Bruno Müller-Oerlinghausen

Adjunctive lithium treatment in the prevention of suicidal behaviour in depressive disorders: a randomised, placebo-controlled, 1-year trial

Objective:u2002 Evidence based on controlled studies is still limited for treatment strategies that prevent recurrence of suicide attempts. Findings from observational as well as meta‐analytic studies strongly suggest that lithium may have suicide‐protective properties.

Influence of atypical features on the quality of prophylactic effectiveness of long-term lithium treatment in bipolar disorders

OBJECTIVESnThere is still debate about whether the quality of long-term efficacy of lithium in patients with bipolar disorders is influenced by atypical features. Extended Cox regression models allow for the use of all follow-up data on diseases with multiple episodes. The aim of the present analysis was to apply the best suited of these models to analyze the influence of atypical features on the widely used outcome measure of time to recurrence in a large multicenter cohort of lithium responders established by the International Group for the Study of Lithium Treated Patients.nnnMETHODSnA conditional extended Cox model with a random frailty term was applied to the data of 336 bipolar I and II disorder patients, all of whom were responders to lithium with treatment for up to 30 years.nnnRESULTSnDifferences were found in the long-term outcome, even in patients who have demonstrated a relatively good response to lithium treatment. The hazard for recurrence was negatively influenced by the presence of atypical features, mainly mood-incongruent psychotic symptoms, interepisodic residual symptomatology, and rapid cycling.nnnCONCLUSIONSnAs a result of the findings, physicians should regularly reassess the quality of response in bipolar disorder patients with atypical features and, if necessary, modify treatment. Extended Cox regression models are well suited for evaluating long-term outcome and should be used more extensively to analyze treatment outcome in psychiatric and somatic disorders.

Is MAO-B activity in platelets associated with the occurrence of suicidality and behavioural personality traits in depressed patients?

Objective:u2002 Low platelet monoaminoxidase B (MAO‐B) activity has been associated with various forms of impulsive behaviour and suicidality. The present study investigated the relationship between MAO‐B activity in platelets and aspects of suicidality in depressed patients and controls.

Psychopharmaka zur Behandlung suizidaler Patienten und zur Suizidprävention

Suicidality represents a frequent phenomenon in affective and psychotic disorders but the treatment of acute and chronic suicidality is still a controversial issue. Especially the efficacy of antidepressant and neuroleptic drugs for prevention of suicide continues to be debated. There is a lack of evidence due to limitations of methodological studies and ethical concerns are a major issue. Considering methodological problems in the conducted studies the often insufficiently valued differentiation between suicidal thoughts and actual suicidal behavior has to be emphasized. With the exception of lithium and clozapine suicide-preventing effects of antidepressants and neuroleptics could not yet be demonstrated. Regarding new antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) even the possible new onset of suicidal thoughts and ideations as an adverse effect needs to be stressed. Considering the frequent occurrence of suicidality the currently available evidence is undoubtedly insufficient. The improvement of study concepts and especially a more differentiated consideration of the vague term suicidality seems to be essential. An underrepresentation of the evidence-based therapeutic options with lithium and clozapine in the treatment of suicidal patients needs to be avoided.ZusammenfassungDie Behandlung suizidaler Patienten stellt ein häufiges, zumeist akutpsychiatrisches Problem dar. Vor dem Hintergrund der Häufigkeit dieses Phänomens imponiert die aktuelle Datenlage zu suizidverhindernden Wirkeffekten von Psychopharmaka insgesamt unzureichend und enttäuschend. Mit Ausnahme von Lithium und Clozapin ist eine suizidverhindernde Wirkung von Psychopharmaka nicht belegt, ja nach bislang vorliegenden Studien unwahrscheinlich. Nach wie vor fehlen zum einen kontrollierte, randomisierte Studien, zum anderen limitieren ethische und methodische Probleme die klinische Forschung auf diesem Gebiet, was insbesondere an der aktuellen Datenlage zu den immer wieder behaupteten suizidpräventiven Wirkeffekten von Antidepressiva deutlich wird. Im Rahmen der Akutbehandlung ist unter Antidepressiva eine Reduktion der depressiven Störung zugeordneten Suizidgedanken möglich, jedoch muss die ebenfalls mögliche suizidprovozierende Wirkung insbesondere der neueren Antidepressiva gleichzeitig berücksichtigt werden. Der zeitnahen symptomatischen Behandlung psychomotorischer Erregung und Ängstlichkeit muss in Form einer sedierenden Pharmakotherapie mit Benzodiazepinen oder niedrig-potenten Neuroleptika höchste Bedeutung beigemessen werden. Im Rahmen der Erhaltungstherapie sollten Patienten vor dem Hintergrund der aktuellen Datenlage nach stattgehabten Suizidversuchen oder chronischer Suizidalität im Rahmen bipolarer oder unipolarer affektiver Erkrankungen von den positiven Effekten einer Behandlung mit Lithium und im Rahmen psychotischer Erkrankungen einer Behandlung mit Clozapin möglichst überzeugt werden.AbstractSuicidality represents a frequent phenomenon in affective and psychotic disorders but the treatment of acute and chronic suicidality is still a controversial issue. Especially the efficacy of antidepressant and neuroleptic drugs for prevention of suicide continues to be debated. There is a lack of evidence due to limitations of methodological studies and ethical concerns are a major issue. Considering methodological problems in the conducted studies the often insufficiently valued differentiation between suicidal thoughts and actual suicidal behavior has to be emphasized. With the exception of lithium and clozapine suicide-preventing effects of antidepressants and neuroleptics could not yet be demonstrated. Regarding new antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) even the possible new onset of suicidal thoughts and ideations as an adverse effect needs to be stressed. Considering the frequent occurrence of suicidality the currently available evidence is undoubtedly insufficient. The improvement of study concepts and especially a more differentiated consideration of the vague term “suicidality” seems to be essential. An underrepresentation of the evidence-based therapeutic options with lithium and clozapine in the treatment of suicidal patients needs to be avoided.

Genetische Tests zur Steuerung der Behandlung mit Antidepressiva

In clinical practice, there is axa0need for axa0more individualized selection of antidepressants and adequate dosage. The investigation of pharmacokinetically relevant genes is a promising approach to assist this selection. In the past 2 years, two commercially available tests have been subject of advertisement, a test from Stada, which analyses variants of the cytochrome P450 isoenzymes CYP2D6 and CYP2C19 and a test from HMNC Brain Health, which analyses variants of the ABCB1 gene. The costs for both kits are not covered by the statutory health insurance and it is therefore proposed that the patients are invoiced directly in the form of individual healthcare payment. The companies claim that by applying the tests antidepressant treatment failure can be avoided and that patients will respond faster to the antidepressant used. These claims are not based on appropriate clinical trials, which are either lacking or reveal conflicting results. Hence, the routine use of these tests is not recommended. In accordance with the German S3 Guideline for unipolar depression, therapeutic drug monitoring (TDM) of serum levels should be carried out in cases of non-response to an antidepressant with adequate dosage and duration. As axa0rule the costs for TDM are covered by the statutory health insurance. Cytochrome P450 genotyping is only indicated when the serum level is not within the expected range and other reasons to explain this discrepancy are excluded. Many laboratories provide these analyses and in individual cases the costs are reimbursed by the statutory health insurance. Further research should be carried out to investigate the importance of the ABCB1 gene for the treatment with antidepressants.ZusammenfassungKlinisch besteht der Bedarf, in der Antidepressivabehandlung das Präparat und die individuell adäquate Dosierung gezielter auswählen zu können. Die Untersuchung pharmakokinetisch relevanter Gene ist hierfür ein vielversprechender Ansatz. In den vergangenen zwei Jahren wurden insbesondere ein Test der Firma Stada, der Varianten der Zytochrom-P450-Isoenzyme CYP2D6 und CYP2C19 untersucht, und ein Test der HMNC Brain Health GmbH, der Varianten des ABCB1-Gens untersucht, bei Ärzten beworben. Beide Tests werden nicht von den gesetzlichen Krankenversicherungen vergütet und dahingehend beworben, sie in Form von IGeL-Leistungen den Patienten selbst in Rechnung zu stellen. Die Anbieter äußern für beide Tests, dass hierdurch auf erfolglose Antidepressivabehandlungen verzichtet werden könne und dass es zu einem schnelleren Ansprechen auf die Behandlung komme. Diese Aussagen sind durch geeignete klinische Studien nicht gedeckt, da solche Studien fehlen bzw. widersprüchliche Ergebnisse liefern. Es wird daher vom routinemäßigen Einsatz dieser Tests abgeraten. In Übereinstimmung mit der S3-Leitlinie Unipolare Depression wird empfohlen, bei Nonresponse auf eine in Dauer und Dosis adäquat durchgeführte Antidepressivamedikation eine Serumspiegelbestimmung durchzuführen. Diese wird in der Regel von den gesetzlichen Krankenkassen übernommen. Nur bei außerhalb des Erwartungsbereichs liegenden Serumspiegeln und Ausschluss anderer Ursachen ist eine Zytochrom-P450-Genotypisierung sinnvoll. Diese kann in vielen Laboren durchgeführt werden, wofür in Einzelfällen die Kosten von den gesetzlichen Krankenkassen übernommen werden. Die weitere Beforschung der Bedeutung des ABCB1-Gens für die Behandlung mit Antidepressiva ist sinnvoll.AbstractIn clinical practice, there is axa0need for axa0more individualized selection of antidepressants and adequate dosage. The investigation of pharmacokinetically relevant genes is a promising approach to assist this selection. In the past 2 years, two commercially available tests have been subject of advertisement, a test from Stada, which analyses variants of the cytochrome P450 isoenzymes CYP2D6 and CYP2C19 and a test from HMNC Brain Health, which analyses variants of the ABCB1 gene. The costs for both kits are not covered by the statutory health insurance and it is therefore proposed that the patients are invoiced directly in the form of individual healthcare payment. The companies claim that by applying the tests antidepressant treatment failure can be avoided and that patients will respond faster to the antidepressant used. These claims are not based on appropriate clinical trials, which are either lacking or reveal conflicting results. Hence, the routine use of these tests is not recommended. In accordance with the German S3 Guideline for unipolar depression, therapeutic drug monitoring (TDM) of serum levels should be carried out in cases of non-response to an antidepressant with adequate dosage and duration. As axa0rule the costs for TDM are covered by the statutory health insurance. Cytochrome P450 genotyping is only indicated when the serum level is not within the expected range and other reasons to explain this discrepancy are excluded. Many laboratories provide these analyses and in individual cases the costs are reimbursed by the statutory health insurance. Further research should be carried out to investigate the importance of the ABCB1 gene for the treatment with antidepressants.

[Anti-suicidal effect of lithium: current state of research and its clinical implications for the long-term treatment of affective disorders].

Treatment of patients with suicidal behaviour is one of the most challenging tasks for health care professionals. Due to the high mortality, morbidity and costs related to suicide, the development of treatment and preventive strategies for suicidal behaviour have been a focus of psychiatric research. For lithium, one of the oldest pharmacological agents used in psychiatry, anti-suicidal effects have been found since the early 90s in many international studies. Despite this unambiguous evidence and corresponding recommendations in national and international guidelines for the acute and maintenance therapy of affective disorders, the use of lithium is still underrepresented. The following article provides a review of studies investigating the anti-suicidal effects of lithium in affective disorders. Clinical implications for the treatment of affective disorders are discussed.ZusammenfassungDie Behandlung suizidaler Patienten gehört zu den anspruchvollsten Herausforderungen für alle Professionen im Gesundheitswesen. Aufgrund der enormen gesundheitspolitischen Bedeutung ist die Therapie suizidalen Verhaltens in den letzten Jahren mehr und mehr in den Mittelpunkt psychiatrischer Forschung gerückt und nimmt einen größeren Stellenwert in der Erarbeitung von Behandlungs- und Präventionsstrategien ein. Für Lithium als eine der ältesten in der Psychiatrie verwendeten psychotropen Substanzen wurde seit Anfang der 1990iger Jahre ein eigenständiger, im Vergleich zu anderen Psychopharmaka wahrscheinlich spezifischer antisuizidaler Effekt nachgewiesen. Trotz dieses Wissens und des heute ebenfalls in nationalen und internationalen Leitlinien dokumentierten Stellenwertes von Lithium in der Akut- und Erhaltungstherapie affektiver Störungen ist Lithium hinsichtlich seiner Verschreibungshäufigkeit im Vergleich zu anderen Psychopharmaka unterrepräsentiert. Der folgende Beitrag gibt eine chronologische Zusammenfassung aller wichtigen Studien, welche die antisuizidale Wirkung von Lithium untersucht haben, und diskutiert die daraus resultierenden therapeutischen Implikationen.SummaryTreatment of patients with suicidal behaviour is one of the most challenging tasks for health care professionals. Due to the high mortality, morbidity and costs related to suicide, the development of treatment and preventive strategies for suicidal behaviour have been a focus of psychiatric research. For lithium, one of the oldest pharmacological agents used in psychiatry, anti-suicidal effects have been found since the early 90s in many international studies. Despite this unambiguous evidence and corresponding recommendations in national and international guidelines for the acute and maintenance therapy of affective disorders, the use of lithium is still underrepresented. The following article provides a review of studies investigating the anti-suicidal effects of lithium in affective disorders. Clinical implications for the treatment of affective disorders are discussed.

Lithium Clinics in Berlin and Dresden: a 50-Year Experience

Although lithiums serendipitous discovery as a medication for depression dates back more than 200 years, the first scientific evidence that it prevents mania and depression arose only in the 1960s. However, at that time there was a lack of knowledge about how to administer and monitor lithium therapy safely and properly. The lithium clinics in Dresden and Berlin were remarkably similar in their beginnings in the late 1960s regarding patient numbers and scientific expertise without being aware of one another due to the Iron Curtain separating Germany into a western and eastern part until 1990. In what were initially lithium-care programs run independently from one another, the lithium clinics embedded in academic settings in Dresden and Berlin represent a milestone in the history of psychopharmacological treatment of affective disorders in Germany and trailblazers for todays lithium therapy. Nowadays, lithiums clinical applications are unquestioned, such as its use in strategies to prevent mood episodes and suicide, and to treat depression. The extensively documented knowledge of lithium treatment is the fruit of more than 50 years of observing disease courses and of studying side effects and influencing factors of lithium prophylaxis. Its safe and proper administration-in determining the correct indication, baseline and follow-up examinations, recommended dosages, monitoring, or the management of side effects-is well established. Subsequently, both national and international guidelines continue recommending lithium as the gold standard in treating patients with unipolar and bipolar disorders.

Psychopharmaka zur Behandlung suizidaler Patienten und zur Suizidprävention@@@Psychopharmaceuticals for treatment of suicidal patients and for suicide prevention

Suicidality represents a frequent phenomenon in affective and psychotic disorders but the treatment of acute and chronic suicidality is still a controversial issue. Especially the efficacy of antidepressant and neuroleptic drugs for prevention of suicide continues to be debated. There is a lack of evidence due to limitations of methodological studies and ethical concerns are a major issue. Considering methodological problems in the conducted studies the often insufficiently valued differentiation between suicidal thoughts and actual suicidal behavior has to be emphasized. With the exception of lithium and clozapine suicide-preventing effects of antidepressants and neuroleptics could not yet be demonstrated. Regarding new antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) even the possible new onset of suicidal thoughts and ideations as an adverse effect needs to be stressed. Considering the frequent occurrence of suicidality the currently available evidence is undoubtedly insufficient. The improvement of study concepts and especially a more differentiated consideration of the vague term suicidality seems to be essential. An underrepresentation of the evidence-based therapeutic options with lithium and clozapine in the treatment of suicidal patients needs to be avoided.ZusammenfassungDie Behandlung suizidaler Patienten stellt ein häufiges, zumeist akutpsychiatrisches Problem dar. Vor dem Hintergrund der Häufigkeit dieses Phänomens imponiert die aktuelle Datenlage zu suizidverhindernden Wirkeffekten von Psychopharmaka insgesamt unzureichend und enttäuschend. Mit Ausnahme von Lithium und Clozapin ist eine suizidverhindernde Wirkung von Psychopharmaka nicht belegt, ja nach bislang vorliegenden Studien unwahrscheinlich. Nach wie vor fehlen zum einen kontrollierte, randomisierte Studien, zum anderen limitieren ethische und methodische Probleme die klinische Forschung auf diesem Gebiet, was insbesondere an der aktuellen Datenlage zu den immer wieder behaupteten suizidpräventiven Wirkeffekten von Antidepressiva deutlich wird. Im Rahmen der Akutbehandlung ist unter Antidepressiva eine Reduktion der depressiven Störung zugeordneten Suizidgedanken möglich, jedoch muss die ebenfalls mögliche suizidprovozierende Wirkung insbesondere der neueren Antidepressiva gleichzeitig berücksichtigt werden. Der zeitnahen symptomatischen Behandlung psychomotorischer Erregung und Ängstlichkeit muss in Form einer sedierenden Pharmakotherapie mit Benzodiazepinen oder niedrig-potenten Neuroleptika höchste Bedeutung beigemessen werden. Im Rahmen der Erhaltungstherapie sollten Patienten vor dem Hintergrund der aktuellen Datenlage nach stattgehabten Suizidversuchen oder chronischer Suizidalität im Rahmen bipolarer oder unipolarer affektiver Erkrankungen von den positiven Effekten einer Behandlung mit Lithium und im Rahmen psychotischer Erkrankungen einer Behandlung mit Clozapin möglichst überzeugt werden.AbstractSuicidality represents a frequent phenomenon in affective and psychotic disorders but the treatment of acute and chronic suicidality is still a controversial issue. Especially the efficacy of antidepressant and neuroleptic drugs for prevention of suicide continues to be debated. There is a lack of evidence due to limitations of methodological studies and ethical concerns are a major issue. Considering methodological problems in the conducted studies the often insufficiently valued differentiation between suicidal thoughts and actual suicidal behavior has to be emphasized. With the exception of lithium and clozapine suicide-preventing effects of antidepressants and neuroleptics could not yet be demonstrated. Regarding new antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) even the possible new onset of suicidal thoughts and ideations as an adverse effect needs to be stressed. Considering the frequent occurrence of suicidality the currently available evidence is undoubtedly insufficient. The improvement of study concepts and especially a more differentiated consideration of the vague term “suicidality” seems to be essential. An underrepresentation of the evidence-based therapeutic options with lithium and clozapine in the treatment of suicidal patients needs to be avoided.

Psychopharmaceuticals for treatment of suicidal patients and for suicide prevention

Suicidality represents a frequent phenomenon in affective and psychotic disorders but the treatment of acute and chronic suicidality is still a controversial issue. Especially the efficacy of antidepressant and neuroleptic drugs for prevention of suicide continues to be debated. There is a lack of evidence due to limitations of methodological studies and ethical concerns are a major issue. Considering methodological problems in the conducted studies the often insufficiently valued differentiation between suicidal thoughts and actual suicidal behavior has to be emphasized. With the exception of lithium and clozapine suicide-preventing effects of antidepressants and neuroleptics could not yet be demonstrated. Regarding new antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) even the possible new onset of suicidal thoughts and ideations as an adverse effect needs to be stressed. Considering the frequent occurrence of suicidality the currently available evidence is undoubtedly insufficient. The improvement of study concepts and especially a more differentiated consideration of the vague term suicidality seems to be essential. An underrepresentation of the evidence-based therapeutic options with lithium and clozapine in the treatment of suicidal patients needs to be avoided.ZusammenfassungDie Behandlung suizidaler Patienten stellt ein häufiges, zumeist akutpsychiatrisches Problem dar. Vor dem Hintergrund der Häufigkeit dieses Phänomens imponiert die aktuelle Datenlage zu suizidverhindernden Wirkeffekten von Psychopharmaka insgesamt unzureichend und enttäuschend. Mit Ausnahme von Lithium und Clozapin ist eine suizidverhindernde Wirkung von Psychopharmaka nicht belegt, ja nach bislang vorliegenden Studien unwahrscheinlich. Nach wie vor fehlen zum einen kontrollierte, randomisierte Studien, zum anderen limitieren ethische und methodische Probleme die klinische Forschung auf diesem Gebiet, was insbesondere an der aktuellen Datenlage zu den immer wieder behaupteten suizidpräventiven Wirkeffekten von Antidepressiva deutlich wird. Im Rahmen der Akutbehandlung ist unter Antidepressiva eine Reduktion der depressiven Störung zugeordneten Suizidgedanken möglich, jedoch muss die ebenfalls mögliche suizidprovozierende Wirkung insbesondere der neueren Antidepressiva gleichzeitig berücksichtigt werden. Der zeitnahen symptomatischen Behandlung psychomotorischer Erregung und Ängstlichkeit muss in Form einer sedierenden Pharmakotherapie mit Benzodiazepinen oder niedrig-potenten Neuroleptika höchste Bedeutung beigemessen werden. Im Rahmen der Erhaltungstherapie sollten Patienten vor dem Hintergrund der aktuellen Datenlage nach stattgehabten Suizidversuchen oder chronischer Suizidalität im Rahmen bipolarer oder unipolarer affektiver Erkrankungen von den positiven Effekten einer Behandlung mit Lithium und im Rahmen psychotischer Erkrankungen einer Behandlung mit Clozapin möglichst überzeugt werden.AbstractSuicidality represents a frequent phenomenon in affective and psychotic disorders but the treatment of acute and chronic suicidality is still a controversial issue. Especially the efficacy of antidepressant and neuroleptic drugs for prevention of suicide continues to be debated. There is a lack of evidence due to limitations of methodological studies and ethical concerns are a major issue. Considering methodological problems in the conducted studies the often insufficiently valued differentiation between suicidal thoughts and actual suicidal behavior has to be emphasized. With the exception of lithium and clozapine suicide-preventing effects of antidepressants and neuroleptics could not yet be demonstrated. Regarding new antidepressant drugs, such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) even the possible new onset of suicidal thoughts and ideations as an adverse effect needs to be stressed. Considering the frequent occurrence of suicidality the currently available evidence is undoubtedly insufficient. The improvement of study concepts and especially a more differentiated consideration of the vague term “suicidality” seems to be essential. An underrepresentation of the evidence-based therapeutic options with lithium and clozapine in the treatment of suicidal patients needs to be avoided.