Table 2.
Double-blind, placebo-controlled clinical trials of antidepressants for treating depressive symptoms in patients with schizophrenia
| Antidepressants | Type of antidepressant | Antipsychotics | Duration | Size | Female (%) | Age (years) | Depression | Effect on depression | Effect on negative symptoms and other effects | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
| Amitriptyline | TCA | FGA | 4 months | 35 | na | na | na | Significant improvement, superior to placebo | na | 70 |
| Amitriptyline, desipramine | TCA | FGA | 4 weeks | 58 | na | na | HAM-D>I7 | No significant difference compared to placebo | na | 86 |
| Imipramine | TCA | FGA | 4 weeks | 52 | 32.7 | 38 | HAM-D 3/4 or anergic 3/4 | No significant difference compared to placebo | na | 132 |
| Impiramine | TCA | FGA | 6 weeks | na | na | na | Post-psychotic | Significant improvement, superior to placebo | AD showed a better global improvement and no significant effect on psychosis or side effects | 133 |
| Fluvoxamine | SSRI | FGA | 6 weeks | 30 | 37 | 41.5 | HAM-D 7.7±4.9 | Depressive features showed significant improvement with time but no significant difference between active and placebo | na | 134 |
| Fluvoxamine | SSRI | FGA | 8 weeks | 32 | 28.10 | 36.6 | HAM-D 12.4±8.6 | No significant difference compared to placebo | na | 135 |
| Fluvoxamine | SSRI | na | 12 weeks | 34 | na | na | na | Slight but significant improvement, superior to placebo | AD showed significant improvement in negative symptoms. Side effects were more common in AD group | 136 |
| Fluoxetine | SSRI | SGA | 8 weeks | 33 | na | na | na | No significant difference compared to placebo | No significant differences in positive, negative, depressive, or obsessive–compulsive symptoms | |
| Sertraline | SSRI | FGA | 8 weeks | 26 | 38.50 | 38 | BPRS ≥3 and BDI ≥ 15 | Significant improvement in the anxiety/depression, superior to placebo | No significant effect on negative or positive symptoms. Sertraline was well tolerated | 88 |
| Sertraline | SSRI | SGA 58.3% | 6 weeks | 48 | 63.50% | 37.8 | CDSS 14.0±1.28; HAM-D 20.6 | Both groups showed improvement in depression, but no significant difference compared to placebo | na | 87 |
| Citalopram | SSRI | SGA ~90% | 12 weeks | 198 | 21.80 | 52.4 | HAM-D ≥8 | Significant improvement, superior to placebo | Significant improvement in negative symptoms, superior to placebo. No differences in positive symptoms, general medical health or other side effects | 72 |
| Escitalopram | SSRI | SGA 79% | 10 weeks | 38 | 28 | 37.2 | HAM-D 6.6±4.9 | No significant difference compared to placebo | No significant difference compared to placebo | 137 |
| Trazodone | SARI | FGA | 6 weeks | 60 | 43.30 | 43 | HAM-D > 18 | Significant improvement, superior to placebo | AD was well tolerated, minimal side effects | 138 |
| Bupropion | Atypical | FGA | 10 weeks | 38 | 36.80 | 41 | HAM-D > 18 | No significant difference compared to placebo | 139 | |
| Mirtazapine | NaSSA | FGA | 6 weeks | 39 | na | 18–65 | CDSS 4.58±5.08 | Significant improvement, superior to placebo | The changes in the CDSS correlated positively with those in the PANSS negative, positive, and total (sub) scales in AD group | 89 |
| Mirtazapine | NaSSA | SGA | 6 weeks | 40 | 15 | 36.8 | HAM-D 12.28±6.31; CDSS 5.44±4.49 | No significant difference compared to placebo | No significant difference compared to placebo | 140 |
| Viloxazine | NRI | FGA | 4 weeks | 28 | na | 19–53 | HAM-D > 18 | No significant difference compared to placebo | na | 141 |
| Reboxetine | NRI | FGA | 6 weeks | 30 | 6.70 | 32.4 | Endpoint HAM-D 6.93±4.16 | No significant difference compared to placebo | No overall difference between the two groups | 142 |
Note: The gray shading highlights those that did not indicate any positive result.
Abbreviations: TCA, tricyclic antidepressant; FGA, first generation antipsychotics; HAM-D, Hamilton Rating Scale for Depression; AD, antidepressant; SSRI, selective serotonin reuptake inhibitor; SGA, second generation antipsychotics; BPRS, Brief Psychiatric Rating Scale; BDI, Beck Depression Inventory; CDSS, Calgary Depression Scale for Schizophrenia; SARI, serotonin antagonist and reuptake inhibitor; NaSSA, noradrenergic and specific serotonergic antidepressant; PANSS, Positive and Negative Syndrome Scale; NRI, norepinephrine reuptake inhibitor; na, not applicable.