Table 2.
Clinical trials of metabolic modulating agents in Bipolar Disorder (BD).
| Reference | Participants (N, % Female, Age) | Age (SD) * | Medication | Comparator | Diagnosis | Enrichment | Outcome Measure and Trial Duration | Result |
|---|---|---|---|---|---|---|---|---|
| Statin | ||||||||
| Fotso Soh et al. 2020 (secondary analysis) |
N = 60, 58.3% | 47.8 (13.8) and 53.1 (11.8) | atorvastatin (20 mg) + lithium | placebo + lithium | DSM-IV BD or MDD | lithium induced diabetes insipidus | global cognition Z-score, 12-week RCT | No between group differences |
| Lotfi et al. 2017 | N = 27 | Not reported | Lovastatin +TAU | Placebo + TAU | DSM-IV BD (mania) | none | YMRS, 4-week RCT | No significant difference found between groups |
| Ghanizadeh et al. 2013 |
N = 54, 44.4% female | 30.5 (8.1) and 29.5 (10.8) | Lovastatin + lithium | Placebo + lithium | DSM-IV BD (mania) | none | YMRS, 4 weeks | No significant difference found between groups |
| Poly Unsaturated Fatty Acid (PUFA) | ||||||||
| Sarris et al. 2012 | 5 RCT (N = 291) for bipolar depression revealed a significant effect size (0.34) in favor of omega-3 (p = 0.029) 5 RCT (N = 291) for bipolar mania revealed a non-significant effect |
|||||||
| McPhilemy et al. 2020 | N = 80, 51.25% | 45 (13) and 48 (12) | EPA (1 g) + TAU | Placebo + TAU | DSM-IV BD (any mood state) | 3 mood relapses in last 5 years and 2 in the last 3 years | mood state relapse (mania or depression), 52-week RCT | no significant differences in the number of mood episode relapses (U = 490.00, p = 0.14) and no significant difference for time to relapse between groups (Log Rank χ2 = 0.41, p = 0.52). |
| Ciappolino et al. 2020 | N = 31, 71%, | 36 (12) and 50.4 (11.3) | DHA supplementation (1250 mg) + TAU | Placebo + TAU | DSM-IV BD (euthymia) | None | BAC-A, 12-week RCT | no significant effects on cognition between groups. |
| Thiazolidinediones (TZD) | ||||||||
| Zeinoddini et al. 2015 | N = 44, 34.1% | 33.6 (3.5) and 31.2 (5.6) | pioglitazone (30 mg) + lithium | Placebo + lithium | DSM-IV BD (depressed) | None | HDRS, YMRS, 6-week RCT | significant effect for time × treatment interaction on the HDRS scores [F (2.78, 116.65) = 4.77, p = 0.005] |
| Aftab et al. 2019 | N = 38, 64.9%, | 46.7 (12.1) and 43.7 (13) | pioglitazone (15–45 mg) + TAU | Placebo + TAU | DSM-IV BD (depressed) | None | IDS-C30, 8-week RCT | mean reduction from baseline to week 8 in IDS-C30 score was−6.59 for pioglitazone and −11.63 for placebo |
| Insulin | ||||||||
| McIntyre et al. 2012 | N = 62, 46.8%, | 40.8 (10.2) and 39.3 (10.4) | intranasal insulin (40 IU q.i.d). + TAU | Placebo + TAU | DSM-IV BD (euthymia) | None | CVLT-II and PDT, 8-week RCT |
significant improvement versus placebo with intranasal insulin therapy on secondary measure of executive function (i.e., TMTB). No group differences on primary measure |
CVLT-II: California Verbal Learning Test, second edition; PDT: Process Dissociation Task; TMTB: Trail-Making test-B; BAC-A: Brief Assessment of Cognition in Affective Disorder; TAU: Treatment as usual; YMRS: Young Mania Rating Scale; HDRS: Hamilton Depression Rating Scale; IDS-C30: Inventory of depressive symptomatology; DHA: docosahexaenoic acid; EPA; eicosapentaenoic acid. * age is reported for active medication group and then comparator group.