Pharmacotherapy for self-injury

There is evidence, albeit limited, for pharmacotherapy. It should be noted that there are no medications currently labeled for the treatment of self-injury or BPD. Medications are used to target the neurotransmitter systems most likely to contribute to self-injury. Opioid, serotonin, and dopamine receptors are commonly implicated.

The opioid system is implicated because of higher pain thresholds and stress-induced analgesia in BPD, likely mediated by increased activity of the dorsal prefrontal cortex with deactivation of the anterior cingulate and amygdala.34 NSSI may also involve addictive qualities, including postcessation withdrawal dysphoria.14 Open-label studies of the opioid antagonist naltrexone have shown reduced self-injury.35,36

Decreased serotonin levels have been linked to impulsive, aggressive, and suicidal behaviors.37 Self-injury is usually an impulsive act, with half of cutters thinking of the behavior less than an hour before committing the act.22 Fluoxetine is the serotonergic medication with the most evidence for use in NSSI, with at least 2 controlled trials showing reductions in impulsive aggression.38,39 In an open-label trial, venlafaxine was also beneficial.40Self-injury may also present in syndromes that involve the dopamine system, such as Lesch-Nyhan syndrome and Tourette syndrome.41 Self-biting behaviors may be elicited by stimulants that primarily work through a dopaminergic mechanism of action. The use of dopamine antagonists has been studied for NSSI. Although there is some evidence for the efficacy of all of the atypical antipsychotics for reducing aggression and/or impulsivity, olanzapine has had the best results in the most rigorous trial designs.39,42-46

There is a paucity of literature regarding combination therapy. Surprisingly, adding fluoxetine to DBT was not found to give any additional benefit.47 A trial of olanzapine plus DBT reduced the frequency of impulsivity/aggressive behavior more than placebo plus DBT, although self-injurious behavior did not decrease significantly.48In addition to serotonergic, dopaminergic, and opioid medications there are other drug categories being studied for NSSI. There are promising case reports for glutamate-decreasing agents, including riluzole, N-acetylcysteine, and topiramate.49 Similarly, the glutamate-modulating agent lamotrigine was found to decrease behavioral dyscontrol, impulsivity, and anger in open-label trials, retrospective trials, and controlled trials.50-52 There have been controlled studies of lithium, divalproex, carbamazepine, and omega-3 fatty acids, which have all demonstrated decreases in impulsive aggression, but not NSSI specifically, in individuals with BPD.53-56 There was also an open-label study of oxcarbazepine that demonstrated statistically significant decreases in impulsivity, affective instability, and outbursts of anger in small sample populations with BPD.57 Clonidine, an a2-agonist, decreased the urge to commit self-injurious behavior in an open study.58

Conclusions

NSSI is common and its prevalence may be increasing in adolescents. There are a number of known risk factors for NSSI, and NSSI may be a risk factor for later suicide attempts and completion. NSSI has a number of psychological functions and may be contagious and/or addictive. DBT, when available, can be considered the standard treatment for cases of NSSI that do not respond to initial interventions.

Medications should be considered the second line of treatment in most instances. The serotonin, opioid, and dopamine systems have been implicated, so medications that target these systems have potential benefit. Before pharmacological treatment is initiated for NSSI, preexisting medications for other mental health concerns should be optimized. In the absence of an existing psychotropic regimen or clear indications for pharmacotherapy of comorbid mental health conditions, fluoxetine, currently the best-studied antidepressant for NSSI, is a good first option. If fluoxetine is poorly tolerated or of insufficient benefit, consider switching to olanzapine, which appears to be the most effective atypical antipsychotic for NSSI.

The suggestion of first initiating a trial of an SSRI, as opposed to an atypical antipsychotic, has more to do with side-effect profile than potential efficacy. In fact, a recent meta-analysis of randomized controlled trials of pharmacotherapy against core traits of BPD found that antidepressants and mood stabilizers did not produce significant benefits against impulsivity and aggression or suicidality (although they were effective against affective instability and anger).59 On the other hand, antipsychotics, as a class, had a positive effect in reducing impulsivity and aggression. For severe and/or refractory cases, consider other SSRIs, serotonin-norepinephrine reuptake inhibitors, other atypical antipsychotics, naltrexone, clonidine, mood stabilizers, or glutamate-modulating agents (Table 2).

Table 2

Given our growing awareness of the magnitude of the NSSI problem and the limited evidence base for its treatment, there are many future directions for research. Studies that specifically target the symptom of self-injury, especially in individuals without BPD, are sorely needed. We must also construct new studies that overcome limitations of past studies including small sample sizes, with a predominance of female, white, and adult participants, lack of controls, over reliance on self-report, low dosing of medications, and short trial durations. There needs to be further investigation of new generation antidepressants, naltrexone, clonidine, omega-3 fatty acids, atypical antipsychotics, mood stabilizers, glutamate-modulating agents, and polypharmacy to target NSSI. Finally, there must be further investigation of the potential efficacy of combined medication and psychotherapy, especially DBT.
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