Antidepressive Effectiveness of Amisulpride, Aripiprazole, and Olanzapine in Patients With Schizophrenia Spectrum Disorders: A Secondary Outcome Analysis of a Pragmatic, Randomized Trial (BeSt InTro)

The rate of depression in schizophrenia is considerable, varying from 7% to 75%,1 and depressive symptoms are associated with a poorer outcome.2 Depressive symptoms reduce quality of life,3 adherence to treatment,4 and chance of recovery,5 while boosting unemployment, risk of relapse,6 frequency of self-harm,7,8 and suicide.9,10 Depressive symptoms are particularly prevalent in the acute and subacute phase of schizophrenia spectrum disorders, making this a highly relevant phase of illness for investigating differential antidepressive efficacy of psychotropics.11,12

Despite the massive impact of depression in schizophrenia, treatment guidelines are often not focused on the subject.13 However, some guidelines and algorithms14–16 give helpful advice, for instance to evaluate the effect of antipsychotic treatment on depressive symptoms during a psychotic episode before introducing antidepressant drugs. Although prescribing antidepressants for depression in schizophrenia is frequently recommended,13 a recent meta-analysis concluded that treatment effects are modest.17 Evidence for nonpharmacological interventions such as physical activity and cognitive behavioral therapy, electroconvulsive treatment, and transcranial magnetic stimulation for depression in schizophrenia is limited.18–24 Given the modest effect size of antidepressants and attempting to limit superfluous polypharmacy with antidepressants, the antidepressive potential of atypical antipsychotics25–27 is of clinical importance.14,15 Knowledge gaps remain, however.

Antipsychotic drugs have documented antidepressive effects in bipolar depression,27 in treatment-resistant depression,28 and in schizophrenia.26,29,30 Several pharmacological actions of atypical antipsychotics indicate an antidepressive potential, particularly for drugs with pronounced 5-HT2A–antagonistic properties such as aripiprazole, olanzapine, and clozapine, or drugs with limbic selectivity, and that increase dopamine in the limbic system by blocking α2-presynaptic receptors, for example, amisulpride.31–33 Additional properties relevant for the antidepressant effects are, for amisulpride, its potent competitive antagonism on 5-HT7A receptors34,35; for olanzapine, activation of dopamine D1 receptors and facilitated NMDA and AMPA-induced currents in pyramidal cells in combination with fluoxetine36 and 5-HT2C–antagonistic property, which facilitates effects on extracellular levels of DA and NA in the prefrontal cortex37; and for aripiprazole, a partial agonistic effect on 5-HT1A receptors; antagonistic effects on 5-HT2A receptors with a partial dopamine D2/D3 agonist effect; and affinity for dopamine D4, 5-HT2C and 5-HT7, α1-adrenergic, and histamine H1 receptors38 may contribute. Antidepressant-like effects have been documented for some antipsychotic drugs, for example, quetiapine and ziprasidone, that is, the inhibition of transmembrane monoamine transporters, which increases levels of serotonin and/or norepinephrine.39–41 First-generation antipsychotics (FGAs) are generally not recommended in the presence of depressive symptoms due to a greater likelihood of extrapyramidal adverse effects such as akinesia and inhibited expression.15,42 Antipsychotics with a high degree of dopaminergic D2-receptor blockade have been linked to dysphoria.15,43–45 Finally, depression after a psychotic episode—postpsychotic depression—occurs in some patients.46 We have previously shown a significant reduction of depressive symptoms in acute psychotic episodes for olanzapine, quetiapine, risperidone, and ziprasidone, albeit with no significant differences between the drugs.47 Half of the participants with depressive symptoms at study inclusion had persistent depressive symptoms.48

Amisulpride,44aripiprazole,49 and olanzapine50,51 have all demonstrated superior antidepressive effectiveness in schizophrenia compared with placebo, risperidone, and haloperidol. However, only amisulpride and olanzapine have been compared directly,52–54 with nonsignificant differences on depressive symptoms. Our limited knowledge of which treatment to choose for patients with a current psychotic episode and depressive symptoms indicates a need for more head-to-head clinical trials comparing atypical antipsychotics. Thus, we aimed to investigate antidepressive effectiveness in a randomized clinical trial of atypical antipsychotics.

The decision to investigate amisulpride, aripiprazole, and olanzapine in the BeSt InTro was primarily because of hypotheses regarding the primary outcome: antipsychotic effectiveness.55–58Olanzapine and amisulpride have proven to be among the most effective in meta-analyses of antipsychotic efficacy.59,60 However, the distinct pharmacologic differences between these 3 drugs are also highly relevant with regards to the comparison of their antidepressive effectiveness.31,32,61Amisulpride, aripiprazole, and olanzapine were all significantly superior to FGAs for depressive symptom improvement in a review by Leucht et al.30 However, they have not previously been investigated head-to-head in a clinical trial for antidepressive effectiveness in schizophrenia spectrum disorders.

The primary aim of this article was to investigate overall differences in antidepressive effectiveness among amisulpride, aripiprazole, and olanzapine as measured by the change of the Calgary Depression Scale for Schizophrenia (CDSS) sum score in patients with a current psychotic episode within schizophrenia spectrum disorder. The CDSS was a secondary outcome measure in the BeSt InTro trial. Further objectives were to investigate differences in antidepressive effectiveness between the study drugs in the subgroup of participants with pronounced depressive symptoms at inclusion and conducting sensitivity analyses.

MATERIALS AND METHODS Study Design

BeSt InTro is a multicenter, randomized, rater-blind head-to-head comparison of amisulpride, aripiprazole, and olanzapine with a 1-year follow-up.55 The aim was to include patients with ongoing psychosis who were eligible for oral antipsychotic drug treatment. Depressive symptom change was a secondary outcome measure. Participants were consecutively recruited from 4 participating centers (Bergen, Trondheim, and Stavanger in Norway and Innsbruck in Austria). Inclusion took place between October 20, 2011, and December 21, 2017.

Sample

Eligible patients were ≥18 years fulfilling diagnostic criteria within the schizophrenia spectrum F20–29 according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), with symptoms of ongoing psychosis defined by a score of 4 or more on at least one of the following Positive and Negative Syndrome Scale (PANSS)62 items: P1 (delusions), P3 (hallucinations), P5 (grandiosity), P6 (suspiciousness/persecution), or G9 (unusual thought content), as scored on the basis of a conducted Structured Clinical Interview for the PANSS (SCI-PANSS) interview.63 This and very similar definitions of ongoing psychosis have been applied in former trials.64,65 All candidates were deemed eligible for oral antipsychotic drug treatment by their attending psychiatrist. Trial participants had to be capable of providing written informed consent before inclusion. Exclusion criteria were inability to understand spoken site language, organic psychosis, hypersensitivity to the active substances, pregnancy, or breastfeeding. Additional drug-specific exclusion criteria for amisulpride were as follows: concomitant prolactin-dependent tumors, for example, pituitary gland prolactinomas and breast cancer; pheochromocytoma; and lactation and combination with medications, which could induce torsade de pointes. Exclusion criteria for olanzapine were a known risk of narrow-angle glaucoma.

Study Medication and Randomization

Study medications were administered as oral tablets and according to the respective summary of product characteristics. Dosing intervals were for amisulpride 50–1200 mg/d, aripiprazole 5–30 mg/d, and olanzapine 2.5–20 mg/d. Serum levels were measured at study visits to determine if effective concentrations were achieved and as a measure of medication adherence.

The randomization was open to the patients and their attending psychiatrist and wider clinical treatment team, whereas the assessment research team remained blinded. Participants were randomized to a sequence, listing the study drugs in a random sequence. These sequences were sealed in separate envelopes, numbered consecutively, and opened by the attending psychiatrist when a new participant was included. If the first study drug in the sequence was inapplicable due to previous negative experience, the next study drug in the sequence was offered and the reason for not selecting the first drug was noted. The same principle applied if the next listed study drug was also deemed inappropriate. The first study drug in the sequence defined the randomization group, which served as the basis for the intention-to-treat (ITT) analyses. The attending physician or psychiatrist made the decisions concerning initiation, dosing, and changes or termination of the study medication.

In line with usual clinical practice, concomitant medications were permitted with the exception of additional antipsychotic drugs. This is in line with leading treatment guidelines, which advocate antipsychotic monotherapy.14,66,67 However, cross-titration during antipsychotic drug switches was permitted.

Measures

We assessed patients at inclusion; 1, 3, and 6 weeks; and 3, 6, 9, and 12 months. Diagnoses were based on a conducted Structured Clinical Interview (SCID) for the DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; American Psychiatric Association). ICD-10 diagnoses were extracted by trained, experienced psychiatrists and psychologists from the SCID interview and information from hospital records based on the ICD-10 research criteria.

The BeSt InTro trial was designed with the reduction of psychotic symptoms (PANSS) as the primary outcome, with results previously published.55 The outcome measure in this article is the sum score of the CDSS.68 The CDSS was conducted at all study visits as a separate semistructured interview and consists of 9 items scored on a 0 to 3 range. The CDSS is specifically developed to assess the level of depressive symptoms in schizophrenia as depression rating scales used in mood disorders may not sufficiently distinguish depressive symptoms from positive and negative symptoms and extrapyramidal adverse effects of medications in psychosis.69,70 Addington and Addington71 have previously shown that a CDSS sum score cutoff >6 has a specificity of 82% and a sensitivity of 85% for detecting a major depressive episode. Consequently, we applied this cutoff in subanalyses to investigate the subcohort with more pronounced depressive symptoms. There is no consensus concerning which magnitude of depressive reduction that may be considered clinically significant. Moreover, there are no established thresholds for response or remission of depression for the CDSS, which are more clearly defined in major depressive disorder, such as a score below a defined threshold on various psychometric scales for depression.72–76

Furthermore, the patients completed a PANSS interview62,77 and the Clinical Drug Use Scale (CDUS) and Clinical Alcohol Use Scale (CAUS).78 The Clinical Global Impression–Severity of Illness Scale (CGI-S)79 was applied to assess illness severity. Global functioning was measured by the Global Assessment of Functioning Scale (GAF) (DSM-IV), and the scores were split into symptom and function scores.80,81 Use of concomitant psychotropic medication was registered. Participants not previously treated with antipsychotic medication were considered medication naive. The CDSS, PANSS, CGI, and GAF were administered at all study visits. The SCI-PANSS was used, and all investigators conducting assessments were trained and calibrated by the PANSS Institute (panss.org) until satisfactory interrater reliability was achieved. Tolerability outcomes were measured by the UKU–Side Effect Rating Scale,82 as well as clinical and biochemical assessments. These have been reported in a previous publication.55 Scales and psychometric interviews were applied in valid, approved translations in Norwegian in the Norwegian sites (English in the few English-fluent participants) and German in Austria.

Statistical Procedures Analysis Strategy

Baseline data were analyzed using SPSS version 2483 by means of exact χ2 tests for categorical data and one-way analyses of variance (ANOVAs) for continuous data. The latent growth curve modeling (LGCM)84,85 was used to analyze the level and change in CDSS with Mplus 8.3.86 First, a linear change model was fitted and evaluated based on fit indices, residual variances, and visual inspection of individual data. Model fit was evaluated based on the threshold values: comparative fit index (CFI) and Tucker-Lewis index (TLI) beyond 0.95; root mean error of approximation (RMSEA) < 0.05 as close fit, RMSEA < 0.08 as fair fit, and RMSEA < 0.10 as mediocre fit.87 The standard LGCM incorporates both mean level and change, as well as the level and change at individual level, represented as intercept and slope variance. As the power analysis below was based on a linear model, these results will be reported independent of the model fit results. In addition to fitting a linear change, latent contrast score models were tested, analyzing change in each study visit interval and thus allowing the data to govern the form of change. First, this model was estimated as a random intercept and fixed slope model (no slope variance). Then, based on modification indices, individual variation (random slopes) was freed up in some intervals to improve model fit. Residual variance was set equal over time.

The 3 study drugs were analyzed with amisulpride as the reference category and aripiprazole and olanzapine tested against this reference medication. In addition, model constraints in Mplus were used to test for differences in changes between aripiprazole and olanzapine.

The primary analyses were ITT analyses88 based on the randomization groups. In ITT analyses, trial participants are analyzed in the trial drug group they were randomized to regardless of which treatment they actually received. Next, per protocol (PP) analyses were based on the antipsychotic drug that ultimately was chosen. The estimator was maximum likelihood with robust standard errors, which handles nonnormality.87 The full information maximization likelihood method uses all available data under the missing at random assumption.89 However, the missing data (MD) could be related to the unobserved values and thus missing not at random (MNAR). Missing not at random models (Diggle-Kenward90 and pattern mixture89) were tested as sensitivity models to investigate potential biases in the estimated parameters. The Diggle-Kenward model tests both whether MD is missing completely at random or missing at random and if MD is MNAR or not. Standard procedure was used, with constrained parameters over time.

Per protocol analyses of CDSS single-item change and analyses restricted to data of the de facto periods of administration of the trial antipsychotics were also conducted. A multisample analysis (PP) was conducted, separating participants into a less depressed and a more depressed group, with a cutoff CDSS sum score of >6 for the latter group, then analyzing antipsychotic antidepressant differences between the study drugs. Finally, a model including level and change in PANSS positive as predictors was conducted. To reduce the model complexity, these models were analyzed as linear, however with estimated time factors.85 A nonlinear model may be indicated if time factors are found to deviate from values of the actual time points. The CDSS sum score and PANSS-positive subscale models were first analyzed separately, then combined in a multivariate model that regressed the level and change in CDSS on level and change in PANSS positive in addition to the PP medications. Effect sizes (Cohen d) were calculated for the ITT data by estimating the difference in CDSS reduction for the drugs and dividing the difference by the pooled standard deviation (SD).91 For the reference drug, the model estimated baseline level was subtracted from the 52-week mean level (intercept values). Then, regression values were added on the intercept values to compute the estimates for the other 2 medications. The pooled SD was based on baseline SD and 52-week SD. The 52-week SD was extracted from a time reversed model to place the intercept factor to the last point of time.

Power Analysis

Power estimations for the linear change model were conducted in R92 by means of linear mixed effects models93: a statistical power of 90% and an overall P value at the 5% level were entered into the model. The initial CDSS total score, slopes, and within-person variation were based on the results of a previous model where the overall reduction of the CDSS sum score was 58%.47 In the BeSt InTro power analysis, we defined assumed clinically relevant differences between the study drugs as CDSS sum score reductions of 10%, 35%, and 70% during the 52 weeks in the respective drug groups. The corresponding slopes were entered into the model. The initial CDSS sum score was set at 5.67 points, and an estimated dropout rate of 5% per month was used. For each level of power, 10,000 simulations were run. Based on these premises for the power calculations, the trial should have 92% power to detect statistically significant differences among the drugs with 48 subjects in each of the 3 treatment groups.

Ethical Considerations, Monitoring, and Funding

The study was carried out in accordance with ethical principles for medical research involving humans (Declaration of Helsinki)94 and approved in Norway by the Regional Committees for Medical and Health Research Ethics and the Norwegian Medicines Agency. In Austria, the trial was approved by the Etikkommission der Medizinische Universität Innsbruck and the Austrian Federal Office for Safety in Health Care. Clinical monitoring according to the Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use–Good Clinical Practice Guideline95 was in Norway conducted by the Department of Research and Development, Haukeland University Hospital. In Austria, clinical monitoring was conducted by the Clinical Trial Centre at the Medical University of Innsbruck. The project was publicly funded by the Research Council of Norway, the Western Norway Regional Health Trust, as well as by the participating hospitals and universities. No pharmaceutical company imbursed the trial.

RESULTS

The patient flowchart is displayed in Figure 1. A total of 144 patients were enrolled and randomized to one of the study drugs. Demographic and clinical characteristics at inclusion are presented in Table 1. Fifty-one of the 144 patients were women (35%), the mean age was 31.7 (SD 12.7) years, and 39% were antipsychotic-naive. Sixty-eight participants (47%) had a Calgary depression sum score >6 at inclusion, and the mean total PANSS score was 81.0, both reflecting a pronounced symptom level. The descriptive statistics for the CDSS is presented in Supplementary Table S1, https://links.lww.com/JCP/A848.

F1FIGURE 1:

Patient flowchart. Lost to follow-up = explicit withdrawal from further participation in the study or not showing up at subsequent study visits; Depot = long-acting formulation of study drug; Protocol violation = use of dosage above upper limit according to the study protocol; Drop out = unknown study drug use status because participant is lost to follow-up. *Based on actual use of randomized drugs at each visit. **Based on originally randomized patients (ITT population).

TABLE 1 - Descriptive Statistics for the Randomization Groups at Baseline Amisulpride (N = 44) n/N (%, CI) Aripiprazole (N = 48) n/N (%, CI) Olanzapine (N = 52) n/N (%, CI) All (N = 144) n/N (%, CI) Men 28/44 (64, 49–78) 32/48 (67, 54–80) 33/52 (63, 50–76) 93/144 (65, 57–73) White 39/44 (89, 80–98) 35/48 (73, 60–86) 44/52 (85, 75–95) 118/144 (82, 76–88) Living alone 21/44 (48, 33–63) 17/48 (35, 22–48) 23/52 (44, 31–57) 61/144 (42, 34–50) Employed 14/44 (32, 18–46) 12/48 (25, 13–37) 10/52 (19, 8–30) 36/144 (25, 18–32) Diagnosis: schizophrenia* 28/44 (64, 50–78) 27/48 (56, 42–70) 29/52 (56, 43–69) 84/144 (58, 50–66) Diagnosis: schizotypal* 1/44 (2, 0–6) 0/48 (0) 1/52 (2, 0–6) 2/144 (1, 0–3) Diagnosis: delusional disorder* 4/44 (9, 1–17) 8/48 (17, 6–28) 9/52 (17, 7–27) 21/144 (15, 9–21) Diagnosis: brief psychotic disorder* 8/44 (18, 7–29) 3/48 (6, 0–13) 7/52 (13, 4–22) 18/144 (12, 7–17) Diagnosis: schizoaffective* 3/44 (7, 0–15) 5/48 (10, 2–18) 2/52 (4, 0–9) 10/144 (7, 3–11) Diagnosis: other* 0/44 (0) 1/48 (2, 0–6) 0/52 (0) 1/144 (1, 0–3) Diagnosis: unspecified* 0/44 (0) 4/48 (8, 0–16) 4/52 (8, 1–15) 8/144 (6, 3–10) Smoking 30/44 (68, 54–82) 29/48 (60, 46–74) 26/52 (50, 36–64) 85/144 (59, 51–67) Abuse/dependence—alcohol† 4/44 (9, 1–17) 7/48 (15, 5–25) 2/52 (4, 0–9) 13/144 (9, 4–14) Abuse/dependence—drugs† 10/44 (23, 11–35) 8/48 (17, 6–28) 9/52 (17, 7–27) 27/144 (19, 13–25) APnaiv 16/44 (36, 22–50) 23/48 (48, 34–62) 17/52 (33, 20–46) 56/144 (39, 31–47) Amisulpride (N = 44) Mean (SD, CI) Aripiprazole (N = 48) Mean (SD, CI) Olanzapine (N = 52) Mean (SD, CI) All (N = 144) Mean (SD, CI) CDSS 7.5 (5.6, 5.8–9.3) 5.6 (4.8, 4.2–7.0) 7.1 (5.1, 5.6–8.5) 6.7 (5.2, 5.8–7.6) Age 30.6 (11.7, 27.0–34.2) 32.1 (13.1, 28.3–35.9) 32.2 (13.3, 28.5–35.9) 31.7 (12.7, 29.6–33.8) Years of education 12.7 (3, 11.8–13.7) 11.9 (2.8, 11.1–12.8) 12.2 (2.7, 11.5–13.0) 12.3 (2.8, 11.8–12.8) PANSS total 80.0 (18.6, 74.4–85.7) 76.6 (13.4, 72.7–80.5) 78.7 (15.5, 74.4–83.0) 78.4 (15.8, 75.8–81.0) PANSS positive 21.4 (4.8, 20.0–22.9) 21.3 (4.9, 19.9–22.7) 21.0 (4.7, 19.7–22.3) 21.2 (4.8, 20.4–22.0) PANSS negative 18.2 (7.0, 16.1–20.3) 17.2 (5.6, 15.5–18.8) 18.1 (5.8, 16.5–19.7) 17.8 (6.1, 16.8–18.8) PANSS general 40.4 (10.2, 37.3–43.5) 38.1 (7.2, 36.0–40.2) 39.7 (8.1, 37.4–41.9) 39.4 (8.5, 38.0–40.8) CGI-S 5.1 (0.9, 4.8–5.4) 4.9 (0.7, 4.7–5.1) 5 (0.8, 4.8–5.2) 5 (0.8, 4.9–5.1) GAF‡ 36 (9.6, 33.1–38.9) 36 (9.6, 33.1–38.9) 35.5 (8.8, 33.1–38.0) 35.8 (9.3, 34.3–37.4)

Medication is registered as being used or not at each visit, thus the precise time of medication change or stop was not registered.

*All diagnoses are ICD-10.

†Abuse/dependence defined by a score ≥3 on the CDUS and CAUS.

‡GAF is reported as the mean value of GAF-S and GAF-F of the split GAF version.

A total of 24 patients (16.7%) chose another study drug than the first one in the sequence, with no statistically significant difference among the randomization groups (Fisher exact test: P = 0.143). The mean study drug doses used with SDs were for amisulpride 396.9 (206.9) mg, aripiprazole 14.6 (7.0) mg, and olanzapine 12.3 (3.8) mg. The corresponding defined daily doses (DDDs) with SDs were 1.0 (0.5), 1.0 (0.5), and 1.3 (0.4) for amisulpride, aripiprazole, and olanzapine, respectively. The overall DDD in the olanzapine group was statistically significantly higher than in the amisulpride group (1-way ANOVA: P = 0.018; mean difference, 0.28; 95% confidence interval [CI], 0.04–0.53) and the aripiprazole group (1-way ANOVA: P = 0.008; mean difference, 0.32; 95% CI, 0.07–0.57). Study drug serum levels were mostly within the reference concentration range for the drugs; however, with lower levels in the start of and the end of the study year and a tendency toward lower concentrations in Austria than in the Norwegian study sites.55 Serum levels were measured in one half to two thirds of participants attending study visits and showed for the majority of patients that the serum levels were within accepted reference range for the drugs. Among amisulpride-treated participants, around one fourth did not reach the lower reference level for the study drug until 12 weeks into the participation, and among aripiprazole-treated patients, one fifth did not reach this level before 6 weeks. Olanzapine-treated patients reached this level faster (>90% within 1 week).

Coprescriptions of psychotropic drugs including antidepressants, mood stabilizers, benzodiazepines/anxiolytics/hypnotics, and anticholinergics, with results published previously,55 were generally equal among the study drug groups except more patients received mood stabilizers at inclusion in the aripiprazole group (n = 5) compared with both the amisulpride (n = 1) and olanzapine groups (n = 0) (Fisher exact test: P = 0.020 for the ITT groups), and 3 participants received anticholinergic drugs in the ITT amisulpride group at 3 months compared with none in the other groups (Fisher exact test: P = 0.026).

Depressive Symptom Change—ITT Analyses

The linear model of the level and change in CDSS over 52 weeks fitted data poorly (χ2 = 94.23, df = 31, P < 0.001, CFI = 0.77, TLI = 0.79, RMSEA = 0.119, RMSEACI = 0.092–0.147, RMSEAclose fit = 0.00). The latent contrast score model improved model fit to a satisfactory level (χ2 = 33.17, df = 23, P = 0.078, CFI = 0.96, TLI = 0.96, RMSEA = 0.056, RMSEACI = 0.000–0.095, RMSEAclose fit = 0.38). The baseline overall CDSS level in the linear model was estimated to be 5.36, and the change was −0.05 per week (P < 0.001). Although the amisulpride group had the greatest depressive symptom reduction and the olanzapine group the smallest reduction per week, there were no statistically significant differences between the study drugs in this linear model: amisulpride (intercept): α = −0.07, P < 0.001 (significance test vs time); aripiprazole: b = 0.02, P = 0.399 (vs amisulpride); olanzapine: b = 0.04, P = 0.142 (vs amisulpride); and b-weights difference = −0.02, P = 0.525 (aripiprazole vs olanzapine) (Supplementary Fig. S1, https://links.lww.com/JCP/A848).

The latent contrast score model is presented in Supplementary Table S2, https://links.lww.com/JCP/A848 (model fit presented in above paragraph) and showed that reduction of depressive symptoms was greatest in the first 6 weeks and flattened in the 6- to 52-week period. The results from comparing the randomized antipsychotic drugs for change in CDSS are presented in Table 2 and Figure 2. No statistically significant differences in reduction of CDSS were found among the 3 medications. Effect size differences between the study drugs were 0.353 between amisulpride and aripiprazole and 0.354 between amisulpride and olanzapine.

TABLE 2 - ITT Analyses (LGCM) of Medication Differences on Level and Changes in CDSS Amisulpride* Aripiprazole† Olanzapine† Aripiprazole vs Olanzapine Weeks I P CDSS´ b1 P CDSS´ b2 P CDSS´ Δb1b2 P Baseline I 6.65 <0.001 6.65 0 6.65 0 6.65 0 0–1 S1 −1.43 0.046 5.23 0.75 0.379 5.97 0.31 0.705 5.53 0.44 0.479 1–3 S2 −0.25 0.441 4.73 −0.41 0.317 4.66 −0.02 0.972 5.01 −0.40 0.277 3–6 S3 −0.24 0.253 4.01 0.25 0.449 4.68 −0.09 0.735 4.02 0.34 0.241 6–12 S4 0.06 0.617 4.37 −0.20 0.319 3.87 0.14 0.474 5.20 −0.33 0.115 12–26 S5 −0.09 0.075 3.11 0.04 0.611 3.16 0.06 0.498

留言 (0)

沒有登入
gif