Clonidine augmentation in patients with schizophrenia: A double-blind, randomized placebo-controlled trial.

INTRODUCTION: Noradrenergic imbalance in the brain of schizophrenia patients may underlie both symptomatology and deficits in basic information processing. The current study investigated whether augmentation with the noradrenergic α2-agonist clonidine might alleviate these symptoms. METHODS: In a double-blind placebo-controlled randomized clinical trial, 32 chronic schizophrenia patients were randomly assigned to six-weeks augmentation with either 50 µg clonidine or placebo to their current medication. Effects on symptom severity and both sensory- and sensorimotor gating were assessed at baseline, 3- and 6-weeks. Results were compared with 21 age- and sex-matched healthy controls (HC) who received no treatment. RESULTS: Only patients treated with clonidine showed significantly reduced PANSS negative, general and total scores at follow-up compared to baseline. On average, also patients treated with placebo showed minor (non-significant) reductions in these scores, likely indicating a placebo effect. Sensorimotor gating of patients was significantly lower at baseline compared to controls. It increased in patients treated with clonidine over the treatment period, whereas it decreased in both the HC and patients treated with placebo. However, neither treatment nor group effects were found in sensory gating. Clonidine treatment was very well tolerated. CONCLUSION: Only patients treated with clonidine showed a significant decrease on two out of the three PANSS subscales, while additionally retained their levels of sensorimotor gating. Given that there are only a few reports on effective treatment for negative symptoms in particular, our current results support augmentation of antipsychotics with clonidine as a promising, low-cost and safe treatment strategy for schizophrenia.

Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder.

Amygdala hyperactivation in major depressive disorder (MDD) might be attenuated by selective serotonin reuptake inhibitors (SSRIs), but the working mechanism remains unclear. We hypothesized that higher amygdala serotonin transporter (SERT) occupancy by paroxetine results in greater attenuation of amygdala activation by negative facial expressions in MDD patients. We treated fifteen MDD patients (22-55 years) with paroxetine 20-50mg/day. After 6 and 12 weeks, we quantified (1) clinical response (≥50% decrease in Hamilton Depression Rating Scale (HDRS), (2) SERT occupancy in both amygdala measured by repeated [123I]ß-CIT single photon emission computed tomography (SPECT), and (3) amygdala activation when viewing fearful and angry (negative) faces with repeated functional MRI scans. Response rates were 4/15 and 9/15 at 6 and 12 weeks, respectively. Attenuation of left amygdala activation was associated with amygdala SERT occupancy (P=0.006) and response (P=0.015). This association may provide a rationale for decreased limbic activity seen during treatment of MDD. It might also explain the rapid decrease in negative attentional bias and amygdala activation caused by SSRIs.