out however that the recommendation that psychotherapy be considered an acceptable treatment option should be applied for patients with milder depression and indicated that a combination of medication and psychotherapy was required in cases of moderate to severe depression. This position was supported by Giardino’s findings that cognitive-behavioral therapy (CBT) was effective in treating mild to moderate cases of depression in children and adolescents but that moderate to severe cases required a combined approach of psychotherapy and medication. (Clark et al, 2012) (Giardino et al, 2016)
In Zach’s research, he compared three types of psychotherapy for the treatment of depression in children and adolescents:
(1) Cognitive-behavioral therapy (CBT)
(2) Interpersonal therapy (IPT)
(3) Dialectical behavior therapy (DBT)
His work correlated with the Practice Parameters of the American Academy of Child and Adolescent Psychiatry (AACAP) that CBT alone was an effective treatment for mildly depressed youths, whereas moderately to severely depressed youths often required CBT (or other psychotherapies) along with antidepressants. Zach reported that the efficacy of IPT had not yet been established and had not been compared with the use of pharmacotherapy in an adolescent population. The NIMH did however conduct a study in which IPT was found to be as effective as imipramine in the treatment of MDD in adults.” (Zach et al, 2012)
Zach did find that “ adolescents who received DBT displayed greater reduction of symptoms, such as mood and self-injurious behavior along with improved relationships and overall functioning. He noted that DBT-A approach had not undergone randomized controlled trial data, and for this reason, Zack indicated that it should not be considered a well-established treatment for adolescents until further research had been performed. (Zach et al, 2012)
“The effects of CBT on depressive symptoms are moderate but it has not been proven more effective than placebo for treating acute depression in adolescents” was the conclusion of Clark. (2015) “Cognitive behavioral therapy (CBT), using behavioral activation techniques and coping skills to address negative thinking patterns and regulate emotions, has been proven effective with both children and adolescents. Interpersonal therapy, which focused on adapting to changes, personal role transitioning and interpersonal relationships, had also been effective with adolescents.” Clark concluded “a combination of CBT and medication has been shown to be more effective than medication alone in attaining remission of depression. Interpersonal therapy has not been compared with medication, combination treatment, or placebo, but it has been proven more effective than wait-list control groups with no therapy, and as effective or more effective than CBT.” (Clark et al, 2012)
Psychotherapy alone can be very slow and require mature insight that young children do not possess. Then there is the problem of impulsive adolescents who require immediate intervention to avoid such serious resultants of depression, such as suicide. It appears that for the severely depressed child or adolescent, the sole use of psychotherapy may not be adequate treatment.
Use of Medication
The health care industry is highly focused on pharmacological solutions for most disorders, including psychological disorders. The rate of antidepressant use in the U.S. continues to grow at alarming rates. Good news for the pharmaceutical industry but a serious concern for society.
Between 1999 and 2012, the number of Americans using antidepressants increased from 6.8% to 13%, according epidemiologist Elizabeth Kantor of Harvard University. The use of antidepressants has steadily grown at every two-year measuring period. (Kantor et al, 2015) The National Center for Health Statistics (NCHS) indicated that the rate of antidepressant use by adolescents and adults (people ages 12 and older) in the U.S. increased by almost 400% between1988–1994 and 2005–2008. (Wehrwein, 2011) Despite an increased use of antidepressants, a meta-analysis of antidepressant trials compared to therapy (published in JAMA Psychiatry in September, 2011) found no significant differences between antidepressants and CBT in response to treatment or remission in patients with severe depression. (Kantor et al, 2015)
Certain drugs marketed for the treatment of depression had been quite ineffective in the treatment of depression in children and adolescents and there was often increased issue of suicidal behavior. (Ryan, 2005)
Tricyclic and tetracyclic antidepressants, depending on the number of rings in their chemical structure — three (tri) or four (tetra) – were thought to lessen depression by impacting chemical messengers (neurotransmitters) used to communicate between neurons in the brain. Changes in brain chemistry and nerve cell communication in mood regulation regions of the brain was thought to help relieve depression. This class of drugs blocked the absorption (reuptake) of the neurotransmitters serotonin and norepinephrine, thereby increasing their levels in the brain. These drugs can however affect other neurotransmitters, resulting in various side effects. (Mayo Clinic Staff – Mayo Clinic, Diseases and Conditions – Depression)
The meta-analysis of 12 randomized double-blind placebo-controlled trials by Hazell et al found an overall small and clinically non-significant treatment effect of tricyclic drugs (TCA) in treating depression in children and adolescents. They reported that tricyclic antidepressants appeared to be no more effective than a placebo and concluded that tricyclic drugs should not be used as a primary treatment for depression for this population. (Hazell et al, 1995)
Findling also eliminated tricyclic drugs as a treatment for child and adolescent depression citing controlled clinical trials that had not demonstrated their efficacy in that population. They further point out the safety concerns of TCAs and the monoamine oxidase inhibitors and recommended newer drugs from the SSRI class. When compared with the TCAs, the SSRAs (fluoxetine/Prozac) were well tolerated by depressed youths based on open-label and double-blind studies and superior to placebo. The SSRI’s were also more reliable in preventing overdose. (Findling et al, 1999)
The National Institute of Care and Clinical Excellence (NICE) recommended SSRI antidepressant treatment in combination with psychosocial interventions as a first line treatment for severe and moderate depression, as well as recurrent depression and as a second-line treatment for short-term mild depression. The American Psychiatric Association also included SSRI antidepressant therapy among its primary treatment options for depression, particularly when there was a patient history of prior positive response to medications.
Emslie (2002) conducted a 9-week acute treatment double-blind clinical trial to test designed to test the findings of previous studies of fluoxetine in the treatment of children and adolescents with MDD. SSRls were recommended because of their low lethality on overdose and ease of administration (AACAP, 1998). Using the Children’s Depression Rating Scale-Revised (CDRS·R) score showed patient s using fluoxetine improved more when compared to patients receiving a placebo after 1 week (p < .05) and throughout the study. Their conclusion was that a 20 mg daily dose of fluoxetine was well tolerated and effective for acute treatment of child and adolescent outpatients with depression. Fluoxetine was noted as the only antidepressant that had demonstrated efficacy In two placebo-controlled, randomized clinical trials of pediatric depression. (Emslie et al, 2002)
In a 36 week, double-blind study, fluoxetine alone or in combination with CBT resulted in an accelerated improvement of depression when compared to CBT or a placebo alone. When CBT was added to the fluoxetine therapy, there was a decrease in persistent suicidal ideation and treatment-emergent suicidal events
Rates of response were:
It was recognized however that patients assigned to the combined treatment experienced somewhat greater contact time than did patients assigned to fluoxetine therapy or CBT alone and that this additional contact time could have impacted the results. March also noted that suicidal ideation decreased with treatment, but less so with fluoxetine therapy than with combination therapy or CBT. Suicidal events were more common in patients receiving only fluoxetine therapy (14.7%) than with patients receiving combination therapy (8.4%) or CBT (6.3%). (March et al, 2012)
Contrary to previous research that indicated that only major depression but not minor depression responded significantly to pharmacological intervention, Judd (2004) suggest that this was not accurate “since pharmacologic treatment with fluoxetine had clear benefit over non-specific intervention for minor depressive disorder.” Their research demonstrated that minor depressive disorder symptoms decreased with 12 weeks of SSRI treatment.
Clark expressed concern in regards to the extrapolation of adult data on antidepressants to children and adolescents indicating that the neural serotonin and norepinephrine pathways in this population were not fully developed. Serotonin and norepinephrine systems had different maturation rates. Still, based on available research, the newer class of SSRIs such as fluoxetine (trade name: Prozac) showed significant results in treating MDD in children and adolescents. (Clark et al, 2012)
In a 2007 press release, the National Institute of Mental Health reported that “a combination of psychotherapy and antidepressant medication appears to be the most effective treatment for adolescents with major depressive disorder—more than medication alone or psychotherapy alone, according to results from a major clinical trial funded by the National Institutes of Health’s National Institute of Mental Health (NIMH). (The study was published in the October 2007 issue of the Archives of General Psychiatry.)
“Depression in teens is a serious illness that can and should be treated aggressively,” said NIMH Director Thomas R. Insel, M.D. (2007) Based on evidence, he stated that “the most effective way to treat depression in teens is with a two-pronged approach. It reassures us that antidepressant medication combined with psychotherapy is an effective and safe way to help teens recover from this disabling illness.”
Use of Electroconvulsive Therapy (ECT)
The mention of electroconvulsive therapy (ECT) typically results in great alarm and fear in the general public. The therapy has a stigma reinforced by stories and movies that portray the treatment as sinister. Research has even been done examining the portrayal of electroconvulsive therapy in American films. Twenty 22 films, created between 1948 and 2000 were identified by McDonald and Walter (2001). These films included “The Snake Pit” (1948), “Fear Strikes Out” (1957), “Shock Corridor” (1963), “One Flew Over the Cuckoo’s Nest” (1975) and “Francis” (1982) and all had one thing in common, the portrayal of ECT as barbaric, unjustified, cruel and of no therapeutic value.
Portrayals of ECT in film greatly influenced public attitudes toward the treatment. A survey by O’Shea and McGennis in 1983 demonstrated that the majority of respondents who had seen the movie “One Flew Over the Cuckoo’s Nest” were uncomfortable with and lacked confidence in ECT as a treatment as reflected in the film (O’Shea et al, 1983). In another study, after watching scenes of ECT in films, one-third of the medical students lowered their support for the treatment. The proportion of medical students who indicated that they would dissuade a family member or friend from having ECT rose from less than 10% prior to viewing the films to almost 25% afterward. (Walter et al., 2002).
Yet, when used properly by a skilled technician, electroconvulsive therapy has proven to be an effective treatment of MDD in children and adolescents. Electroconvulsive therapy (ECT) provided rapid and significant improvements of severe symptoms of several mental health conditions including severe depression, treatment-resistant depression and depression with psychosis. Despite scientific evidence supporting its effectiveness, it is still an underused treatment for adults and an even less frequent option for children and adolescents with MDD. Statistics show that the average ratio of adult-to-minor use of ECT as a treatment is approximately 65:1. Furthermore, many child and adolescent psychiatrists reported little knowledge, training, or experience in the use of this therapy. By their own report, approximately 53% of the practitioners possessed minimal knowledge about ECT use in minors, 52% regarded ECT as unsafe in pre-pubertal children, and 26% considered the procedure unsafe as a treatment for adolescents. There are even legal restrictions both on the federal and state level that obstruct this use of this therapy in many cases. (Sachs et al, 2012)
The electroconvulsive therapy procedure is quite simple. A brief electrical pulse is applied to the head of an anesthetized patient. This electrical pulse excites the neurons in the brain, as seen on EEG, causing these neurons to fire in unison, producing a seizure. While the specific reason why ECT is a successful treatment is not yet known, there are several theories. One theory suggests that the seizure activity in the brain causes an alteration of the neurotransmitters, the chemical messengers of neurons. A second theory suggests that ECT treatments adjust the stress hormone regulation in the brain, thereby affecting energy, sleep, appetite, and mood. (University of Michigan – School of Medicine – Dept. of Psychiatry)
The Mayo Clinic reported that ECT could be a good treatment option when the patient could not tolerate medications and other forms of therapy were unsuccessful. For example, ECT can be used during pregnancy, when medications must be avoided due to potential harm to the developing fetus. Individuals who cannot tolerate the drug side effects of antidepressants are also good candidates. In the United States, ECT treatments are typically administered two to three times weekly for three to four weeks — for a total of six to 12 treatments. A newer technique called right unilateral ultra-brief pulse electroconvulsive therapy that can be performed daily. (Mayo Clinic Staff – Mayo Clinic, Tests and Procedures – ECT)
Despite the successful record of recent ECT as a relatively painless treatment for depression, it still remains a highly controversial treatment for depression. Much of the resistance to ECT was due to public misunderstanding and general fear, reinforced by various movies. (Reti, 2000) The Mayo Clinic also concurred that while electroconvulsive therapy (ECT) provided rapid and significant improvements of severe symptoms of several mental health conditions including severe depression, treatment-resistant depression and depression with psychosis, its use was limited due to generally negative perceptions by the general public. Much of this fear was based on early treatments of ECT in which high doses of electricity were administered to the patient without general anesthesia. Under such inappropriate conditions, memory loss, fractured bones and other serious side effects often resulted. (Mayo Clinic Staff, Mayo Clinic, Tests and Procedures – ECT)
An in-depth review of 39 of 212 retrieved articles demonstrated that the use ECT to treat adolescents with depression was a highly efficient option, with high remission rates, and few and relatively benign adverse effects. The majority of the scientific literature studies demonstrated both the efficiency of ECT use in adolescents and that it was more efficient than single psycho-pharmacotherapy. Administering the technique correctly could mitigate risks. “Despite being as effective in adolescents as it is in adults, ECT is much less frequently used in adolescents. Three of the retrieved studies compared ECT use in adolescents with ECT use in patients of other ages. Adolescents subjected to ECT accounted for only 0.43% of the total in India, 0.93% in Australia, and 1.5% in the USA.“ (Lima et al, 2013) Ghaziuddin, from the Department of Psychiatry, University of Michigan in Ann Arbor, concluded that although there was a lack of scientific evaluation of ECT with youthful patients, “it appears that ECT can be an effective and relatively safe treatment for depressed adolescents who have failed to respond to antidepressant pharmacotherapy.” (Ghaziuddin et al, 1996)
The Department of Psychiatry and Neurobehavioral Sciences at the University of Virginia Health System (Charlottesville, VA), which reported that nearly 75% of practitioners lacked the confidence/skill to provide a second consultant opinion, continues to examine the psychiatric, neurological and ethical issues when using electroconvulsive therapy (ECT) to treat children and adolescents. A major issue is that there is no national standard in the U.S. with regards to minimum age requirement. Some states have established their own individual age restrictions: Colorado and Texas restricts patients younger than 16 years, Tennessee prohibits electroconvulsive therapy use on patients younger than 14 years and California has an age restriction of 12 years. Certain practice parameters also exist which interfere with the use of electroconvulsive therapy as a treatment for young populations. (Sachs et al, 2012)
David Cohen, MD, the lead researcher and chief of the department of child and adolescent psychiatry at the Groupe Hospitalier Pitiè-Salpètrière (Paris) conducted a study of patients who received ECT for a mood disorder before they were 19 years old at five Parisian psychiatry departments. More than a year had elapsed following their 10 treatments, administered two or three times a week. The ECT-treated patients, matched by sex, age, date and place of hospitalization, and diagnosis, were compared with patients who had not received ECT. Cohen stated that “after being given more than six tests that measure brain functioning and memory, the researchers concluded that there were no significant differences between the teens who had received ECT and those who had not and that, “intellectually, both had progressed normally for their age.” As with other knowledgeable colleagues, Cohen reported that fears regarding the use of ECT in youth were not justified. Some misunderstanding of the procedure came from a lack of recognition of the severity of patients’ illnesses and when ECT was used appropriately, the benefits were enormous. Cohen added that in France, there are no restrictions on who can receive the treatments, in contrast to the U.S. where several states forbid the use of ECT for people under the age of 18. His opinion was that in most cases ECT was the most effective treatment for the most severe form of depression, that it was safe and that it did not cause brain damage. Still, both in France and in the U.S., ECT is greatly underutilized as a treatment for depression in teens and adults. (Defino, 2000)
In their policy position, Mental Health America (MHA – formerly known as the National Mental Health Association) recognized the controversy and stigma regarding the use of ECT citing “memory loss and other cognitive damage” as the primary reasons for the ongoing controversy over its use. Referring to the Surgeon General’s 1999 report that asserted that the confusion and disorientation often seen following an ECT procedure was resolved within one hour of treatment, the MHA stated that some memory loss was common. Generally the affected memory was from the period of six months pre- treatment to two months post-treatment. Some of the memory loss may have been caused by the depression that the ECT was being used to treat. Recent studies showed that the risks of memory loss were correlated with the type of ECT administered and how it is administered. Sine wave stimulation carried The highest risk of memory loss appeared to be related to sine wave stimulation and should be avoided. Bilateral stimulation was also associated with greater memory loss than unilateral stimulation. (Mental Health America, 2011)
Despite recent advances in ECT, these devices continue to be designated “class III” which represents the highest risk-based classification for medical devices by the FDA. Many FDA panel members expressed concerns about the lack of data regarding memory loss and cognitive function however appropriate clinical trials to demonstrate the effectiveness and safety of ECT appear unlikely as long as the general public and many practitioners remain confused and fearful of this treatment.
The prevalence of depression in our society and long-term costs in lives, productivity and economics makes research in depression and effective treatments a highly important area of study. Better recognition of this disorder in children and adolescents through better diagnostic screening and more effect and timely treatment methodologies are needed to address this growing health concern. Combined and individualized treatment plans for depression, including ECT, psychotherapy and medication appears to be the best approach at this time. By expanding health care providers training in early and accurate diagnosis of MDD in children and adolescents and skills in more effective treatment options, we can break the cycle in adulthood and the high cost this disease has on our society.
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