Psychopharmacological treatment of self-injury
Research into pharmacological treatment of self-injury tends to fall
into two categories: clinical trials of various drugs (including
single-case studies and other anecdotal reports) and research into
neurotransmitter abnormalities found in self-injurers. In order to
understand what kinds of drug therapy hold promise, it is necessary to
know a bit about neurochemical abnormalities in those who self-injure.
(You can skip this part and proceed to a summary of research
reports concerning specific drug therapies if you like.)
Neurotransmitters
Neurotransmitters are chemicals used to transmit messages in the
brain. Nerve cells have dendrites at one end and an axon (a long
tail-like thing) at the other. Axons communicate with dendrites at
synapses, the spaces between nerve cells. Electrical impulses travel
down the axon of a nerve cell to the synapse; when they get there,
they cause neurotransmitters to be released. The neurotransmitters
bind to receptors on the dendrite of the other cell in the synapse.
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.
Research implicating the serotonergic system
Several researchers have used different methods to demonstrate
serotonergic system dysfunctions in subjects who self-injure. Since it
isn't possible to measure serotonin levels directly, researchers have
to find substances whose levels correlate to serotonin levels. Two
commonly used techniques are measuring serotonin metabolites
(breakdown products) in spinal fluid and measuring the number of
imipramine binding sites on platelets. Lower levels of metabolites or
fewer platelet imipramine binding sites indicate low levels of
serotonin in the brain. Another very useful technique involves
measuring how levels of a hormone called prolactin change in response
to administration of a drug called d-fenfluramine. A blunted response
indicates decreased levels of presynaptic serotonin. This method gives
more precise information about neurotransmitter function.
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.
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