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Drug Trials’ Encouraging Results for Borderline Personality Disorder

Borderline Personality Disorder (BPD) is a mental disorder that develops slowly, usually in adolescence and young adults and resolves slowly. After 4 years about 50 percent of BPD sufferers will remit, and after 10 years nearly 85 percent. When treated with empirically-validated treatments, these figures are considerably better.

To have BPD, a patient must exhibit at least 5 out of 9 specific patterns of behavior. The fact that it is 5 out of 9 criteria means that not all BPD patients will act in similar manners. There are big variations among people with BPD, and this is part of the challenge in discussing treatments for BPD. In general, one can distinguish a type of BPD where anger and irritation are directed externally (let’s call this, extroverted type), and a type of BPD where anger and irritation are directed internally (introverted type).

angry_couple_dreamstime_20150930.jpg Either way, anger and irritation are very difficult to live with for both the patients and his or her family. Angry feelings may even get expressed in forms of aggression, even though the person with BPD may explain that they are simply defending themselves against perceived aggression. Finding ways to reduce aggression is important to help families and patients create a strong social network that can provide support to the person with BPD.

Treatment for Borderline Personality Disorder (BPD) in general falls into two categories: talk therapy and medications. This article is looking at the effects of medications in treating Borderline Personality Disorder.

TALK THERAPY FOR BPD
Forms of psychotherapy which work for BPD include Dialectical Behavioral Therapy (DBT), Transference-Focused Psychotherapy (TFP), Schema Therapy (ST), Mentalization, etc. There are many studies that look at the various efficacies of these therapies. Access (both locations and costs) remains a problem, and due to this, many people end up pursuing general psychotherapies, which help too, yet can be hit-or-miss, and may be slower for complete recovery.

MEDICATIONS FOR BPD
Let’s look here at two important studies of medications and BPD. They will show us that there is good hope with medications for people with BPD.

1. ZYPREXA (OLANZAPINE) AND BPD
In 2008, Marsha Linehan, the creator of Dialectical Behavioral Therapy (DBT), published an article with several colleagues titled: “Olanzapine Plus Dialectical Behavior Therapy for Women With High Irritability Who Meet Criteria for Borderline Personality Disorder: A Double-Blind, Placebo-Controlled Pilot Study”, by Marsha Linehan, Joshua McDavid, Milton Brown, Jennifer Sayrs, and Robert Gallop. J. Clin. Psychiatry (June 2008) Vol. 69, No. 6, pp. 999-1005.
http://depts.washington.edu…/

The purpose of the study was to find out if the medication Olanzapine (commercial name: Zyprexa) reduced anger and hostility. The thought was that if patients’ emotions were less intense, they would benefit more from talk therapy.
Two groups of women were studied, both did Dialectical Behavioral Therapy for 21 weeks; one group took Zyprexa, the other took a placebo pill for the whole duration of the treatment.

Overall, there were large and consistent reductions in irritability, aggression, depression, and self-injury for both groups of subjects receiving DBT. The group taking Zyprexa experienced the effects quicker than the other group; they experienced progress within 7 weeks, and were still ahead of the Placebo group at 14 weeks. The Placebo group experienced similar drecrease in symptoms after 21 weeks.

Intentional self-injury and high suicidality ended up being lower for the group not taking Zyprexa. Yet, the depression ratings were lower for the group taking Zyprexa. These results may appear slightly contradictory. They indicate the limitation of the measurement tools used, and that additional studies on larger groups are needed.

Researchers concluded that “Olanzapine may promote more rapid reduction of irritability and aggression than placebo for highly irritable women with borderline personality disorder.”

Zyprexa became rapidly popular after its introduction in the United States in 1996. However, Zyprexa has also lead to claims of serious side-effects, including occurrences of diabetes in about 1% of cases. Some say a 1% risk is low, others say is too high… It was important to continue looking for other better medications.
(Side effect reference: http://pro.psychcentral.com…)

Relevant details on this drug trial are described here.

2. SEROQUEL (QUETIAPINE) AND BPD
A very encouraging study for the treatment of symptoms of BPD was published last year in 2014 by several noted researchers in the field.

“Comparison of Low and Moderate Dosages of Extended- Release Quetiapine in Borderline Personality Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial”, by Donald Black, Mary Zanarini, Ann Romine, Martha Shaw, Jeff Allen, and Charles Schulz. Am J. Psychiatry (Nov. 2014) Vol. 171, No. 11, pp 1174-1182.
http://ajp.psychiatryonline.org/…

The study found that a low-dosage of Seroquel XR reduced substantially the irritability and aggression of the subjects. Participants treated with 150 mg/day of Quetiapine had a significant reduction in the severity of certain symptoms of borderline personality disorder compared with those who received placebo, especially the symptoms of irritability, anger and physical or verbal aggression.

Symptom reductions were measured on the Zanarini-BPD scale and also on two standard psychological tests: Modified Overt Aggression Scale (MOAS) and Young Mania Rating Scale (YMRS).

As Charles Schulz noted:

“By the 8th week of treatment in our study, patients who took a low-dosage (150 mg/day) of Seroquel XR had a Zanarini-BPD scale of 5.2, that is they were very close to non-BPD people.”

Patients treated with 300 mg/day of quetiapine were more likely to experience adverse events, and did not exhibit additional reduction in severity of BPD symptoms compared to the lower dosage of 150 mg/day. Treatment-emergent adverse events included sedation, change in appetite, and dry mouth.

Time to response (defined as a reduction of 50% or more on the Zanarini scale total score) was significantly shorter for both the low-dosage quetiapine group and the moderate-dosage quetiapine group than for the placebo group.

A reduction in anger and irritability occurred during and at the end of the drug trial. The effects of the medication are expected to continue longer if the drug is taken longer. More research is needed to establish any long lasting effects of the drug after patients stop taking the medication. This is probably where talk therapy can lengthen the effects of the medication.

Relevant details on this drug trial are described here.

NO FDA-APPROVED MEDICATION FOR BPD
There is no medication on the market today that is viewed by psychiatrists as a cure for BPD, nor even for emotional dysregulation. However, as we just saw in the Seroquel XR study, certain medications greatly help reduce some symptoms of BPD. These symptoms are important at least for the people living with a person who has BPD. Symptoms of irritability, aggression and verbal outbursts can be very debilitating for family life, and lead to social isolation, which just creates further problems.

Some psychiatric experts believe that there is no medication for BPD to be found anywhere. At the annual meeting of the American Psychiatric Association, I heard this year a (European) doctor exclaim that “It would be stupid to prescribe medication for BPD, for there is no medication for BPD.”

Indeed the all-powerful US Food and Drug Administration (FDA) has not approved ANY medication for the treatment of BPD thus far as of 2015. Moreover, rumor has it that the National Institute of Health (NIH) will not fund anymore pharmacology research for BPD until we have a better understanding of the whole mechanism of this illness.

This puts BPD in a class by itself as far as illnesses go in general, because although there is no official medication for BPD, if you asked 100 BPD patients currently in treatment or in remission, “Do you or did you take any medication?”, informal polls show that between 85 and 100% of patients have taken or are taking some type of medications that relieved their BPD symptoms.

How is this possible if the FDA says that no medication is currently working for BPD?

The key point to distinguish is  “medication for BPD” vs. “medication for BPD symptoms”.

Some symptoms of BPD are common to other illnesses such as bipolar disorder, especially so-called rapid cycling bipolar disorder (people who go up and down in a matter of hours, rather than weeks in traditional bipolar disorder). There are several medications approved for bipolar disorder. Any psychiatrist – like any medical doctor in the US – has the choice of prescribing medication to patients “off-label”, that is he/she can prescribe medication approved for another disease if he judges personally that his patient’s case is appropriate for this medication. In this way, a psychiatrist can prescribe medication approved for bipolar disorder to a patient who exhibits other signs of BPD, hoping that the medication will relieve the common symptoms found in both illnesses.

Another method that often happens is that if the psychiatrist finds it medically appropriate for these patients, he can diagnose them with bipolar disorder, and then treat them with “on-label” medication. As you can imagine, this process encourages psychiatrists to diagnose – and some patients to be diagnosed – with bipolar disorder, so they will have access to helpful medications.

ON-LABELS VS. OFF-LABELS PRESCRIPTIONS
There is an additional important twist in this story, namely health insurance reimbursements. Some health insurance companies are not willing to reimburse off-label medications, or do not reimburse them at the same rate as on-label prescriptions. Hence, even if the psychiatrist is willing to prescribe a medication to a patient, there could be a real cost issue for the patient. To get around this, the system in effect encourages the patient to get a bipolar diagnosis, to be better reimbursed for the medication.

The question of medication or not for BPD animates big debates among experts and within families too. Medication – when it works – is viewed as effective and convenient. It is quick. It works daily. It is often cheaper and faster than psychotherapy which can be quite costly ($40,000 to $60,000 per month) and lengthy (takes several months). Medication may not work, but then psychotherapy is not guaranteed to work either. And one does not see if it works until after a couple of months of therapy.

happy_couple_dreamstime_20150930

The cost for families can be astronomical. It is not rare to find families that have a member affected by BPD, where the parents have had to take a second-mortgage on their homes in order to pay for psychotherapy. Then after two months of treatment and $100,000 spent, one realizes it did not work… This is not often the case, but it happens, and I have met several families in this case.

In comparison, trying medication is quick. It only costs a few tens of dollars with a good insurance, or at worse a few hundred dollars, and within a few days, one either sees a result or one does not.

Thus it is important to keep searching for medications that worked well for BPD, and to study their effects on symptoms, especially symptoms of irritability and aggression.

PERCEPTION OF BPD MEDICATION RESEARCH IN POPULAR MEDIA

New York Times article about this clinical trial of Seroquel for BPD was published on 17 April 2015. It contained erroneous statements, and provided an overall impression that is harmful to the many patients and families affected by a diagnosis of BPD.

Borderline personality disorder (BPD) is not an “intractable condition”. And although no drug treatment has been approved by the US-FDA for BPD thus far, this does not mean that there could not ever be one.

More importantly, the Seroquel study by Black, Schulz, Zanarini shows clearly that important symptoms common to BPD patients can be successfully attenuated with the use of medications such as Seroquel XR. For families living with someone who suffers from BPD, decreasing key symptoms of BPD can be a huge progress, especially when these symptoms include bursts of anger and severe irritability.

This message is worth telling loudly to patients and families. Good medications help alleviate key symptoms of BPD.

The situation is analogous to medication for common colds or flu (influenza). We know colds are a viral illness, but we do not have a medication that acts on the root cause of it. We have medications that work on the symptoms of colds: fever, running nose or stuffy nose, headaches, fatigue, etc. Now we have medications that alleviate the symptoms of colds: reduce our fever, unstuff our nose or prevent runny nose, vitamins to boost our immune system. After taking these medications, our bodies feel helped and relieved. Add some extra rest and mild temperatures, and our immune system does the rest to heal us.

Taking the analogy of degrees of fever for degrees of anger and irritability, we can look at the two medication studies for BPD as showing that once anger & irritability (equivalent of fever for colds?) is closer to normal, the patient feels better and may get closer to normal. At that point, some talk therapy may help further reduce other symptoms of BPD, and eventually the whole illness.

The title of the New York Times article misled anyone reading it: “A Drug Trial’s Frayed Promise” indicated that a big promised had been made upfront, when in fact the point of any drug trial is to study with an open mind if a particular drug works to treat a condition, how well it does it, and how quickly it does it. Looking at the details, the content of the actual scientific study by Black and Schulz warranted that the popular article be titled “Drug Trial’s Encouraging Results and Great Promise.”

The main objection in the New York Times article was anchored on the fact that a couple of patients involved in the Seroquel trial did not use the drug properly in the trial. This issue was investigated by the University of Minnesota Internal Review Board, who concluded that no investor misconduct had occurred. See the rebuttal published in American Journal of Psychiatryhttp://ajp.psychiatryonline.org…

As was confirmed in email by Don Black and Charles Schulz:

“As soon as we noticed that a patient no longer qualified for the trial, their data was treated as discontinuing patients and therefore not counted in the final results. Our research showed that Seroquel XR treatment at low dosage (150 mg) can noticeably reduce key symptoms of BPD, to the point where the whole disorder in the patient is then below the scale of noticeable diagnosis.”

The results of this study offered more than “a glimmer of hope” as noted in the NY Times article. The results were genuinely an exciting development as stated by Mark F. Lenzenweger, a professor at Binghamton University and Weill Cornell Medical College and an expert in borderline personality disorder.

John Gunderson, Professor of Psychiatry and Director of Personality and Psychosocial Research Program at Harvard Medical School, and one of the most respected doctors and researchers in the field of Borderline Personality Disorder wrote in response to the NY Times article:

“BPD is a very serious disorder that develops slowly, usually in adolescence and young adults and resolves slowly. After four years about 50 percent will remit and after 10 years nearly 85 percent.
When treated with empirically-validated treatments these figures are considerably better. When the disorder remits, it usually stays that way. Most other major psychiatric disorders may remit more quickly, but they almost all recur throughout a lifetime despite having FDA-approved drug therapies.

These facts offer a far more positive, and accurate, portrait of BPD’s prognosis and treatability.”

Personality Disorder Awareness Network (PDAN) encourages scientists to do research in the field of medication and treatment for personality disorders. We hope that the two studies presented here serve to show that great hope and progress for the treatment of personality disorders are possible thanks to medications.

In conclusion, for many families who have to live with the reality of personality disorders, medications can be of great assistance in providing comfort and quicker results, which ultimately lead to encouragements, confidence and faster recovery. Medications may also lower the cost of treatment, as one hour of therapy is typically more expensive than one or two pills per day, and less convenient to take for the person in question.

Undoubtedly personal preferences for talk therapy treatments may prevail for some families. We hope that his article serves to expand knowledge of the range of solutions available for borderline personality disorder.

(Details on the two studies of medication for BPD mentioned here can be found on this page: http://pdan.org/details-on-two-drug-trials-for-bpd/)

— by Frederic Bien, Ph.D.

President, PDAN (Personality Disorder Awareness Network)

13 Comments
  1. What medication can be tried, on a 26 yr old mother of 2, who is expelling her husband out of their home (in constant outbreaks of rage – without rational cause)? We fear her intensifying anger could escalate to suicide or familicide. To outside authorities (child protective services, etc) they see no physical signs of harm – yet.

    She has smoked marijuana heavily and daily for several years, and drives an automobile ‘under the influence’.

    She verbally abuses her husband and any person who recommends therapy.

    If she would comply, might benzodiazepines or lithium be helpful in preventing violence? Oxytocin, ketamine, long-acting low dose opioids (hysingla, zohydro).?

    She has alienated all family members, who now much fear that she will commit suicide or violence against her 2 and 4 yr old sons – especially after she ragefully evicts her 37 yr old husband, the boys’ father and only protector.

    Thank you to the PDAN community for any ideas to aid his desperate family.

    A. Carr MD

  2. People with borderline personality disorder need to not use any recreational drugs whatsoever. Additionally you have to experiment some with either the antipsychotics and or some lithium. Just as important is the individual needs to attempt to resolve conflicts in all of their relationships including a relationship with themselves and even of spiritual matters. Dbt is ok…self validation and love….vital. Attempt to use lowest dose possible if psychotropics, do not alienate the person and try and make everything inclusive and forgive most importantly forgive all past transgressions if you choose to heal the relationshio. This is a very difficult emotional rollercoaster. Best of luck.

    Geoffry Feinberg M.Ed.BA.AA

  3. Did you not read the article? Seroquel and Zyprexa are medications that work.

    • I have BPD, PTSD, chronic anxiety and panic syndrome. I’ve been prescribed both Zyprexa and Seroquel… and these two drugs did more harm than good. Zyprexa turned me extremely manic- I couldn’t sit down, let alone sleep. Seroquel helped the mania- all I did was sleep and eat. I gained 55 pounds in 5 months(and I still haven’t been able to lose them). Gaining weight only increased my self loathing. I’m on Medicare, so I have never been offered the only behavior treatment proven to help BPD. I’m 46, and I never expect to see the government provide better mental health care in my lifetime for those of us with low income who need mental health plans of quality who need it the most. Mental health stigma in “The greatest country on Earth” needs to stop- the sooner the better.

  4. I’ve suffered sytmtoms like these since early childhood.Yet in past year my GP said it was benzo and codiene were to blame.After 30 yrs I was took off.Now I’ve almost died of suicide 3 times,my family can stand my mood,razors arnt allowed near me.over a year two consultants said I’d be better as before,in one year ive fear of phones,doorbells ringing, scared of opening letters.I haven’t eaten in weeks but bloated with menopause. Don’t sleep, no friends,I see a shrink every 3 months for 10 mins,doesn’t care only about keeping of codiene, I suffered 10 yrs before I was given it by them.So I’m gonna get as much information to convince this cow I’m not a addict I was I’ll mentally 20yrs before given medication. By Them now my family suffers and I’m ready for my suicide trys again. All the signs the family was to look for, now I’m so sick of arrogant pigs looking at me ,when they prescribed them without warning me of addiction. Could you send me information abt this new treatment. Thankyou.

  5. Have you done any research with gabapentin for bpd? I’ve found that 600mg twice a day or higher can have a great affect on both aggression and outlook on life as well as make the subject more open and accepting of themselves and others.

  6. Aw, this was an incredibly nice post. Taking the time and actual effort to create a good article… but what can I
    say… I procrastinate a lot and never seem to get anything
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  10. As a BPD sufferer, I am insulted by a couple of ignorant posts. First off, to the first poster, I have never heard of someone with this disorder committing familicide. We usually hurt ourselves when we have a breakdown-not others. If this woman is making homicidal/ suicidal threats, she needs to be hospitalized. Most states will insist on this for at least 72 hrs. Her husband is the one being negligent. She sounds like she is in a psychotic state and is a dangerous to others AND herself.If she isn’t in her right state of mind, she needs to be forcibly hospitized by her husband, for her protection, his protection, and especially the children. If she is this sick, can you imagine how scary and confusing it is for the children?
    Marijuana has nothing to do with this. If she is driving under the influence, that is wrong,, but why are you in this couples business? Why doesn’t CPS believe you? I wonder…
    Anyway Medical Marijuana has actually been the most beneficial treatment for millions of people who suffer from mental illness all across the country. Its about to be decriminalized federally. Its NOT a recreational drug, but it IS a psychoactive plant. Different strains work differently for specific issues and just individually. Prescription meds have horrible side effects. Hell, most of the prescription drugs being released by the FDA these days can give you cancer, low immune function, or worse. Marijuana has few side effects and not a single death EVER ANYWHRE. So a couple of ya,ll are way off. BTW I have been in remission from my illness for many years. Used to cut my body up several times a day. I do take meds, and smoke medical Marijuana, and take suboxone from a opiate use disorder I struggled with years ago after multiple surgeries. My Dr completely supports me in my regimine. I am stable , and thats what matters to him.

  11. BPD is heĺl. I am taking Latuda, after reading a study that 80% in a trial found relief. It helped for awhile, but I’m back to crying all the time and wanting to harm myself. I guess I will try a higher dose. Gabapentin does help anxiety and depression, but you develop a tolerance really fast, so it can’t be used daily.

  12. Thank you for this! I’m not alone. I definitely second the gabapentin recommendation.

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