ABSTRACT
BACKGROUND: This PET study is a continuing investigation of the effects of antidepressant medication and one night of total sleep deprivation on cerebral metabolism in depressed patients. This study was undertaken to confirm previous correlations between symptom improvement ratings and regional changes in glucose metabolism, using a higher resolution scanner than in previous investigations. In addition, we also studied the effect of concomitant antidepressant medication in conjunction with sleep depression. METHOD: Six depressed patients were administered the selective serotonin reuptake inhibitor sertraline for a week and then underwent positron emission tomography (FDG PET) before and after sleep deprivation. Changes in relative glucose metabolism were correlated with symptom improvement ratings in Hamilton Depression Rating Scale scores. RESULTS: Positive correlations (defined as reduced HDRS scores associated with areas having reduced relative cerebral glucose metabolism after TSD) were found in the inferior frontal gyrus and inferior frontal/orbital frontal cortex. Negative correlations (defined as reduced HDRS scores associated with areas of increased relative cerebral glucose metabolism after TSD) were found in the dorsolateral prefrontal cortex. LIMITATIONS: Limitations of this study are that the number of subjects was small (n=6) and they were scanned at a 7.6 mm resolution. CONCLUSIONS: The results of this study support previous findings on the effects of sleep deprivation and antidepressant medications in the treatment of unipolar and bipolar depression, with an emphasis on the significance of cerebral glucose metabolic changes in the ventral and DLPF cortex in mood regulation.
Subject(s)
Brain/metabolism , Depressive Disorder/diagnostic imaging , Depressive Disorder/metabolism , Glucose/metabolism , Positron-Emission Tomography/statistics & numerical data , Sleep Deprivation , Adult , Antidepressive Agents/therapeutic use , Brain/diagnostic imaging , Brain Mapping , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/metabolism , Combined Modality Therapy , Depressive Disorder/therapy , Female , Fluorodeoxyglucose F18/metabolism , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/metabolism , Humans , Male , Middle Aged , Psychiatric Status Rating Scales/statistics & numerical data , Tissue DistributionABSTRACT
BACKGROUND: The development of a rapid-acting and sustainable treatment for bipolar disorder (BPD) depression has been a goal for decades. The most widely documented rapid-onset antidepressant therapy is sleep deprivation (SD), which acts within 24-48 hours in 40%-60% of depressed patients. Conventional antidepressants usually require 2-8 weeks to meet response criteria. The delay, which may prolong suffering and increase suicidal risk, underlines the urgency of alternative treatment strategies. This study evaluates the combined efficacy of three established circadian-related treatments (SD, bright light [BL]), sleep phase advance [SPA]) as adjunctive treatment to lithium and antidepressants. METHODS: Forty-nine BPD patients were randomly assigned to a chronotherapeutic augmentation (CAT; SD+ BL+ SPA) or to a medication-only (MED) group. Clinical outcome was assessed using the Hamilton Rating Scale for Depression. RESULTS: Significant decreases in depression in the CAT versus MED patients were seen within 48 hours of SD and were sustained over a 7-week period. CONCLUSIONS: This is the first study to demonstrate the benefit of adding three noninvasive circadian-related interventions to SD in medicated patients to accelerate and sustain antidepressant responses and provides a strategy for the safe, fast-acting, and sustainable treatment of BPD.