Olanzapine/fluoxetine combination: Evidence for using the first treatment indicated for bipolar depression
Tolerability
Common side effects of OFC include increased appetite, weight gain, somnolence, fatigue, nausea, diarrhea, and dry mouth—the same effects associated with olanzapine or fluoxetine.
Combining the agents does not lessen the side effects, particularly olanzapine-induced weight gain. Simple, assertive dietary and exercise counseling can counteract olanzapine-induced weight gain.13 Sexual dysfunction was reported infrequently in clinical trials but is possible with exposure to fluoxetine.
Extrapyramidal side effects, including akathisia, appear to be relatively infrequent. Tardive dyskinesia (TD) is unlikely, although cases putatively associated with olanzapine have been reported.5 Many patients with TD have taken conventional antipsychotics, however, so the causal link with olanzapine is obscure. Still, alert patients and families to the possibility of TD and its emerging features.
Table 2
Olanzapine-fluoxetine: Fast facts
| Drug brand name: Symbyax |
| Class: Combined atypical antipsychotic/selective serotonin reuptake inhibitor |
| FDA-approved indication: Bipolar type I depression |
| Approval date: Dec. 24, 2003 |
| Manufacturer: Eli Lilly and Co. |
| Dosing forms: 6/25 mg/d, 12/50 mg/d, 12/25 mg/d, 12/50 mg/d |
| Dosing recommendations: Start at 6/25 mg at bedtime. Titrate according to tolerability and therapeutic benefit. Once the antidepressant effect is achieved, continue dosage indefinitely if no adverse effects occur. Dosages up to 18/75 mg/d have been used in clinical trials. |
Although considered rare, isolated cases of neuroleptic malignant syndrome have been attributed to olanzapine.14 Cycle induction has not been reported in clinical trials, but be mindful of this possibility with long-term treatment.
Clinical implications
Taking olanzapine and fluoxetine as a single capsule could save the patient substantial cost. OFC comes in four dosing forms (Table 2), allowing for some flexibility.
It is unclear whether clinicians will prefer the single combination capsule or prescribe each drug separately to increase flexibility. Starting treatment with olanzapine and fluoxetine individually allows the psychiatrist to change the dosages independently and in smaller increments. Taken as separate agents, however, the two products are more expensive than the combined formula. OFC costs about the same as olanzapine alone. On the other hand, if the clinician begins the compounds individually, converting to the dosages in the combined product probably will not be exactly 1:1.
Tolerability is another major advantage of OFC; the combined agent exhibited a 10% dropout rate because of adverse effects compared with 4.6% for placebo.7 Moreover, some patients will prefer the convenience of using a single capsule instead of two medications.
Related resources
- Tollefson GD, Sanger TM. Anxious-depressive symptoms in schizophrenia: a new treatment target for pharmacotherapy? Schizophr Res 1999;35(suppl):S13-S21.
- Symbyax Web site. www.symbyax.com
Drug brand names
- Citalopram • Celexa
- Clomipramine • Anafranil
- Diazepam • Valium
- Fluoxetine • Prozac
- Haloperidol • Haldol
- Imipramine • Tofranil
- Metoprolol succinate • Toprol
- Nortriptyline • Aventyl
- Olanzapine • Zyprexa
- Omeprazole • Prilosec
- Phenytoin • Dilantin
- Proguanil • Malarone
- Propafenone • Rythmol
- Propranolol • Inderal
- Risperidone • Risperdal
- Tolbutamide • Orinase
- Venlafaxine • Effexor
- Warfarin • Coumadin
Disclosure
Dr. Shelton receives research grants from Abbott Laboratories, Eli Lilly and Co., GlaxoSmithKline, Janssen Pharmaceutica, Pfizer Inc., and Wyeth Pharmaceuticals; is a consultant to Janssen Pharmaceutica, Pfizer Inc., and Wyeth Pharmaceuticals; and is a speaker for Abbott Laboratories, Eli Lilly and Co., Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Pfizer Inc., and Wyeth Pharmaceuticals
