Background
First author | Title | Year of publication | Design | Type of SSRI assessed | Information sources | No. of trials | No. of patients | Published protocol | Assessment of adverse events | Assessment of risk of bias | |
---|---|---|---|---|---|---|---|---|---|---|---|
Reviews concluding that SSRIs have beneficial effect on major depressive disorder | Gibbons et al. | Benefits From Antidepressants: Synthesis of 6-Week Patient-Level Outcomes From Double-blind Placebo-Controlled Randomized Trials of Fluoxetine and Venlafaxine | 2012 | Patient level meta-analysis | Flouxetine | Eli Lilly and Co | 16 | 3595 | No | No | No |
Undurraga et al. | Randomized, Placebo-Controlled Trials of Antidepressants for Acute Major Depression: Thirty-Year Meta-Analytic Review | 2011 | Systematic review | Fluoxetine, sertraline, paroxetine, citalopram, escitalopram | Medline, CINAH Library, Cochrane Library, PsycINFO | 51 | 5285 | No | No | Only publication bias | |
Wilson et al. | Antidepressants Versus Placebo for the Depressed Elderly | 2001 | Cochrane review | Fluoxetine | PsycLIT, MEDLINE, EMBASE, LILACS, CINAHL, SIGLE, Psyndex, National Research Register, Dissertation Abstracts International | 2 | 365 | Yes | No | Only allocation concealment | |
Aroll et al. | Antidepressants versus placebo for depression in primary care (Review) | 2009 | Cochrane review | Sertraline, escitalopram, citalopram | CCDANCTR | 4 | 707 | Yes | Yes | Only allocation concealment (QRS) | |
Reviews concluding that SSRIs have no effect on mild to moderat depression but have beneficial effect on severe depression | Fournier et al. | Antidepressant Drug Effects and Depression Severity: A Patient-Level Meta-analysis | 2010 | Patient level meta-analysis | Paroxetine | PubMed, PsycINFO, Cochrane Library | 3 | 240 | No | No | No |
Khan et al. | Severity of Depression and Response to Antidepressants and Placebo: An Analysis of the Food and Drug Administration Database | 2002 | Systematic review | Fluoxetine, sertraline, paroxetine | FDA | 18 | Unclear | No | No | No | |
Reviews concluding that SSRIs have questionable effect on major depressive disorder | Turner et al. | Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy | 2008 | Systematic review | Fluoxetine, sertraline, paroxetine, citalopram, escitalopram | FDA, PubMed, Cochrane Library | 38 | Unclear | No | No | Only publication bias |
Kirsch et al. | Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration | 2008 | Systematic review | Fluoxetine, sertraline, paroxetine, citalopram | FDA, PubMed | 21 | 1708 | No | No | Only publication bias | |
Reviews not showing anything about the effects of SSRIs on major depressive disorder | Moncrieff et al. | Active Placebos Versus Antidepressants for Depression (Review) | 2012 | Cochrane review | No SSRIs studied, only TCAs | CCDANCTR | Yes |
Methods
Outcomes
Primary outcomes
-
Remission (Hamilton <8 points; BDI <10 points; MADRS <10 points).
-
Adverse events during the intervention period which were classified as serious and non-serious adverse events [11]. Serious adverse events were defined as medical events that were life threatening, resulted in death, disability, or significant loss of function, or caused hospital admission or prolonged hospitalisation [11]. The remaining events were classified as non-serious adverse events [11].
Secondary outcomes
-
Suicides, suicide attempts, and suicide ideation during the intervention period.
-
Quality of life (scale used by the trialists).
Handling of missing data
Subgroup analyses
Selection of trials and data extraction
Assessment of the statistical and clinical significance
Results
Primary outcomes
Hamilton depression rating scale (HDRS)
Heterogeneity
Subgroup analysis per risk of bias
Incomplete outcome data
Other subgroup analyses
Trial Sequential Analysis
Bayes factor
Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale, and Beck’s Depression Inventory
Long-term follow-up
No remission
Serious adverse events
Trial | Experimental intervention | SSRI participants assessed for serious adverse events | Placebo participants assessed for serious adverse events | ||
---|---|---|---|---|---|
Numbers and types of serious adverse events | Proportion of participants with a serious adverse event | Numbers and types of serious adverse events | Proportion of participants with a serious adverse event | ||
Bose et al., 2008 | Escitalopram | 1 bowel obstruction, 1 nausea, 1 arrythmia, 1 respiratory arrest, 1 retinal detachment, 1 chest pain | 5 out of 96 | 1 syncope | 1 out of 109 |
Ball et al., 2014 | Paroxetine | No serious adverse event | 0 out of 74 | 1 unspecified serious adverse event | 1 out of 78 |
Andreoli et al., 2002 | Fluoxetine | No serious adverse event | 0 out of 97 | 1 suicide | 1 out of 76 |
Kasper et al., 2011 | Escitalopram | No serious adverse event | 0 out of 128 | 1 hospitalisation due to appendicitis | 1 out of 50 |
Kasper et al. (A), 2005 | Escitalopram | 1 death (suicide) | 1 out of 173 | 1 death (probably drowned) | 1 out of 160 |
Ravindran et al., 1995 | Sertraline | 9 unspecified serious adverse events | 4 out of 25 | 3 unspecified serious adverse events | 2 out of 13 |
March et al., 1990 | Fluvoxamine | 1 hospitalisation due to worsening of depression | 1 out of 13 | 1 suicide attempt | 1 out of 12 |
Rapaport et al., 2009 | Paroxetine | 2 chestpain, 1 osteoarthritis, 1 ankle fracture, 1 atrial fibrillation, 1 femur fracture,1 coronary artery occlusion, 1 pneumonia, 1 confusional state, 1 depression | 10 out of 267 | 1 neprholithiasis, 1 aortic aneurism | 2 out of 127 |
Higuchi et al., 2011 | Paroxetine | 1 suicide and 8 unspecified serious adverse events | 9 out of 213 | 1 unspecified serious adverse event | 1 out of 139 |
Schneider et al., 2003 | Sertraline | 17 unspecified serious adverse events | 17 out of 284 | 11 unspecified serious adverse events | 11 out of 311 |
Sheehan et al., 2009 | Fluoxetine | 1 suicidal ideation/suicidality, 1 worsening of depression, 2 suicide attempts, 1 anxiety/agitation/racing thoughts, 1 syncope, 1 ankle fracture, 1 viral gastro enteritis | 8 out of 76 | 2 suicidal ideation/suicidality, 2 worsening of depression, 1 nose bleed, 1 allergic reaction | 6 out of 67 |
Nemroff et al., 2005 | Fluxetine | 1 unspecified serious adverese event | 1 out of 86 | 1 unspecified serious adverse event | 1 out of 78 |
Fabre et al., 1996 | Fluvoxamine | 1 hospitalisation (non-cardiac chest pain) | 1 out of 22 | 1 hospitalisation, 1 ruptured ectopic pregnancy, 1 hernia repair | 2 out of 19 |
Feighner et al., 1999 | Citalopram | 3 suicide attempts, 1 miscarriage, 1 intestinal flu symptoms, 1 chest pain, 1 severe thinking abnormality, 1 allergic reaction | 8 out of 349 | No serious adverse event | 0 out of 86 |
SCT-MD 01 (B), 2002 | Escitalopram | 1 anaphylaxis, 1 suicide attempt | 2 out of 94 | 1 gallbladder stones | 1 out of 46 |
SCT-MD 01 (C), 2002 | Citalopram | 1 coma, 1 intestinal fistula | 2 out of 93 | 1 non-accidental overdose | 1 out of 45 |
SCT-MD 02 (A), 2002 | Escitalopram | 1 suicidal tendency, suicide attempt; 1 non-accidental overdose, suidal attempt, tachycardia | 2 out of 96 | No serious adverse event | 0 out of 53 |
SCT-MD 02 (B), 2002 | Citalopram | 1 cholestasis intrahepatic, dehydration | 1 out of 99 | No serious adverse event | 0 out of 52 |
Pettinati et al., 2010 | Sertraline | 15 unspecified serious adverse events | 15 out of 40 | 11 unspecified serious adverse events | 11 out of 39 |
Dube et al., 2010 | Escitalopram | 1 suicide attempt, 1 gastro enteritis/malaria | 2 out of 54 | 1 near drowning, 1 gastro enteritis | 2 out of 122 |
Learned et al., 2012 | Paroxetine | 1 intentional over dose, 1 depression, 1 unspecified event | 3 out of 166 | 2 unspecified serious adverese events | 2 out of 156 |
Ratti et al., 2011 | Paroxetine | 1 hemorrhoidal hemorrhage | 1 out of 109 | 1 rash | 1 out of 123 |
Wang et al., 2014 | Escitalopram | 3 unspecified serious adverese event | 3 out of 114 | 1 unspecified serious adverese event | 1 out of 115 |
Detke et al., 2004 | Paroxetine | 1 unspecified serious adverese event | 1 out of 85 | No serious adverse event | 0 out of 93 |
Mancino et al., 2014 | Sertraline | 1 hospitalization | 1 out of 23 | No serious adverse event | 0 out of 27 |
DeRubeis et al., 2005 | Paroxetine | 1 suicide | 1 out of 120 | No serious adverse event | 0 out of 60 |
29060-785 (A), 2005 | Paroxetine CR 25 mg | 3 abnormal laboratory vaue, 1 emotional lability | 4 out of 98 | 1 abnormal laboratory value, 1 gastrointestinal disorder | 2 out of 26 |
29060-785 (B), 2005 | Paroxetine CR 12.5 mg | 1 abnormal laboratory value | 1 out of 94 | 1 abnormal laboratory value, 1 myocardial infarction | 2 out of 26 |
29060-785 (C), 2005 | Citalopram 20 mg | 5 abnormal laboratory value, 1 syncope | 6 out of 105 | 1 abnormal laboratory value, 1 suicide | 2 out of 25 |
29060-785 (D), 2005 | Citalopram 40 mg | 1 abnormal laboratory vaue, 1 emotional lability | 2 out of 97 | 1 abnormal laboratory value | 1 out of 25 |
SCT-MD 27 (A), 2005 | Escitalopram | 1 depression, 1 abnormal mental status, 1 malignant neoplasm | 3 out of 131 | 1 labyrinthitis | 1 out of 66 |
SCT-MD 27 (B), 2005 | Sertraline | 1 appendicitis | 1 out of 135 | No serious adverse event | 0 out of 66 |
SCT-MD 35, 2007 | Escitalopram | 1 abnormal hepatic function | 1 out of 131 | 1 breast cancer, 1 depression, 1 suicidal ideation, 1 suicide | 4 out of 130 |
SCT-MD 26, 2005 | Escitalopram | 1 inflicted injury | 1 out of 143 | No serious adverse event | 0 out of 151 |
MY-1043/BRL-029060/115 (A), 2005 | Paroxetine | 1 hypertension, 1 diabetes and hypothyroidism, 1 Fibrocystic disease, 1 Ovarian cysts, 1 peptic ulcer hemorrhage, 1 spinal surgery, 1 hypomanic episode with suicidal tendency, 2 Suicidal ideation, 1 alcoholism, 1 neoplasm | 11 out of 272 | 1 suicidal ideation, 1 back pain, 1 trauma | 3 out of 57 |
MY-1043/BRL-029060/115 (B) | Fluoxetine | 1 suicidal ideation, 1 neoplasm, 2 acute pyelonephritis, 1 thrombophlebitis, 1 ectopic pregnancy, 1 polycystic granuloma, 2 basal cell carcinomas, 1 myxoid mitral valve | 9 out of 278 (10 SAE in 9 participants) | 1 viral meningitis, 1 infection, 1 myocardial infarction, 1 mole removal | 3 out of 56 (4 SAE in 3 participants) |
MY-1045/BRL-029060/1, (A), 2005 | Paroxetine | 2 depression (worsening), 2 emotional lability, 1 neoplasm, 1 insomnia, 1 nervousness, 1 carcinoma, 1 epistaxis, 1 gastro intestinal disorder, 1 prostate disorder | 9 out of 357 (11 SAE in 9 participants) | 1 depression (worsening), 1 rectal disorder | 2 out of 70 |
MY-1045/BRL-029060/1, 2005 | Fluoxetine | 1 depression (worsening), 2 emotional lability, 1 neo plasm, 1 coronary artery disease, 1 thrombo phlebitis, 1 hypoglycemia | 7 out of 351 | 2 depression (worsening), 1 flu syndrome disorder | 2 out of 70 |
29060/448 (A), 2005 | Paroxetine IR | 1 myocardial infarction, 1 emotional lability | 2 out of 104 | 1 uterine fibroids enlarged, 1 gall bladder disorder | 2 out of 50 |
29060/448 (B), 2005 | Paroxetine CR | 3 emotional lability, 1 hepatocellular jaundice, 1 manic reaction | 6 out of 102 | 1 dehydration, 1 accidental overdose | 2 out of 51 |
29060/449 (A), 2005 | Paroxetine IR | 1 emotional lability, 1 abortion, 2 unintended pregnancy | 3 out of 112 (4 SAE in 3 participants) | No serious adverse event | 0 out of 55 |
29060/449 (B), 2005 | Paroxetine CR | 1 abdominal pain, 1 pancreatitis, 1 accidental over dose, 1 unintended pregnancy | 2 out of 108 (4 SAE in 2 participants) | No serious adverse event | 0 out of 55 |
PAR 29060.07.001, 2008 | Paroxetine | 1 acure depression, 1 acute alcohol intoxication and suicide ideation | 2 out of 13 | No serious adverse event | 0 out of 12 |
Nyth et al., 1992 | Citalopram | 1 cerebral hemorrhage and death | 1 out of 98 | 1 death | 1 out of 51 |
Perahia et al., 2006 | Paroxetine | 1 back pain, 1 breast neoplasm | 2 out of 97 | No serious adverse events | 0 out of 99 |
Mendels et al., 1999 | Citalopram | 1 prostatic hyper trophy, 1 bronchitis | 2 out of 89 | 1 suicide | 1 out of 91 |
NCT00668525 (A), 2010 | Escitalopram | 1 chest pain, 1 pharyngitis 1 multiple sclerosis | 3 out of 319 | 1 asthma, 1 haemothorax | 2 out of 108 |
NCT00668525 (B), 2010 | Escitalopram | 1 chest pain, 1 appendicitis, 2 anxiety, 1 suicidal ideation, 1 suicide attempt, 1 peripheral vasuclar disorder | 7 out of 318 | 1 injury, 1 suicidal ideation | 2 out of 107 |
Nierenberg et al., 2007 | Escitalopram | 1 death and 3 unspecified serious adverse events | 4 out of 274 | 2 unspecified serious adverse events | 2 out of 137 |
WELL AK130926, 2007 | Escitalopram | 1 agitation | 1 out of 144 | No serious adverse event | 0 out of 132 |
WELL AK130927, 2007 | Escitalopram | 2 suicidal ideation, 1 hepatic function abnormal | 3 out of 138 | 1 suicidal ideation, 1 sudden caridac death | 2 out of 141 |
NCT01473381, 2014 | Escitalopram | 1 haemorrhagic anaemia, 1 diverticulitis, 1 ilium fracture, 1 road traffic accident, 1 traumatic renal injury, 1 wrist fracture, 1 abortion missed, 1 suicidal ideation, 1 hospitalisaation | 6 out of 280 (9 SAE in 6 participants) | 1 angina pectoris, 1 gastric disorder, 1 pneumonia, 1 neck abscess, 1 oral abscess, 1 abnormal electrocardiogram ST segment, 1 back pain, 1 suicidal ideation, 1 obstructive airways disorder | 3 out of 281 (9 SAE in 3 participants) |
Adamson et al., 2015 | Citalopram | 1 suicidal ideation, severe abdominal cramps | 2 out of 73 | No serious adverse event | 0 out of 65 |
CIT-MD-03, 2005 | Citalopram | 2 congestive heart failure, 1 cerebro vascular accident, 1 hyponatremia | 4 out of 84 | 1 cerebro vascular accident, 1 cellulitis | 2 out of 90 |
29060/810 (A), 2005 | Paroxetine CR 12.5 mg | 2 abnormal laboratory value, 1 carcinoma of lung | 3 out of 153 | 1 cerebro vascular disorder, 1 depression | 1 out of 73 (2 SAE in 1 participants) |
29060/810 (B), 2005 | Paroxetine CR 25 mg | 1 abnormal laboratory value, 1 gall bladder disorder, 1 anxiety, 1 emotional lability, | 4 out of 148 | 1 pleura disorder, 1 sinusitis, 1 bronchitis | 2 out of 73 (3 SAE in 2 participants) |
Adverse events
Event | No. of trials reporting the event | SSRI | Placebo | Relative risk (95% CI) | Number needed to harm (NNH) | P value | ||
---|---|---|---|---|---|---|---|---|
Number of participants with the event | Number of participants randomised | Number of participants with the event | Number of participants randomised | |||||
Abnormal ejaculation | 15 | 183 | 3236 | 7 | 1903 | 5.43 [3.22, 9.14] | 19 |
P < 0.00001 |
Tremor | 28 | 301 | 3502 | 61 | 2929 | 3.16 [2.37, 4.21] | 16 |
P < 0.00001 |
Anorexia | 19 | 220 | 2350 | 42 | 1680 | 2.78 [2.03, 3.79] | 15 |
P < 0.00001 |
Nausea | 78 | 2524 | 12,257 | 779 | 8491 | 2.48 [2.22, 2.77] | 9 |
P < 0.00001 |
Somnolence | 59 | 1336 | 10,351 | 345 | 6674 | 2.25 [2.00, 2.53] | 13 |
P < 0.00001 |
Sweating | 34 | 440 | 5274 | 124 | 3478 | 2.20 [1.80, 2.70] | 21 |
P < 0.00001 |
Asthenia | 23 | 497 | 3968 | 155 | 2265 | 1.71 [1.43, 2.04] | 18 |
P < 0.00001 |
Diarrhoea | 58 | 1458 | 11,056 | 561 | 7099 | 1.66 [1.51, 1.83] | 19 |
P < 0.00001 |
Constipation | 50 | 606 | 6698 | 273 | 4892 | 1.60 [1.35, 1.89] | 29 |
P < 0.00001 |
Insomnia | 69 | 1500 | 11,934 | 582 | 7956 | 1.49 [1.35, 1.64] | 19 |
P < 0.00001 |
Dizziness | 55 | 849 | 8900 | 398 | 6161 | 1.39 [1.24, 1.57] | 33 |
P < 0.00001 |
Dry mouth | 73 | 1376 | 11,303 | 693 | 7904 | 1.37 [1.25, 1.49] | 30 |
P < 0.00001 |
Libido decreased | 8 | 78 | 1481 | 11 | 1083 | 3.48 [1.92, 6.32] | 24 |
P < 0.0001 |
Sexual dysfunction | 6 | 96 | 719 | 16 | 389 | 2.85 [1.77, 4.59] | 11 |
P = 0.0001 |
Appetite decreased | 8 | 68 | 932 | 24 | 885 | 2.63 [1.66, 4.17] | 22 |
P < 0.0001 |
Fatigue | 26 | 409 | 5098 | 153 | 3545 | 1.69 [1.32, 2.17] | 27 |
P < 0.0001 |
Vomiting or upset stomach | 20 | 189 | 2376 | 101 | 2037 | 1.55 [1.16, 2.08] | 34 |
P = 0.003 |
Flu syndrome | 7 | 57 | 1069 | 19 | 822 | 2.13 [1.28, 3.54] | 34 |
P = 0.004 |
Drowsiness | 5 | 38 | 253 | 19 | 256 | 1.90 [1.18, 3.04] | 14 |
P = 0.004 |
Blurred/abnormal vision or dry eyes | 17 | 116 | 1862 | 55 | 1566 | 1.55 [1.15, 2.10] | 37 |
P = 0.004 |
Nervousness | 22 | 484 | 3863 | 147 | 2043 | 1.35 [1.10, 1.66] | 19 |
P = 0.004 |
Back pain | 11 | 85 | 2404 | 71 | 1594 | 0.66 [0.48, 0.91] | 109 |
P = 0.01 |
Headache | 72 | 2386 | 11,085 | 1427 | 7805 | 1.08 [1.01, 1.14] | 31 |
P = 0.02 |
Dyspepsia | 23 | 331 | 4304 | 159 | 2956 | 1.29 [1.04, 1.59] | 44 |
P = 0.02 |
Weight loss | 3 | 26 | 562 | 9 | 560 | 2.48 [1.17, 5.25] | 34 |
P = 0.02 |
Hypertension | 4 | 17 | 933 | 25 | 761 | 0.51 [0.28, 0.93] | 69 |
P = 0.03 |
Central or peripheral nervous system | 4 | 104 | 221 | 16 | 57 | 1.58 [1.03, 2.43] | 6 |
P = 0.04 |
Lightedness/faint feeling | 3 | 9 | 147 | 1 | 144 | 4.81 [1.06, 21.72] | 19 |
P = 0.04 |
Accidental injury | 3 | 15 | 672 | 23 | 516 | 0.50 [0.25, 0.99] | 45 |
P = 0.05 |
Agitation | 5 | 67 | 613 | 22 | 398 | 1.60 [1.01, 2.54] | 19 |
P = 0.05 |
Impotence | 3 | 19 | 868 | 1 | 603 | 3.12 [0.99, 9.88] | 50 |
P = 0.05 |
Taste perversion | 2 | 9 | 389 | 1 | 390 | 5.80 [1.02, 33.03] | 49 |
P = 0.05 |
Shaking | 2 | 7 | 121 | 0 | 116 | 7.19 [0.91, 57.03] | 18 |
P = 0.06 |
Rhinitis | 14 | 197 | 3004 | 171 | 1969 | 0.78 [0.63, 0.97] | 47 |
P = 0.06 |
Palpitations | 10 | 63 | 1572 | 30 | 1292 | 1.55 [0.97, 2.50] | 60 |
P = 0.07 |
Infection | 7 | 104 | 997 | 57 | 612 | 1.31 [0.97, 1.75] | 90 |
P = 0.08 |
Amnesia | 2 | 5 | 484 | 12 | 486 | 0.44 [0.16, 1.20] | 70 |
P = 0.11 |
Psychiatric adverse effects | 1 | 19 | 40 | 7 | 26 | 1.76 [0.87, 3.60] | 5 |
P = 0.12 |
Sleep distrurbance | 3 | 15 | 240 | 7 | 223 | 1.98 [0.83, 4.73] | 33 |
P = 0.13 |
Sinusitis | 4 | 35 | 751 | 38 | 629 | 0.69 [0.43, 1.11] | 73 |
P = 0.13 |
Urinary frequency | 4 | 40 | 695 | 19 | 624 | 1.80 [0.82, 3.96] | 37 |
P = 0.13 |
Anxiety | 17 | 150 | 2983 | 89 | 2250 | 1.27 [0.91, 1.77] | 94 |
P = 0.15 |
Appetie increased | 3 | 5 | 335 | 10 | 330 | 0.49 [0.17, 1.43] | 65 |
P = 0.19 |
Coughing | 1 | 8 | 100 | 4 | 96 | 1.92 [0.60, 6.17] | 27 |
P = 0.27 |
Tinnitus | 2 | 4 | 319 | 1 | 319 | 2.84 [0.44, 18.44] | 107 |
P = 0.27 |
Adverse events overall | 4 | 32 | 232 | 14 | 160 | 1.36 [0.77, 2.39] | 20 |
P = 0.29 |
Unpleasant taste | 1 | 2 | 21 | 0 | 20 | 4.77 [0.24, 93.67] | 11 |
P = 0.30 |
Congestive heart failure | 1 | 0 | 335 | 2 | 336 | 0.20 [0.01, 4.16] | 168 |
P = 0.30 |
Gastrointestial | 4 | 66 | 194 | 14 | 91 | 1.53 [0.65, 3.62] | 6 |
P = 0.33 |
Autonomic nervous system | 1 | 10 | 40 | 4 | 26 | 1.63 [0.57, 4.64] | 11 |
P = 0.36 |
Respiratory disorder | 10 | 244 | 2764 | 107 | 1276 | 0.90 [0.73, 1.12] | 227 |
P = 0.36 |
Vasodialtion | 4 | 11 | 368 | 4 | 355 | 1.75 [0.44, 6.94] | 54 |
P = 0.43 |
Flatulence | 6 | 94 | 1763 | 34 | 972 | 1.24 [0.72, 2.16] | 55 |
P = 0.44 |
Malaise | 1 | 0 | 21 | 1 | 20 | 0.32 [0.01, 7.38] | 20 |
P = 0.48 |
Depression aggrevated | 1 | 6 | 337 | 1 | 180 | 1.95 [0.31, 12.35] | 82 |
P = 0.48 |
Female genital disorders | 1 | 7 | 310 | 1 | 149 | 1.93 [0.31, 12.10] | 63 |
P = 0.48 |
Weight gain | 1 | 3 | 129 | 5 | 129 | 0.60 [0.15, 2.46] | 65 |
P = 0.48 |
Tachycardia | 6 | 9 | 989 | 6 | 996 | 1.43 [0.52, 3.96] | 326 |
P = 0.49 |
Arrhythmia | 1 | 0 | 335 | 1 | 336 | 0.33 [0.01, 8.18] | 336 |
P = 0.50 |
Atrial fibrillation | 1 | 1 | 335 | 0 | 336 | 3.01 [0.12, 73.60] | 335 |
P = 0.50 |
Abnormal electrocardiogram | 1 | 1 | 335 | 0 | 336 | 3.01 [0.12, 73.60] | 335 |
P = 0.50 |
Migraine | 1 | 1 | 129 | 0 | 129 | 3.00 [0.12, 72.96] | 129 |
P = 0.50 |
Chest discomfort | 1 | 1 | 21 | 0 | 20 | 2.86 [0.12, 66.44] | 21 |
P = 0.51 |
Rash | 5 | 9 | 280 | 12 | 282 | 0.79 [0.37, 1.70] | 97 |
P = 0.55 |
Vertigo | 1 | 10 | 337 | 3 | 180 | 1.58 [0.32, 7.68] | 77 |
P = 0.57 |
Dysuria | 1 | 2 | 21 | 1 | 20 | 1.90 [0.19, 19.40] | 23 |
P = 0.58 |
Pruritus (Itching) | 3 | 8 | 187 | 10 | 185 | 0.79 [0.30, 2.10] | 89 |
P = 0.63 |
Orthostatic hypotension | 2 | 6 | 466 | 3 | 309 | 1.37 [0.37, 5.02] | 316 |
P = 0.64 |
Upper respiratory tract infection | 14 | 164 | 2380 | 123 | 1882 | 0.95 [0.75, 1.20] | 282 |
P = 0.68 |
Body as a whole | 1 | 6 | 40 | 3 | 26 | 1.30 [0.36, 4.75] | 29 |
P = 0.69 |
Loose stools | 1 | 3 | 100 | 2 | 96 | 1.44 [0.25, 8.43] | 110 |
P = 0.69 |
Gastritis | 1 | 3 | 62 | 5 | 138 | 1.34 [0.33, 5.41] | 83 |
P = 0.69 |
Cardiovascular disorder | 2 | 10 | 444 | 3 | 355 | 0.81 [0.22, 2.95] | 72 |
P = 0.75 |
Pain | 5 | 65 | 893 | 59 | 729 | 0.95 [0.68, 1.34] | 123 |
P = 0.77 |
Abnormal thinking | 1 | 7 | 335 | 8 | 336 | 0.88 [0.32, 2.39] | 344 |
P = 0.80 |
Abnormal acne | 1 | 3 | 32 | 1 | 14 | 1.31 [0.15, 11.54] | 45 |
P = 0.81 |
Confusion | 4 | 5 | 640 | 5 | 621 | 0.87 [0.28, 2.74] | 4187 |
P = 0.81 |
Myalgia | 5 | 34 | 692 | 26 | 572 | 0.93 [0.45, 1.94] | 272 |
P = 0.85 |
Irritability | 6 | 18 | 643 | 20 | 642 | 0.92 [0.38, 2.27] | 317 |
P = 0.86 |
Numbness | 2 | 12 | 272 | 8 | 269 | 0.77 [0.04, 13.27] | 70 |
P = 0.86 |
Abdominal pain | 9 | 98 | 1967 | 52 | 1150 | 1.02 [0.73, 1.44] | 218 |
P = 0.89 |
Trauma | 2 | 47 | 883 | 14 | 267 | 0.95 [0.41, 2.20] | 1261 |
P = 0.90 |
Eructation (burping) | 1 | 5 | 100 | 5 | 96 | 0.96 [0.29, 3.21] | 480 |
P = 0.95 |
Over sedation | 3 | 24 | 677 | 7 | 514 | 1.91 [0.83, 4.39] | 46 |
P =0.13 |