Olanzapine No Better Than Placebo for Borderline Personality Disorder
In a double-blind trial, 314 outpatients with borderline personality disorder were randomly assigned to receive olanzapine or placebo. After 12 weeks of treatment, both groups showed significant improvements in borderline symptoms; however, there was no difference between olanzapine and placebo on the primary outcome measure. There were some statistically significant but small advantages for olanzapine on a few of many secondary outcome measures, such as the hostility score on the Symptom Checklist-90-Revised, though placebo outperformed olanzapine by a small but statistically significant margin in reducing suicidal/self-mutilating behavior. A much larger percentage of olanzapine patients gained seven or more percent of their baseline weight relative to patients on placebo (34% vs. 3%). Likewise, olanzapine patients had significantly higher increases in LDL and total cholesterol than did patients on placebo (Schulz SC et al., Br J Psychiatry 2008;193:485-492).
TCPR’s Take: Study participants were not very representative of BPD patients in general, as the study excluded patients with current depression, substance dependence, or PTSD. The authors noted that another large trial found positive results for olanzapine in treating BPD; however, it has not been published. There are few published controlled trials regarding the efficacy of atypicals for BPD and their results have been inconsistent. Research has more consistently supported the efficacy of dialectical behavior therapy in treating BPD; cognitive therapy and other psychotherapies have also received some support (Paris, J. Psychiatr Clin N Am 2008;2008:517-526). For more on treating BPD, please see the September 2008 issue of TCPR.
Risperidone Shows Mixed Results in Augmenting Antidepressant Treatment
A recent trial examined the impact of augmenting antidepressant treatment with risperidone. Participants had not shown a treatment response after taking an antidepressant for at least five weeks, and were then randomly assigned to receive either risperidone or placebo augmentation along with the same dose of their antidepressant. Risperidone was flexibly dosed between 0.5 mg and 3 mg based on clinical response and side effects. At the end of the four-week trial, the remission rate on the Montgomery-Asberg Depression Rating Scale (MADRS) was significantly higher among risperidone augmentation patients than placebo augmentation patients (52% vs. 24%). Response rates on the MADRS were also significantly higher for patients taking risperidone (55% vs. 33%). However, there was no significant advantage for risperidone on Clinical Global Impressions scores or response on the Hamilton Depression Rating Scale (HAM-D). Initially, patients on risperidone showed more change on the MADRS, but this advantage became smaller and statistically nonsignificant by the end of the study. Patients on risperidone gained significantly more weight than those taking placebo (4.3 pounds vs. 0.3 pounds). No EPS symptoms were reported (Keitner GI et al., J Psychiatr Res 2009;43:205-214).
TCPR’s Take: The results of this study imply that risperidone might be a useful short term strategy to “kick-start” a response in patients who have not responded to the antidepressant alone. Short term use would potentially prevent the more extreme side effects of risperidone, although we do not know what the risk of relapse would be after discontinuation.
Headache Is a Risk Factor For Suicidality
The original Epidemiological Catchment Area (ECA) study (based on interviews conducted in the 1980s) examined the prevalence of mental disorders among adults in five American cities. Taking a fresh look, researchers examined data from 6,832 adults who resided in the community in order to ascertain the relationship between headache and suicidality. Participants completed an interview that assessed both mental health and somatic symptoms. Between a year and two years after this assessment, participants completed a followup interview. The presence of severe headache at baseline was associated with increases of 47% to 82% in various forms of suicidality, including wanting to die, contemplating suicide, and making a suicide attempt. Even when controlling for the presence of depression, anxiety, and drug/alcohol abuse and dependence, people who experienced severe headaches were significantly more likely to report some form of suicidality at the follow-up interview (Woolley SB et al., J Nerv Ment Dis 2008;196:822-828).
TCPR’s Take: The assessment of headache in the interview was inexact. People were designated as having “severe headache” if they endorsed that they had “ever had a lot of trouble with headaches.” Thus, it is unclear what type, frequency, or intensity of headache places people at highest risk for increased suicidality. Nonetheless, results from another large epidemiological dataset using very similar methods also linked headache to suicidality (Ilgen MA et al., Gen Hosp Psychiatry 2008;30:521-527). Clinicians should assess for suicidal thoughts and behaviors in patients experiencing difficulties with headache.