Clinical Practice Guideline
The Diagnosis and Treatment of Unipolar Depression
National Disease Management Guideline
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Background: Depression is one of the most common mental disorders worldwide. The German National Disease Management Guideline on Unipolar Depression (NDGM), (Nationale Versorgungsleitlinie, NVL), updated in 2022, contains recommendations on the diagnosis and treatment of acute and chronic depressive disorders.
Methods: The update was based on the findings of a systematic review of the evidence (2013–2022) and was issued by a multidisciplinary panel after a formalized consensus process.
Results: The structure of the guideline was fundamentally revised and is now based on the phases of depression and/or its treatment, as well as on the severity of the disease. There is newly added material with recommendations on Internet- and mobile-device based treatments, esketamine, repetitive magnetic stimulation, psychosocial therapies, rehabilitation, social participation, and complex forms of care. The guideline also emphasizes better coordination of all services in the care of patients with depression. This article covers the most important changes and additions among the 156 recommendations in the guideline. More information and accompanying materials are available at www.leitlinien.de/depression.
Conclusion: There are effective treatments for depression and a variety of supportive measures that can be applied with great benefit by primary care physicians, psychiatrists, psychotherapists, and complementary care providers. The updated guideline aims to further improve the early detection, definitive diagnosis, treatment, and interdisciplinary care of people with depression.
Mortality among depressive patients is around double the rate in the general population, and their mean life expectancy is 7–14 years lower (1, 2). Episodes of depression are among the most common individual diagnoses, as shown by the number of days of inability to work due to this diagnosis (3, 4) and by the fact that depressive disorders are the most frequent reason for early retirement due to reduced capacity for work (5).
The German National Disease Management Guideline (NDMG; in German: Nationale Versorgungsleitlinie, NVL) on Unipolar Depression meets all of the requirements for clinical practice guidelines embodied in the rules for guidelines laid out by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V.; AWMF) (6). These requirements include a multidisciplinary panel with members from 28 professional scientific associations and three organizations representing patients (eTable 1), transparent management of conflicts of interest, systematic research, and assessment of the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria (7, 8), as well as a structured, formalized consensus process. The formulation of the recommendations and their strength also took account of clinical considerations and practical aspects of care provision, together with issues raised by the patient representatives (9).
A draft of the guideline was made available for public scrutiny. Over 200 comments were received; these were discussed by the guideline group and led to incorporation of several revisions in the final version. A detailed account of the methods can be found in the guideline report (10).
The current version (11) does not yet include recommendations on the topics of comorbidity, peripartum depression, and other specific clinical scenarios. These will be dealt with in 2023.
Diagnosis and monitoring
The care offered by primary care physicians and in general hospitals to patients at risk should include screening for depressive disorders (e.g., questioning about previous episodes and particular somatic illnesses, detection of substance abuse) (↑↑). If depression is suspected, a standard ICD diagnostic work-up should ensue, with documentation of symptoms, severity, and features of the disease course (↑↑) (Figure 1). The new NDMG is aligned not only with ICD-10 but also with ICD-11, which received WHO approval in 2018 and will come into force in Germany at the end of a transitional period (eFigure 1).
A new feature is the recommendation for diagnosis according to the criteria of the International Classification of Functioning, Disability and Health (ICF) (↑↑). In this connection, examples of questions were developed for the outpatient setting. Experience shows that this has not yet been sufficiently implemented in practice, although documentation of the negative effects of depression on function, psychosocial status, and participation is crucial for individual treatment planning.
The recommendations on monitoring of the disease course have been made more specific with regard to the intervals between visits and the parameters to be captured (symptoms including suicidality, adverse effects, psychosocial status, need for participation, and adherence). To enable assessment of the response to therapy, the initial findings before the start of treatment should be documented, preferably with validated instruments (↑↑), e.g., the PHQ-9 questionnaire for patients (12).
Treatment planning and treatment options
The new NDMG recommends joint agreement, prioritization, and regular evaluation of treatment goals (↑↑). Decisions affecting diagnosis, treatment, and care should be reached according to the concept of shared decision-making (↑↑).
Psychoeducation and low-intensity interventions
Low-intensity interventions are treatments that are readily accessible and usually of a brief nature. They embrace a large number of different options that essentially aim at strengthening patients’ capacity for self-management (“guided self-help”). Psychoeducational measures form a basic element of treatment for all patients (eBox 1).
Digitally supported interventions
With regard to Internet- and mobile device-based interventions (IMI), the NDMG recommends that they should be employed only after a thorough diagnostic work-up, due consideration of differential diagnoses, clarification of the indication, discussion with the patient, and prescription (↑↑). Moreover, it recommends therapeutic supervision of IMI and regular verification of their efficacy (↑↑). As for the choice of the most appropriate IMI for users in Germany, orientation is provided by the Index for Digital Health Applications at www.diga.bfarm.de/de (in German).
Drug treatment
As in the preceding version, the NDMG supplies recommendations not only on the indications for drug treatment, but also on how to proceed. The specific choice of antidepressants should be based on the safety and interaction profile, the comorbidity, and the individual patient’s preference (eTable 2). A new section is devoted to discontinuation of antidepressants: depending on the clinical situation, e.g., discontinuation after remission or in the case of inefficacy, specific recommendations are given for tapering of the medication and for monitoring. For example, antidepressants should be tapered for at least 8–12 weeks at the end of continuation or maintenance therapy (↑↑). Should symptoms occur in association with discontinuation, switching to an antidepressant that is available in the form of drops and can thus be reduced in particularly small increments may be considered (↔). Because symptoms may first occur after complete withdrawal of the drug concerned, regular follow-up appointments should be arranged for at least the next 6 months (↑↑).
Psychotherapy
The NDMG focuses on the four psychotherapeutic techniques that are available in the outpatient setting in Germany, eligible for reimbursement, and classified as accredited by the psychotherapy guideline of the German Federal Joint Committee (G-BA): psychodynamic psychotherapy (psychoanalysis, depth psychotherapy), behavioral therapy, and systemic therapy. For the first time, there are recommendations on how to proceed in the event of psychotherapy. If there is no improvement after 8–12 weeks, for instance, the possible cause should be investigated and modification of the psychotherapeutic approach considered (↑↑). Furthermore, particularly in patients with a complex disease constellation and/or complicated treatment processes, validated instruments should be considered to document the patient’s symptoms and general wellbeing as well as the therapeutic process at regular intervals (↑). Finally, an extensive section is devoted to the long-neglected potential adverse effects of psychotherapy (13, 14).
Acute treatment according to degree of severity
Two algorithms for the severity-dependent treatment of acute depressive episodes were developed for the revised version (Figures 2, 3). The respective roles of drug treatment and psychotherapy for the various degrees of severity were discussed on the basis of recent meta-analyses. In a meta-analysis of 369 studies, the effect size of psychotherapeutic treatments with regard to depressive symptoms after adjustment for various risks of bias was 0.31 (95% confidence interval [0.24; 0.38]) (15). The effect size of antidepressants compared with placebo in a meta-analysis of 522 studies was 0.3 [0.26; 0.34] (16). Meta-analyses on the direct comparison of psychotherapy with antidepressants found no significant differences in effectiveness, so the choice between the two forms of treatment rests ultimately on clinical considerations.
Acute mild depressive episode
In an acute mild depressive episode, low-intensity measures (guided self-help, talk-based interventions using psychotherapeutic techniques) or IMI should be offered (↑↑). Apart from the evidence that has emerged, this new recommendation is motivated by the low-threshold access and the avoidance of long waiting times. Moreover, this frees consultations for patients in whom low-intensity approaches or IMI alone are inadequate.
In mild depressive episodes, the presence of risk factors for worsening or chronification of the depressive symptoms, e.g., previous episodes of depression, extended duration, or comorbidity, justifies treatment with psychotherapy or antidepressants. On the grounds of safety considerations (adverse drug reactions, discontinuation syndrome), antidepressants are not explicitly recommended but should be considered (↑). Noting a persisting tendency towards excessively rapid treatment with antidepressants alone, the guideline group emphasizes that drug treatment should be embedded in an overall therapeutic concept that embraces psychoeducational elements (↑↑). These include, for example, sleep hygiene and, when indicated, supportive options such as sport therapy (Figure 2).
Acute moderate depressive episode
Patients with acute moderate depressive episodes should continue to be offered psychotherapy or drug treatment as equally effective alternatives (↑↑). Additional IMI may be offered (↔). Benzodiazepines and Z-drugs are not recommended in mild depressive episodes (↓↓) and should be considered only exceptionally in moderate depression, e.g., in the presence of debilitating sleep disorders or marked agitation (↓).
Acute severe depressive episode
The recommendations in favor of combined drug treatment and psychotherapy for the treatment of patients with acute severe depressive episodes remain unchanged (↑↑). Patients who refuse combined treatment should be offered one of the two forms of therapy (↑↑) (Figure 3).
Continuation and maintenance therapy
An antidepressant should be continued at the same dosage as in the acute phase for 6–12 months during remission and beyond (↑↑). Provided there is no indication for longer maintenance treatment, the antidepressant should then be tapered (↑↑). Long-term maintenance therapy should be considered only in patients with 2–3 or more episodes of depression and significant functional impairment in the recent past (i.e., during the previous 5 years) (↑).
Continuation of psychotherapy in an appropriate form should also be offered to patients receiving acute psychotherapeutic care, with the aim of stabilization after successful treatment as well as prevention of recurrence (↑↑). Following pharmacological continuation treatment, tapering in combination with psychotherapy may be considered as an alternative to pharmacological maintenance therapy (↔), and after successful acute drug treatment a combined pharmacological and psychotherapeutic continuation or maintenance therapy should be considered (↑).
Non-response and treatment resistance
In the case of non-response to drug treatment it is important to be thorough in seeking the cause, e.g., poor adherence, comorbidity, comedication, or a low serum concentration (Figure 4). New in the revised guideline is a recommendation for the addition of psychotherapy to drug treatment (↑↑). Alternatively augmentation with low-dose antipsychotics (↑) or with lithium (↑) should be considered, as should a combination of two antidepressants (selective serotonin reuptake inhibitors [SSRI] or serotonin and norepinephrine reuptake inhibitors [SSRI] or tricyclic antidepressants [TCA] with mianserin or mirtazapine or trazodone) (↑). Repetitive transcranial magnetic stimulation (rTMS) may also be considered for augmentation of drug treatment (↔).
It is also important to identify the reason for non-response to psychotherapy (eFigure 2, eTable 3). Intervision and supervision may be helpful in this regard and also facilitate the development of potential solutions (↑). If there is no therapeutic fit between the person giving and the person receiving the treatment, or if the type of psychotherapy does not seem appropriate, the patient concerned should be referred elsewhere (↑↑). If, however, the therapeutic working relationship is stable, the frequency of sessions should be increased (↑↑).
In the case of repeated non-response to drug treatment (Figure 4), trial tapering of the medication should be considered (↑). Another option is augmentation of the antidepressant with administration of esketamine, but because esketamine is available exclusively from hospital pharmacies this may only be considered in the (part-time) inpatient setting (↔). On the basis of consolidation of the evidence, repetitive transcranial magnetic stimulation (rTMS) should now be considered in this scenario too (↑) (Figure 4).
Chronic depression
Chronic (ICD-11: persisting) depressive disorder means that the episode of depression has continued without interruption for more than 2 years. Because the studies on chronic forms of depression have analyzed extremely heterogeneous groups, the certainty of evidence is limited; therefore, the new recommendations in the NDMG are based on clinical considerations: The management of therapy-naive chronic depression should be oriented on the severity-dependent treatment for acute or recurrent episodes (↑↑). If a depressive disorder becomes chronic although the patient has been treated according to the guidelines, the recommendations on how to proceed in cases of non-response or treatment resistance should be followed (↑↑).
Psychosocial therapy and supportive measures
Psychosocial treatments are, in the view of the guideline group, often used too late or not at all—especially in the outpatient setting. The new NDMG therefore explicitly recommends assessing whether occupational therapy and sociotherapy are indicated (↑) and whether
self-help options, advice to relatives, peer support, or recovery support might be helpful (↑↑), as well as providing practical information regarding the prescription of psychosocial therapy.
The NDMG recommends that patients should be encouraged to take part in sporting activity or in structured and supervised exercise, ideally in a group context (↑↑). The evidence in favor of bright light therapy has also become stronger, so the NDMG now recommends its use in cases of depression that show a seasonal pattern (↑↑). The certainty of evidence for depression with no seasonal pattern is still very low; because bright light therapy is such a simple procedure, however, the guideline group believes it is worth trying (↔).
The revised NDMG features detailed recommendations with regard to work incapacity. The guideline group identified a tendency towards too early “knee-jerk” issuing of sickness certificates by primary care physicians. Staying home from work may help to reduce the burden, but can also contribute to worsening and chronification of depressive disorders—particularly in the case of lengthy absence from the workplace. The NDMG recommends that the potential advantages and disadvantages (eTable 4) should be discussed with the patient (↑↑) and that a sickness certificate, particularly if renewed, should be accompanied by therapeutic interventions (↑↑).
Suicidality and other emergencies
The recommendations regarding the management of suicidality were essentially confirmed or, in some cases, modified slightly. A new feature is the explicit recommendation that suicidal patients, too, should be clearly informed about all aspects of treatment and that decisions on the type and setting of the treatment should, whenever possible, be made jointly (↑↑). Furthermore, the guideline group believes that wider availability of outpatient crisis teams would be desirable so that patients can be cared for locally and with less delay. An emergency plan focussing on individual warning signs, coping strategies, social support, and contact addresses should be drawn up (↑↑) (eBox 2).
Nasal administration of esketamine may be considered in addition to an antidepressant in the case of suicidality in the (part-time) inpatient setting (↔), and electroconvulsive therapy may also be an option (↔). All drug treatments should be given during and/or after a psychotherapeutic crisis intervention, not alone. In this regard, the revised NDMG contains new recommendations for other emergency scenarios in the context of depressive disorders (depressive stupor, psychomotor agitation, and psychoses, among others).
Medical rehabilitation and services to support participation
A new section gives details of the rehabilitation and support services available for the mentally ill in Germany (eFigure 3; in German). One recommendation addresses the indications for inpatient rehabilitation (eBox 3). Given that employment has a positive effect on the health of persons with mental illness and that unemployment is a negative prognostic factor (23, 24), the NDMG recommends early counseling of those affected (↑↑). If necessary, they should be assisted in applying for these return-to-work interventions (↑↑).
Coordination of care
Gaps in care provision are common, especially in the transition from inpatient to outpatient setting—a time when patients are especially vulnerable to relapses and suicidality. The overview presented (in German) in eFigure 4 gives details of the services available, the care providers, and the cost units. The structures for provision of mental health care vary widely from region to region, so all those involved should inform themselves accordingly (↑↑) in order to be able to form individual networks for regional cooperation. The NDMG defines the indications for interdisciplinary cooperation or referral (eTable 5) and specifies concrete measures around discharge management (↑↑) (eBox 4). Also addressed is the role of pharmacies, both in the detection of depression and suicidality and in motivating those concerned to undergo treatment.
Especially patients with moderate or severe symptoms who have been ill for ≥ 1 year should be offered multiprofessional, structured, coordinated care (↑↑). Approaches with different intensities can be considered, starting with the as yet unimplemented Disease Management Program (DMP) for depression via multiprofessional networks for community-based complex care (§ 92 Sect. 6b, German Social Code [GSC] V) and psychiatric/psychosomatic outpatient clinics (§ 118, GSC V), as well as home-based forms of care such as inpatient-equivalent psychiatric treatment (§ 115d, GSC V).
Dissemination and patient materials
All materials related to the NDMG on Unipolar Depression are available (in German) free of charge at www.leitlinien.de and at www.awmf.org. The complete version of the NDMG can be downloaded as a PDF or used directly as HTML text on a computer or mobile device. The short version includes all of the recommendations and algorithms together with the principal tables. Decision aids and information material for patients relating to more than 20 prioritized clinical situations are available in language understandable to lay persons. The patient guideline (currently being compiled) presents the entirety of the NDMG’s contents in plain language.
Funding
The National Disease Management Guideline program is funded by the National Association of Statutory Health Insurance Physicians and the German Medical Association.
Conflict of interest statement
MH has received payment for one lecture each from the TK health insurance fund (Techniker Krankenkasse) and Münsterlingen Psychiatric Hospital (Switzerland) and for the compilation of two brochures for patients from the Confederation of Occupational Health Insurance Funds (BKK Dachverband). He receives an expense allowance for his activity as chair of the Scientific Advisory Board and Scientific Director of the Agency for Quality in Medicine (AZQ).
PP has received payment from the publisher MBO-Verlag for the compilation of two brochures for patients on behalf of the Confederation of Occupational Health Insurance Funds (BKK Dachverband). PP is a scientific adviser at the Agency for Quality in Medicine (AZQ).
Manuscript received on 19 February 2023, revised version accepted on 15 March 2023.
Translated from the original German by David Roseveare.
As with many other professional journals, clinical guidelines in the German Medical Journal are not subject to the peer review process, as S3 guidelines are already texts that have been assessed and discussed by experts (peers) and have a broad consensus.
Corresponding author
Prof. Dr. med. Dr. phil. Martin Härter, Dipl.-Psych.
Institut und Poliklinik für Medizinische Psychologie
Universitätsklinikum Hamburg-Eppendorf
Martinistr. 52, 20246 Hamburg, and
Ärztliches Zentrum für Qualität in der Medizin (ÄZQ)
TiergartenTower, Strasse des 17. Juni 106–108, 10623 Berlin, Germany
m.haerter@uke.de
Cite this as:
Härter M, Prien P, on behalf of the NVL Guideline Group: Clinical practice guideline: The diagnosis and treatment of unipolar depression—National Disease Management Guideline. Dtsch Arztebl Int 2023; 120: 355–61. DOI: 10.3238/arztebl.m2023.0074
►Supplementary material
eReferences, eTables, eFigures, eBox:
www.aerzteblatt-international.de/m2023.0074
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