DÄ internationalArchive45/2008Treatment of Depressive Disorders

cme

Treatment of Depressive Disorders

Dtsch Arztebl Int 2008; 105(45): 782-91. DOI: 10.3238/arztebl.2008.0782

Bschor, T; Adli, M

Introduction: A confusing variety of options are available for the treatment of depressive disorders.
Method: Selective literature review under consideration of current guidelines.
Results: The treatment of depression can be divided into acute, maintenance and prophylactic phases. The basic forms of treatment are pharmacotherapy, psychotherapy, and supportive strategies. The approximately 30 antidepressants currently on the market differ mainly with respect to their side effect profiles. Of the specific types of psychotherapy, cognitive behavioral therapy, psychodynamic therapy, and psychoanalysis are funded by the statutory health insurance providers in Germany. All treatment strategies (except for sleep deprivation) show a latency of onset of several weeks and a nonresponse rate of about 30- to 50%. In clinical practice it is essential to follow a stepwise procedure and to perform a standardized evaluation of response after the latency period. In the event of nonresponse, the next step of treatment should be initiated.
Discussion: Depressive disorders have a good prognosis provided one
takes best advantage of the available treatment options. Preconditions are continuation of treatment for an appropriate length of time (for antidepressants ca. 4 to 6 weeks, for psychotherapy ca. 4 to 12 weeks) and standardized evaluation of response thereafter.
Dtsch Arztebl Int 2008; 105(45): 782–92
DOI: 10.3238/arztebl.2008.0782
Key words: depression, antidepressants, stepwise antidepressant treatment, treatment algorithm, psychotherapy
LNSLNS The diagnostic evaluation of depressive disorders and their classification as mild, moderate, or severe was presented a short while ago in an earlier issue of Deutsches Ärzteblatt (1). If depression has been correctly diagnosed, numerous effective treatment options are currently available. The prognosis of a depressive disorder is good if it is treated appropriately and consistently.

The learning aims of this article are

- knowing the fundamentals of the treatment of depressive disorders (indication, setting, treatment phases, treatment steps)
- learning the principles of establishment of the physician-patient relationship
- acquiring basic knowledge about pharmacotherapy with antidepressants
- acquiring knowledge about treating depression with different forms of psychotherapy.

This continuing medical education article is based on a selective review of the literature, combined with the authors' own extensive experience in the ambulatory and in-hospital treatment of depressed patients. It presents the current state of the therapy of depressive disorders, with an emphasis on treatments that can be provided by general practitioners and family physicians.

Evidence of a depressive episode requiring treatment, as opposed to appropriate grief, can include the following:

- Duration of the depressive syndrome > 2 weeks
- Persistently depressed affect that cannot be lightened even by positive experiences
- A sense of paucity of emotion (the patient does not consider himself or herself to be sad, but rather feels "turned to stone" or "dead within")
- Typical circadian fluctuations, with a morning low and improvement toward evening
- Somatic symptoms without any organic cause
- Inappropriate feelings of guilt, or even depressive delusions
- Suicidality
- Previous episodes of severe depression
- A family history of severe depressive disorders.

The treatment setting
Depression is a very common condition (1). Therefore, its diagnosis and treatment, at least in uncomplicated cases, are tasks not just for the psychiatrist, but for the general practitioner and family physician as well.

- The indications for referral to a psychiatrist are

  – diagnostic uncertainty
  – psychiatric comorbidity (e.g., addiction, dementia, personality disorder)
  – severe depressive manifestations
  – delusional depression
  – depression in the setting of a bipolar affective disorder (bipolar depression)
  – suicidality
  – chronified depression
  – intractability, i.e., nonresponse to one or two treatments that have been carried out appropriately
  – need for psychotherapy or for an intensity of care that cannot be delivered in the setting of a family practice.


- The indications for referral for inpatient psychiatric treatment are

  – acute suicidality or other type of self-endangerment (e.g., refusal of food)
  – severe delusional or other psychotic manifestations
  – depressive stupor
  – the inability, because of illness or other causes, to participate in outpatient treatment on a regular basis (e.g., because of a lack of drive)
  – imminent neglect of oneself because of the lack of an adequately supportive social network
  – external living conditions that would impair the success of outpatient treatment, e.g., severe familial conflicts
  – lack of response to outpatient treatment.

Phases and objectives of treatment
The treatment of depression is divided into three phases (2, 3). The goal of acute therapy is complete or near-complete remission of the depressive manifestations. Because the speed of response of depressive disorders to treatment varies, acute therapy may need to be given for no more than a few weeks or for many months.

After the acute phase, maintenance therapy is given, with the main goal of preventing an early relapse. Its duration varies from 6 to 12 months. Maintenance therapy is indicated during this period because there is a high chance of relapse regardless of the form of treatment that was used to induce remission in the acute phase (4). In general, the form of treatment that led to remission is continued unchanged into the maintenance phase. A further goal of maintenance therapy is complete functional recovery, i.e., the patient's complete return to his or her premorbid level of function at home, in the workplace, and elsewhere.

Prophylactic therapy is indicated only in patients whose illness has taken a recurrent course, depending on the likelihood of recurrence in the individual case. The latter can best be judged from the number of prior depressive episodes and from the intervals of time between them. If prophylactic therapy is thought to be indicated, it should be started without any temporal endpoint in view (4). This review article will mainly deal with acute therapy.

Principles of treatment
The three main types of treatment for depression are

- pharmacotherapy,
- psychotherapy, and
- supportive measures.

Because of the considerable rate of spontaneous remission, particularly in milder cases of depression (untreated episodes last for an average of 6 to 8 months), the physician and the patient may agree on a two- to four-week period of "watchful waiting" before any treatment is given (5).

The initial treatment of mild or moderate depression should consist of monotherapy, either with a single medication or with psychotherapy, depending on availability and on the patient's preference. In severe, recurrent, or chronified depression, as well as for elderly depressed patients, a primary combination of these two treatment modalities may be advantageous.

Basic treatment strategy
The foundation of any treatment for depression, including but not restricted to specific forms of psychotherapy, is conversation with an empathic and understanding physician in the framework of a stable therapeutic alliance. The patient should sense the physician's acceptance of his or her worries and fears and should feel relieved as a result of the therapeutic interview, particularly with respect to feelings of guilt and inadequacy. The physician should inspire optimism by assuring the patient that depression is treatable and has a good prognosis. To this end, it often helps to instruct patients with a biological model of their condition, making it possible for them—particularly in the acute stage—to understand their depressive manifestations as the expression of an illness and thus as a legitimate, temporary dispensation from the duties of everyday life. A biological explanation can often also take away the inexplicable and threatening character of depression. Chronically depressed patients, on the other hand, need stepwise activation and promotion of their individual responsibility and initiative. Over-challenged family members often react with reproaches, trivializations ("everything will be OK soon enough, it's not really so bad"), or exhortations to "pull yourself together." All of these are unhelpful, yet they underscore the necessity of educating the patient's family, too, about depression as a treatable illness and of enlisting them in the effort to bring about recovery. Patients and their families can be motivated to participate in a self-help or family group (see German Internet addresses listed at the end of this article). Written patient information can be useful as well (see Internet addresses).

A special danger of depressive disorders is suicidality. 3% to 15% of persons suffering from depression commit suicide (e1), while 40% to 70% of suicide victims had suffered from depression (6).

The issue of suicidality should always be addressed repeatedly over the course of treatment. Patients almost always feel relieved when this topic is discussed. For concrete management, see the article by Rudolf et al. (1). Most suicides are announced beforehand in some way, either directly or indirectly.

Important steps to be taken for suicidal patients are the following:

- The immediate commencement of a psychotherapeutic crisis intervention. A stable physician-patient relationship is the most effective protective factor; thus, the family physician plays a central role in such situations.
- Referral to a specialized psychiatrist
- Short-term follow-up at close intervals and clear, unambiguous agreement on the time and place of the next session—no vague offers such as, "give me a call if things are not going well."
- A concrete, 24-hour offer of help: telephone number of the psychiatric crisis service or rescue center
- Obtain the patient's agreement to put off any thoughts of harming himself or herself and have the patient commit to an anti-suicide pact. The latter is an agreement between the physician and the patient in which the patient promises not to harm himself or herself within a specified period of time.
- Inpatient referral or involuntary commitment, if necessary, in accordance with the relevant laws
- For acute suicidality, give benzodiazepine when indicated.

Because there is no single treatment method to which all patients will respond, depression is treated, as a rule, in sequential therapeutic steps (7). The duration of each step should be long enough to give the method used a chance to be effective, yet also short enough to avoid treating the patient ineffectively for any longer than necessary. Four weeks (or six, for elderly patients) has generally been found to be an appropriate period for treatment with antidepressant medications, four to twelve weeks for specific forms of psychotherapy.

At the end of this period, the patient's response to treatment should be evaluated in a standardized fashion. To this end, a detailed documentation of the patient's disease manifestations at the outset of the treatment step is essential. The established, easy-to-use depression severity scales are also helpful—both external assessment scales (e.g., the Hamilton Depression Scale [8]) and self-assessment scales (e.g., the Beck Depression Inventory [9]). A "response" in terms of these scales is generally said to have occurred when the overall score has gone down by at least half during the treatment step in question (10). If this is the case, further treatment should be aimed at a complete remission of the disease manifestations. In case of nonresponse, on the other hand, a transition should be made to the next treatment step.

Pharmacotherapy
Antidepressants
The antidepressants play a central role in the pharmacotherapy of depression. Approximately 30 substances in this class are approved for use in Germany. All are about equally effective (5), with a nonresponder rate of one-third to one-half. All antidepressants have a similar latency until the onset of their therapeutic effect: for practical clinical purposes, a latency of two to four weeks can be assumed (EBM level A [Ia]).

With very few exceptions, all available antidepressants work mainly by raising the synaptic concentration of serotonin and/or noradrenaline in the central nervous system. They differ only in the precise mechanism by which they do this (11) (table 1 gif ppt).

Phytotherapy (St. John's wort)
Phytotherapy with St. John's wort preparations is very popular in Germany in particular. The scientific evidence with regard to the efficacy of this agent is mixed at present, with many studies fraught with severe methodological deficiencies. A current meta-analysis (5) comes to the conclusion that St. John's wort is probably effective for the treatment of mild and moderate depression. The more than 40 St. John's wort preparations that are now available on the German market contain extremely variable concentrations of more than 400 individual chemical substances (5).

It is not widely known, yet highly clinically relevant, that St. John's wort carries with it a major risk of interactions with other medications: by inducing isoenzymes of the cytochrome P450 system, it can weaken the effect of many medications, including oral contraceptives, anticoagulants, digoxin, theophylline, other antidepressants, cyclosporine, and anti-HIV agents. Likewise, when a patient stops taking St. John's wort, the serum concentrations of these drugs will rise.

Benzodiazepines
Benzodiazepines have no antidepressant effect in the strict sense of the term, yet they have an acute sedative and anxiolytic effect and their use may thus be indicated for severely depressed and suicidal patients for a period no longer than 14 days. Such treatment is often needed because of the long latency of effect of the antidepressants, which was already mentioned above. The risks and contraindications of the benzodiazepines must, however, be taken into account. For instance, a history of addiction may be a risk that contraindicates benzodiazepine use.

Neuroleptics
Neither the older nor the newer neuroleptics have been shown to be effective as monotherapy for unipolar depression. Neuroleptics are indicated only for the treatment of delusional depression and should only be prescribed by a psychiatrist. Studies have shown that some of the atypical neuroleptics are effective when given in addition to an antidepressant (augmentation therapy), but neuroleptics have not been approved for this indication. Weekly injections of fluspirilene should not be given because of the risk of tardive dyskinesia.

Lithium
So-called lithium augmentation plays a role in the acute treatment of depression that has not responded to antidepressants (12). Furthermore, lithium as monotherapy is effective for prophylactic treatment in recurrent depression. Treatment with lithium requires special knowledge and precautionary measures and should thus be prescribed only by experienced physicians.

The course of pharmacotherapy
Patient education and shared decision-making
Thorough patient instruction about the effect, duration, and possible side effects of treatment is an integral component of pharmacotherapy. Patients must also be informed that maintenance therapy will be needed after the acute phase of treatment. When discussing these matters with the patient, the physician must address widespread misgivings and ungrounded fears, e.g., of addiction or a change of personality. Patient compliance with psychiatric medication is often inadequate but can be improved by informing the patient about the latency of the antidepressant effect and by describing possible side effects in advance. Shared decision-making (13) means that the well-informed patient should be able to decide for or against taking any proposed antidepressant medication in tandem with the physician. Letting the patient's family take part in this process also improves compliance.

The choice of antidepressant
The choice of an antidepressant for acute treatment is largely based on the side-effect profile, as the agents used for acute treatment are all comparably effective (table 2 gif ppt). If a particular antidepressant has already been used effectively to treat a previous episode, then this agent should be preferred.

Sedation is a side effect that may be either undesired or beneficial if the patient suffers from sleep disturbance.

Tricyclic antidepressants should be avoided in a number of situations (5):

- In prostatic hyperplasia, glaucoma, cognitive impairment/dementia, constipation, and co-medication with other anticholinergically active substances, because of their anticholinergic side effects;
- In patients with pre-existing heart disease, because they may cause cardiac conduction abnormalities or arrhythmias;
- In suicidal or cognitively impaired patients (risk of deliberate or accidental overdose), because of their greater overdose toxicity compared to other antidepressants.

A reasonable and well-established practice is to give, during the maintenance phase, the same antidepressant that led to remission in the acute phase (4), even though venlafaxine is the only substance officially approved in Germany for maintenance pharmacotherapy. Either antidepressants or, alternatively, lithium can be used for prophylactic therapy in recurrent depression.

Dosing
Each antidepressant has a minimal effective dose; these standard doses are listed in table 2, as are the differing starting doses of preparations that must be given initially in a slowly increasing dose. For elderly patients, but for no others, lower than standard doses may already be effective and may, indeed, be indicated because they cause fewer complications. The same antidepressant dose should be prescribed in the maintenance phase of treatment that induced a remission in the acute phase (4). It is very difficult to recommend specific doses for prophylactic treatment at present because of the limited data that are currently available. For prophylactic treatment, too, the standard dose used for acute treatment is probably more effective than a lower dose.

Monitoring
In the first four weeks of acute therapy, the patient should be seen in follow-up at least once a week. At each follow-up appointment, the patient's toleration of the medication should be evaluated, and any concerns on the patient's part should be addressed. The response should be evaluated after four weeks of treatment.

The following tests are recommended for follow-up:

- Before treatment with an antidepressant, complete blood count and transaminases
- If a tricyclic antidepressant (TCA) is used, an ECG as well
- If a TCA or selective serotonin and noradrenaline reuptake inhibitor (SNRI) is used, blood pressure measurement
- Over the course of treatment, repeated complete blood count and transaminases, as well as (in the situations mentioned above) ECG and blood pressure measurement, particularly if the dose is raised
- If selective serotonin reuptake inhibitors (SSRI) are used, then the serum electrolytes should be measured over the course of treatment because of the risk of hyponatremia, particularly in elderly patients.

What to do in case of nonresponse
If the patient's disease manifestations do not respond to treatment with antidepressants in adequate doses for an adequately long trial period, the treatment strategy should be changed. In this situation, a number of options are available.

A reasonable first step consists of measuring the serum concentration of the antidepressant being used. This is called therapeutic drug monitoring (TDM) and is a helpful check on patient compliance as well as a means of detecting any metabolic particularities that may cause an inadequate serum level in the individual patient when taking a standard dose. Blood must be drawn before the medication is taken. For many newer antidepressants, however, there is still no reliably established connection between a therapeutic serum level and a clinical response; thus, TDM is mainly recommended if the agent being used is either a tricyclic antidepressant or venlafaxine. More information on therapeutic levels, the degree of evidence upon which they are based, and the laboratories that measure them can be found on the Internet (please see list of German-language websites at the end of this article).

A common strategy after nonresponse to initial antidepressant treatment is to switch to another antidepressant; choosing an agent from another antidepressant class is usually recommended. There is, however, no scientific evidence for the effectiveness of this strategy (14). Thus, the antidepressant should not be changed more than once in the acute phase, and, if the second antidepressant also fails to bring about a response, another strategy should be used.

High-dose antidepressant treatment (table 2) is a sensible option for most antidepressants (15). The SSRIs are an exception: these agents have no clear dose-response relationship, so dose escalation of SSRIs lacks a theoretical basis (15). Antidepressants given in high doses can be expected to produce more severe side effects. ECG checks at closer intervals are obligatory when tricyclic antidepressants are given in high doses; with venlafaxine, the blood pressure must be checked at close intervals. The possible response to high-dose therapy should be evaluated no sooner than about four weeks after it has been initiated because of the known latency until the treatment effect sets in.

A further reasonable treatment strategy after nonresponse to antidepressant monotherapy is combination therapy with two antidepressants. The effectiveness of combination therapy, however, has only been documented for one specific type of combination, namely that of a reuptake inhibitor (tricyclic antidepressant or SSRI) together with a presynaptic autoreceptor blocker (mirtazapine, mianserin, or trazodone) (16).

Lithium augmentation is the administration of lithium in addition to an antidepressant that has been used hitherto for monotherapy without effect. Adding on lithium can bring about a response in a considerable number of patients, as has been shown in numerous studies and meta-analyses (12).

Psychotherapy
The effectiveness of various forms of psychotherapy in depression has been well documented. Most of the therapeutic effect seems to be due to common, nonspecific factors that may also be at work in medical care outside the specifically psychotherapeutic setting. The most important among these factors is a systematically established therapeutic relationship with an accepting, actively listening, and empathetic physician. The physician himself or herself thereby becomes a potent "therapeutic agent," whose importance can scarcely be underestimated.

Most psychotherapeutic approaches to the treatment of depression involve the following strategies:

- Resource activation (identification and reinforcement of the patient's current abilities)
- Problem actualization (directed addressing of particular areas of conflict)
- Problem coping (supporting the patient with emotional, cognitive, or active solution strategies)
- Motivational clarification (recognition of problematic modes of perception and behavior and dysfunctional cognitions).

As in pharmacotherapy, patients should be regularly re-evaluated for the possible emergence of side effects, and therapeutic efficacy should be assessed after an adequate period of treatment.

Specific psychotherapeutic techniques
Psychotherapy for depression can be carried out in an outpatient or inpatient setting, individually or in groups, and with or without the participation of the patient's family. In Germany, the statutory health insurance carriers currently reimburse ambulatory behavioral therapy and deep psychology–based and analytic psychotherapy as so-called guideline techniques.

Cognitive behavioral therapy
Cognitive behavioral therapy (CBT) is based on the assumption that dysfunctional cognitions can lead to disturbed emotions and behavior, and vice versa. A lack of positive reinforcement owing to depression worsens the patient's depressive manifestations. CBT thus involves both cognitive and behavioral approaches. Its treatment strategies aim at overcoming the patient's lack of positive reinforcement, social withdrawal, and conviction of his or her own helplessness. The "cognitive errors" that are often identified among depressed patients include inappropriate generalizations, personalization, emotional thinking, and black-and-white thinking. Etiological importance is also attached to "depressiogenic" cognitive schemata that are learned early on in life and may be reactivated by critical life events; a typical example is the so-called "cognitive triad" of automatic negative assumptions about oneself, the environment, and the future. Cognitive therapy aims to correct these dysfunctional cognitions with structured and directed short-term therapy consisting of an average of 20 sessions. The efficacy of ambulatory CBT against depression has been very well studied and has also been confirmed by meta-analyses (17, e2e4).

Deep psychology–based and psychoanalytic psychotherapy
Classical psychoanalytic treatment is performed with the patient lying on a couch, several times weekly, over a long period of time. Deep psychology–based psychotherapy is based on central fundamental assumptions and principles of psychoanalysis, but it is usually performed with the patient sitting in a chair, only once per week, and over a shorter period of time. Both of these types of psychotherapy are based on the assumption that depressive disorders are largely due to unconscious processes whose roots typically lie in the patient's childhood. Depressed persons, in particular, often suffer from uncertainties in their relationships and a negative bonding style with increased vulnerability to losses and affronts. More than in other types of psychotherapy, the therapist-patient relationship itself becomes an object of treatment, because the patient's typical relationship pattern and anxieties are reproduced in this relationship and can be addressed within it.

The currently available data from controlled studies of efficacy are less extensive than for CBT. More structured, short-term deep psychological psychotherapy in mildly or moderately depressed patients has been the type most frequently studied (e5). Other studies and meta-analyses have involved patients with a mixture of diagnoses, so that it is difficult to draw any specific conclusions about the effectiveness of these types of treatment for depression (e6, 18).

Interpersonal psychotherapy (IPT)
IPT is a type of short-term psychotherapy that was developed specifically for the treatment of depression. It consists of 12 to 20 hours of semi-structured psychotherapy, generally in weekly sessions, and focuses on the psychosocial and interpersonal aspects of depressive disorders. Thus, it places particular emphasis on coping with grief, role switching, life changes, and interpersonal conflicts.

Although much evidence for the efficacy of IPT is available from controlled studies and meta-analyses (19), in which it was used alone or in combination with antidepressants, IPT is currently not reimbursed by the statutory health insurance carriers in Germany.

Supportive measures
The importance of involving the patient's family has already been mentioned more than once. The only treatment for depression that has an immediate therapeutic effect is sleep deprivation, which can be done on an inpatient or outpatient basis. The patient is required either to do without sleep for an entire night (complete sleep withdrawal) or simply to get up between 1 a.m. and 2 a.m. (partial sleep deprivation), without making up for the missed sleep either in advance or afterward. It is crucial for the success of this treatment that the patient should not take even a short nap during periods of wakefulness. About 60% of patients so treated have a marked improvement of mood the day after.

The main disadvantage of sleep deprivation treatment is that its beneficial effect lasts no more than 1 or 2 days in about 80% of patients. If the treatment is effective, it can be repeated once every 3 to 4 days. An absolute contraindication is a history of epileptic seizures; relative contraindications include bipolar or psychotic forms of depression.

The effectiveness of light therapy with special apparatus has been unequivocally documented only for seasonal depression (winter depression) (e7). Physical activity probably has a beneficial effect on the resolution of depression and can be recommended as a supplementary treatment, even though the scientific data to support this are as yet inadequate (e8). Treatments that are currently under investigation include aerobic training and endurance training (treadmill running) (20).

The most effective of all treatments for depression is probably electroconvulsive therapy (ECT), for which the current main indication is treatment-resistant depression (21, 22). Because of the specialized personnel and apparatus that this form of treatment requires, and also because of persistent, widespread misgivings about it, ECT is used only when multiple previous therapeutic attempts have failed, or when the patient explicitly requests it. Its beneficial effect typically appears after one to three weeks of treatment with three ECT sessions per week. Its major clinical drawback is the high rate of early recurrences in the first 16 weeks—up to 75% of patients who are not subjected to continuing treatment. With good maintenance therapy, the percentage of early recurrences can be reduced to about 35%, but such recurrences cannot be eliminated.

Conclusion
Depression can be treated effectively at present because multiple forms of treatment are available that complement each other or can be given in combination. Most of them have been well documented as effective in properly designed, controlled studies. No single form of treatment can be considered superior to all of the others, and a relatively high nonresponder rate is a common feature of all of them. Thus, the art of treating depression consists of a methodical and exhaustive use of the available therapeutic options within the framework of an algorithm-based stepwise treatment regimen (figure gif ppt), in which each sequential step of treatment is carried out for an adequate length of time and is then evaluated for effectiveness in standardized fashion. Randomized comparative studies have shown that stepwise treatment leads to more frequent and more rapid treatment responses than unstructured treatment, while simultaneously reducing the amount of psychoactive medication that must be prescribed as well as the frequency of changes in treatment strategy (7).

Conflict of interest statement
Dr. Adli has received research grants from the German Federal Ministry of Education and Research and from the following companies: Pharmacia, Pfizer, Lilly, Janssen Cilag, and Wyeth as well as honoraria from Astra Zeneca, Lilly, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, Sanofi Aventis, Wyeth, and Cyberonics. PD Dr. Bschor has received lecture honoraria from Sanofi Aventis, Lilly, esparma, GlaxoSmithKline, Pfizer, and Astra Zeneca.

Manuscript received on 4 June 2006; revised version accepted on 20 August 2008.

Translated from the original German by Ethan Taub, M.D.


For e-references please see:
www.aerzteblatt-international.de/ref4508
For a case illustration relating to this article,
see the following website:
www.aerzteblatt-international.de/0812
German-language websites for further information:
– Self-help and family groups:
www.nakos.de
– Written information for patients:
www.akdae.de/45/Depression.pdf
www.kompetenznetz-depression.de
– Information about therapeutic serum levels of antidepressants and grades of supportive evidence:
www.agnp.de Þ Arbeitsgruppen Þ AG Therapeutisches Drug-Monitoring

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Solutions to the CME questionnaire in volume 37/2008:
Kainer F, Hasbargen U: Emergencies Associated With Pregnancy and Delivery: Peripartum Hemorrhage:
1/c, 2/d, 4/c, 5/b, 7/d, 8/c, 9/c, 10/e. All answers to questions 3 and 6 were counted as correct.
1.
Rudolf S, Bermejo I, Schweiger U, Hohagen F, Härter M: Zertifizierte medizinische Fortbildung: Diagnostik depressiver Störungen. Dtsch Arztebl 2006; 103(25): A 1754–62. VOLLTEXT
2.
Pöldinger W: Kompendium der Psychopharmakotherapie. Grenzach/Baden: Hoffmann-La Roche AG 1971: 116.
3.
Kupfer DJ: Management of recurrent depression. J Clin Psychiatry 1993; 54 (suppl. 2): 29–33. MEDLINE
4.
Bauer M, Bschor T, Pfennig A, Whybrow PC, Angst J, Versiani M, Möller HJ, WFSBP Task Force on Unipolar Depressive Disorders: World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders in Primary Care. World J Biol Psychiatry 2007; 8: 67–104. MEDLINE
5.
AkdÄ – Arznei­mittel­kommission der deutschen Ärzteschaft: Empfehlungen zur Therapie der Depression. 2. Auflage. Arzneiverordnung in der Praxis (Therapieempfehlungen), Juli 2006; Band 33, Sonderheft 1.
6.
Wolfersdorf M, Mäulen B: Suizidprävention bei psychich Kranken. In: Wedler H, Wolfersdorf M, Welz R, Hrsg.: Therapie bei Suizidgefährdung. Ein Handbuch. Regensburg Roderer 1992: 175–97.
7.
Adli M, Bauer M, Rush AJ: Algorithms and collaborative-care systems for depression: are they effective and why? A systematic review. Biol Psychiatry 2006; 59: 1029–38. MEDLINE
8.
Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56–62. MEDLINE
9.
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J: An inventory for measuring depression. Arch Gen Psychiatry 1961; 4: 561–71. MEDLINE
10.
Bschor T: Definition, klinisches Bild und Epidemiologie therapieresistenter Depressionen. In: Bschor T, Hrsg.: Behandlungsmanual therapieresistente Depression. Pharmakotherapie -somatische Therapieverfahren – Psychotherapie. Stuttgart: Kohlhammer 2008: 11–6.
11.
Bschor T: Behandlung mit Antidepressiva. Pharmakologie, Therapieabschnitte. In: Bschor T, Hrsg.: Behandlungsmanual therapieresistente Depression. Pharmakotherapie – somatische Therapieverfahren – Psychotherapie. Stuttgart: Kohlhammer 2008: 28–39.
12.
Bschor T, Bauer M: Efficacy and mechanisms of action of lithium augmentation in refractory major depression. Curr Pharm Des 2006; 12: 2985–92. MEDLINE
13.
Loh A, Simon D, Kriston L, Härter M: Patientenbeteiligung bei medizinischen Entscheidungen: Effekte der partizipativen Entscheidungsfindung aus systematischen Reviews. Dtsch Arztebl 2007; 104(21): A 1483–8. MEDLINE
14.
Bschor T, Baethge C: Wechsel des Antidepressivums. In: Bschor T, Hrsg.: Behandlungsmanual therapieresistente Depression. Pharmakotherapie -somatische Therapieverfahren – Psychotherapie. Stuttgart: Kohlhammer 2008: 48–56.
15.
Adli M, Baethge C, Heinz A, Langlitz N, Bauer M: Is dose escalation of antidepressants a rational strategy after a medium-dose treatment has failed? A systematic review. Eur Arch Psychiatry Clin Neurosci 2005; 255: 387–400. MEDLINE
16.
Bschor T, Hartung HD: Antidepressiva-Kombinationsbehandlung. In: Bschor T, Hrsg.: Behandlungsmanual therapieresistente Depression. Pharmakotherapie -somatische Therapieverfahren – Psychotherapie. Stuttgart: Kohlhammer 2008: 86–101.
17.
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: 59–72. MEDLINE
18.
Leichsenring F: Are psychodynamic and psychoanalytic therapies effective? A review of empirical data. Int J Psychoanal 2005; 86: 841–68. MEDLINE
19.
de Mello MF, 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 2005; 255: 75–82. MEDLINE
20.
Knubben K, Reischies FM, Adli M, Schlattmann P, Bauer M, Dimeo F: A randomized, controlled study on the effects of a short-term endurance training programme in patients with major depression. Br J Sports Med 2007; 41: 29–33. MEDLINE
21.
UK ECT Review Group: Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003; 361:799–808. MEDLINE
22.
Folkerts H, Remschmidt H, Saß H, Sauer H, Schäfer M, Sewing K-Fr: Stellungnahme zur Elektrokrampftherapie (EKT) als psychiatrische Behandlungsmaßnahme. Dtsch Arztebl 2003; 100(8): A 504–6. MEDLINE
e1.
Bostwick JM, Pankratz VS: Affective disorders and suicide risk: A reexamination. Am J Psychiatry 2000; 157: 1925–32. MEDLINE
e2.
Dobson KS: A meta-analysis of the efficacy of cognitive therapy for depression. J Consult Clin Psychol 1989; 57: 414–9. MEDLINE
e3.
Gaffan EA, Tsaousis I, Kemp-Wheeler SM: Researcher allegiance and meta-analysis: the case of cognitive therapy for depression. J Consult Clin Psychol 1995; 63: 966–80. MEDLINE
e4.
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: 1007–13. MEDLINE
e5.
Leichsenring F: Comparative effects of short-term psychodynamic psychotherapy and cognitive-behavioral therapy in depression: a meta-analytic approach. Clin Psychol Rev 2001; 21: 401–19. MEDLINE
e6.
Crits-Christoph P: The efficacy of brief dynamic psychotherapy: a meta-analysis. Am J Psychiatry 1992; 149: 151–8. MEDLINE
e7.
Golden RN, Gaynes BN, Ekstrom RD, Hamer RM, Jacobsen FM, Suppes T, Wisner KL, Nemeroff CB: The efficacy of light therapy in the treatment of mood disorders: A review and meta-analysis of the evidence. Am J Psychiatry 2005; 162: 656–62. MEDLINE
e8.
Lawlor DA, Hopker SW: The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials. BMJ 2001; 322: 763–7. MEDLINE
Jüdisches Krankenhaus, Abteilung für Psychiatrie und Psychotherapie, Berlin: PD Dr. med. Bschor
Klinik für Psychiatrie und Psychotherapie, Charité – Universitätsmedizin Berlin, Campus Mitte: Dr. med. Adli
1. Rudolf S, Bermejo I, Schweiger U, Hohagen F, Härter M: Zertifizierte medizinische Fortbildung: Diagnostik depressiver Störungen. Dtsch Arztebl 2006; 103(25): A 1754–62. VOLLTEXT
2. Pöldinger W: Kompendium der Psychopharmakotherapie. Grenzach/Baden: Hoffmann-La Roche AG 1971: 116.
3. Kupfer DJ: Management of recurrent depression. J Clin Psychiatry 1993; 54 (suppl. 2): 29–33. MEDLINE
4. Bauer M, Bschor T, Pfennig A, Whybrow PC, Angst J, Versiani M, Möller HJ, WFSBP Task Force on Unipolar Depressive Disorders: World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders in Primary Care. World J Biol Psychiatry 2007; 8: 67–104. MEDLINE
5. AkdÄ – Arznei­mittel­kommission der deutschen Ärzteschaft: Empfehlungen zur Therapie der Depression. 2. Auflage. Arzneiverordnung in der Praxis (Therapieempfehlungen), Juli 2006; Band 33, Sonderheft 1.
6. Wolfersdorf M, Mäulen B: Suizidprävention bei psychich Kranken. In: Wedler H, Wolfersdorf M, Welz R, Hrsg.: Therapie bei Suizidgefährdung. Ein Handbuch. Regensburg Roderer 1992: 175–97.
7. Adli M, Bauer M, Rush AJ: Algorithms and collaborative-care systems for depression: are they effective and why? A systematic review. Biol Psychiatry 2006; 59: 1029–38. MEDLINE
8. Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56–62. MEDLINE
9. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J: An inventory for measuring depression. Arch Gen Psychiatry 1961; 4: 561–71. MEDLINE
10. Bschor T: Definition, klinisches Bild und Epidemiologie therapieresistenter Depressionen. In: Bschor T, Hrsg.: Behandlungsmanual therapieresistente Depression. Pharmakotherapie -somatische Therapieverfahren – Psychotherapie. Stuttgart: Kohlhammer 2008: 11–6.
11. Bschor T: Behandlung mit Antidepressiva. Pharmakologie, Therapieabschnitte. In: Bschor T, Hrsg.: Behandlungsmanual therapieresistente Depression. Pharmakotherapie – somatische Therapieverfahren – Psychotherapie. Stuttgart: Kohlhammer 2008: 28–39.
12. Bschor T, Bauer M: Efficacy and mechanisms of action of lithium augmentation in refractory major depression. Curr Pharm Des 2006; 12: 2985–92. MEDLINE
13. Loh A, Simon D, Kriston L, Härter M: Patientenbeteiligung bei medizinischen Entscheidungen: Effekte der partizipativen Entscheidungsfindung aus systematischen Reviews. Dtsch Arztebl 2007; 104(21): A 1483–8. MEDLINE
14. Bschor T, Baethge C: Wechsel des Antidepressivums. In: Bschor T, Hrsg.: Behandlungsmanual therapieresistente Depression. Pharmakotherapie -somatische Therapieverfahren – Psychotherapie. Stuttgart: Kohlhammer 2008: 48–56.
15. Adli M, Baethge C, Heinz A, Langlitz N, Bauer M: Is dose escalation of antidepressants a rational strategy after a medium-dose treatment has failed? A systematic review. Eur Arch Psychiatry Clin Neurosci 2005; 255: 387–400. MEDLINE
16. Bschor T, Hartung HD: Antidepressiva-Kombinationsbehandlung. In: Bschor T, Hrsg.: Behandlungsmanual therapieresistente Depression. Pharmakotherapie -somatische Therapieverfahren – Psychotherapie. Stuttgart: Kohlhammer 2008: 86–101.
17. 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: 59–72. MEDLINE
18. Leichsenring F: Are psychodynamic and psychoanalytic therapies effective? A review of empirical data. Int J Psychoanal 2005; 86: 841–68. MEDLINE
19. de Mello MF, 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 2005; 255: 75–82. MEDLINE
20. Knubben K, Reischies FM, Adli M, Schlattmann P, Bauer M, Dimeo F: A randomized, controlled study on the effects of a short-term endurance training programme in patients with major depression. Br J Sports Med 2007; 41: 29–33. MEDLINE
21. UK ECT Review Group: Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003; 361:799–808. MEDLINE
22. Folkerts H, Remschmidt H, Saß H, Sauer H, Schäfer M, Sewing K-Fr: Stellungnahme zur Elektrokrampftherapie (EKT) als psychiatrische Behandlungsmaßnahme. Dtsch Arztebl 2003; 100(8): A 504–6. MEDLINE
e1. Bostwick JM, Pankratz VS: Affective disorders and suicide risk: A reexamination. Am J Psychiatry 2000; 157: 1925–32. MEDLINE
e2. Dobson KS: A meta-analysis of the efficacy of cognitive therapy for depression. J Consult Clin Psychol 1989; 57: 414–9. MEDLINE
e3. Gaffan EA, Tsaousis I, Kemp-Wheeler SM: Researcher allegiance and meta-analysis: the case of cognitive therapy for depression. J Consult Clin Psychol 1995; 63: 966–80. MEDLINE
e4. 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: 1007–13. MEDLINE
e5. Leichsenring F: Comparative effects of short-term psychodynamic psychotherapy and cognitive-behavioral therapy in depression: a meta-analytic approach. Clin Psychol Rev 2001; 21: 401–19. MEDLINE
e6. Crits-Christoph P: The efficacy of brief dynamic psychotherapy: a meta-analysis. Am J Psychiatry 1992; 149: 151–8. MEDLINE
e7. Golden RN, Gaynes BN, Ekstrom RD, Hamer RM, Jacobsen FM, Suppes T, Wisner KL, Nemeroff CB: The efficacy of light therapy in the treatment of mood disorders: A review and meta-analysis of the evidence. Am J Psychiatry 2005; 162: 656–62. MEDLINE
e8. Lawlor DA, Hopker SW: The effectiveness of exercise as an intervention in the management of depression: systematic review and meta-regression analysis of randomised controlled trials. BMJ 2001; 322: 763–7. MEDLINE