Felix HaslerFelix HaslerKlinische ForschungKlinische Forschung

HRCHRC ZürichZürich

The Creation ofThe Creation ofPsychopharmacology IIIPsychopharmacology III

David Healy, Harvard University Press, 2002David Healy, Harvard University Press, 2002

Von den Neuroleptika zu den Antipsychotica

Pipamperone (Dipiperon®)

Risperidon (Risperdal®)1993

Von den Neuroleptika zu den Antipsychotica

Lundbeck: Sertindol (Serdolect® 1996)

Komplikation: Verlängerung des QT-Intervalls

Exkurs Herzphysiologie

Erstes EKG (1903)

Sertindol (Serdolect® 1996)

Komplikation: Verlängerung des QT-Intervalls

Rezeptorbindungs-Profil Sertindol

(Seroquel)

ECDEU: Empirische Wissenschaft

Max Fink Nathan Kline Leo Hollister

Positive symptoms Negative symptoms

Cognitive symptoms Behavioral symptoms

„EGO-DISORDER“

Positive and negative schizophrenia

Externe / Interne StimuliExterne / Interne Stimuli Externe / Interne StimuliExterne / Interne Stimuli

Filter intaktFilter intakt Filter „gestört“Filter „gestört“

Thalamus

Frontal Cortex

Striatum Pallidum

Prim.-sensori.Cortex

Extro-ceptive& intro-ceptive Stimuli

CSTC-Loop and Sensorimotor GatingCSTC-Loop and Sensorimotor Gating

Hippocampus

-Glu

RA

+5-HT +5-HT +5-HTVTA

+DA-DA

Parietal cortex

Temporal cortex

C. m.

Agid O, Mamo D, Ginovart N, Vitcu I, Wilson AA, Zipursky RB, Kapur S (2007) Agid O, Mamo D, Ginovart N, Vitcu I, Wilson AA, Zipursky RB, Kapur S (2007) Striatal vs extrastriatal dopamine D2 receptors in antipsychotic response - aStriatal vs extrastriatal dopamine D2 receptors in antipsychotic response - adouble-blind PET study in schizophrenia.double-blind PET study in schizophrenia. Neuropsychopharmacology 32: 1209-15Neuropsychopharmacology 32: 1209-15

D2-Besetzung durch Neuroleptika und D2-Besetzung durch Neuroleptika und klinische Wirksamkeit Iklinische Wirksamkeit I

D2-Besetzung durch Neuroleptika und D2-Besetzung durch Neuroleptika und klinische Wirksamkeit IIklinische Wirksamkeit II

Fluoxetin (Prozac®)Klassischer SSRI(Selektiver Serotonin-Wiederaufnahme-Hemmer)

„Symbol of the 90ies“

Figure 2. Mean Standardized Improvement as a Function of Initial Severity and Treatment Group.Drug improvement is portrayed as red triangles around their solid red regression line and placebo improvement as blue circles around their dashed blue regression line; the green shaded area indicates the point at which comparisons of drug versus placebo reach the NICE clinicalsignificance criterion of d ¼ 0.50. Plotted values are sized according to their weight in analyses.

Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug AdministrationKirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, et al., PLoS Medicine Vol. 5, No. 2, e45 doi:10.1371/journal.pmed.0050045

Figure 3. Mean Standardized Improvement as a Function of Initial Severity and Treatment Group, Including Only Trials Whose Samples Had High Initial Severity Drug improvement is portrayed as red triangles around their solid red regression line and placebo improvement as blue circles around their dashed blue regression line; the green shaded area indicates the point at which comparisons of drug versus placebo reach the NICE clinical significance criterion of d ¼ 0.50. Plotted values are sized according to their weight in analyses.doi:10.1371/journal.pmed.0050045.g003

Neue Allianzen

„Management of behaviour“