Table 2.
Effects of Different Groups of Add-On Antidepressants on Major Psychopathology Domains of Schizophrenia: Summary of Randomized Controlled Trials (RCTs)
| AntidepressantGroup | Effect | Negative Symptoms | Positive Symptoms | Depressive symptoms | Extrapyramidal symptoms | Cognitive symptoms |
|---|---|---|---|---|---|---|
| TCA | + | 1,4 (n=101) | n/a | 4 (n=14) | n/a | n/a |
| 0 | 2 (n=20) | n/a | n/a | n/a | n/a | |
| SSRI | + | 5,7,8,15,29 (n=187) | n/a | 7,21 (n=60) | n/a | n/a |
| 0 | 9,10,13,14,18,20,21,28,35 (n=335) | 5,7,8,9,10,13,14,15,18,20,21,28,2 9 (n=489) | 9,14,20,29,35 (n=163) |
8,13,14,20,21,29,35 (n=233) | 28 (n=19) | |
| NRI | + | n/a | n/a | 22 | n/a | n/a |
| 0 | 17,22 (n=56) | 17,22 (n=56) | 17 (n=30) | 17,22 (n=56) | n/a | |
| SNRI | + | 38 (n=33) | n/a | 38 (n=33) | n/a | n/a |
| 0 | n/a | 38 (n=33) | n/a | n/a | n/a | |
| NDRI | + | n/a | n/a | n/a | n/a | 27 (n=53) |
| 0 | 26, 40 (n=85) | 26, 40 (n=85) | 3, 26 (n=91) | n/a | n/a | |
| Receptor blocking antidepressants | + | 6,11,12,16,19,25,31,32,36,41 (n=325) | 31 (n=39) | 39 (n=41) | 11,24,31,34 (n=140) | 23,33 (n=67) |
| 0 | 23,30,34 (n=83) | 6,11,12,16,19,23,25,30,32,34,36 (n=341) | 19,23,25,30,34 (n=125) |
12,16,23,30,32,37 (n=200) |
n/a |
Abbreviations: n/a, no published RCTs found; NDRI, noradrenaline and dopamine reuptake inhibitor; NRI, selective noradrenaline reuptake inhibitor; SNRI, serotonin and noradrenaline reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; +, result favoring antidepressant over placebo; 0, no difference between antidepressant and placebo.
Worsening of schizophrenia symptoms was not reported in any of the studies. The numbers in the syndrome columns refer to the index number of the RCT listed below. The list is arranged in chronological order, meaning that the larger the number the more recent (and often methodologically more reliable) is the corresponding study. The positive (+) and negative (0) studies ratio depicts roughly the balance of pro et contra evidence for each antidepressant group in each symptom domain. (The studies are not weighted in terms of methodological quality or number of participants and should be thus taken with caution).