Published reports (n = 8) describing the combined use of olanzapine and a non-antipsychotic agent
| Non-antipsychotic agent used with olanzapine | Reference | Study design | Diagnosis | Period of monitoring | No. of patients | Indication for combined therapy | Dose, mg/d | Effects as evaluated by psychometric scales | Side effects | |
|---|---|---|---|---|---|---|---|---|---|---|
| Olanzapine | Other agent | |||||||||
| Fluvoxamine | Hiemke et al (38) | OT | Schizophrenia | 8 wk | 8 | Research with regard to metabolism | 10–20 | 100 | SANS improved by ≥ 20% in 5 of 7 cases | Serum olanzapine concentration increased by 12%–112%. No other side effects |
| Reboxetine | Poyurovsky et al (39) | DbPlacT | Schizophrenia (DSM-IV) | 6 wk | 26 | Weight gain | 10 | 4 | Antidepressive effect in the treatment group (HAM-D) | Significantly less weight gain in the treatment group |
| Glycine | Heresco-Levy et al (40) | DbPlacT | Schizophrenia (DSM-IV) | 6 wk | 12 | Treatment resistance | 14.3 (SD 6.2) | 800 mg/kg/d | Improved NS (improved PS) | Upper gastrointestinal discomfort |
| Lamotrigine | Dursun and Deakin (41) | OT | Schizophrenia (DSM-IV) | 24 wk | 3 | Treatment resistance (BPRS ≥ 30) | 43.3 (SD 5.8) | 100–300 | No significant change of BPRS | No side effects |
| Topiramate | Dursun and Deakin (41) | OT | Schizophrenia (DSM-IV) | 24 wk | 3 | Treatment resistance (BPRS ≥ 30) | 33.3 (SD 5.7) | 225–300 | No significant change of BPRS | No side effects |
| Divalproex | Casey et al (42) | DbPlacT | Schizophrenia (DSM-IV) | 4 wk | 131 | Acute exacerbation (PANSS ≥ 60) | 15 | 2364 | Superiority of combined therapy (PANSS, BPRS) | Side effects not different |
| Divalproex | Citrome et al (43) | DbPlacT | Schizophrenia (DSM-IV) | 4 wk | 249* | Acute exacerbation (PANSS ≥ 60) | 15 | 2363 | Hostility item (PANSS) in combination improved.† Frequency of lorazepam use not different | Abnormal liver function, asthma, hyperglycemia, rash |
| Valproate | Cramer and Sernyak (44) | RetrCR | Chronic psychotic disorder assumed | 270 d | 547 | Insufficient response | 7.3 (SD 3.6) | 411.6 | Significantly longer treatment persistence‡ in combination as compared with olanzapine monotherapy (127 d v. 159 d) | Not reported |
| Valproate | Litrell et al (45) | OT | Schizophrenia (DSM-IV) | 12 mo | 10 | Treatment resistance | 19 (SD 6.6) | 750–2000 (serum level 50–100 μg/mL) | Reduced hostility (PANSS) in combination | Weight gain |
Note: BPRS = Brief Psychiatric Rating scale; DbPlacT = double-blind, placebo-controlled trial; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, fourth edition; HAM-D = Hamilton Rating Scale for Depression; NS = negative symptoms; OT = open trial; PANSS = Positive and Negative Syndrome scale; PS = positive symptoms; RetrCR = retrospective chart review; SANS = Scale for the Assessment of Negative Symptoms; SD = standard deviation.
↵* Subgroups: olanzapine + placebo (n = 65), olanzapine + divalproex (n = 66), risperidone + placebo (n = 60), risperidone + divalproex (n = 58). In total, 166 completers including cohorts treated with risperidone.
↵† As assessed at days 3 and 7, not significant at days 5,10,14,21 and 28.
↵‡ Kaplan–Meier curve.