Careful identification of comorbid psychiatric disorders is a rational first step. Diagnosing comorbid disorders, such as bipolar disorder, will determine medication choice and impact length of treatment. In a double-blind study of 30 women with BPD and comorbid bipolar II disorder, Frankenburg and Zanarini14 found divalproex had a statistically significant effect compared with placebo and could be considered for this specific population.
When treating a BPD patient who has a comorbid illness, it is important not to ignore BPD symptoms. The chronic emotional dysregulation and ongoing safety issues require psychiatrists to educate patients about these symptoms and to address them in a multidisciplinary manner.
Clarifying prominent symptom domains can help steer pharmacologic management. Many trials have attempted to focus on specific symptom domains, including cognitive-perceptual disturbances, impulsivity, and affective dysregulation. Table 124 lists BPD symptom domains and associated characteristics.
Table 1
Symptom domains of BPD
| Cognitive-perceptual symptoms |
| Suspiciousness |
| Referential thinking |
| Paranoid ideation |
| Illusions |
| Derealization |
| Depersonalization |
| Hallucination-like symptoms |
| Impulsive-behavioral dyscontrol |
| Impulsive aggression |
| Deliberate self-harm |
| Impulsive sexual behavior |
| Substance abuse |
| Impulsive spending |
| Affective dysregulation |
| Mood lability |
| Rejection sensitivity |
| Intense anger out of proportion to the stimuli |
| Sudden depressive mood episodes |
| BPD: borderline personality disorder Source: Reference 24 |
Dosing strategy
Developing a medication management strategy for BPD patients requires a thoughtful approach. When faced with a patient who has overwhelming distress, it is tempting to start with high medication doses; however, clinical experience suggests starting cautiously with lower doses will yield better tolerability and adherence. Based on our clinical experience, patients with BPD tend to be highly perceptive to physiologic stimuli and medication side effects.
Further research is needed to answer clinical questions regarding optimal dosing strategy and treatment, but some studies suggest when using SGAs, doses equivalent to one-third or one-half the dose used for treating schizophrenia may be appropriate.1,2,17,18 However, for fluoxetine, investigators have espoused using a dosage higher than generally used for depression.10 For mood-stabilizing anticonvulsants, almost all studies employed the same doses used for bipolar disorder.25 Some studies of valproic acid have verified appropriate blood levels—generally 50 to 100 μg/mL.
Controlled trials have not determined whether medications for patients with BPD should be used briefly during times of stress or for longer periods. Many studies of medication for BPD have been relatively brief trials that explored whether the drug has any potential efficacy. In our opinion, this issue currently is being addressed in clinical practice in a trial-and-error manner.
Clues to targeted treatment
Although pharmacotherapy for BPD subtypes remains controversial, recent meta-analyses by Ingenhoven24 and Nose26 and a Cochrane Review27 (with subsequent online update28) have identified evidence that supports the use of specific medications for treating BPD symptoms. These studies’ authors acknowledge replication studies are required because of the limited nature of the available data. In contrast, a meta-analysis conducted by the National Collaborating Centre for Mental Health29 did not identify sufficient evidence for medication use in BPD on which to base official guidelines to advise health care providers in the United Kingdom. The only medication recommendation in this meta-analysis is to consider prescribing short-term sedative antihistamines during crises; this recommendation is not supported by any clinical trial.
In a meta-analysis of 21 placebo-controlled trials of patients with BPD and/or schizotypal personality disorder, Inghoven et al24 used multiple domains and subdomains, including cognitive-perceptual symptoms, impulsive-behavioral dyscontrol, affective dysregulation, anger, and mood lability, to assess the efficacy of medication use (Table 2).24 They found:
- Antipsychotics seemed to have a moderate effect on cognitive-perceptual symptoms and a moderate-to-large effect on anger.
- Antidepressants had a small effect on anxiety, but no other domains.
- Mood stabilizers had a very large effect on impulsive-behavioral dyscontrol and anger, a large effect on anxiety, and a moderate effect on depressed mood.
- Regarding global functioning, mood stabilizers had a greater effect than antipsychotics. Both led to greater change than antidepressants.
A 2010 Cochrane Review meta-analysis initially conducted by Leib27 with subsequent online update by Stoffers28 included 28 studies with a total of 1,742 patients and also identified symptom-targeted BPD domains. This study analyzed pooled data and found support for the use of specific medications, including certain antipsychotics, mood stabilizers, and antidepressants, for specific BPD symptoms (Table 3).28 The authors recommended data be interpreted cautiously, however, because many of the clinical trials included in their meta-analysis have not been replicated and generalizability from research populations to clinical populations is not well understood.