Different neurotransmitter receptors affect different bodily functions. Serotonin, for example, has as many as seven receptor types, and one of those has five subtypes. These receptors are involved in regulating emotion, mood, impulsivity, aggression, digestion, smooth muscle relaxation, and sexual behavior, among other functions.
Three sorts of neurotransmitters have been of concern to scientists studying self-injurious behavior: serotonin, dopamine, and endorphins. The strongest evidence so far points to serotonergic deficits -- the brain does not have enough serotonin available for use.
Simeon et al. (1992) found no overall difference in serotonin metabolite levels between subjects who did or did not self-injure (although when the sample was controlled for previous suicide attempts, self-injurers did have significantly lower levels of serotonin metabolites). More importantly, they found that self-injurious behavior was significantly negatively correlated with number of platelet imipramine binding sites and note that "a smaller number of imipramine binding sites . . . may reflect central serotonergic dysfunction with reduced presynaptic serotonin release. . . . Serotonergic dysfunction may facilitate self-mutilation."
When these results are considered in light of work such as that by Stoff et al. (1987) and Birmaher et al. (1990), which links reduced numbers of platelet imipramine binding sites to impulsivity and aggression, it appears that the most appropriate classification for self-injurious behavior might be as an impulse-control disorder similar to trichotillomania, kleptomania, or compulsive gambling.
Herpertz (Herpertz et al, 1995; Herpertz and Favazza, 1997) has investigated how blood levels of prolactin respond to doses of d-fenfluramine in self-injuring and control subjects. The prolactin response in self-injuring subjects was blunted, which is "suggestive of a deficit in overall and primarily pre-synaptic central 5-HT (serotonin) function." Stein et al. (1996) found a similar blunting of prolactin response on fenfluramine challenge in subjects with compulsive personality disorder, and Coccaro et al. (1997c) found prolactin response varied inversely with scores on the Life History of Aggression scale. Coccaro and colleagues (1997a, 1997b) showed in two double-blind placebo-controlled studies that fluoxetine, which operates by preventing serotonin from being reabsorbed in synapses and thus makes more presynaptic serotonin available, had an anti-aggressive affect on impulsive aggressive subjects who had been diagnosed with personality disorders.
New et al. (1997) studied prolactin response to d-fenfluramine in 97 subjects who had been diagnosed with personality disorders. They found that subjects with a history of both suicide attempts and self-injury had a significantly more blunted prolactin and cortisol response; subjects with either a history of suicide attempts or of self-injury had a more blunted response than those with a history of neither. This implies very strongly that a serotonin abnormality is involved in self-directed aggression, rather than being a marker of just suicidal behavior.
From this evidence, it would seem that a double-blind placebo-controlled study of the effects of selective serotonin reuptake inhibitors such as fluoxetine on self-injurious behavior is indicated; Favazza (personal communication, 1998) believes that high-dose SSRI therapy might help to control self-injury.
Research concerning the effects of specific drug
therapies
Probably the most investigated drugs for SIB are naltrexone and
naloxone, opiate antagonists. The theory is that self-mutilation
releases endorphins and over time, the body becomes addicted to these
pain-relieving neurotransmitters. The impulse to self-injure arises
from a craving for endorphins.
Almost all of the research on endorphins and self-mutilation has been done with retarded or autistic subjects. In a review of studies using opiate antagonists to treat SIB, Buzan et al. (1995) found that they were effective in reducing rates of self-injury about half the time. They note in closing that "a recent study demonstrated no alteration in pain perception in 11 self-mutilating patients with borderline personality disorder who were administered naloxone during an experimentally induced pain paradigm." This may indicate that the response to naloxone and naltrexone in developmentally disabled subjects is somehow mediated by their unique brain chemistry. It may also reflect a difference in brain function among patients who present with different types of self-injurious behavior; certainly stereotypic SIB is very different from episodic in etiology, onset, and type of injurious activity.
Sonne et al. (1996) reported on open administration of naltrexone to five clients with borderline personality disorder. Although they showed a great deal of improvement while taking the medication, the behavior increased in frequency after the week of naltrexone; this may indicate a pure placebo effect. No one has yet done a placebo-controlled double-blind crossover study of naltrexone that controls for type of behavior (stereotypic vs episodic/repetitive) as well as psychiatric diagnosis.
The new class of atypical neuroleptics, which tend to bind to dopamine and serotonin receptors, seem to show some promise in treating SIB as well. Clozapine (Chengappa et al., 1995; Hammock et al., 1995) has been reported to reduce SIB in personality disordered subjects; Hammock speculates that this is due to its effect on D1 dopamine receptors rather than its effects on serotonin receptors. Risperidone, another relatively new neuroleptic, binds D2 dopamine and 5-HT2 serotonin receptors; it has been reported by Khouzam and Donnelly (1997) to reduce SIB in a patient with borderline personality disorder. Olanzapine (Zyprexa) is another atypical neuroleptic used by some psychiatrists to treat SIB. There are no well-controlled studies of these drugs, however; the literature on them consists mainly of case reports and again, no one has made a distinction between types of SIB. These drugs can also have troublesome side effects -- patients on clozapine, for example, require weekly blood tests because of the risk of white-blood-cell abnormalities.
Carbamazepine (Tegretol) and valproic acid (Depakote) are sometimes given to patients who exhibit SIB. Cowdry and Gardner (1988) reported that carbamazepine and tranylcypromine (Parnate, an MAO inhibitor) reduced "behavioral dyscontrol" in patients with borderline personality disorder. An open trial of valproic acid in mentally retarded self-injurers showed response in 14 of the 18 patients studied (Kastner et al., 1993).
SSRIs have also been studied; as with opiate antagonists, most of the studies have been open trials and many have involved developmentally disabled subjects. Kavoussi et al. (1994), Ricketts et al. (1993), Sovner et al. (1993), and Markovitz et al. (1991) reported finding various SSRIs useful in reducing SIB.
No consensus on how (or whether) to treat SIB pharmacologically has been reached. So far, it appears that the most promising treatments are high-dose SSRIs and, in selected cases, atypical neuroleptics.