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Table 4 Tolerability outcomes (rating scales/outcome measures)

From: Effectiveness of second generation antipsychotics: A systematic review of randomized trials

Studies Main results
FIRST EPISODE  
Crespo-Facorro et al. [24] O = H = R (AIMS)
O = H = R (asthenia, tremor, increased/reduced salivation, erectile and ejaculatory dysfunction, amenorrhoea (UKU))
H > O & R (treatment emergent parkinsonism (SAS) (p < 0.001) and akathisia (BARS) (p < 0.001))
H > O > R (concentration difficulties (p = 0.044), sleepiness/sedation (0.012) increased duration of sleep (p = 0.033) (UKU))
H > R > O (rigidity (p = 0.005), hypokinesia (p = 0.006), akathisia (p = 0.029) (UKU))
O > R > H (weight gain) (p < 0.001) (UKU)
McEvoy et al. [25] O = Q = R (SAS, BARS, AIMS)
O > Q & R(weight gain and BMI change, and male weight gain and BMI change) (p < 0.01)
O > Q (female weight gain and BMI change) (p < 0.001)
R > Q (female weight gain and BMI change) (p < 0.01)
Q & R < O (weight gain > 7 %) (p < 0.05)
O > Q (male weight gain > 7 % (week 12 only)) (p < 0.01)
O > R (male weight gain > 7 %) (p < 0.05)
O > Q (female weight gain > 7% (week 12 only)) (p < 0.01)
R > Q (female weight gain > 7 % (week 52 only)) (p < 0.05)
O > Q (BMI increase ≥ 1 unit) (p < 0.05)
O > R (BMI increase ≥ 1 unit (week 12 only)) (p < 0.01)
O > Q (male BMI increase ≥ 1 unit (week 12 only)) (p < 0.05)
O > R (male BMI increase ≥ 1 unit) (p < 0.05)
O > Q (female BMI increase ≥ 1 unit (week 12 only)) (p < 0.01)
O > R (female BMI increase ≥ 1 unit (week 12 only)) (p < 0.05)
O > R (female waist circumference > 35 inches change (week 12 only)) (p < 0.05)
O & Q > R ((fasting TG levels change (week 52 only) (p < 0.05)
Q > R (increase of proportion with fasting TG level > 150 mg/dl) (p < 0.01)
Q > O (increase of proportion with fasting TG level > 150 mg/dl (week 12 only)) (p < 0.05)
Q > R (fasting total cholesterol change (week 52 only)) (p < 0.05)
O > Q (negative fasting HDL cholesterol change and male negative fasting HDL cholesterol change (week 52 only)) (p < 0.05)
O > R (negative fasting HDL cholesterol change) (p < 0.05)
O > R (male negative fasting HDL cholesterol change (week 52 only)) (p < 0.05)
R > O & Q (prolactin level change) (p < 0.001)
Q > R (systolic blood pressure increase) (p < 0.01)
O > R (systolic blood pressure increase) (p < 0.05)
O > R (diastolic blood pressure increase (week 52 only)) (p < 0.05)
O > R (increase of proportion with systolic blood pressure ≥ 130 mm Hg (week 52 only)) (p < 0.05)
Q > R (increase of proportion with diastolic blood pressure ≥ 85 mm Hg (week 52 only)) (p < 0.05)
Robinson et al. [26] O = R (SAS, BARS)
O > R (weight gain) (p < 0.01)
ACUTE PHASE  
Chrzanowski et al. [27] A = O (insomnia, anxiety, headache, somnolence, infection, nervousness, akathisia, schizophrenic reaction, flu syndrome, CNS stimulation, lightheadedness, tremor, SAS, BARS, AIMS, triglyceride change)
O > A (Weight gain (p < 0.001, Weight gain > 7% (p = 0.008), elevated total (p < 0.01) and LDL cholesterol (p < 0.01), negative influence on HDL cholesterol (p < 0.05), QTc prolongation (p = 0.008), prolactin elevation (p < 0.001)
Kraus et al. [28] No outcomes
McCue et al. [29] A = H = O = Q = R = Z (SAS, BARS, spontaneous reports of adverse events)
A = H = O = Q = R = Z (withdrawals because of side-effects)
CHRONIC PHASE  
Jerrel [30] O = R = FGA (DISCUS, SAS, BARS)
Lieberman et al. [31] O = P = Q = R = Z (any moderate or severe adverse effect, suicide attempt or ideation, hypersomnia, sleepiness, decreased sex drive, arousal, ability to reach orgasm, gynecomastia, galactorrhoea, menstrual irregularities, orthostatic faintness, AIMS, BARS, SAS, discontinuation owing to sedation, change from baseline of blood glucose, change in corrected QT interval, new cataracts)
O > Q > R > P > Z (weight gain > 7%, mean cholesterol and -triglyceride change) (p < 0.001); (meanHbA1c change) (p = 0.01)
O > Q > R > Z* > P* (weight change) (p < 0.001)
O > Z > P > R > Q (HbA1c change) (p = 0.01)
O > Q > P > R* > Z* (cholesterol change, triglyceride change) (p < 0.001)
O > Q > Z > R > P (discontinuation owing to weight gain or metabolic effects) (p < 0.001)
O > Q = P = Z > R (discontinuation owing to intolerability) (p = 0.04)
Q > R > O > P > Z (urinary hesitancy, dry mouth, constipation) (p < 0.001)
Z > P > R > Q > O (insomnia) (p < 0.001)
R > O = Z > Q > P (incontinence, nocturi) (p = 0.04)
P > Z > Q = R > O (discontinuation owing to EPS) (p = 0.002)
R > P > >Z > O > Q (mean prolactin change)(p < 0.001)
Q & R > O & Z (prolonged QTc interval) (p < 0.03)
Mullen et al. [32] Q = R (EPS total (EPS checklist), odds of having an EPS event)
R > Q (for odds of EPS of at least moderate severity (p = 0.03), odds of substantial EPS (p < 0.001), requirement of anti- EPS medication during the trial among baseline EPS patients (p < 0.001)
Q > R (somnolence, dry mouth, dizziness, agitation) (p < 0.05)
Ritchie et al. [33] O = R (SAS, AIMS, BARS, specific side effects)
Ritchie et al. [34] O = R (SAS, AIMS, BARS, sedation, hypotension, dizziness, gastrointestinal side effects, libido, anticholinergics symptoms, weight gain)
Rosenheck et al. [35] No outcomes
Stroup et al. [36] O = Q = R = Z (hypersomnia, sleepiness, urinary hesitancy/dry mouth/constipation, incontinence/nocturia, AIMS, BARS, SAS, discontinuation because of intolerable extrapyramidal side effects or sedation, weight change over course of treatment, change of blood glucose and HbA1c, change in QTc interval)
O > Q = R > Z (> 7% weight gain) (p = 0.009)
O > Q > R* > Z * (average change in weigh and cholesterol change) (p < 0.001)
O > Q > Z* > R* (mean change in triglycerides) (p < 0.001)
Q > O > R > Z (orthostatic faintness) (p < 0.05);discontinuation because of intolerable weight or metabolic side effects) (p = 0.004)
Q > R > Z > O (skin rash) (p < 0.05)
Q > Z > O > R (any spontaneous report of moderate/severe adverse effect) (p < 0.02))
R > O > Z > Q (adverse events related to sex drive/sexual arousal/sexual orgasm) (p < 0.05)
R > O = Z > Q (gynecomastia/galactorrhoea) (p < 0.04)
R > Z* > O* > Q* (change of prolactin level) (p < 0.001)
Z > R > Q > O (any serious adverse event) (p = 0.01)
Z > R >Q > O (insomnia) (p < 0.001)
Stroup et al. [37] O = Q = R (any moderate, severe or serious adverse event, insomnia, hypersomnia, sleepiness, urinary hesitancy, dry mouth, constipation, decreased sexual drive, sexual arousal, orgasm, incontinence, nocturia, sialorrhoea, orthostatic faintness, skin rash, AIMS, weight gain > 7%, rate of weight gain, change of blood glucose, HbA1c, QTc interval)
O > Q > R (amount of weight gain) (p = 0.005;, (triglyceride change) (p = 0.03)
O > R > Q (total cholesterol change) (p = 0.01)
R > Q* > O* (change of prolactin level) (p < 0.001)
Swartz et al. [38] No outcomes
Tunis et al. [39] O = R = FGAS (any serious AE)
O > FGA (probability of not developing EPS over 1 year among those without EPS at baseline) (p = 0.006)
R (p = 0.023) & FGAs (p < 0.0001) > O (time to 7% weight gain)
O > R > FGA (weight gain for patients on initial antipsychotic regimen) (significant1, p = ?)
  1. Abbreviations: A = Aripiprazole, FGAs = First generation antipsychotics, O = Olanzapine, P = Perphenazine, Q = Quetiapine, R = Risperidone, Z = Ziprasidone, DISCUS = the Dyskinesia Identification System Condensed User Scale, BARS = Barnes Akathisia Scale, AIMS = the Abnormal Involuntary Movement Scale, BARS = the Barnes Akathisia Rating Scale, SAS = the Simpson Angus Scale, UKU = UKU Side Effect Rating Scale, EPS = the extrapyramidal syndrome, BMI = Body Mass Index.
  2. * = negative change
  3. 1 The authors state that the difference is significant, but do not reveal the p-value for this comparison.
  4. [24], [25] and [27] provide analyses on both last observation carried forward (LOCF) and observed cases. The main findings are the same, but only p-values for LOCF data are displayed in the table.