BORDERLINE PERSONALITY DISORDER
Robust Support for Mood Stabilizers in Borderline Personality Disorder
While we typically pick and choose among various drug classes to treat patients with borderline personality disorder (BPD), we have a hard time basing our choices on the evidence. Various reviews and metaanalyses of pharmacotherapy for BPD have reached diverging conclusions. A recent well-done meta-analysis reviewed three classes of medications—antipsychotics, mood stabilizers, and antidepressants—in the treatment of BPD and schizotypal personality disorder. The main antipsychotics surveyed included haloperidal, olanzapine, risperidone, and aripiprazole; the main mood stabilizers were carbamazepine, valproate, and topiramate; and the main antidepressants were fluoxetine, amitriptyline, and phenelzine. A total of 21 trials were included, most of which focused on BPD and had small sample sizes of between 20 and 60. On average, antipsychotics improved cognitive-perceptual symptoms (eg, suspiciousness, depersonalization), anger, and global functioning moderately more than placebo, but had no significant effect on impulse control, depressed mood, or anxiety. Mood stabilizers had large effects on impulse control, anxiety, and anger, and moderate effects on depression and global functioning. Antidepressants yielded significant but small effects only on anxiety and anger (and not depression). (Ingenhoven T et al., J Clin Psychiatry online ahead of print).
TCPR’s Take: These results are surprisingly positive for mood stabilizers and surprisingly negative for antidepressants. We’ll temper the endorsement of mood stabilizers a bit by pointing out that their effects varied from small to very large in different studies, which used several different outcome measures. Regarding antipsychotics, the single trial of aripiprazole showed much more positive results than other antipsychotics, while a recent large trial of olanzapine which found little to no benefit for BPD was not included. With some caution, these results suggest that mood stabilizers have a broader effect than either antipsychotics or antidepresssants in treating symptoms of BPD.
Is Intuniv (guanfacine XR) Effective for ADHD?
Guanfacine, an alpha-2 agonist, is sometimes prescribed off-label for ADHD and has now received official FDA approval in a new, extended-release formulation. Shire will soon market the drug under the brand name Intuniv. So how well does it work? Two randomized controlled trials have addressed this question. One trial, with a total of 345 patients, examined dosages of 2 mg, 3 mg, and 4 mg and found that Intuniv improved ADHD symptom scores significantly more than placebo. However, the drug was not more effective than placebo in treating patients with specifically inattentive ADHD symptoms or in patients ages 9 to 17. It beat placebo only for very young children (six to eight) and for patients with combined hyperactive/inattentive ADHD. Its major side effects were sedation/drowsiness /fatigue, which affected 47% – 63% of patients taking Intuniv vs. 11% of those on placebo (Biederman J et al., Pediatrics 2008;121:e73-84). A second trial of 324 patients, using 1 mg, 2 mg, 3 mg, and 4 mg doses, appeared more positive for Intuniv but did not report as much data as the first study, making it difficult to judge Intuniv’s efficacy for particular age groups or symptom domains. In this second study, Intuniv beat placebo by a moderate effect size, but only in 6 to 12 year old patients; there was no Intuniv advantage seen in the 13 to 17 year old range. The authors did not report data separately for 6 to 8 year olds and 9 to 12 year olds, nor did they report data separately for patients with differing ADHD subtypes. Drowsiness (27% vs. 12%) and fatigue (9% vs. 3%) were more common among drug- than placebo-treated patients (Sallee FR et al., J Am Acad Child Adolesc Psychiatry 2009;48:155-165). According to online clinical trial registry entries, both trials used quality of life (QOL) measures, on which Intuniv did not outperform placebo, yet QOL measures were not mentioned in either journal publication.
TCPR’s Take: Intuniv appears to be helpful primarily for younger children, especially for hyperactive symptoms of ADHD. The fact that important quality of life data were left out of the published trials (apparently because they made Intuniv appear less effective) implies that Shire has made an effort to hide negative data. We hope that future publications will present the data less selectively.
Adjunctive Telephone Therapy is Cost-Effective when Added to Antidepressants
In order to test whether phone therapy is helpful as an adjunct to antidepressant medication, researchers enrolled 600 depressed outpatients in a randomized trial. All patients were started on antidepressants as agreed upon by physician and patient—the researchers did not control or conceal the medication or dosage. Patients were then randomly assigned to: a) “care management,” consisting of brief telephone and mail contact to improve antidepressant adherence; b) telephone cognitive-behavioral therapy (nine half-hour sessions) + care management; c) usual care, which included both treatment in primary care and referrals to mental health specialty care. Among the 89% of patients who remained in the study after six months, the rates of antidepressant treatment response were 51% (care management), 58% (phone therapy), and 43% (usual care). Phone therapy was statistically significantly more effective than usual care and was associated with 46 more depression free-days over two years (Simon GE et al., JAMA 2004;292:935-942). In terms of cost-effectiveness, phone therapy was associated with a cost of $9 per additional depression-free day, while care management was significantly more expensive, at about $24 per depression-free day (Simon GE, Arch Gen Psychiatry 2009;66:1081-1089).
TCPR’s Take: Adding nine half-hour sessions of telephone cognitive behavior therapy to antidepressant medications appears to be both efficacious and cost-effective. But the practicality of phone therapy hinges on whether insurance companies will pay for it, because clinicians are not going to provide it for free and not all patients can afford the out of pocket expense. In addition, it would be helpful to see a similar study testing the effectiveness of supportive phone therapy, since supportive techniques are mastered by far more clinicians than CBT.