Addition of Olanzapine for Treatment-Resistant Depression
To the Editor: Olanzapine is a newer atypical antipsychotic with a broad spectrum of affinity for several receptors (serotonin 5-HT2A, 5-HT2C, 5-HT3, and 5-HT6 and dopamine D1–5, α1, histamine H1, and muscarinic M1–5). Some reports have suggested that olanzapine can have antidepressant properties (1–3). We describe the case of a woman with a long history of treatment-resistant nonpsychotic chronic depression who exhibited a dramatic improvement after the addition of olanzapine to her venlafaxine treatment.
Ms. A was a 40-year-old woman with a 10-year history of unipolar nonpsychotic major depression. She had been treated with several antidepressants, including tricyclics such as amitriptyline and clomipramine, which were prescribed at doses higher than 200 mg/day for at least 8 weeks, and selective serotonin reuptake inhibitors (paroxetine, 40 mg/day, fluoxetine, 40 mg/day) for more than 12 weeks. We had also tried augmentation with lithium, 750 mg/day, and carbamazepine, 600 mg/day, without success.
During a particularly severe depressive episode (21-item Hamilton Depression Rating Scale score of 36), Ms. A was consecutively treated with iproclozide, a monoamine oxidase inhibitor, and ECT, but she experienced only a partial response. All of these trials appeared unsuccessful in achieving remission, and Ms. A remained chronically depressed for several years, with a score regularly higher than 15 on the 21-item Hamilton depression scale. Her last treatment with venlafaxine, 300 mg/day, was associated with a moderate improvement in her depressive symptom profile (Hamilton depression scale score of 16). Because of mild nausea and sedation, her venlafaxine dose was decreased to 225 mg/day over about 1 year.
On the basis of the potential antidepressant effect of the newer antipsychotics, we decided to add olanzapine, 5 mg/day, to her treatment with venlafaxine, 225 mg/day. After 2–3 days Ms. A experienced an impressive improvement in her depressive symptoms, achieving a complete remission for the first time in 10 years (Hamilton depression scale score of 0). Olanzapine was well tolerated, with the exception of mild weight gain. Unfortunately, Ms. A considered the weight increase a major side effect and stopped taking olanzapine. After 4–5 days she experienced a new depressive symptom profile, consisting of a depressed mood, sadness, insomnia, a decrease in activities, and feelings of guilt and anxiety (Hamilton depression scale score of 14).
After 1 month she agreed to take olanzapine again, which was associated with a further dramatic antidepressant response after 3 days of administration. Her Clinical Global Impression (CGI) score for severity of illness was 1, and the CGI global improvement score was 1. Ms. A’s family described this improvement as unexpected. Currently, her full remission has been maintained for 15 months.
This report provides additional evidence of the possible usefulness of atypical antipsychotics, and in particular olanzapine, in the management of treatment-resistant depression. Indeed, recently, in a randomized, double-blind, amitriptyline-controlled study, Svestka and Synek (3) demonstrated the antidepressant efficacy of olanzapine in the treatment of depressed patients with bipolar and unipolar disorder. Shelton et al. (4) also observed the superior efficacy of olanzapine with fluoxetine compared to olanzapine or fluoxetine alone. In fact, atypical antipsychotics such as olanzapine could be particularly effective as an adjunctive treatment (5). However, further studies are needed to determine whether the augmentation effect of olanzapine is observed with other antidepressant medications.
1. Weisler RH, Ahearn EP, Davidson JR, Wallace CD: Adjunctive use of olanzapine in mood disorders: five case reports. Ann Clin Psychiatry 1997; 9:259-262Crossref, Medline, Google Scholar
2. Rothschild AJ, Bates KS, Boehringer KL, Syed A: Olanzapine response in psychotic depression. J Clin Psychiatry 1999; 60:116-118Crossref, Medline, Google Scholar
3. Svestka J, Synek O: Does olanzapine have antidepressant effect? a double-blind amitriptyline-controlled study (abstract). Int J Neuropsychopharmacol 2000; 3(suppl 1):S251Google Scholar
4. Shelton RC, Tollefson GD, Tohen M, Stahl S, Gannon KS, Jacobs TG, Buras WR, Bymaster FP, Zhang W, Spencer KA, Feldman PD, Meltzer HY: A novel augmentation strategy for treating resistant major depression. Am J Psychiatry 2001; 157:131-134Link, Google Scholar
5. Stoll AL, Haura G: Tranylcypromine plus risperidone for treatment-refractory major depression (letter). J Clin Psychopharmacol 2000; 20:495-496Crossref, Medline, Google Scholar
