Ketamine in Borderline Personality Disorder

This clinical trial primarily tests the impact of ketamine on suicidal thoughts in Borderline
Personality Disorder (BPD). It also tests the impact of ketamine on symptom intensity (for
mood, BPD, and pain symptoms), social cognition, and neuroplasticity in people with BPD.

Suicidal ideation and action are too common in BPD, occurring at rates similar to those in
people with depression or schizophrenia. Intensive psychotherapy helps, but many people with
BPD do not have access to that treatment, and not everyone responds to psychotherapy if they
do get access. No medication is FDA-approved for BPD, and no medication has been shown to
decrease suicidality in BPD.

Ketamine is a promising medication for this problem. It is an FDA-approved anesthetic
medication with N-methyl D-aspartate activity. Sub-anesthetic doses of ketamine decrease
suicidality and improve mood in people with Major Depressive Disorder (MDD). This effect is
rapid, with symptom improvement within hours that endures approximately two weeks. People
with BPD can have symptoms that overlap with those of MDD, however, the effective treatments
for BPD and MDD differ. This clinical trial will test if ketamine, which is effective in MDD,
is also effective in BPD.

The investigators will use semi-structured interviews and self-report questionnaires to
measure suicidal ideation and clinical symptoms (adverse events, mood symptoms, BPD symptoms,
and pain). Social cognition will be also be measured using both interviews/questionnaires and
cognitive psychology tasks.

One proposed mechanism of ketamine's effect in MDD is increased neuroplasticity - opening a
window during which new learning can occur. This mechanism has been demonstrated in rodent
models of depression. In BPD, negatively-biased social interpretations impede meaningful
recovery and increase suicide risk over time. A post-ketamine neuro-plastic window may
provide an opportunity for revisions of rigid social attributions. The investigators will
test for changes in neuroplasticity using a cognitive psychology task and
electro-encephalography.

Baseline measures of demographics, life experiences, and symptoms may also be used to predict
outcomes or as co-variates in our analyses.

Inclusion Criteria:

- Age 21-60

- Clinical diagnosis of Borderline Personality Disorder

- Has suicidal ideation.

- Fluent in English

- Has a current mental health treater, and agrees for study to communicate with treater

Exclusion Criteria:

- Current suicidal intent

- Med changes in last 4 weeks

- Any ketamine in any context in the last one year.

- Current prescription for topiramate, lamotrigine, or lithium.

- Psychotic disorder in self or first-degree relative

- Current substance dependence including alcohol dependence

- Any history of NMDA (N-methyl-D-aspartate )-antagonist abuse

- Any history of opiate abuse

- History of major medical illness especially neurologic or cardiovascular condition, or
any other medical contra-indication to ketamine administration at the discretion of
the study MD.

- Positive urine test for drugs of abuse screening on day of ketamine administration

- Positive pregnancy test on day of ketamine administration

- At the discretion of study staff