130 A separate small, placebo-controlled study indicated subtle effects of oxytocin in decreasing social stress reactivity, particularly for patients with history of childhood trauma and attachment insecurity.131 Seemingly divergent effects

of oxytocin on social stress on the one hand, and cooperative behavior on the other, suggest that it may have opposing roles Inhibitors,research,lifescience,medical in different social cognitive processing networks in BPD. Further research is needed before advising clinical use of oxytocin in psychopharmacological management of BPD. Future directions Olanzapine89-90 and fluoxetine132 have been studied in conjunction with evidence-based psychotherapy for BPD, but respective treatment effects of psychotherapy versus medication remained unclear in these trials. Whether different medications differ in their capacity Inhibitors,research,lifescience,medical to synergize with psychotherapy in treating specific BPD symptoms or overall functioning

has never been rigorously studied. Many BPD patients are treated with a combined approach, and yet there is limited information for rational clinical decision-making. Further understanding of the neurobiological effects of psychotherapy, relative Inhibitors,research,lifescience,medical to mechanisms of action of specific medications may eventually predict which BPD patients will respond to which approach and how to combine different treatments. BPD patients show lack of psychophysiological and amygdala indicators of habituation to repeated interpersonal affective stimuli of positive or negative valence.81 Working through interpersonal experiences in psychotherapy may be difficult for BPD patients, and adjunctive medication treatment targeting this capacity for habituation may optimize overall treatment efficacy. Dependent on neuroplasticity Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical and changes in receptor density, habituation is fundamentally affected by glutamatergic N-methyl-D-aspartate (NMDA) signaling, suggesting a role for glutamatergic medications in improving impulsivity, interpersonal symptoms, and cognition in BPD.133 Enhancing learning

and psychophysiological habituation modulated by NMDA signaling could synergize psychopharmacology and psychotherapy, analogous to strategies proposed for PTSD with respect to enhancement of fear extinction and interference of traumatic those memory consolidation.134,135 This type of combination strategy has not been studied in CDK inhibitor randomized controlled trials. Endocannabinoid neurotransmission has also been implicated in impulsivity,136 suicidality,137 affective instability, and psychosis,138 perhaps partly via its role in modulating dopaminergic signaling.139 Medications active on CB receptors have also been hypothesized to facilitate extinction and interfere with consolidation of traumatic memories, if used in conjunction with psychotherapy.140 Psychopharmacological applications of cannabinoid medications remain theoretical at best, and associated risks remain too uncertain.