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The British Journal of Psychiatry (2009)194, 252–259. doi: 10.1192/bjp.bp.108.057554
Current episode duration, weeks: mean (s.d.)
Montgomery–A˚sberg Depression Rating Scale
Hamilton Rating Scale for Depression–17
SSRI, selective serotonin reuptake inhibitor.
Antidepressant dosage in milligrams by study week
12 for MADRS (w2(1)=5.87, P=0.015) and BDI (w2(1)=7.14,
Response and remission with last observation
Analysis of clinical trials with missing data has traditionally been
performed with the last observation carried forward (LOCF)procedure. It has been demonstrated that this approach introduces
We caution against the interpretation of the significant differences
a systematic bias and underestimates the level of uncertainty.1,2
in LOCF analysis for several reasons. First, unlike the mixed-effect
Therefore, LOCF is not considered a valid analysis by many
models, the LOCF analysis does not take into account variations
experts in the field.3 However, some researchers still prefer LOCF
between study centres. Second, LOCF introduces systematic bias
analysis for the purposes of simplicity and comparability with
in the context of drop out.1–3 Indeed, the results of LOCF analysis
previous reports. Therefore, we report Montgomery–A˚sberg
replicate a previous report by Joyce et al5 and illustrate the effect
Depression Rating Scale (MADRS), Hamilton Rating Scale for
of differential attrition on the LOCF analysis. The meaning of
Depression–17 (HRSD) and Beck Depression Inventory (BDI) at
differences in ‘remission’ in the absence of any significant
week 8 and week 12 with the LOCF in cases of drop out, switching
differences in ‘response’ or in the rate of change is questionable.
or missing data. We report the rates of response (50% symptom
This discrepancy between analyses is explained by inequality in
reduction) and remission (HRSD=7; MDRS=10; BDI=10) accord-
baseline severity among non-randomly allocated participants
and differential attrition among randomly allocated participants.
Lane P. Handling drop-out in longitudinal clinical trials: a comparison of theLOCF and MMRM approaches. Pharm Stat 2008; 7: 93–106.
Depression severity levels at weeks 8 and 12 with missing valuesinputted following the LOCF rule are presented in online Table
Mallinckrodt CH, Clark WS, David SR. Accounting for dropout bias usingmixed-effects models. J Biopharm Stat 2001; 11: 9–21.
DS3. There were no significant between-drug differences in
Leon AC, Mallinckrodt CH, Chuang-Stein C, Archibald DG, Archer GE, Chartier
response (defined as 50% score reduction on MADRS, HRSD–17
K. Attrition in randomized controlled clinical trials: methodological issues in
or BDI). More participants allocated to escitalopram reached cri-
psychopharmacology. Biol Psychiatry 2006; 59: 1001–5.
teria for remission at week 8 on MADRS (w2(1)=4.02, P=0.045),
Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW, et al.
HDRS (w2(1)=5.69, P=0.017) and BDI (w2(1)=5.69, P=0.017).
Conceptualization and rationale for consensus definitions of terms in major
More participants allocated to escitalopram reached criteria for
depressive disorder. Remission, recovery, relapse, and recurrence. Arch GenPsychiatry 1991; 48: 851–5.
(w2(1)=11.05, P=0.001) and on BDI (w2(1)=3.84, P=0.050).
Joyce PR, Mulder RT, Luty SE, Sullivan PF, McKenzie JM, Abbott RM, et al.
Patterns and predictors of remission, response and recovery in major
Analysis of the randomised sample confirmed differences in rates
depression treated with fluoxetine or nortriptyline. Aust N Z J Psychiatry
of remission at week 8 on BDI (w2(1)=5.57, P=0.018) and at week
Descriptive statistics, response and remission with last observation carried forward (LOCF) procedure
MADRS, Montgomery–A˚sberg Depression Rating Scale; HDRS–17, Hamilton Rating Scale for Depression (17 items); BDI, Beck Depression Inventory.
ACTA SESION ORDINARIA Nº 04/ 2013 CONCEJO MUNICIPAL Viernes 01.02.2013 En Yumbel, en la Sala de Sesiones del Municipio, a las 09:00 horas del día Viernes 01 de Febrero del año 2013, se da inicio a la Sesión Ordinaria Nº 04 del presente año, del Concejo Municipal, presidida por el Alcalde Camilo Enrique Cabezas Vega, y con asistencia de los Concejales señores/as, Gacitúa, Jiménez,
Review Paper Examen critique A review of olanzapine-associated toxicity and fatality in overdose Pierre Chue, MB BCh; Peter Singer, BSc, PhD Chue — Department of Psychiatry, University of Alberta and Alberta Hospitals; Singer — Office of the Chief MedicalExaminer, Edmonton, Alta. Objective: Given the increasing use of atypical antipsychotics in psychiatric populations and th