
                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 [1]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.
   
   [INLINE]
   
  return to [2]SI main page

References

   1. file://localhost/usr/home/llama/Web/psych/pharm.html#drugs
   2. file://localhost/usr/home/llama/Web/psych/injury.html
