Clinical Practice Guideline

Unipolar Depression

Diagnostic and Therapeutic Recommendations From the Current S3/National Clinical Practice Guideline

Dtsch Arztebl Int 2010; 107(40): 700-8. DOI: 10.3238/arztebl.2010.0700

Härter, M; Klesse, C; Bermejo, I; Schneider, F; Berger, M

Background: Depressive disorders are among the most common illnesses and reasons for obtaining health care. Their diagnosis and treatment are still in need of improvement. In Germany, a new S3/National Clinical Practice Guideline has been developed for this purpose.

Methods: The existing guidelines on unipolar depression from Germany and other countries were synoptically compared and supplemented with systematic literature searches. After 14 consensus conferences, a total of 107 evidence-based recommendations were issued.

Results: Unipolar depression should be diagnosed in accordance with ICD-10 criteria. Screening questionnaires are useful aids to diagnostic classification. When a treatment is chosen, shared decision-making with the patient is essential. Mild depressive episodes can be treated initially by watchful waiting for 14 days. For moderate depressive episodes, pharmacotherapy and psychotherapy are equally effective treatment options. For severe depression, a combination of pharmacotherapy and psychotherapy is recommended. If 4 to 6 weeks of acute therapy are insufficiently effective, lithium augmentation is recommended, rather than combination antidepressant therapy or a switch to another antidepressant. After remission, maintenance therapy should be continued for 4 to 9 months. In recurrent depression, pharmacotherapy and/or psychotherapy, where appropriate, should be continued for at least two years. Specific recommendations are given for patients who have somatic or mental comorbidities or are acutely suicidal, and recommendations are also given for coordination of care.

Conclusion: This guideline is a comprehensive set of evidence- and consensus-based recommendations for the diagnosis and treatment of unipolar depression. An improvement in the care of patients with unipolar depression will require broad implementation of the guideline, both in the inpatient and outpatient setting.

LNSLNS

The importance of unipolar depression as a common and widespread illness is continually increasing. With a lifetime prevalence of 16% to 20%, depressive disorders range among the most common pathologies and causes for health consultations in Germany (1). Adequate and timely diagnosis of depressive disorders bear great potential for improvements in health services, and an equally promising approach is to base diagnostic evaluation and treatment on evidence-based recommendations, and stepwise and networked or interdisciplinary health care (2, 3).

The S3 clinical practice guideline was initiated by the German Association for Psychiatry and Psychotherapy (Deutsche Gesellschaft für Psychiatrie, Psychotherapie und Nervenheilkunde, DGPPN), which presided over the guideline development, its funding, and its preparation, in 2005–2009, in collaboration with other medical societies and with the support of the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). Further, the guideline was finalized as a German National Clinical Practice Guideline (Nationale VersorgungsLeitlinie, NVL) under the coordination of the German Agency for Quality in Medicine (Ärztliches Zentrum für Qualität in der Medizin, ÄZQ) and (4, 5).

Methods

The consensus group of the S3 guideline consisted of representatives from 29 medical societies and professional associations, as well as self help groups and associations of family members/relatives (eBox 1 gif ppt and 2 gif ppt). A steering group was formed to develop the clinical practice guideline and coordinate the consensus conferences. This group was consulted for the background texts set out by the coordination team and prepared new suggestions for decisions on this basis (5, 6).

Consensus was reached on a total of 107 statements and recommendations in 14 moderated expert meetings. The recommendations are based on the synoptic integration of national and international guidelines on the one hand (eBox 3 gif ppt); the central source guideline was the British guideline set out by the National Institute for Health and Clinical Excellence (NICE), entitled “Depression: Management of Depression in Primary and Secondary Care.” Where guideline recommendations did not provide satisfactory answers to the key questions or did not fit in with the German healthcare system, systematic literature searches were undertaken, especially for meta-analyses, systematic reviews, and randomized controlled studies.

The recommendations were signed off by the participating experts in a consensus (Figure 1 gif ppt).

Diagnostic evaluation

This guideline applies to depressive episodes, recurring depressive disorders, dysthymia, and recurrent short depressive disorders in patients of 18 years or older.

Diagnostically, this guideline follows the criteria laid out by the International Classification of Diseases (ICD-10) (Figure 2 gif ppt). Patients can be screened for possible depressive episodes by using the following questions (7):

  • In the past month, have you often felt down, sad, worried, or hopeless?
  • In the past month, have you felt notably less inclination to pursue, or enjoyment in doing, things that you normally enjoy?

If the screening questions yield raised scores for depression, then a diagnosis of a depressive disorder that requires treatment should be made by immediate direct and complete capture of the main symptoms and additional symptoms (=degree of severity) and questions relating to duration and course (evidence level B; strength of evidence IIb) (Box 1 gif ppt).

Depressed patients rarely report typical depressive symptoms; rather, they will complain about not being able to sleep and waking up early, loss of appetite, general lack of energy, sustained pain, and/or physical symptoms. For this reason, the presence of a depressive disorder or of further symptoms of a depressive disorder should be actively explored (evidence level 0, strength of evidence III).

In depressive disorders it is important to carefully check for physical diseases, prescribed medications and harmful substances, which may be accompanied by depressive symptoms, and somatic comorbidities. If patients proceed to psychotherapy only, their physical condition should be thoroughly and reliably checked (evidence level 0, strength of evidence III).

In every patient with a depressive disorder, the clinician should assess clinically their suicidality in every encounter and if required explore this further (evidence level clinical consensus point, strength of evidence IV).

Beyond the statutory duty to provide information and in the sense of participatory decision-making, the treating clinician/therapist should talk to the patient about possible treatment strategies and the associated adverse effects and possible risks (advantages and disadvantages of specific therapeutic options) and reach a decision (evidence level B; strength of evidence Ib) (8).

Starting treatment

The basis for the patients’ cooperation, especially when treatment is just starting, is the creation of a stable relationship between therapist and patient, provision of tailored and comprehensible information, and regular information updates. Depressed patients should be informed about the symptoms, disease course, and treatment of depression. Where this is appropriate and the patient agrees, this also applies to their families (evidence level A, strength of evidence IV).

Psychoeducational services for patients and relatives/family members should be provided as a useful add-on in the context of an overall treatment strategy, so as to improve the level of information, acceptance, and the patient’s willingness to cooperate (evidence level B, strength of evidence Ib–IIa).

Patients and relatives should receive information about self help groups and family members’ groups; they should be encouraged to participate in such groups, if needed (evidence level A, strength of evidence IV).

At the start of antidepressant treatment, the patient should be fully informed about possible adverse effects, the possible latency period, and the duration of the treatment (evidence level clinical consensus point, strength of evidence IV).

Important topics that should be covered in the consultation are (8):

  • Recognize and eliminate concerns about antidepressants (for example, development of addiction or tolerance, personality changes)
  • Explain biological mechanisms of action
  • Explain the latency period
  • Explain possible adverse effects
  • Give reasons for the length of treatment (statement, strength of evidence IV).

It may be advantageous to include family members’ groups or self help groups in this.

Thorough explanations and close monitoring (weekly) is recommended for the first 4 weeks of treatment, in order to improve the patient’s cooperation and adherence (evidence level clinical consensus point, strength of evidence IV).

Acute therapy of mild and moderate depressive episodes

In a mild depressive episode, the efficacy of antidepressants and placebo are not statistically significantly different (9). In moderate to severe depressive episodes, the efficacy of antidepressants is notably greater than that of placebo (10).

Most of the evidence for the efficacy of psychotherapeutic monotherapy applies to mild and moderate depression; cognitive behavioral therapy (CBT), interpersonal psychotherapy (IPT), and short-term psychodynamic therapy (STPP) (1113) are the approaches that are backed up by the best evidence.

In a mild depressive episode, specific treatment for depression may initially not be necessary—in the sense of active watchful waiting—if it is to be expected that the symptoms will remit without active treatment (Figure 3 gif ppt). If the symptoms persist after a fortnight or have deteriorated then the therapist and patient should discuss starting specific treatment (evidence level 0, strength of evidence IIb.

Antidepressants should generally not be used for initial treatment of mild depressive episodes, only after critical evaluation of risks versus benefits (evidence level B, strength of evidence Ia).

Antidepressants may be indicated in mild depression in the following scenarios:

  • Patient’s wishes/preference
  • Patient’s positive experiences with responsiveness to medication therapy in the past
  • Continued symptoms after alternative interventions
  • Episodes of moderate or severe depression in the patient’s history.

Psychotherapy should be offered to treat mild to moderate depressive episodes (evidence level A, strength of evidence Ia).

Medication therapy with an antidepressant should be offered to treat an acute moderate depressive episode (evidence level A, strength of evidence Ia).

If considering pharmacotherapy for mild to moderate depressive episodes then an initial therapeutic attempt might be made using St John’s wort, bearing in mind the herb’s specific side effects and interactions (evidence level 0, strength of evidence Ia).

In every patient, antidepressant medication should be started with the lowest, “starter,” daily dose.

In older patients, it makes sense to halve the daily starter dose for tricyclic antidepressants and if required step up the dosage gradually (statement, strength of evidence IIb–IV).

Acute treatment for severe depressive episodes

For severe depressive episodes, the placebo controlled effectiveness of antidepressants and merely CBT or IPT have been confirmed (10, 14). The combination of pharmacotherapy and psychotherapy is superior, especially as psychotherapy as the sole treatment modality may well have a longer latency period. In acute severe depressive episodes, combination treatment consisting of antidepressant drugs and psychotherapy should be offered (evidence level A, strength of evidence Ib) (15).

If considering monotherapy then patients with acute moderate to severe depressive episodes who can be treated on an outpatient basis should be offered psychotherapy as equivalent to medication monotherapy (evidence level A, strength of evidence Ib).

Treating chronic depressive disorders

In patients with dysthymia (a subsyndromal depressive disorder persisting for 2 years or longer) and “double depression” (a depressive episode on top of existing dysthymia), then the indication for pharmacotherapy should be considered (evidence level A, strength of evidence Ia) (16). In patients with a chronic (persisting for longer than 2 years) depressive episode, pharmacotherapy should be considered (evidence level B, strength of evidence Ib). In dysthymia, double depression, and chronic depression, the patient should be informed that combination therapy (medication and psychotherapy) is more effective than monotherapy (evidence level A, strength of evidence Ib).

Effectiveness, non-response to therapy, and therapy resistant depressive disorders

Patients’ response to medication or psychotherapeutic treatment requires regular monitoring in the context of the diagnostic evaluation of the course and process—in the first 4 weeks, this means weekly check-ups. After 3 to 4 weeks, the check-ups should be based on patients’ symptoms (evidence level A, strength of evidence IV).

If no positive results (in the sense of the intended outcome) are seen 3 to 4 weeks after acute treatment was initiated, the treatment that has not yielded results should not be continued unmodified (evidence level 0, strength of evidence Ib). In non-response to pharmacotherapy, 5 strategies are available in principle:

  • Measuring serum concentrations and subsequently adapting the dosage (“therapeutic drug monitoring”)
  • Increasing the dosage
  • Augmentation by adding another pharmaceutical
  • Changing the antidepressant, and/or
  • Combination with another pharmaceutical (Figure 4 gif ppt).

For many antidepressants (for example, tricyclic antidepressants [TCA], venlafaxine, tranylcypromin) stepping up the dosage is a useful measure in non-response, always in accordance with manufacturers’ instructions for use. This is not the case for the selective serotonin reuptake inhibitors (SSRIs) (evidence level 0, strength of evidence III).

Experienced doctors should consider attempting augmentation with lithium in patients whose depression has remained unresponsive to antidepressants (evidence level B, strength of evidence Ia) (17). Patients with a good response to an antidepressant and augmentation with lithium should remain on this regimen for at least 6 months (evidence level B, strength of evidence Ia–Ib). If a patient shows no effect 2 to 4 weeks after an effective lithium concentration has been reached then the lithium should be phased out (evidence level clinical consensus point, strength of evidence IIb).

Changing the antidepressant is not a first choice option in the treatment of non-responders. Each change should therefore be carefully weighed (evidence level B, strength of evidence Ib).

For patients who have not responded to antidepressant monotherapy, the only combination treatment that is recommended is mianserin (while bearing in mind the risk of agranulocytosis) or mirtazapine with an SSRI or TCA.

In therapy resistant depression (where pharmacotherapy has been administered adequately, with at least two drugs, one after the other, at a sufficiently high dosage and given for a long enough time interval), patients should be offered appropriate psychotherapy (evidence level B, strength of evidence Ia).

Maintenance treatment and preventing recurrences

Antidepressants should be taken for a minimum of 4 to 9 months after the remission of a depressive episode; the risk of a recurrence is lowered substantially in this way. In this maintenance phase, the same dosage should be administered as in the acute phase (evidence level A, strength of evidence Ia) (18).

Patients with one or more depressive episodes with important functional impairments in the recent past should be instructed to take the antidepressant for at least 2 years as long-term prophylaxis (evidence level B, strength of evidence Ib). To prevent a recurrence, the antidepressant should be given at the same dosage that was effective during the acute phase (evidence level B, strength of evidence Ib). In patients at risk of suicide, medication with lithium should be considered as prophylactic treatment for a recurrence, in order to reduce suicidal acts (suicide attempts and suicide) (evidence level A, strength of evidence Ia) (19).

To stabilize the therapeutic success and lower the risk of recurrence, appropriate psychotherapeutic treatment (maintenance treatment) should be offered after the acute treatment (evidence level A, strength of evidence Ia) (20). In the longer term, stabilizing psychotherapy (prevention of recurrence) should be offered to patients with a raised risk of recurrence (evidence level A, strength of evidence Ia).

Red flags

The guideline also focuses on situations where a procedure or a measure used thus far is not to be continued or may be particularly critical:

  • After 3 to 4 weeks of unsuccessful, guideline-conform pharmacotherapy, the therapeutic approach should be reconsidered (after 6 weeks in elderly patients)
  • After 6 weeks of unsuccessful treatment by a general practitioner, referral to a specialist should be instigated
  • After 3 months of unsuccessful psychotherapy, referral to a specialist should be instigated
  • Re-examination of patients who were treated as inpatients for suicidal behavior after a maximum of 1 week (direct contact should be sought if the patient does not keep the appointment!).

Pharmacotherapy in particular groups of patients

In elderly patients, treatment with a tricyclic antidepressant should be started with a lowered initial dose (statement, strength of evidence IIb–III). Compared with younger patients, greater attention needs to be paid to the side effect profile and tolerability of antidepressants.

In patients with depression and organic brain disorders, substances with a sedative and/or anticholinergic effect should be avoided (evidence level 0, strength of evidence Ib) (21). In patients with psychotic depression, the combination of the antidepressant with an antipsychotic should be considered, although the optimal dosage and length of use of these medications are not known (evidence level B, strength of evidence III).

In coronary heart disease and comorbid moderate to severe depressive disorder, pharmacotherapy should include preferably sertraline or citalopram (evidence level A, strength of evidence Ia). Patients with depression after stroke should be offered pharmacotherapy while bearing in mind the risks of anticholinergic side effects (empirical clues exist for fluoxetine, citalopram, and nortriptylin) (evidence level B, strength of evidence Ib).

In moderate to severe depression with comorbid tumor disease, pharmacotherapy with an antidepressant—especially one of the SSRIs—may be offered (evidence level 0, strength of evidence Ib).

In pharmacotherapy for depression in patients with comorbid diabetes, substance specific effects on the diabetes need to be given attention—for example, the reduced insulin requirement in SSRIs and weight gain with mirtazapine, mianserin, and sedating tricyclic antidepressants (evidence level B, strength of evidence Ib–IIb).

Further somatic treatment options

Electroconvulsive therapy should be considered in cases of severe, treatment resistant, depressive episodes as a treatment alternative (evidence level A, strength of evidence Ia). Electroconvulsive therapy can also be administered as maintenance treatment in patients who

  • have responded to electroconvulsive therapy during an episode of illness previously,
  • have not responded to any other guideline-conform antidepressant treatment,
  • have psychotic symptoms, or
  • express a preference for this treatment option (evidence level 0, strength of evidence IIa).

Sleep deprivation should be considered to treat depressive episodes if a rapid, albeit not long lasting, response is the therapeutic aim or if the intention is to complement another guideline-conform therapeutic option (evidence level B, strength of evidence Ib). Light therapy should be considered as a treatment option in patients with mild to moderate episodes or recurrent depressive disorders that follow a seasonal pattern (evidence level A, strength of evidence Ia). Exercise can be recommended based on clinical experience, in order to increase the sense of wellbeing and ameliorate depressive symptoms (evidence level clinical consensus point, strength of evidence Ib).

Intersections in healthcare services and outlook

Box 2 (gif ppt) shows numerous examples of intersecting healthcare services for depressed patients (no recommendations in the narrower sense, particularly because studies of the transition between the treatment steps are lacking or are difficult to implement [22, 23]). From the recommendations of this guideline, potential quality indicators have been formulated for the purposes of quality assurance, which are of relevance to healthcare services and clinical practice. These, as well as the benefits of implementing the guideline, should be scientifically evaluated in innovative healthcare models or model projects under conditions of outpatient as well as inpatient practice.

Guidelines are subject to dynamic development and require continuous updating. The steering group of this guideline has collected several subject areas that are receiving priority attention for the new edition 2013 (“gender and sex specific aspects”, “pregnancy and breast feeding”, “patients from a migrant background”, and “unipolar depression in children and adolescents”). With regard to the psychotherapeutic approaches, an evaluation of the evidence for systemic therapy is planned.

Acknowledgements

The authors of this article thank the following for their extraordinary commitment, patience, help in organizing expert meetings, moderation, and contributions to discussions, all of which have all made a vital contribution to the success in finalizing this guideline:

Professor Dr. Ina Kopp (AWMF), moderation of the consensus meeting for the S3 clinical practice guideline “unipolar depression.”

Dr. med. Susanne Weinbrenner, Dr. med. Berit Meyerrose (both German Agency for Quality in Medicine, Berlin) und Dr. med. Monika Lelgemann (German Agency for Quality in Medicine, Berlin, and Medizinischer Dienst des Spitzenverbandes Bund der Krankenkassen [MDS, the medical service of the head organization of the German Federal Association of Statutory Health Insurance Funds], consistent support of the coordinating and editing team of the S3-/German Clinical Practice guideline “Unipolar Depression”

Professor Dr. Dr. med. Günter Ollenschläger (German Agency for Quality in Medicine), who is responsible for the guideline program of the German Medical Association, the National Association of Statutory Health Insurance Physicians, and the Association of Scientific Medical Societies in Germany (AWMF), moderation of the German Clinical Practice Guideline steering group “Unipolar Depression”. The authors also thank the other members of the steering group for contributing their expertise and their readiness to discuss matters (in alphabetical orders):

Angela Bleckmann (BApK)

PD Dr. med. Tom Bschor (AkdÄ)

Prof. Dr. med. Dipl.-Päd. Jochen Gensichen MPH (DEGAM)

Dipl.-Psych. Timo Harfst (BPtK)

Prof. Dr. phil. Martin Hautzinger (DGPs)

Carsten Kolada (BApK)

Prof. Dr. sc. hum. Christine Kühner (DGPs)

Dipl.-Psych. Jürgen Matzat (DAG SHG)

Prof. Dr. med. Christoph Mundt (DGPPN)

Prof. Dr. med. Wilhelm Niebling (DEGAM)

Prof. Dr. phil. Rainer Richter (BPtK; als Gast)

Prof. Dr. med. Henning Schauenburg (DGPM)

PD Dr. phil. Holger Schulz (DGRW)

Conflict of interest statement

Martin Härter received honoraria for speaking from Lilly and Boehringer-Ingelheim in 2008.

Isaac Bermejo received honoraria for speaking from Boehringer-Ingelheim and Wyeth Pharma until 2008.

Frank Schneider received until 2008 honoraria for speaking and participation in external advisory boards from AstraZeneca, Janssen-Cilag, Otsouka, and Wyeth. He has received study funding from AstraZeneca and Lilly.

The remaining authors declare that no conflict of interest exists according to the guidelines of the International Committee of Medical Journal Editors.

Manuscript received on 26 July 2010, revised version accepted on 26 July 2010.

Translated from the original German by Dr. Birte Twisselmann.

Corresponding author
Prof. Dr. med. Dr. phil. Martin Härter, Dipl.-Psych.
Universitätsklinikum Hamburg-Eppendorf
Institut und Poliklinik für Medizinische Psychologie
Martinistr.52 (W 26), 20246 Hamburg, Germany
m.haerter@uke.de

@eBoxes available at:
www.aerzteblatt-international.de/article10m0700

1.
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2.
Wittchen HU, Müller N, Schmidtkunz B, et al.: Erscheinungsformen, Häufigkeiten und Versorgung von Depressionen. Ergebnisse des bundesweiten Zusatzsurveys „Psychische Störungen“. Fortschr Med [Suppl I] 2000; 118: 4–10.
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5.
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depression with psychotherapy or psychotherapy-psychopharmacotherapy combinations. Arch Gen Psychiatry 1997; 54(11): 1009–15. MEDLINE
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Institut und Poliklinik für Medizinische Psychologie, Universitätsklinikum Hamburg-Eppendorf: Prof. Dr. med. Dr. phil. Härter, Dipl.-Psych.
Abteilung für Psychiatrie und Psychotherapie, Universitätsklinikum Freiburg:
Dipl.-Psych. Klesse, Dr. phil. Bermejo, Prof. Dr. med. Berger
Klinik für Psychiatrie und Psychotherapie, Universitätsklinikum Aachen:
Prof. Dr. med. Dr. rer. soc. Schneider, Dipl.-Psych.
1. Jacobi F, Wittchen HU, Hölting C, et al.: Prevalence, co-morbidity and correlates of mental disoders in the general population: results from the German Health Interview and Examination Survey (GHS). Psychol Med 2004; 34: 597–611. MEDLINE
2. Wittchen HU, Müller N, Schmidtkunz B, et al.: Erscheinungsformen, Häufigkeiten und Versorgung von Depressionen. Ergebnisse des bundesweiten Zusatzsurveys „Psychische Störungen“. Fortschr Med [Suppl I] 2000; 118: 4–10.
3. Schneider F, Dausend S, Bermejo I, et al.: Insufficient depression treatment in outpatient settings. German Med Sci 2004; 2: Doc01 (20040226). MEDLINE
4. Härter M, Klesse C, Bermejo I, et al.: Entwicklung der S3- und Nationalen VersorgungsLeitlinie Depression. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 2008; 51(4): 451–7. MEDLINE
5. Klesse C, Berger M, Bermejo I, et al.: Evidenzbasierte Psychotherapie der Depression – Therapiepraxis nach der aktuellen S3-/Nationalen VersorgungsLeitlinie „Unipolare Depression“ Psychotherapeut 2010; 55: 247–63.
6. DGPPN, BÄK, KBV, AWMF, AkdÄ, BPtK, BApK, DAGSHG, DEGAM, DGPM, DGPs, DGRW (eds.) für die Leitliniengruppe Unipolare Depression: S3-Leitlinie/Nationale VersorgungsLeitlinie Unipolare Depression. 1. Auflage 2009. DGPPN, ÄZQ, AWMF – Berlin, Düsseldorf 2009.
7. Whooley MA, Avins AL, Miranda J, Browner WS: Case-finding
instruments for depression. Two questions are as good as many.
J Gen Intern Med 1997; 12(7): 439–45. MEDLINE
8. Loh A, Kremer N, Giersdorf N, Jahn H, Hänselmann S, Bermejo I, Härter M: Informations- und Partizipationsinteressen depressiver Patienten bei der medizinischen Entscheidungsfindung in der hausärztlichen Versorgung. Z Arztl Fortbild Qualitatssich 2004; 98(2): 101–7. MEDLINE
9. Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, Johnson BT: Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. PLoS Med 2008; 5(2): e45. MEDLINE
10. Khan A, Leventhal RM, Khan SR, Brown WA: Severity of depression and response to antidepressants and placebo: an analysis of the Food and Drug Administration database. J Clin Psychopharmacol 2002; 22(1): 40–5. MEDLINE
11. Gloaguen V, Cottraux J, Cucherat M, Blackburn IM: A meta-analysis of the effects of cognitive therapy in depressed patients. J Affect Disord 1998; 49(1): 59–72. MEDLINE
12. Feijo de Mello M, de Jesus Mari J, Bacaltchuk J, Verdeli H, Neugebauer R: A systematic review of research findings on the efficacy of interpersonal therapy for depressive disorders. Eur Arch Psychiatry Clin Neurosci 2004; 255(2): 75. MEDLINE
13.Abbass AA, Hancock JT, Henderson J, Kisely S: Short-term psychodynamic psychotherapies for common mental disorders. Cochrane Database Syst Rev 2006; (4): CD004687. MEDLINE
14. DeRubeis RJ, Gelfand LA, Tang TZ, Simons AD: Medications versus cognitive behavior therapy for severely depressed outpatients:
mega-analysis of four randomized comparisons. Am J Psychiatry 1999; 156(7): 1007–13. MEDLINE
15. Thase ME, Greenhouse JB, Frank E, et al.: Treatment of major
depression with psychotherapy or psychotherapy-psychopharmacotherapy combinations. Arch Gen Psychiatry 1997; 54(11): 1009–15. MEDLINE
16. Lima MS, Moncrieff J: Drugs versus placebo for dysthymia. Cochrane Database Syst Rev 2000; (4): CD001130. MEDLINE
17. Bauer M, Dopfmer S: Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies. J Clin
Psychopharmacol 1999; 19(5): 427–34. MEDLINE
18. Geddes JR, Carney SM, Davies C, et al.: Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 2003; 361(9358): 653–61. MEDLINE
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