Paroxetine treatment of depression with posttraumatic stress disorder: effects on autonomic reactivity and cortisol secretion.

Effects of paroxetine treatment of comorbid depression and posttraumatic stress disorder (PTSD) on subjective symptoms, autonomic reactivity, and diurnal salivary cortisols were assessed prospectively. Cross-sectional baseline psychophysiologic assessments of 22 patients with depression + PTSD, 21 with depression alone, and 20 asymptomatic, previously traumatized controls found that comorbid patients had higher blood pressure and heart rate reactivity to individualized trauma scripts than purely depressed and control groups. On discriminant analyses comparing comorbid patients with each other group, combined autonomic variables correctly classified 55% of comorbid patients (sensitivity) and 75% of traumatized, healthy subjects (specificity) as well as 55% of comorbid patients (sensitivity) and 86% of purely depressed patients (specificity). Although baseline AM and PM salivary cortisol levels were within reference range and did not differ significantly across groups, depression + PTSD patients differed from the other 2 groups in having a flattened diurnal pattern. After 10 weeks of open-label paroxetine, comorbid patients significantly improved in all PTSD symptom evaluations and physiologic reactivity measures but did not change cortisol levels or acquire a robust diurnal cortisol pattern. Ten treated depressed patients did not change in physiologic or cortisol measures. Results demonstrate that sampled comorbid patients had autonomic reactivity patterns similar to PTSD that responded to selective serotonin reuptake inhibitor treatment but had diurnal cortisol secretion patterns different from depression or that expected for PTSD, which did not change with treatment. Results suggest a complexity in the neurobiology of comorbid PTSD and major depression and its response to treatment.

Can physiologic assessment and side effects tease out differences in PTSD trials? A double-blind comparison of citalopram, sertraline, and placebo.

Effects of double-blind treatment of chronic posttraumatic stress disorder (PTSD) with 2 SSRIs and placebo on emotional symptoms and autonomic reactivity were assessed prospectively. PTSD subjects received citalopram (n=25), sertraline (n=23), or placebo (n=10) for 10 weeks, with psychophysiologic assessments performed before and after treatment. Intent-to-treat analysis showed that all treatment groups improved significantly in total symptoms of PTSD (as measured by the Clinician Administered PTSD Scale), all 3 PTSD symptom clusters, and sleep time. However, subtle differences in improvements in PTSD symptom clusters, physiologic reactivity, and reported adverse events were identified. Citalopram treated subjects significantly lowered systolic and diastolic blood pressures, while sertraline and placebo treated patients significantly lowered only systolic blood pressure reactivity to individualized trauma scripts. The sertraline group showed significantly more improvement in avoidance/numbing symptoms than both other groups. Considering side effects, subjects on sertraline reported more gastrointestinal problems, with early terminators having more insomnia. Early terminators on citalopram reported more fatigue and appetite changes than other treatment groups, with completers reporting more sexual dysfunction. Results support a class effect of SSRIs in treating PTSD symptoms, but suggest a possible differential effect of drugs on symptom clusters, physiologic parameters, and side effects that may have clinical relevance. Implications of symptom reduction noted in the smaller placebo group are discussed relative to recent concerns about increasing placebo response in clinical trials.