Aripiprazole as adjunct to a mood stabilizer and citalopram in bipolar depression: a randomized placebo-controlled pilot study.

OBJECTIVE: The use of atypical antipsychotics (AAPs) for the treatment of unipolar and bipolar depression has been more and more frequently evaluated, and aripiprazole showed positive effects in the treatment of unipolar depression. However, no placebo-controlled studies of adjunctive aripiprazole for the treatment of bipolar depression have been performed yet. METHODS: In this prospective, double-blind, placebo-controlled, randomized trial, 23 inpatients with bipolar depression according to DSM-IV criteria were included. Before randomization, patients had to be on a constant mood stabilizer treatment with lithium or valproate for at least 1 week. After inclusion, all patients were openly treated with additional citalopram and with additional aripiprazole or placebo for 6 weeks. The primary outcome parameter was the reduction in depressive symptoms according to the Hamilton Depression Rating Scale (HDRS) within 6 weeks. RESULTS: After 6 weeks of treatment, the HDRS score decreased in both groups. There was no significant difference between both the groups at any point of time with respect to the HDRS. CONCLUSIONS: Derived from this small pilot study, adjunctive aripiprazole does not seem to be a promising strategy for the acute treatment of bipolar depression. However, this lack of additional benefit seems to stem from the already good effectiveness of the control group, namely the treatment with citalopram.

Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial.

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition borderline personality disorder (BPD) seems to constitute a very heterogeneous category. Therefore, pharmacological therapy is symptom-oriented or targets comorbid conditions. A high comorbidity exists between BPD and posttraumatic stress disorder (PTSD). In a double-blind, randomized, placebo-controlled crossover study, we sought to determine whether the antinoradrenergic agent clonidine was effective in reducing hyperarousal and measures of BPD-specific and general psychopathology in a sample of 18 patients with BPD, with or without comorbid PTSD, and with a prominent hyperarousal syndrome. Hyperarousal as measured by the Clinician Administered PTSD scale improved significantly compared with placebo (P = 0.003) irrespective of PTSD comorbidity. Improvements in general and BPD-typical psychopathology were mainly seen in the PTSD-positive subgroup, whereas the subjective sleep latency (P = 0.005) and the restorative qualities of the sleep (P = 0.014) improved in the whole sample. Improvements, despite the small sample size of this pilot study, lead us to conclude that clonidine might be a useful adjunct to pharmacotherapy in patients with BPD who have marked hyperarousal and/or sleep problems and, in particular, in patients with BPD who have a PTSD comorbidity.

Dissociation between reactivity of the hypothalamus-pituitary-adrenal axis and the sympathetic-adrenal-medullary system to repeated psychosocial stress.

OBJECTIVE: This study investigated endocrine and autonomic stress responses after repeated psychosocial stress. A first goal of the study was to investigate whether peripheral catecholamines and cardiovascular parameters would show similar or different habituation patterns after repeated stress. The second aim was to detect possible subgroups with regard to individual habituation patterns in the hypothalamus-pituitary-adrenal (HPA) axis and monitor their respective sympathetic stress responses. METHODS: Sixty-five healthy subjects (19-45 years), 38 men and 27 women, were exposed to the Trier Social Stress Test (TSST) three times with a 4-week interval between stress sessions. Adrenocorticotropic hormone (ACTH), plasma cortisol, salivary cortisol, epinephrine, norepinephrine, and heart rates were measures repeatedly before and after each stress exposure. RESULTS: All endocrine measures as well as heart rates increased significantly after each of the three stress sessions (F values >16.00, all p values <.01). Although salivary free cortisol, total plasma cortisol, ACTH, and heart rate stress responses showed a significant decrease across the three stress sessions (all F values > 5.8, p <.01), no such decrease could be observed for the levels of norepinephrine and epinephrine. A cluster analysis performed on the salivary free cortisol responses to all three stress sessions revealed two response groups consisting of 30 so-called "high responders" and 35 "low responders." The high responders also showed larger ACTH and total plasma cortisol responses compared with the low responders (all F values > 10.00, p <.01). No such differences between high and low responders could be observed with regard to catecholamine and heart rate responses. CONCLUSIONS: From these data we conclude that habituation to psychosocial stress seems to be specific for a given response system. Although HPA responses quickly habituate, the sympathetic nervous system shows rather uniform activation patterns with repeated exposure to psychosocial challenge.

Acute HPA axis responses, heart rate, and mood changes to psychosocial stress (TSST) in humans at different times of day.

There is evidence showing that HPA axis responses to pharmacological provocation depend on time of day with larger cortisol responses in the afternoon and evening compared to the morning hours. However, it is still unknown whether HPA axis responses to psychological stress are affected by time of day and whether they can be assessed with equal reliability in the morning and afternoon, respectively. The present reanalysis is based on five independent studies conducted in the same laboratory by and. All subjects were confronted with the Trier Social Stress Test (TSST) either in the morning or in the afternoon. The total sample consisted of 180 adults with 115 younger (49 females, 66 males) and 65 older adults (32 females, 33 males). All ANCOVA results controlled for possible age and gender effects. Stress-related free salivary cortisol, total plasma cortisol and ACTH net increases did not differ according to time of day (all p = n.s.). However, as expected pre-stress free salivary and total plasma cortisol levels differed significantly between the morning and afternoon group (both p < 0.005), leading to a significantly higher free cortisol area under the curve (AUC) in the morning (p = 0.02). Taken together, these observations suggest that the adrenal glands may be more sensitive to ACTH in the morning. Additionally, higher basal salivary cortisol levels were related to a lower stress-related net increase in salivary cortisol (p = 0.02), total plasma cortisol (p < 0.0001), and marginally ACTH (p = 0.09). Stress-related heart rate increases did not differ between groups (p = n.s.). The finding that the TSST-induced mood change was differentially affected by time of day requires further exploration. We conclude that comparable HPA axis and heart rate stress responses to psychosocial stress can be measured in the morning and afternoon.

The cortisol awakening response - normal values and confounds.

In several recent investigations it could be demonstrated that the free cortisol response to awakening can serve as an useful index of the adrenocortical activity. When measured with strict reference to the time of awakening the assessment of this endocrine response is able to uncover subtle changes in hypothalamus-pituitary-adrenal (HPA) axis activity, which are, for instance, related to persisting pain, burnout and chronic stress. Furthermore, it has been suggested that the HPA axis might serve as an indicator of allostatic load in subjects exposed to prolonged environmental noise. In the present paper four separate studies with a total of 509 adult subjects were combined in order to provide reliable information on normal values for the free cortisol response to awakening. Corresponding with earlier findings, a mean cortisol increase of about 50% within the first 30 minutes after awakening was observed. The intraindividual stability over time was shown to be remarkably high with correlations up to r=.63 (for the area under the response curve). Furthermore, the cortisol rise after awakening is rather consistent, with responder rates of about 75%. Gender significantly influenced early morning free cortisol levels. Although women showed a virtually identical cortisol increase after awakening compared to men, a significantly delayed decrease was observed. Confirming and extending previous findings, the present study strongly suggests that neither age, nor the use of oral contraceptives, habitual smoking, time of awakening, sleep duration or using / not using an alarm clock have a considerable impact on free cortisol levels after awakening. The cortisol awakening response can be assessed under a wide variety of clinical and field settings, since it is non-invasive, inexpensive and easy-to-employ. The present data provide normal values and information on potential confounds which should facilitate investigations into the endocrine consequences of prolonged exposure to environmental noise.

[Skill training and the post-treatment efficacy of dialectic behavior therapy six month after discharge of the hospital]. / Das Skilltraining und die poststationäre Effektivität der stationären Dialektisch-Behavioralen Therapie (DBT) nach sechs Monaten.

Patients with borderline personality disorder (BPD) are getting significantly better under inpatient Dialectic Behavioral Therapy (DBT). Several studies have shown the efficacy of DBT inpatient treatment for patients with BPD. Signs of the efficacy of DBT are mainly reduction of self-injurious behaviour and suicidality as well as reduction of clinical parameters such as depression and general symptom stress (SCL-90-R). In this catamnestic study we evaluated 38 former DBT-inpatients for continuous treatment effects of DBT. The results showed a significant reduction in depression as well as general symptom stress up to 6 month after discharge. Furthermore, these effects were positively correlated with the continuous use of DBT-skills 1 and 6 months after discharge. These skills are central part of DBT-treatment and are especially useful for managing high-tension, suicidality and self-injurious behaviour. Therefore, the use of skills is possibly the reason for the continuous effect of DBT after the end of inpatient treatment.

Moderate psychosocial stress appears not to impair recall of words learned 4 weeks prior to stress exposure.

Recent studies in humans have reported that recall of previously learned material is especially sensitive to the disruptive effects of pharmacologically induced cortisol elevations. Whether similar effects occur after exposure to psychosocial stress remains to be shown. Moreover it is unknown whether stress before or after the initial learning interacts with the later effects of repeated stress on delayed recall (e.g. state-dependent learning). Forty subjects participated in the present experiment. They learned a word list either one hour before or 10 min after exposure to a psychosocial laboratory stressor. Delayed recall was tested 4 weeks later, again either before or after stress. Salivary cortisol levels increased significantly in response to both stress exposures. Stress had no effects on the initial learning and also did not impair delayed recall. Moreover there was no evidence for state-dependent learning. The current data seem to be in conflict with previous studies demonstrating that delayed recall is especially sensitive to elevated cortisol levels. Several reasons for these discrepancies are discussed. Among them is the small sample size, the moderate cortisol increase in response to the second stress exposure but also the long recall delay, which might lead to memory traces less susceptible to stress.