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Depression in children and adolescents: Does psychotherapy lead to better results when compared with other therapies? IQWiG Reports – Commission No. HT19-04 [Internet]. Cologne (Germany): Institute for Quality and Efficiency in Health Care (IQWiG); 2022 Aug 12.
Depression in children and adolescents: Does psychotherapy lead to better results when compared with other therapies? IQWiG Reports – Commission No. HT19-04 [Internet].
Show details1.1. Health policy background and commission
According to § 139b (5) Social Code Book V, Statutory Health Insurance, statutory health insurance members and other interested people may suggest topics for the scientific assessment of medical interventions and technologies to the Institute for Quality and Efficiency in Health Care (IQWiG). The topics for these health technology assessment (HTA) reports can be submitted on the ThemenCheck Medizin (“topic check medicine”) website.
ThemenCheck Medizin aims to promote the involvement of the public in evidence-based medicine and answer questions which are particularly relevant in patient care.
Once yearly, IQWiG, in collaboration with patient representatives and members of the public, selects up to 5 topics on which HTA reports are to be prepared. IQWiG then commissions external experts to investigate the research question. The results prepared by the external experts and a publisher’s comment by IQWiG are then published in the form of an HTA report.
IQWiG disseminates HTA reports to German institutions, for instance, those deciding about healthcare services and structures. The HTA report will be made available to the professional community through the IQWiG website (www.iqwig.de). In addition, a lay summary of the results of the HTA report will be published under the title “HTA compact: The most important points clearly explained”. This is done to ensure that the results of HTA reports will impact patient care.
1.2. Medical background
1.2.1. Definition and epidemiology
The diagnostic criteria for a depressive episode are met when patients exhibit at least 2 of the 3 following core symptoms for at least 2 weeks: marked, persistent depressed mood, loss of joy, desire, and interests (anhedonia) as well as avolition. (according to the International Statistical Classification of Diseases and Related Health Problems, 10th revision, German Modification; ICD-10-GM, version 2020 [1]). Further, the following secondary criteria characterize the clinical image of depression: low self-confidence, low self-esteem, self-blame, guilt, suicidal ideation and behaviour, difficulties concentrating and making decisions, psychomotor agitation or inhibition, sleep problems as well as reduced or increased appetite [2]. With regard to severity, the ICD-10 classification distinguishes between mild, moderate, and severe depressive episodes with(out) symptoms. In mild depressive episodes (F32.0), at least 2 of the above 3 core symptoms and at least 2 secondary criteria are observed.
However, the child or adolescent is able to continue everyday activities. In moderate depressive episodes (F32.1), the patient exhibits at least 2 core symptoms and at least 3 (or better 4) of the above-mentioned secondary criteria. The patient’s daily life is already substantially impacted. For diagnosing a severe depressive episode without psychotic symptoms (F32.2), all 3 core symptoms and at least 8 secondary criteria should be met. Patients with a severe depressive episode typically experience a substantial reduction in self-esteem and strong feelings of guilt as well as suicidal ideation accompanied by somatic symptoms. If patients additionally exhibit hallucinations, delusions, pronounced psychomotor retardation, or stupor (complete loss of activity in an awake, conscious state), they are in a severe depressive episode with psychotic symptoms (F32.3). Recurrent depressive disorder (F33) is characterized by repeated episodes of depression, where the first episode may occur at any age and the episode duration varies from a few weeks to several months. The current episode can be classified by severity as mild (F33.1), moderate (F33.2), severe without psychotic syndromes (F33.2), or severe with psychotic symptoms (F33.3) [3].
Depressive disorder must be distinguished, among others, from 2 other disorders: if manic episodes are observed between the episodes of depression, the patient suffers from bipolar affective disorder (F31). Dysthymia (F34.1) is characterized by chronic depression of mood lasting at least several years which is not sufficiently severe, or in which individual episodes are not sufficiently prolonged, to justify a diagnosis of mild recurrent depressive disorder (F33.1) [1].
The manifestation of depressive disorder in adolescence has already been well researched; its symptoms are the same as those listed for depression in general. Children, on the other hand, predominantly exhibit somatic symptoms such as headache and stomach aches. Often, symptoms overlap with anxiety and social insecurity [4].
In adults, alongside headache, neck pain, and lower back pain, depressive disorders represent the most common contributor to impaired health and quality of life worldwide [5]. According to estimates by the 2017 Global Burden of Disease Study, about 264 million persons 15 years or older worldwide are affected by depressive disorders [5,6]. The 2015 Global Burden of Disease Study shows that, worldwide, 4.4% of the population age 15 or above suffer from depressive disorder [7]. Women are affected more commonly than men (5.1% versus 3.6%). Children and adolescents under the age of 15 years exhibit depressive disorders less commonly than people in other age groups. The international prevalence equals 2.6% for children and adolescents (95% confidence interval [CI]: [1.7; 3.9]); these figures are based on a systematic review of 23 studies with 59 492 children and adolescents worldwide whose psychological health was examined in representative population surveys [8]. The prevalence of depressive disorder is lower in children (< 1% in most studies) than in adolescents (4% to 5%) [9]. During childhood, no differences are found between sexes, but after puberty, depressive disorders are diagnosed twice as often in girls as in boys [9]. Based on data from a survey on mental health, behaviour, and health-related quality of life carried out in Germany (BELLA study), 11.2% of children and adolescents exhibited clinically relevant signs of depression according to the parental survey (7 to 11 year olds) and 16.1% in the self-report (11 to 19 year olds) [10]. The higher prevalence found in the German study when compared to the systematic review is likely due to depressive symptoms not being equivalent to a diagnosed depressive disorder and the evaluation not being performed by qualified professionals.
1.2.2. Causes and course of disease
Since individual, familial, social, and biological risk factors are interrelated and influence one another, the specific contribution of individual risk factors to the development of depression cannot be determined [4,9]. Compared with children of nondepressed parents, children whose parents have a depressive disorder are at 3 to 4 times higher risk of developing depression. In addition to genetic predisposition, however, vulnerable attachment to the child as a result of depression plays an essential role [2]. Critical life events such as the death of a close relative, environmental catastrophes, longer-term burdens such as physical disorders or psychosocial aspects such as neglect, maltreatment, or abuse likewise increase the risk of developing a depressive disorder [9].
Up to 90% of children and adolescents who are treated for a depressive episode recover within 1 to 2 years [4]. However, 45% to 75% of children and adolescents who recover from a depressive episode experience a relapse within 5 years [4,11]. Adolescents who suffer from a depressive disorder are at higher risk of developing anxiety, substance abuse, and bipolar affective disorder as adults [9].
1.2.3. Diagnostics and treatment
The diagnostic workup typically includes a medical history as reported by the patient, including the topics of family, development, and school experiences, a medical history on the basis of information provided by relatives, a family history, an analysis of the social environment, a clinical interview as well as a self-assessment and a third-party assessment, often obtained with the aid of standardized written questionnaires. For purposes of a differential diagnosis, both a physical examination and a survey of drug and medication use are recommended [3]. As part of the diagnostic workup, anxiety, attention deficit hyperactivity disorders, eating disorders, and obsessive-compulsive disorder should additionally be ruled out. The diagnostic workup should be performed only by trained professionals [12].
For the treatment of depressive disorders in children and adolescents between the ages of 3 and 18 years, an S3 guideline has been issued in 2013 by the German Association for Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy (DGKJP) [12]. However, this S3 guideline expired on 1 July 2018 and is currently being revised. Given the current lack of more recent German recommendations, the contents of this S3 guideline are nevertheless used below.
The treatment strategy should be chosen based on episode severity, the extent of preserved functioning in daily life as well as family and individual resources [3]. In case of mild depressive episodes, the DGKJP S3 guideline [12] recommends active monitoring as well as measures to promote mental health, i.e. active support, consultation, or mental health education for a time period of 6 to 8 weeks. Only if symptoms persist should further interventions be planned. Active monitoring is recommended only in the absence of any relevant burden or signs of deterioration. The child or adolescent must be fully capable of managing daily life in an age-appropriate way.
For children under 8 years of age, no recommendation can be made due to a lack of evidence. As the first-choice treatment in older children and adolescents with mild depressive episodes and additional burdens as well as those with moderate or severe depressive episodes, the S3 guideline recommends psychotherapy (cognitive behavioural therapy or interpersonal psychotherapy), the drug fluoxetine, or a combination of both. Psychotherapy is to be preferred over psychopharmacotherapy since the latter can be associated with a risk of intensified suicidal thoughts and other adverse effects. A separate opinion states that adolescents with depressive disorder should receive psychotherapy and that pharmacotherapy is recommended as the second-choice therapy. In severe depressive episodes, the advantages and disadvantages of combination therapy versus psychotherapy alone must be weighed. In cases where the 2 above-mentioned types of psychotherapy cannot be used, the S3 guideline alternatively recommends psychodynamic or systemic psychotherapy as the first-choice treatment. According to the S3 guideline, alternatives to fluoxetine are the drugs escitalopram, citalopram, or sertraline, albeit in “off-label use” since they are not approved for children and adolescents in Germany. Treatment can typically be provided on an outpatient basis. Semi-inpatient or inpatient care should be initiated under the following conditions: suicidality without support by relevant attachment figures, substantial psychosocial burdens, or impaired functioning [12].
Psychotherapy
All psychotherapy types listed as first-choice therapies in the DGKJP S3 guideline [12] are briefly described below. Cognitive behavioural therapy (CBT) is based on empirical psychology and integrates diverse treatment elements: patient information about the symptoms and causes of depressive disorder, promotion of social competencies, enhancement of positive activities, and cognitive restructuring. CBT aims to change patterns of behaviour and thought and to enable children and adolescents to control negative feelings [4]. According to the Guidelines for Psychotherapy published by the Federal Joint Committee (G-BA), the German health insurance funds cover the cost of CBT [13].
Interpersonal psychotherapy (IPT), a short-term therapy, is based on the assumption that dysfunctional relationships and interpersonal problems contribute to the development and persistence of depressive disorders in adolescents. Therefore, IPT focuses on social isolation as well as role conflicts and promotes positive social behaviours [4]. The DGKJP S3 guideline recommends IPT since international studies confirm its effectiveness, but it points out that IPT has not been approved as guideline procedure by the G-BA and no qualification standards have been established [12].
Psychodynamic psychotherapy types (DYN) include depth psychology-based psychotherapy (DP) as well as analytical psychotherapy (APT). DYN emphasizes the importance of the unconscious and instincts in individual behaviour and uses the concept of transference: past experiences are projected onto the therapist so that the experienced conflicts can be processed during therapy [14]. This intervention is recognized in Germany, and its cost is covered by the health insurance funds [13].
Systemic therapy, which includes family therapy, focuses on the social context of mental illnesses. The therapeutic work includes not only the affected children and adolescents, but also important individuals in the relevant social system. Therapy focuses on cognitive emotional, physical as well as interpersonal problems and available resources [12]. This HTA report disregards systemic therapy because it is the topic of a different IQWiG report which is about to be commissioned [15].
The DGKJP S3 guideline [12] does not state the recommended session frequency or duration for the various psychotherapy types. Treatment can be terminated after children and adolescents have not exhibited any clinically relevant symptoms for at least 2 months. According to an open recommendation, however, follow-up appointments should be offered for a period of 12 months. Another relevant aspect in this context is that different psychotherapy session allotments require specific approval steps from the health insurance funds [16].
Antidepressants
In Germany, fluoxetine is currently the only drug approved for the treatment of depressive disorders in children 8 years and older [17]. It is a selective serotonin reuptake inhibitor (SSRI). SSRIs block serotonin transport proteins in the brain and prevent the reuptake of serotonin from the synaptic gap, thereby increasing the concentration of serotonin in the brain. At the start of treatment, the DGKJP guideline [12] recommends a dosage of 10 mg/day; after 1 week, it can be increased to 20 mg/day if clinically necessary. Since the drug’s energizing effect also increases the risk of self-harm behaviours and suicidal thoughts, it should be taken in the morning and the dosage increased slowly. Often, children and adolescents respond to this treatment only after about 2 to 4 weeks. The side effects prevailing during this period often prompt a patient’s wish to discontinue treatment. During this phase, it is critical to advise patients to continue therapy [17]. Based on 10 studies, a network metaanalysis (NMA) [18] showed that fluoxetine more effectively reduces depressive symptoms than a placebo (standardized mean difference [SMD] -0.51; 95% CI: [-0.99; -0.03]). In comparison with placebo, patients taking fluoxetine more commonly exhibited side effects such as headache, diarrhoea, somnolence, sleeplessness, emotional instability, mania, and hypomania [19].
Children or adolescents who have been free from clinically relevant symptoms for at least 2 months should continue to receive treatment for at least 6 more months according to the DGKJP S3 guideline [12]. Thereafter, discontinuation of the psychopharmacological treatment can be considered.
In Germany, no other second-generation SSRIs (escitalopram, citalopram, sertraline) are approved for the treatment of children and adolescents. Due to their shorter half-life and hence easier control, however, these drugs are in off-label use in clinical practice [17].
Active monitoring and measures for promoting mental health
Active monitoring includes consultation and information (mental health education) about the depressive disorder to help patients and their family members understand information about the disorder and treatment measures. Its objective is for patients to adopt potential self-help strategies and utilize treatment where necessary. Mental health education is not an “independent” treatment method such as psychotherapy but a component of the overall psychological intervention. Mental health education can also be viewed as an active monitoring measure. Mental health education is based on behavioural therapy (BT), with several modern variations also including elements of talk therapy. Objectives of mental health education include improving the understanding and management of the disorder and hence achieving emotional relief for patients and their relatives. In addition, mental health education is intended to contribute to better adherence to any administered therapies [20].
According to the DGKJP S3 guideline [12], in mild depressive disorder without additional burdens, active monitoring for a period of 6 to 8 weeks can be sufficient – provided that patients are able to manage their daily lives in an age-appropriate manner. In addition, measures to improve mental health should be offered, such as mindfulness exercises, participation in structured exercise such as running, aerobic, or strength training, and relaxation exercises such as Jacobson’s Relaxation Technique [21]. The health economic part of this HTA report uses progressive muscle relaxation as an example to calculate intervention costs for non-drug interventions. Muscle relaxation is based on the observation that experiencing stress and anxiety is associated with increased muscle tone, while relaxation is associated with lower muscle tone. In this treatment, patients first briefly tense individual muscle groups and then relax them in a stepwise (progressive) manner. Attention remains on the respective muscle group before the next muscle group is tensed.
1.3. Health services situation
In Germany, children and adolescents with mental health issues rarely seek help. Data from the baseline study of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) show that only 11.8% of children and adolescents classified as borderline symptomatic and 18.6% of those classified as symptomatic seek help for their mental health (from psychiatrists, psychologists, youth welfare services) [22]. Even among minors whose parents explicitly reported them to have been diagnosed with a mental disorder, only about half received psychological, psychotherapeutic, or psychiatric treatment [23]. In the second KiGGS survey round from 2014 through 2017, a total of 3.8% of parents of children between 0 and 17 years of age in the overall population reported visiting a practice for psychiatry or child and adolescent psychiatry, while 2.5% reported utilizing psychotherapy for their children. Persons of low sociooeconomic status were 2 times more likely to seek help from a psychiatrist than those of higher sociooeconomic status [24]. Children and adolescents from western German states are less commonly treated than those from eastern German states. In addition, individuals residing in towns with higher populations were more likely to utilize psychosocial services [25].
For insured children and adolescents with depressive episodes and recurrent depressive disorder, statutory health insurance (SHI) funds cover the cost of psychotherapy – the types being defined in the G-BA’s Guidelines for Psychotherapy [13]. For instance, costs are reimbursed for behavioural therapy as well as psychodynamic psychotherapy services such as DP and APT. For DP or APT, up to 150 hours of one-on-one therapy for children or up to 180 hours for adolescents or 90 double-hour sessions of group therapy can be approved; for behavioural therapy, the maximum is 80 hours of one-on-one or group therapy for children and adolescents. SHI funds cover the cost of systemic therapy only for adults. Regarding IPT, G-BA guideline procedures do not provide for cost reimbursement by SHI funds [13]. According to the agreement on psychotherapy provided in contractual care (Psychotherapy Agreement [26]), these types of therapy can be performed by the following professionals: physicians specializing in psychiatry and psychotherapy, physicians specializing in child and adolescent psychiatry and psychotherapy, psychological psychotherapists as well as child and adolescent psychotherapists and therapists with appropriate qualifications.
1.4. Concerns of those proposing the topic
A member of the public asked whether, in children and adolescents with initial depressive symptoms, a wait-and-see approach is preferable to psychotherapy or pharmacological therapy. Particularly since increasing numbers of depressive episodes are diagnosed in children and adolescents and these symptoms are difficult to differentiate from (pre)pubescent symptoms, the member of the public was interested in the comparison of psychotherapy versus no therapy.
The ThemenCheck Medizin staff at IQWiG developed the following HTA research question on the basis of this suggestion. The focus was not on the comparison of pharmacological therapy versus no therapy because ThemenCheck Medizin does not cover the safety and effectiveness of drug therapies. Nevertheless, drug therapy was included as a comparator intervention for psychotherapy.
- Background - Depression in children and adolescents: Does psychotherapy lead to ...Background - Depression in children and adolescents: Does psychotherapy lead to better results when compared with other therapies?
- putative nuclease HARBI1 isoform b [Mus musculus]putative nuclease HARBI1 isoform b [Mus musculus]gi|1252414524|ref|NP_001343448.1|Protein
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