Response acceleration with mirtazapine augmentation of citalopram in obsessive-compulsive disorder patients without comorbid depression: a pilot study.
BACKGROUND
Therapeutic action of selective serotonin reuptake inhibitors (SSRIs) is delayed from 8 to 12 weeks in patients with obsessive-compulsive disorder (OCD). Several different agents have been tested to reduce the SSRI therapeutic latency time. Mirtazapine, an antagonist at alpha2-adrenoceptors, does not enhance serotonin (5-HT) neurotransmission directly but disinhibits the norepinephrine activation of 5-HT neurons and thereby increases 5-HT neurotransmission by a mechanism that may not require a time-dependent desensitization of receptors. The present study was undertaken to determine whether the mirtazapine-citalopram combination could induce an earlier and/or greater effect on the 5-HT system in OCD subjects than citalopram alone.


METHODS
Forty-nine patients with OCD (DSM-IV) without comorbid depression were randomly assigned to a 2-tailed, single-blind, 12-week clinical trial with citalopram (20-80 mg/day) plus placebo or citalopram plus mirtazapine (15-30 mg/day). Assessments were performed weekly with the Yale-Brown Obsessive Compulsive Scale (YBOCS), the Hamilton Rating Scale for Depression, and the Clinical Global Impressions scale. Data were collected from November 2001 to July 2003.


RESULTS
The citalopram plus mirtazapine group achieved a reduction of at least 35% in YBOCS score and a "much improved" or "very much improved" rating on the Clinical Global Impressions-Improvement scale from the fourth week, while the citalopram plus placebo group obtained these results only from the eighth week. The number of responders was higher in the citalopram plus mirtazapine group at the fourth week of treatment, while no difference between groups in the response rate was noted at the eighth and twelfth weeks of treatment.


CONCLUSIONS
We found an earlier onset of response action in OCD symptoms and reduced undesired side effects when mirtazapine was added to citalopram. This augmentation strategy deserves clinical and research consideration through further double-blind, placebo-controlled studies.
Pallanti
Stefano
S
Institute for Neurosciences, Florence, Italy. s.pallanti@agora.stm.it
Quercioli
Leonardo
L
Bruscoli
Matteo
M
D000328:Adult; D017668:Age of Onset; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000627:therapeutic use*; D015283:Citalopram / Q000009:adverse effects / Q000627:therapeutic use*; D015897:Comorbidity; D003866:Depressive Disorder / Q000453:epidemiology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000078785:Mirtazapine; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000453:epidemiology; D010865:Pilot Projects; D015995:Prevalence; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020018:Sexual Dysfunctions, Psychological / Q000139:chemically induced / Q000453:epidemiology; D016037:Single-Blind Method; D007319:Sleep Initiation and Maintenance Disorders / Q000139:chemically induced / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D015430:Weight Gain
D000929:Antidepressive Agents, Tricyclic; D015283:Citalopram; D008803:Mianserin; D000078785:Mirtazapine; D017367:Selective Serotonin Reuptake Inhibitors